Yasar, B.
Suh, Y.-.
Chapman, E.
Nicholls, L.
Henderson, D.
Jones, C.
Morrison, K.
Wells, E.
Henderson, J.
Meehan, C.
Sohaib, A.
Taylor, H.
Tree, A.
Van As, N.
(2024). Simultaneous focal boost with stereotactic radiotherapy for localised intermediate to high-risk prostate cancer: Primary outcomes of the SPARC phase II trial. Int j radiat oncol biol phys,
.
show abstract
PURPOSE: Dose escalated radiotherapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiotherapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease whilst limiting toxicity. This study evaluated the toxicity and quality of life (QOL) with CyberKnife-based SBRT and simultaneous integrated boost in localised prostate cancer. METHODS AND MATERIALS: Eligible participants included newly diagnosed, biopsy-proven unfavourable intermediate to high risk localised prostate cancer (at least one of the following: Gleason ≥ 4+3, MRI defined T3a N0, PSA ≥ 20) with up to two MRI-identified DILs. Participants received 36.25Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5Gy as allowed by organs at risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2 + genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using RTOG scoring, biochemical parameters, IPSS, IIEF5, EQ5D QOL outcomes were assessed. RESULTS: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43Gy. Cumulative acute grade 2 + genitourinary and gastrointestinal toxicity was 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. IPSS score and urinary QOL scores recovered to baseline by 6months. Patient-reported outcomes showed no significant change in EQ-5D QOL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date. CONCLUSIONS: CyberKnife SBRT delivered dose of 36.25Gy to the prostate with a simultaneous integrated boost up to 47.5Gy is well tolerated. Acute and late GU and GI toxicity rates are comparable to other contemporary SBRT trials and series with focal boost..
Brand, D.H.
Brüningk, S.C.
Wilkins, A.
Naismith, O.
Gao, A.
Syndikus, I.
Dearnaley, D.P.
van As, N.
Hall, E.
Gulliford, S.
Tree, A.C.
CHHiP Trial Management Group,
(2023). The Fraction Size Sensitivity of Late Genitourinary Toxicity: Analysis of Alpha/Beta (α/β) Ratios in the CHHiP Trial. Int j radiat oncol biol phys,
Vol.115
(2),
pp. 327-336.
show abstract
full text
PURPOSE: Moderately hypofractionated external beam intensity modulated radiation therapy (RT) for prostate cancer is now standard-of-care. Normal tissue toxicity responses to fraction size alteration are nonlinear: the linear-quadratic model is a widely used framework accounting for this, through the α/β ratio. Few α/β ratio estimates exist for human late genitourinary endpoints; here we provide estimates derived from a hypofractionation trial. METHODS AND MATERIALS: The CHHiP trial randomized 3216 men with localized prostate cancer 1:1:1 between conventionally fractionated intensity modulated RT (74 Gy/37 fractions (Fr)) and 2 moderately hypofractionated regimens (60 Gy/20 Fr and 57 Gy/19 Fr). RT plan and suitable follow-up assessment was available for 2206 men. Three prospectively assessed clinician-reported toxicity scales were amalgamated for common genitourinary endpoints: dysuria, hematuria, incontinence, reduced flow/stricture, and urine frequency. Per endpoint, only patients with baseline zero toxicity were included. Three models for endpoint grade ≥1 (G1+) and G2+ toxicity were fitted: Lyman Kutcher-Burman (LKB) without equivalent dose in 2 Gy/Fr (EQD2) correction [LKB-NoEQD2]; LKB with EQD2-correction [LKB-EQD2]; LKB-EQD2 with dose-modifying-factor (DMF) inclusion [LKB-EQD2-DMF]. DMFs were age, diabetes, hypertension, pelvic surgery, prior transurethral resection of prostate (TURP), overall treatment time and acute genitourinary toxicity (G2+). Bootstrapping generated 95% confidence intervals and unbiased performance estimates. Models were compared by likelihood ratio test. RESULTS: The LKB-EQD2 model significantly improved performance over LKB-NoEQD2 for just 3 endpoints: dysuria G1+ (α/β = 2.0 Gy; 95% confidence interval [CI], 1.2-3.2 Gy), hematuria G1+ (α/β = 0.9 Gy; 95% CI, 0.1-2.2 Gy) and hematuria G2+ (α/β = 0.6 Gy; 95% CI, 0.1-1.7 Gy). For these 3 endpoints, further incorporation of 2 DMFs improved on LKB-EQD2: acute genitourinary toxicity and prior TURP (hematuria G1+ only), but α/β ratio estimates remained stable. CONCLUSIONS: Inclusion of EQD2-correction significantly improved model fitting for dysuria and hematuria endpoints, where fitted α/β ratio estimates were low: 0.6 to 2 Gy. This suggests therapeutic gain for clinician-reported GU toxicity, through hypofractionation, might be lower than expected by typical late α/β ratio assumptions of 3 to 5 Gy..
Brand, D.H.
Brüningk, S.C.
Wilkins, A.
Naismith, O.
Gao, A.
Syndikus, I.
Dearnaley, D.P.
Hall, E.
van As, N.
Tree, A.C.
Gulliford, S.
(2023). Gastrointestinal Toxicity Prediction Not Influenced by Rectal Contour or Dose-Volume Histogram Definition. Int j radiat oncol biol phys,
Vol.117
(5),
pp. 1163-1173.
show abstract
full text
PURPOSE: Rectal dose delivered during prostate radiation therapy is associated with gastrointestinal toxicity. Treatment plans are commonly optimized using rectal dose-volume constraints, often whole-rectum relative-volumes (%). We investigated whether improved rectal contouring, use of absolute-volumes (cc), or rectal truncation might improve toxicity prediction. METHODS AND MATERIALS: Patients from the CHHiP trial (receiving 74 Gy/37 fractions [Fr] vs 60 Gy/20 Fr vs 57 Gy/19 Fr) were included if radiation therapy plans were available (2350/3216 patients), plus toxicity data for relevant analyses (2170/3216 patients). Whole solid rectum relative-volumes (%) dose-volume-histogram (DVH), as submitted by treating center (original contour), was assumed standard-of-care. Three investigational rectal DVHs were generated: (1) reviewed contour per CHHiP protocol; (2) original contour absolute volumes (cc); and (3) truncated original contour (2 versions; ±0 and ±2 cm from planning target volume [PTV]). Dose levels of interest (V30, 40, 50, 60, 70, 74 Gy) in 74 Gy arm were converted by equivalent-dose-in-2 Gy-Fr (EQD2α/β= 3 Gy) for 60 Gy/57 Gy arms. Bootstrapped logistic models predicting late toxicities (frequency G1+/G2+, bleeding G1+/G2+, proctitis G1+/G2+, sphincter control G1+, stricture/ulcer G1+) were compared by area-undercurve (AUC) between standard of care and the 3 investigational rectal definitions. RESULTS: The alternative dose/volume parameters were compared with the original relative-volume (%) DVH of the whole rectal contour, itself fitted as a weak predictor of toxicity (AUC range, 0.57-0.65 across the 8 toxicity measures). There were no significant differences in toxicity prediction for: (1) original versus reviewed rectal contours (AUCs, 0.57-0.66; P = .21-.98); (2) relative- versus absolute-volumes (AUCs, 0.56-0.63; P = .07-.91); and (3) whole-rectum versus truncation at PTV ± 2 cm (AUCs, 0.57-0.65; P = .05-.99) or PTV ± 0 cm (AUCs, 0.57-0.66; P = .27-.98). CONCLUSIONS: We used whole-rectum relative-volume DVH, submitted by the treating center, as the standard-of-care dosimetric predictor for rectal toxicity. There were no statistically significant differences in prediction performance when using central rectal contour review, with the use of absolute-volume dosimetry, or with rectal truncation relative to PTV. Whole-rectum relative-volumes were not improved upon for toxicity prediction and should remain standard-of-care..
Chapman, E.R.
Nicholls, L.
Suh, Y.-.
Khoo, V.
Levine, D.
Ap Dafydd, D.
Van As, N.
(2023). Interobserver variation in clinical target volume (CTV) delineation for stereotactic radiotherapy to non-spinal bone metastases in prostate cancer: CT, MRI and PET/CT fusion. Radiother oncol,
Vol.180,
p. 109461.
show abstract
BACKGROUND AND PURPOSE: The use of SBRT for the treatment of oligometastatic prostate cancer is increasing rapidly. While consensus guidelines are available for non-spinal bone metastases practice continues to vary widely. The aim of this study is to look at inter-observer variability in the contouring of prostate cancer non-spinal bone metastases with different imaging modalities. MATERIALS AND METHODS: 15 metastases from 13 patients treated at our centre were selected. 4 observers independently contoured clinical target volumes (CTV) on planning CT alone, planning CT with MRI fusion, planning CT with PET-CT fusion and planning CT with both MRI and PET-CT fusion combined. The mean inter-observer agreement on each modality was compared by measuring the delineated volume, generalized conformity index (CIgen), and the distance of the centre of mass (dCOM), calculated per metastasis and imaging modality. RESULTS: Mean CTV volume delineated on planning CT with MRI and PET-CT fusion combined was significantly larger compared to other imaging modalities (p = 0.0001). CIgen showed marked variation between modalities with the highest agreement between planning CT + PET-CT (mean CIgen 0.55, range 0.32-0.73) and planning CT + MRI + PET-CT (mean CIgen 0.59, range 0.34-0.73). dCOM showed small variations between imaging modalities but a significantly shorter distance found on planning CT + PET-CT when compared with planning CT + PET-CT + MRI combined (p = 0.03). CONCLUSIONS: Highest consistency in CTV delineation between observers was seen with planning CT + PET-CT and planning CT + PET-CT + MRI combined..
Ratnakumaran, R.
van As, N.
Khoo, V.
McDonald, F.
Tait, D.
Ahmed, M.
Taylor, H.
Griffin, C.
Dunne, E.M.
Tree, A.C.
(2023). Patterns of Failure After Stereotactic Body Radiotherapy to Sacral Metastases. Clin oncol (r coll radiol),
Vol.35
(5),
pp. 339-346.
show abstract
AIMS: Stereotactic body radiotherapy (SBRT) is increasingly used to treat sacral metastases. We analysed our centre's local relapse rates and patterns of failure after sacral SBRT and assessed whether using the consensus contouring recommendation (CCR) may have prevented local relapse. MATERIALS AND METHODS: We conducted a single-centre retrospective review of patients treated with sacral SBRT between February 2012 and December 2021. The cumulative incidence of local relapse, patterns of failure and overall survival were determined. Two investigators reviewed planning computed tomography scans and imaging at relapse to determine if local relapse was potentially preventable with a larger CCR-derived radiotherapy field. RESULTS: In total, 34 patients received sacral SBRT, with doses ranging from 24 to 40 Gy over three to five fractions. The most frequently used schedule was 30 Gy in three fractions. Common primaries treated included prostate (n = 16), breast (n = 6), lung (n = 3) and renal (n = 3) cancers. The median follow-up was 20 months (interquartile range 13-55 months). The cumulative incidence of local relapse (4/34) was 2.9% (95% confidence interval 0.2-13.2), 6.3% (95% confidence interval 1.1-18.5) and 16.8% (95% confidence interval 4.7-35.4) at 6 months, 1 year and 2 years, respectively. The patterns of failure were local-only (1/34), local and distant (3/34) and distant relapse (10/34). The overall survival was 96.7% (95% confidence interval 90.5-100) and 90.6% (95% confidence interval 78.6-100) at 1 and 2 years, respectively. For prostate/breast primaries, the cumulative incidence of local relapse was 4.5% (95% confidence interval 0.3-19.4), 4.5% (95% confidence interval 0.3-19.4) and 12.5% (95% confidence interval 1.7-34.8) at 6 months, 1 and 2 years, respectively. Twenty-nine cases (85.3%) deviated from the CCR. Sacral relapse was potentially preventable if the CCR was used in one patient (2.9% of the whole cohort and 25% of the relapsed cohort). DISCUSSION: We have shown excellent local control rates with sacral SBRT, which was largely planned with a margin expansion approach..
Wu, M.Y.
Shepherd, S.T.
Fendler, A.
Carr, E.J.
Au, L.
Harvey, R.
Dowgier, G.
Hobbs, A.
Herman, L.S.
Ragno, M.
Adams, L.
Schmitt, A.M.
Tippu, Z.
Shum, B.
Farag, S.
Rogiers, A.
O'Reilly, N.
Bawumia, P.
Smith, C.
Carlyle, E.
Edmonds, K.
Del Rosario, L.
Lingard, K.
Mangwende, M.
Holt, L.
Ahmod, H.
Korteweg, J.
Foley, T.
Barber, T.
Hepworth, S.
Emslie-Henry, A.
Caulfield-Lynch, N.
Byrne, F.
Deng, D.
Williams, B.
Brown, M.
Caidan, S.
Gavrielides, M.
MacRae, J.I.
Kelly, G.
Peat, K.
Kelly, D.
Murra, A.
Kelly, K.
O'Flaherty, M.
Popat, S.
Yousaf, N.
Jhanji, S.
Tatham, K.
Cunningham, D.
Van As, N.
Young, K.
Furness, A.J.
Pickering, L.
Beale, R.
Swanton, C.
Gandhi, S.
Gamblin, S.
Bauer, D.L.
Kassiotis, G.
Howell, M.
Walker, S.
Nicholson, E.
Larkin, J.
Wall, E.C.
Turajlic, S.
CAPTURE consortium,
(2023). Sotrovimab restores neutralization against current Omicron subvariants in patients with blood cancer. Cancer cell,
Vol.41
(5),
pp. 821-823.
show abstract
full text
Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants..
Ratnakumaran, R.
Hinder, V.
Brand, D.
Staffurth, J.
Hall, E.
van As, N.
Tree, A.
PACE Trial Investigators,
(2023). The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study. Cancers (basel),
Vol.15
(4).
show abstract
full text
Several studies have demonstrated the association between acute and late radiotherapy toxicity in prostate cancer using older radiotherapy techniques. However, whether this association is present with newer techniques such as stereotactic body radiotherapy (SBRT), remains unclear. We use univariable and multivariable logistic regression to analyse the association between grade 2 or worse acute gastrointestinal (GI) and genitourinary (GU) toxicities with equivalent late toxicities in patients treated with SBRT and conventional or moderately fractionated radiotherapy (CRT) within the PACE-B study. 842 patients were included in this analysis. Common Terminology Criteria for Adverse Events (CTCAE) was the primary clinician reported outcome measure used in this analysis. In univariable analysis, experiencing a grade 2+ acute GU toxicity was significantly associated with developing a grade 2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96-7.25), p < 0.0001) and CRT (OR 2.83, 95% CI (1.69-4.71), p < 0.0001). This association remained significant in multivariable analysis. In univariable analysis, experiencing a grade 2+ acute GI toxicity was also associated with developing a grade 2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91-7.03), p < 0.0001) and CRT (OR 4.4, 95% CI (2.04-9.47), p < 0.0001). This association also remained significant in multivariable analysis. Grade 2+ baseline GU symptoms were also associated with grade 2+ late urinary toxicity in both univariable and multivariable analysis. Overall, acute toxicity is an important predictor variable for late GU/GI toxicity after localised prostate radiotherapy using SBRT and CRT. Future work should test whether optimising symptoms pre-treatment and early intervention in those with significant acute toxicities could mitigate the development late of toxicity..
Nicholls, L.
Chapman, E.
Khoo, V.
Suh, Y.-.
Tunariu, N.
Wang, Y.
van As, N.
(2022). Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease. Clin oncol (r coll radiol),
Vol.34
(1),
pp. 63-69.
show abstract
AIMS: Oligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD. MATERIALS AND METHODS: A retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan-Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system. RESULTS: In total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10-39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13-32) and the 3-year overall survival was 88% (95% confidence interval 80-96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19-17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05-42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression. CONCLUSION: The ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features..
Nicholls, L.
Chapman, E.
Khoo, V.
Suh, Y.-.
van As, N.
(2022). In Reply to Onal et al. Clin oncol (r coll radiol),
Vol.34
(4),
p. e173.
Diez, P.
Hanna, G.G.
Aitken, K.L.
van As, N.
Carver, A.
Colaco, R.J.
Conibear, J.
Dunne, E.M.
Eaton, D.J.
Franks, K.N.
Good, J.S.
Harrow, S.
Hatfield, P.
Hawkins, M.A.
Jain, S.
McDonald, F.
Patel, R.
Rackley, T.
Sanghera, P.
Tree, A.
Murray, L.
(2022). UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy. Clin oncol (r coll radiol),
Vol.34
(5),
pp. 288-300.
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full text
The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice..
Chapman, E.R.
Correa, R.J.
Palma, D.A.
Van As, N.
(2022). Stereotactic Ablative Radiotherapy for Oligometastatic Disease: A Tale of Emperor's New Clothes or New Standard of Care?. Clin oncol (r coll radiol),
Vol.34
(5),
pp. 318-324.
Alexander, S.E.
McNair, H.A.
Oelfke, U.
Huddart, R.
Murray, J.
Pathmanathan, A.
Patel, P.
Sritharan, K.
van As, N.
Tree, A.C.
(2022). Prostate Volume Changes during Extreme and Moderately Hypofractionated Magnetic Resonance Image-guided Radiotherapy. Clin oncol (r coll radiol),
Vol.34
(9),
pp. e383-e391.
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full text
AIMS: Prostate morphological changes during external beam radiotherapy are poorly understood. Excellent soft-tissue visualisation offered by magnetic resonance image-guided radiotherapy (MRIgRT) provides an opportunity to better understand such changes. The aim of this study was to quantify prostate volume and dimension changes occurring during extreme and moderately hypofractionated schedules. MATERIALS AND METHODS: Forty prostate cancer patients treated on the Unity 1.5 Tesla magnetic resonance linear accelerator (MRL) were retrospectively reviewed. The cohort comprised patients treated with 36.25 Gy in five fractions (n = 20) and 60 Gy in 20 fractions (n = 20). The volume of the delineated prostates on reference planning computed tomography (fused with MRI) and daily T2-weighted 2-min session images acquired on Unity were charted. Forty planning computed tomography and 500 MRL prostate volumes were evaluated. The mean absolute and relative change in prostate volume during radiotherapy was compared using a paired t-test (P value <0.01 considered significant to control for multiple comparisons). The maximum dimension of the delineated prostate was measured in three isocentric planes. RESULTS: Significant prostate volume changes, relative to MRL imaging fraction 1 (MRL#1), were seen at all time points for the five-fraction group. The peak mean relative volume increase was 21% (P < 0.001), occurring at MRL#3 and MRL#4 after 14.5 and 21.75 Gy, respectively. Prostate expansion was greatest in the superior-inferior direction; the peak mean maximal extension was 5.9 mm. The maximal extension in the left-right and anterior-posterior directions measured 1.1 and 2.2 mm, respectively. For the 20-fraction group, prostate volume increased relative to MRL#1, for all treatment time points. The mean relative volume increase was 11% (P < 0.001) at MRL#5 after 12 Gy, it then fluctuated between 8 and 13%. From MRL#5 to MRL#20, the volume increase was significant (P < 0.01) for 12 of 16 time points calculated. The peak mean maximal extension in the superior-inferior direction was 3.1 mm. The maximal extension in the left-right and anterior-posterior directions measured 1.7 and 3.7 mm, respectively. CONCLUSION: Significant prostate volume and dimension changes occur during extreme and moderately hypofractionated radiotherapy. The extent of change was greater during extreme hypofractionation. MRIgRT offers the opportunity to reveal, quantify and correct for this deformation..
Tree, A.C.
Ostler, P.
van der Voet, H.
Chu, W.
Loblaw, A.
Ford, D.
Tolan, S.
Jain, S.
Martin, A.
Staffurth, J.
Armstrong, J.
Camilleri, P.
Kancherla, K.
Frew, J.
Chan, A.
Dayes, I.S.
Duffton, A.
Brand, D.H.
Henderson, D.
Morrison, K.
Brown, S.
Pugh, J.
Burnett, S.
Mahmud, M.
Hinder, V.
Naismith, O.
Hall, E.
van As, N.
PACE Trial Investigators,
(2022). Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial. Lancet oncol,
Vol.23
(10),
pp. 1308-1320.
show abstract
full text
BACKGROUND: Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. METHODS: PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. FINDINGS: We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. INTERPRETATION: In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. FUNDING: Accuray..
Fendler, A.
Shepherd, S.T.
Au, L.
Wu, M.
Harvey, R.
Wilkinson, K.A.
Schmitt, A.M.
Tippu, Z.
Shum, B.
Farag, S.
Rogiers, A.
Carlyle, E.
Edmonds, K.
Del Rosario, L.
Lingard, K.
Mangwende, M.
Holt, L.
Ahmod, H.
Korteweg, J.
Foley, T.
Barber, T.
Emslie-Henry, A.
Caulfield-Lynch, N.
Byrne, F.
Deng, D.
Kjaer, S.
Song, O.-.
Queval, C.J.
Kavanagh, C.
Wall, E.C.
Carr, E.J.
Caidan, S.
Gavrielides, M.
MacRae, J.I.
Kelly, G.
Peat, K.
Kelly, D.
Murra, A.
Kelly, K.
O'Flaherty, M.
Shea, R.L.
Gardner, G.
Murray, D.
Popat, S.
Yousaf, N.
Jhanji, S.
Tatham, K.
Cunningham, D.
Van As, N.
Young, K.
Furness, A.J.
Pickering, L.
Beale, R.
Swanton, C.
Gandhi, S.
Gamblin, S.
Bauer, D.L.
Kassiotis, G.
Howell, M.
Nicholson, E.
Walker, S.
Wilkinson, R.J.
Larkin, J.
Turajlic, S.
(2022). Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer. Cell rep med,
Vol.3
(10),
p. 100781.
show abstract
full text
Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination..
Patel, P.H.
Tunariu, N.
Levine, D.S.
de Bono, J.S.
Eeles, R.A.
Khoo, V.
Murray, J.
Parker, C.C.
Pathmanathan, A.
Reid, A.
van As, N.
Tree, A.C.
(2022). Oligoprogression in Metastatic, Castrate-Resistant Prostate Cancer-Prevalence and Current Clinical Practice. Front oncol,
Vol.12,
p. 862995.
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full text
AIMS: Oligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen receptor-targeted therapy (ARTT)]. The aim of this study was to determine the prevalence of oligoprogression, describe the characteristics of oligoprogression in a cohort of patients from a single center, and identify the number of patients potentially treatable with stereotactic body radiotherapy (SBRT). METHODS: Castration-resistant prostate cancer (CRPC) patients who radiologically progressed while on ARTT were included. Patients with oligoprogressive disease (OPD) (≤3 lesions) on any imaging were identified in a retrospective analysis of electronic patient records. Kaplan-Meier method and log-rank test were used to calculate progression-free and overall survival. RESULTS: A total of 102 patients with metastatic CRPC on ARTT were included. Thirty (29%) patients presented with oligoprogression (46 lesions in total); 21 (21% of total) patients had lesions suitable for SBRT. The majority of lesions were in the bone (21, 46%) or lymph nodes (15, 33%). Patients with oligoprogression while on ARTT had a significantly better prostate-specific antigen (PSA) response on commencing ARTT as compared to patients who later developed polyprogression. However, PSA doubling time immediately prior to progression did not predict OPD. Median progression-free survival to oligoprogression versus polyprogression was 16.8 vs. 11.7 months. Time to further progression after oligoprogression was 13.6 months in those treated with radiotherapy (RT) for oligoprogression vs. 5.7 months in those treated with the continuation of ARTT alone. CONCLUSIONS: In this study, nearly a third of patients on ARTT for CRPC were found to have OPD. OPD patients had a better PSA response on ART and a longer duration on ARTT before developing OPD as compared to those developing polyprogressive disease (Poly-PD). The majority of patients (70%) with OPD had lesions suitable for SBRT treatment. Prospective randomized control trials are needed to establish if there is a survival benefit of SBRT in oligoprogressive prostate cancer and to determine predictive indicators..
Brand, D.H.
Brüningk, S.C.
Wilkins, A.
Fernandez, K.
Naismith, O.
Gao, A.
Syndikus, I.
Dearnaley, D.P.
Tree, A.C.
van As, N.
Hall, E.
Gulliford, S.
CHHiP Trial Management Group,
(2021). Estimates of Alpha/Beta (α/β) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial. Int j radiat oncol biol phys,
Vol.110
(2),
pp. 596-608.
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PURPOSE: Changes in fraction size of external beam radiation therapy exert nonlinear effects on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/β ratio. We sought to study individual α/β ratios for different late rectal effects after prostate external beam radiation therapy. METHODS AND MATERIALS: The CHHiP trial (ISRCTN97182923) randomized men with nonmetastatic prostate cancer 1:1:1 to 74 Gy/37 fractions (Fr), 60 Gy/20 Fr, or 57 Gy/19 Fr. Patients in the study had full dosimetric data and zero baseline toxicity. Toxicity scales were amalgamated to 6 bowel endpoints: bleeding, diarrhea, pain, proctitis, sphincter control, and stricture. Lyman-Kutcher-Burman models with or without equivalent dose in 2 Gy/Fr correction were log-likelihood fitted by endpoint, estimating α/β ratios. The α/β ratio estimate sensitivity was assessed using sequential inclusion of dose modifying factors (DMFs): age, diabetes, hypertension, inflammatory bowel or diverticular disease (IBD/diverticular), and hemorrhoids. 95% confidence intervals (CIs) were bootstrapped. Likelihood ratio testing of 632 estimator log-likelihoods compared the models. RESULTS: Late rectal α/β ratio estimates (without DMF) ranged from bleeding (G1 + α/β = 1.6 Gy; 95% CI, 0.9-2.5 Gy) to sphincter control (G1 + α/β = 3.1 Gy; 95% CI, 1.4-9.1 Gy). Bowel pain modelled poorly (α/β, 3.6 Gy; 95% CI, 0.0-840 Gy). Inclusion of IBD/diverticular disease as a DMF significantly improved fits for stool frequency G2+ (P = .00041) and proctitis G1+ (P = .00046). However, the α/β ratios were similar in these no-DMF versus DMF models for both stool frequency G2+ (α/β 2.7 Gy vs 2.5 Gy) and proctitis G1+ (α/β 2.7 Gy vs 2.6 Gy). Frequency-weighted averaging of endpoint α/β ratios produced: G1 + α/β ratio = 2.4 Gy; G2 + α/β ratio = 2.3 Gy. CONCLUSIONS: We estimated α/β ratios for several common late adverse effects of rectal radiation therapy. When comparing dose-fractionation schedules, we suggest using late a rectal α/β ratio ≤ 3 Gy..
Chalkidou, A.
Macmillan, T.
Grzeda, M.T.
Peacock, J.
Summers, J.
Eddy, S.
Coker, B.
Patrick, H.
Powell, H.
Berry, L.
Webster, G.
Ostler, P.
Dickinson, P.D.
Hatton, M.Q.
Henry, A.
Keevil, S.
Hawkins, M.A.
Slevin, N.
van As, N.
(2021). Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study. Lancet oncol,
Vol.22
(1),
pp. 98-106.
show abstract
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is increasingly being used to treat oligometastatic cancers, but high-level evidence to provide a basis for policy making is scarce. Additional evidence from a real-world setting is required. We present the results of a national study of patients with extracranial oligometastases undergoing SABR, representing the largest dataset, to our knowledge, on outcomes in this population so far. METHODS: In 2015, National Health Service (NHS) England launched a Commissioning through Evaluation scheme that funded a prospective, registry-based, single-arm, observational, evaluation study of patients with solid cancer and extracranial oligometastases treated with SABR. Prescribed doses ranged from 24-60 Gy administered in three to eight fractions. The study was done at 17 NHS radiotherapy centres in England. Patients were eligible for the scheme if aged 18 years or older with confirmed primary carcinoma (excluding haematological malignancies), one to three extracranial metastatic lesions, a disease-free interval from primary tumour development to metastases of longer than 6 months (with the exception of synchronous colorectal liver metastases), a WHO performance status of 2 or lower, and a life expectancy of at least 6 months. The primary outcome was overall survival at 1 year and 2 years from the start of SABR treatment. The study is now completed. FINDINGS: Between June 15, 2015, and Jan 30, 2019, 1422 patients were recruited from 17 hospitals in England. The median age of the patients was 69 years (IQR 62-76), and the most common primary tumour was prostate cancer (406 [28·6%] patients). Median follow-up was 13 months (IQR 6-23). Overall survival was 92·3% (95% CI 90·5-93·9) at 1 year and 79·2% (76·0-82·1) at 2 years. The most common grade 3 adverse event was fatigue (28 [2·0%] of 1422 patients) and the most common serious (grade 4) event was increased liver enzymes (nine [0·6%]). Notreatment-related deaths were reported. INTERPRETATION: In patients with extracranial oligometastatic cancer, use of SABR was associated with high overall survival and low toxicity. 'The study findings complement existing evidence from a randomised, phase 2 trial, and represent high-level, real-world evidence supporting the use of SABR in this patient cohort, with a phase 3 randomised, controlled trial to confirm these findings underway. Based on the selection criteria in this study, SABR was commissioned by NHS England in March, 2020, as a treatment option for patients with oligometastatic disease. FUNDING: NHS England Commissioning through Evaluation scheme..
Chalkidou, A.
Patrick, H.
Hatton, M.Q.
Hawkins, M.A.
van As, N.
study authors,
(2021). Stereotactic radiotherapy and oligometastases - Authors' reply. Lancet oncol,
Vol.22
(4),
p. e133.
Jereczek-Fossa, B.A.
Marvaso, G.
Zaffaroni, M.
Gugliandolo, S.G.
Zerini, D.
Corso, F.
Gandini, S.
Alongi, F.
Bossi, A.
Cornford, P.
De Bari, B.
Fonteyne, V.
Hoskin, P.
Pieters, B.R.
Tree, A.C.
Arcangeli, S.
Fuller, D.B.
Franzese, C.
Hannoun-Levi, J.-.
Janoray, G.
Kerkmeijer, L.
Kwok, Y.
Livi, L.
Loi, M.
Miralbell, R.
Pasquier, D.
Pinkawa, M.
Scher, N.
Scorsetti, M.
Shelan, M.
Toledano, A.
van As, N.
Vavassori, A.
Zilli, T.
Pepa, M.
Ost, P.
on the behalf of the European Society for Radiotherapy, Oncology Advisory Committee on Radiation Oncology Practice (ESTRO ACROP),
(2021). Salvage stereotactic body radiotherapy (SBRT) for intraprostatic relapse after prostate cancer radiotherapy: An ESTRO ACROP Delphi consensus. Cancer treat rev,
Vol.98,
p. 102206.
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BACKGROUND AND PURPOSE: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT. MATERIALS AND METHODS: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation. RESULTS: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure). CONCLUSION: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach..
Tree, A.C.
van As, N.J.
(2021). Single dose prostate radiotherapy - a step too far?. Nat rev urol,
Vol.18
(8),
pp. 445-446.
full text
Fendler, A.
Shepherd, S.T.
Au, L.
Wilkinson, K.A.
Wu, M.
Byrne, F.
Cerrone, M.
Schmitt, A.M.
Joharatnam-Hogan, N.
Shum, B.
Tippu, Z.
Rzeniewicz, K.
Boos, L.A.
Harvey, R.
Carlyle, E.
Edmonds, K.
Del Rosario, L.
Sarker, S.
Lingard, K.
Mangwende, M.
Holt, L.
Ahmod, H.
Korteweg, J.
Foley, T.
Bazin, J.
Gordon, W.
Barber, T.
Emslie-Henry, A.
Xie, W.
Gerard, C.L.
Deng, D.
Wall, E.C.
Agua-Doce, A.
Namjou, S.
Caidan, S.
Gavrielides, M.
MacRae, J.I.
Kelly, G.
Peat, K.
Kelly, D.
Murra, A.
Kelly, K.
O'Flaherty, M.
Dowdie, L.
Ash, N.
Gronthoud, F.
Shea, R.L.
Gardner, G.
Murray, D.
Kinnaird, F.
Cui, W.
Pascual, J.
Rodney, S.
Mencel, J.
Curtis, O.
Stephenson, C.
Robinson, A.
Oza, B.
Farag, S.
Leslie, I.
Rogiers, A.
Iyengar, S.
Ethell, M.
Messiou, C.
Cunningham, D.
Chau, I.
Starling, N.
Turner, N.
Welsh, L.
van As, N.
Jones, R.L.
Droney, J.
Banerjee, S.
Tatham, K.C.
O'Brien, M.
Harrington, K.
Bhide, S.
Okines, A.
Reid, A.
Young, K.
Furness, A.J.
Pickering, L.
Swanton, C.
Crick COVID-19 Consortium,
Gandhi, S.
Gamblin, S.
Bauer, D.L.
Kassiotis, G.
Kumar, S.
Yousaf, N.
Jhanji, S.
Nicholson, E.
Howell, M.
Walker, S.
Wilkinson, R.J.
Larkin, J.
Turajlic, S.
CAPTURE Consortium,
(2021). Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study. Nat cancer,
Vol.2
(12),
pp. 1305-1320.
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Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic..
Fendler, A.
Au, L.
Shepherd, S.T.
Byrne, F.
Cerrone, M.
Boos, L.A.
Rzeniewicz, K.
Gordon, W.
Shum, B.
Gerard, C.L.
Ward, B.
Xie, W.
Schmitt, A.M.
Joharatnam-Hogan, N.
Cornish, G.H.
Pule, M.
Mekkaoui, L.
Ng, K.W.
Carlyle, E.
Edmonds, K.
Rosario, L.D.
Sarker, S.
Lingard, K.
Mangwende, M.
Holt, L.
Ahmod, H.
Stone, R.
Gomes, C.
Flynn, H.R.
Agua-Doce, A.
Hobson, P.
Caidan, S.
Howell, M.
Wu, M.
Goldstone, R.
Crawford, M.
Cubitt, L.
Patel, H.
Gavrielides, M.
Nye, E.
Snijders, A.P.
MacRae, J.I.
Nicod, J.
Gronthoud, F.
Shea, R.L.
Messiou, C.
Cunningham, D.
Chau, I.
Starling, N.
Turner, N.
Welsh, L.
van As, N.
Jones, R.L.
Droney, J.
Banerjee, S.
Tatham, K.C.
Jhanji, S.
O'Brien, M.
Curtis, O.
Harrington, K.
Bhide, S.
Bazin, J.
Robinson, A.
Stephenson, C.
Slattery, T.
Khan, Y.
Tippu, Z.
Leslie, I.
Gennatas, S.
Okines, A.
Reid, A.
Young, K.
Furness, A.J.
Pickering, L.
Gandhi, S.
Gamblin, S.
Swanton, C.
Crick COVID-19 Consortium,
Nicholson, E.
Kumar, S.
Yousaf, N.
Wilkinson, K.A.
Swerdlow, A.
Harvey, R.
Kassiotis, G.
Larkin, J.
Wilkinson, R.J.
Turajlic, S.
CAPTURE consortium,
(2021). Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study. Nat cancer,
Vol.2
(12),
pp. 1321-1337.
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full text
Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer..
Scarsbrook, A.F.
Bottomley, D.
Teoh, E.J.
Bradley, K.M.
Payne, H.
Afaq, A.
Bomanji, J.
van As, N.
Chua, S.
Hoskin, P.
Chambers, A.
Cook, G.J.
Warbey, V.S.
Han, S.
Leung, H.Y.
Chau, A.
Miller, M.P.
Gleeson, F.V.
FALCON study group,
(2020). Effect of 18F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial. Int j radiat oncol biol phys,
Vol.107
(2),
pp. 316-324.
show abstract
PURPOSE: Early and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, 18F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of 18F-fluciclovine on management of men with BCR of prostate cancer. METHODS AND MATERIALS: Men with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) according to standardized procedures. Clinicians documented management plans before and after scanning, recording changes to treatment modality as major and changes within a modality as other. The primary outcome measure was record of a revised management plan postscan. Secondary endpoints were evaluation of optimal prostate specific antigen (PSA) threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine-involvement, and safety. RESULTS: 18F-Fluciclovine was well tolerated in the 104 scanned patients (median PSA = 0.79 ng/mL). Lesions were detected in 58 out of 104 (56%) patients. Detection was broadly proportional to PSA level; ≤1 ng/mL, 1 out of 3 of scans were positive, and 93% scans were positive at PSA >2.0 ng/mL. Sixty-six (64%) patients had a postscan management change (80% after a positive result). Major changes (43 out of 66; 65%) were salvage or systemic therapy to watchful waiting (16 out of 66; 24%); salvage therapy to systemic therapy (16 out of 66; 24%); and alternative changes to treatment modality (11 out of 66, 17%). The remaining 23 out of 66 (35%) management changes were modifications of the prescan plan: most (22 out of 66; 33%) were adjustments to planned brachytherapy/radiation therapy to include a 18F-fluciclovine-guided boost. Where 18F-fluciclovine guided salvage therapy, the PSA response rate was higher than when 18F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]). CONCLUSIONS: 18F-Fluciclovine PET/CT located recurrence in the majority of men with BCR, frequently resulting in major management plan changes. Incorporating 18F-fluciclovine PET/CT into treatment planning may optimize targeting of recurrence sites and avoid futile salvage therapy..
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium,
(2020). Pan-cancer analysis of whole genomes. Nature,
Vol.578
(7793),
pp. 82-93.
show abstract
full text
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18..
Chaw, C.L.
deSouza, N.M.
Khoo, V.
Suh, Y.E.
van As, N.
(2020). Clinical Outcomes of Stereotactic Body Radiotherapy With Immediate Versus Delayed Hormone Therapy in Men With Oligometastatic Recurrence of Prostate Cancer. Clin oncol (r coll radiol),
Vol.32
(8),
pp. 509-517.
show abstract
AIMS: Stereotactic body radiotherapy (SBRT) with the delayed option of androgen deprivation therapy (ADT) is the current treatment paradigm in men relapsed with oligometastatic prostate cancer based on the outcome of a phase II randomised controlled study. The immediate (concomitant) use of ADT in this clinical setting potentially augments the efficacy of SBRT by improving systemic disease control. The aim of this study was to compare the clinical outcomes of these two treatment strategies. MATERIALS AND METHODS: Eighty-eight patients with up to three oligometastases and controlled primary disease who had been treated using SBRT with immediate or delayed ADT were included in this retrospective analysis. Progression-free survival (PFS), widespread failure-free survival (WFFS) and freedom from further interventions (FFFI) were assessed using Kaplan-Meier and Cox proportional hazard regression methods. Toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: Thirty-nine patients (44.3%) were treated with SBRT and immediate ADT (continuous ADT, n = 7; intermittent ADT, n = 32) and 49 (55.7%) with SBRT and delayed ADT. The median follow-up was 24 months (interquartile range 13.5-37.0 months). PFS in the immediate and delayed ADT groups were 26 months and 16 months, respectively (P < 0.007). The median WFFS in the immediate ADT group was not reached compared with 21 months in the delayed ADT group (P = 0.025). The 1- and 2-year FFFI in the immediate ADT group were 88% and 64.1%, respectively, significantly higher than those in the delayed ADT group (63.8% and 30.2%, respectively, P < 0.002). Acute toxicities of grade 1-2 occurred in 17.9% of the immediate ADT group and 18.4% of the delayed ADT group (P = 0.96). Only one case of grade 3 late toxicity (pelvic insufficiency) was identified in this study. CONCLUSIONS: SBRT with concomitant ADT improves PFS, WFFS and FFFI as compared with SBRT with delayed ADT; this finding needs validation in a prospective, randomised study..
Tokaca, N.
Cui, W.
Hazell, S.
Nicholson, A.G.
Van As, N.
Popat, S.
(2020). Squamous Non-Small-Cell Lung Cancer Molecularly Reclassified as Transdifferentiated Prostate Cancer Due to Identification of TMPRSS2-ERG Translocation With SOX2 Amplification. Jco oncol pract,
Vol.16
(10),
pp. 695-697.
Nicholls, L.
Suh, Y.-.
Chapman, E.
Henderson, D.
Jones, C.
Morrison, K.
Sohaib, A.
Taylor, H.
Tree, A.
van As, N.
(2020). Stereotactic radiotherapy with focal boost for intermediate and high-risk prostate cancer: Initial results of the SPARC trial. Clin transl radiat oncol,
Vol.25,
pp. 88-93.
show abstract
full text
INTRODUCTION: Dose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR). MATERIALS AND METHODS: Patients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml. Visible disease on mpMRI was mandatory and up to 2 separate nodules were allowed. All patients received androgen deprivation. Patients received 36.25 Gy in 5 fractions using CyberKnife® and the DIL received a simultaneous boost to a maximum of 47.5 Gy, as allowed by OAR constraints. Genitourinary (GU) and gastrointestinal (GI) toxicity was reported using the RTOG scoring criteria. International Index of Erectile Function (IIEF) and EQ-5D global health scores were regularly captured. RESULTS: An interim safety analysis was performed on the first 8 patients, recruited between July 2013 and December 2015. Median follow up was 56 months (range 50-74). Median D95 values for the prostate PTV and boost volume were 36.55 Gy (range 35.87-36.99) and 46.62 Gy (range 44.85-48.25) respectively. Of the dose constraints, 10/80 were not achieved but all were minor dose variations. Grade 2+ acute GU and GI toxicities were 37.5% respectively while grade 2+ late GU and GI toxicities were 12.5% and 0% respectively. IIEF and quality of life scores recovered over time and all patients remain in biochemical remission. CONCLUSION: The first patients have been successfully treated with prostate SABR and focal boost on the SPARC trial, with excellent adherence to the planning protocol. Toxicity and efficacy results are promising and further recruitment is underway..
Bancroft, E.K.
Saya, S.
Page, E.C.
Myhill, K.
Thomas, S.
Pope, J.
Chamberlain, A.
Hart, R.
Glover, W.
Cook, J.
Rosario, D.J.
Helfand, B.T.
Hutten Selkirk, C.
Davidson, R.
Longmuir, M.
Eccles, D.M.
Gadea, N.
Brewer, C.
Barwell, J.
Salinas, M.
Greenhalgh, L.
Tischkowitz, M.
Henderson, A.
Evans, D.G.
Buys, S.S.
IMPACT Study Steering Committee,
IMPACT Collaborators,
Eeles, R.A.
Aaronson, N.K.
(2019). Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations. Bju int,
Vol.123
(2),
pp. 284-292.
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OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening..
Pathmanathan, A.U.
McNair, H.A.
Schmidt, M.A.
Brand, D.H.
Delacroix, L.
Eccles, C.L.
Gordon, A.
Herbert, T.
van As, N.J.
Huddart, R.A.
Tree, A.C.
(2019). Comparison of prostate delineation on multimodality imaging for MR-guided radiotherapy. Br j radiol,
Vol.92
(1095),
p. 20180948.
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OBJECTIVE:: With increasing incorporation of MRI in radiotherapy, we investigate two MRI sequences for prostate delineation in radiographer-led image guidance. METHODS:: Five therapeutic radiographers contoured the prostate individually on CT, T2 weighted (T2W) and T2* weighted (T2*W) imaging for 10 patients. Contours were analysed with Monaco ADMIRE (research v. 2.0) to assess interobserver variability and accuracy by comparison with a gold standard clinician contour. Observers recorded time taken for contouring and scored image quality and confidence in contouring. RESULTS:: There is good agreement when comparing radiographer contours to the gold-standard for all three imaging types with Dice similarity co-efficient 0.91-0.94, Cohen's κ 0.85-0.91, Hausdorff distance 4.6-7.6 mm and mean distance between contours 0.9-1.2 mm. In addition, there is good concordance between radiographers across all imaging modalities. Both T2W and T2*W MRI show reduced interobserver variability and improved accuracy compared to CT, this was statistically significant for T2*W imaging compared to CT across all four comparison metrics. Comparing MRI sequences reveals significantly reduced interobserver variability and significantly improved accuracy on T2*W compared to T2W MRI for DSC and Cohen's κ. Both MRI sequences scored significantly higher compared to CT for image quality and confidence in contouring, particularly T2*W. This was also reflected in the shorter time for contouring, measuring 15.4, 9.6 and 9.8 min for CT, T2W and T2*W MRI respectively. Conclusion: Therapeutic radiographer prostate contours are more accurate, show less interobserver variability and are more confidently and quickly outlined on MRI compared to CT, particularly using T2*W MRI. Advances in knowledge: Our work is relevant for MRI sequence choice and development of the roles of the interprofessional team in the advancement of MRI-guided radiotherapy..
Pathmanathan, A.U.
Schmidt, M.A.
Brand, D.H.
Kousi, E.
van As, N.J.
Tree, A.C.
(2019). Improving fiducial and prostate capsule visualization for radiotherapy planning using MRI. J appl clin med phys,
Vol.20
(3),
pp. 27-36.
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BACKGROUND AND PURPOSE: Intraprostatic fiducial markers (FM) improve the accuracy of radiotherapy (RT) delivery. Here we assess geometric integrity and contouring consistency using a T2*-weighted (T2*W) sequence alone, which allows visualization of the FM. MATERIAL AND METHODS: Ten patients scanned within the Prostate Advances in Comparative Evidence (PACE) trial (NCT01584258) had prostate images acquired with computed tomography (CT) and Magnetic Resonance (MR) Imaging: T2-weighted (T2W) and T2*W sequences. The prostate was contoured independently on each imaging dataset by three clinicians. Interobserver variability was assessed using comparison indices with Monaco ADMIRE (research version 2.0, Elekta AB) and examined for statistical differences between imaging sets. CT and MR images of two test objects were acquired to assess geometric distortion and accuracy of marker positioning. The first was a linear test object comprising straight tubes in three orthogonal directions, the second was a smaller test object with markers suspended in gel. RESULTS: Interobserver variability for prostate contouring was lower for both T2W and T2*W compared to CT, this was statistically significant when comparing CT and T2*W images. All markers are visible in T2*W images with 29/30 correctly identified, only 3/30 are visible in T2W images. Assessment of geometric distortion revealed in-plane displacements were under 0.375 mm in MRI, and through plane displacements could not be detected. The signal loss in the MR images is symmetric in relation to the true marker position shown in CT images. CONCLUSION: Prostate T2*W images are geometrically accurate, and yield consistent prostate contours. This single sequence can be used to identify FM and for prostate delineation in a mixed MR-CT workflow..
Brand, D.H.
Tree, A.C.
Ostler, P.
van der Voet, H.
Loblaw, A.
Chu, W.
Ford, D.
Tolan, S.
Jain, S.
Martin, A.
Staffurth, J.
Camilleri, P.
Kancherla, K.
Frew, J.
Chan, A.
Dayes, I.S.
Henderson, D.
Brown, S.
Cruickshank, C.
Burnett, S.
Duffton, A.
Griffin, C.
Hinder, V.
Morrison, K.
Naismith, O.
Hall, E.
van As, N.
PACE Trial Investigators,
(2019). Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet oncol,
Vol.20
(11),
pp. 1531-1543.
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BACKGROUND: Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer. METHODS: PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing. FINDINGS: Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred. INTERPRETATION: Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity. FUNDING: Accuray and National Institute of Health Research..
De Bleser, E.
Jereczek-Fossa, B.A.
Pasquier, D.
Zilli, T.
Van As, N.
Siva, S.
Fodor, A.
Dirix, P.
Gomez-Iturriaga, A.
Trippa, F.
Detti, B.
Ingrosso, G.
Triggiani, L.
Bruni, A.
Alongi, F.
Reynders, D.
De Meerleer, G.
Surgo, A.
Loukili, K.
Miralbell, R.
Silva, P.
Chander, S.
Di Muzio, N.G.
Maranzano, E.
Francolini, G.
Lancia, A.
Tree, A.
Deantoni, C.L.
Ponti, E.
Marvaso, G.
Goetghebeur, E.
Ost, P.
(2019). Metastasis-directed Therapy in Treating Nodal Oligorecurrent Prostate Cancer: A Multi-institutional Analysis Comparing the Outcome and Toxicity of Stereotactic Body Radiotherapy and Elective Nodal Radiotherapy. Eur urol,
Vol.76
(6),
pp. 732-739.
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BACKGROUND: Stereotactic body radiotherapy (SBRT) and elective nodal radiotherapy (ENRT) are being investigated as metastasis-directed treatments in oligorecurrent prostate cancer (PC); however, comparative data are still lacking. OBJECTIVE: To compare outcome and toxicity between both treatments. Primary endpoint was metastasis-free survival, adjusted for selected variables (aMFS). DESIGN, SETTING, AND PARTICIPANTS: This was a multi-institutional, retrospective analysis of 506 (SBRT: 309, ENRT: 197) patients with hormone-sensitive nodal oligorecurrent PC (five or fewer lymph nodes (LNs; N1/M1a), treated between 2004 and 2017. Median follow-up was 36 mo (interquartile range 23-56). INTERVENTION: SBRT was defined as a minimum of 5 Gy per fraction to each lesion with a maximum of 10 fractions. ENRT was defined as a minimum dose of 45 Gy in up to 25 fractions to the elective nodes, with or without a simultaneous boost to the suspicious node(s). The choice of radiotherapy (RT) was at the discretion of the treating physician, with treatments being unbalanced over the centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In total, 506 patients from 15 different treatment centers were included. Primary treatment was radical prostatectomy, RT, or their combination. Nodal recurrences were detected by positron emission tomography/computer tomography (97%) or conventional imaging (3%). Descriptive statistics was used to summarize patient characteristics. RESULTS AND LIMITATIONS: ENRT was associated with fewer nodal recurrences compared with SBRT (p < 0.001). In a multivariable analysis, patients with one LN at recurrence had longer aMFS after ENRT (hazard ratio: 0.50, 95% confidence interval 0.30-0.85, p = 0.009). Late toxicity was higher after ENRT compared with that after SBRT (16% vs. 5%, p < 0.01). Limitations include higher use of hormone therapy in the ENRT cohort and nonstandardized follow-up. CONCLUSIONS: ENRT reduces the number of nodal recurrences as compared with SBRT, however at higher toxicity. Our findings hypothesize that ENRT should be preferred to SBRT in the treatment of nodal oligorecurrences. This hypothesis needs to be evaluated in a randomized trial. PATIENT SUMMARY: This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal radiotherapy might be the preferred treatment..
Brand, D.H.
Parker, J.I.
Dearnaley, D.P.
Eeles, R.
Huddart, R.
Khoo, V.
Murray, J.
Suh, Y.-.
Tree, A.C.
van As, N.
Parker, C.
(2019). Patterns of recurrence after prostate bed radiotherapy. Radiother oncol,
Vol.141,
pp. 174-180.
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BACKGROUND AND PURPOSE: Prostate bed radiotherapy is a standard treatment after radical prostatectomy. Recent evidence suggests that, for patients with a PSA > 0.34 ng/ml, the radiotherapy treatment volume should include not only the prostate bed but also the pelvic lymph nodes. We describe the patterns of failure after prostate bed radiotherapy, focussing on the proportion of patients with radiologically confirmed pelvic nodal failure only, in the absence of distant disease. MATERIALS AND METHODS: Patients included were men receiving prostate bed radiotherapy at the Royal Marsden Hospital between 1997 and 2013. The key outcome of interest was the pattern of radiologic failure after prostate bed radiotherapy. Baseline characteristics of patients experiencing pelvic nodal failure without distant disease were compared versus all other relapse patterns. Comparisons were by Chi-square test, with multiple testing adjusted p < 0.005 significant. RESULTS: 140 of 322 patients developed biochemical failure after salvage RT. Radiologic failure occurred in 89 patients. 35 of the 89 patients (39%) with radiologic failure had pelvic nodal failure without distant disease, with no significant differences in baseline characteristics when compared to all other patients. The rate of pelvic nodal failure was the same for patients with PSA above or below 0.34 ng/ml (16/149, 95% CI = 6-17% vs 19/171, 95% CI = 7-17%). CONCLUSIONS: Pelvic lymph node disease, without more distant disease, is a common site of failure in men receiving radiotherapy to the prostate bed, including those with PSA < 0.34 ng/ml. This observation informs the case for including the pelvic lymph nodes in the radiotherapy treatment volume..
Patel, P.H.
Chaw, C.L.
Tree, A.C.
Sharabiani, M.
van As, N.J.
(2019). Stereotactic body radiotherapy for bone oligometastatic disease in prostate cancer. World j urol,
Vol.37
(12),
pp. 2615-2621.
show abstract
PURPOSE: There are sparse data describing outcomes of bone-only oligometastatic prostate cancer in comparison with lymph node disease treated with stereotactic body radiotherapy (SBRT). The primary aim of this study was to report progression-free survival (PFS) data for patients with bone-only disease. Influence of hormone sensitivity and androgen deprivation therapy use was also assessed. METHODS: This is a single-centre retrospective cohort study. Hormone-sensitive and castrate-resistant patients with oligometastatic (≤ 3) bone-only prostate cancer treated with SBRT were included. Data were collected using electronic records. Kaplan-Meier survivor function, log rank test, as well as Cox regression were used to calculate PFS and overall survival. RESULTS: In total, 51 patients with 64 bone metastases treated with SBRT were included. Nine patients were castrate resistant and 42 patient's hormone sensitive at the time of SBRT. Median follow-up was 23 months. Median PFS was 24 months in hormone-sensitive patients and 3 months in castrate-resistant patients. No patients experienced grade 3 or 4 toxicities. There were three in-field recurrences. CONCLUSIONS: In this study, patients with bone oligometastatic disease showed potential benefit from SBRT with a median PFS of 11 months. Hormone-sensitive patients showed the greatest benefit, with results similar to that published for oligometastatic pelvic nodal disease treated with SBRT. Prospective randomised control trials are needed to determine the survival benefit of SBRT in oligometastatic bone-only prostate cancer and to determine prognostic indicators..
Kothari, G.
Ost, P.
Cheung, P.
Blanchard, P.
Tree, A.C.
van As, N.J.
Lo, S.S.
Moghanaki, D.
Loblaw, A.
Siva, S.
(2019). Trends in Management of Oligometastatic Hormone-Sensitive Prostate Cancer. Curr oncol rep,
Vol.21
(5),
p. 43.
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PURPOSE OF REVIEW: Systemic therapy for patients with hormone-sensitive oligometastatic prostate cancer is non-curative and associated with toxicities. Meanwhile, this population presents unique clinical opportunities to improve outcomes, including the demonstrated benefits of radiotherapy to the primary tumor or oligometastatic sites. RECENT FINDINGS: Recently published randomized studies have demonstrated benefits with the addition of radiotherapy to the primary disease or metastatic lesions in patients with synchronous or metachronous disease. The introduction of novel PET imaging has improved the sensitivity and specificity for detecting metastatic disease and provides an opportunity to better select patients who will benefit from local therapy. The data presented in this review supports revisiting practice guidelines for patients with hormone-sensitive metastatic prostate cancer, particularly in relation to the role of radiotherapy to the primary tumor and sites of oligometastatic disease. Future trials will aim to further establish the role of metastasis-directed therapies in metachronous, synchronous, and castrate-resistant disease..
Hanna, G.G.
Murray, L.
Patel, R.
Jain, S.
Aitken, K.L.
Franks, K.N.
van As, N.
Tree, A.
Hatfield, P.
Harrow, S.
McDonald, F.
Ahmed, M.
Saran, F.H.
Webster, G.J.
Khoo, V.
Landau, D.
Eaton, D.J.
Hawkins, M.A.
(2018). UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clin oncol (r coll radiol),
Vol.30
(1),
pp. 5-14.
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Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally..
Pathmanathan, A.U.
van As, N.J.
Kerkmeijer, L.G.
Christodouleas, J.
Lawton, C.A.
Vesprini, D.
van der Heide, U.A.
Frank, S.J.
Nill, S.
Oelfke, U.
van Herk, M.
Li, X.A.
Mittauer, K.
Ritter, M.
Choudhury, A.
Tree, A.C.
(2018). Magnetic Resonance Imaging-Guided Adaptive Radiation Therapy: A "Game Changer" for Prostate Treatment?. Int j radiat oncol biol phys,
Vol.100
(2),
pp. 361-373.
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Radiation therapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated α/β ratio, a larger dose per fraction would be beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator allows for accurate soft tissue tracking with the capacity to replan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MRI-only workflow, and real-time adaptive planning. The present report reviews the steps involved in hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the challenges for implementation..
Kothari, G.
Loblaw, A.
Tree, A.C.
van As, N.J.
Moghanaki, D.
Lo, S.S.
Ost, P.
Siva, S.
(2018). Stereotactic Body Radiotherapy for Primary Prostate Cancer. Technol cancer res treat,
Vol.17,
p. 1533033818789633.
show abstract
Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low α/β ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low- to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come..
Henderson, D.R.
Tree, A.C.
Harrington, K.J.
van As, N.J.
(2018). Dosimetric Implications of Computerised Tomography-Only versus Magnetic Resonance-Fusion Contouring in Stereotactic Body Radiotherapy for Prostate Cancer. Medicines (basel),
Vol.5
(2).
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Background: Magnetic resonance (MR)-fusion contouring is the standard of care in prostate stereotactic body radiotherapy (SBRT) for target volume localisation. However, the planning computerised tomography (CT) scan continues to be used for dose calculation and treatment planning and verification. Discrepancies between the planning MR and CT scans may negate the benefits of MR-fusion contouring and it adds a significant resource burden. We aimed to determine whether CT-only contouring resulted in a dosimetric detriment compared with MR-fusion contouring in prostate SBRT planning. Methods: We retrospectively compared target volumes and SBRT plans for 20 patients treated clinically with MR-fusion contouring (standard of care) with those produced by re-contouring using CT data only. Dose was 36.25 Gy in 5 fractions. CT-only contouring was done on two occasions blind to MR data and reviewed by a separate observer. Primary outcome was the difference in rectal volume receiving 36 Gy or above. Results: Absolute target volumes were similar: 63.5 cc (SD ± 27.9) versus 63.2 (SD ± 26.5), Dice coefficient 0.86 (SD ± 0.04). Mean difference in apex superior-inferior position was 1.1 (SD ± 3.5; CI: −0.4–2.6). Small dosimetric differences in favour of CT-only contours were seen, with the mean rectal V36 Gy 0.3 cc (95% CI: 0.1–0.5) lower for CT-only contouring. Conclusions: Prostate SBRT can be successfully planned without MR-fusion contouring. Consideration can be given to omitting MR-fusion from the prostate SBRT workflow, provided reference to diagnostic MR imaging is available. Development of MR-only work flow is a key research priority to gain access to the anatomical fidelity of MR imaging..
Wedge, D.C.
Gundem, G.
Mitchell, T.
Woodcock, D.J.
Martincorena, I.
Ghori, M.
Zamora, J.
Butler, A.
Whitaker, H.
Kote-Jarai, Z.
Alexandrov, L.B.
Van Loo, P.
Massie, C.E.
Dentro, S.
Warren, A.Y.
Verrill, C.
Berney, D.M.
Dennis, N.
Merson, S.
Hawkins, S.
Howat, W.
Lu, Y.-.
Lambert, A.
Kay, J.
Kremeyer, B.
Karaszi, K.
Luxton, H.
Camacho, N.
Marsden, L.
Edwards, S.
Matthews, L.
Bo, V.
Leongamornlert, D.
McLaren, S.
Ng, A.
Yu, Y.
Zhang, H.
Dadaev, T.
Thomas, S.
Easton, D.F.
Ahmed, M.
Bancroft, E.
Fisher, C.
Livni, N.
Nicol, D.
Tavaré, S.
Gill, P.
Greenman, C.
Khoo, V.
Van As, N.
Kumar, P.
Ogden, C.
Cahill, D.
Thompson, A.
Mayer, E.
Rowe, E.
Dudderidge, T.
Gnanapragasam, V.
Shah, N.C.
Raine, K.
Jones, D.
Menzies, A.
Stebbings, L.
Teague, J.
Hazell, S.
Corbishley, C.
CAMCAP Study Group,
de Bono, J.
Attard, G.
Isaacs, W.
Visakorpi, T.
Fraser, M.
Boutros, P.C.
Bristow, R.G.
Workman, P.
Sander, C.
TCGA Consortium,
Hamdy, F.C.
Futreal, A.
McDermott, U.
Al-Lazikani, B.
Lynch, A.G.
Bova, G.S.
Foster, C.S.
Brewer, D.S.
Neal, D.E.
Cooper, C.S.
Eeles, R.A.
(2018). Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets. Nat genet,
Vol.50
(5),
pp. 682-692.
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Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials..
Henderson, D.R.
Murray, J.R.
Gulliford, S.L.
Tree, A.C.
Harrington, K.J.
Van As, N.J.
(2018). An Investigation of Dosimetric Correlates of Acute Toxicity in Prostate Stereotactic Body Radiotherapy: Dose to Urinary Trigone is Associated with Acute Urinary Toxicity. Clin oncol (r coll radiol),
Vol.30
(9),
pp. 539-547.
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full text
AIMS: There are limited data on dosimetric correlates of toxicity in stereotactic body radiotherapy (SBRT) for prostate cancer. We aimed to identify potential relationships between dose and toxicity using conventional dose-volume histograms (DVHs) and dose-surface maps (DSMs). MATERIALS AND METHODS: Urinary bladder trigone and rectum DSMs were produced for a single-institution service evaluation cohort of 50 patients receiving SBRT for localised prostate cancer, together with conventional DVHs for bladder and rectum. Patients had been prospectively recruited to this cohort and treated according to a pre-defined protocol to a dose of 36.25 Gy in five fractions. Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) toxicity data were recorded prospectively. Logistic regression was used to identify dosimetric predictors of acute IPSS+10 (rise of 10 points or more above baseline) and grade 2+ RTOG toxicity. RESULTS: On univariate analysis, trigone area receiving 40 Gy and trigone Dmax were associated with IPSS+10 (odds ratio 1.06 [1.02-1.11], P = 0.007 and odds ratio 1.54 [1.06-2.25], P = 0.024, respectively). These two variables were highly correlated. In a multivariate model, including all baseline variables, trigone Dmax remained associated with IPSS+10 (odds ratio 1.91 [1.13-3.22], P = 0.016). These findings were not significant with Holm-Bonferroni correction for multiple testing (corrected P value threshold 0.006). No associations were seen between rectal toxicity and DVH or DSM parameters. CONCLUSIONS: Our study suggests a potential relationship between high doses to the urinary bladder trigone and patient-reported urinary toxicity in prostate SBRT, and is consistent with previous studies in conventionally fractionated radiotherapy, justifying further evaluation in larger cohorts..
Binzel, K.
Adelaja, A.
Wright, C.L.
Scharre, D.
Zhang, J.
Knopp, M.V.
Teoh, E.J.
Bottomley, D.
Scarsbrook, A.
Payne, H.
Afaq, A.
Bomanji, J.
van As, N.
Chua, S.
Hoskin, P.
Chambers, A.
Cook, G.J.
Warbey, V.S.
Chau, A.
Ward, P.
Miller, M.P.
Stevens, D.J.
Wilson, L.
Gleeson, F.V.
Scheidhauer, K.
Seidl, C.
Autenrieth, M.
Bruchertseifer, F.
Apostolidis, C.
Kurtz, F.
Horn, T.
Pfob, C.
Schwaiger, M.
Gschwend, J.
D'Alessandria, C.
Morgenstern, A.
Uprimny, C.
Kroiss, A.
Decristoforo, C.
von Guggenberg, E.
Nilica, B.
Horninger, W.
Virgolini, I.
Rasul, S.
Poetsch, N.
Woehrer, A.
Preusser, M.
Mitterhauser, M.
Wadsak, W.
Widhalm, G.
Mischkulnig, M.
Hacker, M.
Traub-Weidinger, T.
Wright, C.L.
Binzel, K.
Wuthrick, E.J.
Miller, E.D.
Maniawski, P.
Zhang, J.
Knopp, M.V.
Rep, S.
Hocevar, M.
Vaupotic, J.
Zdesar, U.
Zaletel, K.
Lezaic, L.
Mairinger, S.
Filip, T.
Sauberer, M.
Flunkert, S.
Wanek, T.
Stanek, J.
Okamura, N.
Langer, O.
Kuntner, C.
Fornito, M.C.
Balzano, R.
Di Martino, V.
Cacciaguerra, S.
Russo, G.
Seifert, D.
Kleinova, M.
Cepa, A.
Ralis, J.
Hanc, P.
Lebeda, O.
Mosa, M.
Vandenberghe, S.
Mikhaylova, E.
Borys, D.
Viswanath, V.
Stockhoff, M.
Efthimiou, N.
Caribe, P.
Van Holen, R.
Karp, J.S.
Binzel, K.
Zhang, J.
Wright, C.L.
Maniawski, P.
Knopp, M.V.
Haller, P.M.
Farhan, C.
Piackova, E.
Jäger, B.
Knoll, P.
Kiss, A.
Podesser, B.K.
Wojta, J.
Huber, K.
Mirzaei, S.
Traxl, A.
Komposch, K.
Glitzner, E.
Wanek, T.
Mairinger, S.
Sibilia, M.
Langer, O.
Fornito, M.C.
Russello, M.
Russo, G.
Balzano, R.
Sorko, S.
Gallowitsch, H.J.
Kohlfuerst, S.
Matschnig, S.
Rieser, M.
Sorschag, M.
Lind, P.
Ležaič, L.
Rep, S.
Žibert, J.
Frelih, N.
Šuštar, S.
Binzel, K.
Adelaja, A.
Wright, C.L.
Scharre, D.
Zhang, J.
Knopp, M.V.
Baum, R.P.
Langbein, T.
Singh, A.
Shahinfar, M.
Schuchardt, C.
Volk, G.F.
Kulkarni, H.R.
Fornito, M.C.
Cacciaguerra, S.
Balzano, R.
Di Martino, G.V.
Russo, G.
Thomson, W.H.
Kudlacek, M.
Karik, M.
Farhan, C.
Rieger, H.
Pokieser, W.
Glaser, K.
Mirzaei, S.
Petz, V.
Tugendsam, C.
Buchinger, W.
Schmoll-Hauer, B.
Schenk, I.P.
Rudolph, K.
Krebs, M.
Zettinig, G.
Zoufal, V.
Wanek, T.
Krohn, M.
Mairinger, S.
Stanek, J.
Sauberer, M.
Filip, T.
Pahnke, J.
Langer, O.
Weitzer, F.
Pernthaler, B.
Salamon, S.
Aigner, R.
Koranda, P.
Henzlová, L.
Kamínek, M.
Váchalová, M.
Bachleda, P.
Summer, D.
Garousi, J.
Oroujeni, M.
Mitran, B.
Andersson, K.G.
Vorobyeva, A.
Löfblom, J.N.
Orlova, A.
Tolmachev, V.
Decristoforo, C.
Kaeopookum, P.
Summer, D.
Orasch, T.
Lechner, B.
Petrik, M.
Novy, Z.
Rangger, C.
Haas, H.
Decristoforo, C.
(2018). Abstracts of the 33rd International Austrian Winter Symposium : Zell am See, Austria 24-27 January 2018. Ejnmmi res,
Vol.8
(Suppl 1),
p. 5.
Reis Ferreira, M.
Khan, A.
Thomas, K.
Truelove, L.
McNair, H.
Gao, A.
Parker, C.C.
Huddart, R.
Bidmead, M.
Eeles, R.
Khoo, V.
van As, N.J.
Hansen, V.N.
Dearnaley, D.P.
(2017). Phase 1/2 Dose-Escalation Study of the Use of Intensity Modulated Radiation Therapy to Treat the Prostate and Pelvic Nodes in Patients With Prostate Cancer. Int j radiat oncol biol phys,
Vol.99
(5),
pp. 1234-1242.
show abstract
full text
PURPOSE: To investigate the feasibility of dose escalation and hypofractionation of pelvic lymph node intensity modulated radiation therapy (PLN-IMRT) in prostate cancer (PCa). METHODS AND MATERIALS: In a phase 1/2 study, patients with advanced localized PCa were sequentially treated with 70 to 74 Gy to the prostate and dose-escalating PLN-IMRT at doses of 50 Gy (cohort 1), 55 Gy (cohort 2), and 60 Gy (cohort 3) in 35 to 37 fractions. Two hypofractionated cohorts received 60 Gy to the prostate and 47 Gy to PLN in 20 fractions over 4 weeks (cohort 4) and 5 weeks (cohort 5). All patients received long-course androgen deprivation therapy. Primary outcome was late Radiation Therapy Oncology Group toxicity at 2 years after radiation therapy for all cohorts. Secondary outcomes were acute and late toxicity using other clinician/patient-reported instruments and treatment efficacy. RESULTS: Between August 9, 2000, and June 9, 2010, 447 patients were enrolled. Median follow-up was 90 months. The 2-year rates of grade 2+ bowel/bladder toxicity were as follows: cohort 1, 8.3%/4.2% (95% confidence interval 2.2%-29.4%/0.6%-26.1%); cohort 2, 8.9%/5.9% (4.1%-18.7%/2.3%-15.0%); cohort 3, 13.2%/2.9% (8.6%-20.2%/1.1%-7.7%); cohort 4, 16.4%/4.8% (9.2%-28.4%/1.6%-14.3%); cohort 5, 12.2%/7.3% (7.6%-19.5%/3.9%-13.6%). Prevalence of bowel and bladder toxicity seemed to be stable over time. Other scales mirrored these results. The biochemical/clinical failure-free rate was 71% (66%-75%) at 5 years for the whole group, with pelvic lymph node control in 94% of patients. CONCLUSIONS: This study shows the safety and tolerability of PLN-IMRT. Ongoing and planned phase 3 studies will need to demonstrate an increase in efficacy using PLN-IMRT to offset the small increase in bowel side effects compared with prostate-only IMRT..
de Morrée, E.S.
Vogelzang, N.J.
Petrylak, D.P.
Budnik, N.
Wiechno, P.J.
Sternberg, C.N.
Doner, K.
Bellmunt, J.
Burke, J.M.
Ochoa de Olza, M.
Choudhury, A.
Gschwend, J.E.
Kopyltsov, E.
Flechon, A.
van As, N.
Houede, N.
Barton, D.
Fandi, A.
Jungnelius, U.
Li, S.
Li, J.S.
de Wit, R.
(2017). Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study. Jama oncol,
Vol.3
(1),
pp. 68-75.
show abstract
full text
IMPORTANCE: The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles. OBJECTIVE: To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial. DESIGN, SETTING, AND PARTICIPANTS: The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors. MAIN OUTCOMES AND MEASURES: Total number of docetaxel cycles delivered as an independent factor for OS. RESULTS: Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P < .001), irrespective of lenalidomide treatment (HR, 1.060; 95% CI, 0.924-1.215; P = .41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest that continuation of docetaxel chemotherapy contributes to the survival benefit. Prospective validation is warranted..
Wedlake, L.
Shaw, C.
McNair, H.
Lalji, A.
Mohammed, K.
Klopper, T.
Allan, L.
Tait, D.
Hawkins, M.
Somaiah, N.
Lalondrelle, S.
Taylor, A.
VanAs, N.
Stewart, A.
Essapen, S.
Gage, H.
Whelan, K.
Andreyev, H.J.
(2017). Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy. Am j clin nutr,
Vol.106
(3),
pp. 849-857.
show abstract
full text
Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.Design: Patients were randomly assigned to low-fiber [≤10 g nonstarch polysaccharide (NSP)/d], habitual-fiber (control), or high-fiber (≥18 g NSP/d) diets and received individualized counseling at the start of radiotherapy to achieve these targets. The primary endpoint was the difference between groups in the change in the Inflammatory Bowel Disease Questionnaire-Bowel Subset (IBDQ-B) score between the starting and nadir (worst) score during treatment. Other measures included macronutrient intake, stool diaries, and fecal short-chain fatty acid concentrations.Results: Patients were randomly assigned to low-fiber (n = 55), habitual-fiber (n = 55), or high-fiber (n = 56) dietary advice. Fiber intakes were significantly different between groups (P < 0.001). The difference between groups in the change in IBDQ-B scores between the start and nadir was not significant (P = 0.093). However, the change in score between the start and end of radiotherapy was smaller in the high-fiber group (mean ± SD: -3.7 ± 12.8) than in the habitual-fiber group (-10.8 ± 13.5; P = 0.011). At 1-y postradiotherapy (n = 126) the difference in IBDQ-B scores between the high-fiber (+0.1 ± 14.5) and the habitual-fiber (-8.4 ± 13.3) groups was significant (P = 0.004). No significant differences were observed in stool frequency or form or in short-chain fatty acid concentrations. Significant reductions in energy, protein, and fat intake occurred in the low- and habitual-fiber groups only.Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal toxicity both acutely and at 1 y compared with habitual-fiber intake. Restrictive, non-evidence-based advice to reduce fiber intake in this setting should be abandoned. This trial was registered at clinicaltrials.gov as NCT 01170299..
Bianchini, D.
Lorente, D.
Rescigno, P.
Zafeiriou, Z.
Psychopaida, E.
O'Sullivan, H.
Alaras, M.
Kolinsky, M.
Sumanasuriya, S.
Sousa Fontes, M.
Mateo, J.
Perez Lopez, R.
Tunariu, N.
Fotiadis, N.
Kumar, P.
Tree, A.
Van As, N.
Khoo, V.
Parker, C.
Eeles, R.
Thompson, A.
Dearnaley, D.
de Bono, J.S.
(2017). Effect on Overall Survival of Locoregional Treatment in a Cohort of De Novo Metastatic Prostate Cancer Patients: A Single Institution Retrospective Analysis From the Royal Marsden Hospital. Clin genitourin cancer,
Vol.15
(5),
pp. e801-e807.
show abstract
full text
BACKGROUND: The optimal management of the primary tumor in metastatic at diagnosis (M1) prostate cancer (PCa) patients is not yet established. We retrospectively evaluated the effect of locoregional treatment (LRT) on overall survival (OS) hypothesizing that this could improve outcome through better local disease control and the induction of an antitumor immune response (abscopal effect). PATIENTS AND METHODS: M1 at diagnosis PCa patients referred to the Prostate Targeted Therapy Group at the Royal Marsden between June 2003 and December 2013 were identified. LRT was defined as either surgery, radiotherapy (RT) or transurethral prostatectomy (TURP) administered to the primary tumor at any time point from diagnosis to death. Kaplan-Meier analyses generated OS data. The association between LRT and OS was evaluated in univariate (UV) and multivariate (MV) Cox regression models. RESULTS: Overall 300 patients were identified; 192 patients (64%) experienced local symptoms at some point during their disease course; 72 patients received LRT (56.9% TURP, 52.7% RT). None of the patients were treated with prostatectomy. LRT was more frequently performed in patients with low volume disease (35.4% vs. 16.2%; P < .001), lower prostate-specific antigen (PSA) level at diagnosis (median PSA: 75 vs. 184 ng/mL; P = .005) and local symptoms (34.2% vs. 4.8%; P < .001). LRT was associated in UV and MV analysis with longer OS (62.1 vs. 55.8 months; hazard ratio [HR], 0.74; P = .044), which remained significant for RT (69.4 vs. 55.1 months; HR, 0.54; P = .002) but not for TURP. RT was associated with better OS independent of disease volume at diagnosis. CONCLUSION: These data support the conduct of randomized phase III trials to evaluate the benefit of local control in patients with M1 disease at diagnosis..
Patrikidou, A.
Uccello, M.
Tree, A.
Parker, C.
Attard, G.
Eeles, R.
Khoo, V.
van As, N.
Huddart, R.
Dearnaley, D.
Reid, A.
(2017). Upfront Docetaxel in the Post-STAMPEDE World: Lessons from an Early Evaluation of Non-trial Usage in Hormone-Sensitive Prostate Cancer. Clin oncol (r coll radiol),
Vol.29
(10),
pp. e174-e175.
full text
Ost, P.
Jereczek-Fossa, B.A.
As, N.V.
Zilli, T.
Muacevic, A.
Olivier, K.
Henderson, D.
Casamassima, F.
Orecchia, R.
Surgo, A.
Brown, L.
Tree, A.
Miralbell, R.
De Meerleer, G.
(2016). Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis. Eur urol,
Vol.69
(1),
pp. 9-12.
show abstract
UNLABELLED: The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. PATIENT SUMMARY: This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival..
Henderson, D.R.
Murray, J.R.
Tree, A.C.
Riley, U.
Rosenfelder, N.A.
Murray, D.
Khoo, V.S.
van As, N.J.
(2016). Targeted Antibiotic Prophylaxis for Transrectal Fiducial Marker Insertion for Prostate Radiotherapy. Clin oncol (r coll radiol),
Vol.28
(3),
pp. 226-227.
Henderson, D.R.
de Souza, N.M.
Thomas, K.
Riches, S.F.
Morgan, V.A.
Sohaib, S.A.
Dearnaley, D.P.
Parker, C.C.
van As, N.J.
(2016). Nine-year Follow-up for a Study of Diffusion-weighted Magnetic Resonance Imaging in a Prospective Prostate Cancer Active Surveillance Cohort. Eur urol,
Vol.69
(6),
pp. 1028-1033.
show abstract
full text
BACKGROUND: In active surveillance (AS) for prostate cancer there are few data on long-term outcomes associated with novel imaging markers. OBJECTIVE: To determine long-term outcomes with respect to the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (DW-MRI) in a prospective AS cohort. Early results have already been published; we now present findings with long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS: A subset of patients (n=86) underwent pre-enrolment DW-MRI in a prospective AS study between 2002 and 2006. Inclusion criteria were untreated prostate cancer, clinical T1/T2a/N0M0, Gleason ≤ 3+4, and prostate-specific antigen (PSA) <15 ng/ml. Protocol follow-up was by biopsy at 18-24 mo and then every 24 mo, with regular PSA measurement. INTERVENTION: Men underwent baseline DW-MRI in addition to standard sequences. ADC was measured from the index lesion on T2-weighted images. To avoid influencing treatment decisions, DW-MRI sequence results were not available to the AS study investigators. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline ADC was analysed with respect to time to radical treatment (TRT) and time to adverse histology (TAH). Kaplan-Meier analysis and univariate and multivariate regression analyses were performed. RESULTS AND LIMITATIONS: The median follow-up was 9.5 yr (interquartile range 7.9-10.0 yr). On univariate analysis, ADC below the median was associated with shorter TAH (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.17-3.89; p<0.014) and TRT (HR 2.54, 95% CI 1.49-4.32; p<0.001). Median TRT was 9.3 yr (95% CI 7.0-11.6 yr) for patients with ADC above the median and only 2.4 yr (95% CI 1.5-6.0 yr) for ADC below the median. For TRT, addition of ADC to a multivariate model of baseline variables resulted in a significant improvement in model fit (HR 1.33, 95% CI 1.14-1.54; p<0.001). Receiver operating characteristic analysis for TRT revealed an area under the curve of 0.80 (95% CI 0.70-0.88). The number of variables included in the multivariate model was limited by sample size. CONCLUSIONS: Long-term follow-up for this study provides strong evidence that ADC is a useful marker when selecting patients for AS. Routine DW-MRI is now being evaluated in our ongoing AS study for initial assessment and as an alternative to repeat biopsy. PATIENT SUMMARY: Before entering a study of close monitoring for the initial management of prostate cancer, patients had a type of magnetic resonance imaging scan that looks at the movement of water within cancers. These scans may help in predicting whether patients should receive close monitoring or whether immediate treatment should be given..
Henderson, D.R.
de Souza, N.M.
Parker, C.C.
van As, N.J.
(2016). Reply from Authors re: Tillmann Loch, Pat Fox Fulgham Active Surveillance Challenges in Men with Prostate Cancer: Role of Imaging Today and Tomorrow Eur Urol 2016;69:1034-6: Imaging in Active Surveillance for Prostate Cancer: Where Should We Focus Our Research?. Eur urol,
Vol.69
(6),
p. 1037.
full text
McPartlin, A.J.
Li, X.A.
Kershaw, L.E.
Heide, U.
Kerkmeijer, L.
Lawton, C.
Mahmood, U.
Pos, F.
van As, N.
van Herk, M.
Vesprini, D.
van der Voort van Zyp, J.
Tree, A.
Choudhury, A.
MR-Linac consortium,
(2016). MRI-guided prostate adaptive radiotherapy - A systematic review. Radiother oncol,
Vol.119
(3),
pp. 371-380.
show abstract
full text
Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed..
Ost, P.
Jereczek-Fossa, B.A.
Van As, N.
Zilli, T.
Tree, A.
Henderson, D.
Orecchia, R.
Casamassima, F.
Surgo, A.
Miralbell, R.
De Meerleer, G.
(2016). Pattern of Progression after Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Nodal Recurrences. Clin oncol (r coll radiol),
Vol.28
(9),
pp. e115-e120.
show abstract
full text
AIMS: To report the relapse pattern of stereotactic body radiotherapy (SBRT) for oligorecurrent nodal prostate cancer (PCa). MATERIALS AND METHODS: PCa patients with ≤3 lymph nodes (N1/M1a) at the time of recurrence were treated with SBRT. SBRT was defined as a radiotherapy dose of at least 5 Gy per fraction to a biological effective dose of at least 80 Gy to all metastatic sites. Distant progression-free survival was defined as the time interval between the first day of SBRT and appearance of new metastatic lesions, outside the high-dose region. Relapses after SBRT were recorded and compared with the initially treated site. Secondary end points were local control, time to palliative androgen deprivation therapy and toxicity scored using the Common Terminology Criteria for Adverse Events v4.0. RESULTS: Overall, 89 metastases were treated in 72 patients. The median distant progression-free survival was 21 months (95% confidence interval 16-25 months) with 88% of patients having ≤3 metastases at the time of progression. The median time from first SBRT to the start of palliative androgen deprivation therapy was 44 months (95% confidence interval 17-70 months). Most relapses (68%) occurred in nodal regions. Relapses after pelvic nodal SBRT (n = 36) were located in the pelvis (n = 14), retroperitoneum (n = 1), pelvis and retroperitoneum (n = 8) or in non-nodal regions (n = 13). Relapses after SBRT for extrapelvic nodes (n = 5) were located in the pelvis (n = 1) or the pelvis and retroperitoneum (n = 4). Late grade 1 and 2 toxicity was observed in 17% (n = 12) and 4% of patients (n = 3). CONCLUSION: SBRT for oligometastatic PCa nodal recurrences is safe. Most subsequent relapses are again nodal and oligometastatic..
White, I.D.
Wilson, J.
Aslet, P.
Baxter, A.B.
Birtle, A.
Challacombe, B.
Coe, J.
Grover, L.
Payne, H.
Russell, S.
Sangar, V.
Van As, N.
Kirby, M.
(2015). Development of UK guidance on the management of erectile dysfunction resulting from radical radiotherapy and androgen deprivation therapy for prostate cancer. Int j clin pract,
Vol.69
(1),
pp. 106-123.
show abstract
full text
AIM: To develop a management strategy (rehabilitation programme) for erectile dysfunction (ED) after radiotherapy (RT) or androgen deprivation therapy (ADT) for prostate cancer that is suitable for use in a UK NHS healthcare context. METHODS: PubMed literature searches of ED management in this patient group together with a survey of 28 experts in the management of treatment-induced ED from across the UK were conducted. RESULTS: Data from 19 articles and completed questionnaires were collated. The findings discussed in this article confirm that RT/ADT for prostate cancer can significantly impair erectile function. While many men achieve erections through PDE5-I use, others need combined management incorporating exercise and lifestyle modifications, psychosexual counselling and other erectile aids. This article offers a comprehensive treatment algorithm to manage patients with ED associated with RT/ADT. CONCLUSION: Based on published research literature and survey analysis, recommendations are proposed for the standardisation of management strategies employed for ED after RT/ADT. In addition to implementing the algorithm, understanding the rationale for the type and timing of ED management strategies is crucial for clinicians, men and their partners..
Hawizy, A.
Salji, M.
Kelker, A.R.
Gujral, S.S.
Van As, N.
(2015). Criteria used for the active surveillance of localised prostate cancer in the UK. Journal of clinical urology,
Vol.8
(1),
pp. 4-7.
Henderson, D.
Murray, J.
Tree, A.
Riley, U.
Murray, D.
van As, N.
(2015). Fiducial Marker Insertion for Image-guided Radiotherapy for Prostate Cancer: What is the Infection Rate and can Targeted Antibiotic Prophylaxis Reduce this?. Clinical oncology,
Vol.27
(3),
pp. E5-E5.
Petrylak, D.P.
Vogelzang, N.J.
Budnik, N.
Wiechno, P.J.
Sternberg, C.N.
Doner, K.
Bellmunt, J.
Burke, J.M.
de Olza, M.O.
Choudhury, A.
Gschwend, J.E.
Kopyltsov, E.
Flechon, A.
Van As, N.
Houede, N.
Barton, D.
Fandi, A.
Jungnelius, U.
Li, S.
de Wit, R.
Fizazi, K.
(2015). Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet oncol,
Vol.16
(4),
pp. 417-425.
show abstract
BACKGROUND: Patients with metastatic castration-resistant prostate cancer have few treatment options. We investigated the safety and efficacy of lenalidomide, an immunomodulatory agent with anti-angiogenic properties, in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, we randomly assigned chemotherapy-naive patients with progressive metastatic castration-resistant prostate cancer in a 1:1 ratio to receive docetaxel (75 mg/m(2)) on day 1 and prednisone (5 mg twice daily) on days 1-21 and either lenalidomide (25 mg) or placebo once daily on days 1-14 of each 21 day treatment cycle. Permuted block randomisation was done with an interactive voice response system and stratified by Eastern Cooperative Oncology Group performance status, geographic region, and type of disease progression. Clinicians, patients, and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy analysis was by intention to treat. Patients who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00988208. FINDINGS: 1059 patients were enrolled and randomly assigned between Nov 11, 2009, and Nov 23, 2011 (533 to the lenalidomide group and 526 to the control group), and 1046 patients received study treatment (525 in the lenalidomide group and 521 in the placebo group). At data cutoff (Jan 13, 2012) after a median follow-up of 8 months (IQR 5-12), 221 patients had died: 129 in the lenalidomide group and 92 in the placebo group. Median overall survival was 17·7 months (95% CI 14·8-18·8) in the lenalidomide group and not reached in the placebo group (hazard ratio [HR] 1·53, 95% CI 1·17-2·00, p=0·0017). The trial was subsequently closed early due to futility. The number of deaths that occurred during treatment or less than 28 days since the last dose were similar in both groups (18 [3%] of 525 patients in the lenalidomide group vs 13 [2%] of 521 patients). 109 (21%) patients in the lenalidomide group and 78 (15%) in the placebo group died more than 28 days from last dose, mainly due to disease progression. At least one grade 3 or higher adverse event was reported in 381 (73%) of 525 patients receiving lenalidomide and 303 (58%) of 521 patients receiving placebo. Grade 3-4 neutropenia (114 [22%] for lenalidomide vs 85 [16%] for placebo), febrile neutropenia (62 [12%] vs 23 [4%]), diarrhoea (37 [7%] vs 12 [2%]), pneumonia (24 [5%] vs five [1%]), dyspnoea (22 [4%] vs nine [2%]), asthenia (27 [5%] vs 17 [3%]), and pulmonary embolism (32 [6%] vs seven [1%]) occurred more frequently in the lenalidomide group than in the placebo group. INTERPRETATION: Overall survival with the combination of lenalidomide, docetaxel, and prednisone was significantly worse than with docetaxel and prednisone for chemotherapy-naive men with metastatic, castration-resistant prostate cancer. Further research with this treatment combination is not warranted. FUNDING: Celgene Corporation..
Henderson, D.R.
Tree, A.C.
van As, N.J.
(2015). Stereotactic body radiotherapy for prostate cancer. Clin oncol (r coll radiol),
Vol.27
(5),
pp. 270-279.
show abstract
The use of stereotactic body radiotherapy (SBRT) for localised prostate cancer is now supported by a substantial body of non-randomised data, with medium-term outcomes consistent with current standard radiotherapy. The ability to deliver profoundly hypofractionated treatment, combined with the relatively low α/β ratio of prostate cancer, may result in a more favourable therapeutic ratio, presenting an opportunity for isotoxic dose escalation. Furthermore, as treatment can be given in five attendances, SBRT has the potential both to reduce costs and improve patient quality of life. However, in a treatment landscape with many competing options of broadly similar efficacy, randomised trials are essential to define the relative benefits of this approach. SBRT also has an emerging application in oligometastatic prostate cancer, with promising early outcomes for delaying disease progression and deferring the need for androgen deprivation therapy..
Aitken, K.
Tree, A.
Thomas, K.
Nutting, C.
Hawkins, M.
Tait, D.
Mandeville, H.
Ahmed, M.
Lalondrelle, S.
Miah, A.
Taylor, A.
Ross, G.
Khoo, V.
van As, N.
(2015). Initial UK Experience of Stereotactic Body Radiotherapy for Extracranial Oligometastases: Can We Change the Therapeutic Paradigm?. Clin oncol (r coll radiol),
Vol.27
(7),
pp. 411-419.
show abstract
AIMS: To retrospectively review the toxicity and early outcome data from patients who have received stereotactic body radiotherapy (SBRT) for extracranial oligometastases at a single UK institution. MATERIALS AND METHODS: Eligible patients had ≤3 extracranial metastases and performance status ≤2. Prior systemic therapy and radical treatment of oligometastastic relapse with any standard treatment modality was permitted. Patients with synchronous metastatic disease were excluded unless they had evidence of controlled primary disease after radical therapy. Follow-up consisted of clinical examination, biochemical and radiological assessments in accordance with standard clinical care. Progression events were defined using RECIST. Toxicity was evaluated using CTCAE v4.0. Local control, progression-free survival (PFS), freedom from widespread distant metastasis (defined as disease not amenable to further radical salvage therapy) and overall survival were calculated. RESULTS: Between July 2011 and April 2014, 73 patients with 87 metastases received SBRT (range 1-3 per patient). The median follow-up was 14.5 months (range 0-26.4). The median PFS was 14.5 months (1 year PFS 57%, 2 year 28%); 1 year overall survival 96%, 2 year 79.8%; 2 year local control 88%. At 2 years, 46% of patients were free from widespread distant metastases. No ≥ grade 3 acute or late toxicity was observed. CONCLUSION: At this time point, observed toxicity is minimal with excellent local control rates. This promising treatment paradigm requires further investigation in the context of a randomised controlled trial to establish if the addition of SBRT to standard care improves survival outcomes..
Dearman, C.
van As, N.
Crellin, A.
Slevin, N.
Sharma, R.A.
(2015). Surgery versus SABR for resectable non-small-cell lung cancer. Lancet oncol,
Vol.16
(8),
pp. e373-e374.
Hafeez, S.
Singhera, M.
Huddart, R.
(2015). Exploration of the treatment challenges in men with intellectual difficulties and testicular cancer as seen in Down syndrome: single centre experience. Bmc med,
Vol.13,
p. 152.
show abstract
full text
Down syndrome is the most common chromosomal disorder in humans as well as the most common cause of inherited intellectual disability. A spectrum of physical and functional disability is associated with the syndrome as well as a predisposition to developing particular malignancies, including testicular cancers. These tumours ordinarily have a high cure rate even in widely disseminated disease. However, individuals with Down syndrome may have learning difficulties, behavioural problems, and multiple systemic complications that have the potential to make standard treatment more risky and necessitates individualized approach in order to avoid unacceptable harm. There is also suggestion that tumours may have a different natural history. Further, people with learning disabilities have often experienced poorer healthcare than the general population. In order to address these inequalities, legislation, professional bodies, and charities provide guidance; however, ultimately, consideration of the person in the context of their own psychosocial issues, comorbidities, and possible treatment strategies is vital in delivering optimal care. We aim to present a review of our own experience of delivering individualized care to this group of patients in order to close the existing health inequality gap..
Rosenfelder, N.
Corbett, R.
Long, M.
Meehan, C.
Duncan, N.
Khoo, V.
Van As, N.
(2015). Intensity modulated radiation therapy allows prostate and dose-escalated pelvic radical radiation therapy after renal transplantation. Pract radiat oncol,
Vol.5
(3),
pp. e207-e213.
Tree, A.
Ostler, P.
van As, N.
(2014). New horizons and hurdles for UK radiotherapy: can prostate stereotactic body radiotherapy show the way?. Clin oncol (r coll radiol),
Vol.26
(1),
pp. 1-3.
Tree, A.
Ostler, P.
Hoskin, P.
Dankulchai, P.
Khoo, V.
van As, N.
(2014). First UK Cohort of Prostate Stereotactic Body Radiotherapy (SBRT): Acute Toxicity and Early Prostate-specific Antigen (PSA) Outcomes. Clinical oncology,
Vol.26
(2),
pp. E7-E7.
Tree, A.C.
Khoo, V.S.
van As, N.J.
Partridge, M.
(2014). Is biochemical relapse-free survival after profoundly hypofractionated radiotherapy consistent with current radiobiological models?. Clin oncol (r coll radiol),
Vol.26
(4),
pp. 216-229.
show abstract
AIMS: The α/β ratio for prostate cancer is thought to be low and less than for the rectum, which is usually the dose-limiting organ. Hypofractionated radiotherapy should therefore improve the therapeutic ratio, increasing cure rates with less toxicity. A number of models for predicting biochemical relapse-free survival have been developed from large series of patients treated with conventional and moderately hypofractionated radiotherapy. The purpose of this study was to test these models when significant numbers of patients treated with profoundly hypofractionated radiotherapy were included. MATERIALS AND METHODS: A systematic review of the literature with regard to hypofractionated radiotherapy for prostate cancer was conducted, focussing on data recently presented on prostate stereotactic body radiotherapy. For the work described here, we have taken published biochemical control rates for a range of moderately and profoundly fractionated schedules and plotted these together with a range of radiobiological models, which are described. RESULTS: The data reviewed show consistency between the various radiobiological model predictions and the currently observed data. CONCLUSION: Current radiobiological models provide accurate predictions of biochemical relapse-free survival, even when profoundly hypofractionated patients are included in the analysis..
Tree, A.
Siu, B.
Townsend-Thorn, D.
Murray, D.
Riley, U.L.
Khoo, V.
van As, N.
(2014). The Incidence of Ciprofloxacin Resistance in Patients Undergoing Gold Seed Insertion for Image-guided Prostate Radiotherapy. Clinical oncology,
Vol.26,
pp. S8-S8.
Omlin, A.
Pezaro, C.J.
Zaidi, S.
Lorente, D.
Mukherji, D.
Bianchini, D.
Ferraldeschi, R.
Sandhu, S.
Dearnaley, D.
Parker, C.
Van As, N.
de Bono, J.S.
Attard, G.
(2014). Reply: 'Comment on Anti-tumour activity of abiraterone and diethylstilboestrol when administered sequentially to men with castration-resistant prostate cancer'. Br j cancer,
Vol.110
(1),
pp. 267-268.
Bancroft, E.K.
Page, E.C.
Castro, E.
Lilja, H.
Vickers, A.
Sjoberg, D.
Assel, M.
Foster, C.S.
Mitchell, G.
Drew, K.
Mæhle, L.
Axcrona, K.
Evans, D.G.
Bulman, B.
Eccles, D.
McBride, D.
van Asperen, C.
Vasen, H.
Kiemeney, L.A.
Ringelberg, J.
Cybulski, C.
Wokolorczyk, D.
Selkirk, C.
Hulick, P.J.
Bojesen, A.
Skytte, A.-.
Lam, J.
Taylor, L.
Oldenburg, R.
Cremers, R.
Verhaegh, G.
van Zelst-Stams, W.A.
Oosterwijk, J.C.
Blanco, I.
Salinas, M.
Cook, J.
Rosario, D.J.
Buys, S.
Conner, T.
Ausems, M.G.
Ong, K.-.
Hoffman, J.
Domchek, S.
Powers, J.
Teixeira, M.R.
Maia, S.
Foulkes, W.D.
Taherian, N.
Ruijs, M.
Helderman-van den Enden, A.T.
Izatt, L.
Davidson, R.
Adank, M.A.
Walker, L.
Schmutzler, R.
Tucker, K.
Kirk, J.
Hodgson, S.
Harris, M.
Douglas, F.
Lindeman, G.J.
Zgajnar, J.
Tischkowitz, M.
Clowes, V.E.
Susman, R.
Ramón y Cajal, T.
Patcher, N.
Gadea, N.
Spigelman, A.
van Os, T.
Liljegren, A.
Side, L.
Brewer, C.
Brady, A.F.
Donaldson, A.
Stefansdottir, V.
Friedman, E.
Chen-Shtoyerman, R.
Amor, D.J.
Copakova, L.
Barwell, J.
Giri, V.N.
Murthy, V.
Nicolai, N.
Teo, S.-.
Greenhalgh, L.
Strom, S.
Henderson, A.
McGrath, J.
Gallagher, D.
Aaronson, N.
Ardern-Jones, A.
Bangma, C.
Dearnaley, D.
Costello, P.
Eyfjord, J.
Rothwell, J.
Falconer, A.
Gronberg, H.
Hamdy, F.C.
Johannsson, O.
Khoo, V.
Kote-Jarai, Z.
Lubinski, J.
Axcrona, U.
Melia, J.
McKinley, J.
Mitra, A.V.
Moynihan, C.
Rennert, G.
Suri, M.
Wilson, P.
Killick, E.
IMPACT Collaborators,
Moss, S.
Eeles, R.A.
(2014). Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur urol,
Vol.66
(3),
pp. 489-499.
show abstract
full text
BACKGROUND: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. OBJECTIVE: To report the first year's screening results for all men at enrollment in the study. DESIGN, SETTING AND PARTICIPANTS: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. RESULTS AND LIMITATIONS: We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. CONCLUSIONS: The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. PATIENT SUMMARY: In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment..
Tree, A.C.
Ostler, P.
Hoskin, P.
Dankulchai, P.
Nariyangadu, P.
Hughes, R.J.
Wells, E.
Taylor, H.
Khoo, V.S.
van As, N.J.
(2014). Prostate stereotactic body radiotherapy—first UK experience. Clin oncol (r coll radiol),
Vol.26
(12),
pp. 757-761.
show abstract
AIMS: Stereotactic body radiotherapy (SBRT) combines image-guided radiotherapy with hypofractionation, both of which will probably result in improvements in patient outcomes in prostate cancer. Most clinical experience with this technique resides in North America. Here we present the first UK cohort to receive SBRT for prostate cancer. MATERIALS AND METHODS: Fifty-one prostate cancer patients (10 low risk, 35 intermediate risk and 6 high risk) were treated with 36.25 Gy in five fractions over 1-2 weeks and gold seed image guidance. All patients had toxicity International Prostate Symptom score (IPSS) and Radiation Therapy Oncology Group recorded prospectively and prostate-specific antigen was measured 3-6 monthly during follow-up. RESULTS: The median IPSS was 6, 11, 8 and 5 at baseline, 1-3 weeks, 4-6 weeks and 7-12 weeks after treatment. Radiation Therapy Oncology Group genitourinary and gastrointestinal toxicity of grade 2 was seen in 22% and 14%, respectively, at 1-3 weeks after treatment; no patient had grade 3+ toxicity at this time point, although two patients had grade 3 urinary frequency recorded during treatment. The median follow-up for the 42 patients who did not receive androgen deprivation was 14.5 months. Prostate-specific antigen at 13-18 months after treatment was 1.3 ng/ml. CONCLUSION: Prostate SBRT is a promising treatment for organ-confined prostate cancer and is currently being investigated in a UK-led phase III trial..
Tree, A.C.
Khoo, V.S.
Eeles, R.A.
Ahmed, M.
Dearnaley, D.P.
Hawkins, M.A.
Huddart, R.A.
Nutting, C.M.
Ostler, P.J.
van As, N.J.
(2013). Stereotactic body radiotherapy for oligometastases. Lancet oncol,
Vol.14
(1),
pp. e28-e37.
show abstract
The management of metastatic solid tumours has historically focused on systemic treatment given with palliative intent. However, radical surgical treatment of oligometastases is now common practice in some settings. The development of stereotactic body radiotherapy (SBRT), building on improvements in delivery achieved by intensity-modulated and image-guided radiotherapy, now allows delivery of ablative doses of radiation to extracranial sites. Many non-randomised studies have shown that SBRT for oligometastases is safe and effective, with local control rates of about 80%. Importantly, these studies also suggest that the natural history of the disease is changing, with 2-5 year progression-free survival of about 20%. Although complete cure might be possible in a few patients with oligometastases, the aim of SBRT in this setting is to achieve local control and delay progression, and thereby also postpone the need for further treatment. We review published work showing that SBRT offers durable local control and the potential for progression-free survival in non-liver, non-lung oligometastatic disease at a range of sites. However, to test whether SBRT really does improve progression-free survival, randomised trials will be essential..
Tree, A.
Jones, C.
Sohaib, A.
Khoo, V.
van As, N.
(2013). Prostate stereotactic body radiotherapy with simultaneous integrated boost: which is the best planning method?. Radiat oncol,
Vol.8,
p. 228.
show abstract
BACKGROUND: The delivery of a simultaneous integrated boost to the intra-prostatic tumour nodule may improve local control. The ability to deliver such treatments with hypofractionated SBRT was attempted using RapidArc (Varian Medical systems, Palo Alto, CA) and Multiplan (Accuray inc, Sunnyvale, CA). MATERIALS AND METHODS: 15 patients with dominant prostate nodules had RapidArc and Multiplan plans created using a 5 mm isotropic margin, except 3 mm posteriorly, aiming to deliver 47.5 Gy in 5 fractions to the boost whilst treating the whole prostate to 36.25 Gy in 5 fractions. An additional RapidArc plan was created using an 8 mm isotropic margin, except 5 mm posteriorly, to account for lack of intrafraction tracking. RESULTS: Both RapidArc and Multiplan can produce clinically acceptable boost plans to a dose of 47.5 Gy in 5 fractions. The mean rectal doses were lower for RapidArc plans (D50 13.2 Gy vs 15.5 Gy) but the number of missed constraints was the same for both planning methods (11/75). When the margin was increased to 8 mm/5 mm for the RapidArc plans to account for intrafraction motion, 37/75 constraints were missed. CONCLUSIONS: RapidArc and Multiplan can produce clinically acceptable simultaneous integrated boost plans, but the mean rectal D50 and D20 with RapidArc are lower. If the margins are increased to account for intrafraction motion, the RapidArc plans exceed at least one dose constraint in 13/15 cases. Delivering a simultaneous boost with hypofractionation appears feasible, but requires small margins needing intrafraction motion tracking..
Omlin, A.
Pezaro, C.J.
Zaidi, S.
Lorente, D.
Mukherji, D.
Bianchini, D.
Ferraldeschi, R.
Sandhu, S.
Dearnaley, D.
Parker, C.
Van As, N.
de Bono, J.S.
Attard, G.
(2013). Antitumour activity of abiraterone and diethylstilboestrol when administered sequentially to men with castration-resistant prostate cancer. Br j cancer,
Vol.109
(5),
pp. 1079-1084.
show abstract
BACKGROUND: Abiraterone is a standard treatment for men with castration-resistant prostate cancer (CRPC). We evaluated the antitumour activity of abiraterone following the synthetic oestrogen diethylstilboestrol (DES). METHODS: Castration-resistant prostate cancer patients treated with abiraterone were identified. Demographics, response variables and survival data were recorded. RESULTS: Two-hundred and seventy-four patients received abiraterone, 114 (41.6%) after DES. Pre-chemotherapy abiraterone resulted in ≥50% PSA declines in 35/41 (85.4%) DES-naïve and 20/27 (74.1%) DES-treated patients. Post-docetaxel abiraterone resulted in ≥50% PSA declines in 40/113 (35.4%) DES-naïve and 23/81 (28.4%) DES-treated patients. Time to PSA progression was similar regardless of prior DES. CONCLUSION: Abiraterone has important antitumour activity in men with CRPC even after DES exposure..
Eeles, R.A.
Olama, A.A.
Benlloch, S.
Saunders, E.J.
Leongamornlert, D.A.
Tymrakiewicz, M.
Ghoussaini, M.
Luccarini, C.
Dennis, J.
Jugurnauth-Little, S.
Dadaev, T.
Neal, D.E.
Hamdy, F.C.
Donovan, J.L.
Muir, K.
Giles, G.G.
Severi, G.
Wiklund, F.
Gronberg, H.
Haiman, C.A.
Schumacher, F.
Henderson, B.E.
Le Marchand, L.
Lindstrom, S.
Kraft, P.
Hunter, D.J.
Gapstur, S.
Chanock, S.J.
Berndt, S.I.
Albanes, D.
Andriole, G.
Schleutker, J.
Weischer, M.
Canzian, F.
Riboli, E.
Key, T.J.
Travis, R.C.
Campa, D.
Ingles, S.A.
John, E.M.
Hayes, R.B.
Pharoah, P.D.
Pashayan, N.
Khaw, K.-.
Stanford, J.L.
Ostrander, E.A.
Signorello, L.B.
Thibodeau, S.N.
Schaid, D.
Maier, C.
Vogel, W.
Kibel, A.S.
Cybulski, C.
Lubinski, J.
Cannon-Albright, L.
Brenner, H.
Park, J.Y.
Kaneva, R.
Batra, J.
Spurdle, A.B.
Clements, J.A.
Teixeira, M.R.
Dicks, E.
Lee, A.
Dunning, A.M.
Baynes, C.
Conroy, D.
Maranian, M.J.
Ahmed, S.
Govindasami, K.
Guy, M.
Wilkinson, R.A.
Sawyer, E.J.
Morgan, A.
Dearnaley, D.P.
Horwich, A.
Huddart, R.A.
Khoo, V.S.
Parker, C.C.
Van As, N.J.
Woodhouse, C.J.
Thompson, A.
Dudderidge, T.
Ogden, C.
Cooper, C.S.
Lophatananon, A.
Cox, A.
Southey, M.C.
Hopper, J.L.
English, D.R.
Aly, M.
Adolfsson, J.
Xu, J.
Zheng, S.L.
Yeager, M.
Kaaks, R.
Diver, W.R.
Gaudet, M.M.
Stern, M.C.
Corral, R.
Joshi, A.D.
Shahabi, A.
Wahlfors, T.
Tammela, T.L.
Auvinen, A.
Virtamo, J.
Klarskov, P.
Nordestgaard, B.G.
Røder, M.A.
Nielsen, S.F.
Bojesen, S.E.
Siddiq, A.
Fitzgerald, L.M.
Kolb, S.
Kwon, E.M.
Karyadi, D.M.
Blot, W.J.
Zheng, W.
Cai, Q.
McDonnell, S.K.
Rinckleb, A.E.
Drake, B.
Colditz, G.
Wokolorczyk, D.
Stephenson, R.A.
Teerlink, C.
Muller, H.
Rothenbacher, D.
Sellers, T.A.
Lin, H.-.
Slavov, C.
Mitev, V.
Lose, F.
Srinivasan, S.
Maia, S.
Paulo, P.
Lange, E.
Cooney, K.A.
Antoniou, A.C.
Vincent, D.
Bacot, F.
Tessier, D.C.
COGS–Cancer Research UK GWAS–ELLIPSE (part of GAME-ON) Initiative,
Australian Prostate Cancer Bioresource,
UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology,
UK ProtecT (Prostate testing for cancer and Treatment) Study Collaborators,
PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium,
Kote-Jarai, Z.
Easton, D.F.
(2013). Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat genet,
Vol.45
(4),
pp. 385-391e2.
show abstract
Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies..
Tree, A.
Wells, E.
Khoo, V.
van As, N.
(2013). Hypofractionated Radiotherapy with Cyberknife for Localised Prostate Cancer: Early Experience. Clinical oncology,
Vol.25
(4),
pp. E72-E73.
Beyond TME Collaborative,
(2013). Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. Br j surg,
Vol.100
(8),
pp. 1009-1014.
show abstract
BACKGROUND: The management of primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. METHODS: Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web-based voting. Consensus was achieved with more than 80 per cent agreement; less than 80 per cent agreement indicated low consensus. During conferences held in September 2011 and March 2012, open discussion took place on areas in which there is a low level of consensus. RESULTS: The final consensus document included 51 voted statements, making recommendations on ten key areas of PRC-bTME and RRC. Consensus agreement was achieved on the recommendations of 49 statements, with 34 achieving consensus in over 95 per cent. The lowest level of consensus obtained was 76 per cent. There was clear identification of the need for referral to a specialist multidisciplinary team for diagnosis, assessment and further management. CONCLUSION: The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority..
Tree, A.C.
Alexander, E.J.
Van As, N.J.
Dearnaley, D.P.
Khoo, V.
(2013). Biological dose escalation and hypofractionation: what is there to be gained and how will it best be done?. Clin oncol (r coll radiol),
Vol.25
(8),
pp. 483-498.
show abstract
The evidence supporting dose escalation for localised prostate cancer is widely accepted, but in tandem with improvements in biochemical control, dose escalation increases side-effects. In a scenario where most patients achieve control of their cancer, quality of life concerns predominate. Here we examine the biological ways in which an effective dose can be escalated without an unacceptable increase in toxicity. Possible avenues include exploiting the unusual radiobiology of prostate cancer by hypofractionation, the use of image guidance, adaptive planning and prostate motion management. We await with anticipation the results of large randomised trials of hypofractionation, moderate and profound, to establish whether we can further improve the balance between cure and quality of life..
Amin Al Olama, A.
Kote-Jarai, Z.
Schumacher, F.R.
Wiklund, F.
Berndt, S.I.
Benlloch, S.
Giles, G.G.
Severi, G.
Neal, D.E.
Hamdy, F.C.
Donovan, J.L.
Hunter, D.J.
Henderson, B.E.
Thun, M.J.
Gaziano, M.
Giovannucci, E.L.
Siddiq, A.
Travis, R.C.
Cox, D.G.
Canzian, F.
Riboli, E.
Key, T.J.
Andriole, G.
Albanes, D.
Hayes, R.B.
Schleutker, J.
Auvinen, A.
Tammela, T.L.
Weischer, M.
Stanford, J.L.
Ostrander, E.A.
Cybulski, C.
Lubinski, J.
Thibodeau, S.N.
Schaid, D.J.
Sorensen, K.D.
Batra, J.
Clements, J.A.
Chambers, S.
Aitken, J.
Gardiner, R.A.
Maier, C.
Vogel, W.
Dörk, T.
Brenner, H.
Habuchi, T.
Ingles, S.
John, E.M.
Dickinson, J.L.
Cannon-Albright, L.
Teixeira, M.R.
Kaneva, R.
Zhang, H.-.
Lu, Y.-.
Park, J.Y.
Cooney, K.A.
Muir, K.R.
Leongamornlert, D.A.
Saunders, E.
Tymrakiewicz, M.
Mahmud, N.
Guy, M.
Govindasami, K.
O'Brien, L.T.
Wilkinson, R.A.
Hall, A.L.
Sawyer, E.J.
Dadaev, T.
Morrison, J.
Dearnaley, D.P.
Horwich, A.
Huddart, R.A.
Khoo, V.S.
Parker, C.C.
Van As, N.
Woodhouse, C.J.
Thompson, A.
Dudderidge, T.
Ogden, C.
Cooper, C.S.
Lophatonanon, A.
Southey, M.C.
Hopper, J.L.
English, D.
Virtamo, J.
Le Marchand, L.
Campa, D.
Kaaks, R.
Lindstrom, S.
Diver, W.R.
Gapstur, S.
Yeager, M.
Cox, A.
Stern, M.C.
Corral, R.
Aly, M.
Isaacs, W.
Adolfsson, J.
Xu, J.
Zheng, S.L.
Wahlfors, T.
Taari, K.
Kujala, P.
Klarskov, P.
Nordestgaard, B.G.
Røder, M.A.
Frikke-Schmidt, R.
Bojesen, S.E.
FitzGerald, L.M.
Kolb, S.
Kwon, E.M.
Karyadi, D.M.
Orntoft, T.F.
Borre, M.
Rinckleb, A.
Luedeke, M.
Herkommer, K.
Meyer, A.
Serth, J.
Marthick, J.R.
Patterson, B.
Wokolorczyk, D.
Spurdle, A.
Lose, F.
McDonnell, S.K.
Joshi, A.D.
Shahabi, A.
Pinto, P.
Santos, J.
Ray, A.
Sellers, T.A.
Lin, H.-.
Stephenson, R.A.
Teerlink, C.
Muller, H.
Rothenbacher, D.
Tsuchiya, N.
Narita, S.
Cao, G.-.
Slavov, C.
Mitev, V.
UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology,
UK ProtecT Study Collaborators,
Australian Prostate Cancer Bioresource,
PRACTICAL Consortium,
Chanock, S.
Gronberg, H.
Haiman, C.A.
Kraft, P.
Easton, D.F.
Eeles, R.A.
(2013). A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease. Hum mol genet,
Vol.22
(2),
pp. 408-415.
show abstract
Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis..
Ahmed, H.U.
Akin, O.
Coleman, J.A.
Crane, S.
Emberton, M.
Goldenberg, L.
Hricak, H.
Kattan, M.W.
Kurhanewicz, J.
Moore, C.M.
Parker, C.
Polascik, T.J.
Scardino, P.
van As, N.
Villers, A.
Active, T.C.
(2012). Transatlantic Consensus Group on active surveillance and focal therapy for prostate cancer. Bju international,
Vol.109
(11),
pp. 1636-1647.
Sham, J.
Rosenfelder, N.
Ashley, S.
Lamb, C.
Khoo, V.
van As, N.
Dearnaley, D.
(2011). Does Marker-based Prostate Radiotherapy Cause Worse Acute Toxicity?. Clinical oncology,
Vol.23
(3),
pp. S52-1.
Rosenfelder, N.
Corsini, L.
Lamb, C.
Aitken, A.
van As, N.
Burke, K.
Bidmead, M.
Khoo, V.
Brada, M.
(2011). Can the Accuracy of a Stereotactic Frame be Achieved Using a Thermoplastic Shell?. Clinical oncology,
Vol.23
(3),
pp. S51-1.
Morgan, V.A.
Riches, S.F.
Thomas, K.
Vanas, N.
Parker, C.
Giles, S.
Desouza, N.M.
(2011). Diffusion-weighted magnetic resonance imaging for monitoring prostate cancer progression in patients managed by active surveillance. British journal of radiology,
Vol.84
(997),
pp. 31-7.
Rosenfelder, N.
Lamb, C.
Aitken, A.
Bidmead, M.
van As, N.
Khoo, V.
(2011). On-line Image Verification for Prostate Radiotherapy - is Daily Correction Beneficial?. Clinical oncology,
Vol.23
(3),
pp. S51-S51.
Aitken, K.
Lamb, C.
Rosenfelder, N.
Burke, K.
Bidmead, M.
Van As, N.
Khoo, V.
(2011). Assessing the Stability of Prostate Fiducial Markers over a Course of Radiotherapy. Clinical oncology,
Vol.23
(3),
pp. S28-S28.
Macinnis, R.J.
Antoniou, A.C.
Eeles, R.A.
Severi, G.
Al Olama, A.A.
McGuffog, L.
Kote-Jarai, Z.
Guy, M.
O'Brien, L.T.
Hall, A.L.
Wilkinson, R.A.
Sawyer, E.
Ardern-Jones, A.T.
Dearnaley, D.P.
Horwich, A.
Khoo, V.S.
Parker, C.C.
Huddart, R.A.
Van As, N.
McCredie, M.R.
English, D.R.
Giles, G.G.
Hopper, J.L.
Easton, D.F.
(2011). A risk prediction algorithm based on family history and common genetic variants: application to prostate cancer with potential clinical impact. Genet epidemiol,
Vol.35
(6),
pp. 549-556.
show abstract
full text
Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) that are independently associated with small increments in risk of prostate cancer, opening up the possibility for using such variants in risk prediction. Using segregation analysis of population-based samples of 4,390 families of prostate cancer patients from the UK and Australia, and assuming all familial aggregation has genetic causes, we previously found that the best model for the genetic susceptibility to prostate cancer was a mixed model of inheritance that included both a recessive major gene component and a polygenic component (P) that represents the effect of a large number of genetic variants each of small effect, where . Based on published studies of 26 SNPs that are currently known to be associated with prostate cancer, we have extended our model to incorporate these SNPs by decomposing the polygenic component into two parts: a polygenic component due to the known susceptibility SNPs, , and the residual polygenic component due to the postulated but as yet unknown genetic variants, . The resulting algorithm can be used for predicting the probability of developing prostate cancer in the future based on both SNP profiles and explicit family history information. This approach can be applied to other diseases for which population-based family data and established risk variants exist..
Kote-Jarai, Z.
Olama, A.A.
Giles, G.G.
Severi, G.
Schleutker, J.
Weischer, M.
Campa, D.
Riboli, E.
Key, T.
Gronberg, H.
Hunter, D.J.
Kraft, P.
Thun, M.J.
Ingles, S.
Chanock, S.
Albanes, D.
Hayes, R.B.
Neal, D.E.
Hamdy, F.C.
Donovan, J.L.
Pharoah, P.
Schumacher, F.
Henderson, B.E.
Stanford, J.L.
Ostrander, E.A.
Sorensen, K.D.
Dörk, T.
Andriole, G.
Dickinson, J.L.
Cybulski, C.
Lubinski, J.
Spurdle, A.
Clements, J.A.
Chambers, S.
Aitken, J.
Gardiner, R.A.
Thibodeau, S.N.
Schaid, D.
John, E.M.
Maier, C.
Vogel, W.
Cooney, K.A.
Park, J.Y.
Cannon-Albright, L.
Brenner, H.
Habuchi, T.
Zhang, H.-.
Lu, Y.-.
Kaneva, R.
Muir, K.
Benlloch, S.
Leongamornlert, D.A.
Saunders, E.J.
Tymrakiewicz, M.
Mahmud, N.
Guy, M.
O'Brien, L.T.
Wilkinson, R.A.
Hall, A.L.
Sawyer, E.J.
Dadaev, T.
Morrison, J.
Dearnaley, D.P.
Horwich, A.
Huddart, R.A.
Khoo, V.S.
Parker, C.C.
Van As, N.
Woodhouse, C.J.
Thompson, A.
Christmas, T.
Ogden, C.
Cooper, C.S.
Lophatonanon, A.
Southey, M.C.
Hopper, J.L.
English, D.R.
Wahlfors, T.
Tammela, T.L.
Klarskov, P.
Nordestgaard, B.G.
Røder, M.A.
Tybjærg-Hansen, A.
Bojesen, S.E.
Travis, R.
Canzian, F.
Kaaks, R.
Wiklund, F.
Aly, M.
Lindstrom, S.
Diver, W.R.
Gapstur, S.
Stern, M.C.
Corral, R.
Virtamo, J.
Cox, A.
Haiman, C.A.
Le Marchand, L.
Fitzgerald, L.
Kolb, S.
Kwon, E.M.
Karyadi, D.M.
Orntoft, T.F.
Borre, M.
Meyer, A.
Serth, J.
Yeager, M.
Berndt, S.I.
Marthick, J.R.
Patterson, B.
Wokolorczyk, D.
Batra, J.
Lose, F.
McDonnell, S.K.
Joshi, A.D.
Shahabi, A.
Rinckleb, A.E.
Ray, A.
Sellers, T.A.
Lin, H.-.
Stephenson, R.A.
Farnham, J.
Muller, H.
Rothenbacher, D.
Tsuchiya, N.
Narita, S.
Cao, G.-.
Slavov, C.
Mitev, V.
Easton, D.F.
Eeles, R.A.
UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology,
UK ProtecT Study Collaborators, The Australian Prostate Cancer BioResource,
PRACTICAL Consortium,
(2011). Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat genet,
Vol.43
(8),
pp. 785-791.
show abstract
Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified..
Afaq, A.
Koh, D.-.
Padhani, A.
van As, N.
Sohaib, S.A.
(2011). Clinical utility of diffusion-weighted magnetic resonance imaging in prostate cancer. Bju int,
Vol.108
(11),
pp. 1716-1722.
show abstract
UNLABELLED: What's known on the subject? and What does the study add? This article reviews what is currently known about diffusion weighted MRI (DW-MRI) in prostate cancer. This mini-review concisely summarises, for clinical managing patients with prostate cancer, the clinical utility of diffusion weighted MRI. OBJECTIVE: • To review the clinical utility of diffusion-weighted magnetic resonance imaging (DW-MRI) in patients with prostate cancer. MATERIAL AND METHODS: • The current literature on prostate cancer and DW-MRI was reviewed. RESULTS: • DW-MRI can be readily acquired on a modern scanner with a short image acquisition time and no need for i.v. contrast medium. • The image contrast is based on the diffusion of water molecules and thus reflects tissue cellularity. • There is increasing evidence that DW- MRI improves the sensitivity and specificity of prostate cancer detection as well as the identification of tumour aggressiveness. • DW-MRI is also showing substantial promise as a response biomarker for both local and metastatic disease CONCLUSIONS: • DW-MRI is proving to be a useful adjunct to conventional T2-weighted MRI sequences. • The eventual role of DW-MRI in combination with other MRI techniques for multiparametric assessment of prostate cancer needs to be defined further..
Okines, A.F.
Hawkes, E.A.
Rao, S.
VAN As, N.
Marsh, H.
Riddell, A.
Wilson, P.O.
Osin, P.
Wotherspoon, A.C.
(2010). Metastatic breast cancer presenting as a primary hindgut neuroendocrine tumour. Anticancer res,
Vol.30
(7),
pp. 3015-3018.
show abstract
The examination of limited, potentially non-representative fragments of tumour tissue from a core biopsy can be misleading and misdirect subsequent treatment, especially in cases where a primary tumour has not been identified. This case report is of a 65-year-old woman presenting with a destructive sacral mass, diagnosed on radiological imaging and core biopsy as a hindgut neuroendocrine tumour, which on histopathological review of the subsequently resected tumour was found instead to represent a metastasis from an occult hormone-positive breast cancer with neuroendocrine features..
Teoh, E.M.
Dearnaley, D.P.
Horwich, A.
Van As, N.
Riley, U.
Huddart, R.A.
(2010). The efficacy of preventing neutropenic sepsis in patients with testicular germ cell tumours: results of two consecutive audits. Clin oncol (r coll radiol),
Vol.22
(10),
pp. 891-892.
Gilbert, D.C.
Van As, N.J.
Huddart, R.A.
(2009). Reducing treatment toxicities in the management of good prognosis testicular germ cell tumors. Expert rev anticancer ther,
Vol.9
(2),
pp. 223-233.
show abstract
Testicular germ cell tumors are the most frequent solid tumor to affect young adult males and are increasing in incidence for reasons that are poorly understood. Increasingly, patients present with localized disease where disease-specific survival approaches 100%. Even in the presence of metastatic disease, the majority of patients with good prognostic features should expect to be cured. However, toxicities from treatment are increasingly recognized, with patients experiencing increased rates of second malignancies, cardiovascular disease and a range of circulatory, neurological and endocrine sequelae. High cure rates in a young population make reducing this long-term treatment-related morbidity and mortality imperative. In stage I disease, options following orchidectomy range from surveillance to adjuvant therapy, in the form of carboplatin or para-aortic radiotherapy for seminoma, and combination chemotherapy for nonseminoma. Metastatic disease requires combination chemotherapy with the exception of low-volume para-aortic nodal disease in seminoma, where radiotherapy with or without carboplatin may be curative. These various treatment options are discussed with a focus on reducing long-term treatment-related toxicities while preserving the high rates of long-term disease control..
Ng, M.K.
Van As, N.
Thomas, K.
Woode-Amissah, R.
Horwich, A.
Huddart, R.
Khoo, V.
Thompson, A.
Dearnaley, D.
Parker, C.
(2009). Prostate-specific antigen (PSA) kinetics in untreated, localized prostate cancer: PSA velocity vs PSA doubling time. Bju int,
Vol.103
(7),
pp. 872-876.
show abstract
OBJECTIVES: To compare the accuracy of prostate-specific antigen (PSA) velocity (PSAV) vs PSA doubling time (DT) for predicting the repeat biopsy results in men with localized prostate cancer on active surveillance (AS), as the utility of PSAV vs PSADT in untreated prostate cancer has not been well studied. PATIENTS AND METHODS: Eligible patients had favourable-risk localized prostate cancer (T1/2a, PSA level or=4, >50% cores positive, or initial Gleason score 3 + 3 upgraded to >or=3 + 4. Using all PSA values for the 2 years preceding repeat biopsy, the PSAV and PSADT were calculated using linear regression and the log-slope method (DT = ln2/slope), respectively. RESULTS: In all, 199 patients were assessable; the median PSAV and PSADT were 0.71 ng/mL/year and 5.29 years, respectively. Fifty-three patients (27%) had adverse histology on repeat biopsy. On univariate analyses, PSAV (P < 0.001) and PSADT (P = 0.019) were associated with adverse histology. The area under the receiver operating characteristic curve for predicting adverse histology was 0.70 and 0.63 for PSAV and PSADT, respectively. The mean difference was 0.07 (95% confidence interval 0.03-0.12; P < 0.001). CONCLUSIONS: PSAV is more accurate than PSADT for predicting adverse histology on repeat biopsies. These data suggest that PSAV should be used in preference to PSADT to describe PSA kinetics in untreated, localized prostate cancer..
Eeles, R.A.
Kote-Jarai, Z.
Al Olama, A.A.
Giles, G.G.
Guy, M.
Severi, G.
Muir, K.
Hopper, J.L.
Henderson, B.E.
Haiman, C.A.
Schleutker, J.
Hamdy, F.C.
Neal, D.E.
Donovan, J.L.
Stanford, J.L.
Ostrander, E.A.
Ingles, S.A.
John, E.M.
Thibodeau, S.N.
Schaid, D.
Park, J.Y.
Spurdle, A.
Clements, J.
Dickinson, J.L.
Maier, C.
Vogel, W.
Dörk, T.
Rebbeck, T.R.
Cooney, K.A.
Cannon-Albright, L.
Chappuis, P.O.
Hutter, P.
Zeegers, M.
Kaneva, R.
Zhang, H.-.
Lu, Y.-.
Foulkes, W.D.
English, D.R.
Leongamornlert, D.A.
Tymrakiewicz, M.
Morrison, J.
Ardern-Jones, A.T.
Hall, A.L.
O'Brien, L.T.
Wilkinson, R.A.
Saunders, E.J.
Page, E.C.
Sawyer, E.J.
Edwards, S.M.
Dearnaley, D.P.
Horwich, A.
Huddart, R.A.
Khoo, V.S.
Parker, C.C.
Van As, N.
Woodhouse, C.J.
Thompson, A.
Christmas, T.
Ogden, C.
Cooper, C.S.
Southey, M.C.
Lophatananon, A.
Liu, J.-.
Kolonel, L.N.
Le Marchand, L.
Wahlfors, T.
Tammela, T.L.
Auvinen, A.
Lewis, S.J.
Cox, A.
FitzGerald, L.M.
Koopmeiners, J.S.
Karyadi, D.M.
Kwon, E.M.
Stern, M.C.
Corral, R.
Joshi, A.D.
Shahabi, A.
McDonnell, S.K.
Sellers, T.A.
Pow-Sang, J.
Chambers, S.
Aitken, J.
Gardiner, R.A.
Batra, J.
Kedda, M.A.
Lose, F.
Polanowski, A.
Patterson, B.
Serth, J.
Meyer, A.
Luedeke, M.
Stefflova, K.
Ray, A.M.
Lange, E.M.
Farnham, J.
Khan, H.
Slavov, C.
Mitkova, A.
Cao, G.
UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology,
UK ProtecT Study Collaborators,
PRACTICAL Consortium,
Easton, D.F.
(2009). Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat genet,
Vol.41
(10),
pp. 1116-1121.
show abstract
Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33))..
Al Olama, A.A.
Kote-Jarai, Z.
Giles, G.G.
Guy, M.
Morrison, J.
Severi, G.
Leongamornlert, D.A.
Tymrakiewicz, M.
Jhavar, S.
Saunders, E.
Hopper, J.L.
Southey, M.C.
Muir, K.R.
English, D.R.
Dearnaley, D.P.
Ardern-Jones, A.T.
Hall, A.L.
O'Brien, L.T.
Wilkinson, R.A.
Sawyer, E.
Lophatananon, A.
UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology,
UK Prostate testing for cancer and Treatment study (ProtecT Study) Collaborators,
Horwich, A.
Huddart, R.A.
Khoo, V.S.
Parker, C.C.
Woodhouse, C.J.
Thompson, A.
Christmas, T.
Ogden, C.
Cooper, C.
Donovan, J.L.
Hamdy, F.C.
Neal, D.E.
Eeles, R.A.
Easton, D.F.
(2009). Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat genet,
Vol.41
(10),
pp. 1058-1060.
show abstract
Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility..
van As, N.J.
de Souza, N.M.
Riches, S.F.
Morgan, V.A.
Sohaib, S.A.
Dearnaley, D.P.
Parker, C.C.
(2009). A study of diffusion-weighted magnetic resonance imaging in men with untreated localised prostate cancer on active surveillance. Eur urol,
Vol.56
(6),
pp. 981-987.
show abstract
BACKGROUND: Markers that predict the behaviour of localised prostate cancer are needed to identify patients that require treatment. OBJECTIVE: We have analysed the apparent diffusion coefficient (ADC) generated from diffusion-weighted magnetic resonance imaging (DW-MRI) with respect to repeat biopsy findings and time to radical treatment in patients in a prospective study of active surveillance. DESIGN, SETTING, AND PARTICIPANTS: Some 86 men recruited between 2002 and 2006 were followed for a median of 29 mo. Patients had clinical stage T1/T2a N0/Nx M0/Mx adenocarcinoma of the prostate, prostate-specific antigen (PSA) level<15 ng/ml, Gleason score≤7, primary Gleason grade≤3, and positive biopsy cores (pbc)≤50%. MEASUREMENTS: All patients had DW-MRI in addition to standard MRI sequences. Tumour regions of interest (ROIs) were identified using T2-weighted fast-spin echo images as focal areas of restricted diffusion. Univariate analyses including all clinical variables and tumour ADC data were performed with respect to repeat biopsy findings and time to radical treatment. Receiver operating curves (ROC) compared predictive variables. RESULTS AND LIMITATIONS: Patients in the study had a median age of 66 yr and a median initial PSA level of 6.7 ng/ml. Some 39 patients (45%) received deferred radical treatment, and 34 patients (40%) had adverse histology on repeat biopsy. According to univariate analysis, tumour ADC was a significant predictor of both adverse repeat biopsy findings (p<0.0001; hazard ratio [HR]: 1.3; 95% confidence interval [CI]: 1.1-1.6), and time to radical treatment (p<0.0001; HR: 1.5; 95% CI: 1.2-1.8). ROC curves for ADC showed an area under the curve (AUC) of 0.7 for prediction of adverse repeat biopsy findings and an AUC of 0.83 for prediction of radical treatment. CONCLUSIONS: In patients with low-risk, localised disease, tumour ADC on DW-MRI may be a useful marker of prostate cancer progression and may help to identify patients who stand to benefit from radical treatment. This possibility warrants further study..
Gilbert, D.C.
Vanas, N.J.
Beesley, S.
Bloomfield, D.
Money-Kyrle, J.
Norman, A.
Dearnaley, D.
Horwich, A.
Huddart, R.A.
(2009). Treating IIA/B seminoma with combination carboplatin and radiotherapy. J clin oncol,
Vol.27
(12),
pp. 2101-2102.
deSouza, N.M.
Riches, S.F.
VanAs, N.J.
Morgan, V.A.
Ashley, S.A.
Fisher, C.
Payne, G.S.
Parker, C.
(2008). Diffusion-weighted magnetic resonance imaging: a potential non-invasive marker of tumour aggressiveness in localized prostate cancer. Clinical radiology,
Vol.63
(7),
pp. 774-9.
Van As, N.
Charles-Edwards, E.
Jackson, A.
Jhavar, S.
Reinsberg, S.
Desouza, N.
Dearnaley, D.
Bailey, M.
Thompson, A.
Christmas, T.
Fisher, C.
Corbishley, C.
Sohaib, S.
(2008). Correlation of diffusion-weighted MRI with whole mount radical prostatectomy specimens. Br j radiol,
Vol.81
(966),
pp. 456-462.
show abstract
The purpose of this study was to compare the apparent diffusion coefficient (ADC) of benign central gland (bCG), benign peripheral zone (bPZ) and cancer using diffusion-weighted MRI and whole mount specimens. 11 patients with biopsy-proven prostate cancer underwent diffusion-weighted MRI prior to radical prostatectomy. A single-shot echo planar image technique was used with b-values of 0 s mm(-2), 300 s mm(-2), 500 s mm(-2) and 800 s mm(-2). Whole mount specimens were compared with ADC maps. Areas of cancer, bCG and bPZ were identified, and regions of interest were drawn on ADC maps. Mean ADC values were recorded for all regions of interest, and paired t-tests were performed to compare mean values. Cancer was outlined in nine patients. In two patients, the tumours were too small to correlate with images; bCG was identified in 11 patients and bPZ was identified in 10 patients. Mean ADC values for bCG, bPZ and cancer were, 1.5 x 10(-3) mm(2) s(-1) (standard error (SE) = 0.04), 1.7 x 10(-3) mm(2) s(-1) (SE = 0.1), and 1.3 x 10(-3) mm(2) s(-1) (SE = 0.09), respectively. The most significant difference between benign tissue and cancer existed at b-values of 0-300 s mm(-2) (bCG vs cancer: mean difference = 0. 29, p = 0.001, 95% confidence interval (CI) = 0.17-0.41; bPZ vs cancer: mean difference = 0.34, p = 0.003, 95% CI = 0.18-0.61). In conclusion, we have confirmed, using whole mount verification, a significant difference in the ADC between benign tissue and cancer..
van As, N.J.
Norman, A.R.
Thomas, K.
Khoo, V.S.
Thompson, A.
Huddart, R.A.
Horwich, A.
Dearnaley, D.P.
Parker, C.C.
(2008). Predicting the probability of deferred radical treatment for localised prostate cancer managed by active surveillance. Eur urol,
Vol.54
(6),
pp. 1297-1305.
show abstract
OBJECTIVES: Outcome data from a prospective study of active surveillance of localised prostate cancer were analysed to identify factors, present at the time of diagnosis, that predict subsequent radical treatment. METHODS: Eligible patients had clinical stage T1-T2a, N0-Nx, M0-Mx adenocarcinoma of the prostate with serum PSA<15 ng/ml, Gleason score 1 ng/ml/yr) or histological progression (primary Gleason grade >or= 4, or %pbc > 50%). Multivariate Cox regression analysis of baseline variables was performed with respect to time to radical treatment. RESULTS: The 326 men recruited from 2002 to 2006 have been followed for a median of 22 mo. Median age was 67 yr, and median initial PSA (iPSA) 6.4 ng/ml. Sixty-five patients (20%) had deferred radical treatment, 16 (5%) changed to watchful waiting because of increasing comorbidity, 7 (2%) died of other causes, and 238 (73%) remain on surveillance. On multivariate Cox regression analysis, the free/total PSA ratio (p<0.001) and clinical T stage (p=0.006) were independent determinants of time to radical treatment. CONCLUSIONS: In addition to established prognostic factors, the free/total PSA ratio may predict time to radical treatment in patients with untreated, localised prostate cancer managed by active surveillance. This possibility warrants further study..
van As, N.J.
Gilbert, D.C.
Money-Kyrle, J.
Bloomfield, D.
Beesley, S.
Dearnaley, D.P.
Horwich, A.
Huddart, R.A.
(2008). Evidence-based pragmatic guidelines for the follow-up of testicular cancer: optimising the detection of relapse. Br j cancer,
Vol.98
(12),
pp. 1894-1902.
show abstract
Testicular germ cell tumours (TGCTs) are the most common cause of cancer in men between the ages of 15 and 40 years, and, overall, the majority of patients should expect to be cured. The European Germ Cell Cancer Consensus Group has provided clear guidelines for the primary treatment of both seminoma and nonseminomatous germ cell tumours. There is, however, no international consensus on how best to follow patients after their initial management. This must promptly and reliably identify relapses without causing further harm. The standardising of follow-up would result in optimising risk-benefit ratios for individual patients, while ensuring economic use of resources. We have identified the seven common scenarios in managing seminomas and nonseminomas of the various stages and discuss the pertinent issues around relapse and follow-up. We review the available literature and present our comprehensive TGCT follow-up guidelines. Our protocols provide a pragmatic, easily accessible user-friendly basis for other centres to use or to adapt to suit their needs. Furthermore, this should enable future trials to address specific issues around follow-up giving meaningful and useful results..
van As, N.
Parker, C.
deSouza, N.
Thompson, A.
Khoo, V.
Dearnaley, D.
Sohaib, S.A.
(2007). Magnetic resonance imaging is the modality of choice for accurate assessment of prostate volume. Clinical oncology,
Vol.19
(4),
pp. S4-1.
van As, N.
Charles-Edwards, E.
Jackson, A.
Jhavar, S.
Reinsberg, S.
deSouza, N.
Dearnaley, D.
Baileys, M.
Thompson, A.
Christmas, T.
Fisher, C.
Corbishley, C.
Sohaib, S.A.
(2007). Correlation of diffusion-weighted MRI (DWMRI) with whole mount radical prostatectomy specimen. Clinical oncology,
Vol.19
(4),
pp. S4-1.
van As, N.J.
Parker, C.C.
(2007). Active surveillance with selective radical treatment for localized prostate cancer. Cancer j,
Vol.13
(5),
pp. 289-294.
show abstract
The challenge of managing localized prostate cancer is to distinguish patients with clinically relevant cancers, who may benefit from radical treatment, from the remainder who do not need any intervention. Active surveillance with selective radial intervention is a management strategy that offers patients the hope of avoiding "unnecessary" treatment without detriment to their long-term survival. Here we discuss the rationale for active surveillance, and the early results. There is no consensus on the optimum active surveillance protocol, with uncertainty regarding the interpretation of PSA kinetics, repeat biopsy results and prostate imaging. In the future, it is likely that molecular markers will revolutionize our ability to select patients who will benefit from definitive treatment. In the meantime, active surveillance provides an attractive way of reducing over treatment..
van As, N.
Jackson, A.
Sohaib, S.
South, C.
Charles-Edwards, E.
Reinsberg, S.
Leach, M.
Dearnaley, D.
(2005). Prostate and pelvis radiotherapy using IMRT and ultra small superparamagnetic nano-particles to optimise dose to involved lymph nodes. Ejc supplements,
Vol.3
(2),
pp. 399-2.
Van As, N.
Calonje, E.
Andrews, V.
Griffiths, W.A.
Leslie, M.D.
(2005). Complete resolution of anal cancer after chemotherapy for acute myeloid leukaemia. Lancet oncology,
Vol.6
(11),
pp. 908-909.