Bancroft, E.K., Saya, S., Page, E.C., Myhill, K., Thomas, S., Pope, J., Chamberlain, A., Hart, R., Glover, W., Cook, J., et al.
(2019). Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations. Bju int,
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., et al.
(2019). Comparison of prostate delineation on multimodality imaging for MR-guided radiotherapy. Br j radiol,
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., As, N.J. & Tree, A.C.
(2019). Improving fiducial and prostate capsule visualization for radiotherapy planning usingMRI. Journal of applied clinical medical physics,
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., et al.
(2019). Patterns of recurrence after prostate bed radiotherapy. Radiotherapy and oncology,
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., et al.
(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. European urology,
Brand, D.H., Tree, A.C., Hall, E. & van As, N.
(2019). Optimal patient selection for stereotactic body radiotherapy – Authors' reply. The lancet oncology,
Hanna, G.G., Murray, L., Patel, R., Jain, S., Aitken, K.L., Franks, K.N., van As, N., Tree, A., Hatfield, P., Harrow, S., et al.
(2018). UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clinical oncology,
Binzel, K., Adelaja, A., Wright, C.L., Scharre, D., Zhang, J., Knopp, M.V., Teoh, E.J., Bottomley, D., Scarsbrook, A., Payne, H., et al.
(2018). Abstracts of the 33rd International Austrian Winter Symposium. Ejnmmi research,
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., et al.
(2018). Magnetic Resonance Imaging-Guided Adaptive Radiation Therapy: A “Game Changer” for Prostate Treatment?. International journal of radiation oncology*biology*physics,
Wedge, D.C., Gundem, G., Mitchell, T., Woodcock, D.J., Martincorena, I., Ghori, M., Zamora, J., Butler, A., Whitaker, H., Kote-Jarai, Z., et al.
(2018). Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets. Nature genetics,
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. Clinical oncology,
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., et al.
(2017). Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered. Jama oncology,
Bianchini, D., Lorente, D., Rescigno, P., Zafeiriou, Z., Psychopaida, E., O'Sullivan, H., Alaras, M., Kolinsky, M., Sumanasuriya, S., Sousa Fontes, M., et al.
(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. Clinical genitourinary cancer,
Patrikidou, A., Uccello, M., Tree, A., Parker, C., Attard, G., Eeles, R., Khoo, V., van As, N., Huddart, R., Dearnaley, D., et al.
(2017). Upfront Docetaxel in the Post-STAMPEDE World: Lessons from an Early Evaluation of Non-trial Usage in Hormone-Sensitive Prostate Cancer. Clinical oncology,
Ost, P., Jereczek-Fossa, B.A., As, N.V., Zilli, T., Muacevic, A., Olivier, K., Henderson, D., Casamassima, F., Orecchia, R., Surgo, A., et al.
(2016). Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis. European urology,
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. Clinical oncology,
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. European urology,
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. European urology,
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., et al.
(2016). MRI-guided prostate adaptive radiotherapy – A systematic review. Radiotherapy and oncology,
Ost, P., Jereczek-Fossa, B.A., Van As, N., Zilli, T., Tree, A., Henderson, D., Orecchia, R., Casamassima, F., Surgo, A., Miralbell, R., et al.
(2016). Pattern of Progression after Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Nodal Recurrences. Clinical oncology,
White, I.D., Wilson, J., Aslet, P., Baxter, A.B., Birtle, A., Challacombe, B., Coe, J., Grover, L., Payne, H., Russell, S., et al.
(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,
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..
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,
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., et al.
(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. The lancet oncology,
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,
Henderson, D.R., Tree, A.C. & van As, N.J.
(2015). Stereotactic body radiotherapy for prostate cancer. Clin oncol (r coll radiol),
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., et al.
(2015). Initial UK Experience of Stereotactic Body Radiotherapy for Extracranial Oligometastases: Can We Change the Therapeutic Paradigm?. Clinical oncology,
Dearman, C., van As, N., Crellin, A., Slevin, N. & Sharma, R.A.
(2015). Surgery versus SABR for resectable non-small-cell lung cancer. The lancet oncology,
Hafeez, S., Horwich, A., Omar, O., Mohammed, K., Thompson, A., Kumar, P., Khoo, V., Van As, N., Eeles, R., Dearnaley, D., et al.
(2015). Selective organ preservation with neo-adjuvant chemotherapy for the treatment of muscle invasive transitional cell carcinoma of the bladder. British journal of cancer,
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),
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,
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),
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., Khoo, V. & van As, N.
(2014). The Incidence of Ciprofloxacin Resistance in Patients Undergoing Gold Seed Insertion for Image-guided Prostate Radiotherapy. Clinical oncology,
Omlin, A., Pezaro, C.J., Zaidi, S., Lorente, D., Mukherji, D., Bianchini, D., Ferraldeschi, R., Sandhu, S., Dearnaley, D., Parker, C., et al.
(2014). Reply: 'Comment on Anti-tumour activity of abiraterone and diethylstilboestrol when administered sequentially to men with castration-resistant prostate cancer'. Br j cancer,
Bancroft, E.K., Page, E.C., Castro, E., Lilja, H., Vickers, A., Sjoberg, D., Assel, M., Foster, C.S., Mitchell, G., Drew, K., et al.
(2014). Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study. European urology,
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., et al.
(2014). Prostate stereotactic body radiotherapy—first UK experience. Clin oncol (r coll radiol),
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., et al.
(2013). Stereotactic body radiotherapy for oligometastases. Lancet oncol,
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,
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., et al.
(2013). Antitumour activity of abiraterone and diethylstilboestrol when administered sequentially to men with castration-resistant prostate cancer. Br j cancer,
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., et al.
(2013). Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat genet,
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,
(2013). Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. British journal of surgery,
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,
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..
(2013). Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. British journal of surgery,
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),
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., et al.
(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,
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., et al.
(2012). Transatlantic Consensus Group on active surveillance and focal therapy for prostate cancer. Bju international,
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. Brit j radiol,
Objectives: We studied patients managed by active surveillance to determine whether there was a difference over time in apparent diffusion coefficients (ADCs) derived from diffusion-weighted MRI in those who progressed to radical treatment (progressors, n=17) compared with those who did not (non-progressors, n=33).Methods: 50 consecutive patients (Stage T1/2a, Gleason grade <= 3+4, prostate-specific antigen (PSA) <15 ng ml(-1), <50% cores positive) were imaged endorectally (baseline and 1-3 years follow-up) with T-2 weighted (T2W) and echo-planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps with reference to the T2W images yielded AD(Call) (b=0-800), ADC(fast) (b=0-300) and ADC(slow) (b=300-800) for whole prostate (minus tumour) and tumour (low signal-intensity peripheral zone lesion in biopsy-positive octant).Results: Tumour and whole prostate ADC(all) and ADC(fast) were significantly reduced over time in progressors (p=0.03 and 0.03 for tumours, respectively; p=0.02 and 0.007 for the whole prostate, respectively). There were no significant changes in ADC over time in non-progressors. A 10% reduction in tumour ADC(all) indicated progression with a 93% sensitivity and 40% specificity (A(z) of receiver operating characteristic (ROC) curve = 0.68). Percentage reductions in whole prostate ADC(all), ADC(fast) and ADC(slow) were also significantly greater in progressors than in non-progressors (p=0.01, 0.03 and 0.008, respectively).Conclusion: This pilot study shows that DW-MRI has potential for monitoring patients with early prostate cancer who opt for active surveillance..
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?. Clin oncol-uk,
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?. Clin oncol-uk,
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,
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,
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., et al.
(2011). A risk prediction algorithm based on family history and common genetic variants: application to prostate cancer with potential clinical impact. Genet epidemiol,
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., et al.
(2011). Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat genet,
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,
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,
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),
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,
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., et al.
(2009). Prostate-specific antigen (PSA) kinetics in untreated, localized prostate cancer: PSA velocity vs PSA doubling time. Bju int,
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., et al.
(2009). Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat genet,
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., et al.
(2009). Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat genet,
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,
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,
Van As, N., Charles-Edwards, E., Jackson, A., Jhavar, S., Reinsberg, S., Desouza, N., Dearnaley, D., Bailey, M., Thompson, A., Christmas, T., et al.
(2008). Correlation of diffusion-weighted MRI with whole mount radical prostatectomy specimens. Br j radiol,
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..
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. Clin radiol,
AIM: To evaluate diffusion-weighted magnetic resonance imaging (DW-MRI) as a marker for disease aggressiveness by comparing tumour apparent diffusion coefficients (ADCs) between patients with low- versus higher-risk localized prostate cancer.METHOD: Forty-four consecutive patients classified as low- [n = 26, stageT1/T2a, Gleason score <= 6, prostate-specific antigen (PSA) 10 (group 1)] or intermediate/high- [n = 18, stage >= T2b and/or Gleason score >= 7, and/or PSA > 10 (group 2)] risk, who subsequently were monitored with active surveillance or started neoadjuvant hormone and radiotherapy, respectively, underwent endorectal MRI. T2-weighted (T2W) and DW images (5 b values, 0-800 s/mm(2)) were acquired and isotropic ADC maps generated. Regions of interest (ROIs) on T2W axial images [around whole prostate, central gland (CG), and tumour] were transferred to ADC maps. Tumour, CG, and peripheral zone (PZ = whole prostate minus CG and tumour) ADCs (fast component from b = 0-100 s/mm(2), slow component from b = 100-800 s/mm(2)) were compared.RESULTS: T2W-defined tumour volume medians, and quartiles were 1.2 cm(3), 0.7 and 3.3 cm(3) (group 1); and 6 cm(3), 1.3 and 16.5 cm(3) (group 2). There were significant differences in both ADC(fast) (1778 +/- 264 x 10(-6) versus 1583 +/- 283 x 10(-6) mm(2)/s, p = 0.03) and ADC(slow) (1379 +/- 321 x 10(-6) versus 1196 +/- 158 x 10(-6) mm(2)/s, p = 0.001) between groups. Tumour volume (p = 0.002) and ADC(slow) (p = 0.005) were significant differentiators of risk group.CONCLUSION: Significant differences in tumour ADCs exist between patients with low-risk, and those with higher-risk localized prostate cancer. DW-MRI merits further study with respect to clinical outcomes. (C) 2008 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved..
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,
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,
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. Clin oncol-uk,
van As, N., Charles-Edwards, E., Jackson, A., Jhavar, S., Reinsberg, S., deSouza, N., Dearnaley, D., Baileys, M., Thompson, A., Christmas, T., et al.
(2007). Correlation of diffusion-weighted MRI (DWMRI) with whole mount radical prostatectomy specimen. Clin oncol-uk,
van As, N.J. & Parker, C.C.
(2007). Active surveillance with selective radical treatment for localized prostate cancer. Cancer j,
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 suppl,
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,
Wedlake, L., Shaw, C., McNair, H., Lalji, A., Mohammed, K., Klopper, T., Allan, L., Tait, D., Hawkins, M., Somaiah, N., et al.
Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy. The american journal of clinical nutrition,
Dearnaley, D., reis ferreira, M., khan, A., truelove, L., gao, A., parker, C., huddart, R., eeles, R., khoo, V. & van as, N., et al.
A phase I/II dose escalation study of the use of intensity modulated radiotherapy (IMRT) to treat the prostate and pelvic nodes in patients with prostate cancer. International journal of radiation oncology • biology • physics,
Henderson, D., Tree, A., Harrington, K. & van As, N.
Dosimetric Implications of Computerised Tomography-Only versus Magnetic Resonance-Fusion Contouring in Stereotactic Body Radiotherapy for Prostate Cancer. Medicines,
Hall, E., Brand, D., Tree, A., Ostler, P., van der Voet, H., Loblaw, A., Chu, W., Ford, D., Tolan, S., Jain, S., et al.
Intensity Modulated Fractionated Radiotherapy Versus Stereotactic Body Radiotherapy for Prostate Cancer (PACE-B): Acute Toxicity Results From a Randomised Open-label Phase III Non-inferiority Trial. The lancet oncology,