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• W2029345892 abstract "Anal squamous cell carcinoma affects approximately 1100 patients per year in the UK, with the incidence increasing yearly [[1]Wilkinson J.R. Morris E.J. Downing A. et al.The rising incidence of anal cancer in England 1990–2010; a population-based study.Colorectal Dis. 2014; 16: 0234-0239Crossref Scopus (65) Google Scholar]. The ACT2 trial, delivering radical chemoradiotherapy, determined the UK standard of care; reporting a complete response rates of 90% and a 3 year progression-free survival of 73% [[2]James R.D. Glynne-Jones R. Meadows H.M. et al.Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial.Lancet Oncol. 2013; 14: 516-524Abstract Full Text Full Text PDF PubMed Scopus (510) Google Scholar]. Due to the large parallel-opposed anterior–posterior/posterior–anterior (AP/PA) fields, there was significant associated acute toxicity; grade 3/4 gastrointestinal and haematological toxicity of 16 and 26%, respectively. Acute toxicity results in delays and interruptions; a concern, as there is evidence to suggest overall treatment time is associated with local control [3Weber D.C. Kurtz J.M. Allal A.S. The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy.Int J Radiat Oncol Biol Phys. 2001; 50: 675-680Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar, 4Glynne-Jones R. Sebag-Montefiore D. Adams R. et al.“Mind the gap” – the impact of variations in the duration of the treatment gap and overall treatment time in the first UK Anal Cancer Trial (ACT I).Int J Radiat Oncol Biol Phys. 2011; 81: 1488-1494Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 5Konski A. Garcia Jr., M. John M. et al.Evaluation of planned treatment breaks during radiation therapy for anal cancer: update of RTOG 92-08.Int J Radiat Oncol Biol Phys. 2008; 72: 114-118Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar]. Finally, there is a lack of prospective data quantifying the recognised late side-effects on bowel, urinary and sexual function. Late bowel toxicity culminating in colostomy was seen in 2% of patients in the ACT2 trial [[6]Glynne-Jones R. Kadalayil L. Meadows H. et al.Tumour- and treatment-related colostomy rates following 5Fluorouracil (5FU) and Mitomycin (MMC) or 5FU and Cisplatin (Cisp) chemoradiation (CRT) with or without maintenance chemotherapy in squamous cell carcinoma of the anus: Results of the randomised phase III trial ACT II.2013http://conference.ncri.org.uk/abstracts/2013/abstracts/LB18.htmGoogle Scholar]. Since the completion of ACT2 there have been significant developments in the staging and treatment of anal cancer. There is interest in improving late morbidity by withholding inguinal node irradiation in early disease. This has led to reports addressing the role of sentinel node biopsy and positron emission tomography/computed tomography in staging. Recent trials have individualized radiotherapy dose according to tumour size and nodal status. Finally, there has been widespread implementation of intensity-modulated radiotherapy (IMRT) to reduce acute toxicity and potentially dose-escalate selected patients. The Radiation Therapy Oncology Group (RTOG) 0529 phase II study, open from December 2006 to March 2008, delivered a prophylactic dose to uninvolved nodal groups with a simultaneous integrated boost to the primary tumour and involved nodes using IMRT; acute dermatological toxicity was the primary end point [[7]Kachnic L.A. Winter K. Myerson R.J. et al.RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal.Int J Radiat Oncol Biol Phys. 2013; 86: 27-33Abstract Full Text Full Text PDF PubMed Scopus (443) Google Scholar]. The acute toxicity was compared with that seen in previous RTOG studies using radiotherapy techniques used in the late 1990s, and a statistically significant reduction in grade 2 haematological, grade 3 gastrointestinal and grade 3 dermatological toxicities was reported, although not fulfilling the primary end point. Although not a randomised trial, this study adds further weight to the reduction in toxicity observed in published IMRT series [8Bazan J.G. Hara W. Hsu A. et al.Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal.Cancer. 2011; 117: 3342-3351Crossref PubMed Scopus (112) Google Scholar, 9Call J.A. Prendergast B.M. Jensen L.G. et al.Intensity-modulated radiation therapy for anal cancer: results from a multi-institutional retrospective cohort study.Am J Clin Oncol. 2014; (in press)Google Scholar, 10Chuong M.D. Freilich J.M. Hoffe S.E. et al.Intensity-modulated radiation therapy vs. 3D conformal radiation therapy for squamous cell carcinoma of the anal canal.Gastrointest Cancer Res. 2013; 6: 39-45PubMed Google Scholar, 11Dasgupta T. Rothenstein D. Chou J.F. et al.Intensity-modulated radiotherapy vs. conventional radiotherapy in the treatment of anal squamous cell carcinoma: a propensity score analysis.Radiother Oncol. 2013; 107: 189-194Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 12DeFoe S.G. Beriwal S. Jones H. et al.Concurrent chemotherapy and intensity-modulated radiation therapy for anal carcinoma – clinical outcomes in a large National Cancer Institute-designated integrated cancer centre network.Clin Oncol (R Coll Radiol). 2012; 24: 424-431Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 13Vieillot S. Fenoglietto P. Lemanski C. et al.IMRT for locally advanced anal cancer: clinical experience of the Montpellier Cancer Center.Radiat Oncol. 2012; 7: 45Crossref PubMed Scopus (42) Google Scholar, 14Dewas C.V. Maingon P. Dalban C. et al.Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer?.Radiat Oncol. 2012; 7: 201Crossref PubMed Scopus (27) Google Scholar]. Current controversies regarding IMRT implementation include the optimal duration of treatment with chemoradiotherapy. Since 1987, ACT1 and ACT2 studies have maintained a different approach to European and North American dose and fractionations; with a shorter overall treatment time, no gaps in treatment and lower prescribed and delivered doses. Due to the excellent outcomes within ACT2, this strategy should be maintained moving forward. However, to definitively convert the delivered dose in ACT2 into a simultaneous integrated boost technique remains a challenge. Second, defining and maintaining a consistent planning and delivery technique is of vital importance to facilitate robust outcome comparisons. Thinking towards the future, with an ACT3/4 study on the horizon, a consensus IMRT technique will facilitate set-up and entry into future anal cancer trials. A survey of anal cancer techniques currently in use in the UK was undertaken with the Faculty of Clinical Oncology of The Royal College of Radiologists in October/November 2013. This highlighted a great variation in delineation, volumes and doses currently in use in those centres using IMRT, reflecting the lack of consistency in published series. Finally, the rigorous quality assurance programme in RTOG 0529 highlighted the risks of implementation without adequate guidelines and support; 81% of plans required revisions, with 46% requiring multiple revisions, primarily due to poor delineation. Robust quality assurance will maintain quality of delivery of IMRT and the integrity of future anal cancer trials. A previous editorial published in Clinical Oncology highlighted the need for a UK protocol with robust collection of prospective toxicity and outcome data to maintain quality of planning and delivery [[15]Gilbert D.C. Glynne-Jones R. Intensity-modulated radiotherapy in anal cancer: where do we go from here?.Clin Oncol (R Coll Radiol). 2013; 25: 153-154Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar]. In response to the Editorial, the Anorectal Subgroup of the National Cancer Research Institute (NCRI) Clinical Studies Group met and produced IMRT guidance. A systematic review of the published literature informed decisions regarding immobilisation, delineation, doses and delivery technique. Representatives from a number of large teaching hospitals and all members of the Anorectal Clinical Studies Group, with a wealth of clinical experience and knowledge of the literature, met a number of times to debate different aspects of planning and delivery. Thereafter, the guidance was circulated to a further nine centres for comment, followed by a presentation and further modifications at the annual NCRI cancer conference before reaching a consensus [[16]Muirhead R. Adams R. Gilbert D. et al.An evidence-based UK IMRT solution for anal cancer: the development of the control arm for future UK led clinical trials.2013http://conference.ncri.org.uk/Google Scholar]. There are limitations to these guidelines. As with any rare tumour type, randomised controlled evidence in the literature is lacking, and retrospective studies or small single centre studies are often used to direct guidance. These publications must be interpreted with care and all have limitations; for example, varied staging and treatment strategies, varied follow-up, small sample size, retrospective assessment of toxicity. Therefore, recommendations proposed here are limited by current knowledge from a small number of prospective studies and should not be considered definitive; they will evolve as knowledge expands. The guidance is available from the corresponding author or at www.analimrtguidance.co.uk. The aim of the proposed guidance is to facilitate the adoption and implementation of IMRT in anal cancer treatment. The prospective audit, in collaboration with the Royal College of Radiologists, planned for November 2014 will test if adoption has been successful and document toxicity and outcomes of the novel doses and fractionations in comparison with published data, including ACT2. If outcomes appear favourable, the proposed technique will form the basis of the standard arm for the next national study. Pelvic Intensity-modulated Radiotherapy: Can we Better Quantify the Late Side-effects?Clinical OncologyVol. 27Issue 7PreviewSir — We read with interest the paper by Muirhead and colleagues [1] regarding the development of an intensity-modulated radiotherapy (IMRT) solution for ACT2 fractionation. Full-Text PDF" @default.
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• W2029345892 title "Anal Cancer: Developing an Intensity-modulated Radiotherapy Solution for ACT2 Fractionation" @default.
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