Journal ArticleDOI
Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial
Johan Erlandsson,Torbjörn Holm,David Pettersson,Åke Berglund,Björn Cedermark,Calin Radu,Hemming Johansson,Mikael Machado,Fredrik Hjern,Olof Hallböök,Ingvar Syk,Bengt Glimelius,Anna Martling +12 more
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Recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery is studied in patients with a biopsy-proven adenocarcinoma of the rectum from 18 Swedish hospitals.Abstract:
Summary Background Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. Methods In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 × 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4–8 weeks (short-course radiotherapy with delay) or 25 × 2 Gy radiation dose with surgery after 4–8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1·7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813. Findings Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33·4 months (range 18·2–62·2) in the short-course radiotherapy group and 19·3 months (8·5–39·5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33·3 months (range 17·8–114·3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1·44 [95% CI 0·41–5·11]; long-course radiotherapy with delay 2·24 [0·71–7·10]; p=0·48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient ( vs short-course radiotherapy: short-course radiotherapy with delay 0·59 [95% CI 0·36–0·97], long-course radiotherapy with delay 0·63 [0·38–1·04], p=0·075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0·61 [95% CI 0·45–0·83] p=0·001). Interpretation Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery. Funding Swedish Research Council, Swedish Cancer Society, Stockholm Cancer Society, and the Regional Agreement on Medical Training and Clinical Research in Stockholm.read more
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Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.
Renu R. Bahadoer,Esmée A Dijkstra,Boudewijn van Etten,Corrie A.M. Marijnen,Corrie A.M. Marijnen,Hein Putter,Elma Meershoek-Klein Kranenbarg,Annet G H Roodvoets,Iris D. Nagtegaal,Regina G. H. Beets-Tan,Lennart Blomqvist,Tone Fokstuen,Albert J. ten Tije,Jaume Capdevila,Mathijs P. Hendriks,Ibrahim Edhemovic,Andrés Cervantes,Per Nilsson,Bengt Glimelius,Cornelis J.H. van de Velde,Geke A. P. Hospers,L. Østergaard,F. Svendsen Jensen,P. Pfeiffer,K.E.J. Jensen,M.P. Hendriks,W.H. Schreurs,H.P. Knol,J.J. van der Vliet,J.B. Tuynman,A.M.E. Bruynzeel,E.D. Kerver,S. Festen,M E van Leerdam,G.L. Beets,L.G.H. Dewit,C.J.A. Punt,Pieter J. Tanis,E.D. Geijsen,P. Nieboer,W.A. Bleeker,A.J. Ten Tije,R.M.P.H. Crolla,A.C.M. van de Luijtgaarden,J.W.T. Dekker,J.M. Immink,F.J.F. Jeurissen,A.W.K.S. Marinelli,H.M. Ceha,T.C. Stam,P. Quarles an Ufford,W.H. Steup,A.L.T. Imholz,R.J.I. Bosker,J.H.M. Bekker,G.J. Creemers,G.A.P. Nieuwenhuijzen,H. van den Berg,W.M. van der Deure,R.F. Schmitz,J.M. van Rooijen,A.F.T. Olieman,A.C.M. van den Bergh,Derk Jan A. de Groot,Klaas Havenga,Jannet C. Beukema,J. de Boer,P.H.J.M. Veldman,E.J.M. Siemerink,J.W.P. Vanstiphout,B. de Valk,Q.A.J. Eijsbouts,M.B. Polée,C. Hoff,A. Slot,H.W. Kapiteijn,K.C.M.J. Peeters,F.P. Peters,P.A. Nijenhuis,S.A. Radema,H. de Wilt,P. Braam,G.J. Veldhuis,D. Hess,T. Rozema,O. Reerink,D. Ten Bokkel Huinink,A. Pronk,Janet R. Vos,M. Tascilar,G.A. Patijn,C. Kersten,O. Mjåland,M. Grønlie Guren,A.N. Nesbakken,J. Benedik,I. Edhemovic,V. Velenik,J. Capdevila,E. Espin,R. Salazar,S. Biondo,V. Pachón,J. die Trill,J. Aparicio,E. Garcia Granero,M.J. Safont,J.C. Bernal,A. Cervantes,A. Espí Macías,L. Malmberg,G. Svaninger,H. Hörberg,G. Dafnis,A. Berglund,L. Österlund,K. Kovacs,J. Hol,S. Ottosson,G. Carlsson,C. Bratthäll,J. Assarsson,B.L. Lödén,P. Hede,I. Verbiené,O. Hallböök,A. Johnsson,M.L. Lydrup,K. Villmann,P. Matthiessen,J.H. Svensson,J. Haux,S. Skullman,T. Fokstuen,Torbjörn Holm,P. Flygare,M. Walldén,B. Lindh,O. Lundberg,C. Radu,L. Påhlman,A. Piwowar,K. Smedh,U. Palenius,S. Jangmalm,P. Parinkh,H. Kim,M.L. Silviera +147 more
TL;DR: The Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control.
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S3-Leitlinie – Kolorektales Karzinom.
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The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.
Y. Nancy You,Karin M. Hardiman,Andrea C Bafford,Vitaliy Poylin,Todd D. Francone,Kurt G. Davis,Ian M. Paquette,Scott R. Steele,Daniel L. Feingold +8 more
TL;DR: This paper presents a meta-analyses of EMMARM, a probabilistic approach to estimating the likelihood of EMTs using EMMAR, and its implications for future treatments of central nervous system disorders.
Journal ArticleDOI
Radiation Therapy for Cervical Cancer: Executive Summary of an ASTRO Clinical Practice Guideline
Junzo Chino,Christina M. Annunziata,Sushil Beriwal,Lisa Bradfield,Beth Erickson,Emma C. Fields,Kathryn Jane Fitch,Matthew M. Harkenrider,Matthew M. Harkenrider,Christine H. Holschneider,Mitchell Kamrava,Eric Leung,Lilie L. Lin,Jyoti Mayadev,Marc Morcos,Chika Nwachukwu,Daniel G. Petereit,Akila N. Viswanathan +17 more
TL;DR: This guideline reviews the evidence and provides recommendations for the indications and appropriate techniques of radiation therapy (RT) in the treatment of nonmetastatic cervical cancer and suggests brachytherapy is an essential part of definitive management and volumetric planning is recommended.
Journal ArticleDOI
Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer – Results of the international randomized RAPIDO-trial
Maxime J M van der Valk,Corrie A.M. Marijnen,Corrie A.M. Marijnen,Boudewijn van Etten,Esmée A Dijkstra,Denise E. Hilling,Elma Meershoek-Klein Kranenbarg,Hein Putter,Annet G H Roodvoets,Renu R. Bahadoer,Tone Fokstuen,Albert J. ten Tije,Jaume Capdevila,Mathijs P. Hendriks,Ibrahim Edhemovic,Andrés Cervantes,Derk Jan A. de Groot,Per Nilsson,Bengt Glimelius,Cornelis J.H. van de Velde,Geke A. P. Hospers +20 more
TL;DR: Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications, and high compliance of preoperative systemic treatment could be achieved with the experimental approach.
References
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Rolf Sauer,Heinz Becker,Werner Hohenberger,Claus Rödel,Christian Wittekind,Rainer Fietkau,Peter Martus,Jörg Tschmelitsch,Eva Hager,Clemens F. Hess,Torsten Liersch,Heinz Schmidberger,Rudolf Raab +12 more
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Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC)
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Preoperative Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal Cancer
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Journal ArticleDOI
Chemotherapy with preoperative radiotherapy in rectal cancer
Jean-François Bosset,Laurence Collette,Gilles Calais,Laurent Mineur,Philippe Maingon,L. Radosevic-Jelic,Alain Daban,Etienne Bardet,Alexander Beny,Jean-Claude Ollier +9 more
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Improved survival with preoperative radiotherapy in resectable rectal cancer.
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