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Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04)

Ansari, Nabila MBBS, FRACS*; Solomon, Michael J. MBBCh, MSc, FRACS*; Fisher, Richard J. MBBS, PhD; Mackay, John MBBS, FRACS; Burmeister, Bryan MBChB, MD, FRANZCR§; Ackland, Stephen MBBS, FRACP; Heriot, Alexander MA, MB BChir MD, FRACS; Joseph, David MBBS, FRACR||; McLachlan, Sue-Anne MBBS, MSci, FRACP**,††; McClure, Bev BSc(Hons); Ngan, Samuel Y. MBBS, FRANZCR‡‡

doi: 10.1097/SLA.0000000000001987
Randomized Controlled Trials

Objective: To compare acute adverse events (AE) and postoperative complication rates in a randomized trial of short-course (SC) versus long-course (LC) preoperative radiotherapy.

Background: Evidence demonstrates that adding neoadjuvant radiotherapy to surgery offers better local control in the management of rectal cancer. With both SC and LC therapy there is a potential for acute treatment-related toxicity and increased patient morbidity.

Methods: Eligible patients had clinical-stage T3 rectal adenocarcinoma within 12 cm of the anal verge with no evidence of metastasis. SC consisted of pelvic radiotherapy 5 × 5 Gy in 1 week, early surgery and 6 courses of adjuvant chemotherapy. LC was 50.4 Gy administered in 28 fractions during 5.5 weeks, with infusion 5-fluorouracil, surgery in 4 to 6 weeks, and 4 courses of chemotherapy.

Results: All SC patients and 93% of LC patients received preoperative planned radiotherapy. There was no 30-day operative mortality. A statistically significant higher percentage of at least 1 AE occurred in the LC group (SC, 72.3%; LC, 99.4%; P < 0.001). There were significant differences in favor of SC for grade 3 AE: radiation dermatitis (0% vs 5.6%, P = 0.003), proctitis (0% vs 3.7% P = 0.016), nausea (0% vs 3.1%, P = 0.029), fatigue (0% vs 3.7%, P = 0.016) and grade 3/4 diarrhea rates (1.3% vs 14.2% P < 0.001). No statistically significant differences in surgical complication rates were seen (SC 53.2 vs 50.4% LC, p = 0.68), although permanent stoma (38.0% vs 29.8%, P = 0.13) and anastomotic breakdown (7.1% vs 3.5%, P = 0.26) rates favored LC with perineal wound complications (38.3% vs 50.0%, P = 0.26) in favor of SC.

Conclusions: LC had significantly higher AEs compared with SC with no statistically significant differences in postoperative complications. There were clinical trends in permanent stoma rates and anastomotic leaks in favor of LC but with an increased perineal wound breakdown rate.

*Surgical Outcome Research Centre (SOuRCe, The Institute of Academic Surgery at Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia

Peter MacCallum Cancer Centre, Centre for Biostatistics and Clinical Trials, Melbourne, Victoria, Australia

Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

§Princess Alexandra Hospital, The University of Queensland, Woolloongabba, Queensland, Australia

Department of Oncology, Calvary Mater Hospital, Newcastle, New South Wales, Australia

||Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

**Department of Oncology, St. Vincent's Hospital, Melbourne, Victoria, Australia

††Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia

‡‡Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Reprints: Michael J. Solomon, MBBCh, MSc, FRACS, Surgical Outcomes Research Centre, University of Sydney, PO Box M157, Missenden Rd, New South Wales 2050, Australia. E-mail: professor.solomon@sydney.edu.au.

Disclosure: The trial was supported by the National Health and Medical Research Council (NHMRC, No 209123), Cancer Council Victoria, and The Royal Australian and New Zealand College of Radiologists (RANZCR). Dr Nabila Ansari was supported by the NOTARAS Scholarship of the University of Sydney and the Post Fellowship Training Board in Colorectal Surgery of the Colorectal Surgical Society of Australia and New Zealand (CSSANZ) and the Royal Australasian College of Surgeons (RACS). The authors report no conflicts of interest.

www.clinicaltrials.gov registration number: NCT00145769.

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