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Neoadjuvant Chemoradiation Versus Hyperfractionated Accelerated Radiotherapy in Locally Advanced Rectal Cancer
Authors:Wim Ceelen MD  Tom Boterberg MD   PhD  Piet Pattyn MD   PhD  Marc van Eijkeren MD   PhD  Jean-Marc Gillardin MD  Pieter Demetter MD   PhD  Peter Smeets MD  Nancy Van Damme PhD  Els Monsaert MD  Marc Peeters MD   PhD
Affiliation:(1) Department of Surgical Oncology, University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium;(2) Department of Radiotherapy, University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium;(3) Department of Pathology, Erasmus Hospital, Lenniksebaan 808, B-1070 Brussels, Belgium;(4) Department of Radiology, University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium;(5) Department of Hepatogastroenterology, University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium
Abstract:Background Neoadjuvant therapy is increasingly used in resectable locally advanced rectal cancer. The exact role of the addition of chemotherapy is not established. We compared neoadjuvant therapy using chemoradiation (CRT) or hyperfractionated accelerated radiotherapy (HART). Methods Clinical, pathological, and survival data were obtained from patients with resectable stage II or III rectal cancer within 7 cm from the anal verge. A group of 50 patients was treated with a preoperative dose of 41.6 Gy of radiotherapy (RT) in two daily fractions of 1.6 Gy over 13 days immediately followed by surgery (HART). A second group of 96 patients received 45 Gy of conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 5-fluorouracil–based chemotherapy followed by surgery within 4 to 6 weeks (CRT). Both groups were compared in terms of morbidity, pathological downstaging, local recurrence, and survival. Results Both groups were comparable in terms of preoperative clinicopathological variables. The mean distance from the anal verge was 5.8 cm (HART) versus 4.9 cm (CRT). Sphincter preservation was possible in 74% (HART) versus 83.5% (CRT) of patients (P = .013). The clinical anastomotic leak rate was 2% (HART) versus 2.2% (CRT). Pathological complete response was observed in 4% (HART) versus 18% (CRT) of the resected specimens (P = .002). A pelvic recurrence developed in 6% (HART) versus 4.4% (CRT) of patients (P = .98). Overall 5-year survival was 58% (HART) versus 66% (CRT) (P = .19); disease-free 5-year survival was 51% (HART) versus 62% (CRT) (P = .037). Conclusions Compared with preoperative HART followed by immediate surgery, preoperative CRT followed by a 6-week waiting period enhances pathological response and increases sphincter preservation rate. This could be explained by the addition of chemotherapy or the longer interval between neoadjuvant therapy and surgery. No statistically significant difference was observed in local control or overall survival.
Keywords:Rectal cancer  Neoadjuvant  Total mesorectal excision  Hyperfractionated accelerated therapy  Chemoradiation
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