Chemoradiotherapy of rectal cancer Acute toxicity with intensity modulated radiotherapy versus 3-dimensional conformal radiotherapy during preoperative chemoradiation for locally advanced rectal cancer

Background and purpose: We examined acute toxicity profiles and outcomes among rectal cancer patients treated with pre-operative chemoradiation using intensity modulated radiotherapy (IMRT) or 3dimensional conformal radiotherapy (3DCRT) to identify predictive clinical factors associated with increased acute toxicity. Material and methods: We retrospectively reviewed records of 301 consecutive rectal cancer patients treated with pre-operative chemotherapy and radiotherapy (median dose 5000 cGy) at our institution between 2007 and 2014. Results: Of the 301 patients, 203 (67.4%) were treated with IMRT and 98 (32.6%) with 3DCRT. Significantly more patients experienced Pgrade 2 diarrhea in the 3DCRT group compared to the IMRT group (22% vs 10%, p = 0.004), and those who received 3DCRT had 2.7 times greater odds of a higher diarrhea score than those on IMRT, even after adjusting for patient characteristics and chemotherapy (OR 2.71, p = 0.01) Fewer patients experienced grade 2 genitourinary toxicity in the IMRT group (6% vs 13% 3DCRT, p = 0.04) and there was a trend toward decreased grade 2 proctitis in the IMRT group (22% vs 32% 3DCRT, p = 0.07). Patients over the age of 55 had 45% lower odds of proctitis than patients younger than 55. Conclusion: The use of IMRT significantly reduced grade P2 diarrhea and GU toxicity during chemoradiation. Younger patients were more likely to report grade 2 or higher proctitis. 2016 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 121 (2016) 252–257 Preoperative pelvic radiotherapy (RT) with concurrent 5Fluorouracil (FU)-based chemotherapy remains the current standard of care for patients with locally advanced rectal cancer based on landmark phase III randomized trials published over a decade ago [1–3]. While the outcomes for locally advanced rectal cancer continue to improve with the introduction of more sophisticated surgical techniques, such as the total mesorectal excision (TME) [4] and with more modern chemotherapy agents [5], conventional pelvic RT is still associated with significant acute toxicities that can adversely impact a patient’s quality of life and tolerance of therapy [6,7]. While the more conformal planning approach of intensitymodulated radiotherapy (IMRT) has been introduced for the management of many other malignancies [8–11], it remains controversial for pre-operative pelvic RT for rectal cancer. In fact, although recent prospective phase II data of IMRT in combination with capecitabine and oxaliplatin failed to meet the endpoint of reduced toxicity when compared to historical data, this study did not evaluate the now-standard approach of pre-operative capecitabine and pelvic RT and therefore doesn’t fully address the benefit of IMRT when more standard chemotherapy agents are given. A strong dose–volume relationship has been demonstrated for the small bowel irradiated and acute diarrhea during preoperative chemoradiation [12]. Dosimetric studies have shown that IMRT for rectal cancer can reduce dose to adjacent organs at risk while maintaining superior target coverage, homogeneity and conformality, making it a superior technique to 3D conformal RT (3DCRT) in the treatment of rectal cancer [13,14]. Moreover, several retrospective clinical studies have suggested that the use of IMRT does significantly decrease toxicity and also reduces treatment breaks, emergency department visits and hospitalizations [15–18]. Given the controversy surrounding the use of IMRT in preoperative S.Y. Ng et al. / Radiotherapy and Oncology 121 (2016) 252–257 253 therapy for rectal cancer, we examined acute toxicity profiles and outcomes between patients treated with IMRT and 3DCRT in a large cohort of patients and sought to identify predictive clinical factors associated with increased acute toxicity, thereby characterizing scenarios in which IMRT might be most appropriate. Fig. 1. GradeP 2 toxicity graded according to CTCAE v3.0. Abbreviations: IMRT = intensity modulated radiotherapy; 3DCRT = 3D conformal radiotherapy; GU = genitourinary. ⁄No grade 3 or higher toxicity occurred in these categories. Methods After obtaining a waiver of authorization from our Institutional Review Board, we identified and retrospectively reviewed records of 318 consecutive patients with primary rectal cancer who were treated with preoperative chemoradiation between January 2007 and October 2014 at Memorial Sloan Kettering Cancer Center’s (MSKCC) main campus. All patients had biopsy-confirmed adenocarcinoma by the MSKCC Department of Pathology. Patients underwent pretreatment imaging consisting of computed tomography (CT) chest, abdomen, pelvis, rectal protocol magnetic resonance imaging (MRI), examination by a colorectal surgeon (including proctoscopy and/or endorectal ultrasound), clinical examination and routine laboratory testing. Clinical and tumor characteristics were obtained from the medical record and a prospectively maintained database.