Memorial Sloan-Kettering Cancer Center
T. Jonathan Yang , Jung Hun Oh , Christina Son , Aditya Apte , Joseph Deasy , Abraham Wu , Karyn Goodman
Background: To identify clinical and dosimetric factors associated with acute gastrointestinal (GI) toxicities due to pelvic radiotherapy (PRT) in patients with rectal cancer. Methods: We analyzed 177 consecutive rectal cancer patients treated between 2007-2010. Clinical information including age, gender, stage, chemotherapy, and weekly proctitis and diarrhea grade (CTCAE 3.0) during PRT were obtained. The bowel, rectum, and anal canal were contoured on CT treatment planning images. Doses to GI structures were calculated using the original treatment plan, and dose-volume parameters were extracted for modeling using CERR software. Logistic regression models were used to test the association between GI toxicity grade and predictors. Results: The mean age was 59; 76 (43%) patients were women; 166 (94%) received concurrent 5-FU based chemotherapy. Over half (56%) were treated with intensity modulated radiotherapy (IMRT), 44% were treated with 3D conformal RT (3DCRT). Grade 2+ proctitis and diarrhea were seen in 57 (32%) and 44 (25%) patients, respectively. On univariate analysis, age inversely predicts for Grade 2+ proctitis (Rs=-0.22, p=0.009). 3DCRT (Rs=0.27, p=0.001) and female gender (Rs=0.28, p=0.0008) predict for Grade 2+ diarrhea. On multivariate analysis, the normal tissue complication model including volume of anal canal receiving >15Gy, anal canal minimal dose, and age was most predictive of Grade 2+ proctitis (AUC=0.67, Rs=0.25, p<0.001). The model including bowel volume receiving 45Gy, female gender, and use of 3DCRT was highly predictive of Grade 2+ diarrhea (AUC=0.76, Rs=0.35, p<0.001). Patients treated with IMRT had significantly less bowel volume receiving ≥ 45Gy compared to 3DCRT (V45Gy=10.9% vs. 21.7%, p<0.0001). Conclusions: In this analysis of a large cohort of patients receiving PRT for rectal cancer, we identified clinical and dosimetric predictors of acute GI toxicity. Younger patients and women have higher rates of acute Grade 2+ proctitis and diarrhea, respectively. IMRT resulted in a 50% relative reduction in bowel volume receiving 45Gy and a lower risk for clinically significant diarrhea. Dose-volume constraints using these parameters should be considered, particularly in higher risk patients.
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