Neoadjuvant PET and MRI-based intensity modulated radiotherapy leads to less toxicity and improved pathologic response rates in locally advanced rectal cancer.

Abstract

Neoadjuvant chemoradiation (NeoCRT) is standard of care for the treatment of locally advanced rectal cancer (LARC). Contemporary radiation techniques and pre-treatment imaging may impact toxicities and pathologic response (PR). Herein we compare intensity modulated radiotherapy (IMRT) and advanced pre-treatment imaging in the neoadjuvant treatment of LARC and resulting impact on toxicities and pathologic outcomes relative to 3 dimensional conformal radiotherapy (3DCRT). LARC patients treated at 4 large academic centers in the US from 2007-2016 were reviewed. Patients received 5-FU-based NeoCRT concurrently with IMRT or 3DCRT. PR was recorded as none, partial, or complete. Common terminology for adverse events version 4 was used to grade toxicities. Toxicity rates were compared using Chi-square analysis. Multivariable models were fit adjusting for age, gender, pre-tx CT to identify independent predictors of PR and toxicity. A total of 128 patients were analyzed: 60.1% male and 39.8% female, median age 57.7 years (range, 31-85 years). Clinical characteristics were similar across RT groups. The outcome of partial and complete PR was similar for IMRT and 3DCRT (48.1%, 23.1% vs. 31.7%, 23.3%), respectively. After adjusting for gender, age, and pre-RT chemotherapy type, IMRT and pretreatment PET and/or MRI imaging was significantly associated with increased odds for complete and partial response (OR =2.95, 95% CI: 1.21-7.25, P=0.018; OR =14.70, 95% CI: 3.69-58.78, P<0.0001). Additionally, IMRT was associated with reduced rates of dehydration, dermatitis, rectal pain, rectal bleeding, and diverting ostomy (P<0.05). Overall rates of grade 2 and higher toxicities were significantly reduced in IMRT vs. 3DCRT after adjusting for confounders (OR =0.27, 95% CI: 0.08-0.87). NeoCRT IMRT with pretreatment PET and/or MRI for LARC leads to reduced acute toxicities and improved PR compared to 3DCRT. Given the challenges associated with prospective validation of these data, IMRT with pretreatment PET and/or MRI should be considered standard treatment for LARC.