Predictors of Definitive Treatment Interruptions of Long-Course Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Introduction To identify predictors of definitive treatment interruptions (DTI) of the neoadjuvant long-course radiotherapy (LCRT) in locally advanced rectal cancer (LARC), and to determine their impact on clinical outcomes. Methods Patients with stage II-III LARC treated between 2009-2018 were retrospectively analyzed (n=101, median FU 49.5 months). Logistic regression models evaluated the impact of relevant clinical variables on grade 3 or greater (G3+) acute toxicity, definitive treatment interruption (DTI), pCR, and definitive ostomy (dOST) rates. The secondary outcomes were LRC, MFS, PFS, CSS, and OS. Results The incidences of grade 3 and 4 toxicities were 25.3%, and 1.1%, respectively. The most common G3+ toxicities were peri-anal dermatitis (14.7%) and diarrhea (7.4%), which were more frequent in females (p=0.040) and tumors close to the anal verge (p=0.019). In this study, 11 patients (10.9%) developed DTI, which was associated with these G3+ events (p<0.001). Resection occurred after 7.1 weeks (median, IQR:6.1-8.9). Downstaging occurred in 57.4% (17.8% pCR), 88% achieved negative margins and the dOST rate was 56.4%. The five-year LRC, MFS, PFS, CSS and OS were: 94.4%, 78.9%, 74.7%, 85.2% and 81.6%, respectively. DTI events did not impact any outcome. The factors associated with loco-regional failure were close/positive margins (p<0.001) and stage ypIII (p=0.002). Conclusions: Tumors close to the anal verge and female sex were associated with increased G3+ toxicity, which was predictive of DTI. The resultant partial/complete omission of the planned boost, however, dose did not increase the chance of LR. Further studies to clarify the benefit and optimal timing to deliver the boost are warranted, especially for positive margins.