Impact of Induction Chemotherapy Antecedent to Long Course Neoadjuvant Concurrent Chemo-Radiotherapy on Clinical Outcomes of Patients with Carcinoma Rectum: Retrospective Audit from a Tertiary Cancer Center

Abstract

<h3>Purpose/Objective(s)</h3> The paradigm of management of locally advanced rectal (T3/4; T1-4N1-2) cancers (LARC) have been shifting to induction chemotherapy (NACT) with long course neoadjuvant chemo-radiotherapy (NACRT) followed by total mesorectal excision (TME) inching towards total neoadjuvant therapy approach. We aimed to evaluate the outcomes of NACRT alone (Arm A) versus NACT followed by NACRT (Arm B) in LARC treated at our center. <h3>Materials/Methods</h3> Data of 101 patients of LARC (March 2013 – Jan 2021) were retrieved for this retrospective analysis. NACT in Arm B consisted of 2 cycles of CAPOX [oxaliplatin (130 mg/m² day 1) and capecitabine (1000 mg/m² twice daily for 14 days) repeated every 3 weeks]. Radiotherapy (RT) in both the arms was 50.4 Gray in 28 fractions with capecitabine 825 mg/m² twice daily on days of RT. All patients underwent TME. Adjuvant chemotherapy (ACT) consisted of CAPOX regimen. Pathological complete response (pCR) and overall complete response OCR (pCR plus near complete response) were defined as per modified Ryan grading system. Disease-free survival (DFS) and overall survival (OS) were assessed with Kaplan Meier method. <h3>Results</h3> Patient characteristics are summarized in Table 1. Median number of NACT cycles in Arm B was two (range 2-4). Median radiotherapy dose was 50.4 Gray. pCR rates were 12.7% in arm B and 7.3% (3/41) in arm A (p=0.516). OCR rates were 28.3% (17/60) in Arm B vs 12.1% (5/41) in Arm A (p=0.044). 2-Year DFS and OS in Arm A versus B were 47.5% vs. 73.9% (p=0.781) and 54.3% vs 67.3% (p= 0.371) respectively. Patients with pCR vs no pCR had better 2-year DFS and OS 88.9% vs 50.1% (p = 0.009) and 83.3% vs 55.4% (p = 0.015) respectively. Patients with OCR vs no OCR had better 2-year DFS and OS 88.5% vs 45.2% (p = 0.009) and 94.4% vs 51% (p = 0.015) respectively. Patients with positive circumferential margin (CRM) and regional node at presentation had poorer DFS 18.6% vs 83.6% (p=0.03) and 42.7% vs 54.9% (p=0.004) respectively. <h3>Conclusion</h3> NACT prior to NACTRT leads to higher OCR rates in LARC. pCR and OCR predicted better DFS and OS and positive CRM and node positivity at presentation portended poorer outcome in our cohort of patients.