Long Course Neoadjuvant Concurrent Chemo-Radiotherapy with or Without Pre-Radiation Induction Chemotherapy in the Management of Rectal Cancers: A Mono-Institutional Retrospective Analysis

Abstract

Long course neoadjuvant chemo-radiotherapy (NACRT) followed by total mesorectal excision (TME) with/without adjuvant chemotherapy (ACT) is the standard treatment modality for locally advanced rectal (T3/4; T1-4N1-2) cancers (LARC). While the loco-regional control (LRC) rates have become better with this approach, distant metastasis rates are to the tune of 20-30%. Of several approaches to circumvent this, one is the incorporation of neoadjuvant chemotherapy (NACT) prior to NACRT. This approach may also yield better tumor downstaging and pathological complete response (pCR) rates. At our institution, we have shifted in our approach from NACRT alone (Arm A) to NACT followed by NACRT (Arm B). We aimed to evaluate the outcomes with this novel approach and compare it with the former approach in our cohort of patients. Details of 62 patients of LARC (Jan 2013 – Sep 2018) treated with NACRT or NACT followed by NACRT were retrieved. 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 Gray in 25 fractions with concurrent capecitabine 825 mg/m2 twice daily. All the patients underwent TME by either low anterior resection (LAR) or abdominal perineal resection. ACT consisted of CAPOX regimen. pCR was defined as no viable tumor cells either at primary or regional lymph nodes. LRC was defined as time from registration to local/regional recurrence. Overall survival (OS) was defined as time from registration to death from any cause. Kaplan Meier method was used for all outcome analysis. 44 patients were in Arm A and 18 were in Arm B. Median age was 45 years with 13 females. Patient characteristics are described in the table. The median number of NACT cycles in Arm B was two. Median follow up was 28 months (range 4-42). Median duration from completion of NACRT to surgery was 5 months (range 4 -10). pCR rates were 17% (3/18) in arm B and 10% (4/44) in arm A (p=0.40). 41% and 39% patients in arm A and B received ACT, respectively [median number of cycles was 6 (range 4-8)]. 18-month LRC rate in Arm A versus B were 88.9% vs. 100% (p=0.46). 18-month OS in arm A and B was 70.6% vs 71.4% (p= 0.865), respectively. There were fifteen deaths, 11 in arm A and 4 in arm B. The crude distant metastasis rates were 11% for both arms (5 in arm A & 2 in arm B). Intensification of neo-adjuvant treatment with pre-radiation chemotherapy and NACRT followed by TME in LARC may achieve better pCR rates and possibly better loco-regional control and survival as compared to NACRT alone. This approach needs to be evaluated further in a prospective randomized trial.Abstract 2394; Table 1Patient characteristicsArm A(n=44)Arm B (n=18)TNM Staging (II: III)28:1610:8Lympho-vascular invasion16(36%)6(33%)Tumor grade (1: 2: 3)14:26:44:12:2Median tumor size at Surgery4 cm4 cmPathological stage (T2:T3:T4:N1:N2)7:25:3:10:23:7:3:5:3Circumferential resection margin positive3(7%)4(22%)LAR:APR24:2012:6 Open table in a new tab