Pathologic Response and Postoperative Complications After Short-course Radiation Therapy and Chemotherapy for Patients With Rectal Adenocarcinoma

510 Background: In treatment of rectal adenocarcinoma, an increased time delay (TD) of 6-12 weeks from the end of radiation therapy to surgery may increase the rate of complete pathologic response (pCR), but the optimal TD with respect to survival has not been established. This study evaluates the impact of TD on overall mortality. Methods: The NCDB was queried for patients with adenocarcinoma of the rectum and no evidence of metastasis at diagnosis, who underwent preoperative chemoradiation followed by radical surgical resection. Standard statistical methods were employed for descriptive statistics and Cox model development. Results: The study included 6805 patients, predominantly Caucasian (87.2%) and males (63.9%) who generally were treated with low anterior resection (57.3%), colonanal reanastomosis (8.4%), or abdominoperineal resection (28.4%), and had median survival of 66.6 months. The effects of age, surgical margins (-/+), comorbidity index, time to discharge after surgery, TMN pathologic staging, surgical volume, and patient income significantly impacted mortality after radiation and surgery (p<0.05 for all values). There was a significant relationship between TD and pCR (p=.0002). At TD less than 30 days, 4.0% of patients achieved pCR, while 9.3% of patients have achieved pCR by 75 days. In TD of greater than 75 days, the rate of pCR decreased. Overall, 6.8% of patients (n=461) achieved pCR. Using a refined cox model, a TD of more than 60 days was associated with 20% greater risk of mortality (95% CI 1.068 – 1.367). This effect became more pronounced with increasing TD; a TD of greater than 75 days was associated with 28% (95% CI 1.06-1.55) increased risk of mortality, while patients with TD less than 60 days saw a survival benefit. Conclusions: Though an interval up to 75 days between radiation and surgery may achieve higher rates of complete pathologic response, delay of more than 60 days from radiation to surgical resection and subsequent systemic chemotherapy decreases overall survival in patients with rectal cancer.

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Short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.139 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 139-139

Author(s):

Ali Shamseddine ◽

Youssef Zeidan ◽

Ibrahim Moustafa Khalifeh ◽

Joseph Gergi Kattan ◽

Rim Turfa ◽

...

Keyword(s):

Rectal Cancer ◽

Interim Analysis ◽

Response Rate ◽

Locally Advanced ◽

Rectal Adenocarcinoma ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Pathologic Response ◽

Short Course ◽

Pathologic Response Rate

139 Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer is becoming an accepted approach over the last few years with increasing pathologic complete response (pCR) and compliance of patients for chemotherapy in comparison with the current standard of care i.e., fluoropyrimidine based chemoradiation followed by surgery and adjuvant chemotherapy. Sequential use checkpoint inhibitors after radiation therapy (RT) has demonstrated synergistic effect in vivo leading to decrease in size of irradiated and non-irradiated secondary tumors outside the radiation field (abscopal effect). Methods: This is an investigator initiated; open-label, single-arm multicenter phase II study, adopting Simon’s two-stage aiming at evaluating the pCR rate and safety of using short-course radiation therapy (25 Grays in 5 fractions), followed by 6 cycles of mFOLFOX-6 plus Avelumab (anti PDL1), then total mesorectal excision(TME) in patients with locally-advanced, potentially resectable rectal adenocarcinoma. Results: 13 out of 44 patients were accrued from 20, July till 28, Dec 2018 in the first stage of the study (30% from total sample size). They all met the inclusion criteria and received full protocol treatment. 12 out of the 13 completed TME. 1 of the 13 had progression of disease, so surgery was aborted and patient was dropped out the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33.0, 73.0) years. The first interim analysis revealed 3 patients (25%) achieved pCR (tumor regression grade: TRG = 0) out of 12 as compared to the historical control group with pCR of 16%. For the rest of the patients, 3 (25%) had major pathologic response rate (pRR) with TRG = 1 (< 10% viable cells is tumor bed).In total, 6 out of 12 patients (50%) had major pathologic response rate. As for safety, no serious adverse events of grade 3 and 4 were reported. Conclusions: Based on the first interim analysis results, incorporation of Avelumab and short course radiotherapy is tolerable in patients with locally advanced rectal cancer treated with TNT. The study will resume recruitment to reach the target accrual. Clinical trial information: NCT03503630.

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