Neoadjuvant Chemotherapy and Concomitant Boost Radiotherapy in the Treatment of Locally Advanced Rectal Cancer

Aims: This study aimed to examine the efficacy and toxicities of concomitant boost three-dimensional conformal radiotherapy along with multidrug chemotherapy (capecitabine and oxaliplatin) in neoadjuvant course for locally advanced rectal cancer (LARC).

Study Design: A phase II interventional nonrandomized study.

Place and Duration of Study: This Study was conducted at Clinical Oncology and nuclear medicine department of Mansoura University Hospitals (Egypt) between November 2016 and October 2019.

Methodology: Thirty patients (18 women, 12 men; age range 18-75 years) with (cT3-T4 and/or cN+) histologically confirmed rectal adenocarcinoma located within 12 cm of the anal verge were included in this study. Patients received three-dimensional conformal radiotherapy (3DCRT) to the pelvis of 45 Gy and a concomitant boost of 10 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1–5 weekly). Radical surgery was scheduled six to eight weeks after chemoradiation. Acute toxicities were recorded according to Common Terminology Criteria for Adverse Event (CTCAE) v5.0. Potential prognostic factors were evaluated using a binomial logistic regression. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test.

Results: All patients received chemoradiation. Twenty-seven patients underwent surgical resection. Twenty-five patients underwent sphincter-sparing surgery (92.6%) and nine patients (33.3%) achieved pathological complete response (pCR). The incidences of grade III neutropenia, diarrhea, and radiation dermatitis were 6.7%, 6.7%, 3.3% respectively. The three-year local recurrence (LR), disease-free survival (DFS) and overall survival (OS) rates were 7.4%, 63% and 74.1%, respectively. We found pre-surgical negative nodal status to be significantly associated with pCR (p=0.009). The pathological nodal stage was an independent prognostic factor to DFS.

Conclusion: The combination of oxaliplatin, capecitabine, and dose escalation using concomitant boost 3DCRT is safely administrated in patients with locally advanced rectal adenocarcinoma and it offers high pCR and sphincter preservation rate.