Efficacy and Toxicity of Neoadjuvant Radiotherapy with Concomitant Dose Escalation for Rectal Cancer

Peng WangKai LiuXiaoliang LiuWeiping WangDingchao LiuYidi WangShuai Sun^*Ke Hu^*

• Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, China

Objective: This study aimed to evaluate the efficacy of a neoadjuvant radiotherapy regimen featuring a concomitant dose escalation regimen, followed by surgery, in patients with rectal cancer. Methods: We reviewed the clinical records of rectal cancer patients who received neoadjuvant chemoradiotherapy or radiotherapy alone with a concomitant dose escalation regimen (55-56 Gy) between October 2012 and January 2019. Chemotherapy regimens included capecitabine monotherapy or capecitabine combined with oxaliplatin. Surgery was performed 8-10 weeks after radiotherapy. Primary endpoints included the pathological complete response (pCR) rate and sphincter preservation rate. We also analyzed the impact of radiotherapy-to-surgery interval on pCR rates. Disease-free survival (DFS) was compared between pCR and non-pCR patients. Results: A total of 415 patients were included, with 14 patients received radiotherapy alone. Following neoadjuvant therapy with concomitant dose escalation and subsequent surgery, 99 patients achieved pCR, yielding a pCR rate of 23.9%. A complete primary tumor response (ypT0) was observed in 105 patients (a TpCR rate of 25.3%), while a nodal complete response (ypN0) was achieved in 335 patients (an NpCR rate of 80.2%). Among the 369 patients who underwent lymph node dissection, 295 achieved NpCR. Sphincter preservation was achieved in 359 (86.5%) patients The incidence of grade 3 or higher acute hematologic, gastrointestinal, and genitourinary toxicities was 9.7%, 4.2%, and 1.5%, respectively. With a median follow-up of 5.06 years, an interval between radiotherapy and surgery > 10 weeks was associated with a higher pCR rate (p=0.037) after adjusting for age and sex. Patients achieving pCR demonstrated significantly better DFS compared to non-pCR patients (83.33% vs. 62.55%, p=0.0224), and this difference remained significant in stage III patients (79.15% vs. 58.35%, p=0.0308). Conclusion: Neoadjuvant chemoradiotherapy with concomitant dose escalation yields high pCR rates for both primary tumor and nodal disease, with acceptable toxicity, in a significant number of patients with rectal cancer. Presence of pCR is associated with markedly improved DFS. Moreover, prolonged interval between neoadjuvant radiotherapy and surgery correlates with elevated pCR rates.