Main Session
Sep 28
SS 02 - GI 1: The OPERATIC Side of Rectal Cancer - Organ Preservation, Evaluating Recurrences, and the Immune Checkpoints

111 - Perioperative Chemotherapy Duration Affects the Survival of Locally Advanced Rectal Cancer: A Post-Hoc Analysis of a Multicenter Randomized, Phase III Trial

03:10pm - 03:20pm PT
Room 307/308

Presenter(s)

Tongzhen Xu, MD - Cancer Hospital, Chinese Academy of Medical Science, Bejing, Beijing

T. Xu1, H. Ma1, H. Li1, Y. Chen2, J. Shuai2, N. Wang1, N. Lu1, B. Chen3, Y. Zhai4, H. Fang1, S. Qi3, S. Wang3, W. Zhang4, H. Jing3, Y. Liu3, Y. Song3, N. Li5, Y. LI1, Y. Tang6, and J. Jin1,3; 1State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 2State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (PUMC), Beijing, China, 3State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 4State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 5Department of Radiobiology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China, 6Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China

Purpose/Objective(s):

Evidence regarding the effect of perioperative chemotherapy is limited for locally advanced rectal cancer (LARC) treated with neoadjuvant radiotherapy. To explore the survival impact of perioperative chemotherapy duration, LARC patients in the STELLAR trial were analyzed.

Materials/Methods:

In STELLAR trial, the treatment procedure of the total neoadjuvant therapy (TNT) group consisted of short-course radiotherapy (5 Gy × 5) followed by four cycles of CAPOX (oxaliplatin 130 mg/m2 on day-1 and capecitabine 1,000 mg/m2, bid, from day-1 to day-14). In the chemoradiotherapy (CRT) group, preoperative radiotherapy of 50 Gy in 25 fractions was given, concurrently with capecitabine (825 mg/m2, bid). Total mesorectal excision (TME) was performed in both groups 6 to 8 weeks after preoperative treatment. Postoperative chemotherapy comprised two cycles of CAPOX in the TNT group or six cycles of CAPOX in the CRT group. In this post-hoc analysis, all patients were analyzed to explore the impact of perioperative chemotherapy duration on survival outcomes, including disease-free survival (DFS), overall survival (OS), distant metastasis (DM) and locoregional recurrence (LRR).

Results:

A total of 539 patients were evaluable for the post-hoc analysis. The median duration of perioperative chemotherapy was 18 (IQR: 6-18) weeks. Among patients receiving chemotherapy, 310 (74.2%) were treated with the CAPOX regimen alone, following by 49 (11.7%) who received capecitabine monotherapy during the perioperative phase. Additionally, 44 patients (8.2%) received the CAPOX regimen during the preoperative phase but switched to capecitabine monotherapy postoperatively. The median follow-up was 68.1 (IQR, 43.2-79.6) months. In both univariate and multivariate COX analysis, the duration of perioperative chemotherapy was significantly associated with OS (P < 0.001), DFS (P < 0.001), and DM (P = 0.010), but not with LRR (P = 0.32). Besides, the multivariate model also revealed that cN stage was significantly associated with DFS (P=0.048), OS (P=0.039) and DM (P=0.066), but not with LRR (P=0.381). The duration of perioperative chemotherapy was categorized into four groups: the none (n=121), 3 to 9 weeks (n=46), 12 to 15 weeks (n=97), and = 18 weeks (n=275) groups. As the chemotherapy duration increased, the 5-year DFS rates were 51.0%, 48.2%, 52.7%, and 68.9%, respectively, and 5-year OS rates reached 59.3%, 62.1%, 70.3%, and 83.8%, respectively. The group = 18 weeks had significantly higher DFS and OS comparing to the other three groups (all adj. P < 0.01). In constrast, the 5-year cumulative incidence rates for DM were 33.0%, 28.0%, 32.8%, and 22.9%, respectively. Although the group = 18 weeks had the lowest DM among the four groups, statistical significance was only observed in comparison with the none groups (adj. P = 0.03).

Conclusion:

For LARC patients treated with neoadjuvant radiotherapy, the duration of perioperative chemotherapy impacts OS, DFS and DM.