Risk factors of liver metastasis after preoperative total neoadjuvant chemoradiotherapy for middle and low rectal cancer of Ⅱ–Ⅲ stage_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HONG Kaibin , JI Rongjia , ZHUANG Jianfa ,  CHEN Dachao

Department of Oncology, The 909th Hospital (Dongnan Hospital of Xiamen University), Zhangzhou, Fujian 363000, P. R. China;

Corresponding author：

CHEN Dachao, Email: hkb1202123@163.com

Keywords：

middle and low rectal cancer; liver metastasis; neoadjuvant chemoradiotherapy

DOI：

10.7507/1007-9424.202312097

Video：

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Objective To investigate the risk factors of liver metastasis in patients with middle and low rectal cancer of Ⅱ–Ⅲ stage after preoperative short course radiotherapy combined with chemotherapy. Methods The clinical data of 89 patients with middle and low rectal cancer of Ⅱ–Ⅲ stage admitted to the Dongnan Hospital of Xiamen University from January 2019 to June 2020 were retrospectively analyzed. All patients were treated with short-course radiotherapy combined with chemotherapy before operation. The risk factors of postoperative liver metastasis were analyzed by multivariate logistic regression. Results The 89 patients were followed up for 7–53 months, with a median follow-up time of 33 months. During the follow-up period, 25 patients developed liver metastasis, the onset time was 7–35 months, and the median time of liver metastasis was 17 months. Among them, 5 patients (5.6%) developed liver metastasis in the first year after surgery, 15 patients (16.8%) developed liver metastasis at the second year after surgery, 5 patients (5.6%) developed liver metastasis at the 3rd year after surgery. Multivariate logistic regression results showed that lymph node metastasis [OR=3.550, 95%CI (1.425, 8.953), P=0.041], vascular invasion [OR=3.335, 95%CI (1.011, 11.001), P=0.048], maximum tumor diameter ≥5 cm [OR=4.477, 95%CI (1.273, 15.743), P=0.019], and peri-tumor diameter ≥1/2 [OR=4.633, 95%CI (1.387, 15.475), P=0.013] were risk factors for liver metastasis. Conclusions Lymph node metastasis, vascular invasion, maximum tumor diameter ≥5 cm, and circumferential tumor diameter ≥1/2 are risk factors for liver metastasis in patients with middle and low rectal cancer of Ⅱ–Ⅲ stage after preoperative short course radiotherapy combined with chemotherapy.

Citation： HONG Kaibin, JI Rongjia, ZHUANG Jianfa, CHEN Dachao. Risk factors of liver metastasis after preoperative total neoadjuvant chemoradiotherapy for middle and low rectal cancer of Ⅱ–Ⅲ stage. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(7): 858-862. doi: 10.7507/1007-9424.202312097 Copy

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	黄理宾, 黄秋实, 杨烈. 全球及中国的结直肠癌流行病学特征及防治: 2022《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(5): 530-537.
3.	中国医师协会外科医师分会, 中华医学会外科学分会胃肠外科学组, 中华医学会外科学分会结直肠外科学组, 等. 中国结直肠癌肝转移诊断和综合治疗指南 (2023版). 中华消化外科杂志, 2023, 22(1): 1-28.
4.	Furukawa K, Tsunematsu M, Tanji Y, et al. Impact of C-reactive protein-albumin-lymphocyte (CALLY) index on prognosis after hepatectomy for colorectal liver metastasis. Surg Oncol, 2023, 47: 101911. doi: 10.1016/j.suronc.2023.101911.
5.	Takahashi Y, Matsuo K, Shiozawa T, et al. Prognostic implications of histologic growth patterns and tumor-infiltrating macrophages in colorectal liver metastases. Langenbecks Arch Surg, 2023, 408(1): 6. doi: 10.1007/s00423-022-02741-z.
6.	陈昌江, 杨春康, 简锦亮, 等. 短程放疗联合化疗的全程新辅助治疗在中低位直肠癌治疗中的应用. 中华医学杂志, 2023, 103(4): 271-277.
7.	Lu X, Qi R, Xu Y, et al. Tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy: influencing factors and prognostic significance. Int J Clin Exp Pathol, 2023, 16(6): 124-132.
8.	Sun R, Zeng Y, Fan Y, et al. A new post-operative prognostic system combining CEA and CA199 for locally advanced rectal cancer patients undergoing neoadjuvant chemoradiotherapy followed by total mesorectal excision. Asian J Surg, 2023, 46(7): 2819. doi: 10.1016/j.asjsur.2023.01.061.
9.	Liu S, Jiang T, Xiao L, et al. Total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis. Oncologist, 2021, 26(9): e1555-e1566.
10.	Petrelli F, Trevisan F, Cabiddu M, et al. Total neoadjuvant therapy in rectal cancer: a systematic review and meta-analysis of treatment outcomes. Ann Surg, 2020, 271(3): 440-448.
11.	李干斌, 韩加刚, 王振军. 中低位局部进展期直肠癌全程新辅助治疗的研究进展. 中华外科杂志, 2021, 59(5): 387-391.
12.	Zhang H, Li G, Cao K, et al. Impact of total neoadjuvant therapy consisting of consolidation chemotherapy on locally advanced rectal cancer survival. Int J Colorectal Dis, 2022, 37(7): 1657-1668.
13.	Mui M, Kong JCH, Ramsay R, et al. Total neoadjuvant therapy (TNT) in rectal cancer: to or not to give?. ANZ J Surg, 2022, 92(9): 1978-1979.
14.	Yamaguchi T, Akiyoshi T, Fukunaga Y, et al. Adding induction chemotherapy before chemoradiotherapy with total mesorectal excision and selective lateral lymph node dissection for patients with poor-risk, locally advanced, mid-to-low rectal cancer may improve oncologic outcomes: a propensity score-matched analysis. Ann Surg Oncol, 2023, 30(8): 4716-4724.
15.	Cybulska-Stopa B, Ługowska I, Wiśniowski R, et al. Overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab plus FOLFOX chemotherapy. Contemp Oncol (Pozn), 2020, 24(1): 34-41.
16.	许剑民, 朱德祥. 结直肠癌术前治疗进展. 中华消化外科杂志, 2022, 21(6): 737-742.
17.	Monsellato I, Alongi F, Bertocchi E, et al. Correction to: standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after neoadjuvant chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR). BMC Cancer, 2020, 20(1): 128. doi: 10.1186/s12885-020-6632-y.
18.	Wang H, Hong R, Niu G, et al. Clinical study on risk factors related to postoperative recurrence or metastasis of rectal cancer: a retrospective cohort study. J Gastrointest Oncol, 2022, 13(6): 2973-2988.
19.	赵伽木, 张伟, 周洪渊, 等. 结直肠癌肝转移的最新研究进展. 中华肝胆外科杂志, 2021, 27(2): 156-160.
20.	Zhou S, Jiang Y, Pei W, et al. Neoadjuvant chemoradiotherapy followed by lateral pelvic lymph node dissection for rectal cancer patients: a retrospective study of its safety and indications. J Surg Oncol, 2021, 124(3): 354-360.
21.	Damato A, Ghidini M, Dottorini L, et al. Chemotherapy duration for various indications in colorectal cancer: a review. Curr Oncol Rep, 2023, 25(4): 341-352.
22.	Cerdán-Santacruz C, Cano-Valderrama Ó, Santos Rancaño R, et al. “Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study”. Eur J Surg Oncol, 2023, 49(10): 106962. doi: 10.1016/j.ejso.2023.06.014.
23.	段嘉宇, 唐瑗玲, 古诗渊, 等. 结直肠癌治疗研究进展. 中国普外基础与临床杂志, 2024, 31(5): 523-529.
24.	Borelli B, Germani MM, Carullo M, et al. Total neoadjuvant treatment and organ preservation strategies in the management of localized rectal cancer: a narrative review and evidence-based algorithm. Crit Rev Oncol Hematol, 2023, 186: 103985. doi: 10.1016/j.critrevonc.2023.103985.
25.	Schellenberg AE, Moravan V, Christian F. A competing risk analysis of colorectal cancer recurrence after curative surgery. BMC Gastroenterol, 2022, 22(1): 95. doi: 10.1186/s12876-022-02161-9.
26.	Luo D, Shan Z, Liu Q, et al. The correlation between tumor size, lymph node status, distant metastases and mortality in rectal cancer patients without neoadjuvant therapy. J Cancer, 2021, 12(6): 1616-1622.
27.	Zhao Y, Zhu J, Yang B, et al. Retrospective study of total neoadjuvant therapy for locally advanced rectal cancer. Future Oncol, 2022, 18(6): 691-700.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. 黄理宾, 黄秋实, 杨烈. 全球及中国的结直肠癌流行病学特征及防治: 2022《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(5): 530-537.
3. 中国医师协会外科医师分会, 中华医学会外科学分会胃肠外科学组, 中华医学会外科学分会结直肠外科学组, 等. 中国结直肠癌肝转移诊断和综合治疗指南 (2023版). 中华消化外科杂志, 2023, 22(1): 1-28.
4. Furukawa K, Tsunematsu M, Tanji Y, et al. Impact of C-reactive protein-albumin-lymphocyte (CALLY) index on prognosis after hepatectomy for colorectal liver metastasis. Surg Oncol, 2023, 47: 101911. doi: 10.1016/j.suronc.2023.101911.
5. Takahashi Y, Matsuo K, Shiozawa T, et al. Prognostic implications of histologic growth patterns and tumor-infiltrating macrophages in colorectal liver metastases. Langenbecks Arch Surg, 2023, 408(1): 6. doi: 10.1007/s00423-022-02741-z.
6. 陈昌江, 杨春康, 简锦亮, 等. 短程放疗联合化疗的全程新辅助治疗在中低位直肠癌治疗中的应用. 中华医学杂志, 2023, 103(4): 271-277.
7. Lu X, Qi R, Xu Y, et al. Tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy: influencing factors and prognostic significance. Int J Clin Exp Pathol, 2023, 16(6): 124-132.
8. Sun R, Zeng Y, Fan Y, et al. A new post-operative prognostic system combining CEA and CA199 for locally advanced rectal cancer patients undergoing neoadjuvant chemoradiotherapy followed by total mesorectal excision. Asian J Surg, 2023, 46(7): 2819. doi: 10.1016/j.asjsur.2023.01.061.
9. Liu S, Jiang T, Xiao L, et al. Total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis. Oncologist, 2021, 26(9): e1555-e1566.
10. Petrelli F, Trevisan F, Cabiddu M, et al. Total neoadjuvant therapy in rectal cancer: a systematic review and meta-analysis of treatment outcomes. Ann Surg, 2020, 271(3): 440-448.
11. 李干斌, 韩加刚, 王振军. 中低位局部进展期直肠癌全程新辅助治疗的研究进展. 中华外科杂志, 2021, 59(5): 387-391.
12. Zhang H, Li G, Cao K, et al. Impact of total neoadjuvant therapy consisting of consolidation chemotherapy on locally advanced rectal cancer survival. Int J Colorectal Dis, 2022, 37(7): 1657-1668.
13. Mui M, Kong JCH, Ramsay R, et al. Total neoadjuvant therapy (TNT) in rectal cancer: to or not to give?. ANZ J Surg, 2022, 92(9): 1978-1979.
14. Yamaguchi T, Akiyoshi T, Fukunaga Y, et al. Adding induction chemotherapy before chemoradiotherapy with total mesorectal excision and selective lateral lymph node dissection for patients with poor-risk, locally advanced, mid-to-low rectal cancer may improve oncologic outcomes: a propensity score-matched analysis. Ann Surg Oncol, 2023, 30(8): 4716-4724.
15. Cybulska-Stopa B, Ługowska I, Wiśniowski R, et al. Overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab plus FOLFOX chemotherapy. Contemp Oncol (Pozn), 2020, 24(1): 34-41.
16. 许剑民, 朱德祥. 结直肠癌术前治疗进展. 中华消化外科杂志, 2022, 21(6): 737-742.
17. Monsellato I, Alongi F, Bertocchi E, et al. Correction to: standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after neoadjuvant chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR). BMC Cancer, 2020, 20(1): 128. doi: 10.1186/s12885-020-6632-y.
18. Wang H, Hong R, Niu G, et al. Clinical study on risk factors related to postoperative recurrence or metastasis of rectal cancer: a retrospective cohort study. J Gastrointest Oncol, 2022, 13(6): 2973-2988.
19. 赵伽木, 张伟, 周洪渊, 等. 结直肠癌肝转移的最新研究进展. 中华肝胆外科杂志, 2021, 27(2): 156-160.
20. Zhou S, Jiang Y, Pei W, et al. Neoadjuvant chemoradiotherapy followed by lateral pelvic lymph node dissection for rectal cancer patients: a retrospective study of its safety and indications. J Surg Oncol, 2021, 124(3): 354-360.
21. Damato A, Ghidini M, Dottorini L, et al. Chemotherapy duration for various indications in colorectal cancer: a review. Curr Oncol Rep, 2023, 25(4): 341-352.
22. Cerdán-Santacruz C, Cano-Valderrama Ó, Santos Rancaño R, et al. “Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study”. Eur J Surg Oncol, 2023, 49(10): 106962. doi: 10.1016/j.ejso.2023.06.014.
23. 段嘉宇, 唐瑗玲, 古诗渊, 等. 结直肠癌治疗研究进展. 中国普外基础与临床杂志, 2024, 31(5): 523-529.
24. Borelli B, Germani MM, Carullo M, et al. Total neoadjuvant treatment and organ preservation strategies in the management of localized rectal cancer: a narrative review and evidence-based algorithm. Crit Rev Oncol Hematol, 2023, 186: 103985. doi: 10.1016/j.critrevonc.2023.103985.
25. Schellenberg AE, Moravan V, Christian F. A competing risk analysis of colorectal cancer recurrence after curative surgery. BMC Gastroenterol, 2022, 22(1): 95. doi: 10.1186/s12876-022-02161-9.
26. Luo D, Shan Z, Liu Q, et al. The correlation between tumor size, lymph node status, distant metastases and mortality in rectal cancer patients without neoadjuvant therapy. J Cancer, 2021, 12(6): 1616-1622.
27. Zhao Y, Zhu J, Yang B, et al. Retrospective study of total neoadjuvant therapy for locally advanced rectal cancer. Future Oncol, 2022, 18(6): 691-700.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Risk factors of liver metastasis after preoperative total neoadjuvant chemoradiotherapy for middle and low rectal cancer of Ⅱ–Ⅲ stage

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