Efficacy of multicycle neoadjuvant chemotherapy combined with apatinib in treatment of advanced rectal cancer: a supportive study of Database from Colorectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Jianbo ^1,2 , LÜ Xinyi ^1,2 , ZOU Yuheng ^1,2 , WANG Zixi ^1,2 , WANG Xiaodong ¹ ,  LI Li ¹

1. Gastrointestinal Surgery Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. West China School of Medicine, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

LI Li, Email: drlili116@126.com

Keywords：

rectal cancer; neoadjuvant chemotherapy; apatinib; Database from Colorectal Cancer

DOI：

10.7507/1007-9424.201904064

Video：

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Objective To evaluate the efficacy of multicycle neoadjuvant chemotherapy combined with apatinib in the treatment of advanced rectal cancer through the Database from Colorectal Cancer (DACCA).Methods A total of 173 patients with advanced rectal cancer who underwent surgery after 2–4 cycles of neoadjuvant chemotherapy combined with apatinib were selected from the DACCA (Version January 20, 2019). The patients were grouped by treated cycle and clinical TNM (cTNM) stage, and the overall variation of clinical and pathological indicators before and after treatment were compared.Results Among 173 cases, 63 cases (36.42%), 45 cases (26.01%), and 65 cases (37.57%) were respectively in the 2, 3, and 4-cycle group; 54 cases (31.21%), 91 cases (52.60%), and 28 cases (16.18%) in stage Ⅱ, Ⅲ, and Ⅳ-group. Clinical response degree: complete pathologic response (cPR) was observed in 23 cases (13.29%), and the rate of conversion resection was 100% (173/173). Clinical response grade: complete response (CR) in 58 cases (33.53%), partial response (PR) in 93 cases (53.76%), stable disease (SD) in 21 cases (12.14%), progressive disease (PD) in 1 cases (0.58%). Tumor regression grade: TRG0 in 21 cases (12.57%), TRG1 in 22 cases (13.17%), TRG2 in 84 cases (50.30%), TRG3 in 40 cases (23.95%). There was a statistical difference in CEA before and after the treatment (P<0.001). All cases underwent radical resection, and the successful rate of transformed resection was 100%. There was significant difference on the clinical response grade among the cases of different treatment cycle (H=18.513, P<0.001), and the longer treatment cycle was correlated with better clinical response (G=–0.474, P<0.001). In addition, there was significant difference on the cPR rate among the cases of different cTNM stage (χ²=6.450, P=0.040).Conclusions Multicycle neoadjuvant chemotherapy combined with apatinib in treating patients with advanced rectal cancer is efficient. More treatment cycles lead to better efficacy. The lower cTNM stage maybe means more chance of achieving cPR and a satisfactory rate of conversion resection.

Citation： LIU Jianbo, LÜ Xinyi, ZOU Yuheng, WANG Zixi, WANG Xiaodong, LI Li. Efficacy of multicycle neoadjuvant chemotherapy combined with apatinib in treatment of advanced rectal cancer: a supportive study of Database from Colorectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(6): 728-734. doi: 10.7507/1007-9424.201904064 Copy

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2.	Bruheim K, Guren MG, Skovlund E, et al. Late side effects and quality of life after radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys, 2010, 76(4): 1005-1011.
3.	Jonker FH, Tanis PJ, Coene PP, et al. Impact of neoadjuvant radiotherapy on complications after hartmann procedure for rectal cancer. Dis Colon Rectum, 2015, 58(10): 931-937.
4.	Cheng X, Feng H, Wu H, et al. Targeting autophagy enhances apatinib-induced apoptosis via endoplasmic reticulum stress for human colorectal cancer. Cancer Lett, 2018, 431: 105-114.
5.	汪晓东, 李希, 何欣林, 等. 数据库研究第一部分: 区域性医疗中心的结直肠癌与人群特征. 中国普外基础与临床杂志, 2019, 26(2): 212-220.
6.	汪晓东, 李立. 数据库建设第一部分:个人数据的标签与结构化. 中国普外基础与临床杂志, 2019, 26(3): 335-342.
7.	汪晓东, 安丽珉, 李立. 数据库研究第二部分:结直肠癌的住院流程管理. 中国普外基础与临床杂志, 2019, 26(4): 469-475.
8.	李立. 结直肠癌外科应用技术的规范与创新 (一). 中国普外基础与临床杂志, 2006, 13(1): 106-109.
9.	李立, 汪晓东, 舒晔, 等. 四川大学华西医院?结直肠癌手术治疗指南 (一). 中国普外基础与临床杂志, 2008, 15(10): 778.
10.	Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 2009, 45(2): 228-247.
11.	Moreno CC, Sullivan PS, Mittal PK. MRI evaluation of rectal cancer: staging and restaging. Curr Probl Diagn Radiol, 2017, 46(3): 234-241.
12.	Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer, 2003, 98(7): 1521-1530.
13.	Weiser MR. AJCC 8th edition: colorectal cancer. Ann Surg Oncol, 2018, 25(6): 1454-1455.
14.	Latkauskas T, Pauzas H, Kairevice L, et al. Preoperative conventional chemoradiotherapy versus short-course radiotherapy with delayed surgery for rectal cancer: results of a randomized controlled trial. BMC Cancer, 2016, 16(1): 927.
15.	McCoy MJ, Hemmings C, Hillery S, et al. Neoadjuvant chemoradiotherapy for rectal cancer: how important is tumour regression? ANZ J Surg, 2017, 87(12): E233-E239.
16.	Das P, Skibber JM, Rodriguez-Bigas MA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer, 2007, 109(9): 1750-1755.
17.	Karagkounis G, Thai L, Mace AG, et al. Prognostic implications of pathological response to neoadjuvant chemoradiation in pathologic stage Ⅲ rectal cancer. Ann Surg, 2018, [Epub ahead of print].
18.	Koizumi M, Yamada T, Shinji S, et al. Feasibility of neoadjuvant FOLFOX therapy without radiotherapy for baseline resectable rectal cancer. In Vivo, 2018, 32(4): 937-943.
19.	Habr-Gama A, Gama-Rodrigues J, São Julião GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys, 2014, 88(4): 822-828.
20.	Li J, Liu H, Yin J, et al. Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study. Oncotarget, 2015, 6(39): 42354-42361.
21.	Serra-Aracil X, Pericay C, Mora-Lopez L, et al. Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0 rectal tumors. Local recurrence, complete clinical and pathological response. Cir Esp, 2017, 95(4): 199-207.
22.	Park IJ, You YN, Agarwal A, et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol, 2012, 30(15): 1770-1776.
23.	Koike J, Funahashi K, Yoshimatsu K, et al. Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage Ⅱ/Ⅲ rectal cancer: the FACT trial. Cancer Chemother Pharmacol, 2017, 79(3): 519-525.

1. Benson AB 3rd, Venook AP, Al-Hawary MM, et al. Rectal cancer, version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2018, 16(7): 874-901.
2. Bruheim K, Guren MG, Skovlund E, et al. Late side effects and quality of life after radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys, 2010, 76(4): 1005-1011.
3. Jonker FH, Tanis PJ, Coene PP, et al. Impact of neoadjuvant radiotherapy on complications after hartmann procedure for rectal cancer. Dis Colon Rectum, 2015, 58(10): 931-937.
4. Cheng X, Feng H, Wu H, et al. Targeting autophagy enhances apatinib-induced apoptosis via endoplasmic reticulum stress for human colorectal cancer. Cancer Lett, 2018, 431: 105-114.
5. 汪晓东, 李希, 何欣林, 等. 数据库研究第一部分: 区域性医疗中心的结直肠癌与人群特征. 中国普外基础与临床杂志, 2019, 26(2): 212-220.
6. 汪晓东, 李立. 数据库建设第一部分:个人数据的标签与结构化. 中国普外基础与临床杂志, 2019, 26(3): 335-342.
7. 汪晓东, 安丽珉, 李立. 数据库研究第二部分:结直肠癌的住院流程管理. 中国普外基础与临床杂志, 2019, 26(4): 469-475.
8. 李立. 结直肠癌外科应用技术的规范与创新 (一). 中国普外基础与临床杂志, 2006, 13(1): 106-109.
9. 李立, 汪晓东, 舒晔, 等. 四川大学华西医院?结直肠癌手术治疗指南 (一). 中国普外基础与临床杂志, 2008, 15(10): 778.
10. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 2009, 45(2): 228-247.
11. Moreno CC, Sullivan PS, Mittal PK. MRI evaluation of rectal cancer: staging and restaging. Curr Probl Diagn Radiol, 2017, 46(3): 234-241.
12. Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer, 2003, 98(7): 1521-1530.
13. Weiser MR. AJCC 8th edition: colorectal cancer. Ann Surg Oncol, 2018, 25(6): 1454-1455.
14. Latkauskas T, Pauzas H, Kairevice L, et al. Preoperative conventional chemoradiotherapy versus short-course radiotherapy with delayed surgery for rectal cancer: results of a randomized controlled trial. BMC Cancer, 2016, 16(1): 927.
15. McCoy MJ, Hemmings C, Hillery S, et al. Neoadjuvant chemoradiotherapy for rectal cancer: how important is tumour regression? ANZ J Surg, 2017, 87(12): E233-E239.
16. Das P, Skibber JM, Rodriguez-Bigas MA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer, 2007, 109(9): 1750-1755.
17. Karagkounis G, Thai L, Mace AG, et al. Prognostic implications of pathological response to neoadjuvant chemoradiation in pathologic stage Ⅲ rectal cancer. Ann Surg, 2018, [Epub ahead of print].
18. Koizumi M, Yamada T, Shinji S, et al. Feasibility of neoadjuvant FOLFOX therapy without radiotherapy for baseline resectable rectal cancer. In Vivo, 2018, 32(4): 937-943.
19. Habr-Gama A, Gama-Rodrigues J, São Julião GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys, 2014, 88(4): 822-828.
20. Li J, Liu H, Yin J, et al. Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study. Oncotarget, 2015, 6(39): 42354-42361.
21. Serra-Aracil X, Pericay C, Mora-Lopez L, et al. Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0 rectal tumors. Local recurrence, complete clinical and pathological response. Cir Esp, 2017, 95(4): 199-207.
22. Park IJ, You YN, Agarwal A, et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol, 2012, 30(15): 1770-1776.
23. Koike J, Funahashi K, Yoshimatsu K, et al. Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage Ⅱ/Ⅲ rectal cancer: the FACT trial. Cancer Chemother Pharmacol, 2017, 79(3): 519-525.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Efficacy of multicycle neoadjuvant chemotherapy combined with apatinib in treatment of advanced rectal cancer: a supportive study of Database from Colorectal Cancer

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