A meta-analysis of efficacy and safety on total neoadjuvant therapy for locally advanced rectal cancer

doi:10.3877/cma.j.issn.2095-3224.2021.02.011

Abstract

Abstract:

Objective

To evaluate the efficacy and safety of total neoadjuvant therapy for locally advanced rectal cancer.

Methods

A systemic search of CNKI, WanFang, CBM, PubMed and Embase was conducted for the studies that compared the efficacy of TNT and nCRT for rectal cancer. The quality evaluation of randomized controlled trials was based on the Cochrane's risk of bias tool, while non-randomized trials were assessed using Newcastle-Ottawa Scale. RevMan 5.3 software was used for meta-analisis, and the rate of pCR, T-downstaging, R0 resection and sphincter preservation rate, grade 3/4 acute toxicity during treatment, perioperative complications and survival benefits were compared between the two groups.

Results

A total of 14 studies was included with the amount of 3 797 patients, 1 865 and 1 932 in TNT group and nCRT group respectively. Meta analysis revealed that, a significant difference existed in the rate of pCR (OR=1.57,95%CI:1.30~1.90, P＜0.00001), T-downstaging (OR=2.16,95%CI:1.63~2.57, P＜0.00001) and R0 resection (OR=1.42,95%CI:1.09~1.85, P=0.009). There was no significant difference in the rate of perioperative complication and acute toxicity between the two groups. The 5-OS and 5-DFS were comparable between TNT group and nCRT group, indicating that TNT showed no survival benefits on rectal cancer patients.

Conclusion

Compared to nCRT, though no significant improvement in OS and DFS, the rate of pCR, tumor downstaging and R0 resection rate was improved in TNT group.

Key words: Rectal neoplasms, Total neoadjuvant therapy, Neoadjuvant chemoradiotherapy, Locally advanced rectal cancer, Efficacy, Safety, Meta-analysis

Ganbin Li, Jiagang Han, Zhenjun Wang. A meta-analysis of efficacy and safety on total neoadjuvant therapy for locally advanced rectal cancer[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2021, 10(02): 177-186.

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Figures/Tables 15

References 35

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作者	发表年份	国家	研究类型	总样本量	样本量		纳入研究质量评价
作者	发表年份	国家	研究类型	总样本量	TNT	nCRT	纳入研究质量评价
Garcia^[9]	2015	美国	前瞻性研究	259	199	60	6
翟志伟^[11]	2020	中国	回顾性研究	134	79	55	6
Cercek^[12]	2018	美国	回顾性研究	628	308	320	8
Markovina^[13]	2017	美国	前瞻性研究	138	69	69	6
Zhu^[14]	2019	美国	回顾性研究	1079	372	707	8
Fernandez^[15]	2015	美国	随机对照研究	103	54	49	－
Maréchal^[18]	2012	比利时	随机对照研究	57	28	29	－
Calvo^[19]	2014	西班牙	回顾性研究	335	207	128	7
Bhatti^[20]	2015	巴基斯坦	回顾性研究	154	93	61	7
Bujko^[21]	2016	波兰	随机对照研究	515	261	254	－
Kim^[22]	2018	韩国	随机对照研究	110	54	56	－
Liang^[23]	2019	中国	前瞻性研究	156	76	80	5
Moore^[24]	2017	澳大利亚	随机对照研究	49	25	24	－
李雷蕾^[25]	2017	中国	随机对照研究	80	40	40	－

作者	发表年份	国家	研究类型	总样本量	样本量		纳入研究质量评价
作者	发表年份	国家	研究类型	总样本量	TNT	nCRT	纳入研究质量评价
Garcia^[9]	2015	美国	前瞻性研究	259	199	60	6
翟志伟^[11]	2020	中国	回顾性研究	134	79	55	6
Cercek^[12]	2018	美国	回顾性研究	628	308	320	8
Markovina^[13]	2017	美国	前瞻性研究	138	69	69	6
Zhu^[14]	2019	美国	回顾性研究	1079	372	707	8
Fernandez^[15]	2015	美国	随机对照研究	103	54	49	－
Maréchal^[18]	2012	比利时	随机对照研究	57	28	29	－
Calvo^[19]	2014	西班牙	回顾性研究	335	207	128	7
Bhatti^[20]	2015	巴基斯坦	回顾性研究	154	93	61	7
Bujko^[21]	2016	波兰	随机对照研究	515	261	254	－
Kim^[22]	2018	韩国	随机对照研究	110	54	56	－
Liang^[23]	2019	中国	前瞻性研究	156	76	80	5
Moore^[24]	2017	澳大利亚	随机对照研究	49	25	24	－
李雷蕾^[25]	2017	中国	随机对照研究	80	40	40	－

作者	TNT			nCRT
作者	IT/CT	化疗方案	剂量	放疗方案	同步化疗方案
Garcia^[9]	CT	mFOFLOX	5-FU 400 mg/m²；LV 200 mg/m²；OX 85 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²
翟志伟^[11]	CT	CAPEOX	CAP 1 000 mg/m²; OX 130 mg/m ²	50.4 Gy/28 f	CAP 850 mg/m²
Cercek^[12]	IT	mFOFLOX	5-FU 400 mg/m²；LV 200 mg/m²；OX 85 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²/CAP 850 mg/m²
Markovina^[13]	IT	mFOFLOX	5-FU/LV/OX	45.0 Gy/25 f	5-FU/CAP
Zhu^[14]	IT	FOFLOX/CAPEOX	－	45.0 Gy/25 f 50.4 Gy/25~28 f	－
Fernandez^[15]	IT	CAPEOX	CAP/ OX	45.0 Gy/25 f	CAP
Maréchal^[18]	IT	mFOFLOX	5-FU 400 mg/m²；LV 400 mg/m²；OX 100 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²
Calvo^[19]	IT	mFOFLOX	5-FU 400 mg/m²；LV 200 mg/m²；OX 85 mg/m²	45.0 Gy/25 f	5-FU 425 mg/m²
Bhatti^[20]	IT	CAPEOX	CAP 1 000 mg/m²; OX 130 mg/m²	50.4 Gy/25~28 f	CAP 825 mg/m²
Bujko^[21]	CT	mFOFLOX	5-FU/LV/OX	50.4 Gy/25~28 f	5-FU 325 mg/m²/LV 20 mg/m²
Kim^[22]	CT	CAPEOX	CAP 1 700 mg/m²; OX 100 mg/m²	50.4 Gy/25~28 f	CAP
Liang^[23]	CT	CAPEOX FOFLOX	CAP 1 000 mg/m²; OX 130 mg/m² 5-FU 400 mg/m²; LV 400 mg/m²;OX 85 mg/m²	50.4 Gy/25~28 f	CAP 825 mg/m²
Moore^[24]	CT	5-FU/LV	5-FU 450 mg/m²; LV 50 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²
李雷蕾^[25]	CT	FOFLOX	5-FU 400 mg/m²; LV 200 mg/m²;OX 85 mg/m²	50.4 Gy/25~28 f	5-FU 225 mg/m²

作者	TNT			nCRT
作者	IT/CT	化疗方案	剂量	放疗方案	同步化疗方案
Garcia^[9]	CT	mFOFLOX	5-FU 400 mg/m²；LV 200 mg/m²；OX 85 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²
翟志伟^[11]	CT	CAPEOX	CAP 1 000 mg/m²; OX 130 mg/m ²	50.4 Gy/28 f	CAP 850 mg/m²
Cercek^[12]	IT	mFOFLOX	5-FU 400 mg/m²；LV 200 mg/m²；OX 85 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²/CAP 850 mg/m²
Markovina^[13]	IT	mFOFLOX	5-FU/LV/OX	45.0 Gy/25 f	5-FU/CAP
Zhu^[14]	IT	FOFLOX/CAPEOX	－	45.0 Gy/25 f 50.4 Gy/25~28 f	－
Fernandez^[15]	IT	CAPEOX	CAP/ OX	45.0 Gy/25 f	CAP
Maréchal^[18]	IT	mFOFLOX	5-FU 400 mg/m²；LV 400 mg/m²；OX 100 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²
Calvo^[19]	IT	mFOFLOX	5-FU 400 mg/m²；LV 200 mg/m²；OX 85 mg/m²	45.0 Gy/25 f	5-FU 425 mg/m²
Bhatti^[20]	IT	CAPEOX	CAP 1 000 mg/m²; OX 130 mg/m²	50.4 Gy/25~28 f	CAP 825 mg/m²
Bujko^[21]	CT	mFOFLOX	5-FU/LV/OX	50.4 Gy/25~28 f	5-FU 325 mg/m²/LV 20 mg/m²
Kim^[22]	CT	CAPEOX	CAP 1 700 mg/m²; OX 100 mg/m²	50.4 Gy/25~28 f	CAP
Liang^[23]	CT	CAPEOX FOFLOX	CAP 1 000 mg/m²; OX 130 mg/m² 5-FU 400 mg/m²; LV 400 mg/m²;OX 85 mg/m²	50.4 Gy/25~28 f	CAP 825 mg/m²
Moore^[24]	CT	5-FU/LV	5-FU 450 mg/m²; LV 50 mg/m²	45.0 Gy/25 f	5-FU 225 mg/m²
李雷蕾^[25]	CT	FOFLOX	5-FU 400 mg/m²; LV 200 mg/m²;OX 85 mg/m²	50.4 Gy/25~28 f	5-FU 225 mg/m²

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