直肠癌新辅助放化疗后等待观察策略疗效分析

doi:10.3760/cma.j.cn113030-20210819-00315

摘要
图/表
参考文献(27)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (0 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的比较局部进展期直肠癌新辅助治疗后临床完全缓解(cCR)的患者等待观察(W&W)与直肠癌全系膜切除术(TME)后病理完全缓解(pCR)患者的疗效。方法回顾性队列研究,收集2014—2019年中国医学科学院肿瘤医院收治的新辅助放化疗Ⅱ-Ⅲ期直肠癌患者,纳入标准为完成新辅助治疗后规律随访≥1年且达到cCR者(W&W组),或者TME手术后病理pCR者(pCR组)。研究终点主要为3、5年总生存(OS)、无结肠造瘘生存(CFS)、无瘤生存(DFS)、非局部再生DFS (NR-DFS)、器官保留率。采用Kaplan-Meier法生存分析和log-rank检验,并使用倾向评分配比进行验证。结果共 118例患者入组,中位随访49.5个月(12.1~79.9个月),W&W组、pCR组 3年OS率分别为97.1%、96.7%,5年的分别为93.8%、90.9%(P=0.696);3、5年CFS率分别均为89.1%、43.5%(P<0.001);3年DFS率分别为83.6%、97.0%,5年的分别为83.6%、91.2%(P=0.047);3年NR-DFS率分别为95.9%、97.0%,5年的分别为92.8%、97.0%(P=0.407)。W&W组 6例发生局部再生,87.7%患者成功保留了直肠。经倾向评分匹配后W&W组CFS仍明显优于pCR组(90.1%∶26.5%,P<0.001)。W&W组达cCR的中位时间为17.5周,在放疗结束后 5~12周初次评效时仅23.9%患者达cCR,且与标准长程CRT相比,短程放疗者达cCR间隔时间更长(P<0.001)。结论局部进展期直肠癌新辅助治疗后达cCR者等待观察安全有效,显著改善生活质量,进一步延长cCR评价时间可提高直肠器官保留率。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	赵莹
	唐源
	刘文扬
	李宁
	陈司霖
	史金明
	马慧颖
	曾强
	宋永文
	王淑莲
	刘跃平
	房辉
	卢宁宁
	唐玉
	亓姝楠
	杨勇
	陈波
	李晔雄
	金晶

关键词 ：直肠癌,局部进展期, 等待观察, 直肠癌全系膜切除术, 临床完全缓解, 器官保留

Abstract：Objective To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME). Methods This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group),and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM). Results A total of 118 patients were enrolled,49 of whom had cCR and managed by W&W, 69had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

Key words： Rectal neoplasm, locally advanced Watch and wait Total mesorectal excision Complete clinical response Organ preservation

收稿日期: 2021-08-19

通讯作者: 金晶,Email:jinjing@cicams.ac.cn

引用本文:

赵莹,唐源,刘文扬等. 直肠癌新辅助放化疗后等待观察策略疗效分析[J]. 中华放射肿瘤学杂志, 2022, 31(3): 253-259.

Zhao Ying,Tang Yuan,Liu Wenyang et al. Long-term outcomes of watch&wait (W&W) after neoadjuvant treatment in patients with rectal cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(3): 253-259.

链接本文:

http://journal12.magtechjournal.com/Jweb_fszlx/CN/10.3760/cma.j.cn113030-20210819-00315 或 http://journal12.magtechjournal.com/Jweb_fszlx/CN/Y2022/V31/I3/253

[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424. DOI:10.3322/caac.21492.
[2] Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3):145-164. DOI:10.3322/caac.21601.
[3] Fokas E, Ströbel P, Fietkau R, et al. Tumor regression grading after preoperative chemoradiotherapy as a prognostic factor and individual-level surrogate for disease-free survival in rectal cancer[J]. J Natl Cancer Inst, 2017, 109(12). DOI:10.1093/jnci/djx095.
[4] Karagkounis G, Thai L, Mace AG, et al. Prognostic implications of pathological response to neoadjuvant chemoradiation in pathologic stage Ⅲ rectal cancer[J]. Ann Surg, 2019, 269(6):1117-1123. DOI:10.1097/SLA.0000000000002719.
[5] van der Valk M, Hilling DE, Bastiaannet E, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the international watch&wait database (IWWD):an international multicentre registry study[J]. Lancet, 2018, 391(10139):2537-2545. DOI:10.1016/S0140-6736(18)31078-X.
[6] Garcia-Aguilar J, Patil S, Kim JK, et al. Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial[J]. J Clin Oncol, 2020, 38(15_suppl):4008. DOI:10.1200/JCO.2020.38.15_suppl.4008.
[7] Maas M, Lambregts DM, Nelemans PJ, et al. Assessment of clinical complete response after chemoradiation for rectal cancer with digital rectal examination, endoscopy, and MRI:selection for organ-saving treatment[J]. Ann Surg Oncol, 2015, 22(12):3873-3880. DOI:10.1245/s10434-015-4687-9.
[8] Smith JJ, Chow OS, Gollub MJ, et al. Organ preservation in rectal adenocarcinoma:a phase Ⅱ randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management[J]. BMC Cancer, 2015, 15:767. DOI:10.1186/s12885-015-1632-z.
[9] Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0distal rectal cancer following chemoradiation therapy:long-term results[J]. Ann Surg, 2004, 240(4):711-717;discussion 717-718. DOI:10.1097/01.sla.0000141194.27992.32.
[10] Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer[J]. J Clin Oncol, 2011, 29(35):4633-4640. DOI:10.1200/JCO.2011.37.7176.
[11] Smith JD, Ruby JA, Goodman KA, et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy[J]. Ann Surg, 2012, 256(6):965-972. DOI:10.1097/SLA.0b013e3182759f1c.
[12] Smith JJ, Chow OS, Eaton A, et al. Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy[J]. J Clin Oncol, 2015, 33:509. DOI:10.1200/jco.2015.33.3_suppl.509.
[13] 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[J]. Int J Radiat Oncol Biol Phys, 2014, 88(4):822-828. DOI:10.1016/j.ijrobp.2013.12.012.
[14] Martens MH, Maas M, Heijnen LA, et al. Long-term outcome of an organ preservation program after neoadjuvant treatment for rectal cancer[J]. J Natl Cancer Inst, 2016, 108(12). DOI:10.1093/jnci/djw171.
[15] van der Sande ME, Figueiredo N, Beets GL. Management and outcome of local regrowths in a watch-and-wait prospective cohort for complete responses in rectal cancer[J]. Ann Surg, 2020, 274(6):e1056-e1062. DOI:10.1097/SLA.0000000000003738.
[16] Renehan AG, Malcomson L, Emsley R, et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project):a propensity-score matched cohort analysis[J]. Lancet Oncol, 2016, 17(2):174-183. DOI:10.1016/S1470-2045(15)00467-2.
[17] Dossa F, Chesney TR, Acuna SA, et al. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation:a systematic review and meta-analysis[J]. Lancet Gastroent Hepat, 2017, 2(7):501-513. DOI:10.1016/S2468-1253(17)30074-2.
[18] Ellis CT, Dusetzina SB, Sanoff H, et al. Long-term survival after chemoradiotherapy without surgery for rectal adenocarcinoma:A word of caution[J]. JAMA Oncol, 2017, 3(1):123-125. DOI:10.1001/jamaoncol.2016.3424.
[19] Fernandez LM, São Julião GP, Figueiredo NL, et al. Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the international watch&wait database:a retrospective, international, multicentre registry study[J]. Lancet Oncol, 2021, 22(1):43-50. DOI:10.1016/S1470-2045(20)30557-X.
[20] Smith JJ, Strombom P, Chow OS, et al. Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy[J]. JAMA Oncol, 2019, 5(4):e185896. DOI:10.1001/jamaoncol.2018.5896.
[21] Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23):a multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2021, 22(5):702-715. DOI:10.1016/S1470-2045(21)00079-6.
[22] Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO):a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2021, 22(1):29-42. DOI:10.1016/S1470-2045(20)30555-6.
[23] Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer:ESMO clinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2018, 29(Suppl 4):iv263. DOI:10.1093/annonc/mdy161.
[24] National Committee on Computer Network. NCCN clinical practice guidelines in oncology:rectal cancer. Version 3.2019[EB/OL][2019-08-10].http://guide.medlive.cn/.
[25] Mei SW, Liu Z, Wei FZ, et al. Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients[J]. World J Gastroenterol, 2020, 26(31):4624-4638. DOI:10.3748/wjg.v26.i31.4624.
[26] Habr-Gama A, São Julião GP, Fernandez LM, et al. Achieving a complete clinical response after neoadjuvant chemoradiation that does not require surgical resection:it may take longer than you think![J]. Dis Colon Rectum, 2019, 62(7):802-808. DOI:10.1097/DCR.0000000000001338.
[27] Hupkens B, Maas M, Martens MH, et al. Organ preservation in rectal cancer after chemoradiation:should we extend the observation period in patients with a clinical near-complete response?[J]. Ann Surg Oncol, 2018, 25(1):197-203. DOI:10.1245/s10434-017-6213-8.