Dijkstra Madelon, Nieuwenhuizen Sanne, Puijk Robbert S, Timmer Florentine E F, Geboers Bart, Schouten Evelien A C, Opperman Jip, Scheffer Hester J, de Vries Jan J J, Versteeg Kathelijn S, Lissenberg-Witte Birgit I, Meijerink Martijn R, van den Tol Monique Petrousjka
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, VU Medical Center Amsterdam, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Department of Radiology and Nuclear Medicine, Noordwest Ziekenhuisgroep, Location Alkmaar, 1800 AM Alkmaar, The Netherlands.
Cancers (Basel). 2021 Oct 5;13(19):4997. doi: 10.3390/cancers13194997.
This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan-Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher's exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts ( = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities ( = 0.010) and primary tumor location ( = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416-1.691; = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249-1.756; = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483-1.318; = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications ( = 0.843) and median length of hospital stay ( = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).
这项队列研究旨在评估新辅助化疗（NAC）后重复局部治疗与复发性结直肠癌肝转移（CRLM）直接进行重复局部治疗相比的疗效、安全性和生存结果。来自前瞻性阿姆斯特丹结直肠癌肝转移登记处（AmCORE）的152例患者共267个肿瘤符合纳入标准。比较了两组复发性CRLM患者：在重复局部治疗前接受化疗的患者（32例）与直接进行重复局部治疗的患者（120例）。收集了2002年5月至2020年12月的数据。使用Kaplan-Meier方法回顾了主要终点总生存期（OS）以及次要终点局部无肿瘤进展生存期（LTPFS）和远处无进展生存期（DPFS）的结果。随后，估计了单变量和多变量Cox比例风险回归模型，并考虑了潜在的混杂因素。此外，根据患者、初始和重复局部治疗特征进行了亚组分析。使用卡方检验和Fisher精确检验比较了与手术相关的并发症和住院时间。两组联合起来，自复发性疾病诊断之日起的1年、3年和5年总生存率分别为98.6%、72.5%和47.7%。粗生存率分析未显示两组之间的总生存期有显著差异（P = 0.834），NAC组的1年、3年和5年总生存率分别为100.0%、73.2%和57.5%，直接进行重复局部治疗组分别为98.2%、72.3%和45.3%。在调整了两个混杂因素，即合并症（P = 0.010）和原发肿瘤位置（P = 0.023）后，多变量分析中的校正风险比为0.839（95%置信区间，0.416 - 1.691；P = 0.624）。在LTPFS（风险比 = 0.662；95%置信区间，0.249 - 1.756；P = 0.407）和DPFS（风险比 = 0.798；95%置信区间，0.483 - 1.318；P = 0.378）方面，两组之间未发现差异。根据患者、疾病和治疗特征进行的亚组分析中未检测到异质性治疗效果。两组之间在围手术期并发症（P = 0.843）和中位住院时间（P = 0.600）方面未发现显著差异。46.7%的患者报告了与化疗相关的毒性。在重复局部治疗前加用NAC并未改善总生存期、LTPFS或DPFS，也未影响围手术期发病率或住院时间。这项比较评估的结果并未证实CRLM重复局部治疗前常规使用NAC的合理性。由于NAC（在不同亚组中）的确切作用仍不确定，我们目前正在设计一项III期随机对照试验（RCT），即COLLISION RELAPSE试验，直接比较直接进行重复局部治疗（对照组）与新辅助全身治疗后再进行重复局部治疗（干预组）。
