Tumor Debulking in Combination With Chemotherapy in Multiorgan Metastatic Colorectal Cancer: The ORCHESTRA Randomized Clinical Trial.

However, prospective evidence for a survival benefit of tumor debulking is lacking.

然而，关于肿瘤减容术对生存益处的前瞻性证据尚不充分。

Background

To investigate whether tumor debulking added to palliative chemotherapy improves survival of patients with multiorgan mCRC.

研究肿瘤减容术联合姑息性化疗是否能改善多器官转移性结直肠癌患者的生存期。

DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated, open-label, multicenter, randomized clinical trial enrolled patients with multiorgan mCRC between May 2013 and May 2023.

设计、环境和参与者：这项由研究者发起的、开放标签的、多中心的随机临床试验，招募了2013年5月至2023年5月期间的多器官转移性结直肠癌患者。

The last date of follow-up was April 4, 2024.

最后的随访日期是2024年4月4日。

Patients were enrolled in 27 hospitals in the Netherlands and 1 in the UK.

患者在荷兰的27家医院和英国的1家医院进行了登记。

Adult patients with multiorgan mCRC were considered eligible if more than 80% tumor debulking was deemed feasible by resection, radiotherapy, and/or thermal ablation prior to starting first-line palliative chemotherapy.

如果通过手术、放疗和/或热消融术在开始一线姑息性化疗前被认为可行的肿瘤减灭超过80%，则考虑成年多器官转移性结直肠癌（mCRC）患者符合资格。

Methods

After achieving objective tumor response or stable disease after 3 cycles of capecitabine and oxaliplatin or 4 cycles of 5-fluorouracil and oxaliplatin with or without bevacizumab, patients were randomized 1:1 to receive chemotherapy alone (standard care group) or tumor debulking followed by chemotherapy.

在使用卡培他滨和奥沙利铂治疗3个周期或使用5-氟尿嘧啶和奥沙利铂治疗4个周期（无论是否联合贝伐单抗）后，达到客观肿瘤反应或疾病稳定状态的患者，按1:1的比例随机分配接受化疗（标准治疗组）或肿瘤减灭后化疗。

main_outcomes_and_measures

The primary end point was overall survival. Secondary end points included progression-free survivaland serious adverse events.

主要终点是总生存。次要终点包括无进展生存和严重不良事件。

These outcomes were analyzed in the intention-to-treatpopulation, applicable from randomization.

这些结果在从随机化开始适用的意向治疗人群中进行了分析。

A prespecified interim analysis performed after the initial 100 participants were enrolled revealed that the trial was both safe and feasible to proceed.

在最初招募的100名参与者后进行的事先计划的中期分析显示，该试验既安全又可行，可以继续进行。

Results

A total of 382 of 454 enrolled patients were randomized: 192 in the chemotherapy alone group (133 [69%] male) and 190 in the chemotherapy plus tumor debulking group (127 [67%] male).

在总共454名入组患者中，有382名被随机分配：192名仅接受化疗组（133名[69%]为男性）和190名接受化疗加肿瘤减体积组（127名[67%]为男性）。

The median age was 64 years in both groups.

两组的中位年龄均为64岁。

After a median follow-up of 32.3 months, median overall survivalin the chemotherapy alone group was 27.5 months vs 30.0 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.88 [95% CI, 0.70-1.10]; P = .26).

经过中位随访32.3个月后，仅接受化疗组的中位总生存期为27.5个月，而化疗联合肿瘤减积术组的中位总生存期为30.0个月（调整后的风险比为0.88 [95% 置信区间，0.70-1.10]；P = .26）。

Median progression-free survivalin the chemotherapy alone group was 10.4 months vs 10.5 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.83 [95% CI, 0.67-1.02]; P = .08).

仅化疗组的中位无进展生存期为10.4个月，而化疗加肿瘤减灭组为10.5个月（调整后风险比，0.83 [95% 置信区间，0.67-1.02]；P = .08）。

More patients in the chemotherapy plus tumor debulking vs chemotherapy alone group had any serious adverse events (101 [53%] vs 74 [39%]; P = .006).

与仅化疗组相比，化疗加肿瘤减灭组有更多的患者出现任何严重不良事件（101 [53%] vs 74 [39%]；P = .006）。

conclusions_and_relevance

Tumor debulking in addition to first-line palliative systemic treatment failed to improve overall survivalcompared with systemic treatment alone for patients with multiorgan mCRC and should not be considered standard care.

除了首次全身姑息治疗外，对多器官转移性结直肠癌患者进行肿瘤减积术未能改善总生存期，与仅接受全身治疗相比并无优势，因此不应被视为标准治疗。

trial_registration

ClinicalTrials.gov Identifier: NCT01792934.

ClinicalTrials.gov 注册号：NCT01792934。