Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial.
Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial.
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DOI：
10.1093/jnci/djx015
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发表时间：
2017-09-01
期刊：
影响因子：
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通讯作者：
National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG)
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文献类型：
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作者：
Ruers T;Van Coevorden F;Punt CJ;Pierie JE;Borel-Rinkes I;Ledermann JA;Poston G;Bechstein W;Lentz MA;Mauer M;Folprecht G;Van Cutsem E;Ducreux M;Nordlinger B;European Organisation for Research and Treatment of Cancer (EORTC);Gastro-Intestinal Tract Cancer Group;Arbeitsgruppe Lebermetastasen und tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO);National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG)
背景：肿瘤消融通常用于治疗不可切除的结直肠肝转移瘤。然而，前瞻性随机研究尚未证明生存获益。在这里，我们研究了这种积极方法的长期好处。方法：在这项随机 II 期试验中，119 例不可切除的结直肠肝转移患者（n<10 例且无肝外疾病）接受单独全身治疗或全身治疗加射频消融±切除的积极局部治疗。之前，我们报告了主要终点（30 个月总生存率 [OS] > 38%）得到满足。我们现在报告长期操作系统结果。所有统计检验都是双面的。分析是根据治疗意图进行的。结果：中位随访时间为 9.7 年，119 例患者中有 92 例死亡（77.3%）：联合治疗组 60 例患者中有 39 例死亡（65.0%），全身治疗组 59 例患者中有 53 例死亡（89.8%）。几乎所有患者均死于疾病进展（联合治疗组 35 名患者，全身治疗组 49 名患者）。联合治疗组的 OS 存在统计学显着差异（风险比 [HR] = 0.58，95% 置信区间 [CI] = 0.38 至 0.88，P = 0.01）。联合治疗组的三年、五年和八年 OS 分别为 56.9%（95% CI = 43.3% 至 68.5%）、43.1%（95% CI = 30.3% 至 55.3%）、35.9%（95% CI = 23.8% 至 48.2%）。全身治疗组分别为 55.2%（95% CI=41.6% 至 66.9%）、30.3%（95% CI=19.0% 至 42.4%）、8.9%（95% CI=3.3% 至 18.1%）。联合治疗组的中位 OS 为 45.6 个月（95% CI= 30.3 至 67.8 个月），而全身治疗组为 40.5 个月（95% CI= 27.5 至 47.7 个月）。结论：这项 II 期试验是第一个随机研究，证明积极的局部治疗可以延长不可切除的结直肠肝转移患者的 OS。
Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.