Tumor progression while on chemotherapy - A contraindication to liver resection for multiple colorectal metastases?
Tumor progression while on chemotherapy - A contraindication to liver resection for multiple colorectal metastases?
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DOI：
10.1097/01.sla.0000145964.08365.01
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发表时间：
2004-12-01
影响因子：
9
通讯作者：
Bismuth, H
中科院分区：
文献类型：
--
作者：
Adam, R;Pascal, G;Bismuth, H
目的：为了评估术前化疗的反应，特别是肿瘤的进展，对切除多结直肠肝转移瘤（CRM）后的结果的影响，摘要背景资料：肝切除术是目前唯一的治疗，提供了一个长期生存的机会，虽然它是与多结节CRM患者的预后不良。由于其更好的疗效，化疗越来越多地建议作为新辅助治疗，在这样的患者，以允许或促进根治性切除。然而，这种策略的有效性以及对化疗的反应对肝切除术结果的影响知之甚少。我们回顾性分析了131例因多发性硬化而接受肝切除术的连续患者的病程，1993年至2000年期间全身化疗后的CRM（≥ 4），在此期间，在我们的机构中为CRM进行的所有肝切除术中占30%。化疗主要包括5-氟尿嘧啶、亚叶酸和奥沙利铂或伊立替康，平均9.8个疗程（中位数，9个疗程）。根据术前化疗的反应类型将患者分为3组。所有的肝切除术都是为了治愈。我们分析了患者的结果与术前化疗反应的关系。结果：有58例（44%）患者在客观肿瘤反应后接受肝切除术（第1组），39例（30%）在肿瘤稳定后（第2组），34例（26%）在肿瘤进展后（第3组）。在诊断时，3组的平均肿瘤大小和转移灶数量相似。在患者人口统计学、原发肿瘤特征、肝切除类型和术后病程方面没有观察到差异。一线治疗在组间不同，第1组中基于奥沙利铂和/或伊立替康的治疗比例较高（P < 0.01）。组2中使用了更多的化疗线（P = 0.002）。1年、3年和5年的总生存率分别为86%、41%和28%。与第1组和第2组相比，第3组的5年生存率要低得多（5年时分别为8% vs. 37%和30%，P < 0.0001）。无病生存率分别为3%、21%和20%（P = 0.02）。在多变量分析中，化疗中的肿瘤进展（P < 0.0001），术前血清CA 19-9升高（P < 0.0001），切除的转移灶数量（P < 0.001），化疗线数（P < 0.04），而不是一线治疗的类型，与生存率下降独立相关。如果转移性疾病在手术前通过化疗得到控制，则肝切除能够为患有多发性结直肠转移的患者提供长期生存。手术前肿瘤进展与不良结局相关，即使在可能治愈的肝切除术后。手术前肿瘤控制对于为多发性转移患者提供延长缓解的机会至关重要。
Objective: To evaluate the influence of the response to preoperative chemotherapy, especially tumor progression, on the outcome following resection of multiple colorectal liver metastases (CRM).Summary Background Data: Hepatic resection is the only treatment that currently offers a chance of long-term survival, although it is associated with a poor outcome in patients with multinodular CRM. Because of its better efficacy, chemotherapy is increasingly proposed as neoadjuvant treatment in such patients to allow or to facilitate the radicality of resection. However, little is known of the efficacy of such a strategy and the influence of the response to chemotherapy on the outcome of hepatic resection.Methods: We retrospectively analyzed the course of 131 consecutive patients who underwent liver resection for multiple (greater than or equal to4) CRM after systemic chemotherapy between 1993 and 2000, representing 30% of all liver resections performed for CRM in our institution during that period. Chemotherapy included mainly 5-fluorouracil, leucovorin, and either oxaliplatin or irinotecan for a mean of 9.8 courses (median, 9 courses). Patients were divided into 3 groups according to the type of response obtained to preoperative chemotherapy. All liver resections were performed with curative intent. We analyzed patient outcome in relation to response to preoperative chemotherapy.Results: There were 58 patients (44%) who underwent hepatectomy after an objective tumor response (group 1), 39 (30%) after tumor stabilization (group 2), and 34 (26%) after tumor progression (group 3). At the time of diagnosis, mean tumor size and number of metastases were similar in the 3 groups. No differences were observed regarding patient demographics, characteristics of the primary tumor, type of liver resection, and postoperative course. First line treatments were different between groups with a higher proportion of oxaliplatin- and/or irinotecan-based treatments in group 1 (P < 0.01). A higher number of lines of chemotherapy were used in group 2 (P = 0.002). Overall survival was 86%, 41%, and 28% at 1, 3, and 5 years, respectively. Five-year survival was much lower in group 3 compared with groups 1 and 2 (8% vs. 37% and 30%, respectively at 5 years, P < 0.0001). Disease-free survival was 3% compared with 21% and 20%, respectively (P = 0.02). In a multivariate analysis, tumor progression on chemotherapy (P < 0.0001), elevated preoperative serum CA 19-9 (P < 0.0001), number of resected metastases (P < 0.001), and the number of lines of chemotherapy (P < 0.04), but not the type of first line treatment, were independently associated with decreased survival.Conclusions: Liver resection is able to offer long-term survival to patients with multiple colorectal metastases provided that the metastatic disease is controlled by chemotherapy prior to surgery. Tumor progression before surgery is associated with a poor outcome, even after potentially curative hepatectomy. Tumor control before surgery is crucial to offer a chance of prolonged remission in patients with multiple metastases.