Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Chin Clin Oncol. 2024 Aug;13(4):51. doi: 10.21037/cco-23-128. Epub 2024 May 28.
Patients with surgically resectable BRAF-mutated colorectal liver metastases (CRLM) or limited extrahepatic disease constitute a highly selective subgroup among BRAF-mutated patients, characterized by a more indolent disease biology. This is evident in their suitability for surgical resection. However, initial studies from a decade ago presented a discouraging outlook for these patients, citing early, frequent, multifocal recurrences and a very limited median overall survival (OS) of less than two years. Our objective was to provide an updated, comprehensive, and critically assessed review of the current literature on the prognostic impact of BRAF variants in CRLM, as well as to explore optimal treatment strategies for these patients through a systematic search.
A systematic literature search of the Medline, Scopus, and CENTRAL databases for studies reporting long-term outcomes of patients with a known BRAF status was performed.
A total of 386 unique studies were screened during the study selection process. After applying the exclusion criteria, a total of 18 studies published between 2012 and 2023 were deemed eligible for inclusion.
In contrast to older studies, more recent studies, with larger sample sizes, have revealed that the rate of extrahepatic recurrence is comparable between BRAF-mutated and wild-type patients. Furthermore, they have reported significantly improved survival outcomes, with OS extending up to 52 months. Notably, patients with non-V600E BRAF mutations may even achieve outcomes comparable to those with wild-type BRAF CRLM. Additionally, a few recent studies have compared surgery and systemic therapies, indicating that surgery is associated with improved survival rates, even for patients with the V600E mutation. This challenges the previous belief that BRAF mutations are absolute contraindications to surgical treatment. Surgical denial for technically resectable patients may now be reserved for specific clinical scenarios, such as the presence of a BRAF V600E mutation and concurrent extrahepatic disease.
具有可手术切除 BRAF 突变的结直肠癌肝转移（CRLM）或有限的肝外疾病的患者构成了 BRAF 突变患者中高度选择的亚组，其疾病生物学更为惰性。这在他们适合手术切除方面显而易见。然而，十多年前的初步研究对这些患者提出了令人沮丧的前景，指出早期、频繁、多灶性复发和非常有限的中位总生存期（OS）不到两年。我们的目的是提供对当前 BRAF 变异在 CRLM 中的预后影响的文献进行更新、全面和批判性评估，并通过系统搜索探索这些患者的最佳治疗策略。
对 Medline、Scopus 和 CENTRAL 数据库进行系统文献检索，以检索报告已知 BRAF 状态的患者的长期结果的研究。
在研究选择过程中总共筛选了 386 项独特的研究。在应用排除标准后，共有 18 项发表于 2012 年至 2023 年的研究被认为符合纳入标准。
与旧研究相比，具有更大样本量的最近研究表明，BRAF 突变型和野生型患者的肝外复发率相当。此外，他们报告了显著改善的生存结果，OS 延长至 52 个月。值得注意的是，非 V600E BRAF 突变的患者甚至可能获得与野生型 BRAF CRLM 患者相当的结果。此外，最近的一些研究比较了手术和系统治疗，表明手术与生存率的提高相关，即使对于 V600E 突变的患者也是如此。这挑战了 BRAF 突变是手术治疗绝对禁忌症的先前信念。对于具有技术上可切除性的患者，手术可能不再被保留用于特定的临床情况，例如存在 BRAF V600E 突变和同时存在肝外疾病。
