对于携带v-Ki-ras2 Kirsten大鼠肉瘤病毒癌基因同源物外显子2密码子12突变的患者，围手术期使用贝伐单抗可改善结直肠癌肺转移瘤切除术后的生存率†。

Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†.

作者信息

Renaud Stéphane, Schaeffer Mickaël, Falcoz Pierre-Emmanuel, Seitlinger Joseph, Romain Benoit, Voegeli Anne-Claire, Legrain Michèle, Reeb Jérémie, Santelmo Nicola, Rohr Serge, Brigand Cécile, Olland Anne, Guenot Dominique, Massard Gilbert

机构信息

Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.

Research Unit EA 3430: Tumoral Progression and Microenvironment, Translational and Epidemiological Approaches, Strasbourg University, Strasbourg, France.

出版信息

Eur J Cardiothorac Surg. 2017 Feb 1;51(2):255-262. doi: 10.1093/ejcts/ezw304.

DOI:10.1093/ejcts/ezw304

PMID:28186237

Abstract

OBJECTIVES

The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status.

METHODS

We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known.

RESULTS

A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58–98.42) vs 24 months (1.15–46.86), P = 0.001] and OS [101 vs 55 months (49.77–60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97–118.02) vs 60 months (53–66.99), P < 0.001; median LRRFS: 76 months (64.62–87.38) vs 44 months (35.27–52.73), P < 0.001].

CONCLUSION

Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.

摘要

目的

围手术期化疗（POC）和靶向治疗在结直肠癌（CRC）肺转移瘤切除术中的作用仍存在争议。我们旨在评估POC和靶向治疗是否根据突变状态与不同的预后相关。

方法

我们回顾了1998年至2015年期间223例行CRC肺转移瘤切除术且已知V-Ki-ras2 Kirsten肉瘤病毒癌基因同源物（KRAS）和V-raf鼠肉瘤病毒癌基因同源物B1（BRAF）突变状态的患者的数据。

结果

共有167例患者（74%）接受了POC：62例（37%）接受新辅助治疗，59例（35%）接受辅助治疗，46例（28%）同时接受新辅助和辅助治疗。POC对局部区域无复发生存期（LRRFS）（P = 0.21）或总生存期（OS）（P = 0.29）均无显著影响。此外，在辅助化疗的情况下，新辅助化疗或新辅助与辅助联合治疗的患者预后无显著差异（OS的P = 0.26，LRRFS的P = 0.14）。对于KRAS突变的患者，围手术期使用贝伐单抗与LRRFS [70个月（41.58 - 98.42）对24个月（1.15 - 46.86），P = 0.001]和OS [101对55个月（49.77 - 60.23），P = 0.004]的显著改善相关。然而，这种益处仅在KRAS外显子2密码子12突变的情况下显著[中位OS：101个月（83.97 - 118.02）对60个月（53 - 66.99），P < 0.001；中位LRRFS：76个月（64.62 - 87.38）对44个月（35.27 - 52.73），P < 0.001]。