Thoracic Oncology Unit, National Cancer Institute (INCan), México City, Mexico.
Experimental Oncology Laboratory, National Cancer Institute (INCan), Mexico City, Mexico.
Thorac Cancer. 2020 Apr;11(4):1026-1037. doi: 10.1111/1759-7714.13359. Epub 2020 Feb 19.
Previous studies have identified that patients with EGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT)-related outcomes has not been fully assessed. We studied the impact of common non-small cell lung cancer (NSCLC) genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases.
From 2009-2015, 153 patients with an available genotyping status were treated with whole-brain irradiation (WBI) before receiving systemic therapy. Primary outcome was ORR; secondary outcomes included intracranial progression-free survival (IPFS) and overall survival (OS).
Overall, ORR was 47.1%. ORR to RT varied significantly according to molecular status: EGFR (64.5%) ALK (54.5%) KRAS (20%) and WT (35.4%) (P = 0.001). EGFR mutation was the only independently associated factor for response to WBI (RR 3.52 [95% CI 1.6-7.7]; P = 0.002). Median IPFS was 10.8 months [95% CI 8.2-13.5] overall; however, IPFS also varied significantly according to molecular status: EGFR (18.2 months), ALK (18.4 months), KRAS (6.0 months) and WT (8.7 months) (P < 0.0001). OS for EGFR, ALK, KRAS and WT patients was 36.6, 32.2, 15.5 and 22.4 months, respectively (P = 0.014). Intracranial-ORR (HR 0.4 [95% CI 0.2-0.6], P < 0.001) and mutation status (HR 0.7 [95% CI 0.6-0.9], P < 0.042) were independently associated with a higher OS.
RT response varies as per tumor molecular status. The presence of EGFR mutations favors the organ-specific response to RT, and is associated with longer OS in patients with NSCLC and BM.
This study addressed for the first time the difference in radiotherapy-related outcomes in patients with different genotypes of non-small cell lung cancer (NSCLC) before they received systemic therapy. Results show that response to radiotherapy varies as per tumor molecular status, particularly EGFR-mutated tumors, have a favorable response to radiotherapy, contrary to KRAS-mutated tumors.
先前的研究已经表明，携带 EGFR 突变的患者对靶向治疗和化疗的反应更好；然而，遗传改变对放疗（RT）相关结果的影响尚未得到充分评估。我们研究了常见的非小细胞肺癌（NSCLC）基因改变（EGFR、ALK 和 KRAS）与脑转移患者接受 RT 后的客观缓解率（ORR）之间的关系。
从 2009 年至 2015 年，153 名患者接受了全脑照射（WBI）治疗，然后接受了系统治疗。主要结局是 ORR；次要结局包括颅内无进展生存期（IPFS）和总生存期（OS）。
总体而言，ORR 为 47.1%。根据分子状态，ORR 差异显著：EGFR（64.5%）、ALK（54.5%）、KRAS（20%）和 WT（35.4%）（P=0.001）。EGFR 突变是对 WBI 反应的唯一独立相关因素（RR 3.52 [95% CI 1.6-7.7]；P=0.002）。总体中位 IPFS 为 10.8 个月[95% CI 8.2-13.5]；然而，IPFS 也根据分子状态显著变化：EGFR（18.2 个月）、ALK（18.4 个月）、KRAS（6.0 个月）和 WT（8.7 个月）（P<0.0001）。EGFR、ALK、KRAS 和 WT 患者的 OS 分别为 36.6、32.2、15.5 和 22.4 个月（P=0.014）。颅内 ORR（HR 0.4 [95% CI 0.2-0.6]，P<0.001）和突变状态（HR 0.7 [95% CI 0.6-0.9]，P<0.042）与较高的 OS 独立相关。
RT 反应根据肿瘤的分子状态而变化。EGFR 突变的存在有利于 RT 对器官的特异性反应，并与 NSCLC 和 BM 患者的 OS 延长相关。
本研究首次探讨了 NSCLC 患者在接受系统治疗前不同基因型的放疗相关结局差异。结果表明，放疗反应根据肿瘤的分子状态而变化，特别是 EGFR 突变的肿瘤对放疗有良好的反应，而 KRAS 突变的肿瘤则相反。
