OBJECTIVES Tyrosine kinase inhibitor (TKI) has been the standard of care for advanced non-small cell lung cancers (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, but these tumors invariably develop drug resistance. As progression most frequently advances in sites of original disease, our study sought to explore the time to response for NSCLC to TKI therapy and the patterns of disease progression, to provide evidence for timing and candidates for local therapy intervention. MATERIALS AND METHODS A cohort of 105 EGFR-mutated IIIB or IV NSCLC patients treated with EGFR-TKI were retrospectively analyzed. The disease progression patterns were divided into 3 categories: progression in sites of original disease, progression in new distant sites, and combined progression. RESULTS Before cut-off date, 80 patients had disease progression. Thirty-three (41.25 %) patients had progression in sites of original disease, 34 (42.5 %) patients had progression in new sites and 13 (16.25 %) patients had combined progression, respectively. The median time to response for responders was 2.00 months (95 %CI 1.28-2.92 months), and the median time to maximal tumor shrinkage for SD patients was 2.00 months (95 %CI 1.42-2.58 months). Multivariate logistic regression model showed that the 21 exon mutation is related to the incidence of original site failure. CONCLUSION Over 1/3 of the patients progress at the original sites, which indicated that this subset of patients may benefit from local therapy. Moreover, as the results indicate that considerable shrinkage for TKI therapy occurs in first two months after TKI initiation, local therapy can be adopted after this timepoint, before disease progression. We also propose EGFR gene mutation type as potential inclusion criteria to identify candidates for combined local therapy.

中文翻译：

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EGFR-TKI治疗的非小细胞肺癌的放疗时机和疾病进展的模式。

目的酪氨酸激酶抑制剂（TKI）已成为具有表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）的治疗标准，但这些肿瘤总是会产生耐药性。随着进展在原发病部位的进展最频繁，我们的研究试图探索NSCLC对TKI治疗的反应时间和疾病进展的模式，以提供时机和进行局部治疗干预的证据。材料与方法回顾性分析了105例经EGFR-TKI治疗的EGFR突变IIIB或IV NSCLC患者。疾病进展模式分为3类：原始疾病部位的进展，新的远端部位的进展以及综合进展。结果在截止日期之前，80名患者病情恶化。33例（41.25％）患者在原发病部位进展，34例（42.5％）患者在新部位进展，13例（16.25％）合并进展。响应者的中位反应时间为2.00个月（95％CI为1.28-2.92个月），SD患者达到最大肿瘤缩小的中位时间为2.00个月（95％CI为1.42-2.58个月）。多元logistic回归模型显示21个外显子突变与原始位点失败的发生有关。结论超过1/3的患者在原始部位进展，这表明该部分患者可能会受益于局部治疗。此外，由于结果表明在开始TKI后的前两个月，TKI治疗出现了明显的萎缩，在这个时间点之后，在疾病进展之前，可以采用局部疗法。我们还建议将EGFR基因突变类型作为潜在的纳入标准，以鉴定联合治疗的候选对象。