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Purpose: To examine the impact of epidermal growth factor receptor (EGFR) mutations on objective response to palliative lung radiotherapy in patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: A multicentre retrospective study was conducted of patients with metastatic NSCLC diagnosed between March 2010 and June 2012 who received palliative radiotherapy to the chest. Patients included for study had baseline imaging and follow-up imaging 1–3 months after radiotherapy. The primary endpoint was 1–3 month local objective imaging response by the Response Evaluation Criteria in Solid Tumours (RECIST). Patients were divided into EGFR mutation positive (EGFR+) and EGFR wild type (WT) cohorts for analysis. Results: There were 121 patients for study inclusion: 89 (74%) were EGFR WT and 32 (26%) were EGFR+. The response rate between EGFR WT and EGFR+ cohorts was not significantly different (49 vs. 63%, p = 0.21). On multivariate analysis, initiation of a tyrosine kinase inhibitor (TKI) after radiotherapy was associated with a higher rate of response (OR: 5.07, 95%CI: 1.08–23.69, p = 0.039) but EGFR mutation status was not. For the EGFR+ cohort, patients with disease progression after initial management on a TKI had a worse response rate compared to patients who were TKI-naïve before starting radiotherapy (30 vs. 77%, p = 0.018). Local control was not statistically different between the EGFR cohorts. Conclusion: The EGFR mutation status alone was not an independent predictor of objective radiographic response to palliative thoracic radiotherapy. Acquired resistance to TKI therapy may be associated with disease cross-resistance to palliative radiotherapy.

Introduction: After palliative radiotherapy for bone metastases from NSCLC, up to 30% of patients may derive no symptomatic benefit, and there are a lack of biological predictors for this. The purpose was to investigate whether EGFR and ALK genetic rearrangements were associated with greater rates of pain response to palliative radiotherapy. Methods: Patients were identified from a prospectively collected patient-reported outcomes database for all patients with lung cancer treated with conventional palliative radiotherapy for bone metastases from 2013 to 2016 in the province of British Columbia. Patients were divided on the basis of mutational status into the following: EGFR and ALK wild type (WT), EGFR mutation present (EGFR+), or ALK mutation present (ALK+). Patient-reported outcomes of global pain severity were collected before and after radiotherapy and on an ordinal scale of 0 to 4, with 0 representing no bone pain and 4 representing the maximal possible bone pain. The primary outcome was the rate of partial pain response (any improvement in score), and the secondary outcome was the rate of complete pain response (final pain score of 0). Stepwise, multivariable logistic analysis was used to compare response rates between treatment courses for different mutational statuses. Results: The final cohort consisted of 388 treatment courses for 329 unique patients. For the WT, EGFR+, and ALK+ groups, there were 180, 63, and nine treatment courses, respectively. There were 92 patients with no ALK and EGFR testing. The most common treatment fractionations were 8 Gy in one fraction (188 of 388) and 20 Gy in five fractions (160 of 388), and use of multifraction radiotherapy did not differ between mutation status groups (p = 0.3). Partial pain response rates were as follows: WT 63%, EGFR+ 75%, and ALK+ 78%. On multivariable analysis, rates of partial response were higher for EGFR+ (OR = 5.4, p < 0.001) and for ALK+ (OR = 12.8, p = 0.008) in comparison to WT. Complete response rates were as follows: WT 20.5%, EGFR+ 35%, and ALK+ 67%. On multivariable analysis, complete response was not significantly increased in EGFR+ compared with WT (OR = 1.6, p = 0.127). ALK+ mutation status was associated with a higher rate of complete response compared with WT (OR = 5.2, p = 0.031). Conclusions: There was an association between EGFR+ and ALK+ tumors and increased rates of partial pain response to palliative radiotherapy.