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Abstract Background The optimal timing of thoracic radiotherapy (TRT) in driver‐gene‐negative metastatic non‐small cell lung cancer (mNSCLC) patients was retrospectively investigated based on survival and safety profile. Methods The efficacy and safety data of driver‐gene‐negative mNSCLC patients treated with TRT during maintenance after first‐line therapy was collected. Patients whose primary tumor and metastatic lesions remained no progression during maintenance and then received TRT were categorized as the NP (no progression) group, while patients who experienced slow progression during maintenance without reaching progressive disease and then received TRT were categorized as the SP (slow progression) group. The efficacy and adverse events of TRT were analyzed. Results In total, 149 driver‐gene‐negative mNSCLC patients treated with TRT during maintenance were enrolled into the study, with 119 in the NP group and 30 in the SP group. After a median follow‐up of 30.83 (range: 26.62–35.04) months, the median progression‐free survival (PFS) in the NP group was 11.13 versus 9.53 months in the SP group (HR 0.599, p = 0.017). The median overall survival (OS) in the NP group was 32.27 versus 25.57 months in the SP group (HR 0.637, p = 0.088). The median PFS after radiotherapy (rPFS) was 6.33 versus 3.90 months (HR 0.288, p 0.05). Conclusion The addition of TRT during the pre‐emptive no progression phase was associated with a significantly longer PFS than during the delayed slow progression phase and had an acceptable safety profile. Our results might support the earlier initiation of TRT after induction therapy for some patients with driver‐gene‐negative mNSCLC.

Background: The optimal timing of thoracic radiotherapy (TRT) in driver‐gene‐negative metastatic non‐small cell lung cancer (mNSCLC) patients was retrospectively investigated based on survival and safety profile. Methods: The efficacy and safety data of driver‐gene‐negative mNSCLC patients treated with TRT during maintenance after first‐line therapy was collected. Patients whose primary tumor and metastatic lesions remained no progression during maintenance and then received TRT were categorized as the NP (no progression) group, while patients who experienced slow progression during maintenance without reaching progressive disease and then received TRT were categorized as the SP (slow progression) group. The efficacy and adverse events of TRT were analyzed. Results: In total, 149 driver‐gene‐negative mNSCLC patients treated with TRT during maintenance were enrolled into the study, with 119 in the NP group and 30 in the SP group. After a median follow‐up of 30.83 (range: 26.62–35.04) months, the median progression‐free survival (PFS) in the NP group was 11.13 versus 9.53 months in the SP group (HR 0.599, p = 0.017). The median overall survival (OS) in the NP group was 32.27 versus 25.57 months in the SP group (HR 0.637, p = 0.088). The median PFS after radiotherapy (rPFS) was 6.33 versus 3.90 months (HR 0.288, p < 0.001). The adverse events were tolerable and manageable in both groups without significant difference (p > 0.05). Conclusion: The addition of TRT during the pre‐emptive no progression phase was associated with a significantly longer PFS than during the delayed slow progression phase and had an acceptable safety profile. Our results might support the earlier initiation of TRT after induction therapy for some patients with driver‐gene‐negative mNSCLC. [ABSTRACT FROM AUTHOR]

Abstract In lung squamous cell carcinoma, KEAP1 mutations frequently coexist with TP53 mutations. A preclinical model showed that mutations leading to the activation of the KEAP1–NRF2 pathway contribute to clinical radioresistance. However, there have been few clinical reports on the association between the presence of KEAP1 and TP53 mutations in patients with lung squamous cell carcinoma. Here, we report the case of a 62‐year‐old patient with advanced lung squamous cell carcinoma with KEAP1 and TP53 mutations who experienced primary resistance to thoracic radiotherapy. She was administered pembrolizumab in combination with cytotoxic agents as the first‐line treatment and the best response was a partial response. However, the mediastinal lymph node metastases regrew 11 months after the chemotherapy. Thus, she received thoracic radiation therapy for localized lesions. However, the lesions within the radiation field had apparently progressed. Although she received subsequent chemotherapy, the lesion rapidly progressed. Treatment strategies including radiotherapy based on genetic stratification, such as KEAP1 and TP53 mutation status, should be implemented for lung squamous cell carcinoma.

In lung squamous cell carcinoma, KEAP1 mutations frequently coexist with TP53 mutations. A preclinical model showed that mutations leading to the activation of the KEAP1–NRF2 pathway contribute to clinical radioresistance. However, there have been few clinical reports on the association between the presence of KEAP1 and TP53 mutations in patients with lung squamous cell carcinoma. Here, we report the case of a 62‐year‐old patient with advanced lung squamous cell carcinoma with KEAP1 and TP53 mutations who experienced primary resistance to thoracic radiotherapy. She was administered pembrolizumab in combination with cytotoxic agents as the first‐line treatment and the best response was a partial response. However, the mediastinal lymph node metastases regrew 11 months after the chemotherapy. Thus, she received thoracic radiation therapy for localized lesions. However, the lesions within the radiation field had apparently progressed. Although she received subsequent chemotherapy, the lesion rapidly progressed. Treatment strategies including radiotherapy based on genetic stratification, such as KEAP1 and TP53 mutation status, should be implemented for lung squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background This study investigates the outcome of synchronous stage IV non-small cell lung cancer ( NSCLC) patients who received radical thoracic radiotherapy ( TRT). Methods We retrospectively reviewed the charts of stage IV NSCLC patients treated with TRT between January 2007 and December 2011. Radiotherapy was considered radical if it was the primary therapy with non-symptom driven intent, or consolidation therapy after initial chemotherapy and the biologically equivalent dose ≥53 Gy halted disease progression. The patients' demographics, disease characteristics, and treatment parameters were uniformly collected. Results Eighty-one patients were irradiated with radical intent, including 52% with more than five metastatic lesions. The minimum follow-up was 31.5 months for survivors. The median overall survival ( OS) was 20.8 months, with three and four-year OS rates of 23% and 18%, respectively. The median progression-free survival ( PFS) was 8.2 months, with one and two-year PFS rates of 23% and 9%, respectively. Partial response ( PR) after TRT and administration of targeted therapy were predictive of longer OS. The factors associated with favorable PFS included earlier local tunor node stage, absence of concurrent chemotherapy, and post- TRT PR. No correlation was found between the number of metastatic lesions and survival outcome. Incidences of grade ≥2 toxicities in the lung and esophagus were 9% and 26%, respectively. Conclusions Radical TRT may result in advantageous outcomes for selected stage IV NSCLC patients, regardless of the number of metastatic foci. Patients who achieved post- TRT PR attained the best outcomes. [ABSTRACT FROM AUTHOR]

Background The addition of thoracic radiotherapy improves the outcome of limited stage small cell lung cancer ( LS-SCLC), however, the cost-effectiveness of this process has never been reported. We aimed to estimate the short-term cost-effectiveness of chemotherapy combined with thoracic radiotherapy ( C- TRT) versus chemotherapy alone ( C/T) for LS-SCLC patients from the payer's perspective ( Taiwan National Health Insurance). Methods We identified LS-SCLC patients diagnosed within 2007-2009 through a comprehensive population-based database containing cancer and death registries, and reimbursement data. The duration of interest was one year within diagnosis. We included potential confounding covariables through literature searching and our own experience, and used a propensity score to construct a 1:1 population for adjustment. We used a net benefit ( NB) approach to evaluate the cost-effectiveness at various willingness-to-pay ( WTP) levels. Sensitivity analysis regarding potential unmeasured confounder(s) was performed. Results Our study population constituted 74 patients. The mean cost (2013 USD) and survival (year) was higher for C- TRT (42 439 vs. 28 357; 0.94 vs. 0.88). At the common WTP level (50 000 USD/life-year), C-TRT was not cost effective (incremental NB − 11 082) and the probability for C-TRT to be cost effective (i.e. positive net benefit) was 0.005. The result was moderately sensitive to potential unmeasured confounder(s) in sensitivity analysis. Conclusions We provide evidence that when compared to C/T, C- TRT is effective in improving survival, but is not cost-effective in the short-term at a common WTP level from a payer's perspective. This information should be considered by clinicians when discussing thoracic radiotherapy with their LS-SCLC patients. [ABSTRACT FROM AUTHOR]