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BackgroundThe heterogeneous survival benefit of whole brain radiotherapy (WBRT) in brain metastatic non-small cell lung cancer (NSCLC) was prospectively evidenced in the Quality of Life after Treatment for Brain Metastases (QUARTZ) trial, resulting in inconsistent guideline recommendations and diverse clinical practices for giving WBRT. The objective of this study was to develop and externally validate an individual prediction model to demonstrate the added survival benefit of WBRT to assist decision making when giving WBRT is undetermined.MethodsFor model development, we collected 479 brain metastatic NSCLC patients unfit for surgery or stereotactic radiotherapy techniques at Siriraj Hospital. Potential predictors were age, sex, performance status, histology, genetic mutation, neurological symptoms, extracranial disease, previous systemic treatment, measurable lesions, further systemic treatment, and WBRT. Cox proportional hazard regression was used for survival analysis. We used multiple imputations to handle missing data and a backward selection method for predictor selection. Bootstrapping was used for internal validation, while model performance was assessed with discrimination (c-index) and calibration prediction accuracy. The final model was transformed into a nomogram and a web-based calculator. An independent cohort from Sawanpracharak Hospital was used for external validation.ResultsIn total, 452 patients in the development cohort died. The median survival time was 4.4 (95% CI, 3.8–4.9) months, with 5.1 months for patients who received WBRT and 2.3 months for those treated with optimal supportive care (OSC). The final model contained favorable predictors: female sex, KPS > 70, receiving additional systemic treatment, and WBRT. Having active extracranial disease, experiencing neurological symptoms, and receiving previous systemic treatment were adverse predictors. After optimism correction, the apparent c-index dropped from 0.71 (95% CI, 0.69–0.74) to 0.70 (95% CI, 0.69–0.73). The predicted and observed values agreed well in all risk groups. Our model performed well in the external validation cohort, with a c-index of 0.66 (95% CI, 0.59–0.73) and an acceptable calibration.ConclusionsThis model (https://siriraj-brainmetscore.netlify.app/) predicted the added survival benefit of WBRT for individual brain metastatic NSCLC patients, with satisfactory performance in the development and validation cohorts. The results certify its value in aiding treatment decision-making when the administration of WBRT is unclear.

Background Survival after diagnosis of brain metastases in non-small cell lung cancer (NSCLC) patients was dismal even after local therapy (surgery or brain irradiation), partly because of the systemic burden. Paucities of medical oncologists and molecular testing plus disparities in health care coverage resulted in limited access to systemic chemotherapy, let alone targeted drug or immunotherapy, for brain metastatic non-small cell lung cancer (BM-NSCLC) in Thailand. In this study, we aimed to explore prognostic factors affecting overall survival and evaluate survival outcome in BM-NSCLC limited access to systemic therapy. Methods We retrospectively collected 83 BM-NSCLC from a tertiary care hospital in Thailand. Data regarding clinical characteristics and treatment factors including age, sex, performance status, histology, neurologic symptom, extra-cranial metastasis (ECM), receiving whole brain radiotherapy (WBRT) and receiving systemic treatment were collected as independent factors. Associations between these variables and time to death were analyzed using the Cox proportional hazard regression. Results The patients' mean age was 63.1 year (SD 8.9). Most of the patients had adenocarcinoma (73%), presented with major neurological symptom (84%), and had brain metastases at their initial diagnosis of lung cancer (65%). Nearly 30% had ECM while 14% received systemic treatment. Three-quarters of patients received WBRT. Less than 15% were tested for actionable mutations. The median survival time was 2.7 months (95%CI: 2.2–4.1 months). One-month, three-month, six-month, and one-year survival probability was 78.3% (95%CI: 52.6–73.2%), 47.0% (95%CI: 36.0-57.2%), 26.5% (95%CI: 17.6–36.3%), and 9.6% (95%CI: 4.5–17.1%), respectively. Multivariable analysis showed that having extra-cranial disease was significantly associated with death (HR 4.22, 95%CI:1.27-14.0,p = 0.019 for first diagnosis lung with any ECM; HR 6.33, 95%CI:1.62–24.79, p = 0.008 for controlled lung & ECM; and HR 11.32, 95%CI:2.89–56.1, p = 0.003 for uncontrolled lung or ECM). Receiving systemic treatment was significantly associated with a reduced risk of death (HR0.39, 95%CI:0.18–0.80, p = 0.011). WBRT was insignificantly associated with prolonged survival (HR 0.79, 95%CI:0.43–1.44, p = 0.441). Conclusion Extracranial disease and lack of systemic treatment significantly shortened survival in BM-NSCLC.