A flowchart of the patient selection process is shown in Fig. 1. A total of 580 patients who underwent WBRT were analyzed, and 279 patients were excluded for the following reasons: primary brain tumor, 27; meningeal metastasis, 21; prophylactic WBRT for SCLC, 105; hematological malignancy, 21; post-resection of BM, 63; pediatric patient, 20; and unavailable blood data, 22. Finally, 301 patients who underwent pWBRT were included in this study. Two hundred seventy patients (90%) had died,14 patients were alive, and 17 patients were lost to follow-up. The Patient characteristics are shown in Table 1. The median follow-up duration was 3.9 months (interquartile range, 1.6–9.9), and the median age at the first day of WBRT was 66 years (range, 22–87). The patients with age ≥ 60 years, of male sex, a KPS ≥ 70, and with an ECM were 211 (70%), 171 (57%), 155 (51%), and 245 (81%), respectively. The primary cancers were lung, breast, gastrointestinal, gynecological, and other cancers in 203 (67%), 38 (13%), 33 (11%), 8 (3%), and 19 (6%) patients, respectively. The median NLR and serum albumin level, LDH and Hb before WBRT were 3.6 (range, 0.26–49) and 3.8 (range, 1.9–5.2), 235 (range, 122–4665) and 12.2 (range, 4.0-17.5) respectively.

The patient selection flowchart. BM, brain metastases; SCLC, small cell lung cancer; WBRT, whole-brain radiotherapy

Figure 2A presents the Kaplan–Meier survival curves for patients with BM treated with WBRT. The median OS for all patients was 4.1 months (95% confidence interval [CI]: 3.3–4.7 months). Table 2 shows the factors associated with the OS. In the univariate analysis, the factors associated with a shorter OS were male sex (median OS, 3.2 months; 95% CI: 2.3–4.0 months, P < 0.01), KPS ≤ 60 (median OS, 2.4 months; 95% CI: 2.0–3.1 months, P < 0.01), not lung cancer (median OS, 2.8 months; 95% CI: 2.0–3.6 months, P = 0.02), presence of ECM (median OS, 3.6 months; 95% CI: 2.9–4.3 months, P = 0.04), NLR ≥ 5 (median OS, 2.2 months; 95% CI: 1.8–2.6 months, P < 0.01), serum albumin < 3.5 (median OS, 2.1 months, 95% CI: 1.6–2.4 months, P < 0.01), LDH > ULN (median OS, 2.5 months, 95% CI: 2.1–3.1 months, P < 0.01) and Hb < LLN (median OS, 2.9 months, 95% CI: 2.4–3.7 months, P < 0.01). RPA was a significant predictor of prognosis, but GPA was not. Driver gene mutations such as EGFR/ALK/ROS1 were not significant prognostic factors in patients with non-SCLC (P = 0.56). In the multivariate analysis, the factors associated with a shorter OS were male sex (hazard ratio [HR]: 1.4, 95% CI: 1.1–1.8, P = 0.01), KPS ≤ 60 (HR: 1.7, 95% CI: 1.3–2.2, P < 0.01), presence of ECM (HR: 1.6, 95% CI: 1.1–2.2, P < 0.01), NLR ≥ 5 (HR: 1.6, 95% CI: 1.2–2.1, P < 0.01), and LDH > ULN (HR: 1.3, 95% CI: 1.0–1.7, P = 0.03). The Kaplan–Meier curves for these factors are shown in Fig. 2B and F. Since we aimed to establish a PSS that can be used regardless of primary cancer, the primary site was not included as a factor in the multivariate analysis.

Kaplan–Meier curves of the overall survival. a. All patients. b. Sex of the patients. c. Presence of extracranial metastasis. d. Karnofsky performance status ≥ 70 or ≤ 60. e. Neutrophil-lymphocyte ratio ≥ 5 or < 5. f. Lactate dehydrogenase ≥ upper limit of normal or < upper limit of normal. g. Prognostic score 0–2, 3 and 4–5

A new PSS was introduced to predict the survival of patients after pWBRT. The PSS was associated with male sex and the presence of ECM, KPS, NLR, and LDH, which were independent prognostic factors. A score of one was assigned to male sex, presence of ECM, KPS ≤ 60, NLR ≥ 5, and LDH > ULN, and a score of zero to female sex, absence of ECM, KPS ≥ 70, NLR < 5, and LDH ≤ ULN. Since the HR of each variable was almost equivalent, the weights of the assigned scores were set equally among these factors. The Kaplan–Meier survival curve showed that the median duration of OS for 129 patients with a score of 0–2, 89 patients with a score of 3 and 83 patients with a score of 4–5 were 9.0 (95% CI: 6.4–10.4), 3.5 (95% CI: 2.8–4.7) and 1.7 months (95% CI: 1.3–2.1), respectively (P < 0.001; Fig. 2G; Table 3). Lung cancer patients were almost equally included in each group.