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Background The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed. Methods We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results. Results The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months). Conclusions We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions.

Background: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not yet been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed.Methods: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and received radiotherapy for BM initially at the Hokkaido Cancer Center. Lung-molGPA items, sequence of therapy, use of osimertinib, expression of PD-L1 (classified as high, low, and no) and use of immune checkpoint inhibitors (ICI) were evaluated for influence. The main outcome measure was survival from the day of diagnosis of BM, and log-rank tests were performed to compare the results.Results: The median survival times for adenocarcinoma by groupings of GPA score (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p<0.0001), respectively. The median survival times for non-adenocarcinoma by groupings of GPA score (0‒1.0, 1.5‒2.0, and 2.5‒3.0) Group were 3.2, 11.0, and 16.0 months (p=0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome. The median survival times for the group with and without osimertinib treatment were 34.2 and 17.6 months, respectively (p=0.0164). In a comparison of treatment sequences, no significant differences were found between groups; however, patients who received both irradiation and tyrosine-kinase inhibitor for BM had better prognoses than patients with only irradiation for BM (35.8 months vs 14.8 months, p=0.0007). In patients tested for PD-L1 expression, the median survival times after diagnosis of brain metastasis were 5.6, 22.5, and 9.3 months for high-, low- and no-expression groups (p=0.2198), respectively. Also, in patients with high PD-L1 expression, those with ICI had better survival (median OS, 8.6 months) than those without (median OS, 3.6 months).Conclusions: We conformed that Lung-molGPA successfully classified Japanese NSCLC patients with brain metastasis by prognosis. Osimertinib was shown to extend survival of EGFR-positive NSCLC patients with BM, and ICI proved effective in patients with high PD-L1 expression.Trial registration: Not applicable

Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4–142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.