Aim: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. Patients and Methods: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. Conclusion: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.Lung cancer has the highest mortality rate worldwide of all cancer types (1, 2). In recent years, the emergence of molecular targeted drugs and immune checkpoint inhibitors (ICIs) has drastically changed the strategy for the treatment of advanced lung cancer. ICIs improve the overall survival (OS) of patients with lung cancer (3-5).The expression level of programmed death-ligand 1 (PD-L1) in tumor cells is determined through immunohistochemistry (IHC). PD-L1 is a significant predictive marker of ICIs; however, it is not a sufficient indicator of the efficacy of immunotherapy. Several serum-based parameters related to systemic inflammation and nutritional status of patients have been studied as predictive or prognostic markers during immunotherapy, such as the neutrophil-tolymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) (6-8). However, the unified cutoff points for these metrics and other parameters that are more sensitive than these markers are controversial.This study aimed to investigate factors of the efficacy of immunotherapy that are readily available via routine blood tests. We focused on the combination of hemoglobin (Hb) and serum albumin levels. Patients and MethodsThis retrospective study included consecutive patients with inoperable lung cancer who underwent monotherapy with ICIs,

Background: Pembrolizumab is the recommended first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥50% without driver mutations. However, its efficacy and safety for patients ≥75 years have not been prospectively investigated; this was the aim of this study. Methods: This multicenter and open-label single-arm phase II study was conducted at 12 institutions. Chemotherapy-naïve patients with advanced NSCLC and a PD-L1 TPS of ≥50% without EGFR mutations or translocation of the ALK received pembrolizumab every 3 weeks. The primary endpoint was progression-free survival (PFS) with a threshold of 4.3 months. The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life. Results: Twenty-six patients were enrolled between October 2017 and March 2020. The median PFS was 9.6 (95% confidence interval [CI] 2.1-20.6) months. The lower limit of the 95% CI did not exceed the target. The median OS was 21.6 months. The ORR and DCR were 41.7% and 70.8%, respectively. The proportion of patients with grade ≥3 treatment-related adverse events was 15.4%. The quality of life score did not change significantly during treatment. Conclusion: While this study showed that pembrolizumab was a tolerable treatment for elderly patients, the safety requires further confirmation in a larger study. Although the primary endpoint, the median PFS (9.6 months), was slightly shorter than that (10.3 months) of the previous phase III study (KEYNOTE-024 study), the median PFS did not achieve the expected value.K E Y W O R D S elderly patients, non-small-cell lung cancer, pembrolizumab, programmed death ligand-1

BackgroundWithout explicit prognostic information, patients may overestimate their life expectancy and make poor choices at the end of life. We sought to design the Japanese version of an information aid (IA) to provide accurate information on prognosis to patients with advanced non–small-cell lung cancer (NSCLC) and to assess the effects of the IA on hope, psychosocial status, and perception of curability.MethodsWe developed the Japanese version of an IA, which provided information on survival and cure rates as well as numerical survival estimates for patients with metastatic NSCLC receiving first-line chemotherapy. We then assessed the pre- and post-intervention effects of the IA on hope, anxiety, and perception of curability and treatment benefits.ResultsA total of 20 (95%) of 21 patients (65% male; median age, 72 years) completed the IA pilot test. Based on the results, scores on the Distress and Impact Thermometer screening tool for adjustment disorders and major depression tended to decrease (from 4.5 to 2.5; P = 0.204), whereas no significant changes were seen in scores for anxiety on the Japanese version of the Support Team Assessment Schedule or in scores on the Hearth Hope Index (from 41.9 to 41.5; p = 0.204). The majority of the patients (16/20, 80%) had high expectations regarding the curative effects of chemotherapy.ConclusionThe Japanese version of the IA appeared to help patients with NSCLC maintain hope, and did not increase their anxiety when they were given explicit prognostic information; however, the IA did not appear to help such patients understand the goal of chemotherapy. Further research is needed to test the findings in a larger sample and measure the outcomes of explicit prognostic information on hope, psychological status, and perception of curability.Electronic supplementary materialThe online version of this article (10.1186/s12904-018-0292-6) contains supplementary material, which is available to authorized users.

Immune-related adverse events (irAEs) commonly involve the gastrointestinal tract, endocrine glands, skin, and liver, and rarely the nervous system. The pathomechanism of irAEs in the nervous system is unclear, and so characterizing these severe toxic effects is a priority, even if irAEs are uncommon in the nervous system. Our patient presented subacute muscle weakness and dysesthesia with colitis as irAEs caused by pembrolizumab, one of the antiprogrammed death-1 (PD-1) antibodies. Electromyography revealed abundant fibrillations and fasciculations of upper and lower extremities and severe reduction in motor unit potentials; however, antineutrophil cytoplasmic antibodies, rheumatoid factor, autoantibodies against Hu and Yo, and anti-ganglioside antibodies, such as GQ1b, were undetectable in the serum. Although he was treated with high-dose glucocorticoids, antibiotics, and a monoclonal anti-tumor necrosis factor alpha (TNFα) antibody, he developed colonic perforation. The total colorectal resection was performed, and the resected colon showed mucosal defect and perforation. He died of lung aspergillosis. Postmortem examination revealed CD8-positive lymphocyte infiltration around neurons of dorsal root ganglia. The sciatic nerve displayed the widening of myelin laminae and thinning of myelinated fibers but not a decrease in the density of myelinated nerve fibers. In the sural nerve, the density of myelinated fibers slightly decreased, and some fibers showed less densely myelinated laminae. Drug safety information, including previous randomized trials of anti-PD-1 and anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies, showed that patients treated with anti-PD-1 antibodies appeared to have more frequent and severe peripheral neuropathies compared to those in patients who received anti-CTLA-4 antibodies (1.59% vs. 0.69%; Fisher exact test, P < 0.001; three severe events vs. zero severe events). The present results and drug safety information suggest that the pathomechanism of irAEs caused by anti-PD-1 antibodies is different from that by anti-CTLA-4 antibodies. The neurological irAEs might be clues to solving the pathomechanism of irAEs.