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Background/aim: Amrubicin is recognized as a second-line treatment for refractory small-cell lung cancer (SCLC) and is administered immediately after chemotherapy; however, it has not been evaluated in patients with recurrent SCLC following chemoradiotherapy (CRT). This study aimed to examine the activity and safety of amrubicin monotherapy in patients with relapsed SCLC previously treated with CRT., Patients and Methods: This retrospective study evaluated patients with relapsed SCLC who had been previously treated with CRT, followed by amrubicin monotherapy between April 2007 and June 2021. The clinical efficacy and toxicity were assessed., Results: Overall, 30 patients (20 men and 10 women) were enrolled. The response rate was 50.0% [95% confidence interval (CI)=33.1-66.8%]. The median progression-free survival and overall survival from the first amrubicin treatment was 4.1 months (95%CI=2.3-6.0 months) and 13.5 months (95%CI=7.5-16.0 months), respectively. Grade ≥3 hematological adverse events occurred as follows: decreased white blood cells in 63.3% of patients, decreased neutrophil count in 70.0%, and febrile neutropenia in 10.0%. Grade 3 pneumonitis was observed in one patient. No treatment-related deaths occurred., Conclusion: Amrubicin is both feasible and effective in patients with relapsed SCLC who were previously treated with CRT. The efficacy and toxicity of amrubicin in this study were consistent with those of previous reports, indicating that amrubicin retained its effectiveness post-CRT. Consequently, amrubicin following CRT may be the optimal chemotherapeutic choice for patients with relapsed limited-disease SCLC., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Nivolumab plus ipilimumab (Nivo-Ipi) combination therapy is an effective first-line treatment for advanced non-small cell lung cancer (NSCLC). However, its effectiveness and feasibility in elderly patients (aged ≥ 75 years) remain unclear. This study aimed to investigate the efficacy and safety of first-line Nivo-Ipi therapy in elderly patients with NSCLC., Methods: This retrospective study included 57 patients with NSCLC (52 men and 5 women), aged ≥ 75 years (range: 75-86) who received first-line Nivo-Ipi therapy from December 2020 to November 2022 at four institutes in Japan. Patient characteristics, therapeutic efficacy, and the incidence and severity of adverse events (AE) were assessed., Results: The overall response rate was 42.1%, the disease control rate was 73.6%, the median progression-free survival (PFS) was 7.1 months, and the median overall survival (OS) was 14.1 months. Common Grade ≥ 3 AEs included pneumonitis, elevated aspartate transaminase, elevated alanine transaminase, adrenal insufficiency, and colitis. No treatment-related deaths were reported. PFS and OS were longer in patients who experienced treatment-related AEs. Patients with and without AEs had a median PFS of 11.7 and 2.8 months, respectively. Similarly, the median OS of patients with and without AEs was 20.4 and 9.0 months, respectively., Conclusion: First-line Nivo-Ipi therapy is effective in elderly patients with NSCLC. Although there was an increased incidence of pneumonitis, the treatment was manageable and presented as a viable treatment option. Notably, the occurrence of treatment-related AEs was associated with improved clinical outcomes, suggesting a potential prognostic value of AEs in this population., Competing Interests: Declarations. Conflict of interests: The authors declare no competing interests. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the International Medical Center, Saitama Medical University (number 2023-080). Consent to participate: The need for informed consent was waived by the institutional review boards of the participating institutions owing to the retrospective nature of the study. However, an opportunity to refuse participation through the opt-out method was provided. Consent to publish: Not applicable., (© 2025. The Author(s).)

Introduction: Established biomarkers for predicting chemoradiotherapy efficacy for limited-disease small cell lung cancer (LD-SCLC) are lacking. The inflammation-based Glasgow Prognostic Score (GPS), comprising serum C-reactive protein (CRP) and albumin levels, can predict survival in advanced cancer. This study investigated whether metabolic and inflammatory markers, including the GPS, can predict the efficacy of chemoradiotherapy in patients with LD-SCLC., Methods: We retrospectively analyzed 124 patients who underwent chemoradiotherapy for LD-SCLC at two institutions between April 2007 and June 2021, and assessed the prognostic significance of various metabolic and inflammatory markers. The GPS was calculated using the CRP and albumin concentrations, and categorized as follows: 0, CRP <1.0 mg/dL and albumin ≥3.5 mg/dL; 1, elevated CRP or decreased albumin; and 2, CRP ≥1.0 mg/dL and albumin<3.5 mg/dL. Differences in progression-free survival (PFS) and overall survival (OS) were examined using Kaplan-Meier curves and Cox proportional-hazard models., Results: The overall response rate was 95.1% (95% confidence interval [CI]: 89.6-97.9%). The median PFS and OS from chemoradiotherapy initiation were 12.6 (95% CI: 9.9-15.4) and 29.0 (95% CI: 24.8-45.5) months, respectively. The GPS demonstrated independent predictive ability for the effectiveness of chemoradiotherapy, wherein favorable scores (GPS 0-1) were significantly correlated with superior PFS and OS compared to unfavorable scores (GPS 2: PFS: 14.8 vs. 6.7 months, p = 0.0001; OS: 35.4 vs. 11.0 months, p < 0.0001)., Conclusion: This preliminary examination revealed that the GPS was significantly associated with PFS and OS in patients undergoing chemoradiotherapy for LD-SCLC, indicating its potential utility in assessing the therapeutic outcomes in LD-SCLC., (© 2024 S. Karger AG, Basel.)

Objectives: Programmed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting., Materials and Methods: This was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab., Results: Among the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45-2.70; P < 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low., Conclusion: Comprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiroaki Akamatsu has received grants or contracts from Amgen, Eli Lilly, and Chugai; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Amgen, Ono, AstraZeneca, Pfizer, Boehringer Ingelheim, Takeda, Bristol Myers Squibb, Taiho, Chugai, Eli Lilly, MSD, Nippon Kayaku, and Novartis; and has participated in Data Safety Monitoring Boards or Advisory Boards for Amgen and Janssen. Yasuhiro Koh has received grants or contracts from Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Takeda, Zeon, and Chugai; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Amgen, Takeda, Chugai, Guardant Health, CytoGen, Tosoh, and Novartis; and has participated in Data Safety Monitoring Boards or Advisory Boards for Tosoh. Makoto Nishio has received payment or honoraria for lectures from Ono, Chugai, Taiho, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, and Janssen. Yasushi Goto has received grants or contracts from AstraZeneca, and Pfizer; grants for the institution from AbbVie, Eli Lilly, Bristol Myers Squibb, Ono, Novartis, Kyorin, Daiichi Sankyo, Novartis, and Preferred Network; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis, Merck, and Thermo Fisher; has participated in Data Safety Monitoring Boards or Advisory Boards for AstraZeneca, Chugai, Boehringer Ingelheim, Eli Lilly, Taiho, Pfizer, Novartis, Guardant Health, Illumina, Daiichi Sankyo, Ono, Bristol Myers Squibb, and MSD; and had a leadership or fiduciary role in Cancer Net Japan and JAMT. Hidetoshi Hayashi has received grants or contracts from IQVIA Services, Syneos Health, EPS Corporation, Nippon Kayaku, Takeda, MSD, Amgen, Taiho, Bristol Myers Squibb, Janssen, CMIC, Pfizer, Labcorp Drug Development, Kobayashi, Eisai, EP-CRSU, Shionogi, Otsuka, GlaxoSmithKline, Sanofi, Chugai, Nippon Boehringer Ingelheim, SRL Medisearch, PRA Health Sciences, Astellas Pharma, Ascent Development Services, Bayer Yakuhin, Parexel, Kissei, EPS Corporation, Daiichi Sankyo, Ono, PPD-SNBL, SymBio, Mebix, AstraZeneca, Mochida, Japan Clinical Research Operations, Eli Lilly, Novartis, Otsuka, and SRL; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Ono, Daiichi Sankyo, AstraZeneca, Eli Lilly, Chugai Pharmaceutical, MSD, Pfizer, Nippon Boehringer Ingelheim, Merck, 3H Clinical Trial, Novartis, Bristol Myers Squibb, Amgen, Sysmex Corporation, Takeda, and Guardant Health. Satoru Miura has received payment or honoraria for lectures from Chugai, Taiho, Ono, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Boehringer Ingelheim, and Takeda. Hiroshi Kagamu has received payment or honoraria for lectures from Chugai, Ono, AstraZeneca, and Bristol Myers Squibb. Ichiro Yoshino has received grants or contracts from AstraZeneca, Chugai, Daiichi Sankyo, and Taiho; consulting fees from AstraZeneca, Chugai, Covidien, and Johnson & Johnson; and payment or honoraria for lectures from AstraZeneca, Chugai, Daiichi Sankyo, Eli Lilly, Covidien, Johnson & Johnson, Taiho, Amgen, MSD, CSL Behring, KM Biologics, Intuitive Surgical, Shionogi, Tsumura, and Takeda. Toshihiro Misumi has received honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Chugai, AstraZeneca, and Miyarisan. Atsuto Mouri has received payment or honoraria for lectures from Chugai. Noriko Yanagitani has received consulting fee from Chugai and payment or honoraria for lectures from AstraZeneca, Eli Lilly, Pfizer, Chugai, Takeda, Bayer Yakuhin, Ono, and Bristol Myers Squibb. Hiroshi Nokihara has received payment or honoraria for lectures from MSD, Ono, AstraZeneca, and Chugai. Masahiro Seike has received payment or honoraria for lectures from Chugai, AstraZeneca, Bristol Myers Squibb, Pfizer, Takeda, Nippon Kayaku, Merck Biopharma, MSD, Taiho, Ono, Nippon Boehringer Ingelheim, Novartis, Kyowa-Kirin, and Daiichi-Sankyo. Masahide Mori has received research funding from Chugai, Ono, MSD, and Delta-fly; and payment or honoraria for lectures from AstraZeneca, Boehringer Ingelheim, MSD, Eli Lilly, Novartis, Chugai, Taiho, Kyowa-Kirin, Ono, Otsuka, Nihon-Kayaku, Pfizer, Daiichi Sankyo, Takeda, and Shionogi. Tetsuya Mitsudomi has received grants or contracts from MSD, Ono, AstraZeneca, and Chugai; payment or honoraria for speaker’s bureau from MSD, Ono, Bristol Myers Squibb, AstraZeneca, and Chugai; has participated in Advisory Boards for MSD, Ono, Bristol Myers Squibb, AstraZeneca, and Chugai; and has been a President at IASLC. The remaining authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Cancer cachexia complicates advanced non-small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first-line systemic therapy., Methods: We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first-line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first-line systemic therapy., Results: A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0-2 who were initiated on first-line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first-line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy-associated emesis affecting early appetite-related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: -3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (-1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression-free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003)., Conclusions: Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite-related QOL trends vary based on the type of first-line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Two-deoxy-2-[fluorine-18]-fluoro-d-glucose ( 18 F-FDG) positron emission tomography (PET) is useful for detecting malignant lesions; however, the clinical significance of cardiac 18 F-FDG uptake in patients with cancer remains unclear. This preliminary study explored the relationship between cardiac 18 F-FDG uptake and advanced diseases such as cancer cachexia in non-small cell lung cancer (NSCLC)., Methods: Forty-three patients with advanced NSCLC who underwent 18 F-FDG PET and complained of weight loss before the first-line systemic therapy were retrospectively included in this study. Visual assessment using a 5-point scale based on 18 F-FDG uptake was performed; a cut-off score of 3 was determined, a low score was 1, 2, or 3, and a high score was 4 or 5)., Results: High and low visual cardiac 18 F-FDG uptakes were observed in 27 (62.8%) and 16 (37.2%) patients, respectively. Of the 43 patients, 17 (39.5%) definitely had cachexia, and 26 (60.5%) did not. A low visual score and standardized uptake value max for cardiac 18 F-FDG uptake were significantly associated with high metabolic tumor activity (p = 0.009, and p = 0.009, respectively) and a high neutrophil-to-lymphocyte ratio (p = 0.016, and p = 0.047, respectively), whereas a low visual score for cardiac 18 F-FDG uptake and high metabolic tumor activity were significantly associated with cachexia (p = 0.004). The amount of cardiac 18 F-FDG accumulation depicted a close relationship with body mass index, low weight loss, and inflammation. The combination of cachexia and low visual cardiac 18 F-FDG uptake was identified as a significant predictor for poor overall survival (OS) (p = 0.034)., Conclusion: Decreased visual cardiac 18 F-FDG uptake was associated with poor nutritional status and OS, and cachexia in patients with advanced NSCLC., Competing Interests: Declarations Ethics approval and consent to participate All procedures involving human participants performed in this study were in accordance with the ethical standards of the institutional and/or national research committees and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Real-world, large-scale studies on the association between immune-related adverse events (irAE) and immune checkpoint inhibitor therapy effectiveness are limited. We evaluated overall survival (OS) and progression-free survival based on the occurrence and grade of irAEs., Patients and Methods: We used data from Japanese patients with unresectable advanced or recurrent non-small cell lung cancer (NSCLC) who received atezolizumab and were enrolled in J-TAIL, a multicenter, prospective, single-arm observational study., Results: Among the 1,002 patients, 190 (19.0%) developed irAEs. The most common irAEs were skin disorders (3.8%) of any grade and interstitial lung disease (1.5%) of grade ≥3. Patients who developed irAEs within 4 or 6 weeks of treatment initiation had higher baseline C-reactive protein levels than those without irAEs. OS was longer in patients with irAEs [HR, 0.66; 95% confidence interval (CI), 0.54-0.82], particularly in those with low-grade irAEs (HR, 0.45; 95% CI, 0.33-0.62), than in patients without irAEs. The HR (95% CI) for OS in patients with low-grade and high-grade skin or endocrine disorder-related irAEs was 0.42 (0.28-0.64) and 0.37 (0.15-0.88), respectively. The HR (95% CI) for OS in patients with low-grade and high-grade irAEs other than skin or endocrine disorders was 0.44 (0.30-0.65) and 1.27 (0.96-1.69), respectively., Conclusions: In patients with unresectable advanced or recurrent NSCLC treated with atezolizumab in real-world settings, irAEs are associated with a clinical benefit except in those with high-grade irAEs other than skin and endocrine disorders., Significance: Immune checkpoint inhibitors are useful for treating NSCLC but can cause life-threatening irAEs. This study had a large sample size and stratified the analysis by irAE type and grade. The results suggest that improved management of irAEs may improve the therapeutic effect of atezolizumab., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC., Patients and Methods: From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT., Results: A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference ( p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively ( p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group., Conclusions: Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group., (© 2024 Ayako Shiono et al., published by Sciendo.)

Background: The risk and survival of patients with non-small cell lung cancer (NSCLC) with pre-existing autoimmune disorders (AIDs) receiving immune checkpoint blockade (ICB) therapy have not been clearly established., Patients and Methods: This multi-institutional, retrospective cohort study was conducted in collaboration with 20 centers in Japan., Results: In total, 229 patients with advanced or recurrent NSCLC and pre-existing AID, with or without ICB treatment from January 2010-February 2020, were included and analyzed. Among 69 patients who received ICB, 2 received two lines of ICBs with a total of 71 ICB treatments; 57 (80.3 %) and 14 (19.7 %) patients received ICB monotherapy and combination therapy, respectively. AID flares were observed in 18 patients (25.4 %, 95 % confidence interval [CI], 15.8-37.1 %) receiving ICB. AID exacerbations were more likely when NSCLC was diagnosed less than 1 year after the AID diagnosis (odds ratio 5.26 [95 % CI, 1.40-21.61]; P = 0.016). Immune-related adverse events were observed in 32 patients (45.1 %, 95 % CI, 33.2-57.3 %); 17 had grade 3 or higher. The safety profile of combination immunotherapy was not significantly different from that of the monotherapy. After inverse probability weighting, the use of ICB prolonged survival (hazard ratio 0.43 [95 % CI, 0.26-0.70]; P = 0.0006)., Conclusions: These findings revealed a novel risk factor for AID flares following ICB treatment, that is the diagnosis of NSCLC within 1 year of AID diagnosis, and showed that ICBs may improve survival in this population. These results support the utilization of ICB in patients with NSCLC and pre-existing AID., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Dr. Asao reported receiving personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Merck Biopharma, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. Dr. Shukuya reported receiving grants from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, MSD, and Novartis, outside the submitted work; and personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, outside the submitted work. Dr. Mouri reported receiving personal fees from Chugai Pharmaceutical and Eli Lilly, outside the submitted work. Dr. Tsukita reported receiving personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Meyers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Eli Lilly, MSD, and Taiho Pharmaceutical, outside the submitted work. Dr. Watanabe reported receiving grants from Nippon Kayaku outside the submitted work, personal fees from AstraZeneca, Bristol-Meyers Squibb, Celltrion, Chugai Pharmaceutical, Daiichi-Sankyo, Eli Lilly, Kyowa Kirin, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, outside the submitted work. Dr. Morita reported receiving personal fees from Amgen, AstraZeneca, Bristol-Meyers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eli Lilly, MSD, Nippon Kayaku, Novartis, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, and ThermoFisher Scientific, outside the submitted work. Dr. Yoshioka reported receiving grants from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Delta Fly Pharma, Janssen Pharmaceutical, MSD, and Novartis, outside the submitted work; and personal fees from AstraZeneca, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Kyowa Kirin, MSD, Nippon Kayaku, Nipro Pharma, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Taiho Pharmaceutical, outside the submitted work. Dr. Namba reported receiving personal fees from Chugai Pharmaceutical, Kyowa Kirin, MSD, and Taiho Pharmaceutical, outside the submitted work. Dr. Nakagawa reported receiving personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Japan Blood Products Organization, MSD, Nippon Kayaku, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, and Taiho Pharmaceutical, outside the submitted work. Dr. Watanabe reported receiving grants from MSD, outside the submitted work. Dr. Kobayashi reported receiving personal fees from AstraZeneca and Takeda Pharmaceutical, outside the submitted work. Dr. Takahashi reports grant support from Asahi Kasei Pharma, Bayer, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli-Lilly, Kyorin Pharmaceutical, Kyowa Kirin, Nippon Kayaku, Nippon Shinyaku, Nipro Pharma, Novartis, Ono Pharmaceutical, Pfizer, Sanofi, Shionogi, Takeda Pharmaceutical, Taiho Pharmaceutical, Teijin Pharma, and Tsumura, outside the submitted work; personal fees from Abbott Japan, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Merck Biopharma, MSD, Kyorin Pharmaceutical, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Taiho Pharmaceutical, Takeda Pharmaceutical, ThermoFisher Scientific and Viatris, outside the submitted work.; and serving as a board member of director of the Japan Lung Cancer Society and The Japanese Respiratory Society. No other disclosures were reported., (Copyright © 2024. Published by Elsevier B.V.)

Background/aim: Spontaneous regression (SR) of cancer, which indicates the natural disappearance of malignant tumors, is rare. Little is known about the mechanisms underlying SR; however, immunological reactions, infections, injuries, and medications have been presumed. Among previously reported cases of SR, lung cancer cases have been extremely limited., Case Report: Here, we present a case of lymph node metastasis exacerbation after SR of a primary adenocarcinoma following a biopsy. After complete disappearance of the primary site tumor, metastatic lymph nodes in the mediastinum gradually increased in size as a single lesion. Local treatment with resection and radiotherapy was effective for this metastasis, without recurrence for >3 years., Conclusion: This is an interesting case of SR of pulmonary adenocarcinoma with inconsistent features in the primary and metastatic lesions. When physicians encounter exacerbation of metastatic sites with SR of the primary site in lung cancer, local intervention may be considered as a curative treatment., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Chemo-immunotherapy, including the programmed death ligand 1 (PD-L1) antibody, is an effective treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, no biomarker has been established for the prediction of chemo-immunotherapy. Therefore, we investigated the potential of 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) as a predictive marker., Patients and Methods: Forty-six patients with ES-SCLC who received 18 F-FDG-PET immediately before combined platinum-based chemotherapy with PD-L1 blockade as a first-line treatment were eligible, and the maximum standard uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18 F-FDG uptake were evaluated., Results: PD-L1 and tumor infiltrative lymphocytes (TILs) were immunohistochemically analyzed in 36 of the 46 patients. A high MTV was significantly associated with poor performance status and low albumin levels, and there was a significant association between low albumin and high TLG. Univariate analysis identified sex, Brinkman index, and MTV as significant predictors of progression-free survival (PFS), and sex, SUV max , MTV, and TLG as significant factors of overall survival (OS). Multivariate analysis revealed that sex, Brinkman index, and MTV were independent prognostic factors for PFS, and sex, SUV max , MTV, and TLG were significant predictors of OS. SUV max was significantly higher in patients with positive PD-L1 expression than in those with negative expression but was not significantly different between positive and negative TILs. Moreover, the levels of MTV and TLG were not closely associated with the levels of PD-L1 and TILs., Conclusion: MTV or TLG metabolic tumor activity is suitable for the prediction of chemo-immunotherapy outcomes in patients with ES-SCLC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The relationship between antinuclear antibody (ANA) and the efficacy of programmed death-1 (PD-1) blockade remains controversial. Here, we investigated the prognostic significance of ANA titer in patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab monotherapy as the first-line treatment, compared with that of platinum-based chemotherapy with PD-1 blockade., Methods: Our clinical data based on the ANA titer (1:80) were retrospectively reviewed for patients with advanced NSCLC, who were treated with first-line pembrolizumab monotherapy and platinum-based chemotherapy with PD-1 blockade. Immunohistochemical staining for tumor-infiltrating lymphocytes such as CD4, CD8 and Foxp3 was performed., Results: Among 106 patients treated with pembrolizumab, 19 (17.9%) tested high for ANA. Progression-free survival (PFS) and overall survival (OS) were significantly better in patients with high ANA than in those with low ANA, and high ANA was identified as an independent prognostic predictor, particularly in the subgroup with programmed death ligand-1 (PD-L1) ≥ 50%. However, no statistically significant difference in PFS and OS based on the ANA titer was observed in 59 patients treated with combinational chemotherapy and immunotherapy. High numbers of intratumoral Foxp3 and stromal CD8 were significantly associated with low ANA., Conclusions: Assessment of preexisting ANA titers was useful to prognose PD-1 blockade as a first-line setting, particularly for the PD-L1 ≥ 50% subgroup, but not in the case of combined immunotherapy and chemotherapy., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Introduction: Biomarkers for predicting the outcome of ipilimumab plus nivolumab (Nivo-Ipi) treatment in cancer patients have not been identified. Herein, we investigated the prognostic significance of inflammatory and nutritional markers in patients with advanced non-small cell lung cancer (NSCLC) receiving Nivo-Ipi., Methods: Our study retrospectively analyzed 101 patients with advanced NSCLC who received Nivo-Ipi at a single institution. Inflammatory and nutritional indices were correlated with patient outcomes and included the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS)., Results: The NLR significantly correlated with the PLR, SII, PNI, ALI, and GPS. Regarding therapeutic efficacy, the NLR, SII, and PNI predicted a partial response, and all indices predicted progressive disease. In subgroup analyses, the SII, PNI, and ALI predicted the outcome of patients with adenocarcinoma, whereas only the PNI predicted the outcome of patients with non-adenocarcinoma. The PNI and SII were the most useful indices in patients with a programmed death ligand-1 expression level of &lt;1% and ≥1%, respectively., Conclusion: The NLR, PLR, SII, PNI, ALI, and GPS were significantly associated with the outcome of Nivo-Ipi treatment in patients with NSCLC. The PNI was the most suitable marker regardless of histological type. The SII and PNI were the most promising markers for patients with and without PD-L1 expression, respectively., (© 2023 S. Karger AG, Basel.)

Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the present study evaluated ctDNA during osimertinib administration as a second-line or more setting to identify the relationship between EGFR mutation levels and outcomes in patients with advanced non-small cell lung cancer (NSCLC). Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were registered. Plasma samples were collected at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed by digital polymerase chain reaction. The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib than at pretreatment, and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. No statistically significant difference was observed in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD. The detection of T790M at PD after osimertinib initiation was a significant independent prognostic factor for predicting shorter prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely linked to worse survival after osimertinib initiation. Molecular testing based on ctDNA is helpful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment., (© 2023. The Author(s).)

Purpose: To compare different response criteria using computed tomography (CT) and positron emission tomography (PET) in measuring response and survival in the early phase after programmed death-1 (PD-1) blockade monotherapy in patients with advanced non-small cell lung cancer (NSCLC)., Methods: A total of 54 patients with advanced NSCLC who had 2-deoxy-2-[fluorine-18]-fluoro-D-glucose PET or CT at baseline, and 4 and 9 weeks after PD-1 blockade, were registered. Therapeutic response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), the immune-modified RECIST (irRECIST), the PET Response Criteria in Solid Tumors (PERCIST), the immune-modified PERCIST (iPERCIST), and the European Organization for Research and Treatment of Cancer (EORTC) criteria for dichotomous groups, such as responders vs. non-responders and controlled vs. uncontrolled diseases. Cohen's κ was used to evaluate the concordance among the different criteria., Results: The concordance between CT and PET response criteria was fair or slight for responders vs. non-responders, but the agreement between iPERCIST and irRECIST was moderate for controlled vs. uncontrolled diseases. The agreement between EORTC and PERCIST or iPERCIST in detecting responders was higher in the application of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than in the standardized uptake value corrected for lean body mass (SUL) peak . To distinguish controlled from uncontrolled disease, RECIST, irRECIST, and PET criteria (PERCIST, iPERCIST, and EORTC) defined by MTV or TLG were found to be significant predictors of progression-free survival. To distinguish responders from non-responders, iPERCIST by SUL peak or EORTC by TLG were identified as significant indicators. The EORTC criteria using TLG for the detection of responders or uncontrolled diseases had a significantly higher predictive value for response assessment., Conclusions: The EORTC criteria based on TLG for the early detection of responders and uncontrolled disease were effective as a response assessment at 4 weeks after the PD-1 blockade. When SUL peak was not used but MTV or TLG was, the agreement between EORTC and PERCIST or iPERCIST was almost perfect., (© 2023. The Author(s).)

Purpose: The aim of this study was to assess the effectiveness and tolerability of atezolizumab plus carboplatin and etoposide combination chemotherapy in elderly patients with extensive-disease (ED) small-cell lung cancer (SCLC)., Methods: This retrospective study evaluated 65 SCLC patients who received atezolizumab, carboplatin, and etoposide for ED-SCLC in nine study institutions between August 2019 and September 2020. Clinical efficacy, assessed according to response rate and survival, and toxicity were compared between the elderly (n = 36 patients; median age: 74 years [range: 70-89 years]) and the non-elderly group (n = 29 patients; median age: 67 years [range: 43-69 years])., Results: The response rate was 73.8% (80.5% in the elderly group and 65.5% in the non-elderly group). There was no significant difference in both the median progression-free survival (5.5 months vs. 4.9 months, p = 0.18) and the median overall survival (15.4 months vs. 15.9 months, p = 0.24) between the elderly group and the non-elderly group. The frequencies of grade ≥3 hematological adverse events in the elderly patients were as follows: decreased white blood cells, 36.1%; decreased neutrophil count, 61.1%; decreased platelet count, 8.3%; and febrile neutropenia, 8.3%. One treatment-related death due to lung infection occurred in the elderly group., Conclusion: Despite hematologic toxicities, especially decreased neutrophil count, atezolizumab, carboplatin, and etoposide combination chemotherapy demonstrates favorable effectiveness and acceptable toxicity in elderly patients. Thus, atezolizumab plus carboplatin and etoposide could be the preferred standard treatment modality for elderly patients with ED-SCLC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Angiogenesis serves a crucial role in cancer progression. Vascular endothelial growth factor (VEGF) exhibits an immunosuppressive function in patients with cancer. However, it remains unclear whether expression of VEGF in tumor tissue can predict the outcome of programmed death‑1 blockade in patients with advanced non‑small cell lung cancer (NSCLC). A training (n=32) and validation (n=76) cohort of patients with advanced NSCLC who received first‑line pembrolizumab were enrolled. Immunohistochemical staining for VEGF receptor 2 (VEGFR2) and tumor‑infiltrating lymphocytes (TILs; CD4, CD8 and FOXP3) was performed in tumor specimens of both cohorts and association with clinical outcomes was assessed. The percentages of high VEGFR2 expression were 34.3% (11/32) in training cohort and 25.0% (19/76) in validation cohort. No statistically significant difference in objective response between high and low VEGFR2 expression was observed for training (27.2 vs. 45.0%) and validation (31.2 vs. 35.7%) cohorts. The positive rate of intratumoral FOXP3 was significantly associated with high VEGFR2 expression for validation cohort, but not training cohort. In validation cohort, high VEGFR2 expression in patients with non‑adenocarcinoma (non‑AC) was significantly correlated with positive FOXP3 TILs in intratumoral and stromal sites, but not CD4 and CD8. High VEGFR2 expression in both cohorts indicated a significantly worse overall survival (OS) than low VEGFR2 expression. VEGFR2 was identified as an independent prognostic marker associated with worse OS. High VEGFR2 expression was a significant marker for predicting worse OS in patients treated with first‑line pembrolizumab, particularly in those with non‑AC.

This study examined the activity and safety of amrubicin monotherapy among relapsed small-cell lung cancer (SCLC) patients who had previously been treated with atezolizumab plus carboplatin and etoposide (AteCE). This retrospective study evaluated patients with relapsed SCLC who were treated with previously AteCE combination therapy followed by amrubicin monotherapy between August 2019 and May 2021. Clinical efficacy and toxicity were analyzed. Overall, 40 patients were included: 12 and 28 patients had sensitive and refractory relapse, respectively. The response rate was 32.5% (25.0% in the sensitive group and 35.7% in the refractory group). The median progression-free survival (PFS) and overall survival (OS) from the first amrubicin treatment was 3.4 months (95% CI: 1.9-4.9 months) and 9.9 months (95% CI: 4.5-11.5 months), respectively. There was no significant between-group difference in median PFS (3.6 months vs. 3.2 months, p = 0.42) or median OS (11.2 months vs. 7.3 months, p = 0.78). Grade ≥ 3 hematological adverse events occurred as follows: decreased white blood cells in 52.5% of patients; decreased neutrophil count in 57.5%; and febrile neutropenia in 10.0%. Grade 3 pneumonitis was observed in one patient. There were no treatment-related deaths. Amrubicin is feasible and effective for relapsed SCLC patients previously treated with AteCE therapy. Although immune checkpoint inhibitor treatment (ICI) does not improve the effect of amrubicin, the toxicity is not increased, suggesting that amrubicin remains effective even after ICI administration. Thus, amrubicin after AteCE could be the preferred standard chemotherapeutic choice in patients with relapsed SCLC., (© 2022. The Author(s).)

Combined chemotherapy plus programmed death-1 (PD-1) blockade is an established treatment against patients with advanced non-small cell lung cancer (NSCLC). However, a promising predictor besides programmed death ligand-1 expression remains uncertain. We examined the prognostic significance of baseline 18 F-FDG-positron emission tomography for predicting first-line combined chemotherapy plus PD-1 blockade in NSCLC patients. Forty-five patients with advanced NSCLC who received 18 F-FDG-positron emission tomography immediately before combined platinum-based chemotherapy with PD-1 blockade as first-line setting were eligible for this study, and assessment of maximum of standard uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18 F-FDG uptake was performed. The objective response rate, median progression-free survival, and overall survival were 51.2%, 206 days, and 681 days, respectively. High SUV max , TLG, and MTV significantly correlated with age and performance status (PS), C-reactive protein (CRP), and PS, CRP, albumin, and baseline tumor size, respectively. Univariate analysis identified albumin, TLG and MTV as significant predictors of progression-free survival, and CRP, albumin, TLG and MTV as significant factors for predicting overall survival. High TLG was confirmed as an independent factor associated with poor prognosis in multivariate analysis. In particular, TLG is identified as the most powerful predictor in patients with good PS, adenocarcinoma, programmed death ligand-1≥1%, and low baseline tumor size. The tumor metabolic volume by MTV and TLG at pretreatment was clarified as a significant predictor for combined chemotherapy with PD-1 blockade, but not maximal glycolytic level by SUV max ., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Anti-programmed death-1 (PD-1) blockade is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, no appropriate modality exists for monitoring its therapeutic response immediately after initiation. Therefore, we aimed to elucidate the clinical relevance of 18 F-FDG PET/CT versus CT in predicting the response to PD-1 blockade in the early phase. This prospective study included a total of 54 NSCLC patients. 18 F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SUL max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated. Among all patients, partial metabolic response and progressive metabolic disease after PD-1 blockade were observed in 35.2% and 11.1% on SUL max , 22.2% and 51.8% on MTV, and 27.8% and 46.3% on TLG, respectively, whereas a partial response (PR) and progressive disease (PD), respectively, based on RECIST v1.1 were recognized in 35.2% and 35.2%, respectively. The predictive probability of PR (MTV: 57.9% vs. 21.1%, p = 0.044; TLG: 63.2% vs. 21.1%, p = 0.020) and PD (MTV: 78.9% vs. 47.3%, p = 0.002; TLG: 73.7% vs. 21.1%, p = 0.007) detected based on RECIST at 4 weeks after PD-1 blockade initiation was significantly higher using MTV or TLG on 18 F-FDG uptake than on CT. Multivariate analysis revealed that metabolic response by MTV or TLG at 4 weeks was an independent factor for response to PD-1 blockade treatment. Metabolic assessment by MTV or TLG was superior to morphological changes on CT for predicting the therapeutic response and survival at 4 weeks after PD-1 blockade., (© 2022. The Author(s).)

Background: Biomarker assessments for nivolumab monotherapy efficacy in previously treated patients with non-small cell lung cancer (NSCLC) remain unclear. We evaluated whether body mass index (BMI) and Glasgow prognostic score (GPS) are useful for assessing the efficacy of nivolumab alone as a second-line treatment in patients with pretreated NSCLC., Methods: Data of 99 patients treated with second-line nivolumab monotherapy for NSCLC between January 2016 and December 2019 were evaluated for prognostic values of BMI and GPS to assess their usefulness in predicting progression-free survival (PFS) and overall survival (OS)., Results: The Eastern Cooperative Oncology Group-performance status (PS) independently predicted the second-line nivolumab monotherapeutic effect; good PS (0-1) correlated with significantly longer PFS (4.3 vs. 1.9 months, log-rank; p = 0.0004) and OS (17.7 vs. 4.6 months, log-rank; p < 0.0001) than poor PS. BMI independently predicted survival, with high BMI (≥22.1 kg/m 2 ) associated with significantly longer OS (19.1 vs. 8.5 months, log-rank; p = 0.0023) than low BMI (<22.1 kg/m 2 ). However, GPS showed no significant difference for PFS or OS., Conclusion: Among patients with NSCLC treated with nivolumab monotherapy as second-line treatment, PS was significantly correlated with both PFS and OS and BMI with OS. Thus, BMI could be a useful predictor of survival in these patients., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

We conducted a nationwide survey of tomotherapy for malignant pleural mesothelioma (MPM) in Japan. Fifty-six facilities were surveyed and data on 31 patients treated curatively between 2008 and 2017 were collected from 14 facilities. Twenty patients received hemithorax irradiation after extrapleural pneumonectomy (EPP) (first group). Five patients received irradiation without EPP (second group), while six received salvage radiotherapy for local recurrence (salvage group). Among the seven patients not undergoing EPP, five (four in the second group and one in the salvage group) were treated with lung sparing pleural irradiation (LSPI) and two with irradiation to visible tumors. Two-year overall survival (OS) rates in the first and second groups were 33% and 60%, respectively (median, 13 vs 30 months, P = 0.82). In the first and second groups, 2-year local control (LC) rates were 53 and 67%, respectively (P = 0.54) and 2-year progression-free survival (PFS) rates were 16% and 60%, respectively (P = 0.07). Distant metastases occurred in 15 patients in the first group and three in the second group. In the salvage group, the median OS was 18 months. Recurrence was observed in the irradiated volume in four patients. The contralateral lung dose was higher in LSPI than in hemithorax irradiation plans (mean, 11.0 ± 2.2 vs 6.1 ± 3.1 Gy, P = 0.002). Grade 3 or 5 lung toxicity was observed in two patients receiving EPP and hemithorax irradiation, but not in those undergoing LSPI. In conclusion, outcomes of EPP and hemithorax irradiation were not satisfactory, whereas LSPI appeared promising and encouraging., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Programmed death 1 (PD-1) blockade is a standard treatment for patients with metastatic non-small cell lung cancer (NSCLC). Approximately 20% patients receiving PD-1 blockade monotherapy can survive for more than 5 years. However, there are limited data on the optimal biomarkers for predicting long-term outcomes. Therefore, this study aimed to evaluate the prognostic significance of 18F-FDG uptake in patients with NSCLC responding to PD-1 blockade., Patients and Methods: Thirty-eight patients with advanced NSCLC who underwent 18F-FDG PET after confirmation of clinical response to PD-1 blockade monotherapy were retrospectively included in this study. Visual assessment using a 5-point scale score according to 18F-FDG uptake was performed, and the 18F-FDG uptake cutoff score for prolonged response to PD-1 blockade was defined as 3 (low score: 1, 2, or 3 and high score: 4 or 5)., Results: A significantly greater number of patients with low scores had a performance status of 0 or 1 than patients with high scores. Among the 38 patients, 20 (53%) had a low score and 18 (47%) had a high score. Progression-free survival and overall survival were significantly longer in patients with low scores than in patients with high scores. Low 18F-FDG uptake was an independent prognostic factor for predicting favorable progression-free survival and overall survival, as confirmed by multivariate analysis., Conclusions: Tumors with lower 18F-FDG uptake on PET than normal hepatic lesions exhibit the possibility of prolonged response to PD-1 blockade. Visual assessment on PET is easy for every clinician and is understandable to confirm aggressive tumor activity., Competing Interests: Conflicts of interest and sources of funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. K.K. has received research grants and a speaker honorarium from Ono Pharmaceutical Company, Boehringer Ingelheim, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly Japan, and AstraZeneca. A.M. and O.Y. have received a speaker honorarium from Eli Lilly, Taiho Pharmaceutical, Pfizer, Chugai Pharmaceutical, and AstraZeneca. H.K. has received research grants and a speaker honorarium from Ono Pharmaceutical Company, Bristol Myers Squibb, Boehringer Ingelheim, MSD, Daiichi Sankyo Company, Chugai Pharmaceutical, Taiho Pharmaceutical, Merck Biopharma Company, Eli Lilly Japan, and AstraZeneca. K.K. has received research grants and a speaker honorarium from Boehringer Ingelheim, AstraZeneca, and Bristol Myers Squibb., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown., Methods: Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2-4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety., Results: Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3-5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations., Conclusion: Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs., (© 2021. The Author(s).)

Immune checkpoint inhibitors (ICIs) are standard treatments for patients with lung cancer. PD-1/PD-L1 or CTLA4 antibodies are chosen as the first-line therapy, contributing to the long-term survival and tolerability. Unlike molecular targeting agents, such as gefitinib, lung cancer patients with a poor performance status (PS) display unsatisfactory clinical improvements after ICI treatment. Several previous reports also demonstrated that the PS is identified as one of the most probable prognostic factors for predicting poor outcomes after ICI treatment. However, first-line pembrolizumab seemed to be effective for lung cancer patients with a PS of 2 if PD-L1 expression was greater than 50%. Currently, the induction of ICIs in patients with lung cancer with a poor PS is controversial. These problems are discussed in this review.

Background: There are no established biomarkers for predicting the efficacy of first-line pembrolizumab monotherapy in patients with high programmed death-ligand 1 (PD-L1) expression. In this study, we investigated whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can be used to evaluate the effect of first-line pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) who express high levels of PD-L1., Methods: We reviewed data from 142 patients with high PD-L1 expression who underwent first-line pembrolizumab monotherapy for NSCLC at six Japanese institutions between February 2017 and June 2019 and assessed the prognostic value of the GPS, NLR, and BMI. The Kaplan-Meier method and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). The GPS, NLR, and BMI were calculated using C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively., Results: The GPS independently predicted the first-line pembrolizumab monotherapy efficacy, as a good GPS (GPS 0-1) was associated with a significantly better PFS and OS compared to a poor GPS (GPS 2) (PFS: 11.8 vs. 2.9 months, p < 0.0001; OS: not reached vs. 8.3 months, p < 0.0001). Furthermore, BMI independently predicted efficacy, as patients with high BMI (BMI ≥21.4) exhibited significantly better OS compared to those with low BMI (BMI <21.4) (OS: not reached vs. 14.1 months, p = 0.006)., Conclusions: Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, the GPS is significantly correlated with both PFS and OS, and BMI with OS, indicating that they could be used to predict treatment outcome in these patients. To the best of our knowledge, this is the first study to assess the relationship among the GPS, NLR, and BMI and survival among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The effect of second-line treatment on overall survival (OS) may be affected by subsequent treatment in patients with non-small cell lung cancer (NSCLC); however, in such patients, the correlation between post-progression survival (PPS) and OS is unclear. Our study assessed the correlation of progression-free survival (PFS) and PPS with OS, using individual patient data, in advanced NSCLC patients who were treated with second-line nivolumab monotherapy, METHODS: Between January 2016 and March 2019, we evaluated 92 NSCLC patients who received second-line nivolumab treatment after first-line platinum-based combination chemotherapy. Using individual patient data, the correlations of PFS and PPS with OS were examined., Results: Linear regression and Spearman rank correlation analysis demonstrated that PPS was strongly correlated with OS (r = 0.85, p < 0.05, R 2 = 0.75), while PFS was moderately correlated with OS (r = 0.65, p < 0.05, R 2 = 0.42). Performance status at the beginning of second-line treatment, immune checkpoint inhibitor rechallenge, and the number of treatment regimens used post-progression, after the second-line treatment significantly correlated with PPS (p < 0.05). In advanced NSCLC patients who underwent second-line treatment with nivolumab, in comparison to PFS, there was a stronger correlation between PPS and OS., Conclusions: Our findings suggest that subsequent treatment for disease progression after a second-line nivolumab treatment had a significant impact on OS., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The safety of pembrolizumab monotherapy in treatment-naïve non-small cell lung cancer (NSCLC) patients with high programed death-ligand 1 (PD-L1) expression and pre-existing interstitial lung disease (ILD) has not yet been determined. Here, we aimed to evaluate the prognosis, efficacy and safety associated with pembrolizumab in such settings., Methods: In this single-institution retrospective study conducted from May 2017 to October 2019, pembrolizumab was administered to 72 Japanese patients with treatment-naïve advanced NSCLC with PD-L1 tumor proportion score (TPS) ≥50%. Patients with ILD were assigned to the ILD group, and those without to the non-ILD group. Between-group comparisons were then performed., Results: Of the 72 patients, 61 (84.7%) were male. The median age was 70 years. A total of 64 patients (88.9%) had a smoking history, median PD-L1 TPS status was 77.5%, and 10 of the 72 patients (13.9%) had ILD on pretreatment computed tomography. The objective response rate (ORR) was 45.8% and disease control rate (DCR) was 75.0%. The ORR was 70.0% and DCR was 90.0% in the ILD group, while the ORR was 41.9% and DCR was 72.6% in the non-ILD group. The median overall survival was 568 days; the value in the non-ILD group was 521 days, while in the ILD group was not reached. There was no significant difference between the two groups (log-lank, P = 0.73)., Conclusions: Pembrolizumab was administered to patients with pre-existing ILD with no difference in prognosis compared to patients without ILD. In patients with ILD, physicians should consider the expected long-term prognosis and risk of adverse events., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare tumor with an aggressive clinical course. However, there is limited knowledge of its treatment strategy. This retrospective study aimed to assess the efficacy and safety of anti-programed death-1 (PD-1) blockade monotherapy in previously treated advanced LCNEC., Methods: Eleven patients with previously treated advanced LCNEC who received immune checkpoint inhibitor monotherapy between January 2015 and November 2020 were retrospectively analyzed for efficacy and safety., Results: Of a total of 11 patients (median [range] age, 66 [37-79] years; 8 men [73%] and 3 women [27%]), 8 patients had performance status (PS) 0-1 [73%] and 3 patients had PS 2 [27%]; 9 patients received 1 prior chemotherapy [82%] and 2 patients received 2 prior chemotherapies [18%]. The median follow-up duration was 4.6 months. Although PD-1 blockade was administered at median cycles of 3 (range, 1-12), overall response rate, median progression-free survival, and median overall survival were 9.1%, 2.7 months, and 4.6 months, respectively. Any adverse events were observed in 9 patients (82%), including 1 patient with grade 3 pneumonitis as a serious adverse event., Conclusion: Anti-PD-1 blockade monotherapy as a subsequent line for previously treated advanced LCNEC exhibited usefulness and tolerability and was identified as a valid treatment option., (© 2021 S. Karger AG, Basel.)

Background: Durvalumab is a standard drug used during maintenance therapy after chemoradiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the clinical benefits of durvalumab after chemoradiotherapy in patients with LA-NSCLC with a performance status (PS) of 2 and/or aged > 75 years. As daily carboplatin plus concurrent thoracic radiotherapy is recommended for elderly patients according to guideline, the current phase II study aims to investigate the effect of daily carboplatin plus radiotherapy followed by durvalumab for patients with stage III NSCLC who have a PS of 2 and/or are older., Methods: Daily carboplatin plus radiotherapy followed by durvalumab is performed for the patients with stage III NSCLC who have a PS of 2 and/or are older. This is a trial in progress manuscript., Study Treatment: Daily, intravenous, low-dose carboplatin (30 mg/m 2 in a 30-min infusion) is administered to patients 1 h before radiotherapy for the first 20 fractions. Radiotherapy for all patients consisted of 60 Gy administered as 30 fractions over 6 weeks. Durvalumab at a dose of 10 mg/kg/body is intravenously administered every 2 weeks for up to 12 months after chemoradiotherapy., Exploratory Assessment: In the future, an exploratory investigation will be performed to determine whether the combined assessment of T-cell markers, PD-L1 expression, and tumor mutation burden could predict the outcomes of the regimen., Discussion: The results of our study will exhibit the efficacy and tolerability of durvalumab as maintenance therapy after daily carboplatin plus radiotherapy., Trial Registration: During the first registration (before induction chemoradiotherapy), 70 patients will be included; then, we include 58 patients during the second registration (before durvalumab treatment after chemoradiotherapy). https://jcrb.niph.go.jp/ ., Primary Endpoint: The primary endpoint of the current study is the 12-month progression-free survival (PFS) rate after the initiation of durvalumab., Secondary Endpoints: The secondary endpoints are the feasibility, objective response, PFS, overall survival, and adverse events.

There is a lack of markers for predicting favorable outcomes after pembrolizumab therapy in patients with non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) expression ≥ 50%. This retrospective study examined the prognostic significance of 2-deoxy-2-[18F] fluoro-D-glucose ( 18 F-FDG) uptake as a predictive marker of first-line pembrolizumab. Forty-eight patients with previously untreated NSCLC and PD-L1 expression levels ≥ 50% who underwent 18 F-FDG-positron emission tomography (PET) just before administration of pembrolizumab monotherapy were eligible and underwent assessment of metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum of standardized uptake value (SUV max ) on 18 F-FDG uptake. The objective response rate, median progression-free survival, and median overall survival were 51.1%, 7.1 months, and 18.6 months, respectively. In univariate survival analyses, high MTV was barely a significant prognostic predictor and was confirmed as an independent factor linked to worse outcomes in multivariate analysis, predominantly in patients with a histological diagnosis of adenocarcinoma. A high MTV was significantly associated with distant metastases (especially bone metastasis), C-reactive protein (CRP) level, and PD-L1 expression ≥ 75%. Metabolic tumor activity assessed as MTV from 18 F-FDG uptake predicted the prognosis after first-line pembrolizumab treatment in patients with NSCLC and PD-L1 expression ≥ 50%, especially for adenocarcinoma.

Background: Chemoradiotherapy followed by durvalumab is the standard treatment for the patients with local advanced non-small cell lung cancer (NSCLC). There is a real-world data about the management of adverse events, such as pneumonitis, according to the different institutions. Here, we present the experience regarding the management of adverse events after the initiation of durvalumab as daily practice., Methods: From July 2018 to August 2019, 41 patients with locally advanced NSCLC, who underwent chemoradiotherapy followed by durvalumab, were retrospectively analyzed in the study using our medical records., Results: The median age of patients was 72 years (range: 51-80 years). A total of 33 patients were male and eight were female, and 40 patients (98%) received a total radiation dose of 60 Gy as concomitant chemoradiotherapy. The median V20 for the entire cohort was 18.9% (range: 3.5-29.9). Any adverse events during chemoradiotherapy and durvalumab were observed in 32 patients (78.0%), while three patients (7.3%) experienced grade 3 toxicities. In total, 25 (61.0%) patients experienced pneumonitis, four (9.8%) thyroid dysfunction, three (7.3%) myopathy, two (4.9%) rash or eruption, one (2.4%) bowel disease and one (2.4%) malaise. Grade 3 pneumonitis, thyroid dysfunction and myopathy were observed in one (2.4%), one (2.4%) and one (2.4%), respectively. A total of 22 (53.7%) patients were unable to continue durvalumab due to pneumonitis. However, durvalumab was finally readministered to six patients., Conclusions: The adherence to lung dose constraints such as V20 as well as close treatment monitoring are a prerequisite for the management of pneumonitis during maintenance therapy with durvalumab., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Osimertinib is the most promising treatment option for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) with acquired T790M resistance. However, recent studies have suggested that osimertinib could increase the frequency of serious adverse events (AEs) if administered immediately after immune checkpoint inhibitor (ICI) treatment., Methods: In this single-institution retrospective study conducted from May 2016 to January 2019, osimertinib was administered to 47 patients with pretreated advanced NSCLC harboring the EGFR mutation., Results: Of the 47 patients, 20 (42.6%) were men and 27 (57.4%) were women. The median age was 71 years (range 37-83 years). A total of 19 patients (40.4%) had a smoking history. Furthermore, seven patients (14.9%) received osimertinib immediately after nivolumab therapy, while 40 patients (85.1%) were treated with osimertinib after treatment with drugs other than nivolumab. The frequency of grade 3 or 4 hepatotoxicity was significantly higher in patients with nivolumab prior to osimertinib (4/7; 57.1%) than in those treated with drugs other than nivolumab prior to osimertinib (2/40; 5.0%) (P = 0.0026). Liver biopsies were performed in two patients who received osimertinib immediately after nivolumab. In both patients, CD-8-positive T cell infiltration was predominantly observed in the liver tissues., Conclusions: The use of osimertinib immediately after nivolumab significantly increased the frequency of grade 3 or higher hepatotoxicity in patients with advanced NSCLC harboring EGFR mutation acquired T790M resistance., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background/aim: Thrombocytopenia, one of many immune-related adverse events (irAEs), is a rare entity about which little is known on its treatment, outcomes, and patient demographics. Herein we present a case of severe thrombocytopenia after administration of pembrolizumab as an anti-programmed death-1 (PD-1) antibody., Case Report: A 66-year-old man with advanced non-small cell lung cancer (NSCLC) received pembrolizumab; 21 days later, his platelet count was progressively decreased and he experienced severe thrombocytopenia (grade 4; platelet count 0.4×10 9 /l). With oral steroids 1 mg/kg/day, the platelet count improved sufficiently; thus, a definite diagnosis of severe irAE-related thrombocytopenia was performed., Conclusion: Several reports have described the management and occurrence of severe thrombocytopenia after immune checkpoint inhibitor administration in patients with different neoplasms. Physicians should be alert to the potential of rare irAEs, such as severe thrombocytopenia., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Patients with advanced non-small cell lung cancer greatly care about where they will die. Most people in Japan preferred their location of death as their homes. But only 8.2% of patients with cancer spend their last days at home with palliative care in Japan. Many patients with cancer are still going to spend their last days at a hospital (81.7%)., Objective: We examined the survival times of such patients according to their place of death; that is, whether they died at home, at a hospice, or at a hospital, and investigated patient characteristics., Results: Among the 313 patients recruited, 214 were analyzed in this study: 90, 49, and 75 received hospital-based, home-based, and hospice-based palliative care, respectively. The patients who died at a hospice exhibited significantly longer survival than those who died at hospital (estimated median survival time, 420 days [95% confidence interval [CI]: 325-612 days] versus 252 days [95% CI: 201-316 days]; P < .0001). The characteristics of patients did not differ significantly according to place of death., Conclusions: Patients who died at a hospice or at home exhibited significantly longer survival than those who died at a hospital for advanced non-small cell lung cancer.

Background: After the cessation of immune checkpoint inhibitor (ICI) therapy due to an immune-related adverse event (irAE), it remains unclear whether retreatment with ICI is more effective than its discontinuation. To explore the clinical significance of its retreatment, patients with non-small cell lung cancer (NSCLC) who had treatment interruption of nivolumab due to irAEs were identified and the clinical differences between discontinuation and retreatment with nivolumab were retrospectively reviewed., Methods: 49 (26%) of 187 patients treated with nivolumab experienced the cessation of treatment due to a serious irAE. Retreatment was chosen in 21 patients (retreatment cohort), while 28 patients discontinued treatment (discontinuation cohort)., Results: The most common irAEs requiring treatment cessation in 49 patients included pneumonitis (59.2%), adrenal insufficiency (8.2%), liver dysfunction (8.2%) renal dysfunction (8.2%), colitis (6.1%), hypothyroidism (4.1%), and rash (2.0%). The frequency of grade 3 or 4 initial irAEs did not differ between the retreatment and discontinuation cohorts; however, the incidence of renal dysfunction and colitis was higher in the retreatment cohort than in the discontinuation cohort. Retreatment with nivolumab displayed an overall response rate of 15%, without a significant increase in irAEs. The median overall survival and progression-free survival did not differ significantly between the retreatment and discontinuation cohorts, irrespective of the efficacy of prior nivolumab., Conclusions: Retreatment exhibited a slightly higher efficacy without a significant increase in irAEs; however, the clinical significance of retreatment and discontinuation was similar in NSCLC patients that led to treatment interruption due to any irAE after initial nivolumab.

Background: Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure., Methods: From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study., Results: The overall response rate (ORR) and disease control rate (DCR) of afatinib as re-challenge were 17.0% and 79.2%, respectively. The median time on treatment of 1st generation EGFR-TKI (1st TKI) was 14 months. By multivariate analysis, smoking, performance status (PS), and time on treatment of 1st TKI with more than 10 months were confirmed to be independent prognostic factors predicting a worse progression-free survival (PFS), and significant prognostic markers for overall survival (OS) were PS and time on treatment of 1st TKI with more than 10 months, especially in patients with exon 19 deletion., Conclusions: Re-challenge of afatinib was identified as one of the therapeutic options after 1st TKI failure in the patients with advanced NSCLC harboring EGFR mutation when the time of treatment by prior 1st TKI is more than 10 months.

Background: It remains unclear why radiation clinically provides a synergistic effect when combined with immune checkpoint inhibitors such as nivolumab. The purpose of our study was to retrospectively evaluate whether the therapeutic efficacy of nivolumab is improved as a result of a history of radiotherapy (RT) in patients with previously treated advanced non-small cell lung cancer (NSCLC)., Methods: From February 2016 to December 2017, 124 consecutive patients were administered nivolumab for pretreated advanced NSCLC. The patients were divided into RT and non-RT groups., Results: Sixty-six (53%) of the 124 patients had been administered RT before the initiation of nivolumab, 52 (42%) received extracranial RT, and 40 (32%) were treated with thoracic RT. The median number of nivolumab cycles was 4 (range: 1-43). The overall response rate (ORR) and disease control rate (DCR) of nivolumab in all patients were 28.0% and 58.4%, respectively. The ORR (36.4%) was significantly higher in patients who had received previous RT than in patients who had not received any RT (19%). The therapeutic efficacy of nivolumab was particularly noteworthy in patients with non-adenocarcinoma and squamous cell carcinoma histology administered extracranial RT, with ORRs of 48.3% and 52.6%, and DCRs of 87.1% and 84.2%, respectively., Conclusion: Previous RT was an independent prognostic marker of favorable prognosis after nivolumab administration and improved the response rate to nivolumab treatment. Previous RT was clinically identified to have a synergistic effect with nivolumab treatment, increasing the response rate and improving the outcome of patients with advanced NSCLC., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The aim of our study was to retrospectively assess the incidence of interstitial lung disease (ILD) related to EGFR-tyrosine kinase inhibitor (TKI) treatment immediately before and/or after the administration of a PD-1 antibody., Methods: We analyzed the data of 26 patients who underwent treatment with EGFR-TKIs immediately before and/or after the administration of an anti-PD-1 antibody., Results: Four out of the 26 patients developed ILD during EGFR-TKI treatment: three patients during the administration of osimertinib immediately after, and one during afatinib immediately before treatment with an anti-PD-1 antibody. Three of 12 patients who underwent EGFR-TKI therapy immediately after anti-PD-1 antibody treatment experienced osimertinib-induced ILD. ILD was not observed in the five patients administered an anti-PD-1 antibody followed by first or second-generation EGFR-TKIs., Conclusion: ILD was observed in the treatment sequence of an anti-PD-1 antibody followed by osimertinib, but not with first or second-generation EGFR-TKIs., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: It is unclear whether the chemotherapy response improves after exposure to immunotherapy. Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects that stimulate tumor shrinkage. We conducted a retrospective study to evaluate improvement of the efficacy of ramucirumab plus docetaxel after the failure of nivolumab as a PD-1 inhibitor., Methods: From February 2016 to December 2017, 152 patients with non-small cell lung cancer (NSCLC) administered nivolumab in our institution were identified. We reviewed the records of 20 NSCLC patients administered ramucirumab plus docetaxel after nivolumab failure. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Pegylated granulocyte colony-stimulating factor was prophylactically administered to 18 patients (90%) after the administration of ramucirumab plus docetaxel., Results: The median age of the patients was 70 (range: 55-77) years. Twelve patients were male and eight were female. The histology was adenocarcinoma in 16 patients, squamous cell carcinoma in three, and other in one. The ORR of ramucirumab plus docetaxel was 60%, and the PFS and OS were 169 and 343 days, respectively. Among the 20 patients, 12 achieved a partial response, giving an ORR of 60.0%. Six patients had stable disease and two had progressive disease. The disease control rate was 90%. Gastrointestinal adverse events were frequently observed in 19 patients., Conclusions: Ramucirumab plus docetaxel achieved a higher response rate when administered immediately after nivolumab failure compared to regimens without prior nivolumab administration., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Whether primary prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF) should be administered immediately after the initiation of ramucirumab plus docetaxel (DR) to prevent the occurrence of febrile neutropenia (FN) is unclear. Our retrospective study aimed to elucidate whether PEG-G-CSF could control the occurrence of FN as a result of DR in patients with previously treated non-small-cell lung cancer. Thirty-three patients with previously treated non-small-cell lung cancer who had received DR were eligible for our analysis. Of the 33 patients, 29 received prophylactic PEG-G-CSF immediately after DR, but none developed FN. However, FN was observed in 2 (50%) of the 4 patients that were not administered PEG-CSF. The overall response and disease control rates in the 29 patients with prophylactic PEG-GSF were 31% and 62%, respectively. The median progression-free and overall survival rates of the patients with and without prophylactic PEG-GSF were 177 and 163 days (P = 0.20), and 628 and 274 days (P = 0.13), respectively. Primary prophylactic PEG-G-CSF suppressed the occurrence of FN secondary to the administration of DR., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Although small cell lung cancer (SCLC) is an aggressive cancer, few useful treatment options exist after relapse. Information concerning the efficacy and safety of carboplatin plus paclitaxel in patients with SCLC is limited., Methods: From April 2007 to October 2016, 318 patients with SCLC received chemotherapy at our institution. The medical records of patients treated with carboplatin and paclitaxel after first-line chemotherapy with platinum plus etoposide or irinotecan were retrospectively analyzed. The objectives were to investigate the frequency at which a carboplatin and paclitaxel regimen was administered to patients with SCLC in clinical practice, and to determine the response rate, progression-free survival (PFS), and tolerability of such agents., Results: A total of 24 (7.5%) patients (male, n = 21; female, n = 3; median age, 67 years; performance status, 0-1/≥2, 15/8 patients; limited/extensive disease, 6/15 patients; sensitive/refractory relapse, 3/21 patients) were treated with carboplatin plus paclitaxel. This regimen was chosen due to interstitial lung disease (ILD) (n = 17), radiation pneumonitis (n = 3), combination with palliative radiation therapy (n = 2), and the presence of other cancers (n = 2). The response rate was 33.3%, and the disease control rate was 62.5%. The median PFS and overall survival were 4.1 and 8.7 months, respectively. Grade 3/4 hematologic toxicities observed included neutropenia (54.2%), anemia (4.2%), and thrombocytopenia (8.3%). With the exception of grade 3 neuropathies (n = 2), non-hematologic toxicities were mild. No patients experienced an acute exacerbation of ILD., Conclusion: A combination of carboplatin plus paclitaxel as second-line chemotherapy is effective and feasible in patients with SCLC, especially in those with ILD., (Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of malignant pleural effusion (MPE). Here, a multicenter phase II trial to evaluate bevacizumab in non-squamous non-small cell lung carcinoma patients with MPE was conducted., Methods: Patients having MPE with no prior treatment and performance status of 0-2 received carboplatin (area under the curve: AUC 6; up to 6 cycles) and pemetrexed (500mg/m(2)) with bevacizumab (15mg/kg) every 3 weeks. The primary endpoint was the control rate of MPE without pleurodesis at 8 weeks after treatment. VEGF levels in plasma and MPE were measured by enzyme immunoassay., Results: Of 30 patients entered (median 66 years; 24 males; adenocarcinoma; 4 epidermal growth factor receptor: EGFR mutations), 28 patients (2 withdrawn patients) were given a median of 4 cycles of carboplatin, and 68% of the patients received maintenance pemetrexed with bevacizumab (median 8 cycles). At eight weeks, MPE was controlled without pleurodesis in 93% of treated patients (95% confidence interval: 77-99%). At the median follow-up time of 12.8 months, 78.6% of the cases required no pleurodesis. Response rate was 46%, and median progression-free survival (PFS) and overall survival (OS) were 8.2 months and 18.6 months, respectively. Toxicities of grade ≥3 included neutropenia (28.6%), thrombocytopenia (28.6%), proteinuria (3.6%), and hypertension (3.6%). Assessment of VEGF levels before treatment indicated that patients with low VEGF (<1000pg/ml) in MPE frequently needed pleurodesis (p=0.011), and that high VEGF (≥100pg/ml) in plasma was indicative of poor prognosis in the context of PFS (p=0.012)., Conclusion: The combination of bevacizumab with carboplatin and pemetrexed demonstrated efficacy with acceptable toxicities in patients with MPE., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Virtual fluoroscopic preprocedural planning (VFPP) is a figure in which the trace lines between the trachea and the target lesions are constructed along the connecting bronchus on Ray Summation image similar to fluoroscopy. The lines can be displayed at any angle with 3D imaging. This system was applied to bronchoscopy as a reference for forceps guidance under the fluoroscopy, as a new type of navigation. The objective of this study was to demonstrate the feasibility of VFPP., Methods: Patients with pulmonary peripheral lesions (PPLs) with long axis ≤30 mm were recruited. Bronchoscopy with endobronchial ultrasonography with a guide sheath (EBUS-GS) was performed by using simultaneous display of VFPP., Results: For 27 patients with 27 lesions, endobronchial ultrasonography with a guide sheath with simultaneous display of VFPP was performed. The median lesion size was 20.2 mm (range, 10 to 30 mm). The median examination time was 24.5 minutes (range, 12 to 50 min). Diagnosis was made for 17 lesions of the total 27. Lung cancer was diagnosed in 12 lesions, nontuberculous mycobacterial disease in 1 lesion, lymphoid hyperplasia in 1 lesion, and inflammation in 3 lesions. In 10 lesions, no diagnosis was made. The diagnostic rate of the procedure was 63.0%. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for malignant disease were 66.7%, 100%, 45.5%, 100%, and 73.9%, respectively., Conclusion: VFPP was easy to prepare and useful for selecting target bronchi. This study confirms feasibility of the VFPP as an adjunct to minimally invasive transbronchial biopsy of pulmonary peripheral lesions.

S-1 is one of the effective chemotherapy regimens for treating non-small cell lung cancer. We report of an elderly patient with non-small cell lung cancer who responded to S-1 monotherapy following gefitinib therapy. An 83-year-old woman was diagnosed with advanced adenocarcinoma of the lungs (cT3N3M1a, Stage IV). Considering her age, monotherapy with vinorelbine was administered as first-line chemotherapy. Despite the completion of four courses, she was diagnosed with progressive disease. Thereafter, after considering her status as a non-smoking woman, gefitinib was introduced as second-line chemotherapy, which resulted in significant tumor size reduction.Tumor regrowth was identified 16 months later, and gefitinib was switched to erlotinib, but the tumor kept increasing in size.S -1 monotherapy was introduced as fourth-line chemotherapy, and the tumor began to decrease in size again. A partial response was obtained after 10 months, without serious adverse effects. Gefitinib following S-1 monotherapy resulted in long-term tumor size control for a total of 27 months in an elderly patient with advanced non-small cell lung cancer.S -1 monotherapy might be one of the options for salvage therapy after gefitinib treatment becomes ineffective.