Efficacy and Safety of First-line Pembrolizumab Plus Platinum and Pemetrexed in Elderly Patients with Non-squamous Non-small-cell Lung Cancer.

Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with nonsquamous NSCLC. Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed. Results Thirty patients [20 men and 10 women; median age: 76 (range: 75-82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, and 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively. Conclusion First-line pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.

Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101).

BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.

Efficacy of Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) Monotherapy Can Be Improved after Treatment with Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer: Long-Term Follow-Up and Updated Analysis of Two Previous Prospective Clinical Studies.

INTRODUCTION: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. METHODS: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). RESULTS: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. CONCLUSION: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.

Prognostic Potential of the Prognostic Nutritional Index in Non-Small Cell Lung Cancer Patients Receiving Pembrolizumab Combination Therapy with Carboplatin and Paclitaxel/Nab-Paclitaxel.

INTRODUCTION: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients. METHODS: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI <45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS. CONCLUSION: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC.

Human T-cell Lymphotropic Virus Type-1-associated Bronchioloalveolar Disorder with Non-necrotizing Granulomas: A Case Report and Literature Review.

Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a pulmonary disorder characterized by lymphocytic infiltration of the peribronchiolar space and interstitium in HTLV-1 carriers and in adult T-cell leukemia/lymphoma (ATLL). We herein report an 85-year-old woman carrying HTLV-1 with HABA who presented with a miliary pattern of micronodules in both lungs on high-resolution computed tomography and a lymphocytic infiltrate with non-necrotizing granulomas on pathology. This rare case of HABA should be differentiated from sarcoidosis, hypersensitivity pneumonitis, or miliary tuberculosis.

Multicenter, Retrospective Study to Evaluate Necitumumab Plus Cisplatin and Gemcitabine After Immune Checkpoint Inhibitors in Advanced Squamous Cell Lung Cancer in Japan: The NINJA Study.

Introduction: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown. Methods: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS). Results: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths. Conclusions: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.

Using the neutrophil-to-lymphocyte ratio to predict the outcome of individuals with nonsquamous non-small cell lung cancer receiving pembrolizumab plus platinum and pemetrexed.

BACKGROUND: Factors predicting the response to pembrolizumab plus platinum and pemetrexed combination therapy (Pemb-Plt-PEM) in nonsquamous non-small cell lung cancer (non-sq NSCLC) are unclear. We investigated the Glasgow Prognostic (GP) score, neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) as predictors of response to initial treatment with combination therapy in individuals with advanced non-sq NSCLC. METHODS: We retrospectively reviewed 236 patients who received initial treatment with combination therapy for non-sq NSCLC at 13 institutions between December 2018 and December 2020. The usefulness of the GP score, NLR, and BMI as prognostic indicators was assessed. Cox proportional hazard models and the Kaplan-Meier method were used to compare progression-free survival (PFS) and overall survival (OS). RESULTS: The response rate was 51.2% (95% CI: 44.9-57.5%). The median PFS and OS after beginning Pemb-Plt-PEM were 8.8 (95% CI: 7.0-11.9) months and 23.6 (95% CI: 18.7-28.6) months, respectively. The NLR independently predicted the efficacy of Pemb-Plt-PEM-the PFS and OS were more prolonged in individuals with NLR <5 than in those with NLR ≥5 (PFS: 12.8 vs. 5.3 months, p = 0.0002; OS: 29.4 vs. 12.0 months, p < 0.0001). BMI predicted the treatment response-individuals with BMI ≥22.0 kg/m2 had longer OS than did those with BMI < 22.0 kg/m2 (OS: 28.4 vs. 18.4 months, p = 0.0086). CONCLUSIONS: The NLR significantly predicted PFS and OS, whereas BMI predicted OS, in individuals who initially received Pemb-Plt-PEM for non-sq NSCLC. These factors might be prognosis predictors in non-sq NSCLC.

Safety and utility of Endoscopic Ultrasound with Bronchoscope-guided Fine Needle Aspiration (EUS-B-FNA) in suspected lung cancer patients with poor respiratory or general conditions: a prospective three-center observational study.

BACKGROUND: Although transbronchial diagnostic procedures are sometimes difficult to perform because of the patient's respiratory or general conditions, endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA), a known transesophageal diagnostic procedure, might be useful for such cases. We conducted this prospective three-center observational study to evaluate the safety and efficacy of EUS-B-FNA in suspected lung cancer patients with poor respiratory or general conditions. METHODS: Patients with suspected lung cancer with respiratory failure, Eastern Cooperative Oncology Group performance status of 2 or higher, or severe respiratory symptoms, were enrolled. The primary endpoints were the diagnostic yield of lung cancer and its safety, and the secondary endpoints were the success rate of molecular and programmed death ligand 1 (PD-L1) analyses, and the 6-month survival rate in patients with lung cancer. RESULTS: We enrolled 30 patients, of which 29 were included in the analysis. Among them, 26 were eventually diagnosed with lung cancer. The diagnostic yield for lung cancer was 100% (26/26). There were no adverse events associated with EUS-B-FNA requiring procedure discontinuation. The success rates of molecular analysis for EGFR, ALK, ROS-1, and BRAF were 100% (14/14), 100% (11/11), 100% (9/9), and 75% (6/8), respectively. The success rate of the PD-L1 analysis was 100% (15/15). The 6-month survival rate in patients with lung cancer was 53.8% (95% confidence interval [CI]: 33.4-76.4), and the median overall survival (OS) was 196 days (95% CI: 142-446). CONCLUSIONS: EUS-B-FNA is a safe and effective diagnostic method, even in patients with suspected lung cancer with poor respiratory or general conditions. TRIAL REGISTRATION: This clinical trial was registered at https://www.umin.ac.jp/ctr/index.htm (UMIN000041235, approved on 28/07/2020).

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial.

BACKGROUND: Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a treatment for advanced non-small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD-(L)1] inhibitor failure. METHODS: Nab-paclitaxel (100 mg/m2 ) was administered on Days 1, 8, and 15 of a 28-day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD-(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%-79.6%) and the DCR was 86.2% (95% CI: 65.9%-97.0%). The median PFS was 5.6 months (95% CI: 4.4-6.7 months), and PFS rates at 1- and 2-year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8-23.0 months). Good performance status and responder of previous PD-(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%). CONCLUSIONS: Nab-paclitaxel therapy improved ORR after PD-(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC.

Comparative analysis of different response criteria at early phase after PD-1 blockade in non-small lung cancer.

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 SULpeak 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 SULpeak was not used but MTV or TLG was, the agreement between EORTC and PERCIST or iPERCIST was almost perfect.

Intermittent administration of atezolizumab with combined carboplatin and etoposide therapy for patients with extensive­disease small cell lung cancer.

To the best of our knowledge, no published reports have examined the significance of additional immune checkpoint inhibitors in treating malignancies, including lung cancer. Therefore, the present study aimed to examine the efficacy and feasibility of adding atezolizumab to carboplatin and etoposide combination chemotherapy for small cell lung cancer with extensive disease (ED-SCLC). The present retrospective analysis examined 16 patients with ED-SCLC who received the addition of atezolizumab to carboplatin and etoposide therapy during treatment at four institutions between August 2019 and September 2020. The effectiveness of treatment was evaluated based on tumor response, survival time and adverse events. Within the study cohort, there were 14 males (87.5%) and 2 females (12.5%), with a median age of 73.5 years (range, 62-79 years); 7 patients had a performance status (PS) of 0-1 (43.8%) and 9 had a PS of 2-3 (56.3%). The median follow-up period was 12.1 months. The overall response rate, median progression-free survival time and median overall survival time were 75.0%, 5.3 and 13.0 months, respectively. Regarding the frequency of hematological adverse events, the occurrence of grade ≥3 adverse events was observed, including decreased neutrophil (56.3%), white blood cell (50.0%) and platelet (43.8%) counts, as well as febrile neutropenia (12.5%). Although 1 patient developed grade 3 pneumonitis as a serious adverse event, no treatment-related deaths were observed. Despite the aforementioned hematological toxicities, the addition of atezolizumab to carboplatin and etoposide therapy during treatment demonstrated favorable efficacy and acceptable toxicity in ED-SCLC. Thus, adding atezolizumab to carboplatin and etoposide combination chemotherapy may be a treatment option for ED-SCLC.

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer.

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.

Clinical impact of amrubicin monotherapy in patients with relapsed small cell lung cancer: a multicenter retrospective study.

Background: Topoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear. In the present study, we aimed to evaluate the efficacy of second-line amrubicin in patients with relapsed SCLC who were previously treated with platinum-based chemotherapy, including topoisomerase I and II inhibitors. Methods: This study retrospectively analyzed patients with ES-SCLC who experienced recurrence and were treated with amrubicin at 22 institutions in Japan between April 2015 and November 2020. The progression-free survival of amrubicin monotherapy was investigated using the Kaplan-Meier method. Results: A total of 320 patients were enrolled in this study, with 59 (18%) receiving platinum plus topoisomerase I inhibitor irinotecan and 261 (82%) receiving platinum plus topoisomerase II inhibitor etoposide as first-line treatment. The progression-free survival of amrubicin was significantly longer in the irinotecan group than in the etoposide group (3.2 vs. 2.5 months; P=0.034). Conclusions: These results showed that different types of topoisomerase inhibitors could affect the efficacy of amrubicin monotherapy in the second-line treatment of patients with relapsed ES-SCLC.

Post-progression survival after atezolizumab plus carboplatin and etoposide as first-line chemotherapy in small cell lung cancer has a significant impact on overall survival.

BACKGROUND: The effect of first-line chemotherapy on overall survival (OS) may be significantly influenced by subsequent therapy for patients with extensive disease small cell lung cancer (ED-SCLC). Therefore, we evaluated the relationship between progression-free survival (PFS), post-progression survival (PPS), and OS of ED-SCLC patients treated with atezolizumab plus carboplatin and etoposide as first-line therapy. METHODS: We analyzed the data of 57 patients with relapsed ED-SCLC treated with atezolizumab plus carboplatin and etoposide (AteCE) as first-line chemotherapy between August 2019 and September 2020. The respective correlations between PFS-OS and PPS-OS following first-line AteCE treatment were examined at the individual patient level. RESULTS: Spearman's rank correlation analysis and linear regression analysis showed that PPS strongly correlated with OS (r = 0.93, p < 0.05, R2  = 0.85) and that PFS moderately correlated with OS (r = 0.55, p < 0.05, R2  = 0.28). Performance status at relapse (0-1/≥2), number of cycles of atezolizumab maintenance therapy (<3/≥3), and platinum rechallenge chemotherapy all significantly positively correlated with PPS (p < 0.05). CONCLUSIONS: Upon comparing OS-PFS and OS-PPS in this patient population, OS and PPS were found to have a stronger correlation. These results suggest that performance status at relapse, atezolizumab maintenance, or chemotherapy rechallenge could affect PPS.

Successful treatment with lenvatinib in a patient with thymic carcinoma presenting with cardiac tamponade: a case report and review of literature.

Thymic carcinoma (TC) presenting with cardiac tamponade has a poor prognosis because of the difficulty in controlling malignant pericardial effusion using conventional chemotherapy. Lenvatinib, a multitargeted kinase inhibitor of vascular endothelial growth factor receptor and other kinases, has recently been proven effective against TC. As the inhibition of vascular endothelial growth factor signaling is effective in malignant pericardial effusion, lenvatinib may also be effective in TC presenting with cardiac tamponade. However, no reports have shown that lenvatinib is effective in such cases. Herein, we present a case of successful treatment with lenvatinib in a patient with TC presenting with cardiac tamponade. The present case suggests that lenvatinib should be considered an effective treatment option for such cases.

Prospective assessment using 18F-FDG PET/CT as a novel predictor for early response to PD-1 blockade in non-small-cell lung cancer.

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 18F-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. 18F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SULmax), 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 SULmax, 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 18F-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.

Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a malignant neoplasm of the pleura caused by asbestos exposure. For diagnosis of MPM, immunohistochemistry using multiple markers is recommended to rule out differential diagnoses, such as pulmonary adenocarcinoma. However, the specificity of currently used markers is not fully satisfactory. We previously developed a monoclonal antibody named S1, which recognizes 6-sulfo sialyl Lewis x, an L-selectin ligand expressed on high endothelial venules. During the screening process, we discovered that this antibody stained normal pleural mesothelium. This finding prompted us to hypothesize that the epitope recognized by S1 might serve as a new diagnostic marker for MPM. METHODS: To test this hypothesis, we immunostained human MPM (n = 22) and lung adenocarcinoma (n = 25) tissues using S1 antibody. RESULTS: 77.3% of MPM were S1 positive, and if limited to epithelioid type, the positivity rate was 100%, while that of lung adenocarcinoma was only 36.0%. Statistical analysis revealed a significant difference in the S1 positivity rate between each disease. Furthermore, immunohistochemistry using a series of anti-carbohydrate antibodies combined with glycosidase digestion revealed the structure of sulfated glycans expressed in MPM to be 6-sulfo sialyl N-acetyllactosamine attached to core 2-branched O-glycans. CONCLUSION: We propose that the S1 glycoepitope could serve as a new diagnostic marker for MPM.

COVID-19 pneumonia detected by [18F]FDG PET/MRI: a case with negative antigen test and chest X-ray results.

Since the outbreak of pneumonia caused by a novel coronavirus (SARS-CoV-2) named Coronavirus disease 2019 (COVID-19) in China, researchers have reported the fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) manifestations of COVID-19 infection. We present a 37-year-old female with early-stage cervical cancer and fever without a focus who had negative SARS-CoV-2 antigen test and chest X-ray results. FDG PET/MRI performed for preoperative evaluation incidentally detected pneumonia showing high FDG uptake and diffusion-weighted imaging signals in right lung base. She retested positive for SARS-CoV-2 and was diagnosed as having COVID-19 pneumonia. Whole-body PET/MRI can provide multi functional images and could be useful for evaluating the pathophysiology of COVID-19.

Pretreatment glasgow prognostic score predicts survival among patients administered first-line atezolizumab plus carboplatin and etoposide for small cell lung cancer.

Background: There are no established predictive biomarkers for the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with small-cell lung cancer (SCLC). Therefore, the current study aimed to investigate whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can predict the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with extensive-disease SCLC. Methods: We reviewed data from 84 patients who received first-line atezolizumab plus carboplatin and etoposide therapy for SCLC at nine Japanese institutions between August 2019 and May 2021. Further, we evaluated the prognostic value of the GPS, NLR, and BMI. The Kaplan-Meier and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). Moreover, the GPS, NLR, and BMI consisted of C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively. Results: The response rate was 72.6% (95% confidence interval: 63.0-82.1%). The median PFS and OS from the initiation of treatment were 5.4 (95% CI: 4.9-5.9) months and 15.4 (95% CI: 11.4-16.8) months, respectively. The GPS independently predicted the effectiveness of first-line atezolizumab plus carboplatin and etoposide treatment, as a favorable GPS (GPS 0-1) was correlated with significantly better PFS and OS rates compared to a poor GPS (GPS 2) (PFS: 5.8 vs. 3.8 months, p = 0.0005; OS: 16.5 vs. 8.4 months, p<0.0001). Conclusions: This is the first analysis to evaluate the association between the GPS, NLR, and BMI and the treatment effectiveness of survival among patients receiving first-line atezolizumab plus carboplatin and etoposide therapy for SCLC. Among patients receiving this treatment for SCLC, GPS was significantly associated with the PFS and OS rates, suggesting that GPS might be useful for evaluating therapeutic outcomes in these patients.

Metal-Stimulated Interleukin-6 Production Through a Proton-Sensing Receptor, Ovarian Cancer G Protein-Coupled Receptor 1, in Human Bronchial Smooth Muscle Cells: A Response Inhibited by Dexamethasone.

PURPOSE: Human bronchial smooth muscle cells (BSMCs) contribute to airway obstruction and hyperresponsiveness in patients with bronchial asthma. BSMCs also generate cytokines and matricellular proteins in response to extracellular acidification through the ovarian cancer G protein-coupled receptor 1 (OGR1). Cobalt (Co) and nickel (Ni) are occupational agents, which cause occupational asthma. We examined the effects of Co and Ni on interleukin-6 (IL-6) secretion by human BSMCs because these metals may act as ligands of OGR1. METHODS: Human BSMCs were incubated in Dulbecco's Modified Eagle Medium (DMEM) containing 0.1% bovine serum albumin (BSA) (0.1% BSA-DMEM) for 16 hours and stimulated for the indicated time by exchanging the medium with 0.1% BSA-DMEM containing any of the metals or pH-adjusted 0.1% BSA-DMEM. IL-6 mRNA expression was quantified via reverse transcription polymerase chain reaction (RT-PCR) using the real-time TaqMan technology. IL-6 was measured using an enzyme-linked immunosorbent assay. Dexamethasone (DEX) was added 30 minutes before each stimulation. To knock down the expression of OGR1 in BSMCs, small interfering RNA (siRNA) targeting OGR1 (OGR1-siRNA) was transfected to the cells and non-targeting siRNA (NT-siRNA) was used as a control. RESULTS: Co and Ni both significantly increased IL-6 secretion in human BSMCs at 300 µM. This significant increase in IL-6 mRNA expression was observed 5 hours after stimulation. BSMCs transfected with OGR1-siRNA produced less IL-6 than BSMCs transfected with NT-siRNA in response to either Co or Ni stimulation. DEX inhibited Co- and Ni-stimulated IL-6 secretion by human BSMCs as well as pH 6.3-stimulated IL-6 secretion in a dose-dependent manner. DEX did not decrease phosphorylation of ERK1/2, p38 MAP kinase, and NF-κB p65 induced by either Co or Ni stimulation. CONCLUSION: Co and Ni induce secretion of IL-6 in human BSMCs through activation of OGR1. Co- and Ni-stimulated IL-6 secretion is inhibited by DEX.