Evaluation of the association between predictive factors and the development of immune-related adverse events and prognostic factors for chemoimmunotherapy in patients with non-small cell lung cancer: A multicenter retrospective study.

INTRODUCTION: Chemoimmunotherapy is widely used as the first-line management of advanced non-small cell lung cancer (NSCLC) in clinical settings. However, predictive factors associated with the development of immune-related adverse events (irAEs) and prognostic factors for NSCLC patients undergoing chemoimmunotherapy remains largely unexplored. Therefore, in this study, we aimed to evaluate predictive factors for irAE development and prognostic factors associated with chemoimmunotherapy in NSCLC patients. METHODS: This study enrolled 199 patients with advanced and recurrent NSCLC who underwent chemoimmunotherapy across eight institutions in Nagano prefecture from December 2018 to January 2023. We examined predictive factors associated with irAE development and prognostic factors associated with overall survival (OS). RESULTS: Among the patients, 106 experienced irAEs, while 93 patients did not. A total of 44 (22.1%) patients developed multiple irAEs. High serum albumin levels (Alb >3.5 g/dL) emerged as an independent predictive factor associated with irAE development in logistic regression analysis (odds ratio; 2.35, 95% confidence interval 1.27-4.34, p = 0.007). Furthermore, the development of multiple irAEs (p = 0.016), lower lactate dehydrogenase level (<223 U/L, p = 0.002), and decreased neutrophil-to-lymphocyte ratio (<3, p = 0.049) were identified as independent favorable prognostic factors associated with OS in multivariate Cox hazard analyses. CONCLUSION: The study results suggest that high serum Alb is a predictive factor for irAE development and that the presence of multiple irAEs is a favorable prognostic indicator for NSCLC patients undergoing chemoimmunotherapy.

Prognostic Value of the Geriatric Nutritional Risk Index in Previously Untreated Patients with Advanced Non-Small Cell Lung Cancer Treated with a Combination Therapy of Anti-PD-1/-PD-L1 Antibodies and Platinum-Based Chemotherapy: A Multicenter Retrospective Study.

INTRODUCTION: Combination therapy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies and platinum-based chemotherapy has been widely used as a first-line treatment for patients with unresectable advanced non-small cell lung cancer (NSCLC) in clinical settings; however, prognostic biomarkers associated with survival outcomes have not been sufficiently investigated. METHODS: We enrolled 147 previously untreated patients with advanced NSCLC who were treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy at eight institutions in Nagano Prefecture between December 2018 and April 2023. We evaluated the prognostic value of the geriatric nutritional risk index (GNRI), a systemic inflammatory nutritional biomarker calculated from body weight and serum albumin level, for patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy. RESULTS: The cutoff value of the GNRI was set at 92. The high GNRI and low GNRI groups included 88 and 59 patients, respectively. The median follow-up period was 15.9 months. The overall survival (OS) in the high GNRI group was significantly longer than that in the low GNRI group (27.9 vs. 15.6 months, p = 0.015). Multivariate analysis revealed that a high GNRI was an independently favorable prognostic predictor for OS (hazard ratio, 1.73; 95% confidence interval, 1.06-2.86; p = 0.031). CONCLUSION: The present study demonstrates that the GNRI is a useful prognostic predictor in patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy in clinical settings.

Pulmonary Spindle Cell Carcinoma Presenting Anaplastic Lymphoma Kinase Rearrangement.

Pulmonary spindle cell carcinoma is a subtype of pulmonary sarcomatoid carcinoma and a very rare tumor type with a poor prognosis. A few case reports have documented patients with pulmonary sarcomatoid carcinoma with anaplastic lymphoma kinase rearrangement, and the efficacy and outcomes of anaplastic lymphoma kinase inhibitors remain unclear. Herein, we present the case of a 60-year-old woman with stage IVB disease who was diagnosed with a metastatic brain tumor. This patient showed high levels of programmed cell death ligand 1 expression and anaplastic lymphoma kinase rearrangement and received pembrolizumab as the first-line treatment. Three weeks later, pembrolizumab failed to reduce the size of the primary pulmonary tumor, and the patient's general condition did not improve. The patient received alectinib as the second-line treatment. Two months later, multiple brain metastases were observed. Hence, whole-brain irradiation was performed as treatment for multiple brain metastases, while another anaplastic lymphoma kinase inhibitor was administered; however, both treatments remained ineffective. The patient eventually died 9 months after the initiation of first-line treatment. The present case report describes the therapeutic course of a patient with pulmonary spindle cell carcinoma with an anaplastic lymphoma kinase rearrangement.

Predictive Factors Associated with Long-Term Response to Combination Immunotherapy in Patients with Untreated Advanced Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

INTRODUCTION: Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. METHODS: This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. RESULTS: The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (p = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, p = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, p = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, p < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses. CONCLUSION: The CAR and best objective response were suggested to be useful predictors of long-term response in NSCLC patients who received combination immunotherapy.

C-PLAN index as a prognostic factor for patients with previously untreated advanced non-small cell lung cancer who received combination immunotherapy: A multicenter retrospective study.

BACKGROUND: Combination immunotherapy (immune checkpoint inhibitors and cytotoxic anticancer agents) is widely used as first-line treatment for advanced non-small cell lung cancer (NSCLC). However, the therapeutic effect of combination immunotherapy has not been fully investigated. C-reactive protein, performance status, lactate dehydrogenase, albumin, and derived neutrophil-to-lymphocyte ratio (C-PLAN) are useful biomarkers for predicting the prognosis of NSCLC; however, there are no reports examining the C-PLAN index, which combines these five factors in a single prognostic factor. METHODS: We retrospectively collected data from 178 patients with previously untreated advanced NSCLC who received combination immunotherapy at multicenter institutions in Nagano Prefecture between December 2018 and April 2022. We investigated the utility of the C-PLAN index as a prognostic factor using Cox regression analysis and correlated it with survival. RESULTS: The good and poor C-PLAN index groups included 85 and 93 patients, respectively. The good C-PLAN index group had a longer median progression-free survival (PFS) (10.7 vs. 6.0 months; p = 0.022) and overall survival (OS) (25.3 vs. 16.5 months; p = 0.003) than the poor C-PLAN index group. The C-PLAN index was an independent favorable prognostic factor that correlated with PFS and OS in multivariate analysis. The good C-PLAN index group had a higher proportion of never-smokers (16.5 vs. 4.3%; p = 0.007) and stage III disease/postoperative recurrence (32.9 vs. 15.1%; p = 0.005) than the poor C-PLAN index group. CONCLUSION: The C-PLAN index is a useful prognostic factor for patients with previously untreated advanced NSCLC undergoing combination immunotherapy.

Characteristics of airway resistance in obstructive sleep apnea patients with asthma on oscillometry.

BACKGROUND: Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders with a high tendency to coexist. Both diseases involve increased airway resistance in the upright position because of narrow upper or lower airways. Moreover, there is a marked increase in airway resistance in the supine position in patients with OSA. We verified the characteristics of OSA in combination with asthma. METHODS: Airway resistance was measured by oscillometry in the upright and supine position in 11 healthy participants (control), 59 patients with OSA alone, and 33 OSA patients with asthma (coexistence) in the hospital between April 2014 and July 2020. We compared the differences in airway resistance between the upright and supine positions among the three groups. In addition, we performed cephalometry to evaluate the upper airway structure in patients with OSA alone and in patients with both OSA and asthma. RESULTS: A marked increase in airway resistance due to postural change was observed in the "OSA alone" group compared to that in the control group. However, this was not observed in the "coexistence" and control groups. Moreover, the "coexistence" group had fewer structural abnormalities in the upper airway than the "OSA alone" group on cephalometry. CONCLUSIONS: The airway resistance of patients with OSA alone markedly increased with posture change because of upper airway abnormalities. However, there was a smaller increase with postural changes in OSA patients with asthma, suggesting the possibility of a smaller degree of upper airway abnormality compared to patients with OSA alone. CLINICAL TRIAL REGISTRATION NUMBER: This study is approved by the research ethics committee of the Shinshu University School of Medicine (permission number: 4272).

Sleep architecture of short sleep time in patients with obstructive sleep apnea: a retrospective single-facility study.

PURPOSE: Sleep architecture consists of rapid eye movement (REM) sleep and non-REM sleep time. Non-REM sleep time is further classified into three stages by depth (stage N1-N3). Some studies have reported that short sleep time predicts all-cause mortality. Short sleep time can have characteristics of sleep architecture which contribute to poor prognosis. Obstructive sleep apnea (OSA) is a disease which causes cessation or decline of ventilation during sleep due to upper airway stenosis and affects sleep architecture. Few studies have reported on the sleep architecture of short sleep time in patients with OSA. Therefore, we aimed to observe this phenomenon. METHODS: From May 2008 to September 2021, patients diagnosed with OSA at our facility were assessed for clinical history and underwent full-night polysomnography (PSG). These patients were classified into two groups: total sleep time (TST) recorded on PSG consisting of a short TST (< 7 h) group and a not short TST (≥ 7 h) group. RESULTS: Of 266 patients with OSA, compared to the not short TST group (n = 131), the short TST group (n = 135) had a lower REM sleep time (%) and a higher stage N1 sleep time (%). There was a significant difference in age between the two groups, so sub-analyses classified the patients by age: non-elderly patients (< 65 years) and elderly patients (≥ 65 years) to adjust for age. Both sub-analyses showed similar results to the analysis for the combined ages regarding sleep architecture. CONCLUSION: Patients with OSA who had short sleep time had disordered sleep architecture with a lower REM sleep time (%) and more stage N1 sleep time.

The positional characteristics of patients with obstructive sleep apnea: a single institute retrospective study in Japan.

Obstructive sleep apnea (OSA) causes sleep-disordered breathing (SDB) due to upper airway obstruction. The severity of OSA changes with position during sleep. Patients with marked significant improvement in apnea-hypopnea index (AHI) level by sleep position change are defined as ''positional patients'' (PP), while those without improvement are defined as ''non-positional patients'' (NPP). We aimed to verify their clinical characteristics. Between May 2008 and May 2020, 237 patients with OSA were registered retrospectively and classified into two groups: PP (n = 158) and NPP (n = 79). The differences in clinical background and full-night polysomnography (PSG) between the two groups were observed. A logistic regression analysis was conducted to identify the risk factors for severe AHI (≥ 30 events/h) in the PP group. Moreover, confounding factor-adjusted sub-analysis by a propensity score matching method was performed, and the PSG results were compared between the two groups. The PP group was older than the NPP group. Furthermore, the PP group had lower body mass index (BMI) and AHI levels compared with the NPP group. The independent risk factors for severe AHI in the PP group were BMI and being in the supine position during sleep. The PP group had a significantly milder nocturnal hypoxemia despite having no significant difference in AHI levels between the two groups. The characteristics of PP were old age, low BMI, and low AHI associated with milder nocturnal hypoxemia. Moreover, they were less likely to worsen with nocturnal hypoxemia compared with NPP having similar severity.

Double venous compression due to duplicated inferior vena cava-induced right common iliac vein thrombosis.

Venous compression syndromes are caused by extrinsic venous compression of anatomical structures, such as the adjacent arteries and bones. Chronic venous compression and pulsative vibratory arterial pressure accelerate the development of deep vein thrombosis. Herein, we report the first case of double venous compressions due to a duplicated inferior vena cava-induced right-sided common iliac vein thrombosis. The thrombus was induced by left-sided inferior vena cava entrapment and right-sided common iliac vein compression, resembling nutcracker syndrome and May-Thurner syndrome, respectively. Bypass flow of the right inferior vena cava rendered the right lower extremity asymptomatic. Once daily anticoagulation edoxaban was effective. Congenital venous anomalies and bypass formations should be considered when a common iliac vein thrombus without symptoms in the lower extremities is observed, and a lifelong periodical follow-up is mandatory, even after remission.

Associations between the distance covered in the incremental shuttle walk test and lung function and health status in patients with chronic obstructive pulmonary disease.

BACKGROUND: Field walk tests such as the incremental shuttle walk test (ISWT) are simple tests for assessing the degree of disability in individuals with chronic obstructive pulmonary disease (COPD). In the present study, the correlations between exercise performance in the ISWT, lung function, and health status were examined in patients with COPD of varying severities. METHODS: A retrospective examination of 277 COPD patients was performed using the ISWT and lung function tests along with assessment of health status using St. George׳s Respiratory Questionnaire (SGRQ). In addition, we assessed the correlations between the walking distance, lung function parameters, and SGRQ scores. RESULTS: ISWT distances were poorly correlated with lung function parameters and SGRQ scores in mild COPD patients. In contrast, ISWT distances were significantly correlated with pulmonary function parameters, such as vital capacity (%predicted) and forced expiratory volume in one second, and SGRQ scores in moderate and severe COPD patients. CONCLUSIONS: The ISWT is more independent of health status and pulmonary function in patients with mild COPD compared to moderate or severe cases. Therefore, the exercise capacity of patients with mild COPD should be estimated by the ISWT.