Unfavorable response to capmatinib for MET exon14 skipping after first-line osimertinib in a patient with EGFR-mutated lung adenocarcinoma: A case report and literature review.

MET exon14 skipping mutations (METex14s) are rarely reported as a potential resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). The efficacy of targeted therapy against METex14s emerging after osimertinib resistance is uncertain. Herein, we report a case of EGFR-mutated metastatic lung adenocarcinoma in which METex14 was detected in a re-biopsy upon first-line osimertinib resistance. The patient received capmatinib monotherapy as third-line therapy, which was ineffective, followed by an exceptional response to salvage therapy with afatinib. This report highlights the heterogeneity of EGFR-TKI resistance and that targeting rare resistance mechanisms remains challenging.

Prognostic Value of the Geriatric Nutritional Risk Index in Previously Untreated Patients With Advanced NSCLC 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.

Impact of Interventional Bronchoscopy on Long-Term Survival in Patients with Primary Tracheal Adenoid Cystic Carcinoma: A Single-Center Experience.

Introduction: Primary tracheal adenoid cystic carcinoma (TACC) is a rare low-grade lung cancer of bronchial gland origin. Surgery is the first choice of treatment; however, in cases of recurrence or inoperability, a combination of radiation and chemotherapy is administered as a multimodality treatment. Interventional bronchoscopy is also used as a multidisciplinary treatment; however, its impact on long-term prognosis has not been thoroughly investigated. Case Presentation: Eight patients diagnosed with TACC and treated at Shinshu University Hospital between December 2000 and August 2023 were analyzed retrospectively. We investigated the duration of intervention and overall survival (OS) in 3 patients with recurrence who underwent interventional bronchoscopy in combination with chemotherapy and evaluated whether interventional bronchoscopy prolonged the survival. The initial treatment for the 3 patients was surgery in 1 patient and chemoradiotherapy in 2. In all patients, raised lesions were observed in the trachea at the time of recurrence. The duration of interventional bronchoscopy, the time from recurrence of the first-line treatment to death, and OS, which was defined time from induction of the first-line treatment to death, were 69.3/70.7/112.5 months, 179.2/196.1/220.4 months, and 15.4/66.3/104.4 months, respectively. Conclusion: Long-term survival benefits may be obtained with concomitant interventional bronchoscopy in combination with chemotherapy in patients with locally recurrent TACC.

EGFR-TKI rechallenge in patients with EGFR-mutated non-small-cell lung cancer who progressed after first-line osimertinib treatment: A multicenter retrospective observational study.

BACKGROUND: Rechallenge therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is known to confer some clinical benefit for patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). However, little is known about the efficacy of EGFR-TKI rechallenge after resistance to first-line (1L) osimertinib. This study aimed to assess the efficacy and safety of EGFR-TKI rechallenge therapy after resistance to 1L osimertinib in a Japanese clinical setting. METHODS: Between April 2018 and August 2022, 26 patients who progressed after treatment with 1L osimertinib and received EGFR-TKI rechallenge were included in this multicenter retrospective analysis. Patients in whom 1L osimertinib was discontinued owing to toxicity and had subsequent disease progression were also included in the analysis. RESULTS: Overall, the objective response rate for rechallenge therapy was 23.1%. The disease control rate was 53.9%, and the median progression-free survival (PFS) was 3.4 months. Patients who discontinued 1L osimertinib for toxicity had a higher response rate (42.9% vs. 15.8%) and longer PFS than those who discontinued it due to disease progression (median: 11.4 vs. 2.7 months, P = 0.001). Three patients (11.5%) developed rechallenge therapy-associated pneumonitis, two of which were grade ≥3. CONCLUSIONS: Rechallenge with EGFR-TKI after 1L osimertinib resistance showed limited clinical efficacy. However, it could be considered as a subsequent salvage therapeutic option for patients in whom 1L osimertinib was discontinued owing to toxicity.

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.

Rechallenge of afatinib for EGFR-mutated non-small cell lung cancer previously treated with osimertinib: a multicenter phase II trial protocol (REAL study).

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC) and contributed to the development of precision medicine. Osimertinib is a standard first-line (1L) treatment for EGFR-mutated NSCLC and has demonstrated superior survival benefits over previous-generation TKIs. However, resistance to osimertinib is nearly inevitable, and subsequent treatment strategies remain unmet medical needs in this setting. Afatinib, a second-generation EGFR-TKI, exhibits activity against certain uncommon EGFR mutation types in the 1L setting. There are a few case reports on the efficacy of afatinib against EGFR-dependent resistance after osimertinib treatment, although these have not been prospectively investigated. Methods: The present phase II, single-arm multicenter trial aims to verify the efficacy and safety of afatinib rechallenge after 1L osimertinib resistance. Patients (aged ≥20 years) with advanced or recurrent non-squamous NSCLC harboring drug-sensitive EGFR mutations (deletion of exon 19 or L858R) who were previously treated with 1L osimertinib and second-line chemotherapy other than TKIs are considered eligible. Undergoing next-generation sequence-based comprehensive genomic profiling is one of the key inclusion criteria. The primary endpoint is the objective response rate; the secondary endpoints are progression-free survival, overall survival, and tolerability. Thirty patients will be recruited in December 2023. Discussion: The results of this study may promote incorporating afatinib rechallenge into the treatment sequence after 1L osimertinib resistance, a setting in which concrete evidence has not been yet established. Registration: UMIN Clinical Trial Registry: UMIN000049225.

Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance.

Osimertinib, a third-generation EGFR TKI, is the standard therapy for previously untreated EGFR-mutated non-small cell lung cancer patients following the landmark FLAURA study. However, resistance inevitably hinders patient prognosis, increasing the need for new therapeutic strategies beyond osimertinib. Frontline osimertinib-based combination strategies (platinum-based chemotherapy and angiogenesis inhibitors) are currently being tested primarily to prevent initial resistance. In the later-line setting after osimertinib, many next-line therapeutic candidates have been actively examined in clinical trials. Notably, several drugs with novel mechanisms of action, such as antibody-drug conjugates and EGFR -MET bispecific antibodies, have shown promising efficacy despite the resistance mechanisms and are close to clinical application. In addition, genotype-based target strategies have been investigated for a better understanding of osimertinib resistance mechanisms based on molecular profiling tests at relapse. The C797S mutation and MET gene alterations are commonly identified following osimertinib resistance, for which targeting strategies are actively tested. This review describes current pharmacotherapeutic strategies for EGFR-mutated non-small cell lung cancer based on the results of clinical trials and the latest published data, broadly grouped into two sections: 1) EGFR TKIs-based combination therapy in the front-line setting and 2) novel therapeutic strategies after osimertinib resistance.

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.

Epidemiological and Therapeutic Analyses in Lung Cancer Patients Over 80 Years Old in the Hokushin Region: A Retrospective Hospital Administrative Database Study.

OBJECTIVE: This study was performed to validate the epidemiology, initial treatment, and clinical practice in lung cancer patients < 80 and ≥ 80 years in Hokushin region, Japan. METHODS: We retrospectively surveyed data of 5481 newly diagnosed and registered lung cancer patients (4311 [78.7%] < 80 years; 1170 [21.3%] ≥ 80 years ) in 22 principal hospitals in Hokushin region linked with health insurance claims data between 2016 and 2017. Stage, initial treatment, and clinical practice were compared between the 2 groups. RESULTS: The distributions of clinical stage I/II/III/IV/unknown were 2535/387/654/1371/111 in non-small cell lung cancer (NSCLC) and 37/32/114/237/3 in SCLC. Initial surgery for stage I NSCLC was performed in 90.0% and 60.2% of cases in the < 80 and ≥ 80 years groups, respectively. Rates of treatment with best supportive care (BSC) for stage IV disease were significantly higher in the ≥ 80 than the < 80 years group (NSCLC:58.9% vs. 18.7%; SCLC: 42.3% vs. 6.8%, respectively), regardless of the presence/absence of comorbidities. Propensity score matching showed that age ≥ 80 years itself was significantly related to choice of BSC in patients with lung cancer. The ratio of initial cytotoxic chemotherapy for NSCLC was low (49.9%) but that of biomarker-based therapy including tyrosine kinase inhibitors and immune checkpoint inhibitors (50.0%) was significantly higher in the ≥ 80 than < 80 years group (70.2% vs. 29.8%, respectively). CONCLUSION: There are several differences in treatment pattern between patients < 80 and ≥ 80 years. Age ≥ 80 years may be related to BSC choice in patients with lung cancer.

Is using a consolidation tumor ratio 0.5 as criterion feasible in daily practice? Evaluation of interobserver measurement variability of consolidation tumor ratio of lung cancer less than 3 cm in size.

BACKGROUND: Consolidation tumor ratio (CTR) calculated as the ratio of the tumor consolidation diameter to the tumor maximum diameter on thin-section computed tomography (CT) of lung cancer has been reported as an important prognostic factor. It has also been used for treatment decision-making. This study aimed to investigate the interobserver variability of CTR measurements on preoperative CT and propose a clinically useful CTR-based classification criterion. METHODS: We enrolled 119 patients who underwent surgery for suspected or diagnosed small-sized lung cancer (≤3.0 cm in diameter). Nine doctors reviewed preoperative CT scans to measure CTR. Interobserver variability of CTR measurements was evaluated using the coefficient of variation (CV) and Fleiss' κ. The prognostic effect of the CTR-based classification was assessed using the Kaplan-Meier method. RESULTS: Interobserver variability of CTR measurement was the highest for tumors with the lowest CTR (CTR = 0); it decreased as CTR increased and reached a plateaued level of low variability (CV <0.5) at CTR of 0.5. We proposed a three-group classification based on the findings of CTR interobserver variability (CTR < 0.5, 0.5 ≤ CTR < 1, and CTR = 1). Interobserver agreement of the judgment of the CTR-based classification was excellent (Fleiss' κ = 0.81). The classification significantly stratified patient prognosis (p < 0.001, 5-year overall survival rates with CTR < 0.5, 0.5 ≤ CTR < 1, and CTR = 1 were 100, 88, and 73.8%, respectively). CONCLUSIONS: CTR 0.5 is a clinically relevant and helpful cutoff for treatment decision-making in patients with early-stage lung cancer based on high interobserver agreement and good prognostic stratification.

Predictive value of post-treatment C-reactive protein-to-albumin ratio in locally advanced non-small cell lung cancer patients receiving durvalumab after chemoradiotherapy.

BACKGROUNDS: The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation-related parameters in patients with LA-NSCLC treated with CCRT plus durvalumab. METHODS: We recruited 76 LA-NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre-treatment) and 2 months after (post-treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression-free survival (PFS) after durvalumab therapy. RESULTS: The median follow-up time was 17 (range, 3.3-35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non-infectious pneumonitis being the most common reason. Post-treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not-reached vs. 9.6 months. Log-rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post-treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003). CONCLUSIONS: This study suggests that post-treatment CAR has predictive value for LA-NSCLC patients treated with CCRT plus durvalumab consolidation therapy.

Association of lung immune prognostic index with survival outcome in advanced thymic carcinoma patients treated with palliative intent chemotherapy.

BACKGROUND: The prognostic implications of palliative chemotherapy for advanced or recurrent thymic carcinomas require full elucidation. The lung immune prognostic index (LIPI) is a novel prognostic index whose effectiveness has recently been reported in lung cancer patients. This study aimed to evaluate the clinical value of the LIPI in advanced or recurrent thymic carcinoma patients. METHODS: We retrospectively analyzed 41 advanced or recurrent thymic carcinoma patients undergoing palliative chemotherapy between January 2001 and December 2020. Survival-time analysis was conducted using the Kaplan-Meier method and log-rank test. Multivariate analysis using the Cox proportional hazards model was performed to investigate the predictive and/or prognostic value of the LIPI. RESULTS: Median progression-free survival (PFS) for first-line chemotherapy and overall survival (OS) were significantly longer in the good-LIPI group (LIPI: 0) than in the intermediate/poor-LIPI group (LIPI: 1 or 2) (PFS: 13.4 vs. 6.8 months, p = 0.025; OS: 48.2 vs. 28.9 months, p = 0.00506). Multivariate analysis revealed that intermediate/poor LIPI was the adverse prognostic factor for PFS. With regard to OS, serum albumin <3.5 g/dl and an intermediate/poor LIPI were identified as independent adverse prognostic factors. CONCLUSIONS: Our study indicates that the LIPI is a potential prognostic marker in patients with advanced or recurrent thymic carcinoma undergoing palliative chemotherapy.

Predictive Factors Correlated with the Development of Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

PURPOSE: Similar to the neutrophil-to-lymphocyte ratio and lung immune prognostic index (LIPI), immune-related adverse events (irAEs) were favorable prognostic factors in several studies, for patients with non-small cell lung cancer who received immune checkpoint inhibitors (ICIs). However, few studies have investigated patient characteristics and markers that predict the development of irAEs, and factors predicting the development of irAEs have not been clarified. Thus, the present study aimed to examine the predictive factors correlated with the development of irAEs in non-small cell lung cancer (NSCLC) patients who received anti-programmed cell death protein 1/programmed cell death ligand 1 inhibitor monotherapy. PATIENTS AND METHODS: The present study was retrospectively enrolled 113 advanced NSCLC patients who received ICIs between February 2016 and May 2021 and was conducted at Shinshu University Hospital. All patients were divided into two groups according to with or without of irAEs. We compared the clinical findings and laboratory data between the two groups and considered predictive factors correlated with the development of irAEs. RESULTS: Forty-four (38.9%) patients developed irAEs of any grade. The most common irAEs were hypothyroidism (12.4%), followed by skin rash (7.1%) and interstitial lung disease (7.1%). The survival time in patients with irAEs was significantly more prolonged compared to those without irAEs (median progression-free survival: 6.8 vs 2.1 months, p < 0.001; median overall survival: 25.3 vs 9.6 months, p = 0.001). Multivariate analyses based on logistic regression revealed independent predictive factors that correlated with the development of irAEs to be first-line ICI treatment and a score of 0 or 1 on LIPI. CONCLUSION: The present study revealed that lines of immunotherapy and LIPI were correlated with the development of irAEs in NSCLC patients who received ICIs and can help clinicians who manage patients experiencing irAEs receiving ICIs.

Prognostic value of geriatric nutritional risk index for aspiration pneumonia: a retrospective observational cohort study.

BACKGROUND: The clinical characteristics and prognostic factors of aspiration pneumonia remain poorly defined. Geriatric nutrition risk index (GNRI) has recently been reported to exhibit a prognostic value for several diseases in older adults. AIMS: We investigated the clinical characteristics and prognostic significance of GNRI for aspiration pneumonia in older adult patients. METHODS: In this retrospective observational cohort study, conducted in a single-institute acute-phase community hospital, patients with aspiration pneumonia diagnosed at our institute between April 2014 and March 2016 were enrolled. Data on patient characteristics, microbiological findings, and clinical course were collected. The outcome was in-hospital mortality. Receiver operating characteristic curve (ROC) analysis was conducted to compare the predictive value of each parameter. Logistic regression analysis was performed to identify independent prognostic factors. RESULTS: Overall, 587 aspiration pneumonia patients aged ≥ 65 years were enrolled. Their mean age was 86 years. Among them, 97 (16.5%) died. In ROC analysis for in-hospital mortality, as compared to albumin, body mass index, and A-DROP score, GNRI had a greater area under the curve value, with a significant difference between GNRI and albumin (p = 0.0058). Male sex (p = 0.028), chronic heart failure (p = 0.023), history of malignancy (p = 0.0025), lower GNRI (p < 0.001), and initial antibiotic change (p < 0.001) were identified as independent adverse prognostic factors in multivariate analysis. DISCUSSION AND CONCLUSIONS: Our findings indicate that GNRI is a potential prognostic marker for older adults with aspiration pneumonia and may act as a proxy for disease severity. Our results support the use of GNRI in the clinical management of aspiration pneumonia.

Pembrolizumab-Induced Adrenal Insufficiency in Patients with Untreated Advanced Non-Small Cell Lung Cancer: A Case Series.

Pembrolizumab-induced adrenal insufficiency (AI) is recognized as a rare immune-related adverse event (irAE) that can be fatal if diagnosis is delayed. Clinical features of AI in patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab as the first-line treatment were observed. Five out of 49 patients with untreated advanced NSCLC developed AI between April 2017 and February 2021. Of the 5 patients, 4 developed AI with a grade >3 and were hospitalized. The median time of the onset of AI from the start of first-line treatment was 4.63 months. All the patients improved after corticosteroid replacement therapy. The efficacy of treatment was complete response in 1 patient and partial response in 4 patients. Median progression-free survival was 37.7 months, and overall survival had not been reached. This case series revealed the efficacy of immunotherapy in AI as an irAE.

Prognostic implication of erector spinae muscles in non-small-cell lung cancer patients treated with immuno-oncology combinatorial chemotherapy.

BACKGROUND: The quantity of skeletal muscles has recently been reported to have prognostic value in patients with non-small-cell lung cancer (NSCLC) treated with second-line immunotherapy. However, the prognostic role of skeletal muscle assessment in NSCLC patients undergoing first-line immuno-oncology (IO) combinatorial treatment (IO-chemotherapy) has not been elucidated. METHODS: We retrospectively reviewed 36 patients with NSCLC undergoing first-line IO-chemotherapy between April 2018 and June 2021 in our hospital. The cross-sectional area of the erector spinae muscle (ESMCSA ) was evaluated by manual tracing on computed tomography scans at the level of the 12th thoracic vertebra before initiating IO-chemotherapy. To minimize deviation due to physique, the ESMCSA was adjusted by body surface area (BSA) (ESMCSA to BSA ratio: ESMCSA /BSA). A survival time analysis was performed using the Kaplan-Meier method and log-rank test. A multivariate analysis with Cox proportional hazards model was conducted to investigate the prognostic value of the ESMCSA /BSA and inflammatory and nutritional indices. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 6.5 and 16.6 months, respectively. Intergroup comparison by the log-rank test revealed that there was no significant difference in the median PFS, but the median OS was significantly long in the high ESMCSA /BSA (>19 cm2/ m2 ) (high ESMCSA /BSA group, p = 0.0373). The multivariate analysis showed that ESMCSA /BSA was an independent prognostic factor for OS (hazard ratio 0.79, p = 0.044). CONCLUSIONS: The results of this study indicate that the pretreatment ESMCSA /BSA may be a potential prognostic factor in NSCLC patients receiving first-line IO-chemotherapy.

Thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular tumor biopsy: A report of two cases.

Thymic epithelial tumor is a rare, potentially progressive disease that commonly infiltrates mediastinal structures. In rare cases, it may cause superior vena cava syndrome. Pretreatment histopathological diagnosis is essential to determine the most effective treatment strategy. Percutaneous endovascular biopsy is a rarely reported non-surgical diagnostic option for large vessel tumoral involvement. We report two cases of thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular biopsy. No procedural complications occurred, and subsequent systemic treatment was promptly administered. This procedure may have potential as a useful diagnostic method for patients with mediastinal tumors involving large vessels.

Prognostic value of the geriatric nutritional risk index among patients with previously treated advanced non-small cell lung cancer who subsequently underwent immunotherapy.

BACKGROUND: The geriatric nutritional risk index (GNRI) is a simple and useful marker for predicting prognosis and treatment efficacy among patients with various cancers. However, to the best of our knowledge, there are no previous reports regarding the prognostic value of GNRI among patients with non-small cell lung cancer (NSCLC) who were treated with immune checkpoint inhibitors (ICIs). METHODS: We retrospectively evaluated 85 patients with previously treated advanced NSCLC who were administered ICIs at Shinshu University Hospital between February 2016 and October 2020. Progression-free survival (PFS) and overall survival (OS) were compared between groups with high (≥89.5) and low (<89.5) GNRI values. We used univariate and multivariate Cox regression analyses to identify prognostic factors that were associated with PFS and OS. RESULTS: The high and low GNRI groups included 61 and 24 patients, respectively. Relative to the low GNRI group, the high GNRI group had significantly longer median PFS (3.7 vs. 2.4 months, p = 0.041) and significantly longer median OS (14.2 vs. 6.1 months, p = 0.008). Multivariate analyses revealed that independent predictors of favorable OS were high GNRI, performance status of 0-1, and age of ≥70 years. The high GNRI group was significantly more likely to undergo subsequent therapy after immunotherapy (68.6 vs. 33.3%, p = 0.008). CONCLUSIONS: The present study revealed that high GNRI was associated with good outcomes among patients with previously treated NSCLC who were treated with ICIs.

The Role of Immune-Related Adverse Events in Prognosis and Efficacy Prediction for Patients with Non-Small Cell Lung Cancer Treated with Immunotherapy: A Retrospective Clinical Analysis.

PURPOSE: The development of immune-related adverse events (irAEs) in patients undergoing immunotherapy has been reported to be a favorable prognostic factor in several studies. We aimed to examine the correlation between irAEs and prognosis in patients with non-small cell lung cancer (NSCLC) and further reveal the patient characteristics associated with response to immunotherapy among treatment responders who developed irAEs. METHODS: We retrospectively enrolled 80 patients with NSCLC who received immunotherapy at Shinshu University Hospital between February 2016 and February 2020. Progression-free survival (PFS) and overall survival (OS) were compared between patients with and those without irAEs. We examined the prognostic factors associated with PFS and OS using univariate and multivariate Cox proportional-hazards models. We further analyzed the patients who developed irAEs by classifying them into responders and non-responders. RESULTS: Twenty-five patients developed irAEs. The median PFS and OS of the patients with irAEs were significantly longer than those of the patients without irAEs (6.8 vs. 1.9 months, p < 0.001, and 37.8 vs. 8.1 months, p < 0.001, respectively). Multivariate analysis associated with PFS and OS indicated that the development of irAEs was an independent favorable prognostic factor. Among the patients developing irAEs, the responder group had a significantly higher incidence of multiple irAEs than the non-responder group (41.7 vs. 0.0%, p = 0.009). CONCLUSION: Our findings revealed that the development of irAEs was associated with clinical benefits in NSCLC patients who received immunotherapy. In particular, patients with multiple irAEs might have good prognoses.