Clinical application of the Lung Cancer Compact PanelTM using various types of cytological specimens in patients with lung cancer.

BACKGROUND: The Lung Cancer Compact PanelTM (compact panel) is a gene panel that can detect driver alterations with high sensitivity in liquid samples, including tumor cells. This study examined the ability of a compact panel to detect genetic mutations in liquid specimens used in clinical practice. METHODS: Three cohorts, bronchoscopic biopsy forceps washing (washing cohort), pleural effusion (pleural cohort), and spinal fluid (spinal cohort), were analyzed using the compact panel. Liquid samples were added into the GM (Genemetrics) tubes and analyzed. The washing cohort assessed the concordance rate of gene panel analysis outcomes in tissue specimens derived from the primary tumor. Meanwhile, the pleural cohort investigated the impact of storing specimens for 8 weeks and more on nucleic acid and mutation detection rates. RESULTS: In the washing cohort (n = 79), the concordance rate with mutations detected in tissues was 75/79 (94.9 %). This rate reached 100 % when focusing solely on driver alterations for treatment. The pleural cohort (n = 8) showed no deterioration in nucleic acid quality or quantity after 8 weeks of storage in GM tubes. Similarly, in the spinal cohort (n = 9), spinal fluid with malignant cells exhibited driver alterations similar to those in the primary tumor. These findings underscore the efficacy of the compact panel in accurately identifying genetic mutations in different liquid specimens. CONCLUSIONS: The compact panel is a reliable tool for detecting driver alterations in various cytological specimens. Its consistent performance across diverse sample types emphasizes its potential for guiding targeted therapies for patients with lung cancer and enhancing precision medicine approaches.

Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma.

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer associated with poor prognosis and resistance to conventional chemotherapy. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, were found to have clinical benefits in PSC in recent studies. Nevertheless, because these studies included a small number of patients owing to disease rarity, larger studies are needed to evaluate the effectiveness and safety of ICI-based therapy for PSC. Methods: This multicenter retrospective study evaluated patients with ICI-naive advanced or metastatic PSC who were treated with ICI-based therapy at 25 hospitals in Japan. Results: A total of 124 patients were evaluated. The overall response rate, median progression-free survival (PFS), and median overall survival (OS) were 59.0%, 10.5 months, and 32.8 months, respectively. The PFS and OS rates at 24 months were 35.3% and 51.5%, respectively. Programmed death-ligand 1 expression, concomitant chemotherapy, and the treatment line were not significantly associated with PFS or OS. Immune-related adverse events (irAEs) were observed in 70 patients (56.5%), including 30 (24.2%) with grade 3 to 5 events. Patients with mild irAEs (grades 1-2) had longer PFS and OS than did those with severe (grades 3-5) or no irAEs. In a multivariate analysis, any-grade irAEs and the absence of liver metastases were independently associated with PFS, whereas any-grade irAEs and Eastern Cooperative Oncology Group performance status less than or equal to 1 were independently associated with OS. Conclusions: ICI-based therapy was found to have promising effectiveness in patients with advanced or metastatic PSC, regardless of programmed death-ligand 1 expression, concomitant chemotherapy, or treatment line.

Utility of needle biopsy in centrally located lung cancer for genome analysis: a retrospective cohort study.

BACKGROUND: It is essential to collect a sufficient amount of tumor tissue for successful next-generation sequencing (NGS) analysis. In this study, we investigated the clinical risk factors for avoiding re-biopsy for NGS analysis (re-genome biopsy) in cases where a sufficient amount of tumor tissue could not be collected by bronchoscopy. METHODS: We investigated the association between clinical factors and the risk of re-genome biopsy in patients who underwent transbronchial biopsy (TBB) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and required re-genome biopsy in cases enrolled in LC-SCRUM Asia, a prospective nationwide genome screening project in Japan. We also examined whether the frequency of re-genome biopsy decreased between the first and second halves of the enrolment period. RESULTS: Of the 572 eligible patients, 236 underwent TBB, and 134 underwent EBUS-TBNA. Twenty-four TBBs required re-genome biopsy, and multivariate analysis showed that the risk of re-genome biopsy was significantly increased in lesions where the tumor lesion was centrally located. In these cases, EBUS-TBNA should be utilized even if the lesion is a pulmonary lesion. However, it should be noted that even with EBUS-TBNA, lung field lesions are at a higher risk of re-canalization than mediastinal lymph node lesions. It was also found that even when tumor cells were detected in rapid on-site evaluation, a sufficient amount of tumor tissue was not always collected. CONCLUSIONS: For centrally located pulmonary mass lesions, EBUS-TBNA, rather than TBB, can be used to obtain tumor tissues that can be analyzed by NGS.

Subsequent treatment for locally advanced non-small-cell lung cancer that progressed after definitive chemoradiotherapy and consolidation therapy with durvalumab: a multicenter retrospective analysis (TOPGAN 2021-02).

PURPOSE: For patients with locally advanced non-small-cell lung cancer (LA-NSCLC) that progressed after definitive chemoradiotherapy (CRT) and durvalumab consolidation therapy, no subsequent standard treatment exists. The type of treatment selected for each timing of disease progression and its efficacy have not been investigated. METHODS: We retrospectively enrolled patients with LA-NSCLC or inoperable NSCLC that progressed after definitive CRT and durvalumab consolidation therapy at 15 Japanese institutions. Patients were classified into the following: Early Discontinuation group (disease progression within 6 months after durvalumab initiation), Late Discontinuation group (disease progression from 7 to 12 months after durvalumab initiation), and Accomplishment group (disease progression from 12 months after durvalumab initiation). RESULTS: Altogether, 127 patients were analyzed, including 50 (39.4%), 42 (33.1%) and 35 (27.5%) patients from the Early Discontinuation, Late Discontinuation, and Accomplishment groups, respectively. Subsequent treatments were Platinum plus immune checkpoint inhibitors (ICI) in 18 (14.2%), ICI in 7 (5.5%), Platinum in 59 (46.4%), Non-Platinum in 35 (27.6%), and tyrosine kinase inhibitor in 8 (6.3%) patients. In the Early Discontinuation, Late Discontinuation, and Accomplishment groups, 4 (8.0%), 7 (16.7%), and 7 (20.0%) patients were receiving Platinum plus ICI; 21 (42.0%), 22 (52.4%), and 16 (45.7%) were receiving Platinum, and 20 (40.0%), 8 (19.0%), and 7 (20.0%) were receiving Non-Platinum, respectively. No significant difference in progression-free survival was observed in the timing of disease progression. CONCLUSION: In patients with LA-NSCLC hat progressed after definitive CRT and durvalumab consolidation therapy, subsequent treatment may change depending on the timing of disease progression.

Increased Oxygen Extraction by Pulmonary Rehabilitation Improves Exercise Tolerance and Ventilatory Efficiency in Advanced Chronic Obstructive Pulmonary Disease.

BACKGROUND: In cardiopulmonary exercise testing (CPET), oxygen uptake (V'O2) is calculated using the product of minute ventilation (V'E) and the difference between inspiratory and expiratory O2 concentrations (ΔFO2). However, little is known about the response of ΔFO2 to pulmonary rehabilitation (PR). The aim of the present study was (1) to investigate whether PR increases peak V'O2, based on whether ΔFO2 or V'E at peak exercise increase after PR, and (2) to investigate whether an improvement in ΔFO2 correlates with an improvement in ventilatory efficiency. METHODS: A total of 38 patients with severe and very severe COPD, whose PR responses were evaluated by CPET, were retrospectively analyzed. RESULTS: After PR, peak V'O2 was increased in 14 patients. The difference in ΔFO2 at peak exercise following PR correlated with the difference in peak V'O2 (r = 0.4884, p = 0.0019), the difference in V'E/V'CO2-nadir (r = -0.7057, p < 0.0001), and the difference in V'E-V'CO2 slope (r = -0.4578, p = 0.0039), but it did not correlate with the difference in peak V'E. CONCLUSIONS: The increased O2 extraction following PR correlated with improved exercise tolerance and ventilatory efficiency. In advanced COPD patients, a new strategy for improving O2 extraction ability might be effective in those in whom ventilatory ability can be only minimally increased.

The Diagnosis of Nontuberculous Mycobacterial Pulmonary Disease by Single Bacterial Isolation Plus Anti-GPL-Core IgA Antibody.

Although serum anti-glycopeptidolipid (GPL)-core IgA antibody is a highly specific test for infection with Mycobacterium avium complex (MAC), Mycobacterium abscessus, and its subspecies abscessus, subsp. massiliense, and subsp. bolletii (MAB), its use for the definitive diagnosis of MAC pulmonary disease (PD) and MAB-PD are unknown. To clarify the diagnostic accuracy of the anti-GPL-core IgA antibody test among patients with radiologically suspected MAC-PD or MAB-PD who already have a single positive sputum culture test. The first isolations of MAC and MAB from patients with radiologically suspected MAC-PD or MAB-PD at the Osaka Toneyama Medical Center between January 2006 and December 2020 were collected. Patients were enrolled when their serum anti-GPL-core IgA antibody was measured during the 3 months before and after the first isolation. We retrospectively compared the results of anti-GPL-core IgA antibody testing with the final diagnoses based on the current guidelines. We included 976 patients for analysis. The serum anti-GPL-core IgA antibody was positive in 699 patients (71.6%). The positive predictive value of anti-GPL-core IgA antibody for the diagnosis of MAC-PD or MAB-PD was 97.4%. The median time required for the second positive culture after the first isolation was 51 days (interquartile range 12 to 196 days). The positive serum anti-GPL-core IgA antibody test allowed an early and definitive diagnosis of MAC-PD or MAB-PD in those who already had a single positive sputum culture test. IMPORTANCE To satisfy the microbiologic criteria of the current diagnostic guideline for nontuberculous mycobacterial pulmonary disease (PD), at least two positive sputum cultures of the same species of mycobacteria from sputum are required to avoid the casual isolation of mycobacteria. This study showed that the positivity of a serum anti-glycopeptidolipid (GPL)-core IgA antibody test has an excellent diagnostic ability among patients with radiologically suspected Mycobacterium avium complex (MAC)-PD or Mycobacterium abscessus (MAB)-PD who already had a single positive sputum culture test. The usage of single culture isolation plus anti-GPL-core IgA antibody as another diagnostic criterion has a time, cost, and effort-saving effect. Furthermore, it will facilitate the diagnosis of MAC-PD or MAB-PD in the early stage of disease because serum anti-GPL-core IgA antibody becomes high in these patients. Therefore, we proposed adding single culture isolation plus anti-GPL-core IgA antibody as "combined microbiological and serological criteria" to the diagnostic guidelines for MAC-PD and MAB-PD.

Spontaneous regression of lung metastases after transarterial chemoembolization for hepatocellular carcinoma.

Spontaneous regressions of primary and/or metastatic lesions have been rarely reported in hepatocellular carcinoma (HCC). Herein, we report the case of a 71-year-old man with HCC, focusing on shape changes of lung metastases over time. Lung metastasis of HCC was histologically diagnosed by percutaneous computed tomography (CT)-guided needle biopsy after the treatment of primary HCC lesion. Lung lesions had been observed on enhanced contrast computed tomography for >3 years without any local or systemic treatment for them. During this period, treatments including surgical procedure for relapsed bladder cancer and transarterial chemoembolization for HCC were performed. Metastatic lung lesions immediately regressed after these treatments. Therefore, accumulation of such cases may help elucidate spontaneous regression mechanisms in primary HCC or its lung metastases.