Conduction time from left bundle branch pacing to the left ventricular lateral wall in two patients in whom cardiac resynchronization therapy pacemaker was implanted.

The efficacy of left bundle branch pacing (LBBP) as cardiac resynchronization therapy (CRT) has been reported, but LBBP may not always improve conduction disturbance in the left ventricle (LV). To evaluate LV electrical conduction delay during LBBP, we measured conduction time from the pacing at left bundle branch to LV lead sensing (LBBP-LV) in two patients in whom left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) was attempted. Case 1 was a 77-year-old female with dilated cardiomyopathy (DCM) and left bundle branch block. The QRS duration during LBBP was 160 ms and the interval between the stimulus artifact and peak of the R wave in lead V6 (Stim-V6RWPT) was 74 ms. LBBP-LV at the LV mid-lateral wall and LV mid-posterolateral wall were 112 ms and 102 ms, respectively. Case 2 was a 75-year-old female with DCM and nonspecific intraventricular conduction delay. The QRS duration during LBBP was 156 ms and Stim-V6RWPT was 66 ms. LBBP-LV at the LV mid-anterolateral wall, LV mid-lateral wall, and LV mid-posterolateral wall were 96 ms, 107 ms, and 121 ms, respectively. In conclusion, LBBP-LV at the LV mid-lateral area was relatively long. If LBBP does not improve LV conduction disturbances, LOT-CRT may be more effective. Learning objective: The efficacy of left bundle branch pacing (LBBP) for cardiac resynchronization therapy (CRT) has been reported. However, if the conduction time from pacing to the left ventricular (LV) lateral area during LBBP is long, LBBP may not improve LV conduction disturbance, resulting in ineffective CRT. In such cases, more effective CRT would be expected with LV lead implantation at the area of the LV conduction delay during LBBP.

Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations.

Introduction: Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, is the standard treatment for patients with naive EGFR-mutant NSCLC. Nevertheless, information on how the mutation subtype affects disease progression after the failure of OSI treatment is scarce. Methods: We retrospectively reviewed patients with EGFR-mutant NSCLC who received OSI as a first-line treatment between April 2015 and December 2021. Results: This study included 229 patients. The objective response rate was 71%, with intracranial and extracranial response rates of 71% and 90%, respectively. The median progression-free survival was 23.3 mo (95% confidence interval [CI]: 19.6-26.7), and the median overall survival was 33.7 mo (95% CI: 31.3-58.6). Multivariate analysis revealed that the EGFR exon 21 L858R point mutation (L858R) (hazard ratio [HR] = 1.56, 95% CI: 1.04-2.34, p = 0.0328) and liver metastasis (HR = 2.63, 95% CI: 1.53-4.49, p = 0.0004) were significant predictors of progression-free survival in OSI treatment. The concomitant disease progression involving the central nervous system metastasis was significantly more common in patients with L858R (p = 0.048), whereas concomitant disease progression involving primary lesions was significantly more common in patients with exon 19 deletion mutation (p = 0.01). In addition, the probability of disease progression over time was higher for L858R compared with that for exon 19 deletion mutation, in patients with central nervous system metastasis (log-rank test, p = 0.027). Conclusions: The mutation subtype had an impact not only on the clinical outcome of the first-line OSI treatment but also on progression patterns after OSI treatment in patients with NSCLC harboring EGFR mutations.

The remarkable antitumor efficacy of corticosteroid treatment in patients with refractory thymomas.

BACKGROUND: Some case reports have found that corticosteroid treatments shrunk thymoma lesions remarkably after the failure of chemotherapy or surgery. However, few studies have comprehensibly evaluated the antitumor effects of corticosteroids in patients with invasive thymomas. METHODS: We reviewed the medical records of 13 consecutively enrolled patients with locally advanced or metastatic thymomas treated via corticosteroid monotherapies from January 2010 to March 2021 in our institute. A Cox's proportional hazard model and the Kaplan-Meier method were used to identify factors associated with survival. RESULTS: The median follow-up time was 26 months (range, 13-115 months). The median initial dose of corticosteroid was 0.90 mg/kg/day prednisolone equivalent (range, 0.4-1.1 mg/kg/day). Of the 13 cases, 7 (53.8%, 95% CI: 0.25-0.81) exhibited a partial response and 5 (38.5%, 95% CI: 0.14-0.68) stable disease. The median progression-free survival was 5.7 months [95% confidence interval (CI): 1.5-9.6 months]. The median overall survival was 25.3 months (95% CI: 7.1-not attained). The median duration of corticosteroid use was 3 months (range, 1-64 months). Patients with WHO subtype B thymomas exhibited a better overall response rate to corticosteroids than did patients with other disease subtypes (75%, 95% CI: 0.19-0.99). Adverse events of Grade 3 or more were not observed. CONCLUSIONS: Corticosteroids are clinically valuable for patients with thymomas.

Efficacy and safety of chemoimmunotherapy in advanced non-small cell lung cancer patients with antibiotics-induced dysbiosis: a propensity-matched real-world analysis.

PURPOSE: The gut microbiota is hypothesized as a prognostic biomarker for cancer immunotherapy. Antibiotic-induced dysbiosis negatively affects the clinical outcomes of immunotherapy. However, the effect of dysbiosis on the efficacy and safety of Chemoimmunotherapy (chemo-IOs), the frontline standard of care, in advanced non-small cell lung cancer (NSCLC) remains unknown. We aimed to compare the efficacy and safety of chemo-IOs in patients exposed to antibiotics before treatment with those of patients who were not exposed. METHODS: We retrospectively reviewed patients with advanced NSCLC treated with first-line chemo-IOs between 2018 and 2020 at the National Cancer Center Hospital. The patients were divided into two groups: those exposed to antibiotics within 30 days before induction therapy (ABx group) and those did not antibiotics (Non-ABx group). Propensity score matching was used to control for potential confounding factors. Clinical outcomes including progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared. RESULTS: Of 201 eligible patients, 21 were in the ABx group, and 42 were in the non-ABx group after propensity score matching. No differences in PFS or OS emerged between the two groups (ABx group vs. Non-ABx group) (PFS:7.0 months vs. 6.4 months, hazard ratio [HR] 0.89; 95% confidence interval [CI], 0.49-1.63, OS:20.4 months vs. 20.1 months, HR 0.87; 95% CI 0.44-1.71). The frequency of irAEs before propensity score matching was similar across any-grade irAEs (39.4% vs. 42.9%) or grade 3 or higher irAEs (9.1% vs. 11.3%). CONCLUSION: Antibiotic-induced dysbiosis may not affect the efficacy of chemo-IOs in patients with advanced NSCLC.

Clinical significance of inter-assay discrepancy in PD-L1 evaluation for the efficacy of pembrolizumab in advanced NSCLC with high PD-L1 expression.

INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for the efficacy of anti-programmed cell death receptor-1/PD-L1 antibodies in advanced non-small cell lung cancer (NSCLC). Although several assays have been approved for evaluating PD-L1 expression status, inter-assay discordance has been observed between some assays. The clinical significance of these discrepancies is still unclear. METHODS: We retrospectively reviewed treatment-naïve NSCLC patients whose PD-L1 expression was evaluated using both 22C3 and SP142 assays. Among those, efficacy analysis was performed for patients with PD-L1 tumor proportion score (TPS) ≥ 50 % (22C3), who had received first-line pembrolizumab monotherapy. Additionally, transcriptome analysis was conducted in the available tumors with TPS ≥ 50 % to investigate the distinct immune profiles that accompany inter-assay discordance. RESULTS: In total, 611 patients were eligible. Among 198 patients with TPS ≥ 50 %, 91 (46 %) had tumor cell score ≤ 1 (SP142, i.e., inter-assay discrepancy). In the 52 patients who received first-line pembrolizumab monotherapy, treatment efficacy was significantly lower in patients with the discrepancy than that in those without (objective response rate: 18 % vs. 83 %, p < 0.001; median progression-free survival [months]: 3.2 vs. 8.3, p < 0.001). Transcriptome analysis revealed significantly more CD274 splice variants with aberrant 3'-terminal sequences in tumors with the inter-assay discrepancy than in those without. CONCLUSION: The inter-assay discrepancy in the PD-L1 status of tumor cells between the 22C3 and SP142 assays, reflecting an imbalance in the CD274 splice variants, could be a biomarker for primary resistance against pembrolizumab monotherapy in high PD-L1-expressing NSCLCs.