担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lung Cancer  

Introduction: Uncommon epidermal growth factor receptor (EGFR) mutations (UCM) account for approximately 10% of EGFR-mutant lung adenocarcinoma (LUAD) cases; however, their prognostic impact remains unclear. This study aimed to evaluate postoperative outcomes in patients with UCM compared to those with common mutations (CM) using a large multicenter database. Materials and methods: This retrospective study included 1,636 patients with EGFR-mutant LUAD who underwent complete resection between 2015 and 2018 at 21 Japanese institutions. Patients were classified into the CM and UCM groups. Recurrence-free survival (RFS), overall survival (OS), lung cancer-specific survival (LCSS), and survival after recurrence (SAR) were analyzed using univariable and multivariable analyses and the inverse probability of treatment weighting (IPTW) method. Results: Among the patients, 1,441 (88.1%) had CM and 195 (11.9%) had UCM. RFS was comparable between the groups. However, patients with UCM showed significantly shorter OS and LCSS than those with CM (OS: multivariable hazard ratio [HR] 1.538, 95% confidence interval [CI] 1.003–2.359; LCSS: multivariable HR 1.803, 95% CI 1.064–3.056). This trend was consistently validated using IPTW methods. SAR was also significantly shorter in patients with UCM. Subtype-specific analyses revealed that patients with exon 20 insertions (Ex20ins) had a significantly worse prognosis than those with other UCMs. Conclusion: Patients with UCM had significantly worse OS, LCSS, and SAR than those with CM despite similar RFS. These survival disadvantages in UCM were strongly associated with the Ex20ins subtype. These findings highlight the urgent need for novel perioperative treatments for patients with UCM, especially Ex20ins.

DOI： 10.1016/j.lungcan.2026.108908

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Cardio Thoracic Surgery  

Objectives: Osteopenia is an independent risk factor for a poor prognosis in several malignant tumours. However, its significance in lung cancer is unclear. In this retrospective cohort study, we aimed to evaluate the prognostic impact of preoperative osteopenia in patients with surgically resected non-small cell lung cancer. Methods: We included 546 patients who underwent curative resection for clinical stage I-IIIA non-small cell lung cancer at our institute during 2013-2018. Bone mineral density was evaluated with computed tomographic measurement of pixel density in the core at the bottom of the 11th thoracic vertebra. The cutoff value was 148 and 111 Hounsfield units for men and women, respectively, based on the time-dependent receiver operating characteristic curve for overall survival. Patients were divided into osteopenia and non-osteopenia groups, and the associations of osteopenia with clinicopathological features and prognosis were analyzed. Results: Two hundred fifty-one patients (46.0%) were classified into the osteopenia group. The rates of patients ≥70 years old and ever-smokers in the osteopenia group were higher than those in the non-osteopenia group. The 5-year overall survival (77.1% vs 91.5%) and recurrence-free survival (63.7% vs 80.0%) rates of the osteopenia group were worse than those of the non-osteopenia group. Multivariable analysis revealed that osteopenia was an independent poor prognostic factor for overall survival (hazard ratio [HR]: 2.2, 95% confidence interval [CI], 1.38-3.51, P < .001) and recurrence-free survival (hazard ratio: 1.5, 95% CI, 1.05-2.11, P ¼ .024). Conclusions: Preoperative osteopenia is an independent poor prognostic factor for patients with resected clinical stage I-IIIA non-small cell lung cancer.

DOI： 10.1093/ejcts/ezaf481

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Thoracic and Cardiovascular Surgery  

Objective: Living-donor lobar lung transplantation (LDLLT) with a single lobar graft is required when a small pediatric patient receives an oversized graft or only one donor is available. This study aimed to evaluate the posttransplant outcomes of single living-donor lobar lung transplantation (SLDLLT). Methods: A total of 110 LDLLTs, including 16 SLDLLTs and 94 bilateral living-donor lobar lung transplantations (BLDLLTs), were performed from 2008 to 2021. Patient characteristics and posttransplant outcomes were compared between the 2 groups. Results: The SLDLLT group included 14 pediatric patients and 2 adult patients, whereas the BLDDT group included 20 pediatric patients and 74 adult patients. Median functional size matching with forced vital capacity was similar between SLDLLT (64.5%; range, 38.0%-94.6%) and BLDLLT (65.2%; range, 37.3%-247.3%) (P = .379). Early posttransplant outcomes did not differ significantly between the 2 groups. Retransplantation was performed in 3 of 4 patients who underwent SLDLLT and 2 of 19 patients who underwent BLDLLT, all of whom developed chronic lung allograft dysfunction. The 5- and 10-year survival rates after SLDLLT were both 93.3% and comparable with those after BLDLLT (P = .057). Conclusions: SLDLLT may produce acceptable short- and long-term posttransplant outcomes when meticulous anatomical and functional size matching is implemented; nevertheless, retransplantation may be required when chronic lung allograft dysfunction develops in a single lobar graft.

DOI： 10.1016/j.jtcvs.2026.01.009

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担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1016/j.annonc.2025.10.611

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Respirology Case Reports  

A 10-year-old patient underwent metallic stent implantation in the trachea and right main bronchus for tracheal stenosis caused by extramural compression from a posterior mediastinal malignant rhabdoid tumour. Following chemoradiotherapy, the tumour entered remission. One year and 6 months after stent placement, refractory granulation tissue formed in the tracheal stent. The stent was removed using a rigid bronchoscope under general anaesthesia with extracorporeal membrane oxygenation to prevent granulation recurrence. Thereafter, no recurrence of granulation occurred in the tracheal stent within 2 years; however, refractory granulation developed in the right main bronchial stent. Removal of the right main bronchial stent was considered. However, as sputum frequently adhered to the retention suture of the stent, the retention suture was removed using a flexible bronchoscope. Since then, there has been no granulation for more than 10 months.

DOI： 10.1002/rcr2.70411

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

SLC38A7遺伝子がコードするSNAT7はリソソームからのグルタミン輸送を促進するトランスポーターである。本研究では、非小細胞肺癌(NSCLC)で最も頻度の高いサブタイプである肺腺癌におけるSNAT7発現と臨床病理学的特徴や予後との関連性について検討した。免疫組織化学染色(IHC)を完全に切除された肺腺癌患者373例(年齢34～88歳)の検体について実施した。IHC分析に基づき、患者をSNAT7高発現群226例(60.6%)とSNAT7低発現群147例(39.4%)に分類した。SNAT7高発現は、SNAT7低発現と比較して、男性、喫煙歴、高い最大標準取込値、進行した病理学的病期、胸膜・リンパ管・血管浸潤と有意に関連していた。SNAT7高発現群は、無再発生存率および全生存率が著しく低かった。多変量解析の結果、SNAT7高発現は無再発生存率に対する独立した予後因子であることが示された。さらに、SLC38A7のノックダウンは、肺腺癌細胞株においてG1期停止を伴う増殖の低下を誘導した。以上より、SNAT7が腫瘍の悪性度促進に重要な役割を果たし、肺腺癌における予後不良と有意に関連していることが示された。

担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1007/s10147-025-02851-w

PubMed

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：シュプリンガー・ジャパン(株)  

担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：European Journal of Cardio Thoracic Surgery  

Objectives Adjuvant osimertinib is currently the standard of care after pulmonary resection in patients with non-small cell lung cancer (NSCLC) harbouring an activating epidermal growth factor receptor (EGFR) mutation. Several guidelines recommended up to 4 cycles of adjuvant platinum-doublet before adjuvant osimertinib treatment. However, whether adjuvant platinum-doublet prolongs the overall survival (OS) of patients with EGFR-mutated NSCLC as it did in the unselected LACE meta-analysis cohort is unclear. Methods A multicentre retrospective observational study was conducted at 21 centres in Japan, enrolling 4181 patients with lung adenocarcinoma who received pulmonary resection between 2015 through 2018. In this study, we compared the efficacy of adjuvant platinum-doublet between EGFR mutated and EGFR wild-type cohort focusing on 706 patients with pathological stage II-III disease. Propensity score matching (1:1 ratio, caliper = 0.2) was used to balance patient characteristics (age, sex, smoking, preoperative performance status, pathological stage, and EGFR status) between patients who received adjuvant treatment and those who did not. Results Among the 706 patients, 391 (55%) received adjuvant platinum-doublet. After 1:1 propensity score matching, patient characteristics were well balanced in the 2 groups (201 patients each). In subgroup analysis of overall and recurrence-free survival, the hazard ratios of adjuvant treatment were similar in the EGFR-mutated and EGFR wild-type groups (eg, OS, 0.56 [95% CI, 0.29-1.10] and 0.52 [95% CI, 0.33-0.82] in EGFR-mutated and EGFR wild-type subgroup, respectively). Conclusions Adjuvant platinum-doublet chemotherapy showed similar trends of benefit in the EGFR-mutated and EGFR wild-type subgroups.

DOI： 10.1093/ejcts/ezaf239

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Background: Sublobar resection is the standard procedure for cT1N0 stage I non-small cell lung cancer (NSCLC) size ≤2 cm. However, its efficacy for high-risk pathologic stage I cases with a preoperative diagnosis of cT1N0 stage I NSCLC size ≤2 cm remains unclear. This study compared the outcomes of sublobar resection with those of lobectomy from a pathologic perspective. Methods: A multicenter retrospective analysis of patients with pathologic stage I NSCLC was performed following the eighth edition of tumor-node-metastasis (TNM) classification. The study enrolled patients with completely resected clinical stage I NSCLC and a tumor size of ≤2 cm determined by computed tomography. High-risk pathologic feature was defined as evidence of pleural invasion, lymphovascular invasion, or invasive component (>2 cm). Survival rates were compared between the patients who underwent sublobar resection and those who underwent lobectomy. Results: The study enrolled 875 patients (715 [81.7%] low-risk and 160 [18.3%] high-risk NSCLC patients). The high-risk patients in the lobectomy group had significantly better 5-year recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) rates than those in the sublobar resection group (RFS: 80.5% vs 44.3% [P < 0.001], OS: 84.9% vs 54.6% [P = 0.001], CSS: 91.6% vs 72.4% [P = 0.019]). In the low-risk group, lobectomy and sublobar resection resulted in equivalent 5-year RFS, OS, and CSS (RFS: 92.8% vs 88.6% [P = 0.13], OS: 93.8% vs 91.7% [P = 0.26], CSS: 98.9% vs 98.4% [P = 0.67]). Multivariate analysis indicated that sublobar resection was independently associated with poor RFS, OS, and CSS for the high-risk patients. Conclusions: Sublobar resection is feasible for low-risk pathologic stage I NSCLC, whereas lobectomy may have a prognostic benefit for high-risk NSCLC.

DOI： 10.1245/s10434-024-16700-z

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

DOI： 10.1245/s10434-025-16907-8

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担当区分：筆頭著者,　責任著者   記述言語：日本語   出版者・発行元：日本肺高血圧・肺循環学会  

担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1016/j.clc.2024.12.011

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：Clinical Lung Cancer  

Background: While Epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LUAD) has favorable outcomes with targeted therapy, early-stage prognosis remains influenced by pathological factors and central nervous system (CNS) recurrence. The study aimed to clarify prognostic factors in pathological stage (pStage) I EGFR mutation-positive LUAD. Methods: Between 2015 and 2018, 2,191 pStage I LUAD cases with known EGFR status (excluding EGFR testing after recurrence) who received anatomical resection were included from multiple institutions in Japan. Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed. Results: 1,073 (49.0%) cases harbored EGFR mutations, including 419 (19.1%) with 19del and 529 (24.1%) with L858R. In cases with major EGFR mutation (n = 948), multivariate analysis showed that the absence of noninvasive area (NIA) (hazard ratio [HR]: 1.778, 95% confidence interval [CI]: 1.174-2.692, P = .0065), pStage (IA2 vs. IA1, HR: 2.079, 95% CI: 1.129-3.827, P = .0345; IA3 vs. IA1, HR: 4.009, 95% CI: 2.088-7.696, P = .0001; IB vs. IA1, HR: 5.280, 95% CI: 2.871-9.709, P < .0001), and presence of lymphatic invasion (HR: 1.855, 95% CI: 1.103-3.119, P = .0197) were independent predictors of shorter DFS, and only advanced pStage was an independent predictor of CNS recurrence (relative risk for pStage IA3 or more: 9.729, P < .0001). Conclusion: In EGFR mutation-positive pStage I LUAD, those without NIA, with higher pStage and lymphatic invasion were independent predictive factors for DFS, and pStage ≥ IA3 was an independent predictor of CNS recurrence.

DOI： 10.1016/j.cllc.2024.12.011

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：International Journal of Cancer  

The expression of programmed cell death-ligand 1 (PD-L1) and mutation in epidermal growth factor receptor (EGFR) are biomarkers used for perioperative treatment of lung adenocarcinoma. However, the clinical significance of PD-L1 expression in surgically resected EGFR-mutant lung adenocarcinoma remains unclear. We conducted a real-world database of patients with surgically resected lung adenocarcinoma from 2015 to 2018 was constructed across 21 centers in Japan. The association among PD-L1 expression, EGFR mutations, and prognosis was evaluated. Among 847 patients, PD-L1 expression was negative (tumor proportion score [TPS] < 1%) in 429 (51%), weakly positive (TPS = 1%–49%) in 275 (32%), and strongly positive (TPS ≥50%) in 143 (17%) patients. EGFR mutations were detected in 331 (39%) patients. PD-L1 expression was associated with poor recurrence-free survival (RFS) (p <.001) in both EGFR-mutant and wild-type patients. However, in EGFR-mutant patients, PD-L1 expression was not associated with overall survival (OS) (p =.506). Multivariable analysis confirmed an association between PD-L1 expression and RFS but not OS. Furthermore, in EGFR-mutant patients treated with EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment post-relapse, PD-L1 expression was not associated with overall response rate (p =.714), disease control rate (p =.554), or progression-free survival (p =.660). In conclusion, PD-L1 expression predicted poor RFS-independent EGFR status but did not show any association with OS in EGFR-mutant patients. The efficacy of post-relapse EGFR-TKI treatment was independent of PD-L1 expression. The significance of PD-L1 expression in perioperative EGFR-TKI therapy should be evaluated.

DOI： 10.1002/ijc.35270

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担当区分：筆頭著者,　責任著者   出版者・発行元：株式会社　医学書院  

DOI： 10.11477/mf.243232680730010120

CiNii Research

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Thoracic Surgery  

Background This real-world study investigated the feasibility and profile of adverse events (AEs) associated with neoadjuvant chemoimmunotherapy in patients with resectable non-small cell lung cancer (NSCLC) in the real world. Methods We conducted a multicenter retrospective study using real-world data of patients with resectable stage II or III NSCLC treated with neoadjuvant chemoimmunotherapy with nivolumab between March 2023 and July 2024 at 29 Japanese institutions. The safety, AE profiles, and risk factors for grade ≥3 AEs were evaluated. Results A total of 126 patients were analyzed. In the neoadjuvant phase, grade ≥3 treatment-related AEs and immune-related AEs (irAEs) occurred in 36 (28.6%) and 12 (9.5%) patients, respectively. One patient (0.8%) died of a neoadjuvant treatment-related cytokine storm AE and subsequent multiorgan failure. Definitive surgery after neoadjuvant treatment was performed in 114 patients (90.5%), with only 1 death within 90 days of surgery. Half of endocrine-related irAEs occurred in the postoperative phase. Among the demographic characteristics, a history of coronary artery disease was a significant risk factor for grade ≥3 treatment-related AEs (odds ratio, 16.556; 95% CI, 1.698-161.479; P = .016) and irAEs (odds ratio, 10.196; 95% CI, 1.193-87.166;, P = .034). Conclusions Real-world data from the era of neoadjuvant chemoimmunotherapy showed feasibility consistent with the results of randomized controlled trials. The incidence of grade ≥3 AEs was not particularly high but was clinically significant, and a history of coronary artery disease may be a predictor.

DOI： 10.1016/j.athoracsur.2025.09.054

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

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担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1245/s10434-024-15246-4

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

DOI： 10.1245/s10434-024-15177-0

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Background: Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified. Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance. Results: qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS. Conclusions: GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

DOI： 10.1245/s10434-024-15116-z

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：Clinical Lung Cancer  

Introduction: Atezolizumab following platinum chemotherapy and complete pulmonary resection has become the new standard of adjuvant care for patients with stage II-III non-small cell lung cancer (NSCLC) expressing programmed death-ligand 1 (PD-L1). However, the efficacy and safety of postoperative adjuvant therapy and subsequent atezolizumab in patients aged 75 and older have not been established. Methods: Patients with completely resected stage II–III NSCLC aged 75 and older will be prospectively registered in this single-arm phase II study. The enrolled patients will receive cisplatin plus vinorelbine (CDDP + VNR) followed by atezolizumab for up to 12 months. PD-L1 expression in at least 1% of cells will be confirmed by immunohistochemical staining. We plan to enroll 33 patients over 1 year at 25 institutions in Japan. The primary endpoint is the completion rate of adjuvant treatment (CDDP + VNR initiation to atezolizumab completion). Conclusion: The present study represents the first prospective trial of the tolerability of postoperative adjuvant therapy with immune checkpoint inhibitors in elderly individuals. The results of this trial might help promote postoperative adjuvant immunotherapy in the future for the elderly.

DOI： 10.1016/j.cllc.2024.01.009

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：European Journal of Cancer  

Objectives: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. Methods: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. Results: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2–3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. Conclusion: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

DOI： 10.1016/j.ejca.2024.113951

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：JAMA Network Open  

Importance: Biomarker testing for driver mutations is essential for selecting appropriate non-small cell lung cancer (NSCLC) treatment but is insufficient. Objective: To investigate the status of biomarker testing and drug therapy for NSCLC in Japan for identifying problems in treatment. Design, Setting, and Participants: The REVEAL cohort study included retrospective data collection and prospective follow-up from 29 institutions across Japan. Of 1500 patients diagnosed with advanced or recurrent NSCLC between January 1 and March 18, 2021, 1479 were eligible. Cases recognized at the wrong clinical stage (n = 12), diagnosed outside the study period (n = 6), not treated according to eligibility criteria before recurrence (n = 2), and with deficient consent acquisition procedure (n = 1) were excluded. Main Outcomes and Measures: The primary end point was the biomarker testing status. Treatment-related factors were examined. Results: Among the 1479 patients included in the analysis, the median age was 72 (range, 30-95) years; 1013 (68.5%) were men; 1161 (78.5%) had an Eastern Cooperative Oncology Group performance status 0 or 1; 1097 (74.2%) were current or past smokers; and 947 (64.0%) had adenocarcinoma. Biomarker status was confirmed in 1273 patients (86.1%). Multigene testing was performed in 705 cases (47.7%); single-gene testing, in 847 (57.3%); and both, in 279 (18.9%). Biomarker testing was performed for EGFR in 1245 cases (84.2%); ALK, in 1165 (78.8%); ROS1, in 1077 (72.8%); BRAF, in 803 (54.3%); and MET, in 805 (54.4%). Positivity rates among 898 adenocarcinoma cases included 305 (34.0%) for EGFR, 29 (3.2%) for ALK, 19 (2.1%) for ROS1, 11 (1.2%) for BRAF, and 14 (1.6%) for MET. Positivity rates among 375 nonadenocarcinoma cases were 14 (3.7%) for EGFR, 6 (1.6%) for ALK, 1 (0.3%) for ROS1, 3 (0.8%) for BRAF, and 8 (2.1%) for MET. Poor physical status, squamous cell carcinoma, and other comorbidities were associated with hampered multigene testing. Targeted therapy was received as first-line treatment by 263 of 278 cases (94.6%) positive for EGFR, 25 of 32 (78.1%) positive for ALK, 15 of 24 (62.5%) positive for ROS1, 9 of 12 (75.0%) positive for BRAF, and 12 of 19 (63.2%) positive for MET. Median overall survival of patients with positive findings for driver gene alteration and who received targeted therapy was 24.3 (95% CI, not reported) months; with positive findings for driver gene alteration and who did not receive targeted therapy, 15.2 (95% CI, 7.7 to not reported) months; and with negative findings for driver gene alteration, 11.0 (95% CI, 10.0-12.5) months. Multigene testing for nonadenocarcinomas and adenocarcinomas accounted for 705 (47.7%) of all NSCLC cases. Conclusions and Relevance: These findings suggest that multigene testing has not been sufficiently implemented in Japan and should be considered prospectively, even in nonadenocarcinomas, to avoid missing rare driver gene alterations..

DOI： 10.1001/jamanetworkopen.2023.47700

Scopus

担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：Molecular Psychiatry  

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2–3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

DOI： 10.1038/s41380-023-02141-9

Web of Science

Scopus

PubMed

担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1016/j.annonc.2023.09.234

Web of Science

担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：European Journal of Cancer  

Background: We previously validated in European patients with NSCLC treated with programmed death-1 (PD-1) checkpoint inhibitors the cumulative detrimental effect of concomitant medications. Materials and methods: We evaluated the prognostic ability of a “drug score” computed on the basis of baseline corticosteroids, proton pump inhibitors, and antibiotics, in an independent cohort of Japanese patients with advanced NSCLC treated with PD-1 monotherapy. Subsequently, we assessed the impact of baseline probiotics on the score's diagnostic ability and their interaction with antibiotics in influencing survival. Results: Among the 293 eligible patients, good (19.5 months), intermediate (13.4 months), and poor (3.7 months) risk groups displayed a significantly different overall survival (OS) (log-rank test for trend: p = 0.016), but with a limited diagnostic ability (C-index: 0.57, 95%CI: 0.53–0.61), while no significant impact on progression-free survival (PFS) was reported (log-rank test for trend: p = 0.080; C-index: 0.55, 95%CI: 0.52–0.58). Considering the impact of the probiotics∗antibiotics interaction (p-value 0.0510) on OS, we implemented the drug score by assigning 0 points to concomitant antibiotics and probiotics. With the adapted drug score good, intermediate, and poor risk patients achieved a median OS of 19.6 months, 13.1 months, and 3.7 months, respectively, with a similar diagnostic ability (log-rank test for trend: p = 0.006; C-index: 0.58, 95%CI: 0.54–0.61). However, the diagnostic ability for PFS of the adapted score was improved (log-rank test for trend: p = 0.034; C-index: 0.62, 95%CI: 0.54–0.69). Conclusions: Although we failed to validate the drug score in this independent Japanese cohort, we showed that probiotics may have an antibiotic-dependent impact on its prognostic value. Further investigation looking at the effect of concomitant medications and probiotics across cohorts of different ethnicities is warranted.

DOI： 10.1016/j.ejca.2022.06.002

Web of Science

Scopus

PubMed

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