Language：English  

DOI： 10.1038/s41420-025-02673-9

PubMed

Language：English  

DOI： 10.3233/SHTI250996

PubMed

Language：English  

DOI： 10.1007/s10147-025-02771-9

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PubMed

Language：English   Publisher：Mediastinum  

Background and Objective: Thymic epithelial tumors (TETs) are the most common mediastinal neoplasms and include thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms (TNENs). The staging system of TETs has been based on the Masaoka-Koga system or the 8th edition of the TNM classification, which does not consider tumor size as a T descriptor. The 9th edition of the TNM classification was released in January 2025, and tumor size was incorporated, with the T1 category subdivided into T1a (≤5 cm) and T1b (>5 cm). Thus, the clinical importance of tumor size in TETs has attracted increasing attention. This review summarizes previous reports focusing on tumor size as a prognostic factor for TETs and highlights the association between tumor size, prognosis, and clinicopathological features of TETs. Methods: The literature search was performed using PubMed for the narrative review. Eligible articles were published in English between January 1, 2004 and December 1, 2024. Key Content and Findings: We identified 35 articles investigating the effect of TET tumor size. Tumor size assessed using surgical specimens was a useful predictor for prognosis in all stages of thymomas. A large tumor size was associated with tumor invasion into adjacent tissues, which contributes to advanced-stage disease and incomplete resection. Thus, large tumor size was shown to be related to a high recurrence rate and poor prognosis. In addition, tumor size had a strong prognostic impact in patients with early-stage thymoma. Consistent with the evaluation of surgical specimens, preoperative assessment of tumor size using computed tomography also contributed to the postoperative prognosis. Furthermore, evaluation of tumor size may help determine treatment strategies, such as surgical approaches and adjuvant radiotherapy. However, the prognostic role of tumor size in thymic carcinoma and TNENs was unclear because of their rarity. Conclusions: Primary tumor size was identified as an important prognostic factor in patients with thymoma. However, the significance of thymic carcinoma or TNEN remains unclear. Further prospective large-scale studies are warranted to investigate the clinical significance of tumor size in TETs.

DOI： 10.21037/med-25-3

Scopus

PubMed

Language：English   Publisher：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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PubMed

Language：English   Publisher：Annals of Surgical Oncology  

Background: DNA polymerase delta 2 (POLD2) plays a crucial role in DNA repair and replication. POLD2 is upregulated and related to poor prognosis in several types of cancer. However, the biological and clinical importance of POLD2 in lung adenocarcinoma remains unclear. Patients and Methods: We investigated the relationship between POLD2 expression and tumor malignancy in lung adenocarcinoma cell lines. Immunohistochemistry (IHC) was performed on 373 patients with completely resected lung adenocarcinoma, and the association between POLD2 expression, clinicopathological features, and prognosis was examined. Results: POLD2 knockdown decreases cell proliferation and migration, resulting in apoptosis and G1 arrest in the cell cycle in lung adenocarcinoma cells. Additionally, POLD2 knockdown attenuates MYC expression, which may decrease the expression of cyclin-dependent kinases 4 and 6, pRb, Rb, and E2F1. Furthermore, among 373 patients with completely resected lung adenocarcinoma, smoking history, advanced pathological stage, and vascular invasion were significantly more prevalent in patients with high POLD2 expression (n = 146, 39.3%) than in those with low POLD2 expression (n = 227, 60.7%). Patients with high POLD2 expression also had a significantly worse recurrence-free survival (RFS) and overall survival. In the multivariable analysis, high POLD2 expression was an independent poor prognostic factor of RFS. Conclusions: We provide the possibility of POLD2 as a potential new therapeutic target because high POLD2 expression is associated with high malignancy and poor prognosis in specimens from patients with lung adenocarcinoma and POLD2 depletion triggers the suppression of cell migration, cell cycle progression, and cell proliferation.

DOI： 10.1245/s10434-025-17118-x

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PubMed

Language：English   Publisher：Annals of Surgical Oncology  

Background: Tumor microvasculature is an important component of the tumor microenvironment (TME), and it has been reported that tumor microvasculature induces TME to become immunosuppressive via vascular endothelial growth factor. However, the significance of this in adenocarcinoma with epidermal growth factor receptor (EGFR) common mutations has not been fully investigated. Methods: We analyzed 262 patients with adenocarcinoma harboring EGFR common mutations who underwent surgery at Kyushu University Hospital between 2006 and 2021. Microvessel density (MVD) was calculated by CD34 immunohistochemistry. Patients were categorized into high and low MVD status, which was compared with the clinicopathological characteristics. Results: A total of 136 (51.9%) patients had L858R mutation, and 126 (48.1%) had Exon 19 Del. Regarding MVD status; 133 patients (50.8%) were classified as high and 129 (49.2%) as low. Fisher’s exact test revealed a significant association of high MVD status with high CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.0187), low GZMB+ TILs (p = 0.0019), and high Foxp3+ TILs (p = 0.0003). On multivariate analysis, MVD status was significantly associated with Foxp3+ TILs and GZMB+ TILs. Fisher’s exact test also revealed that tumors with L858R mutation had a high MVD status (p = 0.0136) compared with tumors with deletions of exon 19 (Exon 19 Del), and multivariate analysis revealed that L858R mutation was significantly associated with high MVD status. Conclusions: In adenocarcinomas harboring EGFR common mutations, abundant tumor microvasculature might induce the TME to be immunosuppressive. Tumors with L858R mutation compared with Exon 19 Del might be more likely to form an immunosuppressive TME owing to the abundance of tumor microvasculature.

DOI： 10.1245/s10434-024-16806-4

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PubMed

Language：English   Publisher：Learning Health Systems  

Introduction: The reliability of data-driven predictions in real-world scenarios remains uncertain. This study aimed to develop and validate a machine-learning-based model for predicting clinical outcomes using real-world data from an electronic clinical pathway (ePath) system. Methods: All available data were collected from patients with lung cancer who underwent video-assisted thoracoscopic surgery at two independent hospitals utilizing the ePath system. The primary clinical outcome of interest was prolonged air leak (PAL), defined as drainage removal more than 2 days post-surgery. Data-driven prediction models were developed in a cohort of 314 patients from a university hospital applying sparse linear regression models (least absolute shrinkage and selection operator, ridge, and elastic net) and decision tree ensemble models (random forest and extreme gradient boosting). Model performance was then validated in a cohort of 154 patients from a tertiary hospital using the area under the receiver operating characteristic curve (AUROC) and calibration plots. Results: To mitigate bias, variables with missing data related to PAL or those with high rates of missing data were excluded from the dataset. Fivefold cross-validation indicated improved AUROCs when utilizing key variables, even post-imputation of missing data. Dichotomizing continuous variables enhanced performance, particularly when fewer variables were employed in the decision tree ensemble models. Consequently, regression models incorporating seven key variables in complete case analysis demonstrated superior discriminatory ability for both internal (AUROCs: 0.77–0.84) and external cohorts (AUROCs: 0.75–0.84). These models exhibited satisfactory calibration in both cohorts. Conclusions: The data-driven prediction model implementing the ePath system exhibited adequate performance in predicting PAL post-video-assisted thoracoscopic surgery, optimizing variables and considering population characteristics in a real-world setting.

DOI： 10.1002/lrh2.10469

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PubMed

Language：English   Publisher：Annals of Surgical Oncology  

Background: Thymic epithelial tumor (TET) staging has been based on Masaoka-Koga systems or the 8th edition of the TNM classification, which do not use tumor size as a T descriptor. The 9th edition of the TNM classification incorporates tumor size; however, the study on which this classification is based included only 4.4% of patients from North America. This study investigated the prognostic impact of primary tumor size in TET patients in the US population. Methods: Using data from the National Cancer Database (NCDB), we analyzed patients with surgically resected TETs diagnosed in 2004–2020. Survival analysis was performed by using the Kaplan–Meier method and multivariate Cox regression analyses; propensity score matching (PSM) analyses were performed. Thymoma data from our facilities (n = 166) were used for validation. Results: Of 4,151 and 647 thymoma and thymic-carcinoma patients, respectively, we classified 1,618 and 268 patients into small-tumor (primary tumor size ≤ 5 cm) and large-tumor groups, respectively. Thymoma patients in the small-tumor group had a significantly longer overall survival (OS) than those in the large-tumor group (>5 cm) (median OS 193.2 vs. 161.4 months, respectively; log-rank P < 0.0001; hazard ratio 0.72; 95% confidence interval 0.64–0.82). After PSM, multivariate analysis showed that tumor size was an independent prognostic factor for OS (P < 0.0001). Validation cohort analysis supported these results. Tumor size did not have a significant impact on OS (P = 0.0994) in thymic-carcinoma patients. Conclusions: Tumor size in thymoma, but not in thymic carcinoma, was an important prognostic factor in the U.S. population.

DOI： 10.1245/s10434-024-16732-5

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PubMed

Language：English   Publisher：International Journal of Clinical Oncology  

Background: Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated. Materials and methods: We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. Results: Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan–Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group. Conclusion: Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.

DOI： 10.1007/s10147-024-02640-x

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PubMed

Language：English   Publisher：The Japanese Society of Internal Medicine  

<p><b>Background and objective </b>Endobronchial ultrasound with a guide sheath (EBUS-GS) is used to accurately position a bronchoscope in lung lesions using a guide sheath. Previous studies have focused on diagnostic success as the endpoint. The achievement of 'within' defined as reaching the lesion, is considered crucial in EBUS-GS procedures. This study investigated cases wherein 'within' is likely to be achieved and cases that can be diagnosed after achieving 'within'. </p><p><b>Methods </b>This retrospective study evaluated 258 bronchoscopic examinations using EBUS-GS. We analyzed the relationship between patient background, lesion size and characteristics, achieving 'within', definitive diagnosis after achieving 'within', and complications. </p><p><b>Results and Conclusion </b>A multivariate analysis revealed that lesion size ≥20 mm (odds ratio 12, 95% confidence interval [CI]: 6.0-21, p<0.01) and lesions with solid components (odds ratio 13, 95% CI: 1.3-120, p=0.03) were associated with achieving 'within'. For cancer cases, lesion size ≥20 mm was associated with a higher diagnostic rate following achieving 'within' than smaller lesions (odds ratio 4.23, 95% CI: 1.38-12.9, p=0.01). The occurrence of complications was linked to lesion size ≥20 mm (odds ratio 2.7, 95% CI: 1.02-6.9, p=0.045). The factors associated with 'within'-achieving bronchoscopy via EBUS-GS included lesion size ≥20 mm and solid components. Larger lesions were associated with a definitive diagnosis. Lesion size was a determinant in improving diagnostic rates, both for achieving within and for successful diagnosis after achieving 'within'. </p>

DOI： 10.2169/internalmedicine.5777-25

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PubMed

CiNii Research

Language：English   Publisher：Interdisciplinary Cardiovascular and Thoracic Surgery  

OBJECTIVES: Spread through air spaces (STAS) is considered a poor prognostic factor in patients with resected non-small lung cell cancer; however, the clinical significance of STAS extent remains unclear. We hypothesized that the further the tumour cells spread from the tumour edge, the worse the prognosis becomes. METHODS: This study retrospectively reviewed the data of 642 patients with completely resected pathological stage I-III non-small lung cell cancer between 2008 and 2018. The maximum spread distance (MSD) from the tumour edge to the farthest STAS was quantitatively evaluated, and STAS was categorized as limited (MSD ≤1000 μm) or extended (MSD >1000 μm), based on the median MSD. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS classification. RESULTS: Patients were classified into STAS-negative (n = 382, 59.6%), limited STAS (n = 130, 20.2%) and extended STAS (n = 130, 20.2%) groups. Extended STAS was associated with a high maximum standardized uptake value, advanced pathological stage and vascular invasion compared with limited STAS. The extended STAS group demonstrated significantly shorter RFS and OS than both the limited STAS and STAS-negative groups (both P < 0.001 for RFS; P = 0.007 and P < 0.001 for OS, respectively). Multivariable analysis showed that extended STAS was an independent prognostic factor for both RFS and OS (P < 0.001, P < 0.001, respectively). CONCLUSIONS: The distance from tumour edge to STAS affects prognosis in patients with completely resected non-small lung cell cancer.

DOI： 10.1093/icvts/ivae181

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PubMed

Language：English   Publisher：Chest  

Background: The eighth edition of lung cancer nodal staging assignment includes the location of lymph node metastasis, but does not include single-nodal and multiple-nodal descriptors. Research Question: Do the single-nodal and multiple-nodal statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Study Design and Methods: Using the National Cancer Database, we analyzed patients with pathologically staged N1 and N2 NSCLC. Nodal descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pathological single N2 (pSingle-N2), and pathological multiple N2 (pMulti-N2). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox regression models. Results: In the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 patients with NSCLC demonstrated pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2 disease, respectively. Patients with pMulti-N1 and pMulti-N2 disease showed a shorter survival than those with pSingle-N1 and pSingle-N2 disease, respectively (hazard ratio, 1.22 [P <.0001] for N1 and 1.39 [P <.0001] for N2). After adjusting age, sex, and histologic findings, the hazard ratio for pSingle-N2 compared with pMulti-N1 disease was 1.05 (P =.0031). Patients with pN1 disease were categorized by metastatic lymph node count (1, 2, 3, ≥ 4), showing significant prognostic differences among groups (P <.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy, or more; survival ≥ 30 days; ≥ 10 examined lymph nodes; and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708), analyses supported these results. Interpretation: Patients with NSCLC with one metastatic lymph node, whether in N1 or N2 stations, showed better survival than those with more than one lymph node involved. Patients with NSCLC with a single-skip N2 lymph node metastasis showed survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to four or more was sequentially prognostic.

DOI： 10.1016/j.chest.2024.06.3797

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PubMed

Language：English   Publisher：Transplant International  

Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% (p = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% (p < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% (p < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% (p < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms.

DOI： 10.3389/ti.2024.13227

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Language：English  

Web of Science

Language：English   Publishing type：Research paper (other academic)  

Web of Science

Language：English   Publisher：European Journal of Surgical Oncology  

Introduction: High recurrence rate following curative surgery for non-small cell lung cancer (NSCLC) presents a major clinical challenge. Understanding the site and timing of recurrence and their impact on post-recurrence survival (PRS) is important for optimal postoperative surveillance and therapeutic intervention. In this study, we investigated the influence of the time to recurrence (TTR) and initial recurrence site on PRS. Materials and methods: This multicentre prospective cohort study included patients who experienced recurrence after NSCLC resection between 2010 and 2015. The relationship between TTR and initial recurrence site, and their impact on PRS, was further evaluated. The hazard ratio (HR) for PRS was analysed using the Cox proportional hazards model. Results: Among 495 patients, the median TTR was 14 (range, 1–158) months; the mode of recurrence was 11 months. Early recurrence within 6 months was observed in 17 % of patients, and 68 % of patients showed recurrence within 2 years post-surgery. The HR for PRS was the highest in patients with a TTR within 6 months, and a noticeable decline was observed after the first 6 months. The HRs of TTRs beyond 2 years were not significantly different. The liver was a significantly unfavourable prognostic site for metastases (HR 2.2; P = 0.01), and metastases frequently recurred within 6 months after surgery. The timing of brain metastasis did not significantly impact the PRS. Conclusion: Earlier recurrence after surgery was associated with shorter PRS. In contrast, recurrences occurring >2 years after surgery do not significantly affect PRS.

DOI： 10.1016/j.ejso.2024.108374

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PubMed

Language：English   Publisher：Annals of Surgical Oncology  

Background: Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression. Patients and Methods: Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry. Results: There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ. Conclusion: Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.

DOI： 10.1245/s10434-024-15649-3

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PubMed

Language：English   Publisher：Journal of Thoracic Disease  

Background: The preoperative serum creatine kinase (CK) concentration is a prognostic factor for malignant diseases. We investigated the significance of CK in surgically resected thymic epithelial tumors and the relationship between CK and clinicopathological factors. Methods: We retrospectively evaluated the relationship between preoperative CK levels and prognosis in 120 patients with thymic epithelial tumors who underwent surgical resection at two centers. The cutoff for CK was determined by the standard value in our institution (<62 IU/L for men and <45 IU/L for women). The paravertebral muscle at the Th12 level was used to assess skeletal muscle area to investigate sarcopenia. Results: Eighteen patients (15.0%) were categorized into the low CK group. The CK level was not associated with age, sex, performance status, myasthenia gravis, and pathological findings. Preoperative serum albumin and total cholesterol concentrations were significantly lower in the low CK group than in the normal CK group (both P<0.001). Moreover, the Th12 muscle index was lower in the low CK group (P=0.03), indicating that low CK was related to sarcopenia. Kaplan-Meier curve analysis illustrated that patients in the low CK group had significantly shorter disease-free survival (DFS) and overall survival (OS) than those in the normal CK group (P=0.03 and P=0.002, respectively). Multivariate analysis identified low CK as an independent prognostic factor for DFS (P=0.03) and OS (P=0.005). Conclusions: Preoperative serum CK might reflect the host nutritional status in patients with resected thymic epithelial tumors; therefore, CK could be a biomarker of postoperative prognosis.

DOI： 10.21037/jtd-23-1797

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PubMed

Language：English   Publisher：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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Language：English  

Language：Japanese   Publisher：(NPO)日本肺癌学会  

目的. 日本肺癌学会は,2023年にアーリーキャリア支援委員会を設立.今回,学会員のニーズ・現状把握を目的にアンケート調査を実施した.方法. 日本肺癌学会会員7,734名を対象にSurveyMonkeyを用いて回答を依頼し,回答者個人の状況に関する質問6項目,アーリーキャリア支援委員会の企画する事業・講演会に関する質問が4項目であった.結果. 回答数は595名で回収率は7.7%.年齢分布は20～29歳21名(3.5%),30～39歳172名(28.9%),40～49歳226名(38.0%),50～59歳117名(19.7%),60歳以上59名(9.9%)であった.性別は男性444名(74.6%),女性149名(25.0%),無回答2名(0.3%)であった.実現の要望が多かった事業・講演会は,半数以上が「国際学会派遣」や「留学奨学金」,もしくは「キャリアアップのための講演会」と回答.他方,キャリア形成で支障となっていると感じる事項については回答者の43.7%が「医局などの人事制度」と回答した.結論. 学会員の多様な立場や価値観を踏まえた支援を立案,実施する必要性が改めて明らかとなった.(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jtho.2023.10.017

Language：English   Publishing type：Research paper (scientific journal)   Publisher：General Thoracic and Cardiovascular Surgery  

Objectives: In non-small cell lung cancer (NSCLC), T factor plays an important role in determining staging. The present study aimed to determine the validity of preoperative evaluation of clinical T (cT) factor by comparing radiological and pathological tumor sizes. Methods: Data for 1,799 patients with primary NSCLC who underwent curative surgery were investigated. The concordance between cT and pathological T (pT) factors was analyzed. Furthermore, we compared groups with an increase or decrease of ≥ 20% and groups with an increase or decrease of < 20% in the size change between preoperative radiological and pathological diameters. Results: The mean sizes of the radiological solid components and the pathological invasive tumors were 1.90 cm and 1.99 cm, respectively, correlation degree = 0.782. The group with increased pathological invasive tumor size (≥ 20%) compared with the radiologic solid component was significantly more likely female, consolidation tumor ratio (CTR) ≤ 0.5, and within cT1. Multivariate logistic analysis identified CTR < 1, cT ≤ T1, and adenocarcinoma as independent risk factors for increased pT factor. Conclusion: The radiological invasive area of tumors with cT1, CTR < 1, or adenocarcinoma on preoperative CT may be underestimated compared with pathological invasive diameter.

DOI： 10.1007/s11748-023-01938-3

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.21873/invivo.13402.

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research  

Background/Aim: Recent advances in surgery, such as thoracoscopic surgery, have made it possible to treat patients with chronic obstructive pulmonary disease (COPD) more safely than before. This study evaluated the short- and long-term prognosis of lobectomy in non-small cell lung cancer (NSCLC) patients with COPD. Patients and Methods: This retrospective, propensity-matched, cohort analysis was conducted from January 2014 to December 2018. Among 441 patients who underwent lobectomy for NSCLC, 158 (35.8%) had a preoperative diagnosis of COPD. Propensity-matched analysis, incorporating preoperative variables, was used to compare postoperative hospital stay and complications, and long-term prognosis between the groups. Results: Propensity matching estimated 145 patients in each group. There was no difference between the two groups for length of postoperative hospital stay (12 vs. 11 days, p=0.306). Postoperative complications were more frequent in the COPD group (24.1%) than in the non-COPD group (16.6%), but the difference was not significant (p=0.108). The 5-year overall survival rate was 86.2% in the COPD group and 82.1% in the non-COPD group after matching (p=0.580). The corresponding 5-year recurrence-free survival rate was 72.8% in the COPD group and 67.2% in the non-COPD group after matching (p=0.601). Conclusion: In case of Global Initiative for Chronic Obstructive Lung Disease (GOLD) I/II classification, COPD did not significantly worsen the prognosis of patients with NSCLC after lobectomy.

DOI： 10.21873/anticanres.16723

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1245/s10434-023-13864-y

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Annals of Surgical Oncology  

Background: Granzyme B (GZMB) is a serine protease produced by cytotoxic lymphocytes that reflects the activity of anti-tumor immune responses in tumor-infiltrating lymphocytes (TILs); however, the prognostic significance of GZMB+ TILs in lung adenocarcinoma is poorly understood. Methods: We analyzed 273 patients with pathological stage (pStage) I–IIIA lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We evaluated GZMB+ TIL counts by immunohistochemistry. We set the cut-off values at 12 cells/0.04 mm² for GZMB+ TILs and divided the patients into GZMB-High (n = 171) and GZMB-Low (n = 102) groups. Then, we compared the clinicopathological characteristics of the two groups and clinical outcomes. Programmed cell death ligand-1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression in tumor cells was also evaluated, and combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 were performed. Results: GZMB-Low was significantly associated with pStage II–III, PD-L1 positivity, and IDO1 positivity. Disease-free survival (DFS) and overall survival (OS) in the GZMB-Low group were significantly worse than in the GZMB-High group. In multivariable analysis, GZMB-Low was an independent prognostic factor for both DFS and OS. Furthermore, combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 showed that GZMB-Low with high expression of these immunosuppressive proteins had the worst prognosis. Conclusions: We analyzed GZMB+ TIL counts in lung adenocarcinoma and elucidated its prognostic significance and association with PD-L1 and IDO1. GZMB+ TIL counts might reflect the patient’s immunity against cancer cells and could be a useful prognostic marker of lung adenocarcinoma.

DOI： 10.1245/s10434-023-14085-z

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Language：English   Publisher：Cancer Science  

Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer. Comprehensive miRNA screening with target prediction programs and a dual-luciferase reporter assay identified miR-346, miR-328-3p, miR-326, and miR-330-5p as miRNAs that bind to the 3′-UTR of CD155 mRNA. Forced expression of these miRNAs suppressed CD155 expression in lung cancer cell lines. Immunohistochemical staining of CD155 in tissue specimens from 57 patients with lung adenocarcinoma revealed the median tumor proportion score for CD155 to be 68%. The abundance of miR-326 in these specimens with a low level of CD155 expression was significantly greater than in specimens with a high level (p < 0.005). Our results thus suggest that miR-326 negatively regulates CD155 expression in lung adenocarcinoma and might therefore play a role in the development of resistance to PD-1/PD-L1 inhibitors.

DOI： 10.1111/cas.15921

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DOI： 10.1038/s41598-023-42964-8.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.celrep.2023.112899

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research  

Background/Aim: Adjuvant therapy using third-generation tyrosine kinase inhibitors (TKI) demonstrated improved central nervous system (CNS) disease-free survival after surgery in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, the prognostic impact of CNS recurrence in surgical patients remains unknown. We evaluated the effect of CNS recurrence on post-recurrence survival (PRS) in patients with postoperatively recurrent NSCLC. Patients and Methods: We assessed the prognostic impact of CNS recurrence using a cohort from a prospective observational study (Kyushu University Lung Surgery Group Study 2: KLSS-2). Based on data from 340 patients in whom EGFR mutations were assessed among 498 total patients in the KLSS-2 cohort, factors related to CNS recurrence and prognosis after postoperative recurrence were analyzed. Results: We noted no marked differences in the presence of EGFR mutations (p=0.14) between patients with CNS recurrence and those without CNS recurrence. Among the patients tested for EGFR mutations with stage IV recurrences (n=219), survival analysis of patients with EGFR mutations showed that the CNS group had a significantly poorer PRS than the no-CNS group (MST: 36.8 vs. 43.9 months, p=0.035). In multivariate survival analysis of stage IV EGFR mutation-positive cases, recurrence in multiple organs and recurrence of brain metastases were independent poor prognostic factors (hazard ratio=2.2, p=0.029; hazard ratio=3.2, p=0.0006, respectively). Conclusion: Postoperative CNS recurrence was associated with a poor prognosis among patients with EGFR mutation-positive lung cancer in the period when third-generation EGFR-TKIs were not available. In EGFR mutation-positive lung cancer, prevention of CNS recurrence after surgery may improve post-recurrence prognosis.

DOI： 10.21873/anticanres.16532

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cancer Medicine  

Background: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. Materials and Methods: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. Results: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51–0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32–0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). Conclusion: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.

DOI： 10.1002/cam4.6110

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cancer Immunology Immunotherapy  

Background: Ectopic lymphoid formations are called tertiary lymphoid structures (TLSs). TLSs in cancer have been reported to be associated with good prognosis and immunotherapy response. However, the relationship between TLSs and lymph node (LN) metastasis is unclear. Methods: We analyzed 218 patients with radically resected lung adenocarcinoma. TLSs were defined as the overlap of T cell zone and B cell zone. Granzyme B ⁺ cells were defined as cytotoxic lymphocytes. We evaluated phenotypes of lymphocytes in TLSs, tumor-infiltrating lymphocytes (TILs) and LNs by immunohistochemistry. We divided the patients into mature TLS (DC-Lamp high) and immature TLS (DC-Lamp low) groups. The relationship between TLS maturation and clinicopathological factors was analyzed. Results: The mature TLS group was associated with significantly lower frequency of LN metastasis (P < 0.0001) and early cancer stage (P = 0.0049). The mature TLS group had significantly more CD8 ⁺ (P = 0.0203) and Foxp3 ⁺ (P = 0.0141) cells in TILs than the immature TLS group had. Mature TLSs were independently associated with a favorable overall survival (hazard ratio [HR] = 0.17, P = 0.0220) and disease-free survival (HR = 0.54, P = 0.0436). Multivariate analysis showed that mature TLS was an independent low-risk factor for LN metastasis (odds ratio = 0.06, P = 0.0003). The number of cytotoxic lymphocytes in LNs was higher in the mature TLS group than in the immature group (20.0 vs. 15.1, P = 0.017). Conclusion: Mature TLSs were associated with an increased number of cytotoxic lymphocytes in draining LNs, a lower frequency of LN metastasis, and favorable outcomes. Mature TLSs may support antitumor immunity by lymphocyte activation.

DOI： 10.1007/s00262-022-03353-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Thoracic Cancer  

Background: Long-term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non-small cell lung cancer (NSCLC). Here, we evaluated post-recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. Methods: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data (e.g., treatment and survival outcomes) were obtained and analyzed. Results: From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation-positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5-year survival rates for all cases were 64 months and 53.2%, respectively. The 5-year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence-free for more than 3 years after recurrence with only initial treatment. Conclusions: Although radical local therapy may be curative in some patients, chemotherapy including EGFR-TKI treatment is expected to provide long-term survival comparable to that of radical local therapy.

DOI： 10.1111/1759-7714.14911

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Interdisciplinary Cardiovascular and Thoracic Surgery  

OBJECTIVES: Sarcopenia correlates with poor prognosis in various malignancies. However, the prognostic significance of sarcopenia remains to be determined in patients with non-small-cell lung cancer who undergo surgery after receiving neoadjuvant chemoradiotherapy (NACRT). METHODS: We retrospectively reviewed the patients with stage II/III non-small-cell lung cancer who underwent surgery following NACRT. The paravertebral skeletal muscle area (SMA) (cm2) at the 12th thoracic vertebra level was measured. We calculated the SMA index (SMAI) as SMA/squared height (cm2/m2). Patients were divided into low and high SMAI groups, and the association of SMAI with clinicopathological factors and prognosis was assessed. RESULTS: The patients' [men, 86 (81.1%)] median age was 63 (21-76) years. There were 106 patients including 2 (1.9%), 10 (9.4%), 74 (69.8%), 19 (17.9%) and 1 (0.9%) patients with stage IIA, IIB, IIIA, IIIB and IIIC, respectively. Of the patients, 39 (36.8%) and 67 (63.2%) were classified in the low and the high SMAI groups, respectively. Kaplan-Meier analysis showed that the low group had a significantly shorter overall survival and disease-free survival than the high group. Multivariable analysis identified low SMAI as an independent poor prognostic factor for overall survival. CONCLUSIONS: Pre-NACRT SMAI correlates with poor prognosis; therefore, assessing sarcopenia based on pre-NACRT SMAI may help determine optimal treatment strategies and suitable nutritional and exercise interventions.

DOI： 10.1093/icvts/ivad020

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DOI： 10.21037/tcr-22-2104

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Annals of Surgical Oncology  

Background: Many inflammatory and nutritional markers have been used to predict prognosis in lung cancer. The C-reactive protein (CRP)-to-lymphocyte ratio (CLR) is a useful prognostic factor in various cancers. However, the prognostic value of preoperative CLR in patients with non-small cell lung cancer (NSCLC) remains to be established. We examined the significance of the CLR compared with known markers. Methods: A total of 1380 surgically resected NSCLC patients treated at two centers were recruited and divided into derivation and validation cohorts. After CLRs were calculated, patients were classified into high and low CLR groups based on the cutoff value determined by receiver operating characteristics curve analysis. Subsequently, we determined the statistical associations of the CLR with clinicopathological factors and prognosis and further analyzed its prognostic impact by propensity-score matching. Results: Of all the inflammatory markers examined, CLR yielded the highest area-under-the-curve value. The prognostic impact of CLR remained significant after propensity-score matching. Prognosis was significantly worse in the high-CLR group than in the low-CLR group (5-year, disease-free survival [DFS]: 58.1% vs. 81.9%, P < 0.001; 5-year overall survival [OS]: 72.1% vs. 91.2%, P < 0.001). The results were confirmed in the validation cohorts. Multivariable analysis also showed high CLR as an independent factor for both DFS and OS (DFS: hazard ratio [HR] 1.42, P = 0.027; OS: HR 1.95, P = 0.0037). Conclusions: Preoperative CLR is a useful marker for predicting the prognosis of NSCLC patients who have undergone surgery.

DOI： 10.1245/s10434-023-13250-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Microbiology and Immunology  

Smoking is one of the risk factors most closely related to the severity of coronavirus disease 2019 (COVID-19). However, the relationship between smoking history and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is unknown. In this study, we evaluated the ACE2 expression level in the lungs of current smokers, ex-smokers, and nonsmokers. The ACE2 expression level of ex-smokers who smoked cigarettes until recently (cessation period shorter than 6 months) was higher than that of nonsmokers and ex-smokers with a long history of nonsmoking (cessation period longer than 6 months). We also showed that the efficiency of SARS-CoV-2 infection was enhanced in a manner dependent on the angiotensin-converting enzyme 2 (ACE2) expression level. Using RNA-seq analysis on the lungs of smokers, we identified that the expression of inflammatory signaling genes was correlated with ACE2 expression. Notably, with increasing duration of smoking cessation among ex-smokers, not only ACE2 expression level but also the expression levels of inflammatory signaling genes decreased. These results indicated that smoking enhances the expression levels of ACE2 and inflammatory signaling genes. Our data suggest that the efficiency of SARS-CoV-2 infection is enhanced by smoking-mediated upregulation of ACE2 expression level.

DOI： 10.1111/1348-0421.13034

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Thoracic Cancer  

Main Problems: In non-small-cell lung cancer, ground-glass opacity on computed tomography imaging reflects pathological noninvasiveness and is a favorable prognostic factor. However, the significance of pathological noninvasive areas (NIAs) has not been fully revealed. In this study, we aimed to elucidate the prognostic impact of NIAs on lung adenocarcinoma. Methods: We analyzed 402 patients with pathological stage (p-Stage) IA lung adenocarcinoma who underwent surgery in 2013–2016 at two institutions and examined the association of the presence of NIAs with clinicopathological factors and prognosis. Furthermore, after using propensity-score matching to adjust for clinicopathological factors, such as age, sex, smoking history, pathological invasive area size, pathological T factor (p-T), p-Stage, and histological subtype (lepidic predominant adenocarcinoma [LPA] or non-LPA), the prognostic impact of NIAs was evaluated. Results: Patients were divided into NIA-present (N = 231) and NIA-absent (N = 171) groups. Multivariable analysis showed that NIA-present was strongly associated with earlier p-T, earlier p-Stage, LPA, and epidermal growth factor receptor mutation. Kaplan–Meier survival analysis showed that the NIA-present group displayed a better prognosis than the NIA-absent group in disease-free survival (DFS) and overall survival (OS) (5-year DFS 94.6% vs. 87.2%, 5-year OS 97.2% vs. 91.1%). However, after adjusting for clinicopathological factors by propensity score matching, no significant differences in prognosis were identified between the NIA-present and NIA-absent groups (5-year DFS 92.4% vs 89.6%, 5-year OS 95.6% vs 94.3%). Conclusions: Our current study suggests that the prognostic impact of the presence of NIAs on lung adenocarcinoma is due to differences in clinicopathological factors.

DOI： 10.1111/1759-7714.14910

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DOI： 10.1186/s40792-022-01554-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：European Journal of Medical Research  

Introduction: Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy. Methods: We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models. Results: We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72–0.87) for males and 0.69 (0.54–0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55–0.66) for males and 0.56 (0.44–0.70) for females. Conclusions: In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients.

DOI： 10.1186/s40001-022-00789-7

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DOI： 10.1186/s40792-022-01540-4

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Thoracic Cancer  

Background: Preoperative maximum standardized uptake value (SUVmax) of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography and serum carcinoembryonic antigen (CEA) have been reported as prognostic factors for lung adenocarcinoma. However, the significance of combined SUVmax and CEA in early-stage lung adenocarcinoma is not well known. Methods: We retrospectively evaluated the relationship between the combination of SUVmax and CEA and the prognosis of 410 patients with clinical stage IA lung adenocarcinoma who underwent resection. The cutoff values for SUVmax and CEA were determined by receiver operating characteristic curve analysis, and patients were categorized into high SC (SUVmax and CEA) group (SUVmax ≥2.96 and CEA ≥5.3), moderate SC group (either SUVmax <2.96 and CEA ≥5.3 or SUVmax ≥2.96 and CEA <5.3) and low SC group (SUVmax <2.96 and CEA <5.3). Results: Kaplan–Meier curve analysis showed that patients with clinical stage IA lung adenocarcinoma in the high SC group had significantly shorter overall survival (OS) and recurrence-free survival (RFS) than the other groups (p = 0.011 and p < 0.0001, respectively). Multivariate analysis showed that high SC was an independent prognostic factor of OS (p = 0.029) and RFS (p < 0.0001). Conclusions: High values of SUVmax and CEA were associated with poor OS and RFS in patients with stage IA lung adenocarcinoma. Simultaneous evaluation of SUVmax and CEA may be an effective prognostic marker to determine the optimal treatment strategy of early-stage lung adenocarcinoma.

DOI： 10.1111/1759-7714.14599

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cancer Management and Research  

Purpose: The incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in patients with non-small cell lung cancer (NSCLC) receiving carboplatin (CBDCA)-based chemotherapy (CBDCA + pemetrexed or paclitaxel) has not been clearly described. Therefore, we attempted to evaluate whether delayed CINV could be controlled using a combination of three antiemetics and identify individual risk factors. Methods: We pooled data from two prospective observational studies, namely a nationwide survey of CINV and a prospective, observational study in Japan, to assess whether delayed CINV could be controlled using a combination of three antiemetics and identified individual risk factors via inverse probability treatment-weighted analysis. Results: In total, 240 patients were evaluable in this study (median age, 66 years; male, 173; female, 67). The three-antiemetic regimen controlled delayed nausea (31.6% vs 47.3%) and vomiting (5.1% vs 23.1%) better than two antiemetics. Younger age (<70 years; odds ratio [OR] = 2.233), motion sickness (OR = 3.472), drinking habits (OR = 1.972), receipt of the CBDCA + pemetrexed regimen (OR = 2.041), and the use of two antiemetics (OR = 1.926) were risk factors for delayed nausea. Female sex (OR = 3.372), drinking habits (OR = 2.272), receipt of the CBDCA+ pemetrexed regimen (OR = 2.314), and the use of two antiemetics (OR = 6.830) were risk factors for delayed vomiting. Conclusion: Female sex, younger age, and receipt of the CBDCA + pemetrexed regimen increased the risk of CINV. Therefore, we recommend additional supportive antiemetics treatment for these patients.

DOI： 10.2147/CMAR.S370961

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Thoracic Cancer  

Background: Consolidation tumor ratio (CTR) is associated with cancer progression and histological invasiveness in lung adenocarcinoma (LAD). However, little is known about the association between CTR and immune-related factors, including tumor-infiltrating lymphocytes (TILs) density or tumor expression of programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) in small-sized LAD. Methods: This study included 258 patients with LAD (<3 cm) who underwent surgery. Patients were assigned to four groups: CTR = 0; 0 < CTR <0.5; 0.5 ≤ CTR <1 (ground-glass opacity [GGO] group); and CTR = 1 (pure-solid group). CD4⁺, CD8⁺, and FoxP3⁺ TIL density and PD-L1 and IDO1 tumor expression were assessed by immunohistochemistry. Results: Among the GGO group, CD8⁺ and FoxP3⁺ TIL density increased significantly with increasing CTR (p < 0.001 and p < 0.001, respectively). Moreover, PD-L1 and IDO1 expression was significantly higher in the pure-solid group than in the GGO group (p < 0.001 and p < 0.001, respectively). Conclusions: CTR was correlated with the abundance of CD8⁺ and FoxP3⁺ TILs in the GGO group. PD-L1 and IDO1 positivity rates were significantly higher in the pure-solid group than in the GGO group. Increased CTR may be correlated with immunosuppressive condition.

DOI： 10.1111/1759-7714.14524

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Jtcvs Open  

Objectives: The optimal treatment for recurrent non–small cell lung cancer (NSCLC) has not been standardized. In this prospective cohort study, we evaluated post-recurrence survival (PRS) after treatment of recurrent NSCLC and identified prognostic factors after recurrence. Methods: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data, such as treatment and survival outcomes, were obtained every 3 months. Results: From 2010 to 2015, 505 cases were enrolled, and 495 cases were analyzed. As initial treatment for recurrence, 263 patients (53%) received chemotherapy, 46 (9%) received chemoradiotherapy, 98 (20%) had definitive radiotherapy, 14 (3%) received palliative radiotherapy, and 31 (6%) underwent surgical resection. The remaining 43 patients (9%) received supportive care. The median PRS and 5-year survival rates for all cases were 30 months and 31.9%, respectively. The median PRS according to the initial treatment was as follows: supportive care, 8 months; palliative radiotherapy, 16 months; definitive radiotherapy, 30 months; chemotherapy, 31 months; chemoradiotherapy, 35 months; and surgery, not reached. A multivariate analysis showed that the age, gender, performance status, histology presence of symptoms, duration from primary surgery to recurrence, and number of recurrent foci were independent prognostic factors for PRS. Conclusions: The PRS of patients with recurrent NSCLC was different depending on the patient's background characteristics and initial treatment for recurrence.

DOI： 10.1016/j.xjon.2022.03.004

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DOI： 10.1016/j.annonc.2022.02.071

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research  

Background/Aim: Sublobar resection is widely performed for early-stage non-small cell lung cancer in the clinical setting. This study evaluated the optimal surgical procedures of clinical stage 0 or IA adenocarcinoma from the perspective of recurrence. Patients and Methods: A total of 508 lung adenocarcinoma patients diagnosed as c-stage 0 or IA were retrospectively investigated. Results: The types of surgical procedures were lobectomy (n=328), segmentectomy (n=73), and wedge resection (n=107). Clinical T descriptors were cTis in 74, cT1mi in 68, cT1a in 94, cT1b in 181 and cT1c in 91 patients. Recurrence was observed in 46 cases (9%), including 3 (3.1%) with cT1a, 23 (12.7%) with cT1b and 20 (22.0%) with cT1c. The patients who received sublobar resection developed recurrence more often than the patients who received lobectomy among cT1b cases (10.1% vs. 21.4%) and cT1c cases (18.0% vs. 46.2%) (p=0.053 and p=0.023). Conclusion: The cT1b and cT1c cases should be considered for lobectomy to prevent recurrence.

DOI： 10.21873/anticanres.15577

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DOI： 10.21037/tcr-21-1140

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DOI： 10.1097/SLA.0000000000005001

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DOI： 10.1371/journal.pone.0256894

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DOI： 10.1093/ejcts/ezab046

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DOI： 10.1007/s11748-021-01620-6

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DOI： 10.21873/anticanres.14924

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Background: Smoking cessation is a highly important preparation before thoracic surgery. We examined the effects of short-term smoking cessation intervention before pulmonary resection on postoperative pulmonary complications (PPCs).

Methods: A retrospective analysis of prospectively collected data was performed for 753 patients who underwent curative surgical resection for thoracic malignancy at 3 institutions. Patients with a smoking history were instructed to quit smoking. After confirming smoking cessation by at least four weeks before surgery, surgical resection was performed. Subjects were classified into three groups based on their smoking status: abstainers (anyone who had stopped smoking for at least 4 weeks but less than 2 months), former smokers (anyone who had abstained from smoking for more than two months prior to surgery), and never smokers (those who had never smoked). We examined the relationship between the preoperative smoking status and PPCs.

Results: Surgery was performed for 660 primary lung cancers and 93 metastatic lung tumors. The smoking statuses were classified as follows: abstainers (n=105, 14%), former smokers (n=361; 48%) and never smokers (n=287, 38%). The incidence of PPCs among abstainers, former smokers and never smokers was 15%, 8% and 6%, respectively (P=0.01). The mean duration of post-operative chest tube drainage among abstainers, former smokers and never smokers was 3.2, 2.2 and 2.2 days, respectively (P=0.04). The mean post-operative hospital stay among abstainers, former smokers and never smokers was 12.1, 10.6 and 10.2 days, respectively (P=0.07). There was no 30-day mortality in the cohort.

Conclusions: Short-term smoking cessation intervention did not enough reduce the PPCs as much as in former or never smokers.

DOI： 10.21037/jtd-20-2574

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES In the tumour, node and metastasis (TNM) classification (8th edition) of non-small-cell lung cancer, T (tumour size) is determined solely according to the size of the solid component determined using computed tomography (CT). However, it is unclear whether tumours of equal size but with differing solid and part-solid components should be similarly treated. Herein, we assessed the prognostic significance of the newly proposed T1 descriptors with respect to the size of the solid component. METHODS We analysed overall survival (OS) and disease-free survival (DFS) between groups of patients (n = 255) with solid or part-solid tumours using propensity score matching. The new staging system was used for classification and comparison of survival. RESULTS Chest CT detected 7 non-solid tumours, 123 part-solid tumours and 125 solid tumours. The 5-year OS and DFS rates differed significantly between the solid tumour (OS 71.2%; DFS 65.4%) and part-solid tumour (OS 83.2%; DFS 78.2%) groups. However, among 81 propensity score matching pairs (including those matched according to the size of the solid component), OS and DFS did not significantly differ between groups. The 5-year OS rates according to disease stage were as follows: cIA1 88.0%; cIA2 79.4% and cIA3 67.6%. CONCLUSIONS Propensity score matching of solid tumour and part-solid tumour groups did not reveal a significant difference in survival as a function of the size of the solid component. A study of a larger cohort is required to validate this result.

DOI： 10.1093/icvts/ivy164

Language：English   Publishing type：Research paper (scientific journal)  

Purpose: We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy. Methods: We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival. Results: The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively (p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS. Conclusions: CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function.

DOI： 10.1007/s00595-017-1577-8

Language：English   Publishing type：Research paper (scientific journal)  

Purpose: The purpose of this study was to evaluate the outcomes of elderly patients 75 years of age or older with recurrent non-small cell lung cancer (NSCLC). Methods: A total of 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of these patients, 280 experienced postoperative recurrence. The rate of the post-recurrence survival and predictors were analyzed independently in a group of younger patients (<75 years) and a group of elderly patients (≥75 years). Results: There were 215 younger patients (<75 years) and 65 elderly (≥75 years) patients at the time of diagnosis of recurrence. The median post-recurrence survival time and the five-year survival rate of all cases were 25 months and 20.8 %, respectively. There were no significant survival differences between the younger and elderly groups (p = 0.20). A univariate analysis determined that gender, Eastern Cooperative Oncology Group performance status, smoking status, histological type and epithelial growth factor receptor (EGFR) mutation status were factors influencing the post-recurrence survival among the elderly patients. In addition, a multivariate analysis determined the EGFR mutation status to be an independent prognostic factor for the post-recurrence survival. Conclusions: Elderly patients 75 years of age or older in this study achieved satisfactory long-term outcomes.

DOI： 10.1007/s00595-015-1200-9

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: There have been no previous reports examining how the travel distance affects the outcomes of non-small-cell lung cancer (NSCLC) patients. In this study, we examined the influence of the distance from home to the hospital on patients with NSCLC who underwent surgical resection. METHODS: From 2006 to 2011, 607 consecutive patients with NSCLC who had undergone pulmonary resection were enrolled. The patients were divided into three groups according to the distance from their home to the hospital: 0 < 10, 10-30 and > 30 km. We analysed the short-term and long-term outcomes according to the group. RESULTS: Two hundred and ninety-six patients lived less than 10 km from the hospital, 111 patients lived 10-30 km and 200 patients lived more than 30 km. There were no differences in the demographics, including age, European Cooperative Oncology Group performance status, histological type, surgical procedure and pathological stage, between the three groups. The mean postoperative hospital stay was as follows: 13.9 days in the < 10 km group, 13.3 days in the 10-30 km group and 14.3 days in the > 30 km group (P = 0.04). There were no significant differences in the median length of follow-up (50, 47, 43 months, P = 0.24), disease-free survival (DFS) (5-year DFS, 68.1, 68.2 and 70.1%, P = 0.89) or overall survival (OS) (5-year OS, 80.6, 78.8 and 79.4%, P = 0.99) between the three groups. CONCLUSIONS: The distance between home and the hospital was not found to influence the long-term outcomes of the patients with surgically resected NSCLC. Therefore, the travel distance should not represent a contraindication to surgical resection and postoperative therapy for NSCLC.

DOI： 10.1093/ejcts/ezv253

Language：English   Publishing type：Research paper (scientific journal)  

Introduction: Tumor volume promises to be an important factor for predicting the prognosis of patients with non- small cell lung cancer (NSCLC). Methods: A total of 255 patients who underwent curative surgical resection for clinical stage IA NSCLC were included. We performed semiautomated measurement of the whole tumor volume and the volume of the solid part (referred to as the solid part volume) from a volumetric analysis of chest three-dimensional computed tomography scans using the SYNAPSE VINCENT imaging software program (Fujifilm Medical, Tokyo, Japan). We evaluated the relationships among tumor size, tumor volume, and survival. Results: The mean whole tumor size, the ratio of the maximum diameter of consolidation to the maximum tumor diameter (CTR), the whole tumor volume, and the solid part volume were 20 mm (range 0-30 mm), 0.84 (range 0-1.0), 3080 mm³ (range 123-17509 mm³), and 2032 mm³ (0- 12466 mm³), respectively. The receiver operating characteristic area under the curve for the whole tumor size, CTR, whole tumor volume, and solid part volume used to identify recurrence were 0.60, 0.68, 0.58, and 0.69, respectively. A univariate analysis revealed that the whole tumor size, CTR, whole tumor volume, and solid part volume were associated with disease-free survival (DFS). A multivariate analysis of these factors identified the solid part volume to be the only independent factor for the prediction of DFS. Conclusions: The whole tumor volume and the solid part volume were associated with DFS. In particular, the solid part volume was a very useful factor for predicting prognosis in clinical stage IA NSCLC.

DOI： 10.1016/j.jtho.2016.02.005

Language：English   Publishing type：Research paper (scientific journal)  

Although chemotherapy and radiotherapy are recommended for patients with limited disease small cell lung cancer (LD-SCLC), several series have reported favorable survival outcomes even in patients with stages II and III disease who underwent surgical resection. The purpose of this study is to compare the outcomes of the use of surgical resection to the other conventional non-surgical treatments in patients with LD-SCLC with respect to each clinical stage. Materials and methods: We retrospectively reviewed 277 patients who received treatment for LD-SCLC and compared the outcomes of the use of surgical resection to the other conventional non-surgical treatments. Results: The clinical stage was stage I in 50 cases (18%), stage II in 53 cases (19%) and stage III in 174 cases (63%). Eighty-eight patients received surgical resection and 189 patients were treated with non-surgical treatment. Surgery was performed in 44 patients (88%) with stage I, 27 patients (52%) with stage II and 17 patients (10%) with stage III disease. The five-year survival rates of the patients according to clinical stage were 58% in stage I, 29% in stage II and 18% in stage III. The five-year survival rates of the patients with and without surgical resection according to clinical stage were as follows: 62% and 25% in stage I (. p<. 0.01), 33% and 24% in stage II (. p=. 0.95), 18% and 18% in stage III (. p=. 0.35), respectively. In 44 propensity score-matched pairs with stages II and III disease, including matching for variables such as age, gender and the PS, the five-year survival rates was better in patients with surgical resection than in those without surgery (. p=. 0.04). Conclusion: Surgical resection is effective for the patients with stage I LD-SCLC and some cases of stage II or III disease.

DOI： 10.1016/j.lungcan.2015.01.010

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: The impact of epidermal growth factor receptor (EGFR) status and the use of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy have not been well discussed only in recurrent non-small-cell lung cancer (NSCLC). The purpose of this study was to identify the prognostic factors associated with post-recurrence survival after surgical resection of NSCLC in terms of the EGFR mutation status and the use of EGFR-TKI therapy. METHODS: From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of these patients, 280 experienced postoperative recurrence by the end of 2012. We reviewed the cases of recurrence and analysed the predictors and length of post-recurrence survival. RESULTS: The median post-recurrence survival time and the 5-year survival rate of all patients were 25 months and 20.8%, respectively. A multivariate analysis identified the Eastern Cooperative Oncology Group (ECOG) performance status (PS), brain metastasis, number of sites of recurrence and EGFR mutation status to be independent prognostic factors for post-recurrence survival. Among all cases, the median post-recurrence survival time according to the use of EGFR-TKI therapy was as follows: 49 months in the EGFR mutation-positive patients treated with EGFR-TKI therapy, 20 months in the EGFR wild or unknown cases treated with EGFR-TKI therapy and 17 months in the patients not treated with EGFR-TKI therapy. As to EGFR mutation-positive cases, the patients treated with EGFR-TKIs exhibited significantly longer post-recurrence survival time than the patients treated without EGFR-TKIs (49 vs 12 months). CONCLUSIONS: It is essential for recurrent NSCLC patients to be examined for the EGFR mutation status. Patients with a positive EGFR mutation status receive significant benefits from EGFR-TKI therapy.

DOI： 10.1093/ejcts/ezu227

Language：English   Publishing type：Research paper (scientific journal)  

Background A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with postoperative recurrence of non-small cell lung cancer (NSCLC). Patients and Methods From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of those, 280 patients had experienced postoperative recurrence by the end of 2012. Thirty-five patients received concurrent CRT as initial treatment of the recurrent disease. We retrospectively reviewed these cases, analyzed the outcomes of concurrent CRT after surgical resection, and examined the factors that predict long-term postrecurrence survival. Results The most common sites of recurrence in this cohort were the lymph nodes in 24 patients, followed by the lung in 5 patients and bone in 6 patients. The median radiation dose given as the initial treatment of recurrence was 60 Gy (range, 30-60 Gy). Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered in 23 cases, and a carboplatin-based chemotherapy regimen was administered in 12. The median progression-free and postrecurrence survival after CRT was 13 months (range, 4-127 months) and 31 months (range, 5-127 months), respectively. Seven patients were still alive without evidence of disease for > 3 years after the recurrence diagnosis. The ECOG performance status (PS), surgical procedure, and types of platinum agents used were independent prognostic factors for postrecurrence survival. Conclusion Concurrent CRT for recurrent NSCLC is a promising therapy for selected patients. A poor PS and postpneumonectomy state were poor prognostic factors for patients who received concurrent CRT.

DOI： 10.1016/j.cllc.2014.06.001

Language：English   Publishing type：Research paper (scientific journal)  

Background: The T3 category of the 7th Edition of the TNM classification of non-small cell lung cancer (NSCLC) has added two factors that do not appear in the 6th Edition, large tumor size (>7 cm) and pulmonary metastasis of the same lobe. These factors are considered to have different biological and clinical features. In the present study we assessed the outcome of surgical resection as a first line therapy for T3 NSCLC. Methods: A total of 145 patients who were diagnosed according to the TNM 7th Edition with pathologic T3 NSCLC received surgical resection in our institution as a first line treatment. The outcomes of their treatment were analyzed. Results: The 5-year survival rate was 46.9 %. On the basis of the 6th TNM Edition, the 5-year survival rate was 63.1 % for patients diagnosed with T2 disease (large tumor size), 44.3 % for patients diagnosed with T3 disease, and 33.1 % for patients diagnosed with T4 disease (pulmonary metastasis of the same lobe). There were no significant correlations between these categories and overall survival (OS). Nevertheless, 6th Edition T factors were found to be significantly correlated with lymph node status (p < 0.01). The univariate analyses showed that age, lymph node metastasis, and curative resection had significant effects on OS. In addition, the multivariate analysis identified age and N factor as independent prognostic factors in this cohort. Conclusions: Indications for surgical resection as a first line therapy in T3 NSCLC should be based on N factors and patient age. Lymph node metastasis, especially N2 disease, was increasingly frequent in patients with 6th Edition T classifications.

DOI： 10.1007/s00268-013-2174-7

Language：English   Publishing type：Research paper (scientific journal)  

Objectives The presence of cardiovascular comorbidity in non-small-cell lung cancer (NSCLC) patients increases with age. Therefore, the influence of cardiovascular comorbidity in NSCLC patients on their short-or long-term prognosis remains controversial. This study evaluated the possible risk factors related to the short-term and long-term survivals in NSCLC patients with cardiovascular comorbidity. Methods One thousand one hundred and sixty-two consecutive patients with NSCLC who had undergone a surgical resection between 1984 and 2010 were enrolled in this study. A total of 360 (31%) patients with cardiovascular comorbidities were analysed to identify the risk factors for postoperative complications and prognostic factors. Results The patients with cardiovascular comorbidity included 301 with hypertension, 28 with coronary artery disease, 35 with peripheral vascular disease, 23 with arrhythmia and 11 with abdominal aortic aneurysm. Eighty-three patients exhibited more than one type of comorbidity. The postoperative cardiovascular morbidity rates were 3.6% in the cardiovascular comorbidity patients and 3.3% among patients without cardiovascular comorbidity (P = 0.73). No correlation was observed between preoperative cardiovascular comorbidity and postoperative pulmonary complications (P = 0.52). The operative mortality rates were 1.0% for the cardiovascular comorbidity patients and 0.8% for the other patients (P = 0.51). No difference in the postoperative outcomes was observed between the patients with and without cardiovascular comorbidity. The 5-year survival rates were 62.5% in comparison with 65.4% among patients without cardiovascular comorbidity (P = 0.48). Conclusions Patients with cardiovascular comorbidity were not found to be at increased risk of mortality and morbidity following surgery for NSCLC. In addition, cardiovascular comorbidity did not influence the long-term outcomes of patients after a pulmonary resection for NSCLC.

DOI： 10.1093/icvts/ivs489

Language：English   Publishing type：Research paper (scientific journal)  

Purpose We developed a method for predicting truenegative lymph node metastases in clinical IA non-small lung cancer (NSCLC) by the combined evaluation of computed tomography (CT), 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) findings and the maximum standardized uptake value (SUVmax) of primary tumors. Methods The subjects of this study were 94 patients with clinical stage IA NSCLC who underwent both preoperative CT and FDG-PET. We analyzed the relationship between the SUVmax of primary tumors and various clinicopathological factors to find the best method available for assessing true-negative lymph node metastasis. Results The pathological stages were IA (n = 80), IB (n = 4), IIA (n = 5), IIIA (n = 4), and IV (n = 1). Pathologic lymph node metastasis was recognized in nine patients and the SUVmax of these tumors ranged from 3.3 to 20.3. A SUVmax of 3.0 was defined as the cut-off point and patients were dichotomized according to this point. Tumors with SUVmax of 3.0 or less were associated with a significantly lower incidence of pleural and vascular invasion and were characterized by the degree of differentiation. Conclusion The SUVmax of primary tumors reflects the grade of malignancy; therefore, the combined evaluation of FDG-PET/CT findings with the SUVmax of primary tumors may help predict lymph node metastasis negativity.

DOI： 10.1007/s00595-012-0277-7

Language：English   Publishing type：Research paper (scientific journal)  

Background: Excision repair cross-complementation group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process. Two polymorphisms of ERCC1, T19007C (rs11615) and C8092A (rs3212986), have been reported to affect both the carcinogenesis and the survival of the patients who received platinum-based chemotherapy, but the mechanism by which these polymorphisms influence the survival is unclear. In this study, we determined the function of these ERCC1 polymorphisms in the survival of NSCLC patients. Method: The ERCC1 T19007C and C8092A single nucleotide polymorphisms (SNPs) were evaluated in 122 Japanese non-small cell lung cancer (NSCLC) patients who underwent a complete resection and analyzed the clinicopathological significance of these SNPs. None of the patients received peri-operative platinum-based chemotherapy. The relationship between these SNPs and ERCC1 protein expression and the platinum sensitivity of the primary tumors were also examined. Result: Regarding T19007C SNP, the distribution of the CC, CT, and TT genotypes was 45%, 48% and 7%, respectively. As for C8092A SNP, the distribution of CC and CA genotypes was 70% and 30%, respectively. The patients with C8092A CA genotype were significantly poorer disease-free survival (DFS) and overall survival (OS) than those with the CC genotype (p = 0.037 and 0.004). In addition, no relationship was observed between T19007C SNP and DFS or OS. These two SNPs also did not correlate with either ERCC1 protein expression or platinum sensitivity. Conclusion: The ERCC1 C8092A polymorphism may influence the NSCLC prognosis regardless of the ERCC1 protein expression and platinum sensitivity.

DOI： 10.1016/j.lungcan.2009.03.007

Language：English   Publishing type：Research paper (scientific journal)  

Background: The 2-[¹⁸F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has recently become an important non-invasive tool for the diagnosis and staging in several cancers. The standardized uptake value (SUV) of primary tumor has been reported to relate to cancer progression and prognosis, however, biological mechanism is still unclear. Method: Seventy-nine patients with non-small cell lung cancer (NSCLC) who had undergone preoperative FDG-PET and a surgical resection were enrolled in this study. NSCLC tissue samples prepared from the surgical specimens were subjected to an immunohistochemical analysis for the expression of Ki-67 and vascular endothelial growth factor (VEGF) proteins. The relationships between the expression status of these proteins and SUVmax of primary tumors were evaluated. Result: Concerning the relationship with various clinicopathological findings, SUVmax of primary tumors was associated with histology, tumor proliferation, pleural or vascular invasion, and pathological stage. A significant correlation was observed between the SUVmax and either the Ki-67 or VEGF expression (P<0.001, P=0.006), respectively. Cases with both Ki-67-negative and VEGF-negative findings exhibited a significantly lower SUVmax than those with single positive or double positive cases (P=0.006, P<0.001). Conclusion: The SUVmax was associated with the expression of Ki-67 and VEGF in NSCLC. These findings indicated that the SUVmax of primary tumors might therefore reflect the biological malignant potential in NSCLC.

DOI： 10.1002/jso.21386

Language：English   Publishing type：Research paper (scientific journal)  

DNA repair enzyme expression in tumor cells possibly affects sensitivity to anti-cancer agents. The aim of this study was to determine the relationship between expression status of DNA repair enzymes and chemosensitivity in patients with non-small cell lung cancer (NSCLC). NSCLC tissues prepared from the surgical specimens of 41 patients were subjected to immunohistochemical analysis for Rad51 and ERCC1 proteins and to a chemosensitivity test using the MTT assay. The relationships between the expression status of the DNA repair enzymes and ex vivo chemosensitivity to various agents were evaluated. A positive expression for Rad51 and ERCC1 was observed in 17 cases (41%) and 20 cases (49%), respectively. The positivity of Rad51 was closely related to a certain histologic type of squamous cell carcinoma and poor differentiation, and the positivity of ERCC1 tended to be related to squamous cell carcinoma. In chemosensitivity tests, sensitivities to CDDP and CBDCA were significantly lower when both 2 enzymes were positive (p = 0.012 and 0.04 in CDDP, 0.014 and 0.03 in CBDCA). Both Rad51 and ERCC1 expressions showed no significant relationship with sensitivities to paclitaxel, etoposide, vinorelbine, gemcitabine, 5-FU, or irinotecan. In conclusion, combined expression of Rad51 and ERCC1 expression is associated with resistance to platinum agents in the ex vivo study of clinical NSCLC, and evaluation of expression status of both DNA repair enzymes would be a predictor for clinical response to platinum-based chemotherapies.

DOI： 10.1002/ijc.22738

Event date： 2024.4

Event date： 2023.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2023.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2022.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2022.5

Language：Japanese  

Country：Japan  

Event date： 2022.5

Language：Japanese  

Country：Japan  

Event date： 2021.11

Language：Japanese  

Country：Japan  

Event date： 2021.10

Language：Japanese  

Country：Japan  

Event date： 2020.11

Language：Japanese  

Venue：Web開催   Country：Japan  

Event date： 2019.9

Language：English  

Country：Spain  

Event date： 2018.9

Language：English  

Country：Canada  

Event date： 2017.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2014.9 - 2014.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2013.11 - 2020.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2013.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2013.9 - 2013.10

Language：English  

Country：Netherlands  

Event date： 2013.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2020.9

Language：Japanese  

Venue：Web開催   Country：Japan  

Language：Japanese