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Background The prognosis of patients with NSCLC harboring oncogenic driver gene alterations, such as EGFR gene mutations or ALK fusion, has improved dramatically with the advent of corresponding molecularly targeted drugs. As patients were followed up for about five years in most clinical trials, the long-term outcomes beyond 5 years are unclear. The objectives of this study are to explore the clinical course beyond five years of chemotherapy initiation and to investigate factors that lead to long-term survival. Methods One hundred and seventy-seven patients with advanced, EGFR -mutated or ALK -rearranged NSCLC who received their first chemotherapy between December 2008 and September 2015 were included. Kaplan Meier curves were drawn for the total cohort and according to subgroups of patients’ characteristics. Results Median OS in the total cohort was 40.6 months, the one-year survival rate was 89%, the three-year survival rate was 54%, and the five-year survival rate was 28%. Median OS was 36.9 months in EGFR -mutated patients and 55.4 months in ALK -rearranged patients. The OS curve seemed to plateau after 72 months, and most of the patients who were still alive after more than five years are on treatment. Female sex, age under 75 years, an ECOG PS of 0 to 1, ALK rearrangement, postoperative recurrence, and presence of brain metastasis were significantly associated with longer OS. Conclusions A tail plateau was found in the survival curves of patients with advanced, EGFR -mutated and ALK -rearranged NSCLC, but most were on treatment, especially with EGFR -mutated NSCLC.

Background Palliative interventions, such as chest tube drainage and radiotherapy for bone and brain metastases, are crucial for managing survival and quality of life in patients with advanced lung cancer. Methods This retrospective study analyzed 8171 patients with unresectable Stage IV lung cancer from the Japanese Joint Committee of Lung Cancer Registry (JJCLCR) database. At treatment initiation, 8.6% of patients underwent chest tube drainage, 9.9% underwent bone radiotherapy, and 11.5% underwent brain radiotherapy. In this study, associated factors for palliative interventions were evaluated, and their impact on patient survival was also assessed. Results High‐associated factors for upfront chest tube drainage included age ≥ 75 years, ECOG‐PS ≥ 2, pleural nodules, and adenocarcinoma, while EGFR mutation, serum albumin ≥ 3.2 mg/dL, adrenal gland, and brain metastases were low‐associated factors. For upfront brain radiotherapy, low‐associated factors included malignant pleural effusion (MPE) and bone metastases, whereas ECOG‐PS ≥ 2 was a high‐associated factor. High‐associated factors for upfront bone radiotherapy were serum albumin ≥ 3.2 mg/dL, ECOG‐PS ≥ 2, adenocarcinoma, and squamous cell carcinoma, while pleural nodules, MPE, liver, and brain metastasis were low‐associated factors. Patients receiving upfront bone radiotherapy had shorter survival, whereas survival did not significantly differ for those with or without upfront chest tube drainage or brain radiotherapy. Conclusion This study identified associated factors for palliative interventions in advanced lung cancer and their association with overall survival. Future prospective studies with more detailed data are necessary to confirm these findings and improve clinical decision‐making. Trial Registration: Approval No. 15,321 This retrospective study analyzed 8171 patients with unresectable Stage IV lung cancer from the JJCLCR database to assess associated factors for palliative interventions (chest tube drainage, bone radiotherapy, and brain radiotherapy) and their impact on survival. It identified high‐ and low‐associated factors for each intervention. Patients undergoing upfront bone radiotherapy had shorter survival, while no significant survival differences were observed for chest tube drainage or brain radiotherapy. The study highlights the need for future prospective research to validate these findings and improve palliative care decision‐making in advanced lung cancer.

Objectives This study aimed to investigate the characteristics of patients with recurrent or advanced non‐small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) or immune‐checkpoint inhibitors (ICIs) who developed secondary malignancies, as well as evaluate the impact of these secondary malignancies on the course of lung cancer. Materials and Methods This study included 112 patients with postoperative recurrent or advanced NSCLC, who received TKIs, ICIs, or immune combination therapy as the primary treatment modality between April 1, 2013, and March 31, 2020, and achieved long‐term survival (≥2 years). Secondary malignancies were defined as newly diagnosed cancers in other organs occurring after NSCLC treatment initiation. Results Among the 112 patients, 10 (8.9%) developed 12 carcinomas, including third primary malignancies. Univariate analysis, considering secondary malignancies as the outcome, revealed a non‐significant trend towards a higher incidence of secondary malignancies in smokers compared to non‐smokers. Conclusion This study found that 8.9% of patients with advanced NSCLC who received TKIs, ICIs, or immune combination therapy and survived ≥2 years developed secondary malignancies. This underscores the importance of early diagnosis and treatment, even during lung cancer treatment, to identify suspicious lesions in other organs either via imaging or physical examinations. The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) for the treatment of advanced non‐small cell lung cancer has resulted in an increasing number of long‐term survivors. Consequently, the emergence of second malignancy may have implications for their prognosis. This study found that 8.9% of patients with advanced NSCLC who received TKIs, ICIs, or immune combination therapy and survived ≥ 2 years developed second malignancy. It was suggested that by performing screening and examinations for the second malignancy, both malignancies could be controlled.

Background Thymic squamous cell carcinoma and type B3 thymoma are primary neoplasms of the anterior mediastinum that are sometimes difficult to differentiate from one another histologically. However, only a few immunohistochemical markers are available for the differential diagnosis. The purpose of this study was to discover a novel marker for differentiating between thymic squamous cell carcinoma and type B3 thymoma. Methods We used histological samples of thymic carcinomas (n = 26) and type B3 thymomas (n = 38) which were resected between 1986 and 2017. To search for candidates of differential markers, gene expression levels were evaluated in samples using promoter analysis by cap analysis of gene expression (CAGE) sequencing. Results Promoter level expression of CALML5 genes was significantly higher in thymic carcinomas than in type B3 thymomas. We further validated the results of the CAGE analysis in all 26 thymic carcinomas and 38 type B3 thymomas by immunohistochemistry (IHC). CALML5 was strongly expressed in the cytoplasm in 19 of 26 cases with thymic carcinoma, whereas positivity at the protein level was shown in two of 38 type B3 thymomas. Thus, the sensitivity (73.1%) and specificity (94.7%) of CALML5 as markers for immunohistochemical diagnosis of thymic carcinoma were extremely high. Conclusion We identified CALML5 as a potential marker for differentiating thymic squamous cell carcinoma from type B3 thymoma. It is assumed that future clinical use of CALML5 may improve the diagnostic accuracy of differentiating between these two diseases. Type B3 thymoma, the most malignant type of thymoma, is associated with cytological atypia, making its differentiation from thymic carcinoma difficult. CD5, c‐kit, and GLUT‐1 have been used as markers for differentiating thymic carcinoma from thymoma, although their sensitivity and specificity are not sufficient. We performed cap analysis of gene expression (CAGE) sequencing and immunohistochemistry (IHC) using histological samples of thymic carcinomas (n = 26) and type B3 thymomas (n = 38) which were surgically resected. CALML5 was identified as a potential marker for differentiating thymic squamous cell carcinoma from type B3 thymoma.