Thoracic Cancer最新文献

The mesenchymal-epithelial transition factor (MET) Y1003 mutation, like MET ex14 skipping, is an oncogenic driver mutation that suppresses MET degradation. Herein, we report the case of a 63-year-old female patient with lung adenocarcinoma harboring the MET Y1003N mutation, who was treated with tepotinib, a selective type 1b MET tyrosine kinase inhibitor. To the best of our knowledge, no such cases have been reported. The woman was referred to our hospital with the chief complaint of chest pain. After a detailed examination, she was diagnosed with stage IVB lung adenocarcinoma. Next-generation sequencing revealed an MET Y1003N mutation in the tumor. Tepotinib was administered as the eighth-line treatment, and the best overall response was a partial response that lasted for 8 months. In lung adenocarcinomas harboring the MET Y1003 mutation, selective type 1b MET tyrosine kinase inhibitors may be an important treatment option, even in heavily pretreated settings.

Objective: Among the different subtypes of invasive lung adenocarcinoma, lepidic predominant adenocarcinoma (LPA) has been recognized as the lowest-risk subtype with good prognosis. The aim of this study is to provide insight into the heterogeneity within LPA tumors and to better understand the influence of other sub-histologies on survival outcome.

Methods: Overall, 75 consecutive patients with LPA in pathologic stage I (TNM 8th edition) who underwent resection between 2010 and 2022 were included into this retrospective, single center analysis. The proportions of different growth patterns were reported in 5% increments according to the WHO classification.

Results: All tumors exhibited a predominantly lepidic growth pattern (median proportion 70%, IQR 60%-85%). The invasive component included acinar (n = 66, 88%), papillary (n = 41, 55%), micropapillary (n = 14, 19%), and solid growth patterns (n = 4, 5%), with most tumors exhibiting more than one invasive growth pattern. The presence of high-risk growth, that is, micropapillary and solid, was associated with higher T stage (r = 0.423, p = 0.0002). A classification of patients as lepidic/high-risk or lepidic/low-risk based on the presence of micropapillary and solid growth patterns resulted in a significantly worse disease-free survival (p = 0.0169, 5-year DFS: lepidic/high-risk 73% vs. lepidic/low-risk: 95%) for the lepidic/high-risk group, while the groups did not differ in age, gender, smoking status, or extent of resection.

Conclusion: Patients with stage I LPA exhibit considerable intratumor heterogeneity regarding growth patterns, which can be used for prognostic stratification. The occurrence of micropapillary and solid growth patterns in LPA is associated with poorer disease-free survival.

Histologic transformation from non-small cell to small cell lung cancer (SCLC) is a resistance mechanism to immune checkpoint inhibitors. We report herein a case of lung adenocarcinoma who developed liver and brain metastases during adjuvant atezolizumab therapy. The patient underwent a craniotomy to resect a brain metastasis, which was pathologically diagnosed as SCLC. He subsequently received platinum-based chemotherapy with durvalumab, resulting in sustained regression of the liver metastases. This case demonstrates a metastatic brain tumor-acquired resistance to atezolizumab through histologic transformation from adenocarcinoma to SCLC. Therefore, rebiopsy is needed if recurrent disease appears during immune checkpoint inhibitor treatment in patients with non-small cell lung cancer.

The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on mesenchymal-epithelial transition factor (MET) inhibitor-induced edema remain unclear. In a patient with tepotinib-induced edema and an N-terminal pro-brain natriuretic peptide (NTproBNP) level ≥ 300 pg/mL, the addition of empagliflozin to loop diuretics reduced the edema. This suggests that empagliflozin may be a treatment option for MET inhibitor-induced edema.

Background: Sentinel lymph node biopsy (SLNB) using radioisotope tracer plus blue dye is the gold standard after neoadjuvant chemotherapy (NAC) in initially cN1 breast cancer patients, but clinical use still has limitations. This study aims to examine diagnostic performance of dual indocyanine green (ICG) and methylene blue tracing for SLNB in patients who have completed NAC for breast cancer with initially cN1 disease.

Methods: Adult women (20-80 years of age) scheduled to undergo NAC for biopsy-proven cT0-3N1M0 primary invasive breast cancer were consecutively enrolled in this prospective, multicenter, cohort study. Upon the completion of NAC, SLNB was conducted using ICG and methylene blue, followed by axillary lymph node dissection. The primary outcome was the detection rate (DR); secondary outcomes included the false-negative rate (FNR) and adverse events associated with the use of tracers.

Results: A total of 156 patients were enrolled; all underwent SLNB after NAC. The median number of lymph nodes retrieved during SLNB was 3 (range: 0-11). The DR was 97.4% (152/156; 95% CI, 93.6%-99.0%). The FNR was 6.7% (4/60; 95% CI, 2.6%-15.9%). Negative predictive value was 95.7% (88/92; 95% CI, 89.4%-98.3%). In the subgroup analysis stratified by ycN status, FNR was 4.0% (1/25; 95% CI, 0.7%-19.5%) and 8.6% (3/35; 95% CI, 3.0%-22.4%) in the ycN0 and ycN+ subgroups, respectively. No allergic reaction was reported.

Conclusions: SLNB with ICG plus methylene blue achieved a high DR and a very low FNR in breast cancer patients with initially cN1 disease.

Trial registration: ClinicalTrials.gov (https://www.

Clinicaltrials: gov/), NCT02869815.

Background: Multiple studies have demonstrated the intracranial efficacy of immune checkpoint inhibitors (ICI) +/- chemotherapy. The efficacy of chemoimmunotherapy compared to ICI alone in patients with metastatic NSCLC and brain metastases (BM) remains unknown.

Methods: A systematic review and network meta-analysis were performed to evaluate ICI efficacy and the influence of additional chemotherapy on survival outcomes in treatment-naïve metastatic NSCLC with BM. Randomized phase II/III studies with at least one treatment arm with an ICI were eligible. Overall survival (OS) and progression-free survival (PFS) in patients with and without BM were assessed.

Results: Ten studies were included, totaling 6560 patients, 770 with BM. Pairwise meta-analysis revealed that patients with BM treated with ICI +/- chemotherapy had improved PFS (hazard ratio [HR] 0.49; 95% CI 0.40-0.60) and OS (HR 0.55; 95% CI 0.44-0.68) versus chemotherapy alone. Patients without BM treated with ICI +/- chemotherapy also had improved PFS and OS compared to chemotherapy alone. In the network meta-analysis of patients with BM, chemoimmunotherapy demonstrated improved PFS compared to ICI alone (HR 0.64; 95% CI 0.43-0.96; p = 0.03). No significant difference was observed in OS. In the population of patients without BM, no significant differences in PFS or OS were observed between chemoimmunotherapy versus ICI alone.

Conclusion: This meta-analysis confirms that ICIs with or without chemotherapy are superior to chemotherapy alone for the first-line management of metastatic NSCLC with and without BM. This network meta-analysis suggests combination chemoimmunotherapy offers PFS benefit over ICI monotherapy in BM patients, warranting direct comparisons in clinical trials.

Trial registration: PROSPERO: CRD42024501345.

Mucoepidermoid carcinoma (MEC) is a subtype of epithelial neoplasms commonly found in salivary glands, but can also be seen in the thymus. Diagnosing MEC of the thymus is sometimes challenging due to its histological similarities with adenosquamous carcinoma (ASC). This case report describes a 64-year-old female with a history of metastatic endometrial adenocarcinoma who presented to an oncology clinic with a thymic mass as well as multiple mass lesions in the liver, bone, and abdominal wall. Initially diagnosed as thymic ASC based on histopathology, further genomic profiling revealed a CRTC1/MAML2 translocation, leading to the diagnosis of metastatic MEC of the thymus. Comprehensive genomic testing played a crucial role in distinguishing MEC from ASC. This case highlights the importance of genetic testing in cases of uncertain primary origins and in differentiating between morphologically similar tumors.

The main problem: Squamous cell carcinoma is the second most prevalent type of non-small cell lung cancer. Analyzing the molecular mechanisms underlying lung carcinoma requires useful tools, such as squamous lung cancer cell lines.

Methods: A novel new lung squamous cell carcinoma cell line, OMUL-1, was developed from the primary lung cancer of a 74-year-old man. We assessed the characteristics and behavior of OMUL-1 cells were examined, including their growth kinetics, tumorigenicity in mice, histological properties, gene expression profiles using reverse transcription polymerase chain reaction (RT-PCR), and RNA sequencing and invasion assays.

Results: OMUL-1-an adherent cell line-resulted in 100% tumor formation when subcutaneously injected into mice. Histological analysis of the subcutaneous tumor using hematoxylin and eosin staining revealed squamous cell carcinoma with characteristics similar to those of the primary tumor (p40 and p63 were positive, and TTF-1 was negative). An invasion assay demonstrated that OMUL-1 had a lower invasion ability compared to that of other developed cell lines. RT-PCR analysis and RNA sequencing indicated that OMUL-1 cells expressed FGFR1, FGFR2, FGFR3, FGFR4, EGFR, HER2, ErbB3, ErbB4, VEGFR3, IGF1R, c-MET, PDGFRa, and PDGFRb. Additionally, picropodophyllin (an IGF1R inhibitor) significantly inhibited the growth of OMUL-1 cells. Immunohistochemistry revealed that IGF1R and PD-L1 were expressed in both the primary and subcutaneous tumors.

Conclusions: We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.

Background: Circular RNA (circRNA) plays a significant role in esophagus squamous cell carcinoma (ESCC) progression. Nevertheless, circ-TTC17 roles in ESCC have not fully understood.

Methods: The levels of circ-TTC17, miR-145-5p and sirtuin 1 (SIRT1) were determined using qRT-PCR. ESCC cell functions were examined by CCK8 assay, flow cytometry, transwell assay and colony formation assay. The relative protein levels of autophagy marker and SIRT1 were determined by western blot (WB). The interactions among circ-TTC17, miR-145-5p, and SIRT1 were verified by dual-luciferase reporter assay and RIP assay.

Results: circ-TTC17 was overexpressed and miR-145-5p was underexpressed in ESCC. circ-TTC17 knockdown restrained ESCC cell proliferation and metastasis, while enhance apoptosis and autophagy-mediated radiosensitivity. Circ-TTC17 could sponge miR-145-5p, and its inhibitor reversed the inhibitory effect of circ-TTC17 knockdown on ESCC cell progression. Additionally, SIRT1 was targeted by miR-145-5p, and SIRT1 overexpression abolished miR-145-5p-mediated the suppressive effect on ESCC cell progression. Also, circ-TTC17 interference reduced ESCC tumor growth via miR-145-5p/SIRT1 axis.

Conclusion: circ-TTC17 promoted ESCC cell growth, metastasis and inhibited autophagy-mediated radiosensitivity by miR-145-5p/SIRT1 axis.

Background: Lung cancer is a pathology with an important incidence. It is a multifactorial disease characterized by epigenetic and nutritional factors. Indeed, there is a strong association between adipose tissue and the pulmonary system, and low-grade inflammation of obese and/or overweight subjects have a pivotal role in lung cancer establishment.

Methods: In this study, we analyzed body composition through bioelectrical impedance analysis (BIA) and biochemical parameters such as glycemic and lipidic profile, inflammation profile and adiponectin serum levels in 30 patients (19 male; 11 women) undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer from September 2021 to May 2022 at the Thoracic Unit of Luigi Vanvitelli University of Naples. A control group were also recruited (15 male; 15 female) consisting of age and sex matched volunteered subjects at the Thoracic Unit of Luigi Vanvitelli University of Naples. The control group and lung cancer patients were monitored for anthropometric and biochemical parameters before VATS lobectomy. Furthermore, the lung cancer patients were also monitored after 6 months of surgery.

Results: Body composition is modified after surgery and also albumin and C-reactive protein (CRP) serum levels. In the overweight patients in our study, adiponectin levels were found to be reduced compared with the control group and increased in the same patients after VATS lobectomy.

Conclusions: Tumor removal as well as weight loss could affect adiponectin levels, and thus also a reduction in inflammation. In addition, weight loss could also be due to a psychological condition given by the intervention and not to malnutrition related to therapy.