Thoracic Cancer

Background Lung cancer continues to be the primary cause of cancer‐related deaths globally, with the majority of cases identified at advanced stages. Genetic alterations, including mutations and gene fusions, are central to its molecular pathogenesis. The discovery of therapeutically targetable gene fusions, such as ALK, RET, ROS1, and NTRK1, has significantly advanced lung cancer management. Conventional methods, such as tissue biopsies, are invasive and unsuitable for continuous molecular monitoring. Consequently, noninvasive approaches, such as liquid biopsies and exhaled breath condensate (EBC), offer promising options for real‐time molecular surveillance. Methods This study evaluates the feasibility of identifying fusion transcripts in 30 patients with lung adenocarcinoma by using next‐generation sequencing (NGS) on formalin‐fixed paraffin‐embedded (FFPE) tissue, plasma, and EBC samples. Results Clinically significant fusion transcripts, including KIF5B‐ALK, KIF5B‐RET, and SQSTM1‐ALK, were detected across different sample types. EBC samples showed strong concordance with tissue biopsy results, particularly in detecting ALK, ROS1, and RET fusions, and demonstrated greater sensitivity than plasma in detecting NTRK1 fusions. Additionally, 30 fusion transcripts of uncertain clinical significance were identified, highlighting the need for further research into their role in lung cancer pathogenesis. Conclusion In conclusion, EBC samples provide a valuable, noninvasive medium for detecting clinically relevant and previously uncharacterized fusion transcripts in non‐small cell lung cancer (NSCLC). The high concordance between EBC and tissue biopsies suggests that EBC could complement tissue biopsy for effective diagnosis and monitoring of NSCLC. These findings underscore the importance of comprehensive molecular profiling using multiple sample types to enhance diagnostic precision and optimize therapeutic outcomes in lung cancer management.

Background Schlafen 11 (SLFN‐11) has been identified as a sensitizer of tumor cells to DNA‐damaging agents. However, the relationship between SLFN‐11 expression and clinical outcomes in patients with small cell lung cancer (SCLC) remains unexplored. Thus, we aimed to evaluate the impact of SLFN‐11 expression on survival in patients with limited‐stage (LS) SCLC. Methods We conducted a retrospective review of data from patients pathologically diagnosed with LS‐SCLC post‐surgery between January 2008 and December 2018. SLFN‐11 expression was assessed using immunohistochemistry in tissue microarrays and scored using a histology (H)‐score (range: 0–300). Results Overall, 86 patients were included in the analysis with a median H‐score of 43 for SLFN‐11 expression. Among the patients, 44 had high SLFN‐11 expression (provisionally defined as H‐score ≥ 43). No significant differences in clinical profiles were observed between the two groups (high and low SLFN expression). The median survival durations were not reached (NR; 95% confidence interval [CI]: 65.1 months to NR) and 33.5 months (95% CI: 24.2 months to NR) for patients with high and low SLFN‐11 expression, respectively (hazard ratio [HR]: 0.40, 95% CI: 0.19–0.81; p = 0.012). Among patients who relapsed post‐surgery (n = 21), the median survival durations were 22.0 (95% CI: 7.6–44.9 months) and 8.1 (95% CI: 1.8–24.6 months) months in patients with high and low SLFN‐11 expression, respectively (HR: 0.22, 95% CI: 0.06–0.84; p = 0.026). Conclusions High SLFN‐11 expression is associated with relatively longer survival in patients with LS‐SCLC in both those undergoing surgery and those who have relapsed.

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.

Background The long‐term real‐world effect of immunotherapy (IO) is uncertain in metastatic nonsmall cell lung cancer (mNSCLC). This retrospective observational study aimed to describe treatment patterns following the introduction of IO, estimate real‐world treatment effects of IO compared to standard of care, and evaluate the impact of introduction of IO on a real‐world population, based on a large dataset of over 10 000 patients with several years of follow‐up. Methods Data from routine care of lung cancer patients were extracted from Flatiron Health including those who received either IO or platinum‐based doublet chemotherapy (PBDC) in the first line (1L), or either IO or chemotherapy (CT) in the second line (2L). Real‐world overall survival (rwOS) and real‐world time to next therapy (rwTTNT) were estimated using Cox regression. Flexible parametric models, relaxing proportional hazard assumptions, were used to evaluate long‐term IO effects. Results After 1:1 nearest neighbor matching among 16 754 1L and 6548 2L patients, the hazard ratio (HR) was 0.942 (95% CI, 0.902–0.984) in 1L and 0.853 (95% CI, 0.795–0.915) in 2L. Adjusting for crossover effects, HR was 0.887 in 1L and 0.775 in 2L. Over the 7‐year follow‐up, the mean rwOS benefit was 3.2 months for 1L and 2.7 months for 2L. IO significantly delayed rwTTNT in both 1L and 2L. The IO effects increased and persisted over time, with uncertainty in the time‐varying HR estimate. Conclusion IO improves survival in patients with mNSCLC, though the effect size is smaller than in trials and long‐term survival estimates are uncertain.

This illustrates the outcomes of patients with esophageal cancer undergoing neoadjuvant concurrent chemoradiation and esophagectomy, specifically focusing on those who develop new‐onset atrial fibrillation (NOAF). Statistically significant findings (p < 0.05, dark red) increased mortality and ventricular fibrillation, as well as trends of (p > 0.05, light red) myocardial infarction and pericardial effusion among NOAF patients. The data emphasize the significant cardiovascular risks associated with NOAF in this population. image

Objectives This study aimed to analyze lymph node metastasis (LNM) distribution in superficial esophageal squamous cell carcinoma (ESCC) and its impact factors on survival. Methods We reviewed 241 pT1N+ ESCC cases between February 2012 and April 2022 from 10 Chinese hospitals with a high volume of esophageal cancer (EC). We analyzed clinicopathological data to identify overall survival (OS) risk factors and LNM distribution in relation to tumor invasion depth. Results Of the 241 patients, 26 (10.8%) had pT1a cancer and 215 (89.2%) had pT1b cancer. We showed that N3 stage, ≤ 28 lymphadenectomies, and nerve infiltration (NI) were negative factors for OS in superficial pN+ ESCC, whereas the OS was not definitively affected by the tumor depth and the choice of adjuvant therapy. In general, the LNM rates of the 193 pT1N+ ESCC cases can be ranked in the following order: station 106recR > station 106recL > station 1 > station 7 > station 2. With deeper tumor invasion, the higher LNM rate was observed near the bilateral recurrent laryngeal nerves (RLN), but there was no statistically significant difference. Conclusions In superficial ESCC, LNM was frequently observed along the 106recR (35.8%) and 106recL (25.6%) stations. Advanced N‐staging (N3) was a major negative impact factor in prognosis, and adequate lymph nodes dissected (LND) (N > 28) improved OS of pT1N+ ESCC. However, in superficial ESCC, tumor infiltration depth did not affect patients' OS or the distribution of positive LNs. The optimal adjuvant treatment that favors survival for these patients required further investigation.

Anatomical variation of the pulmonary vessels poses challenges to thoracoscopic lung resection and may be associated with an increased risk of intraoperative bleeding and damage to pulmonary circulation. Herein, we reported a rare and dangerous variation as the partial anomalous venous drainage of the right upper lobe into the superior vena cava in a patient undergoing thoracoscopic lobectomy for management of lung cancer of right upper lobe. The preoperative identification of such variation by 3D computed tomography scan allowed to plan a safe and accurate resection, and to prepare additional strategies for overcome unexpected intraoperative bleeding. No intraoperative and/or postoperative complications were observed. Chest drainage was removed on postoperative day two and patient discharged the day after. At 3 months follow up, the patient was well without recurrence.

Chronic obstructive pulmonary disease (COPD) is confirmed as an independent risk factor for the development of lung cancer. Although low‐dose CT screening significantly reduces the mortality rate of lung cancer, the misdiagnosis and missed diagnosis rates remain high in the COPD population. Additionally, several COPD patients are unable to undergo invasive histological examinations. Therefore, there is an urgent need for minimally invasive biomarkers to screen or diagnose lung cancer in COPD patients. In this study, peripheral blood samples were collected from COPD patients with and without lung cancer. Plasma exosomes (EVs) were extracted for proteomic analysis. Sixteen differentially expressed proteins (DEPs) were preliminarily selected via label‐free quantification (LFQ) proteomic technology and comprehensive bioinformatics analysis. Parallel reaction monitoring (PRM) targeted validation identified five candidate proteins associated with COPD with lung cancer. Compared to the COPD group, KRT1, KRT9, and KRT10 were significantly upregulated in the COPD with lung cancer group, while GPLD1 and TF were downregulated. The biomarkers identified in our study provide a foundation for non‐invasive screening and diagnosis of lung cancer in COPD patients and exploration of the mechanisms shared between COPD and lung cancer.

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

Concurrent mutations in tumor protein p53 (TP53) or Kelch‐like ECH‐associated protein 1‐nuclear factor erythroid 2‐related factor 2‐pathway components are linked to poor outcomes in epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC), but the impact of triple mutations remains unclear. We report a case of EGFR‐, TP53‐, and Cullin 3 (CUL3)‐mutant NSCLC in a 43‐year‐old woman with widespread metastases at diagnosis, including those in the contralateral lung, distant lymph nodes, pericardium, liver, bones, left adrenal gland, and brain. She received osimertinib as first‐line therapy, but pericardial effusion and liver metastases progressed rapidly over 3 months, and she was switched to carboplatin and pemetrexed. By the eighth cycle of pemetrexed, the bone metastases had progressed, resulting in disseminated intravascular coagulation (DIC) due to bone marrow carcinomatosis. The patient received third‐line therapy with albumin‐bound paclitaxel and fourth‐line therapy with docetaxel, but further treatment was suspended owing to DIC progression. She passed away 23 months after the initiation of osimertinib. Public database analysis revealed that the EGFR/TP53/CUL3 triple mutation accounts for 0.4% of EGFR‐mutant NSCLC cases, yielding significantly shorter survival than EGFR mutations alone and likely shorter than EGFR/TP53 double mutations. Gaining a deeper understanding of the clinical significance of coexisting genetic mutations in patients with EGFR‐mutant NSCLC will be crucial to develop future therapies.

Introduction Small cell lung cancer (SCLC) is known for its high proliferative rate and poor prognosis. Although Delta‐like ligand 3 (DLL3) is specifically expressed on the surface of SCLC, the association of DLL3 with prognosis in SCLC remains uncertain. Hence, we aimed to evaluate prognostic role of DLL3 in extensive stage of SCLC treated with first‐line chemotherapy. Materials and Methods A total of 54 patients with extensive stage of SCLC (ES‐SCLC) who were treated with first‐line chemotherapy were included for our analysis. In addition, tissue specimen should be available for immuno‐histochemical staining for DLL3, and their clinico‐pathologic data, including progression‐free survival (PFS) and overall survival (OS), were obtained. DLL3 expression and the percentage of tumor cells with DLL3 positive among total cancer cells were analyzed microscopically and DLL3 high and DLL3 low were defined as the percentage of DLL3 positive tumor cells versus total cancer cells ≧ 75% and < 75%, respectively. Results DLL3 expression was not associated with any of the clinico‐pathological characteristics such as age at diagnosis, sex, response to first‐line chemotherapy, second‐line chemotherapy (Yes or No), and number of metastatic sites. However, response to first‐line chemotherapy and number of metastatic sites were correlated to PFS, while DLL3 expression and number of metastatic sites were correlated to OS. Conclusion DLL3 was highly expressed in SCLC, and not associated with any clinico‐pathological characteristics. In survival outcome, DLL3 was correlated with worse OS, which suggests the prognostic role of DLL3 in ES‐SCLC.

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.

Background The cancer cell marker poliovirus receptor‐like protein 4 (PVRL4) has been shown to be highly expressed in many cancers, including lung cancer. Myeloid‐derived suppressor cells (MDSCs) are a population of immature myeloid cells with immunosuppressive roles that can attenuate the anticancer response. Here, the precise functions and the relationship between PVRL4 and MDSCs in lung adenocarcinoma (LUAD) progression were investigated. Methods Detection of levels of mRNAs and proteins was conducted using qRT‐PCR and western blotting. The CCK‐8, colony formation, transwell, wound healing assays, and flow cytometry were used to explore cell growth, invasion, migration, and apoptosis, respectively. ELISA analysis detected TGF‐β1 contents. LUAD mouse models were established for in vivo assay. Exosomes were isolated by ultracentrifugation. MDSCs were induced from peripheral blood mononuclear cells (PBMCs) by cytokine or co‐culture with cancer cells. Results LUAD tissues and cells showed high PVRL4 expression, and PVRL4 deficiency suppressed LUAD cell proliferation, invasion, migration, and induced cell apoptosis in vitro, and impeded LUAD growth in vivo. Thereafter, we found that PVRL4 was packaged into exosomes in LUAD cells, and could be transferred into PBMCs to promote MDSC induction and the expression of MDSC‐secreted TGF‐β1. Functionally, the silencing of exosomal PVRL4 impaired LUAD cell proliferation, invasion, migration, and evoked cell apoptosis, which could be reversed by the incubation of TGF‐β1‐overexpressed MDSCs. Conclusion Exosomal PVRL4 promoted LUAD progression by inducing the secretion of TGF‐β1 in MDSCs, indicating a novel direction for LUAD immunotherapy.

Introduction To identify high‐risk patients for recurrence in resected stage IA lung adenocarcinoma and evaluate the impact of adjuvant chemotherapy (ACT) on their prognosis, as well as explore potential novel adjuvant therapies. Methods Consecutive stage IA patients with ≥ 5% solid or micropapillary subtypes were analyzed. A nomogram was developed using Cox proportional hazards regression to predict recurrence‐free survival (RFS). In the high‐risk group after stratification, RFS was compared between patients receiving ACT and those under observation, as well as between patients with and without driver gene alterations. Results This real‐world study included 1328 patients, with a 5‐year RFS of 79.0%. T stage and predominant subtype were independent risk factors for RFS. Patients with T1c or solid/micropapillary‐predominant tumors were stratified into a high‐risk group (n = 483) using the nomogram. A significant difference in 5‐year RFS was observed between the high‐ and low‐risk groups (73.6% vs. 84.3%, p < 0.001). Among high‐risk patients, sixty‐seven (13.8%) received ACT; however, there was no improvement in 5‐year RFS compared to observation alone (69.1% vs. 75.0%, p = 0.655). Testing rates for EGFR mutation and ALK fusion among high‐risk patients were only 52.4% and 43.9%, respectively, while mutation rates reached up to 55.7% and 9.4%, respectively. These molecular alterations exhibited numerically worse 5‐year RFS compared to wild‐type (EGFR mutation, 70.6% vs. 87.8%, p = 0.108; ALK fusion, 66.3% vs. 73.6%, p = 0.404), though not significant. Conclusions ACT failed to meet the needs of stage IA patients with histological high‐risk features. Further exploration of effective adjuvant target therapies is warranted for this patient subgroup.

Tracheal obstruction can arise from multiple conditions, including chronic obstructive pulmonary disease, asthma, foreign bodies, tumors, and acute heart failure. We report a case of a 43‐year‐old man with cervical liposarcoma who, following surgical excision, chemotherapy, and radiation, presented with severe dyspnea and was admitted to our hospital. A CT scan detected an endotracheal mass causing significant obstruction, suspected to be malignant. The patient required intensive care due to respiratory distress. Bronchoscopy revealed a red polypoid lesion causing nearly 90% tracheal narrowing, which was successfully resected using high‐frequency electrotrap and argon coagulation, confirming it as a metastasis from the previously treated liposarcoma. Remarkably, there were no significant recurrences after 6 months. While lung metastases are frequent, intratracheal metastasis is rare; this case is the first documenting bronchial and tracheal metastasis of liposarcoma. It highlights the dangers of airway obstruction and the need for timely intervention. Although CT scans are helpful in identifying intrabronchial tumors, bronchoscopy remains the gold standard for diagnosis and treatment, with several options available for urgent cases.

Background Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy, and the molecular underpinnings of its aggressive behavior are not fully understood. FYN proto‐oncogene, Src family tyrosine kinase (FYN) has been linked to cancer progression, yet its role in ESCC remains elusive. This study investigated the influence of FYN on ESCC malignancy. Methods Quantitative real‐time polymerase chain reaction was used to assess the mRNA expression of FYN, while western blotting and immunohistochemistry (IHC) assays were performed to detect the protein expression of FYN, ubiquitin specific peptidase 8 (USP8) and protein tyrosine kinase 2 (PTK2). Cell viability was measured with a cell counting kit‐8 assay, and cell apoptosis was evaluated using flow cytometry. Results FYN expression was increased in ESCC tissues and cells when compared with normal esophageal tissues and normal esophageal epithelial cells. Knockdown of FYN inhibited cell invasion, migration, stem‐like traits, and glycolysis, while promoting apoptosis. USP8 was shown to stabilize FYN protein expression through its deubiquitinating activity in ESCC cells. Overexpression of FYN reversed the effects of USP8 silencing on the malignant phenotypes of ESCC cells in vitro and in vivo. FYN upregulated PTK2 expression in both TE1 and KYSE150 cell lines. Furthermore, PTK2 overexpression reversed the effects of FYN silencing on the malignant phenotypes of ESCC cells. Further, USP8 silencing‐induced inhibitory effect on PTK2 protein expression was counteracted after FYN overexpression. Conclusion USP8‐dependent FYN contributed to the malignant progression of ESCC by interacting with PTK2. Targeting this pathway may offer a novel therapeutic strategy for ESCC treatment.

We herein describe a patient with non‐small‐cell lung cancer who achieved pCR with a single dose of pembrolizumab‐based chemoimmunotherapy followed by surgery. A 61‐year‐old man was referred to our hospital with wheezing and an abnormal chest shadow. Squamous cell carcinoma of the left lower lobe, cT2aN1M0 stage IIB, was diagnosed and pembrolizumab‐based chemoimmunotherapy was initiated at the patient's request. One month later, chest CT revealed new ground‐glass opacities of the lungs, which were judged to be a CTCAE grade 2 pneumonitis due to an immune‐related adverse event (irAE). Therefore, steroid therapy was initiated. Prednisolone was tapered and discontinued as symptoms improved. A sleeve resection of the left lower lobe was performed, and a pathological complete response (pCR) was confirmed in a resected specimen. There has been no recurrence for 1 year and 7 months without treatment. This is the first case report of pCR to a single dose of chemoimmunotherapy followed by surgery for lung cancer. The present results suggest the potential of a single dose of chemoimmunotherapy to achieve pCR and cause irAEs in some patients.

Background This study aims to investigate the factors influencing false‐negative results in ultrasound‐guided percutaneous transthoracic needle lung biopsy results (US‐PTLB). Materials and Methods This ambispective cohort study included patients with subpleural pulmonary lesions who underwent US‐PTLB with benign pathological findings between April 2017 and June 2022 (retrospective cohort) and between July 2022 and October 2022 (prospective cohort). In the retrospective cohort, comparative and logistic regression analyses were performed to identify independent risk factors for false‐negative biopsy results. Stratified analyses based on these risk factors were performed in the prospective cohort. Results The retrospective cohort included 1747 (true‐negative: false‐negative, 1321:426) patients with negative biopsy results, which were analyzed by comparative and logistic regression analyses, and the results demonstrated that advanced age (> 56 years) (OR = 1.08, 95% CI: 1.07–1.09), small‐sized lesions (< 3 cm) (OR = 1.80, 95% CI: 1.38–2.34), lesions with necrosis (OR = 3.00, 95% CI: 2.29–3.92), contrast‐enhanced ultrasound (CEUS) showing hyper‐enhancement (OR = 5.87, 95% CI: 4.09–8.42) or iso‐enhancement (OR = 2.81, 95% CI: 2.05–3.83), and the presence of hemoptysis (OR = 11.82, 95% CI: 5.16–27.08) or pneumothorax (OR = 7.90, 95% CI: 2.89–21.58) during the puncture were independent predictors of false‐negative US‐PTLB results. The results of stratified analyses in the prospective cohort were consistent with the retrospective cohort. Conclusion Risk factors associated with false‐negative results included advanced age (> 56 years), small‐sized lesion (< 3 cm), presence of necrosis in the lesion, CEUS showing hyper‐enhancement or iso‐enhancement of the lesion, and hemoptysis or pneumothorax during puncture. Trial Registration: Number: ChiCTR2000029749

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 Stereotactic ablative radiotherapy (SABR) is renowned for its high local control (LC) rates. Nonetheless, for tumors that are either large in volume or in close proximity to critical organs at risk, the application of SABR to the entire tumor becomes impractical. This study aims to evaluate the efficacy and safety of partial SABR boost before conventional radiotherapy (P‐SABR) for the treatment of large (> 5 cm) unresectable stage III nonsmall cell lung cancer (NSCLC). Methods From April 2014 to January 2024, 44 patients with > 5 cm unresectable T3‐4N0‐3M0 stage III NSCLC were analyzed. The median diameter was 9 cm (5.2–22.7 cm). The P‐SABR plan is combined with a partial SABR boost part and a conventional fractionated radiotherapy (CFRT) part. In the partial SABR boost plan, the prescription dose for planning target volume (PTV) was 1.8–3 Gy per fraction over 3–4 fractions, and the artificially delineated gross tumor boost volume (GTVb) within GTV received a simultaneously integrated SABR dose (6 or 8 Gy per fraction). In the following CFRT plan, the median dose for the entire PTV was 54 Gy in 22 fractions. For the synthetic P‐SABR plan, the median cumulative dose delivered to the PTV was 62.1 Gy, while the median cumulative dose to the GTVb was escalated to 78 Gy. Results The median follow‐up time was 36 months (95% CI, 14.6–57.4 months). The LC rates at 1 and 2 years were 90.2% and 76.8%, respectively. The median OS was 47.0 months (95% CI, 16.8–77.2 months) and 15.0 months (95% CI, 6.0–24.0 months) for the chemoradiotherapy and radiotherapy groups, respectively. Univariate analysis showed that P‐SABR combined with immunotherapy was associated with significantly longer OS (HR, 0.163; 95% CI, 0.038–0.704). Only one (2.3%) patient experienced grade 3 acute pneumonitis. Conclusions The P‐SABR treatment has shown a high rate of LC and tolerable toxicity in patients with large unresectable stage III NSCLC.

Background The effects of lobectomy at various lung sites on postoperative function and recovery vary. This study aimed at assessing the long‐term impact of upper versus lower lobectomy on patients' postoperative daily function by analyzing patient‐reported outcomes. Methods This multicenter prospective cohort study enrolled patients from six hospitals in China. Functional impairments and symptom severity were measured using the MD Anderson Symptom Inventory‐Lung Cancer. A mixed‐effects linear model was employed to analyze the average trajectories of each functional item and the top five symptoms over the first year following surgery between patients undergoing upper and lower lobectomy. The median recovery days for daily function were estimated using the Kaplan–Meier method, with the log‐rank test comparing differences between upper and lower lobectomy. Results Two hundred twenty‐six patients met the final analysis criteria, with 137 undergoing upper and 89 undergoing lower lobectomies. Those in the lower lobectomy group reported significantly greater interference with daily activities (estimate = 0.872, SE = 0.306, p = 0.004), mood (estimate = 0.667, SE = 0.297, p = 0.025), and work (estimate = 0.856, SE = 0.358, p = 0.017), indicating a more pronounced impact on postsurgical functional recovery compared to the upper lobectomy group within the first year after surgery. They also experienced longer median recovery times for daily activities (15 vs. 4 days), mood (6 vs. 3.5 days), and walking (7 vs. 4 days) compared to the upper lobectomy group. Conclusions Within the first year after surgery, lower lobectomy patients experienced greater impairment in daily functions and required longer recovery times compared to upper lobectomy patients. Trial Registration NCT03341377

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.

Purpose Lung cancer (LC) is a leading cause of death and presents a substantial societal burden. This article compares its disease burden and risk factors between China and Australia to support health policymakers for LC prevention and treatment. Materials and Methods The data from the 2019 Global Burden of Disease Study were used to analyze disease temporal trends using Joinpoint regression model. The Bayesian age‐period‐cohort model was used for prediction. The population‐attributable fraction (PAF) was used to analyze LC risk factors. Results In 2019, the age‐standardized rates (ASR) of incidence and of mortality of LC in China were 41.71/100 000 and 38.70/100 000, while Australia's rates were 30.45/100 000 and 23.46/100 000. It showed an increasing trend in China but a decreasing trend in Australia. By 2030, the ASR of incidence and mortality are predicted to be 47.21/100 000 and 41.54/100 000 in China, while Australia's rates will reach 30.09/100 000 and 23.3/100 000, respectively. Smoking is the most common risk factor for LC, followed by particulate matter and occupational carcinogenesis. The PAF of smoking dropped in Australia (from 68.38% to 53.75% in females; 77.41% to 58.47% in males) but increased in China (from 19.56% to 26.58% in females; 80.45% to 82.03% in males) from 1990 to 2019. Conclusions The disease burden of LC in China is rising, whereas in Australia, it is declining. China still faces a heavy LC burden. Risk factor analysis supported for further improving the compliance and enforcement of polices on tobacco control and environmental management to reduce this disease burden.

Background Testing for targeting programmed death ligand 1 (PD‐L1) is standard of care for patients with newly diagnosed non‐small cell lung cancer (NSCLC) but is only approved for use with core biopsy specimens. Endobronchial ultrasound guided miniforceps biopsy (EBUS‐MFB) is an approach to obtain core biopsy material but data assessing the ability of EBUS‐MFB to adequately test for PD‐L1 is lacking. We evaluate the feasibility of EBUS‐MFB to acquire adequate tissue for PD‐L1 testing and look to compare the quality of specimens between EBUS‐MFB and endobronchial ultrasound guided transbronchial needle aspiration (EBUS‐TBNA) using a standard method of tissue analysis. Methods Twenty patients with suspected non‐small cell lung cancer undergoing bronchoscopy were recruited for enrollment. For each patient with NSCLC diagnosed on rapid onsite pathology with EBUS‐TBNA, EBUS‐MFB was performed. PD‐L1 immunostaining was completed to assess for adequacy. A comparison of tissue collection was performed using the total surface area measured by digital imaging. Results Among 20 patients, 65% were male with a mean age of 66 years with a total procedure time of 50 min and an average of 14 biopsy passes per procedure. 15 (75%) patients were diagnosed with NSCLC, and PD‐L1 analysis was successfully performed in 12 of the 15 (80%). The mean total tissue area obtained by the MFB technique was 9.757 mm² compared to 6.941 mm² with TBNA (p = 0.427). Conclusion In this feasibility study, EBUS‐MFB was successful in performing PD‐L1 testing in 80% of patients with NSCLC.

Background Cachexia is a poor prognostic factor in many advanced cancers. Cachexia diagnostic criteria of the European Palliative Care Research Collaboration (EPCRC) may underestimate cachexia in Asians; therefore, new criteria have been proposed by the Asian Working Group for Cachexia (AWGC). We compared both criteria to determine differences in diagnostic rates and their association with lung cancer prognosis. Patients and Methods This single‐center, retrospective cohort study considered lung cancer outpatients receiving chemotherapy. Survival was analyzed using Kaplan–Meier curves and log‐rank tests. The association between cachexia diagnosis and prognosis was examined for each set of criteria using a Cox proportional hazards model. C‐statistic analysis was performed to compare the discriminative power for prognosis. Results Among the 106 participants analyzed (median age, 75 [71–79] years; 75 males [70.8%]; 91 [85.9%] with performance status [PS] 0–1), 58 (54.7%) and 77 (72.6%) cachexia cases were diagnosed using the EPCRC and AWGC criteria, respectively. The latter encompassed all but one patient diagnosed using the EPCRC criteria. Patients with cachexia had a significantly poorer prognosis according to both criteria (EPCRC, p = 0.002; AWGC, p = 0.001). Both criteria had almost equal discriminative power for prognosis (EPCRC, C‐statistic = 0.658; AWGC, C‐statistic = 0.658). CRP in the AWGC criteria was most strongly related to prognosis. Conclusions Cachexia was an independent poor prognostic factor in lung cancer patients receiving chemotherapy under the AWGC and EPCRC criteria, both of which had similar prognostic discriminatory power. Among CRP, anorexia, and grip strength, elevated CRP may be the most prognostically relevant parameter in the AWGC criteria.