Overall survival (OS) among patients with limited-disease small-cell lung cancer (LD-SCLC) receiving chemoradiotherapy can be significantly influenced by subsequent treatments. Thus, the present study aimed to examine the interplay between progression-free survival (PFS), post-progression survival (PPS) and OS in patients with LD-SCLC undergoing chemoradiotherapy. This study retrospectively analyzed 84 patients with relapsed LD-SCLC who received chemoradiotherapy between April 2007 and June 2021. The correlations between PFS and OS as well as PPS and OS post-chemoradiotherapy were analyzed at the individual patient level. Spearman's rank correlation and linear regression analyses revealed a robust correlation between PPS and OS (r=0.76; P<0.05; R2=0.85). PFS was moderately correlated with OS (r=0.57; P<0.05; R2=0.25). Furthermore, the presence of liver metastases upon relapse and the administration of platinum re-challenge chemotherapy were significantly associated with PPS (P<0.05). The analysis of relationships between OS and PFS as well as OS and PPS in this patient cohort revealed that OS was more strongly correlated with PPS than PFS. These findings suggest that factors such as liver metastases at relapse and the administration of platinum re-challenge chemotherapy may influence PPS.

Centrally located early-stage non-small cell lung cancer (ES NSCLC) with tumors close to the bronchi is potentially curable with stereotactic body radiation therapy (SBRT). To evaluate the clinical benefit of the treatment, both the risk of high-grade toxicity as well as the treatment efficacy need to be assessed.

From the expanded HILUS cohorts, 72 patients with T1-T3N0M0 NSCLC were included in the current analysis. All patients had been treated with SBRT in 8 fractions to 56 Gy for a tumor located within 2 cm from the tracheobronchial tree. Primary endpoint was progression free survival (PFS) and secondary endpoints included pattern of failure, local control (LC), lung cancer-specific survival (LCSS), overall survival (OS) and toxicity. The Kaplan-Meier method and Cox regression analysis were used.

The median age of the cohort was 73 years and all patients suffered from comorbidities prior to SBRT. T2-T3 tumors were seen in 65 % of the patients. Seventeen patients relapsed after SBRT and distant recurrence was the most common form of relapse. Three-year PFS was 31 % (95 % CI 22-44) and largely explained by the short overall survival (38 % (95 % CI 22-44) at 3 years). Three-year rates of LC and LCSS were 97 % (95 % CI 92-100) and 76 % (95 % CI 65-89), respectively. Twelve patients (17 %) suffered from grade 5 toxicity, of which 9 were bronchopulmonary bleedings.

The severe toxic profile limits the clinical benefit using SBRT with the investigated approach for patients with centrally located ES NSCLC.

Chemoradiotherapy (CRT) followed by adjuvant durvalumab is the standard of care for fit patients with unresectable stage III non-small cell lung cancer (NSCLC). However, 20-25 % of the patients do not survive longer than 1 year after treatment initiation, i.e. receive futile treatment. We aimed to develop a prognostic model that can identify patients at high risk of early mortality during and after CRT.

Patients with stage III NSCLC treated with CRT were included in the development- (N = 328; MAASTRO Biobank, 2004-2020, NCT01084785) and validation cohorts (N = 39; NCT02921854, NCT04432142). Both clinical parameters (age, sex, body mass index, performance status (PS), tumor stage (UICC 8), and sequence of chemotherapy administration) and peripheral immune-related biomarkers were included in the model development. Futile treatment was defined as death within one year after the first fraction of RT.

In the multivariable logistic regression analysis, PS ≥ 2 (OR = 2.89, 95 % CI 1.25-6.66, p = 0.013), stage IIIC (OR = 3.07, 95 % CI 3.07-6.9, p = 0.007), sequential chemotherapy (OR = 2.07, 95 % CI 1.19-3.62, p = 0.010), IL-6 (OR = 2.17, 95 % CI 1.27-3.70, p = 0.005), IP-10 (OR = 1.58, 95 % CI 0.92-2.73, p = 0.099), and soluble programmed death-ligand 1 (sPD-L1) (OR = 3.24, 95 % CI 1.90-5.54, p < 0.001) were identified as independent risk factors of early mortality. A nomogram was developed to calculate the risk of receiving futile treatment for each patient. The AUC of the development and validation cohort was 0.774 (95 % CI 0.716-0.832) and 0.734 (95 % CI 0.568-0.902), respectively. Patients classified as intermediate or high risk to receive futile treatment presented 23.7 % of the total cohort.

A prognostic model was developed that can identify patients who are at high risk of early mortality during and after CRT. These patients may be included in clinical trials aiming to improve their outcome.

Lung adenocarcinoma is a common type of cancer that can lead to bone metastasis and has a poor prognosis. Although previous studies have established nomograms for lung adenocarcinoma, these nomograms do not effectively predict the prognosis of lung adenocarcinoma patients with bone metastasis. This study aims to establish and validate a new nomogram to solve this problem.

Data were collected from the SEER database and from patients at our hospital who had been diagnosed with lung adenocarcinoma and developed bone metastases. The patients were randomly assigned into the training and internal validation sets in a 7:3 ratio. External validation was conducted using an independent patient cohort from two hospitals. Different methods were used to evaluate the nomogram's performance. The relationship between different metastatic sites and radiotherapy and chemotherapy was also analyzed to evaluate patient prognosis.

The following factors were identified as significant prognostic indicators: age, sex, marital status, T stage, N stage, tumor grade, tumor size, presence of brain and liver metastases, and receipt of chemotherapy. The nomogram's concordance indices for predicting overall survival were consistently above 0.7, and the area under the curve values, calibration plots, and decision curves all confirmed the nomogram's strong predictive accuracy. Moreover, our analysis revealed that chemotherapy was the most effective treatment modality.

This study developed a nomogram that can predict the prognosis of lung adenocarcinoma patients with bone metastasis. The results showed that patients with liver metastasis had the worst prognosis and that chemotherapy was the most effective treatment regimen for patients with different metastatic sites.

This study aimed to investigate the characteristics and clinical courses of patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) and compare the differences across lung cancer types.

This prospective study included 11,310 patients with LCNEC, small cell lung cancer (SCLC), squamous cell carcinoma, and adenocarcinoma from the Japanese Joint Committee of Lung Cancer Registry (JJCLCR) database. The registry was opened in January 2012, and the follow-up was completed in April 2016.

In total, 80 patients (0.7 %) were diagnosed with LCNEC. LCNEC shared similar patient characteristics with SCLC, characterized by a median age of 68 years and a high prevalence of men (93.8 %) and smokers (97.5 %). In stage IV patients, the best overall response and disease control rates for first-line cisplatin-based chemotherapy were 34.8 % and 43.5 % for LCNEC but 60.6 % and 69.7 % for SCLC. Similarly, the overall response and disease control rates for first-line carboplatin-based chemotherapy in stage IV patients were 29.4 % and 41.2 % for LCNEC, but 56.1 % and 68.4 % for SCLC. The 3-year survival rates for LCNEC, SCLC, squamous cell carcinoma, and adenocarcinoma were 14.2 %, 15.9 %, 17.8 %, and 27.1 %, respectively. Kaplan-Meier curves of overall survival showed similarity between LCNEC and SCLC, with no statistical significance in the Cox hazard analysis (hazard ratio 0.818, 95 % confidence interval 0.611-1.096, p = 0.178).

Although patient characteristics and survival curves were similar in LCNEC and SCLC, our data demonstrate that LCNEC had inferior overall response and disease control rates in response to first-line chemotherapy compared to SCLC.

Lung cancer is the leading cause of cancer-related mortality in the United States, which disproportionately affect racial and ethnic minorities. Disparities in lung cancer screening, diagnosis, treatment, and survival outcomes are due to a complex interplay of socioeconomic factors, structural racism, and limited access to high-quality care. This review aims to examine the underlying causes of these disparities and explore potential mitigation strategies to improve lung cancer care equity.

A review of the literature was conducted, evaluating racial and ethnic disparities in lung cancer care. Disparities in lung cancer screening, genomic testing, surgical and systemic treatment, and survival were explored. Additionally, interventional strategies such as risk-based screening, patient navigation programs, and policy reforms were examined.

Racial and ethnic minority patients are diagnosed at younger ages with fewer pack-years yet are less likely to qualify for screening under current guidelines. They receive lower rates of guideline-concordant treatment, including surgery, radiation, chemotherapy, and biomarker testing, and have reduced access to specialty care. Socioeconomic barriers, medical mistrust, and geographic disparities further contribute to these inequities. Targeted interventions, including mobile screening programs, financial assistance initiatives, and culturally competent care, have shown promise in improving lung cancer outcomes.

A multi-level approach, incorporating healthcare policy changes, improved screening criteria, and an enhanced community engagement strategy, is essential for achieving equitable lung cancer care, ultimately improving outcomes for racial minority populations.

Exosome complex gene 5 (EXOSC5), a member of the exosome complex family, is highly tumorigenic in various cancers. However, its prognostic value and underlying mechanisms in lung adenocarcinoma (LUAD) remain unclear.

We analysed LUAD data from The Cancer Genome Atlas (TCGA) via bioinformatics tools. Logistic regression was used to assess the associations between clinical information and EXOSC5 expression in LUAD patients. EXOSC5 expression was validated by immunohistochemistry (IHC) and western blotting, and its functional role was investigated through gene set enrichment analysis (GSEA) and in vitro experiments.

EXOSC5 was significantly upregulated in LUAD and associated with poor prognosis. The risk model based on EXOSC5 expression outperformed the traditional staging system for prognosis prediction. EXOSC5 promoted tumor progression by regulating the cell cycle, proliferation, and immune cell infiltration. High EXOSC5 expression was correlated with resistance to anti-PD1 immunotherapy.

EXOSC5 is a novel oncogenic factor in LUAD that promotes tumor progression and immune evasion and may serve as a prognostic biomarker and therapeutic target.

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.

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.

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.

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.

Approval No. 15,321.

This multicenter single-arm confirmatory trial (CRES3T) investigated the efficacy and safety of S-1 + cisplatin and concurrent radical-dose radiotherapy followed by surgery in patients with a superior sulcus tumor.

Patients received induction therapy comprising three cycles of S-1 + cisplatin with concurrent radiotherapy (66 Gy in 33 fractions) followed by surgery. S-1 was administered orally at 40 mg/m2 twice/day on days 1-14, with an intravenous infusion of cisplatin (60 mg/m2) on day 1. The primary endpoint was the 3-year overall survival rate; key secondary endpoints included progression-free survival rate, objective response rate, pathological complete response rate, and toxicity.

Sixty-one patients with a superior sulcus non-small cell lung cancer received induction therapy. Radiological tumor invasion sites were the chest wall (n = 57), subclavian artery (n = 18), and subclavian vein (n = 10). Forty-nine patients underwent a lobectomy and combined resection of the involved structures. The objective and pathological complete response rates were 42 % (95 % confidence interval: 29-54 %) and 33 % (95 % confidence interval: 20-46 %), respectively. The 3-year overall survival and progression-free survival rates were 73.2 % (95 % confidence interval: 60.1-82.7 %) and 53.3 % (95 % confidence interval: 40.0-65.0 %), respectively. The patterns of first tumor relapse were locoregional only in one, distant metastasis only in 18, and both in four patients. Two pneumonia cases during induction therapy and one cardiac-arrest case on postoperative day 3 resulted in death.

Induction therapy using S-1 + cisplatin and concurrent radical-dose radiotherapy followed by surgery maximized local control and improved overall survival without impairing safety, potentially representing a new standard treatment.

Osimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation.

FLAIR is a prospective, multicenter, randomized, open label study, which is initiated by Chinese Thoracic Oncology Group (CTONG2002). Patients age ≥18 years with primary recurrent or metastatic nonsquamous NSCLC who are treatment-naïve with documented EGFR exon 21 L858R mutation is eligible. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until progression or another discontinuation criterion is met. The primary endpoint is investigator-assessed progression free survival (PFS). Secondary endpoints include: overall survival rate at 24 months, time to treatment failure (TTF), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), central nervous system (CNS) PFS, CNS ORR and safety.

FLAIR has completed the enrollment, and results are expected in the fourth quarter of 2025 (depending on the actual event rate).

This study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.

Lung cancer is the leading cause of cancer-related deaths, of which adenocarcinoma is the most common subtype. Despite this, lung adenocarcinoma and its metastasis are poorly understood, due to difficulties in feasibly recapitulating disease progression and predicting clinical benefits of therapy. We outline a methodology to develop immunogenic orthotopic lung adenocarcinoma mouse models, by injecting cell-specific cre viruses into the lung of a genetically engineered mouse, which mirrors cancer progression defined by the International Association for the Study of Lung Cancer. Evaluation of different cre virus/concentrations models demonstrate remarkable consistency in cancer initiation and metastasis, allowing for high throughput, while showing differences in timing and severity, offering greater flexibility when selecting models. Histological and immune profiles reflect clinical observations suggesting similar mechanisms are recapitulated and preliminary data show resultant tumors to be responsive to clinical treatments. We present a clinically relevant, next-generation murine model for studying lung adenocarcinoma.

Inflammatory myofibroblastic tumors (IMTs), rare soft tissue neoplasms, are characterized by a blend of myofibroblastic proliferation and inflammatory features. While generally characterized by slow growth, IMTs can exhibit locally aggressive behavior, and in rare instances, metastasize to distant sites. This study elucidated the clinical characteristics, molecular profile, and tumor microenvironment of thoracic IMTs.

We retrospectively analyzed cases of IMTs diagnosed at the National Taiwan University Hospital between 2000 and 2020. ALK immunohistochemistry (IHC) was performed, followed by fluorescence in situ hybridization (FISH) for confirmation. Next-generation sequencing (NGS) was employed to detect unknown oncogenic drivers, and multiplex immunofluorescence staining was used to characterize the tumor microenvironment. Demographic, clinicopathological characteristics, and treatment outcomes were systematically recorded and analyzed.

We identified a total of 8 patients with thoracic IMTs, whose median age of the participants was 33.8 years (range: 18.6-58.7). The disease status of all tumors were early-stage, and all patients underwent surgical excision. ALK fusions were detected in 6 tumors (all spindle-cell patterns), with fusion partners including 3 TPM3, 2 DCTN1, and one EML4. In the remaining 2 tumors without ALK fusion, NGS showed NTRK3 alteration with high gene expressions. Multiplex IHC of three cases identified a pronounced infiltration of macrophages cells within the tumor microenvironment.

Patients with thoracic IMT patients are typically young with early-stage disease. ALK fusion were the most common genetic alteration, particularly in spindle-cell patterns. Characterization of the tumor microenvironment indicates the potential of immune profiling in the tumor biology and targeted immunotherapy approaches.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated crystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.

Delayed surgery is significantly associated with an increased risk of disease progression and adverse outcomes in lung cancer. Evidence is available on the variation in delayed surgical treatment among patients with Non-Small Cell Lung Cancer (NSCLC). However, the relative contribution of patient- and area-level risk factors to the geographic patterns of delayed surgery in patients with NSCLC is poorly understood. Therefore, we aimed to explore the geographic variation in delay to surgical treatment among patients with NSCLC.

This study utilized data from the Victorian Lung Cancer Registry (VLCR) and the Australian Bureau of Statistics (ABS). A total of 3,088 patients with NSCLC who had undergone surgery were included. We applied a Bayesian spatial multilevel model incorporating spatially structured and unstructured random effects to examine patient and area-level risk factors associated with delays to surgical treatment. Model comparison was conducted using the Deviance Information Criterion (DIC).

Over one-third (40.45 %) of NSCLC patients experienced delayed surgical treatment. Significant geographic variation in delayed surgical treatment among NSCLC patients across Local Government Areas (LGAs) was observed. Factors significantly associated with higher odds of delayed surgical treatment included clinical stage II (AOR = 1.56, 95 % CrI: 1.26-1.92), stage III (AOR = 1.90, 95 % CrI: 1.46-2.47), stage IV (AOR = 2.04, 95 % CrI: 1.15-3.61), treatment at inner regional hospitals (AOR = 2.86, 95 % CrI: 2.17-3.70), presence of comorbidities (AOR = 1.19, 95 % CrI: 1.02-1.40), and diagnosis during the COVID-19 pandemic (AOR = 1.32, 95 % CrI: 1.10-1.57).

This study highlights the need to improve the treatment pathway for patients with NSCLC by reducing the time between diagnosis and surgery. Future targeted initiatives are essential to promote timely surgeries for NSCLC patients, especially in high-need areas.

Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.

Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.

A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.

Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

This study aimed to assess the efficiency of artificial intelligence (AI) in the detection of visceral pleural invasion (VPI) of lung cancer using high-resolution computed tomography (HRCT) images, which is challenging for experts because of its significance in T-classification and lymph node metastasis prediction.

This retrospective analysis was conducted on preoperative HRCT images of 472 patients with stage I non-small cell lung cancer (NSCLC), focusing on lesions adjacent to the pleura to predict VPI. YOLOv4.0 was utilized for tumor localization, and EfficientNetv2 was applied for VPI prediction with HRCT images meticulously annotated for AI model training and validation.

Of the 472 lung cancer cases (500 CT images) studied, the AI algorithm successfully identified tumors, with YOLOv4.0 accurately localizing tumors in 98% of the test images. In the EfficientNet v2-M analysis, the receiver operating characteristic curve exhibited an area under the curve of 0.78. It demonstrated powerful diagnostic performance with a sensitivity, specificity, and precision of 76.4% in VPI prediction.

AI is a promising tool for improving the diagnostic accuracy of VPI for NSCLC. Furthermore, incorporating AI into the diagnostic workflow is advocated because of its potential to improve the accuracy of preoperative diagnosis and patient outcomes in NSCLC.

Background Lymph node staging is a critical component in managing lung cancer, as it determines prognosis and guides treatment decisions. Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) has emerged as a highly sensitive and specific imaging modality for evaluating nodal involvement, surpassing conventional imaging techniques. Therefore, this study evaluated the diagnostic accuracy of PET-CT in lymph nodal staging of lung cancer, using histopathology as the gold standard. Methodology This cross-sectional study was conducted at the Radiology and PET Scan Department, Jinnah Postgraduate Medical Centre (JPMC), Karachi, over six months, from January 28, 2021, to July 28, 2021, using a non-probability consecutive sampling. It included 127 biopsy-proven lung cancer patients aged 21-80 years. FDG PET-CT scans were evaluated by an experienced radiologist, with findings compared against histopathology results after surgery and biopsy. Using IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States), data analysis included calculating the sensitivity, specificity, and predictive values of FDG PET-CT for nodal metastasis, with histopathology as the gold standard. Results The study findings showed that out of 127 lung cancer patients, with a mean age of 54.14 ± 10.41 years, 99 (78.0%) were male, and 111 (87.4%) were aged >40 years. Symptoms persisted for a mean of 12.04 ± 6.82 weeks, and 88 (69.30%) had standardized uptake value (SUV)>3.0. Nodal staging showed N1 nodes in 64 (50.40%), N2 in 37 (29.10%), and N3 in 26 (20.50%). PET-CT detected nodal metastasis in 89 (70.18%) of cases, with histopathology confirming metastasis in 95 (74.88%). PET-CT achieved a sensitivity of 91.50%, specificity of 93.75%, positive predictive value (PPV) of 97.75%, and negative predictive value (NPV) of 78.95%. The overall accuracy of PET-CT was 92.13%, with a strong correlation to histopathology, emphasizing its reliability in staging nodal metastasis. Conclusion This study concluded the high diagnostic accuracy of PET-CT in detecting nodal metastasis in lung cancer, with an overall accuracy of 92.13%. PET-CT demonstrated excellent sensitivity (91.50%) and specificity (93.75%). These results confirm PET-CT as a reliable imaging modality for lymph nodal staging.

Tumor growth and progression involve coordinated regulation by internal, microenvironmental, and systemic signals and often display conspicuous sexual dimorphism. The mechanisms governing the integration and coordination of these signals, along with their sex-based differences, remain largely unknown. Using a Drosophila tumor model originating from nonreproductive tissue, we show that female-biased tumor growth involves multifaceted communications among tumor cells, hemocytes, and neuroendocrine insulin-producing cells (IPCs). Notch-active tumor cells recruit hemocytes carrying the tumor necrosis factor-α (TNF-α) homolog Eiger to the tumor microenvironment (TME), activating the c-Jun N-terminal kinase (JNK) pathway in tumor cells, instigating the sexually dimorphic up-regulation of cytokine Unpaired 2 (Upd2). Upd2, in turn, exerts a distal influence by modulating the release of a Drosophila insulin-like peptide (Dilp2) from IPCs. Dilp2 then activates the insulin signaling in the tumor, thereby fostering sexual-dimorphic tumor growth. Together, these findings reveal a relay mechanism involving the TME and systemic signals that collectively control the sexual dimorphism of tumor growth.

Lung cancer in Australia contributes 9% of all new cancer diagnoses and is the leading cause of cancer death and burden. Clinical practice guidelines provide evidence-based treatment recommendations for best practice management. We aimed to determine the extent of delivery of guideline-concordant treatment (GCT) and to identify modifiable variables influencing receipt of GCT and survival.

Data was sourced from the Victorian Lung Cancer Registry (VLCR) in Victoria, Australia. Descriptive statistics were used to summarize patient and disease characteristics according to treatment type: GCT versus non-GCT versus no/declined treatment. Statistical analyses included multiple logistic regression, multiple COX regression and Kaplan-Meier survival estimates.

52% of patients were treated with GCT, 32.8% non-GCT and 15.2% declined or received no treatment. GCT treated patients were younger, never smoked, had no comorbidities, had better performance status, had early stage cancer, were discussed at a multidisciplinary meeting or had treatment at a higher volume hospital. Overall, patients that received GCT had a 24% lower risk of mortality compared to patients that received non-GCT.

Modifiable variables impacting likelihood of receiving GCT included age, smoking status and treating hospital characteristics. Several modifiable variables were identified with positive impacts on survival including increased treatment of the elderly, smoking cessation, delivery of GCT, and treatment in higher volume hospitals. The measurement and reporting of delivery of GCT has positive impacts on survival and therefore merits consideration as an evidence-based quality indicator in the reporting of lung cancer quality and safety outcomes.

This study aimed to clarify the relationship between preoperative sarcopenia and prognostic nutritional index (PNI) statuses and clinicopathological factors in patients with non-small cell lung cancer (NSCLC) who underwent surgical resection, and to evaluate short- and long-term outcomes by stratifying groups according to sarcopenia and PNI status as prognostic predictors.

This study included 300 patients with p-Stage I-IIIA NSCLC who underwent complete resection with lobectomy. Sarcopenia was assessed using the skeletal muscle index (SMI) and the immunonutritional index was evaluated using the PNI. The first quartile was used as the cutoff for the sarcopenia/non-sarcopenia and low/high-PNI groups.

The median patient age was 70 years, and 184 patients (61.3 %) were male individuals. The median PNI was 50.2, and the median SMI was 48.1 and 37.5 for male and female patients, respectively. The median follow-up period was 64 months (60 patients died). Survival analysis showed that overall survival was significantly worse in the sarcopenia and low-PNI groups than in the control group (p = 0.002 and p < 0.001, respectively). When stratified by sarcopenia and PNI status, the sarcopenia with low-PNI group had a particularly poor prognosis (5-year survival rate, 52.8 % [p < 0.001]). Multivariable Cox regression analysis revealed that sarcopenia with low PNI was an independent prognostic factor that indicated a poor outcome. The response to drug treatment for postoperative recurrence was significantly worse in the sarcopenia with low-PNI group than inthe other group.

The combination of preoperative sarcopenia and immunonutritional impairment had a negative clinical impact independent of tumor factors, and patients with these two indications had a particularly poor prognosis. These factors may be associated with poor responses to drug treatment for postoperative recurrence. The evaluation of skeletal muscle mass using preoperative imaging and nutritional assessment using serum markers may be useful for perioperative management and prognosis prediction.

Atrial fibrillation (AF) is an important side effect of thoracic Radiotherapy (RT), which may impair quality of life and survival. This study aimed to develop a prediction model for new-onset AF in patients with Non-Small Cell Lung Cancer (NSCLC) receiving RT alone or as a part of their multi-modal treatment.

Patients with stage I-IV NSCLC treated with curative-intent conventional photon RT were included. The baseline electrocardiogram (ECG) was compared with follow-up ECGs to identify the occurrence of new-onset AF. A wide range of potential clinical predictors and dose-volume measures on the whole heart and six automatically contoured cardiac substructures, including chambers and conduction nodes, were considered for statistical modeling. Internal validation with optimism-correction was performed. A nomogram was made.

374 patients (mean age 69 ± 10 years, 57 % male) were included. At baseline, 9.1 % of patients had AF, and 42 (11.2 %) patients developed new-onset AF. The following parameters were predictive: older age (OR=1.04, 95 % CI: 1.013-1.068), being overweight or obese (OR=1.791, 95 % CI: 1.139-2.816), alcohol use (OR=4.052, 95 % CI: 2.445-6.715), history of cardiac procedures (OR=2.329, 95 % CI: 1.287-4.215), tumor located in the upper lobe (OR=2.571, 95 % CI: 1.518-4.355), higher forced expiratory volume in 1 s (OR=0.989, 95 % CI: 0.979-0.999), higher creatinine (OR=1.008, 95 % CI: 1.002-1.014), concurrent chemotherapy (OR=3.266, 95 % CI: 1.757 to 6.07) and left atrium Dmax (OR=1.022, 95 % CI: 1.012-1.032). The model showed good discrimination (area under the curve = 0.80, 95 % CI: 0.76-0.84), calibration and positive net benefits.

This prediction model employs readily available predictors to identify patients at high risk of new-onset AF who could potentially benefit from active screening and timely management of post-RT AF.

We externally validated the proposed 9th edition of the TNM staging classification with our institution's prospectively collected data and compared it to the 8th edition for overall survival (OS) and freedom from recurrence (FFR).

A retrospective analysis was conducted of 4029 cases of stage I-III non-small cell lung cancer that underwent surgical treatment from January 2004 to December 2020. Survival was compared using Kaplan-Meier curves and multivariable Cox regression analysis. The concordance index (C-index), Alkaike information criterion (AIC), and R2 were used to assess the discriminatory ability.

In the 9th edition, the N2 category (n = 352) was subdivided into N2a (n = 256, 72.7%) and N2b (n = 96, 27.3%). The TNM stage changes were as follows: (1) IIB to IIA, 151 cases (26.0%); (2) IIIA to IIB, 52 cases (11.5%); (3) IIIB to IIIA, 57 cases (61.3%); (4) IIIA to IIIB, 56 cases (12.4%). The survival curves of the proposed 9th edition demonstrated similar patterns to those of the 8th edition, but with a greater discriminative ability for OS and FFR. Subdividing N2 into N2a and N2b refined prognosis prediction. The C-index, AIC, and R2 demonstrated improved values in the proposed 9th edition compared to the 8th edition.

The proposed 9th edition of the TNM staging classification for lung cancer showed favorable prognostic validity and better discrimination ability than the 8th edition.

Osimertinib shows higher effectiveness than first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the initial treatment of EGFR-mutated non-small cell lung cancer. However, its superiority in terms of overall survival in the Asian population, especially Japanese patients, remains uncertain.

To evaluate the survival benefit of osimertinib over other EGFR-TKIs in Japanese patients, using real-world data. METHODS : As part of the Tokushukai REAl-world Data project, a retrospective multi-institutional study across 46 hospitals in Japan was conducted to evaluate the overall survival of patients with advanced EGFR-mutated non-small cell lung cancer using propensity score matching. The study involved patients receiving osimertinib as the first-line treatment (1L-Osi), those initially treated with other EGFR-TKIs (1L-non-Osi), and those receiving osimertinib after initial EGFR-TKI treatment (2L/later-Osi) between April 2010 and December 2022 and followed up until April 2023.

Among 1062 Japanese patients with EGFR-mutated non-small cell lung cancer, 416 (39.2%) received 1L-Osi, while 646 (60.8%) received 1L-non-Osi, including 139 (13.1%) who received 2L/later-Osi. Within these groups, 416 (39.2%), 293 (27.6%), and 75 (7.1%) patients received first-line EGFR-TKI treatment post-osimertinib approval as a later-line treatment in Japan (March 2016). After propensity score matching, the overall survival of the 1L-Osi group was comparable to that of the 1L-non-Osi group in the post-March 2016 subset (n = 283, 42.0 vs 42.4 months). Similar trends were observed in the Del19 and L858R subgroups. The median overall survival of the 2L/later-Osi group was notably long: 60.2 months post-March 2016 (n = 75). A subgroup analysis based on initial EGFR-TKI treatment in the 1L-non-Osi and 2L/later-Osi groups revealed no significant differences among the gefitinib, erlotinib, and afatinib groups.

Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population.

This study was registered at the University Hospital Medical Information Network Clinical Trials Registry on 9 March, 2023 (identification UMIN000050552).

This study aimed to elucidate the therapeutic significance of lung resection for primary lung cancer after pancreatic cancer surgery in contemporary cases.

This retrospective cohort study included patients who had lung nodules and performed pulmonary resection after pancreatic cancer surgery at seven hospitals affiliated with the Thoracic Surgery Study Group of Osaka University between January 2009 and December 2021. Patients in which surgery was performed for biopsy purposes, those with a history of other cancers with potential for lung metastasis, patients who did not give their consent for enrollment, and patients determined to be ineligible by the attending physician were excluded from the study.

A demographic analysis revealed that 17 patients were eligible for inclusion. Pathological diagnoses were established by institutional pathologists and occasionally aided by immunostaining and genetic testing. A survival analysis revealed a 3-year survival rate of 61.9% and a 5-year survival rate of 54.2% after lung resection. Subgroup analyses highlighted the impact of the interval between pancreatic cancer surgery and lung nodule detection, tumor diameter, and procedure on survival outcomes.

This study underscores the therapeutic implications of lung resection for primary lung cancer following surgery for pancreatic cancer. Despite the challenges in preoperative diagnosis and treatment decisions, surgical intervention demonstrates promise, especially in select cases. Further research is needed to determine the best therapeutic strategies for this group.

Surgical manipulation of the lungs increases the number of circulating tumor cells and the subsequent risk of metastasis in patients with lung cancer. This study investigated whether or not ligating the tumor-draining pulmonary vein first during lobectomy could improve the prognosis of these patients.

We retrospectively evaluated patients who underwent curative lobectomy for solitary nonsmall-cell lung carcinoma between January 2012 and December 2016. We divided the patients into the vein-first group, in which all associated pulmonary veins were dissected and severed before cutting the pulmonary artery, bronchus, or pulmonary fissure, and the other procedure group.

Overall, we included 177 and 413 patients in the vein-first and other procedure groups, respectively. Propensity score matching yielded 67 pairs of patients. The 5-year overall survival (85.6% [95% confidence interval, 77.3-94.8%] vs. 69.4% [58.7-81.9%], P = 0.03%) and recurrence-free survival (73.4% [63.3-85.1%] vs. 53.5% [42.5-67.3%], P = 0.02) were significantly better in the vein-first group than in the other procedure group. The cumulative recurrence rate at 5 years post-surgery was significantly lower in the vein-first group than in the other procedure group (21.7% vs. 38.3%, P = 0.04).

Our study suggests that ligating the pulmonary vein first during lobectomy for lung cancer can improve the overall survival, recurrence-free survival, and cumulative recurrence rate.

Surgery is the standard of care for early-stage non-small cell lung cancer (NSCLC), with SBRT reserved for patients who are not surgical candidates. We hypothesized overall survival (OS), lung cancer-specific survival (LCSS), progression free survival (PFS), and recurrence rates following SBRT or surgery in medically operable patients with Stage I NSCLC from the Veterans' Health Care System (VAHS) would be equivalent.

Medically operable patients diagnosed with Stage I NSCLC between 2000-2020 from the VAHS, determined by an FEV1 or DLCO > 60 % of predicted and Charlson comorbidity index (CCI) of 0 or 1, treated with SBRT or surgery were identified. SBRT patients were propensity score matched in a 1:1:1 ratio to those undergoing resection (SBRT:lobectomy:sub-lobar resection). OS, LCSS, and PFS and site of recurrence were determined.

103 patients were included in each cohort. With a median follow-up of 7.9 years 5-year OS for all patients was 51 % (95 % CI 46-57 %). After propensity score matching, OS (HR 2.08, 1.59), LCSS (HR 2.28, 1.97), and PFS (1.97, 1.45) were significantly worse with SBRT compared to either lobectomy or sub-lobar resection, respectively, (p < 0.05 for each comparison). Regional recurrence was significantly higher following SBRT (15.5 % vs 6.8 % or 4.9 %; p < 0.05), but there was no significant difference in local (28.2 % vs 21.4 % or 21.4 %; p > 0.05) or distant recurrence (10.7 % vs 9.7 % or 13.6 %; p > 0.05) when compared to lobectomy or sub-lobar resection, respectively.

In medically operable patients, OS, LCSS, and PFS following either lobectomy or sub-lobar resection were superior to that for SBRT for Stage I NSCLC, likely due in part to higher regional recurrence following SBRT. This suggests that pulmonary function test results and CCI alone are insufficient to define a cohort of medically operable patients suited for SBRT. These data support strategies to overcome regional recurrences seen with SBRT.

The ALINE trial demonstrated the superiority of alectinib over platinum-based chemotherapy in resected Anaplastic Lymphoma Kinase (ALK)-positive non-small-cell lung cancer (NSCLC). Considering the high cost of alectinib, this study aimed to evaluate the economic value of alectinib compared to platinum-based chemotherapy for treating early-stage ALK-positive NSCLC from the perspective of the Chinese health care system.

We developed a five-state Markov model with monthly cycles to estimate the lifetime costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) in terms of cost per LY gained and per QALY gained. Costs were obtained from database, expert opinions and published literature, and utilities were primarily derived from a multicenter cross-sectional study based on the Chinese population. Costs and outcomes were discounted at 5% per year. Sensitivity analyses and scenario analyses were conducted to assess uncertainty in model results.

Compared to platinum-based chemotherapy, alectinib increased total costs by $16,245 and provided gains of 2.02 LYs and 1.84 QALYs over a lifetime horizon. ICERs were $8,052/LY and $8,806/QALY. The ICER in terms of cost per QALY gained was most sensitive to the outcome discount rate. Probabilistic sensitivity analysis indicated a 93% probability of alectinib being cost-effective at a willing-to pay (WTP) threshold of $12,367/QALY (1 GDP per capita), rising to 100% at $37,100/QALY (3 GDP per capita).

Alectinib appears to be the preferred cost-effective option in the adjuvant treatment for Chinese patients with resected early-stage ALK-positive NSCLC.

Malignant tumors of the lung are the leading cancers worldwide. Prognostic biomarkers continue to be investigated for the detection and stratification of lung cancer for clinical use. In breast cancer cells and in lymphomas, the overexpression of galectin-7 led to increased metastasis. In lung cancer, squamous cell carcinoma, galectin-7 was also identified as a factor promoting metastasis. In this study, we investigated the expression of galectin-7 in relation to clinicopathological features and overall survival in patients with different types of lung cancer. By immunohistochemistry, expression of galectin-7 was analyzed in 308 cases of lung cancer; 108 cases of adenocarcinoma, 193 cases of squamous cell lung carcinoma and 7 cases of small cell lung cancer (SCLC) and correlated with clinicopathological characteristics as well as patients' overall survival. Immunohistochemical detection of galectin-7 expression was most evident in squamous cell lung carcinoma (36.27%), followed by adenocarcinoma (5.55%). Negative expression of galectin-7 was found in all patients with SCLC. No significant correlation was found in patients with squamous cell lung carcinoma. Within the adenocarcinoma and squamous cell lung carcinoma subgroups, there were statistically significant correlations between the expression of galectin-7 and some clinicopathologic features of the patients. In our study, we were able to show that galectin-7 could serve as a new prognostic biomarker and is also a potential new drug target in non-small cell lung cancer.

Previous studies investigating whether metastatic lymph node count is a relevant prognostic factor in pathological N1 non-small cell lung cancer (NSCLC), showed conflicting results. Hypothesizing that outcome may also be related to histological features, we determined the prognostic impact of single versus multiple metastatic lymph nodes in different histological subtypes for patients with stage II-N1 NSCLC.

We performed a retrospective cohort study using data from the Netherlands Cancer Registry, including patients treated with a surgical resection for stage II-N1 NSCLC (TNM 7th edition) in 2010-2016. Overall survival (OS) was assessed for patients with single (pN1a) and multiple (pN1b) metastatic nodes. Using multivariable analysis, we compared OS between pN1a and pN1b in different histological subtypes.

After complete resection of histologically proven stage II-N1 NSCLC, 1309 patients were analyzed, comprising 871 patients with pN1a and 438 with pN1b. The median number of pathologically examined nodes (N1 + N2) was 9 (interquartile range 6-13). Five-year OS was 53% for pN1a versus 51% for pN1b. In multivariable analysis, OS was significantly different between pN1a and pN1b (HR 1.19, 95% CI 1.01-1.40). When stratifying for histology, the prognostic impact of pN1a/b was only observed in adenocarcinoma patients (HR 1.44, 95% CI 1.15-1.81).

Among patients with stage II-N1 adenocarcinoma, the presence of multiple metastatic nodes had a significant impact on survival, which was not observed for other histological subtypes. If further refinement as to lymph node count will be considered for incorporation into a new staging system, evaluation of the role of histology is recommended.

A universal nomenclature of the anatomic extent of lung cancer has been critical for individual patient care as well as research advances. As progress occurs, new details emerge that need to be included in a refined system that aligns with contemporary clinical management issues. The ninth edition TNM classification of lung cancer, which is scheduled to take effect in January 2025, addresses this need. It is based on a large international database, multidisciplinary input, and extensive statistical analyses. Key features of the ninth edition include validation of the significant changes in the T component introduced in the eighth edition, subdivision of N2 after exploration of fundamentally different ways of categorizing the N component, and further subdivision of the M component. This has led to reordering of the TNM combinations included in stage groups, primarily involving stage groups IIA, IIB, IIIA, and IIIB. This article summarizes the analyses and revisions for the TNM classification of lung cancer to familiarize the broader medical community and facilitate implementation of the ninth edition system.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified.

Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined.

A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMH-AMHR2 pathway suppressed cell proliferation.

In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation.