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Purposes: To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance. Methods: Limited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis. Results: Between June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23–0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25–0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41–0.79, P = 0.001) were favorable prognostic factors for OS in PR patients. Conclusions: In this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted. [ABSTRACT FROM AUTHOR]

Background: Autoimmune encephalitis (AE) is a disease caused by an abnormal reaction between the body's autoimmunity and the central nervous system, in which the abnormal immune response targets antigenic components within or on the surface of neuronal cells. The main manifestations are mental and behavioural changes, cognitive impairment, impaired consciousness, seizures, movement disorders, etc. Most cell surface antibodies respond well to immunotherapy, intracellular antibodies, on the other hand, are usually associated with more tumours and are relatively difficult to treat with a poor prognosis. In recent years, autoimmune encephalitis that is positive for multiple anti-neuronal antibodies has been gradually recognized in the clinic, with complex and varied clinical manifestations, especially in combination with malignant tumours, which have worse treatment and prognosis. Current clinical studies on the coexistence of multiple anti-neuronal antibodies in patients with AE are mainly disseminated case reports. Patients with AE in which four anti-neuronal antibodies coexist are even rarer. Case presentation: We report a patient who initially presented with an irritating dry cough and hyponatraemia and a chest CT suspicious for malignancy, followed by progressive deterioration of persistent status epilepticus, consciousness and cognitive deficits, and psycho-behavioural abnormalities. Serum and cerebrospinal fluid antibodies against neuronal surface or intracellular antigens were detected using a cell-based assay (CBA) method. Serum and cerebrospinal fluid were found to be positive for anti-GABABR, GAD65, SOX1 and Ma2 antibodies. And a definitive diagnosis of small cell lung cancer was made by immunohistochemistry. He eventually received gammaglobulin, steroid pulsed therapy and tumour chemotherapy. Conclusions: The coexistence or overlap of multiple anti-neuronal surface antibodies with anti-neuronal intracellular antibodies is rare and increases the likelihood of underlying malignancy. Elucidating the impact of individualized immunotherapy and coexisting antibodies on the clinical presentation of patients has the potential to improve long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Some pathogenic mechanisms suggest a potential relationship between gastroesophageal reflux disease (GERD) and respiratory diseases. However, evidence regarding the association between GERD and lung cancer is mixed. We aim to explore this relationship based on data from the large-scale UK Biobank study. Materials and methods: We performed a cross-sectional and prospective cohort study in 501,569 (45.58% male) individuals included in the UK Biobank at baseline (2006–2010). The Cox proportional hazards model and logistic regression models were used to assess the relationship between GERD and lung cancer, small cell lung cancer (SCLC), lung squamous cell carcinoma (LUSC), and lung adenocarcinoma (LUAD). Results: During a mean follow-up of 11.54 years, 3,863 (0.84%) incident lung cancer cases were identified. In the cross-sectional analysis using logistic models, significant associations were found between GERD and prevalent lung cancer cases (odds ratio [OR] = 1.87, 95% confidence interval [95% CI]: 1.45–2.38) and subtypes of lung cancer, with an OR (95% CI) of 3.19 (1.47–6.79) for SCLC, 2.08 (1.33–3.21) for LUSC, 1.85 (1.15–2.91) for LUAD. In the follow-up analysis using Cox models, GERD was associated with an increased risk of lung cancer (hazard ratio [HR] = 1.24, 95%CI: 1.14–1.34). Similar associations were also observed between GERD and SCLC (HR = 1.39, 95% CI: 1.09–1.78), LUSC (HR = 1.40, 95% CI: 1.18–1.65), and LUAD (HR = 1.17, 95% CI: 1.02–1.33). The risk of lung cancer resulting from GERD was mainly elevated in former smokers (HR = 1.38, 95% CI: 1.23–1.54) and current smokers (HR = 1.18, 95% CI: 1.04–1.34), but not in never-smokers (HR = 0.89, 95% CI: 0.70–1.14). No significant association was observed in former smokers who had quit smoking for at least 25 years. Conclusions: We found that GERD was positively associated with an increased risk of lung cancer, especially among smokers. Awareness of this association may be beneficial for prevention and treatment strategies of both diseases. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumor (NET) is a rare malignant tumor, notably small cell lung cancer (SCLC), a type of lung neuroendocrine tumor, which has a survival rate of less than 7%. Although various biomarkers including CHGA (Chromogranin A), INSM1 (Insulinoma-associated protein 1), and SYP (Synaptophysin) are extensively used for the diagnostic testing of NET, their diverse specificities and sensitivities are acknowledged as limitations. Here, we demonstrate that RepID (Replication initiation determinant protein), a component of CRL4 (Cullin-RING ubiquitin E3 ligase 4), holds promise as a biomarker for identifying NET and SCLC. Analysis of the Cancer Cell Line Encyclopedia (CCLE) via the CellMinerCDB portal reveals a high correlation between RepID transcript levels and mRNA expression of NE signature genes. Additionally, RepID protein is highly expressed in SCLC patient tissues and a subset of SCLC cell lines. Viability analysis following treatment with pevonedistat and SZL-P1-41 in SCLC cell lines and human SCLC-organoid models indicates that RepID expression determines the sensitivity to CRL-targeting anti-cancer drugs. These findings suggest that RepID represents a novel biomarker for NET and SCLC, and insights from RepID research in these cancers could lead to innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Lung cancer, categorized into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), remains a significant global health challenge. The development of drug resistance and the heterogeneity of the disease necessitate the identification of novel therapeutic targets to improve patient outcomes. Methods: We conducted a genome-wide Mendelian randomization (MR) and colocalization analysis using a comprehensive dataset of 4,302 druggable genes and cis-expressed quantitative trait loci (cis-eQTLs) from 31,884 blood samples. The study integrated genomic analysis with eQTL data to identify key genes associated with lung cancer risk. Results: The analysis revealed five actionable therapeutic targets for NSCLC, including LTB4R, LTBP4, MPI, PSMA4, and TCN2. Notably, PSMA4 demonstrated a strong association with both NSCLC and SCLC risks, with odds ratios of 3.168 and 3.183, respectively. Colocalization analysis indicated a shared genetic etiology between these gene expressions and lung cancer risk. Conclusion: Our findings contribute to precision medicine by identifying druggable targets that may be exploited for subtype-specific lung cancer therapies. [ABSTRACT FROM AUTHOR]

Background: Observational studies and experimental evidence have shown that chemokines play important roles in lung cancer development, progression, and treatment. However, few studies have examined the causal association between them. Methods: Summary data of chemokines and lung cancer were obtained from genome-wide association studies. Mendelian randomization (MR) analyses were performed by five methods, Inverse variance weighted (IVW), Weighted median estimation, MR-Egger, Simple mode and Weighted, with IVW as the primary analysis method. Sensitivity analysis was used to assess the reliability of the MR results. Multivariate Mendelian randomization studies were used to infer whether causality was influenced by potential mediators. The expression levels of CCL21 were analyzed by quantitative real-time PCR. Results: We found that CCL21 was negatively associated with lung adenocarcinoma risk. CCL25 was positively associated with lung squamous cell carcinoma risk. CCL5 was negatively associated with small cell lung cancer risk. CCL21, CCL24, CCL27, and CCL28 was positively associated with small cell lung cancer risk. After multivariate Mendelian randomization adjustment for smoking behavior, it was found that the effect of CCL25 on lung squamous cell cancer disappeared, and the effect of CCL21 on small cell lung cancer was quite opposite to the univariate. The receiver operating characteristic curve indicated that chemokines had high accuracy in the diagnosis of lung cancer. CCL21 expression levels showed large differences in lung adenocarcinoma cells. Conclusion: These results highlighted the causal effects of chemokines on lung cancer and suggested a mediating role of smoking behavior in the association between chemokines and lung cancer. [ABSTRACT FROM AUTHOR]

Background: Nowadays, the characteristics and treatment of combined small-cell lung carcinoma (CSCLC) remain controversial. This study aimed to analyze the features of clinical demographics, survival outcomes and treatment modalities among IV CSCLC, IV SCLC and IV NSCLC, to provide more evidence for the study of IV CSCLC. Methods: All CSCLC, SCLC and NSCLC patient data were obtained from the SEER database (2010–2020). Pearson's χ2 test was used to compare the differences in clinical characteristics. Propensity score matching (PSM) was utilized to balance the bias of the variables between patients. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. KM analysis was used to calculate survival. Adjusted analyses for the primary outcome of different treatment modalities of IV CSCLC, IV SCLC and IV NSCLC were performed using Cox regression models. Results: A total of 493 patients with IV CSCLC, 35503 patients with SCLC, 122807 patients with IV NSCLC were included in this study. The demographic characteristics and tumor characteristics of the three groups were different. Before PSM, there were significant differences in OS and CSS among IV CSCLC, IV SCLC and IV NSCLC, After PSM, there was a significant difference in OS and CSS between the IV CSCLC and IV NSCLC. Risk/protective factors for OS and CSS were different in three groups. Chemotherapy, radiotherapy, and surgery can improve IV CSCLC's survival time. The combination of surgery and chemoradiotherapy treatment group for patients with IV CSCLC demonstrated best OS compared to control treatment groups, and the surgery combined chemotherapy treatment group exhibited the best CSS. Additionally, for select patients with stage IV CSCLC who have missed the window for surgical intervention at the time of initial diagnosis, chemoradiotherapy presents a viable and effective treatment option. Conclusions: The clinical characteristics IV CSCLC, IV SCLC and IV NSCLC were significantly different. The prognosis for IV CSCLC is notably poorer than IV NSCLC, similar to IV SCLC. Surgery combined therapy emerged as the preferred treatment modalities and chemoradiotherapy was a good choice for patients who have lost the indication of surgery for patients diagnosed with IV CSCLC. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) exhibits a comparatively slower rate of metastasis in contrast to small cell lung cancer, contributing to approximately 85% of the global patient population. In this work, leveraging CT scan images, we deploy a knowledge distillation technique within teaching assistant (TA) and student frameworks for NSCLC classification. We employed various deep learning models, CNN, VGG19, ResNet152v2, Swin, CCT, and ViT, and assigned roles as teacher, teaching assistant and student. Evaluation underscores exceptional model performance in performance metrics achieved via cost-sensitive learning and precise hyperparameter (alpha and temperature) fine-tuning, highlighting the model's efficiency in lung cancer tumor prediction and classification. The applied TA (ResNet152) and student (CNN) models achieved 90.99% and 94.53% test accuracies, respectively, with optimal hyperparameters (alpha = 0.7 and temperature = 7). The implementation of the TA framework improves the overall performance of the student model. After obtaining Shapley values, explainable AI is applied with a partition explainer to check each class's contribution, further enhancing the transparency of the implemented deep learning techniques. Finally, a web application designed to make it user-friendly and classify lung types in recently captured images. The execution of the three-stage knowledge distillation technique proved efficient with significantly reduced trainable parameters and training time applicable for memory-constrained edge devices. [ABSTRACT FROM AUTHOR]

Purpose: To assess the potential added value of the lung immune prognostic index (LIPI) in patients with small cell lung cancer (SCLC), treated with programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) inhibitors, who lived in the Chinese alpine region. Methods: 120 SCLC patients treated with PD-L1/PD-1 inhibitors were divided into three LIPI groups, from July 2018 to April 2021. Cox regression models were used to evaluate the prognostic effect of three LIPI groups on overall survival (OS) and progression-free survival (PFS). Logistic regression analysis was conducted to explore the association between immune-related adverse events (irAEs) and the pretreatment of neutrophil-to-lymphocyte ratio (dNLR), lactate dehydrogenase (LDH), and LIPI. Results: The median OS was 4.5, 6.3, and 10.0 months (p=0.001) and the median PFS was 2.5, 4.3, and 5.3 months (p=0.049) for Poor, Intermediate, and Good LIPI, respectively. The disease control rate (DCR) was also higher in the Good LIPI group (p=0.003). Moreover, multivariate analysis confirmed that worse LIPI was correlated with shorter OS and PFS. dNLR was associated with the onset of irAEs, not LIPI. Conclusion: The LIPI might be a promising predictive and prognostic biomarker in SCLC patients treated with PD-L1/PD-1 inhibitors in the Chinese Alpine region. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). Methods: Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. Results: Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29–41), DCR was 67% (95%CI 58–76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11–9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78–100) and 37% (95%CI 19–57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68–91), 74% (57–88), 73% (35–98) and 57% (46–68), respectively. Conclusion: As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer for which platinum‐based chemotherapy is the standard of care. Despite an initial response to this therapy, patients eventually develop resistance to the chemotherapy.To investigate the potential of capivasertib, an approved drug for advanced breast cancer, to enhance the efficacy of cisplatin in preclinical SCLC models and explore the underlying mechanisms.SCLC cell lines were treated with capivasertib and cisplatin, alone or in combination, to assess cell viability, proliferation, colony formation, and apoptosis. Next, capivasertib's effects, alone and combined with cisplatin, were evaluated in an SCLC mouse model. Mechanistic studies focused on Akt and MYC signaling, with constitutively active Akt overexpression used to assess its role.Capivasertib is active against a panel of SCLC cell lines regardless of cellular origin and genetic profiling with IC50 at a clinically achievable range. Particularly, capivasertib inhibits proliferation and anchorage‐independent colony formation and induces apoptosis in SCLC cells. It significantly augments cisplatin's inhibitory effects in all tested cell lines. Importantly, capivasertib at a non‐toxic dose is effective in delaying SCLC growth in mice and its combination with cisplatin achieves nearly complete tumor growth inhibition. Mechanistic studies confirm that capivasertib inhibits Akt and MYC signaling, and furthermore, that overexpression of constitutively active Akt reversed anti‐SCLC activity of capivasertib.Our work is the first to reveal that Akt inhibition can augment chemotherapy in SCLC, and capivasertib is a useful addition to the treatment armamentarium for SCLC. [ABSTRACT FROM AUTHOR]

Purpose: Small cell lung cancer (SCLC) has an extremely poor prognosis. Despite high initial response rates to chemotherapy and modest survival improvements with the addition of immune checkpoint inhibitors (ICI), almost all patients experience relapse and fatal outcomes. Recent genomic insights uncovered extensive molecular heterogeneity in addition to the almost uniform loss of RB1 and TRP53. Additionally, defective DNA mismatch repair (MMR) has recently been described in some SCLC cases. Here, we generated a novel SCLC mouse model capturing MMR deficiency and assessed immunotherapy responses. Methods: We developed an MMR-deficient genetically engineered mouse model (GEMM) of SCLC by introducing a conditional Msh2 gene, crucial for maintaining MMR integrity, into the standard Rb1fl/fl;Trp53fl/fl (RP) model. Genomic characteristics and preclinical therapy responses were evaluated by focusing on overall survival and whole exome sequencing (WES) analyses. Results: MMR-defective SCLC tumors (Rb1fl/fl;Trp53fl/fl;Msh2fl/fl (RPM)) developed later than tumors in MMR-proficient mice. However, the time from tumor manifestation to death of the affected animals was substantially shortened (median survival 55 days in RP vs. 46.5 days in RPM), indicating increased aggressiveness of MMR-defective tumors. RPM tumors exhibited MMR deficiency, high tumor mutational burden (TMB), and an elevated load of candidate neoantigens, compared to RP lesions (p = 0.0106), suggesting increased immunogenicity. Importantly, the overall survival of RPM animals was significantly improved when exposed to ICI. Conclusion: We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), a significant clinical benefit of SSTR2-targeted radionuclide therapies of SCLC was not observed so far. We hypothesize that combination treatment with a PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness of SSTR2-targeted therapy in SCLC. Methods: SSTR2-ligand uptake of the SCLC cell lines H69 and H446 was evaluated in vitro using flow cytometry, and in vivo using SPECT imaging and cut-and-count biodistribution. Single-agent (Olaparib, Rucaparib, [177Lu]Lu-DOTA-TOC) and combination treatment responses were determined in vitro via cell viability, clonogenic survival and γH2AX DNA damage assays. In vivo, we treated athymic nude mice bearing H69 or H446 xenografts with Olaparib, Rucaparib, or [177Lu]Lu-DOTA-TOC alone or with combination treatment regimens to assess the impact on tumor growth and survival of the treated mice. Results: H446 and H69 cells exhibited low SSTR2 expression, i.e. 60 to 90% lower uptake of SSTR2-ligands compared to AR42J cells. In vitro, combination treatment of [177Lu]Lu-DOTA-TOC with PARPi resulted in 2.9- to 67-fold increased potency relative to [177Lu]Lu-DOTA-TOC alone. We observed decreased clonogenic survival and higher amounts of persistent DNA damage compared to single-agent treatment for both Olaparib and Rucaparib. In vivo, tumor doubling times increased to 1.6-fold (H446) and 2.2-fold (H69) under combination treatment, and 1.0 to 1.1-fold (H446) and 1.1 to 1.7-fold (H69) in monotherapies compared to untreated animals. Concurrently, median survival was higher in the combination treatment groups in both models compared to monotherapy and untreated mice. Fractionating the PRRT dose did not lead to further improvement of therapeutic outcome. Conclusion: The addition of PARPi can markedly improve the potency of SSTR2-targeted PRRT in SCLC models in SSTR2 low-expressing tumors. Further evaluation in humans seems justified based on the results as novel treatment options for SCLC are urgently needed. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer is the most aggressive form of lung neoplasia, treated in recent decades with chemoradiotherapy in case of limited stage and chemotherapy alone at the metastatic stage. In the last few years, the advent of immunotherapy has changed the landscape in the treatment of non-small-cell lung cancer, and to a lesser degree in small-cell lung cancer. Despite the recent advances in research, small-cell lung cancer is still considered an aggressive and lethal disease characterized by high recurrence or metastatic potential. As stereotactic radiotherapy has established itself as the standard of care in the early stage of inoperable non-small-cell lung cancer and in metastatic disease to treat brain and extracranial metastases, these same issues now arise in the management of small-cell lung cancer. This article aims to review the current knowledge and the potential of stereotactic radiotherapy in small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Large cell neuroendocrine carcinoma (LCNEC) is a rare and enigmatic tumor, characterized by neuroendocrine features and a poor prognosis similar to small cell lung cancer (SCLC). The present report details the case of a 45-year-old male with oligometastatic stage IV LCNEC who achieved clinical cure after undergoing perioperative immunochemotherapy. Despite the typical non-recommendation of surgery for stage IV cases, based on the insistence of the patient, the present study initiated three cycles of neoadjuvant therapy combining serplulimab (a programmed cell death protein 1 inhibitor) with chemotherapy, resulting in the radiological disappearance of the tumor. Pathological complete response was confirmed following resection of the primary tumor. The treatment continued with three cycles of adjuvant therapy using serplulimab and chemotherapy, followed by maintenance therapy with serplulimab alone. After 17 cycles of maintenance therapy, a positron emission tomography-computed tomography scan revealed a complete metabolic response of the metastasis, and radiological scans revealed no visible tumor or distant metastasis, indicating a clinical cure. Event-free survival has exceeded 11 months, and overall survival has exceeded 14 months. The present case highlights the efficacy of immunochemotherapy in treating advanced LCNEC. [ABSTRACT FROM AUTHOR]

Objectives: Differences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations. Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy. We also reviewed main conferences from January 1, 2021 to October 1, 2023. A trial-specific hazard ratio (HR) ratio for each subgroup was calculated, and these ratios were then pooled using the deft approach. Results: A total of 9 RCTs with 4099 patients were finally included. The pooled ratios were 0.92 (95% CI = 0.77 to 1.09) for OS-HRs and 0.79 (95% CI = 0.55 to 1.13) for PFS-HRs in women versus men. The pooled ratios of OS-HRs and PFSHRs in patients with positive versus negative PD-L1 expression were 1.26 (95% CI = 0.91 to 1.73) and 1.08 (95% CI = 0.77 to 1.52), respectively. The pooled ratios of OS-HRs and PFS-HRs in patients without versus with brain metastasis were 0.77 (95% CI = 0.59 to 1.01) and 0.71 (95% CI = 0.44 to 1.12). No statistically significant differences were also found in terms of subgroups for age, liver metastasis, smoking status, ECOG PS, LDH level, type of platinum salt and race. Conclusion: Women or patients with negative PD-L1 expression or with LDH ≤ ULN or without brain metastasis tend to benefit more from first-line chemoimmunotherapy in ES-SCLC. More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) stands as one of the most lethal malignancies, characterized by a grim diagnosis and prognosis. The emergence of multi-drug resistance poses a significant hurdle to effective therapy. Although previous studies have implicated the long noncoding RNA LYPLAL1-DT in the tumorigenesis of SCLC, the precise role of the highly expressed LYPLAL1-DT in SCLC chemoresistance and the underlying mechanism remain inadequately understood. Methods: cDDP-, VP-16- and PTX-resistant SCLC cells lines were established. The viabilities of SCLC cells were assessed by CCK-8 assay in vitro and xenograft tumor formation assay in vivo. Apoptosis was evaluated by FACS, Western blot and JC-1 fluorescence staining, while autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of LYPLAL1-DT were further investigated by gain- and loss-of-function assays in vitro. Furthermore, the therapeutic efficacy of the combination of venetoclax and HCQ with cDDP, VP-16 or PTX was evaluated by cell line, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice model. Results: Our findings revealed that LYPLAL1-DT is upregulated in chemoresistant SCLC cell lines. Gain- and loss-of-function assays demonstrated that LYPLAL1-DT impairs sensitivity to cDDP, VP-16, or PTX both in vitro and in vivo. Overexpression of LYPLAL1-DT significantly enhanced autophagy and inhibited apoptosis in SCLC cells. Further analyses, including RIP and RNA pull-down assays, revealed that LYPLAL1-DT promotes the expression of BCL2 by sponging miR-204-5p and is implicated in the assembly of the autophagy-specific complex (BECN1/PtdIns3K complex). Combining venetoclax and HCQ with cDDP, VP-16, or PTX effectively mitigated chemoresistance in SCLC cells and suppressed tumor growth in CDX and PDX models without inducing obvious toxic effects. Conclusions: Our findings demonstrate that upregulation of LYPLAL1-DT sequesters apoptosis through the LYPLAL1-DT/miR-204-5p/BCL2 axis and promotes autophagy by facilitating the assembly of the BECN1/PtdIns3K complex, thereby mediating multi-drug resistance of SCLC. The triple combination of venetoclax, HCQ, in conjunction with cDDP, VP-16 or PTX overcomes refractory SCLC, shedding light on a potential therapeutic target for combating SCLC chemoresistance. [ABSTRACT FROM AUTHOR]

Background: The shaping of the tumor immune microenvironment does not only rely on tumor-infiltrating lymphocytes but on the recruitment of lymphocytes in peripheral blood. Monitoring peripheral blood lymphocyte subsets level (PBLSL) can predict treatment response and prognosis with immune checkpoint inhibitors. This study investigated the heterogeneity of PBLSL in response to chemoradiotherapy (CRT) or combined with immunotherapy (CRIT) in advanced lung cancer patients. Methods: 77 patients with advanced lung cancer receiving CRT or CRIT were divided into treatment-responsive and non-responsive groups based on efficacy. The study analyzed short-term efficacy and progression-free survival (PFS) according to baseline PBLSL and explored the impact under different stratifications, including treatment modality, pathology type, and age. Results: In all patients, higher levels of B cells, higher CD4+/CD8+ T cell ratios, and lower CD8+ T cell levels were associated with better short-term outcomes (P = 0.0035, P = 0.044, P = 0.022). Subgroup analysis revealed that in the CRT group, higher B cell levels correlated with improved efficacy (P = 0.011) and superior PFS (P = 0.048, HR = 0.3886, 95% CI = 0.1696 to 0.8902). In the CRIT group, higher CD4+ T cell levels, lower CD8+ T cell levels, and higher CD4+/CD8+ T cell ratios were linked to better efficacy (P = 0.038, P = 0.047, P = 0.017). For adenocarcinoma patients, higher CD4+/CD8+ T cell ratios and lower CD8+ T cell levels predicted better efficacy (P = 0.0155, P = 0.0119). B cell levels were significant in squamous cell carcinoma (P = 0.0291), while no PBLSL was predictive for small cell lung cancer. Among patients under 65, higher B cell levels were linked to improved efficacy and prolonged PFS (P = 0.0036, P = 0.0332, HR = 0.4111, 95% CI = 0.1973 to 0.8563). For patients over 65, differences in CD4+ T cell levels and CD4+/CD8+ T cell ratios were significant (P = 0.0433, P = 0.0338). Conclusion: PBLSL predicted efficacy and prognosis in various patient stratifications, suggesting PBLSL is a reliable predictor for CRT and CRIT in advanced lung cancer. Detecting different cellular subpopulations helps identify patients with significant treatment responses across different stratifications. [ABSTRACT FROM AUTHOR]

Background: Rapid on-site evaluation (ROSE) plays an important role during transbronchial sampling, providing an intraoperative cytopathologic evaluation. However, the shortage of cytopathologists limits its wide application. This study aims to develop a deep learning model to automatically analyze ROSE cytological images. Methods: The hierarchical multi-label lung cancer subtyping (HMLCS) model that combines whole slide images of ROSE slides and serum biological markers was proposed to discriminate between benign and malignant lesions and recognize different subtypes of lung cancer. A dataset of 811 ROSE slides and paired serum biological markers was retrospectively collected between July 2019 and November 2020, and randomly divided to train, validate, and test the HMLCS model. The area under the curve (AUC) and accuracy were calculated to assess the performance of the model, and Cohen's kappa (κ) was calculated to measure the agreement between the model and the annotation. The HMLCS model was also compared with professional staff. Results: The HMLCS model achieved AUC values of 0.9540 (95% confidence interval [CI]: 0.9257–0.9823) in malignant/benign classification, 0.9126 (95% CI: 0.8756–0.9365) in malignancy subtyping (non-small cell lung cancer [NSCLC], small cell lung cancer [SCLC], or other malignancies), and 0.9297 (95% CI: 0.9026–0.9603) in NSCLC subtyping (lung adenocarcinoma [LUAD], lung squamous cell carcinoma [LUSC], or NSCLC not otherwise specified [NSCLC-NOS]), respectively. In total, the model achieved an AUC of 0.8721 (95% CI: 0.7714–0.9258) and an accuracy of 0.7184 in the six-class classification task (benign, LUAD, LUSC, NSCLC-NOS, SCLC, or other malignancies). In addition, the model demonstrated a κ value of 0.6183 with the annotation, which was comparable to cytopathologists and superior to trained bronchoscopists and technicians. Conclusion: The HMLCS model showed promising performance in the multiclassification of lung lesions or intrathoracic lymphadenopathy, with potential application to provide real-time feedback regarding preliminary diagnoses of specimens during transbronchial sampling procedures. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

The use of electronic health records (EHRs) holds the potential to enhance clinical trial activities. However, the identification of eligible patients within EHRs presents considerable challenges. We aimed to develop a CriteriaMapper system for phenotyping eligibility criteria, enabling the identification of patients from EHRs with clinical characteristics that match those criteria. We utilized clinical trial eligibility criteria and patient EHRs from the Mount Sinai Database. The CriteriaMapper system was developed to normalize the criteria using national standard terminologies and in-house databases, facilitating computability and queryability to bridge clinical trial criteria and EHRs. The system employed rule-based pattern recognition and manual annotation. Our system normalized 367 out of 640 unique eligibility criteria attributes, covering various medical conditions including non-small cell lung cancer, small cell lung cancer, prostate cancer, breast cancer, multiple myeloma, ulcerative colitis, Crohn's disease, non-alcoholic steatohepatitis, and sickle cell anemia. About 174 criteria were encoded with standard terminologies and 193 were normalized using the in-house reference tables. The agreement between automated and manual normalization was high (Cohen's Kappa = 0.82), and patient matching demonstrated a 0.94 F1 score. Our system has proven effective on EHRs from multiple institutions, showing broad applicability and promising improved clinical trial processes, leading to better patient selection, and enhanced clinical research outcomes. [ABSTRACT FROM AUTHOR]

Cancer prognosis requires precision to identify high-risk patients and improve survival outcomes. Conventional methods struggle with the complexity of genetic biomarkers and diverse medical data. Our study uses deep learning to distil high-dimensional medical data into low-dimensional feature vectors exploring shared patterns across cancer types. We developed a multi-task bimodal neural network integrating RNA Sequencing and clinical data from three The Cancer Genome Atlas project datasets: Breast Invasive Carcinoma, Lung Adenocarcinoma, and Colon Adenocarcinoma. Our approach significantly improved prognosis prediction, especially for Colon Adenocarcinoma, with up to 26% increase in concordance index and 41% in the area under the precision-recall curve. External validation with Small Cell Lung Cancer achieved comparable metrics, indicating that supplementing small datasets with data from other cancers can improve performance. This work represents initial strides in using multi-task learning for prognosis prediction across cancer types, potentially revealing shared mechanisms among cancers and contributing to future applications in precision medicine. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Hippo‐avoidance prophylactic cranial irradiation (HA‐PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall‐off and compensate for setup errors. Most studies recommend a 5‐mm margin, while it could be optimized to a 2‐mm expansion. Here, we showed the details of optimized HA‐PCI for limited‐stage small cell lung cancer (LS‐SCLC).This cohort study reviewed patients with LS‐SCLC receiving optimized HA‐PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo‐related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test—Revised (HVLT‐R) scores in different time points was conducted. The Kaplan–Meier method was used to calculate the survival rates.A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40–7.44) and 7.63 Gy (IQR: 7.14–8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric‐modulated arc therapy [VMAT]). The decline of HVLT‐R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow‐up of 52 months (95% CI: 47.2–56.7), the 2‐year overall survival and progression‐free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus.Optimized HA‐PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity. [ABSTRACT FROM AUTHOR]

As one of the most prevalent malignancies, lung cancer displays considerable biological variability in both molecular and clinical characteristics. Lung cancer is broadly categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) with the latter being most prevalent. The primary histological subtypes of NSCLC are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In the present work, we primarily extracted mRNA count data from a publicly accessible database followed by differentially expressed genes (DEGs) and differentially expressed mitophagy-related genes (DEMRGs) identification in case of both LUAD and LUSC cohorts. Next, we identified important DEMRGs via clustering approach followed by enrichment, survival, and mutational analyses. Lastly, the finalized prognostic biomarker was validated using wet-lab experimentations. Primarily, we obtained 986 and 1714 DEGs across LUAD and LUSC cohorts. Only 7 DEMRGs from both cohorts had significant membership values as indicated by the clustering analysis. Most significant pathway, Gene Ontology (GO)-biological process (BP), GO-molecular function (MF), GO-cellular compartment (CC) terms were macroautophagy, GTP metabolic process, magnesium ion binding, mitochondrial outer membrane. Among all, only TDRKH reported significant overall survival (OS) and 14% amplification across LUAD patients. Lastly, we validated TDRKH via immunohistochemistry (IHC) and semi-quantitative polymerase chain reaction (PCR). In conclusion, our findings advocate for the exploration of TDRKH and their genetic alterations in precision oncology therapeutic approaches for LUAD, emphasizing the potential for target-driven therapy and early diagnostics. [ABSTRACT FROM AUTHOR]

Introduction: Anti-GABABR encephalitis is a rare disease reported to be often associated with tumors. The current study aims to summarize the clinical characteristics, imaging features, treatments, outcomes and explore the potential prognosis risk factors of patients with anti-GABABR encephalitis. Methods: Patients tested positive for anti-GABABR were retrospective studied from a single medical center in China over a period of 3 years. They were followed up for a maximum period of 18 months. Clinical data were summarized and prognostic factors including demographic characteristics, laboratory tests, and neurological functions were compared between survived and deceased patients at 18 months follow-up. Results: Twenty-six patients, 10 females (38.5%) and 16 males (61.5%), diagnosed with anti-GABABR encephalitis were studied. The median age was 58 years. Of the 23 cases with complete clinical data, their main manifestations were epileptic seizures (65%), mental and behavioral abnormalities (52%), and cognitive impairment (48%). 7 (30.4%) cases had tumors: 5 small cell lung cancer (SCLC), 1 rectum adenocarcinoma (moderately differentiated) and 1 esophageal squamous cell carcinoma. MRI showed 5 (22%) cases had T2 FLAIR increased signals in cortex but with different regions affected. One of the two patients scanned for PET-CT showed hypermetabolism in the left temporal lobe region. The disease course ranged from 5 days to 3 years. 2 patients (one had esophageal carcinoma) without immunotherapy and 3 patients (one had SCLC) that did not response to immunotherapy died soon after diagnosis. 18 patients improved after immunotherapy while 3 (all had SCLC) died after relapses. The prevalence of epileptic seizures and malignancies was significantly lower in the survival group than in the deceased group at 18-months follow-up, the same as the admission mRs score. Serum fibrinogen, cerebrospinal fluid immunoglobulin G quotient, and 24-hour intrathecal synthesis rate were significantly lower in the survival groups as well. Conclusions: Cortex T2 FLAIR abnormalities were only observed in a small proportion of anti-GABABR encephalitis patients with heterogeneous MRI phenotypes. High mRS score at admission, epileptic seizures and the presence of a tumor indicated a poor prognosis, while the underlying mechanism of the later two factors should be investigated further. [ABSTRACT FROM AUTHOR]

Background: In small cell lung cancer (SCLC), the pathological N category is identical to it in non-small cell lung cancer (NSCLC) and remains unchanged over a decade. Here we verified the discriminability of number of involved nodal stations (nS) in SCLC and compared its efficacy in predicting survival with currently used pathological nodal (pN) staging. Methods: We retrospectively analyzed the patients who received operations and were pathologically diagnosed as SCLC at Shanghai Pulmonary Hospital between 2009 and 2019. X-tile software was adopted to determine optimal cut-off values for nS groups. Kaplan–Meier method and Cox regression analysis were used to compare survival between different groups. Decision curve analysis (DCA) was employed to evaluate the standardized net benefit. Results: A total of 369 patients were included. The median number of sampled stations was 6 (range 3–11), and the median number of positive stations was 1 (range 0–7). The optimal cutoff for nS groups was: nS0 (no station involved), nS1-2 (one or two stations involved), and nS ≥ 3 (three or more stations involved). Overall survival (OS) and relapse-free survival (RFS) were statistically different among all adjacent categories within the nS classification (p < 0.001, for both OS and RFS between each two subgroups), but survival curves for subgroups in pN overlapped (OS, p = 0.067; RFS, p = 0.068, pN2 vs. pN1). After adjusting for other confounders, nS was a prognostic indicator for OS and RFS. The DCA revealed that nS had improved predictive capability than pN. Conclusions: Our cohort study demonstrated that the nS might serve as a superior indicator to predict survival than pN in SCLC and was worth considering in the future definition of the N category. [ABSTRACT FROM AUTHOR]

Simple Summary: Small cell lung cancer (SCLC) is a deadly cancer that is treated by chemo- and radiotherapy, which work by damaging DNA. However, most SCLC patients will develop resistance to these treatments, resulting in a poor outlook with few effective treatment options available. This review summarizes our understanding of the causes of treatment resistance and the treatments which have been studied to overcome resistance. While there is still much to be understood, new methods being developed may improve our ability to study this disease and find effective treatments. Background: Small cell lung cancer (SCLC) is a lethal form of lung cancer with few treatment options and a high rate of relapse. While SCLC is initially sensitive to first-line DNA-damaging chemo- and radiotherapy, relapse disease is almost universally therapy-resistant. As a result, there has been interest in understanding the mechanisms of therapeutic resistance in this disease. Conclusions: Progress has been made in elucidating these mechanisms, particularly as they relate to the DNA damage response and SCLC differentiation and transformation, leading to many clinical trials investigating new therapies and combinations. Yet there remain many gaps in our understanding, such as the effect of epigenetics or the tumor microenvironment on treatment response, and no single mechanism has been found to be ubiquitous, suggesting a significant heterogeneity in the mechanisms of acquired resistance. Nevertheless, the advancement of techniques in the laboratory and the clinic will improve our ability to study this disease, especially in patient populations, and identify methods to surmount therapeutic resistance. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is characterized by rapid development of chemoresistance and poor outcomes. Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6is) are widely used in breast cancer and other cancer types. However, the molecular mechanisms of CDK4/6 in SCLC chemoresistance remain poorly understood. Here, Rb1flox/flox, Trp53flox/flox, Ptenflox/flox (RTP) and Rb1flox/flox, Trp53flox/flox, MycLSL/LSL (RPM) spontaneous SCLC mouse models, SCLC cell line‐derived xenograft (CDX) models, and SCLC patient‐derived xenograft (PDX) models are established to reveal the potential effects of CDK4/6is on SCLC chemoresistance. In this study, it is found that CDK4/6is palbociclib (PD) or ribociclib (LEE) combined with chemotherapeutic drugs significantly inhibit SCLC tumor growth. Mechanistically, CDK4/6is do not function through the classic Retionblastoma1 (RB) dependent axis in SCLC. CDK4/6is induce impair autophagy through the AMBRA1‐lysosome signaling pathway. The upregulated AMBRA1 protein expression leads to CDK6 degradation via autophagy, and the following TFEB and TFE3 nuclear translocation inhibition leading to the lysosome‐related genes levels downregulation. Moreover, it is found that the expression of CDK6 is higher in SCLC tumors than in normal tissue and it is associated with the survival and prognosis of SCLC patients. Finally, these findings demonstrate that combining CDK4/6is with chemotherapy treatment may serve as a potential therapeutic option for SCLC patients. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions To evaluate the efficacy and safety of programmed cell death 1 (PD‐1)/programmed cell death ligand 1 (PD‐L1) inhibitors in the treatment of extensive‐stage small‐cell lung cancer (ES‐SCLC), we conducted a systematic review and meta‐analysis that included randomized controlled trials (RCTs) and real‐world studies (RWS).By scanning PubMed, Web of science, Embase, and other relevant clinical information public databases, nine RCTs and eight RWSs involving 5205 patients were included in the study. We directly compared the differences between chemotherapy and PD‐1/PD‐L1 inhibitors plus chemotherapy, and determined the optimal treatment strategy through network meta‐analysis (NMA).Compared to chemotherapy, the addition of PD‐1/PD‐L1 inhibitors significantly improves the overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR) in SCLC patients. Regarding safety, both RCTs and RWSs indicated no significant difference in grade 3–4 adverse events between chemotherapy and chemoimmunotherapy. NMA showed serplulimab plus chemotherapy (Serp_Chemo) appears to provide the best OS, PFS, and ORR benefit, while nivolumab plus chemotherapy shows higher toxicity than other regimens. In subgroup analysis, for elderly patients (age ≥65) and non‐elderly (age <65) patients, the most promising quality regimens for achieving better OS extension are atezolizumab plus chemotherapy (Atez_Chemo) and Serp_Chemo, respectively. For patients with PD‐L1 ≥ 1% and lactate dehydrogenase (LDH) > upper limit of normal (ULN), there is no apparent OS benefit from immune therapy.In ES‐SCLC treatment, adding PD‐1/PD‐L1 inhibitors to standard chemotherapy improves OS, PFS, and ORR, with Serp_Chemo shows the most promise. Atez_Chemo and Serp_Chemo provided better survival for elderly and non‐elderly patients, respectively. [ABSTRACT FROM AUTHOR]

Purpose: To assess the potential added value of the lung immune prognostic index (LIPI) in patients with small cell lung cancer (SCLC), treated with programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) inhibitors, who lived in the Chinese alpine region. Methods: 120 SCLC patients treated with PD-L1/PD-1 inhibitors were divided into three LIPI groups, from July 2018 to April 2021. Cox regression models were used to evaluate the prognostic effect of three LIPI groups on overall survival (OS) and progression-free survival (PFS). Logistic regression analysis was conducted to explore the association between immune-related adverse events (irAEs) and the pretreatment of neutrophil-to-lymphocyte ratio (dNLR), lactate dehydrogenase (LDH), and LIPI. Results: The median OS was 4.5, 6.3, and 10.0 months (p=0.001) and the median PFS was 2.5, 4.3, and 5.3 months (p=0.049) for Poor, Intermediate, and Good LIPI, respectively. The disease control rate (DCR) was also higher in the Good LIPI group (p=0.003). Moreover, multivariate analysis confirmed that worse LIPI was correlated with shorter OS and PFS. dNLR was associated with the onset of irAEs, not LIPI. Conclusion: The LIPI might be a promising predictive and prognostic biomarker in SCLC patients treated with PD-L1/PD-1 inhibitors in the Chinese Alpine region. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is associated with tumour growth, infiltration, and metastasis. This study aimed to detect the mechanisms of angiogenesis-related genes (ARGs) in multiple myeloma (MM) and to construct a new prognostic model. Methods: MM research foundation (MMRF)-CoMMpass cohort, GSE47552, GSE57317, and ARGs were sourced from public databases. Differentially expressed genes (DEGs) in the tumour and control cohorts in GSE47552 were determined through differential expression analysis and were enriched with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Weighted gene coexpression network analysis (WGCNA) was applied to derive modules linked to the ARG scores and obtain module genes in GSE47552. Differentially expressed ARGs (DE-ARGs) were selected for subsequent analyses by overlapping DEGs and module genes. Furthermore, prognostic genes were selected using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Depending on the prognostic genes, a risk model was constructed, and risk scores were determined. Moreover, MM samples from MMRF-CoMMpass were sorted into high- and low-risk teams on account of the median risk score. Additionally, correlations among clinical characteristics, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), immune analysis, immunotherapy predictions and the mRNA‒miRNA‒lncRNA network were carried out. Results: A total of 898 DEGs, 211 module genes, 24 DE-ARGs and three prognostic genes (AKAP12, C11orf80 and EMP1) were selected for this study. Enrichment analysis revealed that the DEGs were related to 86 GO terms, such as 'cytoplasmic translation', and 41 KEGG pathways, such as 'small cell lung cancer'. A prognostic gene-based risk model was created in MMRF-CoMMpass and confirmed with the GSE57317 dataset. Moreover, a nomogram was established on the basis of independent prognostic factors that have proven to be good predictors. In addition, the immune cell infiltration results suggested that memory B cells were enriched in the high-risk group and that immature B cells were enriched in the low-risk group. Finally, the mRNA‒miRNA‒lncRNA network demonstrated that hsa-miR-508-5p was tightly associated with EMP1 and AKAP12. RT‒qPCR was used to validate the expression of the genes associated with prognosis. Conclusion: A new prognostic model of MM associated with ARGs was created and validated, providing a new perspective for exploring the connection between ARGs and MM. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common types of malignant cancer worldwide, causing a serious social and economic burden. It is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for 80–85% of cases. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in NSCLC, playing an important role in regulating tumor growth, angiogenesis, malignant transformation, and phagocytosis. Ubiquitin-specific protease 10 (USP10) functions as a deubiquitinating enzyme to regulate substrate protein deubiquitination and reverse the ubiquitin proteasome degradation pathway. Our previous study identified an interaction between EIF4G1 and USP10; however, their regulatory mechanism remains unclear. Herein, we found that USP10 positively regulates EIF4G1 in NSCLC cells. An in vivo ubiquitination assay demonstrated deubiquitination of EIF4G1 by USP10, which reversed the ubiquitin proteasomal degradation of EIF4G1, thereby increasing its stability. Upregulation of EIF4G1 promoted cell proliferation, migration, and invasion in NSCLC cells. The current study not only reveals a novel mechanism through which USP10 positively regulates EIF4G1 in NSCLC, but also demonstrates the potential of USP10 as a therapeutic target to treat NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: To assess the potential added value of the lung immune prognostic index (LIPI) in patients with small cell lung cancer (SCLC), treated with programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) inhibitors, who lived in the Chinese alpine region. Methods: 120 SCLC patients treated with PD-L1/PD-1 inhibitors were divided into three LIPI groups, from July 2018 to April 2021. Cox regression models were used to evaluate the prognostic effect of three LIPI groups on overall survival (OS) and progression-free survival (PFS). Logistic regression analysis was conducted to explore the association between immune-related adverse events (irAEs) and the pretreatment of neutrophil-to-lymphocyte ratio (dNLR), lactate dehydrogenase (LDH), and LIPI. Results: The median OS was 4.5, 6.3, and 10.0 months (p=0.001) and the median PFS was 2.5, 4.3, and 5.3 months (p=0.049) for Poor, Intermediate, and Good LIPI, respectively. The disease control rate (DCR) was also higher in the Good LIPI group (p=0.003). Moreover, multivariate analysis confirmed that worse LIPI was correlated with shorter OS and PFS. dNLR was associated with the onset of irAEs, not LIPI. Conclusion: The LIPI might be a promising predictive and prognostic biomarker in SCLC patients treated with PD-L1/PD-1 inhibitors in the Chinese Alpine region. [ABSTRACT FROM AUTHOR]

The article from the Journal of Medical Imaging & Radiation Oncology discusses the use of low-dose VMAT radiotherapy for treating actinic keratosis, a condition that can affect large areas of the skin. The study conducted at Sir Charles Gairdner Hospital in Perth, Australia, analyzed patients treated for actinic keratosis and found that VMAT radiotherapy resulted in a complete response in 100% of treated areas, with favorable patient-reported outcomes. The study demonstrated excellent short-term response with lower doses than previously published data, highlighting the potential of this treatment for actinic keratosis. [Extracted from the article]

Background: In Australia, lung cancer is the leading cause of cancer‐related deaths. In Victoria, the mortality risk is assumed to vary across Local Government Areas (LGAs) due to variations in socioeconomic advantage, remoteness, and healthcare accessibility. Thus, we applied Bayesian spatial survival models to examine the geographic variation in lung cancer survival in Victoria. Methods: Data on lung cancer cases were extracted from the Victorian Lung Cancer Registry (VLCR). To account for spatial dependence and risk factors of survival in lung cancer patients, we employed a Bayesian spatial survival model. Conditional Autoregressive (CAR) prior was assigned to model the spatial dependence. Deviance Information Criterion (DIC), Watanabe Akaike Information Criterion (WAIC), and Log Pseudo Marginal Likelihood (LPML) were used for model comparison. In the final best‐fitted model, the Adjusted Hazard Ratio (AHR) with the 95% Credible Interval (CrI) was reported. The outcome variable was the survival status of lung cancer patients, defined as whether they survived or died during the follow‐up period (death was our interest). Results: Our study revealed substantial variations in lung cancer mortality in Victoria. Poor Eastern Cooperative Oncology Group (ECOG) performance status, diagnosed at a regional hospital, Small Cell Lung Cancer (SCLC), advanced age, and advanced clinical stage were associated with a higher risk of mortality, whereas being female, presented at Multidisciplinary Team (MDT) meeting, and diagnosed at a metropolitan private hospital were significantly associated with a lower risk of mortality. Conclusion: Identifying geographical disparities in lung cancer survival may help shape healthcare policy to implement more targeted and effective lung cancer care services. [ABSTRACT FROM AUTHOR]

This study evaluates the efficacy of [131I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [131I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [131I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [131I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is one of the leading causes of cancer-related mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) differ in aggressiveness, proliferation speed, metastasis propensity, and prognosis. Since tumor cells notably change lipid metabolism, especially phospholipids and fatty acids (FA), this study aimed to identify FA alterations in lung cancer tissues. We detected significant changes in lipid metabolism in both lung cancer types compared to healthy tissues (especially higher levels of pro-inflammatory arachidonic acid), and we pointed out differences in FA profiles in tissue between SCLC and NSCLC. Our findings can be useful for further research concerning molecular lung cancer therapies. Background: Lung cancer is one of the leading causes of cancer-related mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) differ in aggressiveness, proliferation speed, metastasis propensity, and prognosis. Since tumor cells notably change lipid metabolism, especially phospholipids and fatty acids (FA), this study aimed to identify FA alterations in lung cancer tissues. Methods: Our study included patients with newly diagnosed, histologically confirmed SCLC (n = 27) and NSCLC (n = 37). Samples were collected from both malignant and healthy tissues from each patient, providing they were within subject design. Results: In both NSCLC and SCLC tumor tissues, FA contents were shifted toward pro-inflammatory profiles, with increased levels of some individual n-6 polyunsaturated FA (PUFA), particularly arachidonic acid, and elevated activity of Δ6 desaturase. Compared to healthy counterparts, lower levels of alpha-linolenic acid (18:3n-3) and total saturated FA (SFA) were found in NSCLC, while decreased levels of linoleic acid (18:2n-6) and all individual n-3 FA were found in SCLC tissue in comparison to the healthy tissue control. When mutually compared, SCLC tissue had higher levels of total SFA, especially stearic acid, while higher levels of linoleic acid, total PUFA, and n-3 and n-6 PUFA were detected in NSCLC. Estimated activities of Δ6 desaturase and elongase were higher in SCLC than in NSCLC. Conclusions: Our findings indicate a notable impairment of lipid metabolism in two types of lung cancer tissues. These type-specific alterations may be associated with differences in their progression and also point out different therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Despite initial dramatic responses, metastatic small cell lung cancer (SCLC) invariably recurs. Irinotecan is one of the active agents for patients with recurrent SCLC. In the second line, weekly or three-weekly irinotecan regimens have been adopted, however, the optimal dose and schedule is not defined. In our institution, we use a bi-weekly regimen of irinotecan. In this study, we aimed to investigate the safety and efficacy of the bi-weekly irinotecan in the second- or third-line treatment of SCLC patients. Methods: The study population consisted of advanced stage SCLC patients who were followed at Hacettepe University Cancer Institute between January 2007 and March 2021 and received salvage irinotecan 180 mg/m2 every two weeks, following progression after platinum-etoposide treatment. Results: One hundred patients were included. At diagnosis, nineteen patients (19%) had limited stage and 81 patients (81%) had extensive stage SCLC. Objective response rates (ORR) were 44.6% and 46.2% for patients who received irinotecan treatment in second line, and in third line, respectively. Seventeen percent of all the patients had grade 3 and above adverse events during irinotecan treatment. In our study, 45.8% of patients were able to complete at least 6 cycles of irinotecan treatment and 69.8% were able to receive at least 3 cycles of irinotecan treatment without any dose interruption or reduction. Conclusions: Irinotecan 180 mg/m2 every two weeks appears to be safe and effective in the 2nd- and 3rd-line treatment of advanced stage SCLC. Bi-weekly administration allows G-CSF prophylaxis in between doses, leading to an uninterrupted administration. [ABSTRACT FROM AUTHOR]

The goal of the work described here was to investigate the role of multimodal contrast-enhanced ultrasound in the differential diagnosis of peripheral lung cancer. From April 2017 to July 2021, 109 patients with confirmed pulmonary malignant lesions who underwent CEUS examination were involved in our study. Seven patients were excluded because of the short duration of CEUS video or unsatisfactory imaging. Finally,102 patients with peripheral lung cancer were enrolled in this study. The maximum diameter of the lesions ranged from 1.6 to 13.0 cm (mean 6.2 ± 2.3 cm). On the basis of the pathological results, the patients were divided into the small cell lung cancer (SCLC) group and non-small cell lung cancer (NSCLC) group (including adenocarcinoma, lung squamous cell carcinoma and large cell neuroendocrine carcinoma). A Logiq E9 ultrasonic machine equipped with a 3.5 to 5.0 MHz C5-1 probe was used. Patient clinical information, CEUS features, CPI patterns and TIC parameters were analyzed and compared between different groups. Statistical analyses were performed with SPSS software and MedCalc software. The receiver operating characteristic curve was plotted. In the differential diagnosis of SCLC and NSCLC, color parametric imaging indicated great performance. NSCLC exhibited a centripetal enhancement pattern more frequently (72.7%), while SCLC exhibited an eccentric enhancement pattern more frequently (92.9%) (p < 0.001). In the differential diagnosis of adenocarcinoma and squamous cell carcinoma, logistic regression analysis revealed that patient age of onset ≤60 y, difference in arrival time between lung and tumor ≤3.8 s, drop time of the time–intensity curve >23.2 s and absence of internal necrosis on CEUS were independent predictors for adenocarcinoma (area under the curve = 0.861). In our study, multimodal contrast-enhanced ultrasound provided useful information in the differential diagnosis between small cell lung cancer and non-small cell lung cancer, especially between adenocarcinoma and squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

There is limited clinical data for recommendations on how to deliver thoracic radiation therapy (TRT) concurrently with chemotherapy in limited-stage small cell lung cancer. We reviewed radiation therapy treatment plans in a randomized phase 2 trial comparing high-dose with standard-dose twice-daily TRT to assess treatment planning techniques, dose-volume data for target volumes and organs at risk (OARs), evaluate compliance with the protocol, associations with radiation-induced toxicity, and whether an imbalance in treatment planning parameters might be a reason for the large survival benefit of the higher dose (median overall survival 43.6 vs 22.6 months). In the study, 170 patients were to receive 4 courses of platinum/etoposide and were randomized to receive twice-daily TRT of 60 Gy/40 fractions (fx) or 45 Gy/30 fx. TRT treatment plans for those who received 1 or more fx of TRT (n = 166) were analyzed. The most common treatment planning technique was 3-dimensional conformal radiation therapy (67%). The 75th percentile of the reported dose-volume parameters for the OARs were within the protocol-recommended limits for both groups. Mean doses to the esophagus of 25.5 Gy (IQR, 20.2-31.3; 60 Gy/40 fx) and 24.3 Gy (IQR, 20.3-27.5; 45 Gy/30 fx) were associated with 21% and 18% ≥ grade 3 acute esophagitis, respectively. In the 60 Gy/40 fx group, a mean dose to the lungs of 16.5 Gy (IQR, 15.8-16.9), V20 Gy of 29.5% (IQR, 28.8-30.4), and V5 Gy of 65.6% (IQR, 61.5-68.7) led to ≥ grade 3 pneumonitis in 4% of the patients. There was no ≥ grade 3 pneumonitis in the 45 Gy/30 fx group. The treatment planning techniques, the percentage change in volumes between original and redelineated OARs, planning target volumes, relative doses, and laterality were well balanced between the randomly assigned groups. Considering the incidences of severe radiation-induced toxicities were within the range of other recent trials, the reported doses to the OARs appear to be safe. Treatment planning parameters were well balanced between the randomly assigned groups, supporting that the survival benefit of the twice-daily 60 Gy/40 fx TRT schedule was due to the higher dose. [ABSTRACT FROM AUTHOR]

Tooth development, or odontogenesis, is a complex process in which several molecular pathways play a key role. Recently, microRNAs, a class of approximately 20-nucleotide small RNA molecules that regulate gene expression, have been implicated in the odontogenesis process. This study aimed to assess the role of miRNAs in odontogenesis anomalies, specifically agenesis and impaction. We analyzed a manually curated list of 82 miRNAs associated with human odontogenesis, sourced from literature data. Employing two different approaches to validate findings, we conducted functional enrichment analysis to evaluate the cell pathways, diseases, and phenotypes enriched for those miRNAs. Our findings indicate that the analyzed miRNAs regulate pathways linked to tooth anomalies, including the TGFꞵ and Wnt signaling pathways, and those governing the pluripotency of stem cells, known to mediate various cellular processes, and interconnected with odontogenesis-related pathways. Furthermore, the analysis disclosed several pathways associated with tumors, including small cell lung and gastric cancer. These results were confirmed also by diseases and phenotypes enrichment evaluation. Moreover, cell network analysis disclosed that miRNAs are embedded and interconnected in networks associated with dental diseases and cancer development, thus confirming the functional enrichment analyses. In summary, our results offer a quantitative measure of the potential involvement of miRNAs in regulating pathways crucial for developmental processes, notably odontogenesis, and provide results suggesting potential association with oncogenesis processes as well. [ABSTRACT FROM AUTHOR]

Introduction The number of new diagnosed cancer cases and cancer deaths are increasing worldwide. Perfluorinated compounds (PFCs) are synthetic chemicals, which are possible inducers of cancer in human and laboratory animals. Studies showed that PFCs induce breast, prostate, kidney, liver and pancreas cancer by inducing genes being involved in carcinogenic pathways. Methodology This study reviews the association between PFCs induced up-regulation/down-regulation of genes and signaling pathways that are important in promoting different types of cancer. To obtain chemical-gene interactions, an advanced search was performed in the Comparative Toxicogenomics Database platform. Results Five most prevalent cancers were studied and the maps of their signaling pathways were drawn, and colored borders indicate significantly differentially expressed genes if there had been reports of alterations in expression in the presence of PFCs. Conclusion In general, PFCs are capable of inducing cancer in human via altering PPARα and PI3K pathways, evading apoptosis, inducing sustained angiogenesis, alterations in proliferation and blocking differentiation. However, more epidemiological data and mechanistic studies are needed to better understand the carcinogenic effects of PFCs in human. [ABSTRACT FROM AUTHOR]

Neuroendocrine transdifferentiation (NEtD), also commonly referred to as lineage plasticity, emerges as an acquired resistance mechanism to molecular targeted therapies in multiple cancer types, predominately occurs in metastatic epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer treated with EGFR tyrosine kinase inhibitors and metastatic castration‐resistant prostate cancer treated with androgen receptor targeting therapies. NEtD tumors are the lethal cancer histologic subtype with unfavorable prognosis and limited treatment. A comprehensive understanding of molecular mechanism underlying targeted‐induced plasticity could greatly facilitate the development of novel therapies. In the past few years, increasingly elegant studies indicated that NEtD tumors share key the convergent genomic and phenotypic characteristics irrespective of their site of origin, but also embrace distinct change and function of molecular mechanisms. In this review, we provide a comprehensive overview of the current understanding of molecular mechanism in regulating the NEtD, including genetic alterations, DNA methylation, histone modifications, dysregulated noncoding RNA, lineage‐specific transcription factors regulation, and other proteomic alterations. We also provide the current management of targeted therapies in clinical and preclinical practice. [ABSTRACT FROM AUTHOR]

The prognosis of extensive-stage small cell lung cancer is usually poor. In this study, a combined model based on pre-treatment CT radiomics and clinical features was constructed to predict the OS of extensive-stage small cell lung cancer after chemotherapy with immunotherapy.Clinical data of 111 patients with extensive stage small-cell lung cancer who received first-line immunotherapy combined with chemotherapy in our hospital from December 2019 to December 2021 were retrospectively collected. Finally, 93 patients were selected for inclusion in the study, and CT images were obtained through PACS system before treatment. All patients were randomly divided into a training set (n = 66) and a validation set (n = 27). Images were imported into ITK-SNAP to outline areas of interest, and Python software was used to extract radiomics features. A total of 1781 radiomics features were extracted from each patient’s images. The feature dimensions were reduced by MRMR and LASSO methods, and the radiomics features with the greatest predictive value were screened. The weight coefficient of radiomics features was calculated, and the linear combination of the feature parameters and the weight coefficient was used to calculate Radscore. Univariate cox regression analysis was used to screen out the factors significantly associated with prognosis from the radiomics and clinical features, and multivariate cox regression analysis was performed to establish the prognosis prediction model of extensive stage small cell lung cancer. The degree of metastases was selected as a significant clinical prognostic factor by univariate cox regression analysis. Seven radiomics features with significance were selected by LASSO-COX regression analysis, and the Radscore was calculated according to the coefficient of the radiomics features. An alignment diagram survival prediction model was constructed by combining Radscore with the number of metastatic lesions. The study population was stratified into those who survived less than 11 months, and those with a greater than 11 month survival. The C-index was 0.722 (se = 0.044) and 0.68(se = 0.074) in the training and the validation sets, respectively. The Log_rank test results of the combination model were as follows: training set: p < 0.0001, validation set: p = 0.00042. In this study, a combined model based on radiomics and clinical features could predict OS in patients with extensive stage small cell lung cancer after chemotherapy with immunotherapy, which could help guide clinical treatment strategies. [ABSTRACT FROM AUTHOR]

This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010–2019) to identify primary lung cancers with DM at presentation (M1). Kaplan–Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p < 0.001). Male gender, age < 50, primary tumor site (main bronchus, lower lobe), large tumor diameter, ADC/SCLC/SCC pathology, and regional lymph node involvement were significant risk factors for multiorgan metastasis. Age ≥ 50, male, large tumor diameter, positive lymph nodes, and multiorgan metastases were associated with lower CSS. In contrast, radiotherapy, chemotherapy, systemic therapy, and surgery were associated with higher CSS rates. Primary tumor resection improved survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases (KM log rank p < 0.001, HR = 0.6165; 95% CI (0.5468–0.6951)), especially in brain (p < 0.001, HR = 0.6467; 95% CI (0.5505–0.7596)) and bone (p = 0.182, HR = 0.6289; p < 0.01), but not in liver or intrapulmonary metastases after IPTW. Significant differences in DM patterns and corresponding survival rates exist among lung cancer subtypes. Primary tumor resection improves survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases, with better outcomes in patients with brain and bone metastases, while no significant benefit was seen in patients with liver and intrapulmonary metastases. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the relationship between serum uric acid level at diagnosis and asymptomatic brain metastasis in patients with extensive-stage small cell lung cancer. Methods: A total of 69 patients with extensive-stage small cell lung cancer without symptomatic brain metastases, whose serum uric acid level was measured at the time of diagnosis, were included in this retrospective cross-sectional study. The patients were divided into two groups as those with and without asymptomatic brain metastases. The Mann–Whitney U test was used for comparison between groups, and Spearman's correlation test was used for correlation analysis. The cut-off level of serum uric acid level was analyzed, and sensitivity, specificity, and accuracy rates were determined for brain metastasis. Independent factors affecting asymptomatic brain metastasis were determined by multivariate Cox regression analysis. Results: The median serum uric acid level of all patients was 6.9 mg/dL. Twenty-two percent of patients had asymptomatic brain metastases, and serum uric acid levels were significantly higher in these patients (P = 0.0014). The cut-off value for serum uric acid level was calculated as 6.2 mg/dL. The sensitivity, specificity, and accuracy of this value for brain metastasis were 84%, 76%, and 78%, respectively. High serum uric acid level was an independent risk factor for asymptomatic brain metastasis (OR 3.446 95% CI 1.337–5.480; P = 0.005). Conclusion: In conclusion, a serum uric acid level of 6.2 mg/dL and above at the time of diagnosis may predict asymptomatic brain metastasis in patients. [ABSTRACT FROM AUTHOR]

Background: Small Cell Lung Cancer (SCLC) presents a significant clinical challenge due to its aggressive nature and the need for effective biomarkers for treatment monitoring. This study aimed to compare ProGRP and CEA as serological markers in the monitoring of SCLC treatment. Methods: We retrospectively analyzed data from 80 SCLC patients and 80 matched controls. ProGRP and CEA levels were measured, and their associations with clinical parameters, including tumor stage and treatment response, were assessed using Spearman's rank correlation coefficient. Multivariate logistic regression models were employed to identify independent predictors of treatment response and disease progression. Results: ProGRP and CEA levels were considerably higher in cases than controls, with median ProGRP levels at 198.5 pg/mL versus 48.7 pg/mL and median CEA levels at 5.2 ng/mL versus 2.9 ng/mL (both p < 0.001). ProGRP levels correlated positively with tumor stage (ρ = 0.58, p < 0.001) and negatively with treatment response (ρ = − 0.45, p = 0.001). CEA levels also showed positive correlation with tumor stage (ρ = 0.48, p = 0.002) and negative correlation with treatment response (ρ = − 0.35, p = 0.005). Multivariate analysis revealed that ProGRP was an independent predictor for treatment response (OR 1.25 per 100 pg/mL increase, p = 0.001) and disease progression (OR 1.25 per 50 pg/mL increase, p = 0.012), while CEA was a marginal predictor for treatment response (OR 0.95 per 1 ng/mL increase, p = 0.045). Conclusion: Both ProGRP and CEA are significant serological markers in SCLC patients, with ProGRP showing a stronger correlation with tumor stage and treatment response. ProGRP may serve as a superior independent predictor of treatment response and disease progression compared to CEA. These findings support the incorporation of ProGRP in SCLC treatment monitoring protocols. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 74-year-old female patient with rheumatoid arthritis who developed adenosquamous carcinoma within a long-standing intrapulmonary bronchogenic cyst. The patient was asymptomatic for 43 years before experiencing dropping serum sodium levels, which led to the discovery of the malignancy. The article emphasizes the importance of surgical excision for bronchogenic cysts due to the risk of malignant transformation, even after a long period of time. It also discusses the molecular characteristics of adenosquamous carcinomas and potential targeted therapies. [Extracted from the article]

Background Methods Results Conclusions Small cell lung cancer (SCLC) is the most aggressive neuroendocrine lung cancer, with a dismal 5‐year survival rate. No reliable biomarkers or imaging are available for early SCLC detection. In a search for a specific marker of SCLC, this study identified that hepatocyte cell adhesion molecule 2 (HEPACAM2), a member of the immunoglobulin‐like superfamily, is highly and specifically expressed in SCLC.This study investigated HEPACAM2 expression in patients with SCLC via RNA sequencing and evaluated its relationship to progression‐free survival (PFS) and overall survival (OS). Immunofluorescence microscopy was used to assess the cellular location of HEPACAM2 and to conduct in vitro and in vivo studies to understand its expression and functional significance. These findings were integrated with databases of patients with SCLC.HEPACAM2 is highly expressed and specific to SCLC. HEPACAM2 levels are inversely correlated with PFS and OS in patients with SCLC and are expressed at all stages. Moreover, HEPACAM2 messenger RNA and its peptides can be detected in the secretomes in cell lines. Positively correlated with ASCL1 expression in SCLC tumors, HEPACAM2 is localized primarily to the plasma membrane and linked to extracellular matrix signaling and cellular migration. A loss of HEPACAM2 in SCLC cells attenuated ASCL1 and MYC expression. Consistent with clinical data, in vitro and in vivo studies suggested that HEPACAM2 promotes cancer cell growth.With its remarkable specificity, high expression, presence in early disease, and extracellular secretion, HEPACAM2 could be a potential diagnostic cell surface biomarker for early SCLC detection. These findings warrant further investigation into its role in the pathobiology of SCLC. [ABSTRACT FROM AUTHOR]

Background: Measurement of tumor markers from peripheral venous blood is an emerging tool to assist in the early diagnosis of lung cancer. Samples from the pulmonary artery and pulmonary artery wedge position (trans-pulmonary samples) are accessible via right-heart catheterization and, by virtue of their proximity to lung tumors, may increase diagnostic yield. Case presentation: We report a case of a 64 year-old woman from whom trans-pulmonary samples were obtained and who was diagnosed 16 months later with recurrent metastatic small cell lung cancer. Carcinoembryonic antigen, cytokeratin fragment 21 − 1 (CYFRA), and human epididymis protein 4 (HE4) levels demonstrated increasing concentrations across the pulmonary circulation. These gradients exceeded the assays' coefficient of variation by several-fold. For CYFRA and HE4, pulmonary artery wedge concentrations exceeded peripheral venous levels by more than 10% and peripheral arterial levels were up to 8% higher than peripheral venous levels. Conclusions: Evaluating the feasibility and utility of trans-pulmonary tumor markers for lung cancer diagnosis in a larger cohort should be considered. The addition of a peripheral arterial sample to standard peripheral venous samples may be a more practical alternative. [ABSTRACT FROM AUTHOR]