Small Cell Lung Cancer Cases Research Articles

Clinical features and prognosis of advanced intra- and extra-pulmonary neuroendocrine carcinomas.

We examined the clinical features and prognosis of advanced intra- and extra-pulmonary neuroendocrine carcinomas (NECs) to offer additional guidance for the clinical treatment of small-cell lung cancer (SCLC), which is a type of advanced intrapulmonary NEC (IPNECs). The clinical data and survival of 123 patients with advanced IPNECs and extrapulmonary NECs (EPNECs) were obtained. We retrospectively examined the corresponding clinical diagnosis and treatment and investigated the significant factors influencing the survival prognosis of patients with NECs. There were 90 cases of IPNECs (including 81 cases of SCLC), and 33 cases of EPNECs. The median overall survival (OS) of IPNECs was significantly longer than that of the EPNECs in the gastrointestinal tract and in the other regions (P < 0.05). The median OS of patients with other IPNECs was longer than that of patients with SCLC (P > 0.05). Multivariate analysis demonstrated that age, liver metastasis, number of cycles of first-line chemotherapy, and chest radiotherapy were risk factors influencing OS in patients with NECs (P < 0.05). The survival of IPNECs was significantly longer than that of EPNECs in the gastrointestinal tract and other regions. Nevertheless, patients with advanced NECs who were older and had liver metastases had a poorer prognosis. Multidisciplinary treatments including multicycle chemotherapy and a combination of chemotherapy and radiotherapy should function significantly in extending the survival of NECs.

A Genome-Wide Association Study of Small Cell Lung Cancer

IntroductionSmall cell lung cancer (SCLC) comprises 10–15% of all lung cancer cases and is the most aggressive histological type. Survival is poor and the molecular landscape of this disease is extraordinarily complex. The objective of this paper was to perform a Genome-Wide Association Study (GWAS) of this disease using a case–control study specifically designed for small cell lung cancer (SCLC). MethodsIncident cases were consecutively recruited from 8 hospitals from different regions of Spain. Controls were recruited from the same hospitals using a frequency sampling based on age and sex distribution of cases. Biological samples were obtained along with detailed information on cases and controls lifestyle, including tobacco and radon exposure. ResultsWe included 271 SCLC cases and 557 controls. We found evidence (p-values<10−5) of an association in the complete dataset for several loci, while MAP4 showed a significant association in the gene-based analysis. Pathway analysis suggested that ATR, ATRIP, MCM4, MCM5, ORC4, RPA3 and CDC25A genes have a role on the onset of SCLC. ConclusionThis study provides biological evidence for pathways related to SCLC, offering novel loci for further research.

POU2F3: A Sensitive and Specific Diagnostic Marker for Neuroendocrine-low/negative Small Cell Lung Cancer.

POU2F3 (POU class 2 homeobox 3) is a novel transcription factor used to define the special molecular subtype of small cell lung cancer (SCLC) known as SCLC-P. Nevertheless, the sensitivity and specificity of POU2F3 immunohistochemical (IHC) staining have not been fully investigated. In this study, we explored the expression of POU2F3 by IHC in a large cohort of SCLC clinical samples (n=246), other common lung cancer types (n=2207), and various other cancer types (n=194). The results showed that POU2F3 was strongly nuclear stained in 13.41% (33/246) of SCLC cases, with negative or minimal labeling for thyroid transcription factor-1 and neuroendocrine (NE) markers. Compared with POU2F3-negative SCLC, SCLC-P harbored fewer TP53 and RB1 mutations. POU2F3 was also expressed in 3.13% (8/256) of squamous cell carcinomas (SCCs) and 20% (2/10) of large cell NE carcinomas (LCNECs), whereas other lung cancer types were negative. In addition to lung cancer, POU2F3 was positive in 22.2% (4/18) of thymic tumors. All other tumors were POU2F3-negative except for thymic carcinoma, although sparsely distributed weak nuclear staining was observed in lung adenocarcinoma, cervical SCC, and colorectal carcinoma. The sensitivity and specificity of POU2F3 in NE-low/negative SCLC were 82.1% and 99.4%, respectively. Notably, some rare unique patterns of POU2F3 expression were observed. One case of thymic SCC was characterized by diffuse and uniform cytomembrane staining. One case of esophageal NE tumor was nuclear-positive, while the normal proliferating squamous epithelium was strongly membrane-stained. This is the largest cohort of clinical samples to confirm that POU2F3 is a highly sensitive and specific diagnostic marker for NE-low/negative SCLC.

Risk factors of early mortality in patients with small cell lung cancer: a retrospective study in the SEER database.

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine cancer with a high risk of early mortality (i.e., survival time less than 1month). This study aimed to identify relevant risk factors and predict early mortality in SCLC patients. A total of 27,163 SCLC cases registered between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) data. Significant independent risk factors were identified by univariate and multivariate logistic regression analyses. Nomograms for all-causes and cancer-specific early death were constructed and evaluated. Age, sex, clinical stage, presence of metastasis (liver and lung), and absence of treatment (surgery, radiotherapy and chemotherapy) were identified for significant association with all-causes and cancer-specific early death. Nomograms based on these predictors exhibited high accuracy (area under ROC curve > 0.850) and potential clinical practicality in the prediction of early mortality. We identified a set of factors associated with early mortality from SCLC and developed a clinically useful nomogram to predict high-risk patients. This nomogram could aid oncologists in the administration of individualized treatment regimens, potentially improving clinical outcomes of SCLC patients.

Dissecting small cell lung cancer subtypes with cell-free DNA fragmentomes.

8592 Background: Although small cell lung cancer (SCLC) is managed as a single cancer type, new evidence supports that subtypes (high vs low neuroendocrine) of SCLC acquire diverse transcriptional and epigenetic states. Furthermore, distinct SCLC subtypes acquire unique therapeutic vulnerabilities, such as the low-neuroendocrine highly inflamed SCLC subtype that has been linked to immunotherapy sensitivity. We have previously shown that DELFI (DNA evaluation of fragments for early interception) can be used to non-invasively distinguish SCLC from non-small cell lung cancer (NSCLC). Here, we report a preliminary analysis of using the DELFI approach for distinguishing among SCLC subtypes. Methods: Circulating cell-free DNA (cfDNA) was isolated from plasma samples of patients diagnosed with relapsed SCLC and treated with durvalumab plus olaparib in a phase II trial (NCT02484404). Over 200 cfDNA libraries were prepared for whole genome sequencing in batches with internal controls. To infer tumor gene expression profiles in cfDNA, we investigated genome-wide signals of tissue-specific transcription factors differentially regulated in SCLC, and applied a novel DELFI-based approach to inform SCLC molecular subtypes. Clinical information, patient-matched tissue transcriptome (RNA-seq), and chromatin accessibility data (ATAC-seq) were examined in orthogonal analyses. Results: The DELFI classifier detected SCLC cases (N = 47) with a median DELFI score of 1.0 (95% CI 0.99-1), significantly higher than previously reported scores for other lung cancer subtypes. Comparison of DELFI fragmentome signals to publicly available tumor transcriptomes shows subtype-level concordance ( r = 0.78, p &lt; 0.001, Pearson), particularly in pre-treatment SCLC cases separating high- vs low- neuroendocrine subtypes. High-neuroendocrine SCLCs exhibited a decrease in aggregate cfDNA fragment coverage at ASCL1 transcription factor binding sites relative to low-neuroendocrine SCLCs (r = 0.90, p &lt; 0.001, Pearson). Additionally, low-neuroendocrine SCLCs revealed a significant decrease in aggregate cfDNA fragment coverage at genomic binding sites regulated by hematopoietic transcription factors, reflecting the inflamed phenotype of this SCLC subtype. Integration of these approaches provided a cfDNA fragmentation-based machine learning model that distinguished SCLC subtypes with high performance. Conclusions: Genome-wide cfDNA fragmentome analyses can differentiate high- and low-neuroendocrine SCLC subtypes. Given the challenges for performing SCLC biopsies in a clinical setting, we believe this approach could be a viable method of subtyping SCLC in a non-invasive manner.

Metastasis of small cell lung carcinoma to the appendix: A case report and literature review

Small cell lung cancer (SCLC) is an aggressive tumor with rapid growth and metastasis. Common sites of metastasis include lymph nodes, adrenal glands, liver, bone, and brain, while gastrointestinal metastasis is less and appendicular metastasis is much rarer. Here, we reported a rare case of appendiceal metastasis from small cell lung cancer presented with acute gangrenous perforated appendicitis, periappendiceal abscess and retroperitoneal abscess. The patient, a 63-year-old male, was diagnosed as small-cell lung cancer due to cough, expectoration and blood in sputum. After chemotherapy, local radiotherapy and whole brain prophylactic radiotherapy, the disease progressed continuously and recurred 1 year later, then presented with acute gangrenous perforated appendicitis combined with periappendiceal abscess and retroperitoneal abscess 2 years later. Histopathological and immunohistochemical findings after appendectomy suggested malignant metastasis of small cell lung cancer. Therefore, in the diagnosis and treatment of SCLC cases, SCLC metastasis occurs not only in the common lymph nodes, kidney, adrenal gland, brain, liver, etc., but also in the appendix. This report is expected to provide new guidance for the diagnosis and treatment of such cases.

Abstract 931: Comprehensive analysis of 3,600 small cell lung cancer cases reveals rare genetic subtypes and multiple mechanisms of histological transformation

Abstract Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with limited treatment options and extremely poor survival outcomes. A major barrier in the field has been the relative paucity of human tumors studied and lack of access to longitudinal samples to understand tumor evolution. Methods: Here we provide a comprehensive analysis of 3,600 patients with SCLC who underwent targeted genomic profiling of at least 324 cancer-related genes as part of routine clinical care, including 678 cases with additional clinical and treatment information obtained from a US-based de-identified SCLC clinico-genomic database that originated from approximately 280 US cancer clinics. This large cohort allowed us to examine for new genetic subtypes, ancestry-associated genomic alterations, biopsy site-specific patterns, survival trends and histological transformation of SCLC from non-small cell lung cancer (NSCLC). Results: Consistent with prior studies, SCLCs were predominantly TP53/RB1 altered. Yet, 5.5% of the cases in our cohort were TP53/RB1 wild-type tumors. These tumors often lacked a tobacco mutational signature, exhibited alternate mechanisms of p53/Rb pathway inactivation (e.g., CDKN2A, CCND1, MDM2), and had a high fraction of human papillomavirus-positive cases (12.7%). Another rare subtype of SCLCs included STK11-altered tumors (1.7%), which were observed more frequently in patients of African ancestry, and were associated with a decreased overall survival (OS) compared with the STK11 wild-type cohort. In our cohort, gene amplifications on 4q12 (KDR, KIT, PDGFRA) were associated with increased OS while CCNE1 amplification was associated with decreased OS. Interestingly, alterations in PTEN were more common in brain metastases compared to lung biopsies and liver metastases, suggesting its potentially unique role in brain metastases of SCLCs. Profiling of over 100 putative transformed SCLCs demonstrated that lineage plasticity may occur at variable lengths of time from the original NSCLC diagnosis and include multiple distinct molecular cohorts of NSCLC, beyond EGFR-mutant NSCLC (e.g., kinase fusion+ tumors: RET, ALK, ROS1, NTRK1). Conclusion: Our work underscores the existence of genetic subtypes in SCLC, including rare subtypes with potential clinical utility. Findings from this study provide an improved understanding of genetic subtypes in SCLC and better inform mechanisms of transformation to SCLC from NSCLC, that may further guide the development of personalized therapies for subsets of patients with this fatal tumor. Citation Format: Smruthy Sivakumar, Jay A. Moore, Meagan Montesion, Douglas I. Lin, Zoe Fleischmann, Ericka M. Ebot, Justin Newberg, Jennifer M. Mills, Priti S. Hegde, Garrett M. Frampton, Julien Sage, Christine M. Lovly. Comprehensive analysis of 3,600 small cell lung cancer cases reveals rare genetic subtypes and multiple mechanisms of histological transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 931.

Wood dust exposure and small cell lung cancer: a systematic review and meta-analysis.

Occupational exposure role on small cell lung cancer (SCLC) onset has been little studied. Wood dust has been recognized as a human carcinogen, and many occupations have high wood-dust exposure. The aim of this study was therefore to perform a systematic review and meta-analysis of the scientific literature to summarize and analyse the risks of wood dust-related occupations on development of SCLC, taking tobacco use into account. We conducted a literature search of PubMed, EMBASE, Web of Science and Cochrane using a predefined strategy and including case-control and cohort studies assessing occupational exposure to wood dust or wood dust-related occupations. To perform the meta-analysis, the odds ratio (OR) and 95% confidence interval (CI) of each of the studies were extracted. A random-effects model was fitted using the DerSimonian Laird method. Sensitivity and subgroup analyses were performed. Quality was assessed using the Office and Health Assessment and Translation (OHAT) for human and animal studies instrument. Eleven studies with a total of 2,368 SCLC cases and 357,179 controls were included. Overall, exposure to wood dust significantly increases risk of SCLC (RR = 1.41, 95% CI 1.11-1.80), with low heterogeneity between studies (I2 = 40%). The association was maintained in studies conducted on males (RR = 1.41, 95% CI 1.12-1.78) but not in those conducted on females/both sexes (RR = 1.37, 95% CI 0.35-3.44). Sensitivity analysis showed that none of the studies significantly modified the results. Our results support that exposure to wood-dust can increase the risk of SCLC. Although the level of evidence is low, there are strong arguments to recommend the implementation of effective control measures to reduce exposure in occupational settings, as a means of preventing SCLC. The results of this study support that exposure to wood-dust can increase the risk of developing small cell lung cancer. Determining the impact of occupational exposure on workers is essential to improve their individual protection and prevention. There is a strong case for recommending the implementation of control measures to reduce occupational exposure to wood dust, specifically for highly exposed occupations such as carpenters and sawmills, in order to prevent small cell lung cancer.

Antigene MYCN Silencing by BGA002 Inhibits SCLC Progression Blocking mTOR Pathway and Overcomes Multidrug Resistance.

Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in MYC family members are biomarkers of poor prognosis for a large number of SCLC. In particular, MYCN alterations define SCLC cases with immunotherapy failure. MYCN has a highly restricted pattern of expression in normal cells and is an ideal target for cancer therapy but is undruggable by traditional approaches. We propose an innovative approach to MYCN inhibition by an MYCN-specific antigene-PNA oligonucleotide (BGA002)-as a new precision medicine for MYCN-related SCLC. We found that BGA002 profoundly and specifically inhibited MYCN expression in SCLC cells, leading to cell-growth inhibition and apoptosis, while also overcoming multidrug resistance. These effects are driven by mTOR pathway block in concomitance with autophagy reactivation, thus avoiding the side effects of targeting mTOR in healthy cells. Moreover, we identified an MYCN-related SCLC gene signature comprehending CNTFR, DLX5 and TNFAIP3, that was reverted by BGA002. Finally, systemic treatment with BGA002 significantly increased survival in MYCN-amplified SCLC mouse models, including in a multidrug-resistant model in which tumor vascularization was also eliminated. These findings warrant the clinical testing of BGA002 in MYCN-related SCLC.

Comparative study of the genomic landscape and tumor microenvironment among large cell carcinoma of the lung, large cell neuroendocrine of the lung, and small cell lung cancer.

Deciphering the genomic profiles and tumor microenvironment (TME) in large cell carcinomas of the lung (LCC), large cell neuroendocrine of the lung (LCNEC), and small cell lung cancer (SCLC) might contribute to a better understanding of lung cancer and then improve outcomes. Ten LCC patients, 12 LCNEC patients, and 18 SCLC patients were enrolled. Targeted next-generation sequencing was used to investigate the genomic profiles of LCC, LCNEC, and SCLC. Tumor-infiltrating lymphocytes (TILs) within cancer cell nests and in cancer stroma were counted separately. Precise 60% of LCNEC patients harbored classical non-small cell lung cancer driver alterations, occurring in BRAF, KRAS, ROS1, and RET. More than 70% of SCLC patients harbored TP53-RB1 co-alterations. Moreover, 88.9%, 40%, and 77.8% of LCC, LCNEC, and SCLC cases had a high tumor mutation burden level with more than 7 mutations/Mb. Furthermore, high index of CD68+ CD163+ (TILs within cancer cell nests/ TILs within cancer cell nests and in cancer stroma, P = .041, 548 days vs not reached) and CD163+ TILs (P = .041, 548 days vs not reached) predicted a shorter OS in SCLC. Our findings revealed the distinct genomic profiles and TME contexture among LCC, LCNEC, and SCLC. Our findings suggest that stratifying LCNEC/SCLC patients based on TME contexture might help clinical disease management.

Abstract A025: Enrollment of older adults in small cell lung cancer (SCLC) clinical trials compared with population-based U.S. incidence estimates

Abstract Background: Small cell lung cancer (SCLC) is an aggressive form of cancer characterized by rapid progression, early metastases, and poor prognosis. Clinical trials (CTs) leading to approval of various classes of medical products have recently increased the treatment options available for SCLC patients. Older adults ≥65 years of age are historically under-enrolled in CTs. The U.S. population continues to age. There is often limited evidence supporting safety and effectiveness of treatment among this population because of disproportionate enrollment of older adults in CTs. To characterize patterns of SCLC CT enrollment by age, selected SCLC CTs (immunotherapy and cytotoxic agents) were compared to U.S. SCLC incidence data. Methods: We identified six CTs for treatment of SCLC to support marketing applications submitted to the FDA between 2018-2019. Descriptive statistics based on the pooled CT data were calculated and compared with incident U.S. SCLC cases diagnosed between the same period, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. While SEER is a U.S. population-based representative sample, data from the trials included patients outside the U.S. that were submitted to support marketing applications with applicability to U.S. clinical practice. Results: A total of 1,642 patients were enrolled in the six included SCLC CTs. In this sample, 42.9% were age ≥65 years, compared to 66.6% of incident U.S. SCLC cases. This disparity persists with increasing age: 8.5% of CT enrollees were age ≥75 years and 1.8% of CT enrollees were age ≥85 years, compared to 27.5% and 4.5% of incident U.S. SCLC cases, respectively. Discussion: Based on these findings, older adults are underrepresented in SCLC CTs, while representing a substantially larger proportion of incident U.S. cases. The number of SCLC patients over 65 years is likely to increase the U.S. population continues to age. Aging presents specific challenges with respect to cancer care due to increased presence of comorbidities and the potential for variance in patient and provider treatment preferences, which might partially explain the results. These results demonstrate an opportunity to evaluate and fix barriers to trial entry for older adults to ensure representative evidence generation that is reflective of the epidemiology of the disease and the real-world population. Citation Format: Felice Yang, Oladimeji Akinboro, Catherine Lerro, Fatima Rizvi, Pallavi Mishra-Kalyani, Paul G. Kluetz, Harpreet Singh, Donna R. Rivera. Enrollment of older adults in small cell lung cancer (SCLC) clinical trials compared with population-based U.S. incidence estimates [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A025.

Methods and techniques for lung cancer detection, diagnosis, and treatment

For a very long time, lung cancer was a major health problem and the leading cause of death worldwide. Small cell lung cancer (SCLC) accounts for 15% of cases and non-small cell lung cancer (NSCLC) accounts for 85% of cases. Although many people believe that smoking is the primary cause of lung cancer, there are numerous other contributing factors as well. Nonsmokers have a higher risk of lung cancer from radon than smokers do. Smoke from household fuel, infections caused by bacteria and viruses, as well as inflammatory diseases like asthma and sarcoidosis, are additional risk factors for nonsmokers to develop lung cancer. This review aims to summarize recent studies of SCLC and NSCLC cases in the world and asses the methods used for diagnosis. Further, the most recent risk factors and characteristics of the disease, particularly in nonsmokers, as are novel treatment options, are outlined in this review.

Abstract B025: ASCL1 and SOX2 expression levels predict sensitivity to LSD1 inhibition with iadademstat in small cell lung cancer

Abstract Lysine Specific Demethylase 1 (LSD1, also known as KDM1A) is a member of the FAD-containing family of lysine demethylases and is generally involved in repressing transcription by specifically removing methyl groups from mono- and di-methylated lysine 4 of histone 3 - epigenetic marks commonly associated with actively transcribed genes. LSD1 over-expression has been associated with disease progression and worse prognosis in several human cancers, and its inhibition has been shown to reduce cancer cell growth, migration and invasion. LSD1 has therefore been recognized as a target of interest for the development of new drugs to treat cancer. Iadademstat (aka ORY-1001), a highly potent and selective LSD1 inhibitor (LSD1i) in clinical development for malignant indications, and other LSD1is, have been reported to be effective for the treatment of small cell lung cancer (SCLC) in in vitro and in vivo models. However, the published data indicate that while certain SCLC are highly sensitive to LSD1 inhibition this sensitivity is not a universal feature of SCLC cells raising the need to develop methods for identifying sensitive SCLC tumors. Herein, we report the identification of the predictive biomarkers ASCL1 and SOX2 for the enrichment of the SCLC population more likely to respond to iadademstat and other LSD1is. Response to LSD1is was evaluated in a broad panel of SCLC cell lines (from viability assay data obtained internally at Oryzon Genomics with iadademstat and from data published elsewhere using other LSD1is). Additionally, analysis of gene expression was performed in this cell line panel using internal and publicly available datasets (Affymetrix, CCLE). This analysis revealed that the transcription factors ASCL1 and SOX2 are more likely to be highly expressed in SCLC cell lines that respond to LSD1 inhibition. Moreover, the mRNA levels of these biomarkers were highly correlated with their protein levels in both SCLC cell lines and in patient-derived xenografts. In particular, immunofluorescence staining of these patient-derived SCLC samples can discriminate different degrees of ASCL1 and SOX2 protein expression levels (none, low, medium, high), which correlate with their mRNA levels determined by RNAseq in the same samples. Moreover, analysis of ASCL1 and SOX2 protein levels analyzed internally by immunofluorescence in 40 SCLC biopsies showed that 58% samples concomitantly expressed medium to high levels of both biomarkers. Taken together, these data suggest that medium to high expression of both ASCL1 and SOX2 define a SCLC population more likely to respond to LSD1 inhibition, and that this population could account for nearly 60% of SCLC cases. Therefore, ASCL1 and SOX2 expression could be used as predictive biomarkers for personalized medicine with iadademstat in SCLC patients and clinical research to validate this hypothesis is warranted. Citation Format: Natalia Sacilotto, Serena Lunardi, Filippo Ciceri, Cristina Mascaro, Tamara Maes, Ana Limon, Douglas V. Faller. ASCL1 and SOX2 expression levels predict sensitivity to LSD1 inhibition with iadademstat in small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr B025.

NOL4 is a novel nuclear marker of small cell carcinoma and other neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) such as small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have characteristic histologies, but immunohistochemistry using neuroendocrine markers is still desirable to confirm diagnosis. CD56 is the most sensitive marker, but also stains various normal tissues and other tumors. Recently, we reported that nucleolar protein 4 (NOL4) is present in the blood of SCLC patients and found it was stained in the SCLC nuclei. In this study, we compared expressions of NOL4 and CD56, using 64 cases of SCLC, 18 cases of LCNEC, 6 cases of atypical carcinoid tumor, 7 cases of typical carcinoid tumor, 68 cases of lung adenocarcinoma, and 62 cases of lung squamous cell carcinoma. For primary lung NENs, sensitivity, specificity, positive predictive value (PPV) and negative predictive value of NOL4 were 77.5%, 95.8%, 93.2%, and 85.1%, respectively, while those of CD56 were 92.1%, 93.3%, 91.1%, and 94.1%. The specificity and PPV of NOL4 were higher than those of CD56, although the differences were not statistically significant. However, NOL4 retains its nuclear immunoreactivity in areas of crush artifact or necrosis. Furthermore, NOL4 was not expressed in adjacent normal tissues including bronchial cells and pneumocytes. Therefore, a combination of NOL4 staining with other cytoplasmic or membranous neuroendocrine markers might enhance diagnostic utility for SCLC and other NENs.

Association of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP with Clinicopathological Characteristics and Chemotherapeutic Outcomes of Lung Cancer.

The aim of this study was to investigate the association of serum carcinoembryonic antigen (CEA), nerve-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag), and pro-gastrin-releasing peptide (ProGRP) with the clinicopathological characteristics and chemotherapeutic outcomes of patients with lung cancer. A total of 189 patients with lung cancer (lung cancer group) diagnosed at the Fourth Affiliated Hospital of Anhui Medical University from January 2020 to December 2021 were included. During the same period, 199 patients with benign lung disorders were included as the benign lung disease group and 75 healthy people were selected as the control group. The serum concentrations of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP in all the 3 groups were analyzed and compared in patients with different lung cancer tumor-node-metastasis (TNM) stages and pathological classifications. Atotal of 11 patients with small cell lung cancer (SCLC) and 18 patients with lung adenocarcinoma (LAC) were further evaluated forthe dynamic changes of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP before chemotherapy and during the 6 courses of chemotherapy, and the outcome of chemotherapy was evaluated every 2 courses. The serum concentrations of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP in the lung cancer group were significantly higher than those in the control group (P < .05). We found statistically significant differences in serum CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP among patients with different pathological types (LAC, squamous cell carcinoma, or SCLC) and different stages (I-IV). The ProGRP and NSE had the highest expression in SCLC, CEA showed the highest expression in LAC, whereas CYFRA21-1 and SCC-Ag showed the highest expression in lung squamous cell carcinoma (LSCC). The concentrations of all the markers were elevated in the advanced pathological stages. The receiver operating characteristic curve analysis showed that the diagnostic value of the combined detection of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP for lung cancer was significantly higher than using a single biomarker (P < .05). Our dynamic monitoring results show that ProGRP progressively decreased in remission cases of SCLC and CEA progressively decreased in LAC remission cases. CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP have good clinical value in the early diagnosis, differential diagnosis, and progression monitoring of lung cancer. The ProGRP and CEA concentrations are beneficial for evaluating the outcome of chemotherapy in SCLC and LAC. The combined detection of multiple biomarkers shows improved clinical value in the early diagnosis of lung cancer.

Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans

The current standard of care for the treatment of small cell lung cancer (SCLC) is concurrent chemoradiation for patients with limited-stage SCLC (LS-SCLC) and chemoimmunotherapy for extensive-stage SCLC (ES-SCLC). The backbone of chemotherapy regimens in both is a platinum-etoposide doublet: cisplatin is traditionally the preferred platinum agent in the curative intent setting, whereas carboplatin is preferred in ES-SCLC because of its favorable toxicity profile. To determine whether cisplatin is associated with better survival outcomes than carboplatin in treating LS-SCLC and ES-SCLC. In this cohort study, data were compiled from the National Veterans Affairs Central Cancer Registry for patients with SCLC who received platinum-based multiagent chemotherapy between 2000 and 2020 for ES-SCLC and 2000 and 2021 for LS-SCLC. Only patients with pathologically confirmed cases of LS-SCLC who received concurrent chemoradiation and ES-SCLC who received chemotherapy were included. The primary end point was overall survival (OS). The secondary end points included OS by Eastern Cooperative Oncology Group performance status, age, and laterality. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median OS and hazard ratios (HRs), respectively. Survival curves were compared by a Wald test. A total of 4408 SCLC cases were studied. Most patients were White (3589 patients [81.4%]), male (4252 [96.5%]), and non-Hispanic (4142 [94.0%]); 2262 patients (51.3%) were 60 to 69 years old, followed by 1476 patients (33.5%) aged 70 years or older, 631 patients (14.3%) aged 50 to 59 years, and 39 patients (0.9%) aged 30 to 49 years. Among 2652 patients with ES-SCLC, 2032 were treated with carboplatin-based therapy and 660 received cisplatin; the median OS was 8.45 months (95% CI, 7.75-9.20 months) for cisplatin and 8.51 months (95% CI, 8.07-8.97 months) for carboplatin (HR, 1.01; 95% CI, 0.91-1.12; P = .90). Subset analysis showed no survival difference between the 2 agents in different age or performance status groups except for patients aged 70 years and older, for whom the median OS was 6.36 months (95% CI, 5.31-7.56 months) for cisplatin and 8.47 months (95% CI, 7.79-9.19 months) for carboplatin (HR, 0.77; 95% CI, 0.61-0.96; P = .02). Multivariable analysis of performance status and age did not show a significant difference in survival between the 2 groups (HR, 0.96; 95% CI, 0.83-1.10; P = .54). Of 1756 patients with LS-SCLC, 801 received carboplatin, and 1018 received cisplatin. The median OS was 26.92 months (95% CI, 25.03-28.81 months) for cisplatin and 25.58 months (95% CI, 23.64-27.72 months) for carboplatin (HR, 1.04; 95% CI, 0.94-1.16; P = .46). The median OS was not significantly different between 2 agents according to cancer stage (I-III), performance status, and age groups. A multivariable analysis of factors associated with OS accounting for stage (I-III), performance status, and age did not demonstrate a significant difference in survival between carboplatin and cisplatin in patients with LS-SCLC (HR, 0.995; 95% CI, 0.86-1.15; P = .95). Cisplatin is not associated with a survival advantage over carboplatin among patients with either ES-SCLC or LS-SCLC, irrespective of performance status and age. The favorable toxicity profile of carboplatin and comparable OS support its use in both LS-SCLC and ES-SCLC in clinical practice and may allow more room for combination with novel treatment strategies in clinical trials.

Parameters of Dual-layer Spectral Detector CT Could be Used to Differentiate Non-Small Cell Lung Cancer from Small Cell Lung Cancer.

Differentiating non-small cell lung cancer (NSCLC) from small cell lung cancer (SCLC) remains a substantial challenge. This study aimed at evaluating the performance of dual-layer spectral detector CT (DLCT) in differentiating NSCLC from SCLC. Spectral images of 247 cancer patients confirmed by pathology were retrospectively analyzed in both the arterial phase (AP) and the venous phase (VP), including 197 cases of NSCLC and 50 cases of SCLC. Effective atomic number (Z-eff), Spectral CT-Mono Energetic (MonoE [40keV~90keV]), iodine density (ID) and thoracic aorta iodine density (IDaorta) in contrast-enhanced images were measured and compared between the SCLC and NSCLC subgroups of tumors. The slope of the spectral curve (λ, interval of 10 keV) and normalized iodine density (NID) were also calculated between the SCLC and NSCLC. Through the statistical analysis, the diagnostic efficiency of each spectral parameter was calculated, and the difference in their efficiency was analyzed. Both in NSCLS and SCLC, all parameters in VP were significantly higher than those in AP (p<0.001), except for λ90. There were significant differences in all spectral parameters between NSCLS and SCLC, both in AP and VP (p < 0.001). Except for VP-λ90, there was no significant difference in ROC curves of all spectral parameters. VP-NID exhibited the best diagnostic performance with an AUC value of 0.917 (95%[CI]: 0.870~0.965), sensitivity and specificity of 92.9% and 80%, and a diagnostic threshold of 0.217. All parameters of DLCT have high diagnostic efficiency in differentiating NSCLC from SCLC except for VP-λ90, and VP-NID has the highest diagnostic efficiency.

Adjuvant treatment for patients with incidentally resected limited disease small cell lung cancer-a retrospective study.

BackgroundWith the exception of very early-stage small cell lung cancer (SCLC), surgery is not typically recommended for this disease; however, incidental resection still occurs. After incidental resection, adjuvant salvage therapy is widely offered, but the evidence supporting its use is limited. This study aimed to explore proper adjuvant therapy for these incidentally resected SCLC cases.MethodsPatients incidentally diagnosed with SCLC after surgery at the Shanghai Pulmonary Hospital in China from January 2005 to December 2014 were included in this study. The primary outcome was overall survival. Patients were classified into different group according to the type of adjuvant therapy they received and stratified by their pathological lymph node status. Patients’ survival was analyzed using a Kaplan-Meier analysis and Cox regression analysis.ResultsA total of 161 patients were included in this study. Overall 5-year survival rate was 36.5%. For pathological N0 (pN0) cases (n=70), multivariable analysis revealed that adjuvant chemotherapy (ad-chemo) was associated with reduced risk of death [hazard ratio (HR): 0.373; 95% confidence interval (CI): 0.141–0.985, P=0.047] compared to omission of adjuvant therapy. For pathological N1 or N2 (pN1/2) cases (n=91), taking no adjuvant therapy cases as a reference, the multivariable analysis showed that ad-chemo was not associated with a lower risk of death (HR: 0.869; 95% CI: 0.459–1.645, P=0.666), while adjuvant chemo-radiotherapy (ad-CRT) was associated with a lower risk of death (HR: 0.279; 95% CI: 0.102–0.761, P=0.013).ConclusionsPatients who incidentally receive surgical resection and are diagnosed with limited disease SCLC after resection should be offered adjuvant therapy as a salvage treatment. For incidentally resected pN0 cases, ad-chemo should be considered and for pN1/2 cases, ad-CRT should be received.

Small cell lung cancer in young patients: trends in sociodemographic factors, diagnosis, treatment, and survival.

BackgroundSmall cell lung cancer (SCLC) in patients <50 years old has unique socioeconomic and clinical implications. We aimed to examine the demographics, treatment patterns, and survival of young patients with SCLC and compared them to older adults.MethodsThe National Cancer Database (NCDB) was queried to identify SCLC cases diagnosed from 2004 to 2016. Patients were divided into three age groups: ≥18–<50, ≥50–<70, and ≥70 years. Patient characteristics were evaluated for survival within each age group. Kaplan-Meier and Cox regression analyses were used to assess survival.ResultsOf the 172,453 evaluated SCLC patients (median age 66 years), 8,792 were ≥18–<50 years old. Compared to the older groups, patients under 50 were more likely to be Black, uninsured or on Medicaid, have household income <$30,000, and present with stage III or IV disease (P<0.0001 for all). While young patients were more likely to receive guideline-concordant care (GCC), the hazard of death increased to 1.96 (95% CI: 1.80–2.14; P<0.0001) with receipt of nonstandard therapy. Private insurance, female gender, non-White race, Hispanic ethnicity, and higher income were associated with better survival. The youngest cohort had significantly better survival overall when compared to the older patients (P<0.0001), but the survival advantage was reduced with the advancing stage.ConclusionsSCLC patients under 50 years old represent a socioeconomically disadvantaged group with advanced disease at presentation. Despite having fewer comorbidities and being offered guideline-concordant treatment, younger patients with SCLC have only marginally better survival than older patients in advanced stages.

Küçük hücreli akciğer kanserinde tedavi sonuçları ve etki eden prognostik faktörler

Giriş ve Amaç: Küçük hücreli akciğer kanseri (KHAK) tüm akciğer kanserlerinin yaklaşık %15’ini oluşturmaktadır. Küçük hücreli akciğer kanserinde prognoz; yeni kemoterapotik ajanların kullanılması, radyoterapi (RT) tekniklerinin gelişmesi ve profilaktik kraniyal ışınlamanın (PKI) eklenmesi ile tedavi sonuçları iyileşmesine rağmen halen kötüdür. Akciğer kanserinde prognostik faktörlerin önceden belirlenmesi tedavi ve takip açısından çok önemlidir. Bu tür çalışmaların çoğu küçük hücreli dışı akciğer kanserli hastalarla yapıldığı için çalışmamızda küçük hücreli akciğer kanserli olgularımızda tedavi sonuçlarını ve prognostik faktörleri değerlendirdik. &#x0D; Gereç ve Yöntemler: Hastanemizde 2002–2017 yılları arasında tedavi edilen 123 küçük hücreli akciğer kanserli olgu değerlendirmeye alındı. Retrospektif olarak hasta dosyaları tarandı.&#x0D; Bulgular: Hastaların 102’si erkek olup, medyan yaş 61 (29-81) olarak saptandı. Başlangıçta 59 hastada kilo kaybı vardı, en sık şikayet öksürüktü. 72’si (58.5) sınırlı, 51’i (%41,5) yaygın evreydi. Tümör 68 hastada sağ taraf yerleşimliydi. 24 hastada aile öyküsü vardı. 48 hastada ek hastalık ve119’unda sigara öyküsü vardı. Radyoterapi 63 (%51,2) hastada küratif, 60 hastada palyatif olarak uygulandı. 55 hasta radyokemoterapi aldı.79 hastada kemoterapi kür sayısı 5 ve üzerinde olup,44 hastada 4 ve daha az sayıda kür uygulandı.68 hasta PKI aldı. Ortalama izlem süresi 19.2 aydı. Bir yıllık genel sağ kalım%62,2, 2 yıllık sağkalım%30,1 ve genel sağ kalım 15 ay ve progresyonsuz sağkalım %15 olarak bulunmuştur. 59 hastada lokal nüks, 47 hastada uzak metastaz gelişti. Evre, yaş, ECOG, kilo kaybı, kraniyal metastaz gelişmesi, başlangıçta başağrısı, dispne ve kemoterapi kür sayısı; genel sağ kalımda istatistiksel olarak anlamlı bulunmuştur. ECOG, kilo kaybı, cinsiyet ve KT kür sayısı progresyonsuz sağ kalımda anlamlı bulunmuştur. &#x0D; Sonuç: KHAK’nin tedavisinde önemli mesafeler alınmasına karşılık, sağ kalım oranlarında beklenen artış henüz sağlanamamaktadır. Çalışmamızda sağ kalım oranları literatürle uyumludur. PKI’nın sınırlı evrede tedaviye eklenmesi belirgin şekilde beyin metastazını azaltmaktadır. Beyin metastazsız yaygın evre hastalıkta PKI’nın tedaviye eklenmesi genel sağ kalım üzerine etkili bulunmamakla birlikte beyin metastazı gelişme süresinin uzadığı görülmüştür. Küçük hücreli akciğer kanserinde torasik radyoterapi ve PKI uygulamasıyla bir çok çalışmada sağ kalımda artış görülmüş olup, radyoterapinin rolü giderek artmaktadır. Her hasta için potansiyel fayda ve riskler başlangıç tedavisinden önce belirlenmeli ve kişiye özel tedavi planlanmalıdır.