Incidence Of Small Cell Lung Cancer Research Articles

Abstract 6891: Establishment and characterization of a panel of naïve and pretreated small cell lung cancer (SCLC) XPDX models

Abstract SCLC is an aggressive cancer of neuroendocrine origin, accounting for approximately 15% of all lung cancer cases. While the incidence of SCLC in the US has declined over past decades due to changes in smoking habits, this disease provides a poor prognosis and few effective treatment options for advanced disease. To better identify useful therapies for SCLC, we established and characterized a panel of 18 XPDX models representing primary and metastatic disease from either naïve or clinically treated patients and tested sensitivities towards chemotherapies and targeted agents. 18 models were established in immune-deficient mice including 8 from newly diagnosed patients (2 from lung primary), and 10 from recurrent disease (3 from lung primary). Models were IHC stained for Nectin-4, Trop2 protein and ERBB2 and profiled using WES and RNAseq. For in vivo studies, models were evaluated against several chemotherapies including cisplatin, etoposide, topotecan, and temozolomide, as well as ADC agents trastuzumab deruxtecan (T-DXd), enfortumab vedotin (EV), and sacituzumab govitecan (SG). Targeted therapies toward CDK4/6, KRASG12C, and PARP were evaluated in some models. Endpoints in all studies included tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion; a %T/C of ≤ 20% versus control was considered sensitive. Tumor regression (%T/C<0%) versus Day 0 tumor volume was also reported. Less than 10% of models stained positive for Nectin-4, Trop-2 or ERBB2. Molecular characterization revealed RB1 frameshifts or deletions in most models, KRAS/NRAS point mutations in 3 models, and 2 gene fusions SEPTIN7P2-PSPH and TVP23C-CDRT4. In vivo studies reported differential responses to chemotherapies with the most sensitive models established from treatment-naïve patients. Temozolomide was active in several studies including tumor regressions in both naïve and pretreated models. ADCs also reported differential activity toward the tested panel. We have established and characterized a panel of SCLC XPDX models and benchmarked them against various cancer therapies. This panel can be utilized as a valuable tool in developing novel therapies for SCLC patients. Citation Format: Gabriela Huelgas Morales, Peter Forofontov, Johnnie Flores, Alyssa Simonson, Armando Diaz III, Jim Lund, Natalia Banos, Kyriakos Papadopoulos, Drew Rasco, Amita Patnaik, Ali Abedi, Napoleon Puente, Emiliano Calvo, Victor Moreno, Ronald Drengler, Lon Smith, Michael Wick. Establishment and characterization of a panel of naïve and pretreated small cell lung cancer (SCLC) XPDX models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6891.

OA04.06 The Global Landscape of Lung Squamous Cell Carcinoma, Lung Adenocarcinoma, Small Cell Lung Cancer Incidence in 2020

OA04.06 The Global Landscape of Lung Squamous Cell Carcinoma, Lung Adenocarcinoma, Small Cell Lung Cancer Incidence in 2020

The changing landscape of small-cell lung cancer.

e20634 Background: Small-cell lung cancer (SCLC) is an aggressive histologic subtype of lung cancer with distinct biology and clinical course. The aim of this study is to investigate the trends in demographics and outcomes. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess the incidence, demographics, and survival for SCLC using SEER 8 (8 registries), which include data from 1975 to 2019. The pattern of metastases was evaluated using SEER 17 from 2010 to 2019. Jointpoint analysis was used to calculate the trends in annual percentage change according to year of diagnosis. Results: There were 530,198 patients with lung cancer, including 73,362 (13.8%) patients with SCLC in the SEER 8. The percentage of SCLC among all lung tumors progressively increased from 13.3% in 1975 to a peak of 17.5% in 1986, followed by steadily decrease since 1990, reaching 11.1% in 2019. The incidence per 100,000 population increased from 9.5 in 1975 to 15.3 in 1986 followed by a gradual decline to 6.5 in 2019. Among patients with SCLC included in SEER 8, demographic changes from 1975-1979 to 2015-2019 included increased median age at diagnosis from 63 years to 69 and increased percentage of women from 31.4% to 51.2%. The percentage of patients with stage IV increased from 56.9% to 63.8% from 1995-1999 to 2000-2004, and to 69.5% in 2010-2014 without further increase. Among the 55,035 patients with SCLC in SEER 17 from 2010 to 2019, the most common sites of metastasis at diagnosis were mediastinal lymph nodes (69.9%) liver (30.5%), bone (22.8%), and brain (15.8%). The median, 1-year, and 5-year overall survival increased from 6 months, 23%, and 3.6% respectively in 1975-1979 to 7 months, 30.8%, and 6.8% respectively in 2010-2019 (P < 001). Conclusions: The incidence of SCLC in the United States reached a peak in 1985 to 1989 followed by a gradual decline. Demographic changes included an increased median age at diagnosis and the percentage of women, which surpassed men in the last study period. There was also an increase in the percentage of stage IV. The improvement in 5-year OS has been statistically significant but clinically modest.

Temporal trends in small cell lung cancer: Analysis of the U.S. Surveillance, Epidemiology and End Results (SEER) database.

e20641 Background: Prior studies reported that the incidence of small cell lung cancer (SCLC) had decreased, while overall survival (OS) had improved, from 1973-2002. In 2019, immunotherapy was integrated into the standard therapy for patients with extensive-stage (ES) SCLC based on studies demonstrating an improvement in OS. This study aims to provide an update on SCLC incidence and survival at the dawn of this new therapeutic age. Methods: We analyzed data on all patients with primary lung cancer in the SEER17 database from 2000-2019. Patients with ICD-O codes 8002 and 8041-8044 were classified as SCLC. Incidence rates were calculated based on the standard U.S. population. OS was calculated based on censored time to death or last follow-up, whichever occurred earlier. Temporal trends in incidence and OS were evaluated using the Mantel-Haenszel chi-square statistic. Results: Of 847,747 patients with primary lung cancer, 111,263 (13.1%) had SCLC. The incidence rate of SCLC steadily declined from 8.8/100,000 in 2000 to 4.8/100,000 in 2019. Over this time, the incidence rate decreased among both males (10.7 to 5.1/100,000) and females (7.5 to 4.6/100,000), and among all examined races (NHW: 10.1 to 6.0/100,000, NHB: 8.3 to 4.7/100,000, NHA/PI: 3.5 to 1.6/100,000, Hispanic: 4.0 to 1.9/100,000). The proportional incidence of SCLC relative to NSCLC also continued to decline, from 14.5% in 2000 to 11.8% in 2019. The male:female ratio of SCLC patients decreased from 1.14:1 in 2000 to 0.93:1 in 2019. The percentage of patients with limited-stage (LS) SCLC decreased from 31.1% in 2000 to 26.4% in 2019. The majority of patients with LS-SCLC were female throughout the study period (53.9%), while most of those with ES-SCLC were male (51.8%). Among patients with LS-SCLC, 2-year OS increased from 26.7% in 2000 to 36.7% in 2017, while 5-year OS increased from 11.3% in 2000 to 15.6% in 2014. Among patients with ES-SCLC, 2-year OS increased from 6.4% in 2000 to 8.4% in 2017, while 5-year OS increased from 2.2% in 2000 to 2.9% in 2014. Both 2-year and 5-year OS increased in LS-SCLC over the study period in both males and females (M: 2-year: 23.4% to 36.2%, 5-year: 9.9% to 15.2%; F: 2-year: 29.9% to 37%, 5-year: 12.8% to 16.0%). In ES-SCLC, 2-year OS increased in both males and females (M: 5.8% to 7.3%, F: 7.0% to 9.5%), while 5-year OS increased in females (2.2% in 2000 to 3.9% in 2014), but remained stable in males (2.3% in 2000 to 2.0% in 2014). Conclusions: Both the incidence and proportional incidence of SCLC have continued to decline in the U.S. over the past 20 years. The male:female ratio also declined, with women now accounting for the majority of patients with SCLC. The percentage of patients with LS-SCLC decreased, likely due to improvements in staging procedures. Overall survival has continued to improve, with greater gains seen in LS-SCLC than in ES-SCLC prior to the integration of immunotherapy.

Brain Metastasis in Patients with Small Cell Lung Cancer.

PurposeTo characterize the risk factors for brain metastasis (BM) at presentation and analyze the prognostic factors for patients with small cell lung cancer (SCLC).Patients and MethodsPatients were recruited from the SEER database between 2010 and 2016. They were divided into two groups according to BM status. The incidence trends of SCLC and its BM were analyzed by joinpoint software. The risk factors for BM in SCLC were identified by binary logistic regression models. The prognostic factors for SCLC patients with BM were identified by Cox proportional hazard models.ResultsThe incidence of SCLC and its BM significantly decreased after 2010. Totally 11,093 patients were collected, including 1717 (15.5%) patients with BM and 9376 (84.5%) patients without BM. In multivariate logistic regression analysis, age, male and higher T stage were independent risk factors for BM in SCLC patients at presentation. SCLC patients with BM showed inferior survival to those without BM. In multivariate Cox regression analysis, increasing age, large tumor size, and higher N stage were risk factors for poor prognosis, while other race, surgery, adjuvant radiotherapy, and chemotherapy were protective factors for SCLC patients with BM. A nomogram was developed for prognosis evaluation of such patients.ConclusionAge, male and higher T stage were risk factors for BM in SCLC patients at presentation. Increasing age, large tumor size, and advanced N stage may predict poor survival for SCLC patients with BM. Multidisciplinary therapies may provide clinical benefits. This study will help identify patients with higher BM risk and hopefully improve their clinical outcome.

Racial differences in incidence, outcomes, and genomic alterations in small cell lung cancer.

8514 Background: While the incidence of small cell lung cancer (SCLC) has been decreasing in recent years, an increasing proportion of our patients are younger African American (AA) women. There have been no studies describing these changes as well its impact on outcome and potential genomic differences amongst white and AA populations. Methods: We maintain a clinical/genomic/pathological database of all patients with SCLC treated at our comprehensive cancer center starting from 1998. We compared the baseline characteristics and outcomes (Overall survival [OS] and progression-free survival [PFS]) between AA and white patients, and between females and males. In addition, we looked at genomic alterations in >350 cancer-related genes and compared the frequency and types of mutations in our study population. Results: A total of 917 patients with SCLC were included (median age 66 years, 486 female, 179 African American). Amongst the African American patients, 67.6% were female, a striking difference compared to the white population, where only 49.1% were women (P<0.001). In multivariable analysis, there was no association between gender or race with OS or PFS (P> 0.05). There was an increase in mutational frequency in AA women compared to both AA men and white patients. PIK3CA and KIT mutations were more frequent in females while APC mutations were more frequent in males (P=0.041 for all comparisons). There was a trend toward increased mutational frequencies in TP53, PTEN, and NOTCH1 in AA patients. The relative frequency of gene alterations is shown in the table. In univariable analysis, NOTCH1 mutation was associated with improved OS (HR 0.24 [0.06-0.96], P=0.04). Conclusions: In this large cohort of patients with SCLC followed over 2 decades, there was a striking 2-fold higher incidence of SCLC in AA females than in AA males, although there were no differences in OS or PFS by sex or race. Several genomic alterations occur in higher frequencies in AA patients and AA women, in particular, have higher mutational frequencies.[Table: see text]

Incidence and Survival Outcomes in Patients with Lung Neuroendocrine Neoplasms in the United States.

Simple SummaryNeuroendocrine tumors are a rare group of neoplasms characterized by strikingly heterogeneous pathological features and clinical behavior. The incidence and prevalence of these tumors are rising. Studies have reported the incidence and prevalence of neuroendocrine tumors; however, specific data targeting lung neuroendocrine tumors are lacking. We conducted a retrospective analysis using a national database to report the incidence and survival trends of lung neuroendocrine neoplasms. We found that the overall survival and disease-specific survival trends varied significantly not only by stage and histological type but also by age, race, marital status, and insurance type. A small difference was also noted between the rural and urban populations. The rarity of these tumors poses several diagnostic and therapeutic challenges. Our findings generate the following hypothesis that increased awareness of these tumors, as well as better diagnostic modalities, may contribute to a higher incidence. Furthermore, newer therapeutic advances may have caused an improvement in the survival trends in recent years. Such population-based analysis is important to allot resources and guide future research in the field.Background: The incidence and prevalence of neuroendocrine neoplasms (NENs) are rapidly rising. Epidemiologic trends have been reported for common NENs, but specific data for lung NENs are lacking. Methods: We conducted a retrospective analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Associated population data were utilized to report the annual age-adjusted incidence and overall survival (OS) trends. Trends for large-cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC) were reported from 2000–2015, while those for typical carcinoid (TC) and small cell lung cancer (SCLC) were reported from 1988–2015. Results: We examined a total of 124,969 lung NENs [103,890—SCLC; 3303—LCNEC; 8146—TC; 656—AC; 8974—Other]. The age-adjusted incidence rate revealed a decline in SCLC from 8.6 in 1988 to 5.3 in 2015 per 100,000; while other NENs showed an increase: TC increased from 0.57 in 1988 to 0.77 in 2015, AC increased from 0.17 in 2001 to 0.22 in 2015, and LCNEC increased from 0.16 in 2000 to 0.41 in 2015. The 5-year OS rate among SCLC, LCNEC, AC, and TC patients was 5%, 17%, 64%, and 84%, respectively. On multivariable analyses, OS and disease-specific survival (DSS) varied significantly by stage, sex, histological type, insurance type, marital status, and race, with a better survival noted in earlier stages, females, married, insured, Hispanic and other races, and urban population. Similarly, TC and AC had better survival compared to SCLC and LCNEC. Conclusion: The incidence of lung NENs is rising, possibly in part because of advanced radiological techniques. However, the incidence of SCLCs is waning, likely because of declining smoking habits. Such population-based studies are essential for resource allocation and to prioritize future research directions.

Trends in the incidence and survival outcomes in patients with lung neuroendocrine neoplasms in the United States.

e19120 Background: The incidence and prevalence of Neuroendocrine Neoplasms (NENs) are rapidly rising. Epidemiologic trends have been reported for common NENs, but specific data for lung NENs has been lacking. Methods: We conducted a retrospective population-based analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database, and studied lung NENs patients from 1988 to 2015. Associated population data was utilized to report the annual age-adjusted incidence and overall survival trends. Trends in the incidence and survival of large-cell lung cancer (LCLC) and atypical carcinoid (AC) were reported from 2000-2015, while that for typical carcinoid (TC) and small cell lung cancer (SCLC) were reported from 1988-2015. Results: We examined a total of 115,995 lung NENs [103,980 – SCLC; 3,303 – LCLC; 8,146 – TC; 656 – AC]. The age-adjusted incidence rate revealed decline in SCLC from 8.6 in 1988 to 5.3 in 2015 per 100,000; while other NENs showed an increase: TC increased from 0.57 in 1988 to 0.77 in 2015 per 100,000, AC increased from 0.17 in 2001 to 0.22 in 2015 per 100,000, and lastly, LCLC increased from 0.35 in 2001 to 0.41 in 2015 per 100,000. On multivariable analyses, the median overall survival (OS) and disease-specific survival (DSS) rate varied significantly by stage, grade, age at diagnosis, histological type, insurance type, marital status, and race. The 5-year OS rate among SCLC and LCLC patients was 5% and 17%, respectively, consistent with their high-grade nature. On the other hand, TC and AC, representing low-grade neuroendocrine tumors, had good 5-year OS: 84% and 64%, respectively. Conclusions: The incidence of lung NENs is rising, possibly because of advanced radiological techniques. However, we have seen a downtrend in the incidence of SCLCs likely because of declining smoking habits. Such population-based studies are essential for resource allocation and to prioritize future research directions.

Identifying Lung Cancer Risk Factors in the Elderly Using Deep Neural Networks: Quantitative Analysis of Web-Based Survey Data.

BackgroundLung cancer is one of the most dangerous malignant tumors, with the fastest-growing morbidity and mortality, especially in the elderly. With a rapid growth of the elderly population in recent years, lung cancer prevention and control are increasingly of fundamental importance, but are complicated by the fact that the pathogenesis of lung cancer is a complex process involving a variety of risk factors.ObjectiveThis study aimed at identifying key risk factors of lung cancer incidence in the elderly and quantitatively analyzing these risk factors’ degree of influence using a deep learning method.MethodsBased on Web-based survey data, we integrated multidisciplinary risk factors, including behavioral risk factors, disease history factors, environmental factors, and demographic factors, and then preprocessed these integrated data. We trained deep neural network models in a stratified elderly population. We then extracted risk factors of lung cancer in the elderly and conducted quantitative analyses of the degree of influence using the deep neural network models.ResultsThe proposed model quantitatively identified risk factors based on 235,673 adults. The proposed deep neural network models of 4 groups (age ≥65 years, women ≥65 years old, men ≥65 years old, and the whole population) achieved good performance in identifying lung cancer risk factors, with accuracy ranging from 0.927 (95% CI 0.223-0.525; P=.002) to 0.962 (95% CI 0.530-0.751; P=.002) and the area under curve ranging from 0.913 (95% CI 0.564-0.803) to 0.931(95% CI 0.499-0.593). Smoking frequency was the leading risk factor for lung cancer in men 65 years and older. Time since quitting and smoking at least 100 cigarettes in their lifetime were the main risk factors for lung cancer in women 65 years and older. Men 65 years and older had the highest lung cancer incidence among the stratified groups, particularly non–small cell lung cancer incidence. Lung cancer incidence decreased more obviously in men than in women with smoking rate decline.ConclusionsThis study demonstrated a quantitative method to identify risk factors of lung cancer in the elderly. The proposed models provided intervention indicators to prevent lung cancer, especially in older men. This approach might be used as a risk factor identification tool to apply in other cancers and help physicians make decisions on cancer prevention.

Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history.Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models.Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis.Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.

Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor characterized by rapid growth, early metastatic spread, and initial responsiveness to therapy. Although the incidence of SCLC is declining, it remains one of the common causes of cancer-related mortality. Initial evaluation of patients with SCLC should focus on determining the extent of disease and the ability of the patient to tolerate specific therapy. Positron emission tomography (PET) can improve the accuracy of staging and treatment planning in many patients. Limited-stage (LS) SCLC is a potentially curable disease with long-term survival of 20 to 25% when treated with platinum-based chemotherapy plus concurrent thoracic radiation. Hyperfractionated (twice daily) thoracic radiation and prophylactic cranial irradiation (PCI) may improve survival in selected patients with LS-SCLC. For patients with extensive-stage (ES) SCLC, combination chemotherapy prolongs survival and improves quality of life, but long-term survival is rare. The use of PCI and sequential thoracic radiation has been reported to improve survival in selected patients with ES-SCLC. Many chemotherapeutic drugs have activity in SCLC, but little progress has been made in the systemic treatment of SCLC in almost three decades. Although many potential molecular targets have been identified in the preclinical studies of SCLC, molecularly targeted therapy has yet to demonstrate consistent clinical activity. Nevertheless, future advances in SCLC will depend on the development of rational therapeutic strategies which target the molecular mechanisms that drive cellular proliferation, survival, and immunological avoidance.

Changing trends in incidence of lung cancer by histological type in Montenegro

Lung cancer is one of the most common malignant neoplasms, as well as the most common cause of death cancer. Most lung cancers are squamous cell carcinomas, small cell carcinomas or adenocarcinomas. Examining changes in trends of lung cancer incidence in Montenegro by histological type during a 15-year period, from 1997 to 2011. During the study period, histopathological confirmation was obtained for all primary lung cancer cases in the only hospital for lung diseases in the country. Based on the data from medical records, patients were classified by time period, sex, age groups and smoking history. Descriptive method was used. Ratio between incidences of adenocarcinoma and squamous cell carcinoma changes in males, with a significant increase in the incidence rate of adenocarcinoma and drop in the rate of squamous cell carcinoma (p < 0.001). In addition, statistically significant (p < 0.05) decrease in the incidence of NSCLC (non-small cell lung cancer) and an increase in the incidence of SCLC (small cell lung cancer) was found. A statistically significant increase in linear trend in the incidence of small cell carcinoma was noted in females (p < 0.005). Incidence rates of adenocarcinoma and small cell carcinoma have increased during the study period.

An innocent appearing subcutaneous nodule diagnoses a small cell lung cancer in a never-smoker female.

Lung cancer among never-smokers is recognized as the 7th most common cause of cancer death globally. Adenocarcinoma is the most commonly reported histology. Small cell lung cancer (SCLC) has the strongest association with smoking and is rarely reported in never-smokers. Although lung cancer in never-smokers is more common in women, the overall incidence of SCLC in female never-smokers still remains low. Soft tissue metastases from any cancer are rare with an overall prevalence of 1.8%. Soft tissue metastases from lung primary are uncommon, mostly from adenocarcinoma, and portend a poor prognosis. Cutaneous metastases from SCLC are exceptionally rare with reported incidence of 0.3% to 0.8%. We believe ours is the first reported case of SCLC presenting as subcutaneous nodule, in a never-smoker, otherwise asymptomatic female. The diagnosis of SCLC was made incidentally by the excisional biopsy of the subcutaneous nodule. Subsequent CT chest and PET scan revealed a hypermetabolic right lower lobe spiculated lung mass with adrenal and liver involvement. Platinum and etoposide chemotherapy with prophylactic cranial irradiation was initiated for advanced SCLC, and she required further irinotecan and taxol for subsequent pancreatic and adrenal metastases. With continued deterioration, she died approximately 36 months from diagnosis, while under hospice care.

Prognostic factors and trends in outcome for small cell lung cancer over 20 years.

e17518 Background: There has been little change in the chemotherapeutic treatment of small cell lung cancer (SCLC) over the last 30 years but changes in radiotherapy have demonstrated a survival benefit in clinical trails. There is substantial disagreement in the literature on whether or not there has been an improvement in survival for SCLC patients and which patient characteristics serve as important prognostic factors. The majority of the data comes from the selective population of patients included in clinical trials, which do not necessarily reflect real world therapeutic effectiveness. Methods: Using the Manitoba Cancer Registry and Manitoba’s physician billing database, we extracted information on all patients receiving a pathologic diagnosis of SCLC in the Canadian province of Manitoba between Jan 1, 1985 and Dec 31, 2004. Linear regression and Cox proportional hazard regression were then used to determine trends in SCLC incidence, survival, sex distribution, treatment, and prognostic factors. Results: Over the course of the study, the number of cases of SCLC diagnosed each year decreased by 1.41 cases/year (p=0.007), due entirely to a decrease in male cases. The proportion of females increased by 1%/year (p&lt;0.001, 95% CI [0.007, 0.013]). In the whole study population, the proportion of patients receiving no antineoplastic treatment increased dramatically with age, from 11.7% in those ≤50 to 50.6% in patients &gt;80 years old (p&lt;0.001). There has been no change in 2 or 5-year survival (p&gt;0.05 at both time points), which is true for both males and females. Two-year survival was 12.7% for females vs 8% for males (p&lt;0.001), and at 5 years 5.3% of females vs 2.6% of males survive (p=0.002). Male sex was a negative prognostic factor with an adjusted hazard ratio of 1.27 (95% CI [1.16, 1.39]). Conclusions: Female sex is a positive prognostic factor in SCLC. In this population based trial, evolution of therapy over 20 years did not translate into improved survival. A further decline solely in the number of male cases may independently improve survival in the future.

Small-Cell Lung Cancer: Prognostic Factors and Changing Treatment Over 15 Years

BackgroundThe incidence of small-cell lung cancer (SCLC) has decreased over several decades. Sixty-eight thousand six hundred eleven patients with SCLC in the National Cancer Data Base (NCDB) were analyzed to describe demographic, treatment, and survival changes between 1992 and 2007. Methods and MaterialsFour patient cohorts—diagnosed in 1992, 1997, 2002, and 2007—were examined. Univariate and multivariate analyses were performed to determine changes in demographic and treatment factors and their effect on survival of limited SCLC (LSCLC) and extensive SCLC (ESCLC). ResultsThe proportion of female patients increased, whereas the proportion of non-Hispanic white patients decreased. Median survival for patients with ESCLC and LSCLC was 6.1 and 12.9 months, respectively, and was not significantly improved between patients diagnosed in 1992 and 2002. Improved survival was associated with female sex, age < 70 years, and receipt of surgery for patients with LSCLC. Radiation therapy decreased the hazard ratio (HR) for patients with stage III LSCLC but not for patients with earlier stage disease. Chemotherapy decreased the HR for all patients with LSCLC. Patients with ESCLC treated with radiation in addition to chemotherapy had better survival than those who received only chemotherapy. ConclusionsDespite changes in demographics and treatment, the median and 5-year survival rates for patients with SCLC have not significantly improved over the past 15 years. Surgery was associated with improved survival in LSCLC. The benefit of chemotherapy and/or radiation therapy was dependent on American Joint Committee on Cancer (AJCC) stage. AJCC staging information had prognostic and treatment ramifications and should be collected in future studies and databases.

Trends in incidence of small cell lung cancer and all lung cancer

BackgroundThe incidence of small cell lung cancer (SCLC) is often quoted as ‘around 20%’ of all lung cancers but is reportedly decreasing over time. We analysed the trends in incidence of SCLC and compared these with the trends in lung cancer overall among males and females in South East England. MethodsWe identified 237,792 patients diagnosed with lung cancer (ICD-10 C33-C34) between 1970 and 2007. We used a Poisson regression age-cohort model to estimate the age-specific rates in the 1890–1960 birth cohorts. We computed age-standardised incidence rates using the European standard population. In addition, we analysed the trends of lung cancer subtypes according to morphology. ResultsIn the most recent time period, SCLC accounted for 10% and 11% of cases of all lung cancer among males and females, respectively. Among the morphologically specified lung cancers, SCLC accounted for 15% and 17% among males and females, respectively. There was a decrease of SCLC incidence over time and by birth cohort in both sexes. The decrease in SCLC was more marked than that in all lung cancers. ConclusionThe decrease in SCLC incidence rates may reflect decreases in the prevalence of cigarette smoking, and changes in the type of cigarettes smoked.

Advances in the Treatment of Small-Cell Lung Cancer

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastatic dissemination and responsiveness to initial therapy. The incidence of SCLC has been declining over the past decade, mainly due to a decreased incidence in men. Positron-emission tomographic (PET) scans appear to improve the accuracy of staging and treatment planning in patients with SCLC. Limited-stage (LS) SCLC is a potentially curable disease, with long-term survival of ~20% when treated with platinum-based chemotherapy plus concurrent thoracic radiation. Hyperfractionated thoracic radiation and prophylactic cranial irradiation (PCI) may significantly improve overall survival in selected patients with LS-SCLC. For patients with extensive-stage (ES) SCLC, survival can be increased with combination chemotherapy, but the disease remains incurable, and long-term survival is rare. The use of PCI has recently been reported to further improve overall survival in ES-SCLC. Several newer cytotoxic agents, such as amrubicin, have promising activity in early clinical trials. Although many potential molecular targets have been identified in preclinical studies of SCLC, molecularly targeted therapy has yet to demonstrate any substantial activity in clinical trials. Nonetheless, future advances in this disease will undoubtedly depend on improvements in our understanding of the molecular mechanisms that drive the proliferation and survival of SCLC cells.

Small Cell Lung Cancer: Past, Present, and Future

Small cell lung cancer (SCLC) accounts for about 10% to 15% of all lung cancers. It is characterized by its rapid doubling time, high rate of dissemination, and increased sensitivity to chemotherapy and radiation. Although the incidence of SCLC has been steadily decreasing over time, it remains a serious public health problem given its aggressive clinical behavior and the lack of effective therapies. This review looks at the evolution of SCLC treatment and the standard treatments that are currently available, including platinum-based combination chemotherapy, hyperfractionated thoracic radiation, and prophylactic cranial irradiation. The development of novel therapies for SCLC has been lagging behind, but completed clinical trials and ongoing investigations are helping us define what will be the best therapeutic targets for this disease.

Small cell lung cancer in women: The Spanish female-specific database WORLD07.

e12044 Background: Lung cancer is the leading cause of cancer mortality among women in many countries. Small cell lung cancer (SCLC) incidence has decreased during the last years and gender differences have been reported. Methods: WORLD07 is a prospective, multicenter, epidemiologic female-specific lung cancer database analyzing characteristics and treatments of women with lung cancer from several Spanish cancer centers. Inclusion criteria: women > 18 years with a diagnosis of lung cancer, regardless of being treated or not. Written informed consent was required. Results: From October 2007 to December 2009, 629 female newly diagnosed of lung cancer were included in an e-database at 36 Spanish centers. Of those, 68 (10.8%) presented with SCLC. Characteristics were the following: Median age 60 years (y) (range: 39-82); Caucasian 98.5%; marital status (%): married 54.5, unmarried 13, divorced 15, widow 16; educational level (%): basic 44, secondary 22, university 13; median age of menarche: 13 y; children: 74% (median: 2); median age of first child: 25.5 y; premenopausal 13%, postmenopausal 84%; median age of menopause: 47 y; oral contraceptive: 37%; smoking habit (%): never 13, former smoker 16, current smoker 71; family history of cancer: 47%; previous history of cancer: 15%. stage of disease: limited: 51%, extensive: 49%. Conclusions: The incidence of SCLC among women is similar to what is described in the general lung cancer population. Our results indicate that the percentage of never smokers and limited disease is slightly higher in that subgroup. No significant financial relationships to disclose.

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up