bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of patients with small cell lung cancer admitted to the intensive care unit.
Authors: Huang Joy , Kwon Daniel H , Brondfield Sam 
Published: June 2023

e20620 Background: Small cell lung cancer (SCLC) is aggressive and carries a poor prognosis. National Comprehensive Cancer Network guidelines recommend considering systemic therapy even for patients with poor performance status, if cancer-related. However, little is known about the prognosis and effectiveness of treatment for patients with SCLC in the intensive care unit (ICU), and thus clinicians lack guidance in this scenario. Therefore, we characterized outcomes and predictors of overall survival (OS) for patients with SCLC in the ICU for cancer-related complications, with or without chemotherapy. Methods: This is a single-institution retrospective study in which we used diagnosis codes to identify all patients with SCLC who were admitted to the ICU from 2012 to 2022. We then manually selected patients admitted to the ICU for cancer-related complications and excluded those admitted for chemotherapy complications, post-operative observation, or other reasons not directly related to SCLC. Demographic and clinical data were collected via manual chart review. OS from ICU admission date was evaluated using the Kaplan-Meier method and compared between those who received chemotherapy and those who did not using the log-rank test. Multivariate analysis was performed using Cox proportional hazards regression analysis to identify predictors of OS. Sensitivity analysis was performed by excluding patients with limited stage (LS) disease. Results: Twenty-three patients met inclusion criteria, of whom 20 had extensive-stage (ES) and three had LS disease. Six patients received chemotherapy in the ICU (five with ES, one with LS) and 17 did not. Of those who received chemotherapy, two died during their stay, and four had partial responses. Median OS from ICU admission for all patients was 2.4 weeks. Median OS from ICU admission did not differ significantly between those who received chemotherapy and those who did not (21.0 vs 1.6 weeks, p = 0.12). A three-variable model significantly predicted OS: pulmonary vs non-pulmonary reason for ICU admission (HR for death = 6.18 [95% CI 2.01-19.00], p < 0.01), TNM stage IVB vs IVA or III (HR = 5.34 [1.58-18.00], p = 0.01), and Charlson Comorbidity Index (HR = 0.76 [0.56-1.04], p = 0.09). Results were similar when patients with LS disease were excluded. Conclusions: In this single-institution study of patients with SCLC admitted to the ICU for cancer-related complications, OS was short. Chemotherapy given in the ICU was not associated with longer OS. Potential clinical predictors of OS at the time of ICU admission were identified: pulmonary reason for ICU admission and TNM stage IVB were both associated with shorter OS. The trend toward improved OS associated with higher Charlson comorbidity index may reflect reversible non-malignant contributors to ICU-level illness. Conclusions apply primarily to patients with ES disease. These findings require validation in larger, multicenter studies.
Impact of systemic immune-inflammation index in patients with limited-stage small cell lung cancer.
Authors: Zhang Ziling , Li Juan , Liu Huijuan , Wang Yuxiang , Li Xiaomei , Jia Fangfei , Wen Junpeng , Zhao Yan 
Published: June 2023

e20626 Background: The systemic immune-inflammation index (SII) has been suggested as a prognostic marker in several solid malignant neoplasms. However, there are few studies on the prognostic value of SII in patients with limited-stage SCLC. This study explored the impact of SII on overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer, and compared the predictive ability of SII and platelet/lymphocyte ratio (PLR) to find a better prognostic marker. Methods: In total, 572 patients with new diagnosis of limited-stage SCLC were included in this study. The optimal threshold of SII and PLR were determined using the outcome(OS)-based method by maximizing the log-rank test statistic and the survival differences.The predictive ability of SII and PLR were compared by drawing the continuous time-dependent receiver operating characteristic curves (time-dependent ROC). Logistic multivariable analysis was performed to identify factors associated with high SII. Propensity score matching (PSM) was used to balance confounders between groups and adjust observed selection bias. Kaplan-Meier methods and Cox proportional hazards models were used to assess the impact of pre-treatment SII on OS and PFS. Results: The median age of the whole group was 60.0 (25.0-81.0) years, and the median follow-up time was 56.5 (2.5-95.4) months. The optimal cutoff value of SII and PLR were 760.6 and 137.3, respectively. The area under the time-dependent ROC curves of SII and PLR in 1-, 2- and 3-year were 0.727, 0.708, 0.680 and 0.680, 0.669, 0.649, respectively. The high SII group was correlated with pleural effusion (P = 0.001), T stage (P = 0.009), N stage (P = 0.048), and pretreatment serum sodium (P = 0.003). The median OS and PFS of the whole group was 26.0 months (95%CI 23.8-28.2) and 13.0 months (95%CI 11.3 -14.7), and the 1-, 3-, 5-year OS rates and the 1-, 3-, 5-year PFS rates were 81.1%, 35.5%, 27.1% and 52.8%, 24.8%, 19.9%, respectively.There were 414 patients after PSM. In multivariable survival analysis, SII remained an independent prognostic factor for OS (HR1.792; 95%CI 1.416-2.268; P < 0.001) and PFS (HR1.410; 95%CI 1.043-1.906; P = 0.025). Conclusions: Elevated SII is an independent adverse prognostic factor in patients with limited-stage SCLC and is superior to PLR in terms of prognostic ability.
Combinatorial analysis of CD4+Tregs and CD8+Teff to predict response to ICI in patients with ES-SCLC.
Authors: Tsapakidis Konstantinos , Xagara Anastasia , Kokkalis Alexandros , Markou Alexandra , Aidarinis Chrysovalantis , Lazarou Alexandros , Kallergi Galatea , Papadopoulos Vasileios , Saloustros Emmanouil S. , Samaras Ioannis , Kotsakis Athanasios 
Published: June 2023

e20633 Background: Recently, the antiPD-L1 agent, durvalumab, was approved in first line treatment in combination with chemo. However, there is not a clear benefit from this regimen for the majority of patients. In this study, we explored the predictive role of regulatory T-cells in response of patients with ES-SCLC treated with the aforementioned regimen. Moreover, we evaluated the potential role of inflammatory hematological indices such as Neutrophil to Lymphocyte ratio (NLR) and CRP levels to predict responders. Methods: Blood was collected before initiation of immunotherapy from 24 patients with ES-SCLC. PBMCs were isolated with Ficoll density gradient centrifugation from patients and 1O healthy donors (HD). Immunophenotyping was performed by multi-color flow cytometry using antibodies against CD3,CD8,CD45RA,CD45RO,CCR7,PD-1, for CD8 T-cells and CD3,CD4,FoxP3,CD25,CD127,CTLA-4,CD39 for Tregs. Results: High percentages of CD39+ (p = 0.0061) and CTLA-4+ (p = 0.012) Tregs were detected in circulation of ES-SCLC compared to healthy individuals. Additionally, higher percentages of CD8+ Teff were detected in SCLC patients (p = 0.027). Patients with high numbers of Teff had significant higher PFS (p = 0.021, median 183 and 97 days) and better OS (p = 0.075, median 318 and 202 days) in response to immunotherapy compared to those with low numbers. Spearman analysis revealed a significant negative correlation between Tregs and Teff (Spearman r2 = -0.39,p = 0.043) that was accompanied with significant higher PFS (p = 0.041, median 207 and 130 days ) and OS (p = 0.029, median 318 and 202 days ) in patients with high levels of Teff and low Tregs comparing to the rest. Further analysis on inflammatory clinical signatures demonstrated that patients with better clinical response to immunotherapy have significantly lower NLR (p = 0.034) while no significant difference was revealed for CRP (p = 0.401) levels before therapy initiation. Conclusions: Combinatorial analysis of Tregs and Teff cells may be used as a predictive tool for response to immunotherapy in ES-SCLC patients.
Survival outcomes of stage I small cell lung cancer (SCLC) treated with stereotactic body radiation therapy (SBRT) versus external beam radiation therapy (EBRT): An NCDB analysis.
Authors: Heckman Patrick , Hao Zhonglin , Bernard Mark Edmund , Chen Quan , Huang Bin 
Published: June 2023

e20638 Background: Patients with stage I (T1/T2a, N0) SCLC have a 5-year survival of 48% after surgical resection. Unfortunately, 70% of limited stage patients are inoperable and thus reliant on definitive radiation. The use of SBRT has increased 16-fold from 2004-2013 with continued widespread acceptance due to its safety and projected efficacy; however, there is no category one evidence to support this practice. Currently NCCN guidelines cite experience of SBRT in 117 patients from two studies. The impact of SBRT versus EBRT with or without chemotherapy is not yet well defined and requires more evidence to influence treatment decisions. Methods: We used National Cancer Database (NCDB) to identify 4,012 patients with clinical stage I SCLC treated with surgery, or EBRT with chemotherapy, or SBRT with or without chemotherapy from 2011 to 2020. The primary outcome analyzed was overall survival (OS). Secondary analyses evaluated differences amongst age, gender, race, institution, and Charlson Comorbidity Index (CCI). Kaplan-Meier (KM) plots were used to examine survival outcomes and descriptive analysis was performed to examine the characteristics of clinical variables by the different treatment modalities. Cox regression analysis was used to identify factors associated with OS. Results: The utilization of surgery and SBRT in stage I SCLC has increased over the last fifteen years. As of 2020, SBRT volume has increased 657-fold and is combined with chemotherapy in more than 50% of cases. From 2010-2019, those who were treated with surgery-based therapy had a survival advantage (HR 0.64 95%CI 0.58-0.71, p < 0.01) compared to multimodality radiotherapy techniques. For those treated with definitive radiation, there was no significant difference between EBRT with chemotherapy and SBRT with or without chemotherapy (HR 1.11 95%CI 0.97-1.28, p = 0.135). Patients treated with SBRT alone experienced a significantly shorter median OS of 20.4 months compared to those who received SBRT with chemotherapy (median OS 34.3 months, HR 1.74 95%CI 1.38-2.20, p < 0.01). Multivariate analysis revealed better OS for patients under the age of 64 (HR 0.51 95%CI 0.44-0.58, p <0.01) and those with lower CCI (CCI 0, HR 0.82 95%CI 0.70-0.90, p< 0.01); worse OS for males (HR 1.26 95%CI 1.16-1.37, p < 0.01); and no difference between academic or non-academic institutions (HR 0.92 95%CI 0.84-1.01, p= 0.094), white versus black (HR 0.84 95%CI 0.71-1.00, p = 0.054) or non-white patients (HR 1.06 95%CI 0.75-1.50, p = 0.736). Conclusions: Our preliminary results suggest surgery-based multimodality therapy is associated with a higher survival for medically operable patients. There was no survival advantage of EBRT with chemotherapy compared to SBRT especially when chemotherapy is given. Further statistical analysis is underway to confirm these trends and survival differences.
The role of adjuvant chemotherapy (CT) for early stage resectable node negative small cell lung cancer with size of ≤ 2 cm post-surgical resection: A SEER plus based statistical analysis.
Authors: Budhathoki Pravash , Shah Anish Kumar , Gaire Suman , Potluri Lakshmi Bhavani , Uprety Dipesh 
Published: June 2023

e20643 Background: Small cell lung cancer (SCLC) is a poorly differentiated neuroendocrine tumor accounting for 15% of all lung cancers. Surgical resection followed by adjuvant platinum-etoposide is recommended for patients with limited-stage SCLC (T1 N0M0). In this study, we sought to evaluate the survival benefit of adjuvant chemotherapy for patients with ≤2 cm size SCLC following surgical resection. Methods: We utilized Surveillance, Epidemiology and End Results (SEER) plus 18 registries to identify adult patients (≥18 years) diagnosed with small cell cancer of the lung with tumor size of ≤ 2 cm from 2010 to 2018. The study population comprised of patients who underwent surgical resection followed by adjuvant chemotherapy and patients who received surgical resection alone. Kaplan-Meier and long rank tests were used to compare overall survival between the two groups. Multivariate survival analysis was done using the Cox proportional hazards regression model. Results: 419 patients were identified, with 203 (48%) receiving adjuvant CT while 216 (52%) not receiving adjuvant CT. The population who received adjuvant chemotherapy was younger than those who did not (Median years: 67 years vs 71 years, p < 0.001). The 5-year overall survival rate was significantly higher for those receiving adjuvant CT (49% vs 40.9%, P value < 0.001). On multivariate analysis after adjusting for age, gender, race, and origin, adjuvant chemotherapy was associated with better overall survival (HR:0.67; 95% CI 0.54 - 0.88, p = 0.003). Conclusions: Our study demonstrates that adjuvant CT should be used for early-stage small cell lung cancer irrespective of tumor size following surgical resection.
Application of a contralateral esophageal-sparing technique to reduce radiation esophagitis in limited-stage small cell lung cancer treated with twice-daily radiotherapy and concurrent chemotherapy.
Authors: Hu Min , Yang Shuangyan , Chen Yun , Kang Jingjing , Xu Yaping 
Published: June 2023

e20644 Background: Acute esophagitis (AE) is a common radiation-related toxicity after concurrent twice-daily hyperfractionated radiotherapy and chemotherapy in limited-stage small cell lung cancer (LS-SCLC) patients, which could limit dose-escalation of the target and make treatment postponed to decrease local tumor control. More esophageal protective techniques should be proposed to reduce radiation severe esophagitis of LS-SCLC patients. Methods: We retrospectively applied a contralateral esophagus sparing technique (CEST) in 20 unresectable LS-SCLC patients, who had gross tumor within 1 cm of the esophagus and received a total dose of 45 Gy of concurrent twice-daily radiation and standard chemotherapy regimen. The contralateral esophagus (CE) was contoured as an avoidance structure, and the feasibility of CEST on promoting a steep dose falloff beyond the target volume near esophagus was analyzed. The appropriate dose constraints of CE were also investigated. The AE events were recorded according to the RTOG acute toxicity grading system. Results: We performed CEST in 20 LS-SCLC consecutive patients, among whom three patients experienced severe AE after concurrent chemoradiotherapy. Each treatment plan of eligible patients assured high radiation doses delivering, with the planning and gross tumor volume covered by 95% and 100% of the prescription dose. Among these patients, the median maximum esophagus dose declined from 47.9 Gy (range, 46.6-49.7 Gy) to 41.3 Gy (range, 35.9-48.2 Gy), as well as V30 and V36 of esophagus decreased from 9.22 Gy (range, 0.42-17.71 Gy) and 7.39 Gy (range, 0-16.19 Gy) to 2.40 Gy (range, 0-5.68 Gy) and 0.53 Gy (range, 0 -2.69 Gy) after CEST applying, respectively (all p < 0.001). The CE’s median maximum dose, V30, and V36 were 41.3 Gy, 2.13 cc, and 0.24 cc, respectively. Conclusions: By using proposed CE dose constraints of Dmax≤42 Gy, V30 ≤3.5 cc and V36 ≤0.5 cc, we confirmed the feasibility and efficacy of CEST to avoid exposing the esophagus cross-section to high prescription doses in LS-SCLC patients receiving twice-daily hyperfractionated IMRT and concurrent chemotherapy. These findings support the clinical practice of CEST in LS-SCLC patients, while more prospective and large-scale studies are warranted.
Racial and ethnic differences in thymic epithelial tumors: A single-institution retrospective analysis.
Authors: Wuthrich Brice , Maniar Rohan , Heldman Emily , Laniak Louis , Davis Hannah , Ardeshir-Larijani Fatemeh , Spittler Aaron John , Kesler Kenneth , Loehrer Patrick J. 
Published: June 2023

e20649 Background: Thymic epithelial tumors (TETs) are a rare, heterogeneous group of malignancies that arise from the thymus. While the etiology of TETs remains unknown, variation in incidence rates amongst racial/ethnic groups has raised the possibility of germline predispositions. Unfortunately, due to the rarity of this disease, there is a limited understanding of the impact of race/ethnicity on tumor characteristics and treatment outcomes for TET patients. We sought to characterize patient/tumor data and investigate treatment outcomes based on race and ethnicity. Methods: We conducted a single-institution, retrospective database analysis of TET patients evaluated at the IUSCCC from 1979 – 2021 from which clinical annotations were available for 477 thymoma and 164 thymic carcinoma (TC) patients. We identified 112 thymoma and 35 TC patients who were deemed to have sufficient data for evaluation of racial/ethnic characteristics. Demographic/clinical variables and therapeutic interventions, including treatment outcomes, were analyzed. Data was compiled and analyzed using descriptive statistics and the Kaplan Meier method for survival analysis via GraphPad Prism software. Results: Of the 112 thymoma patients, 29 thymoma patients presented with de novo metastatic disease at the time of diagnosis. The median age at the time of diagnosis of all patients revealed a statistically significant difference between White and Black TET patients (53.0 v. 42.0 years, *p = 0.0195). There was a trend towards significance when median age of diagnosis between White and Asian TET patients was compared (53.0 v. 48.0 years, p = 0.0633, NS). Advanced histologic subtypes, include B3 and TC, appeared predominantly in Asian and Black patients at 77.7% and 56.3%, respectively, compared to White patients (44.9%), though the finding was not statistically significant. No statistically significant differences between racial/ethnic groups regarding progression free survival for unresectable or metastatic disease were observed, regardless of histology. There was a non-significant difference in recurrence free survival for resectable thymoma in White (30.0 months) and Asian/Pacific Islander (47.0 months) patients compared to Black patients (24.0 months). Conclusions: Overall, this analysis suggests differences in the median age of diagnosis for patients with thymic malignancies based on race, raising the possibility of inherent biologic differences driving oncogenesis and symptoms at the time of presentation. While no statistically significant differences in treatment outcomes were found based on race and ethnicity, Black patients appeared to experience shorter times to recurrence after definitive surgery. Further studies to understand the mechanistic differences driving tumorigenesis and potential disparities in treatment outcomes are greatly needed in this rare tumor type.
Tumor immune microenvironment in BRAF V600E mutant lung adenocarcinoma.
Authors: Liu Yutao , Wang Mingzhao , Chen Tong , Li Weihua , Hu Xingsheng , Jiang Jun , Li Fang , Wan Zhiyi , Zhang Jie , Zhang Chunmei 
Published: June 2023

e21003 Background: The efficacy of immune checkpoint inhibitors (ICIs) is closely related to tumor immune microenvironment (TIME). However, little is known about the role of BRAF V600E mutation in the TIME of lung adenocarcinoma (LUAD). Methods: Here, we analyzed the TIME of LUAD with the BRAF V600E mutation using RNA sequencing and multiplex immunofluorescent (MIF) stained with CD8, CD68, CD163, CD57, PD-1, and PD-L1 antibodies. Patients were divided into the BRAF V600E (n = 31) and driver gene ( ALK, BRAF, EGFR, HER2, KRAS, MET, RET, and ROS1) wild-type groups (WT, n = 32). Results: There were no significant differences between the BRAF V600E and driver gene WT groups in terms of immunological signature scores, including T cell–inflamed gene expression profiles, adhesion molecules, chemokines, cytolytic activity, immunocostimulators, immunoinhibitors, MHC Class I, MHC Class II, MHC Non-Class, IFNg signature, tertiary lymphoid structure, and most of infiltrating immune cell subtypes. MIF showed that the proportions of PD-L1+ cells and CD68-associated tumor-associated macrophages (TAMs) were significantly higher in the BRAF V600E group in the tumor, stroma, and total regions. Notably, the majority of CD68-associated macrophages were CD68+CD163- TAMs. However, the proportions of CD8+, CD8+PD-L1+, and CD8+PD-1+ tumor-infiltrating lymphocytes (Tils) in the BRAF V600E and driver gene WT groups were all comparable in the tumor, stroma, and total region. Conclusions: The TIME was generally similar between the BRAF V600E mutant and driver gene wild-type groups, particularly in the proportion of CD8+ Tils. This may support that BRAF V600E mutation does not affect the efficacy of immune checkpoint inhibitors in LUAD.
An exploratory analysis of lung cancer survival using NGS genetic predictors and partial least squares.
Authors: Sequero-Lopez Silvia , Martinez-Murcia Francisco Jesus , Castillo-Barnes Diego , Moreno-Garcia Javier , Segura-Perez Ana , Gallego-Molina Nicolas , Ortiz Andres , Ramirez Javier 
Published: June 2023

e21007 Background: According to the IARC, lung cancer is one of the most common types of cancer worldwide (2.09 million of cases in 2018). Some genetic alterations (ALK, ROS1, EGFR, etc.) are known to play a key role in its origin. Fortunately, target therapies have been developed in the last years increasing patients Overall Survival (OS). Methods: Next-Generation Sequencing (NGS) is a powerful tool to determine which specific mutations occur in these genes. Nevertheless, despite some of them have been labeled as pathogenic, we still do not know exactly their effect on the OS. In this context, we have evaluated the NGS (Ion Torrent™ S5, kit Oncomine™ Focus Assay, Oncomine Focus-520- W3.0-DNA v5.14) results of 119 patients diagnosed with lung adenocarcinoma (89 variants in 28 genes) with a cross-validated (k = 5) schema using Partial Least Squares (PLS) and multiple repetitions to determine the coefficient variability from the genetic alterations modeling the OS. This gives us a measure of the proportion of variance in the OS (dependent variable) that is explained by the mutations (independent variables) in our statistical model. Results: Analyzing our results, alterations on ALK EML4-ALK V1 (CI -58.7 to -18.8); BRAF SNV exon15 p.Val600Glu (CI -66.1 to 0.0); CTNNB1 SNV exon3 p.Thr41Ala (CI -84.3 to 8.8) and p.Thr41Ile (CI -26.0 to 0.6); EGFR CNV (CI -68.5 to -5.1) and DEL exon19 p.Glu746-Ala750 (CI -66.9 to 16.4); KRAS SNV exon2 p.Gly12Val (CI -76.1 to -39.3) and p.Gly13Cys (CI -66.0 to -36,9); MET CNV (CI -50.0 to 1.3) and FUS exon13 to exon15 (CI -46.8 to 33.6); and PIK3CA SNV exon10 p.Glu545Lys (CI -99.0 to -35.6) have a negative impact on the OS. In contrast, mutations in CTNNB1 SNV exon3 p.Ser37Phe (CI -26.3 to 105.5); EGFR SNV exon21 p.Leu858Arg (CI -32.7 to 121.3); KRAS SNV exon2 p.Gly12Ala (CI 1.3 to 39.3); KRAS SNV exon3 p.Gln61His (CI -53.32,50,11) lead to a better prognosis on OS. Note that our analysis involved patients not treated due to their tumoral progression: CTNNB1 SNV exon3 p.Thr41Ile (1); EGFR SNV exon21 p.Leu858Arg (3); CTNNB1 SNV exon3 p.Thr41Ala (1); PIK3CA SNV exon10 p.Glu545Lys (1); ALK EML4-ALK V1 (1) and KRAS SNV exon2 p.Gly12Val (1). Conclusions: Though alterations in the EGFR and ALK genes usually present a favorable prognosis, our work suggests that some of their variants are associated with a poor survival. This study also reveals other mutations like alterations on PIK3CA and CTNNB1 genes, which may impact lung cancer prognosis and will require further exploration.