bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nodule vascularity as novel radiomics imaging endpoint for lung cancer diagnosis and prognosis.
Authors: Blistein François , Goffart Sebastien , Belmans Flore , van Peufflik Ingrid , Walsh Sean , Occhipinti Mariaelena , Vos Wim , Vaidyanathan Akshayaa 
Published: June 2022

e20580 Background: The vascularization of lung nodules has been proven as severe risk factor for malignancy, and in lung cancer, indication of worse prognosis (1,2). For this reason, we developed a novel imagining endpoint based on the vasculature surrounding a lung mass and we tested this endpoint for the prediction of malignancy for lung nodules. Methods: The vasculature of the nodules (both arteries and veins) has been computed using the surface intersection between the nodule and the vascular structure 3D meshes. Both 3D structures were obtained by converting the segmentations of the nodule and of the vessels to meshes with a marching cubes algorithm. Nodule and vessels segmentation has been obtained with an in-house deep learning segmentation model. The features considered are the numbers of intersections, the total area of intersection and the mean area of intersection. These features have been used to predict nodule malignancy on thoracic CT scans from the Lung Image Database Consortium image collection (3). Quality controls on clinical data completeness and imaging parameters resulted in a cohort of 894 scans (715 for training and 179 for testing), from the original 1018 cases. The malignancy status is defined as high risk and low risk, based on the consensus classification of a panel of four radiologists. Firstly, an univariate analysis is performed to assess the variability of the features grouped by the malignancy score by using Mann-Whitney and ANOVA tests. After, seven combinations of features have been used to train generalized linear models (GLM) to predict nodule malignancy. To compare the models, the Area Under the Curve (AUC) is used as the main performance metric. Results: Univariate analysis of each feature grouped by the malignancy outcome showed that all the three features have good univariate discriminative power between high risk and low risk categories ( p value ≤ 0.05), with nb_connections as the most predictive singular feature ( p value of 1.343277 × 10-36). All the GLM models developed showed a good performance (AUC equal or higher than 0.7), with the best model in testing based on the combination of mean_area and sum_area (AUC of 0.84). Conclusions: The radiomics vascularity endpoint has been proven capable of predicting nodule malignancy with very good performance. The singular feature that is most related to malignancy is the number of vessels intersecting the nodule while the total area of intersection followed by the number of intersections are the most useful to model risk of malignancy. Wang et al., Lung Cancer 114: 38–43, 2017. Hamanaka et al., Diagn Pathol 10,17, 2015. G. Armato et al., Med. Phys., 38: 915-931, 2011.
Laterality and survival in mesothelioma: A SEER database analysis.
Authors: Parekh Jay , Yerlikaya Aslihan , Xie Yiyu , Eralp Yesim , Adjepong Yaw 
Published: June 2022

e20594 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive and rare cancer type that carries dismal prognosis with a median survival of only 12 months. Often patients are diagnosed at advanced age and tend to have many co-morbid conditions. More precise prognostication should help physicians to decide on the best treatment approach for patients. Previous three studies suggest right sided involvement is associated with poorer prognosis. However, these were very small studies and estimates were not precise. We therefore decided to assess prognostic indicators, including laterality, using the large SEER database. Methods: Using SEER database, a total of 5064 cases diagnosed between 1975-2003 were included in this study. R software (4.0.5) was used. Prognostic indicators assessed included age, stage at diagnosis (distant versus regional/early), gender, and tumor laterality. We evaluated all-cause mortality using multivariate regression and introduced a competing risk regression to explore the association of clinical features and mesothelioma-related death. In analyses, we treated non-cancer related death as a competing factor. The prognostic significance of laterality was assessed at each stage of diagnosis. Results: The patients were predominantly male (81%), aged 60 years or older (79.1%) with right side predominance (58.9%). The overall median survival time was 8 months. The cumulative incidence of mesothelioma-specific death was 42% at 6 months and 62% at 12 months. In the multivariate analysis, male gender (HR = 1.23, p < 0.01), age 60 year or older (HR = 1.52, p < 0.01) and distant stage at diagnosis (HR = 1.2, p < 0.01) were independent predictors of shorter overall survival. In subgroup analyses of different stages, right sided mesothelioma was an independent predictor of mesothelioma-related death(HR = 1.14, CI 1.00-1.28, p = 0.042) in patients with regional/early-stage disease (Table) after adjustment for age and gender. When included all cohort with both early and late stages, there was no statistically significant association between laterality and all-cause mortality(HR = 1.02, CI 0.958-1.08, p = 0.61). Conclusions: Our study confirms that right-sided involvement is independently associated with increased risk of death in early stage/localized mesothelioma patients. The lack of association between laterality and survival in those with distant spread may be explained by the overall shorter survival in that group.[Table: see text]
High-definition PCR (HDPCR) detection of DNA and RNA variants in non-small cell lung cancer (NSCLC) samples.
Authors: Tsongalis Gregory J. , Leatham Bryan , McNall Katie , Subramanian Hari , Alvarado John G , Jacky Lucien , Yurk Dominic , Green Donald , Rajagopal Aditya , Schwartz Jerrod 
Published: June 2022

e20603 Background: Digital PCR (dPCR) is an emerging technology platform for detecting genomic variants in cancer genomes due to its high sensitivity and fast time to results compared to sequencing. However, translational oncology applications often require the measurement of more biomarkers than there are color channels available on dPCR platforms. One approach to address this limitation with dPCR is to split a sample across many wells and profile a subset of variants in each well. For input-limited samples, however, this results in fewer molecules being profiled in each dPCR well, resulting in a reduction in sensitivity and fewer patient samples processed per instrument run. ChromaCode has developed a research use only (RUO) digital High Definition PCR (HDPCR) NSCLC assay, for multiplexed detection of 14 DNA variants and 15 RNA fusion variants relevant in non-small cell lung cancer samples. The assay is constructed using both amplitude modulation and multi-channel resilient signal encoding methods. Amplitude modulation enables different variants to generate a distinguishable signal at different intensity levels in a single color channel, allowing for multiple targets to be detected within that single-color channel. In addition, resilient encoding generates a signal in more than one color channel to create a form of error detection in the assay design. Methods: Assay benchmarking was performed using over 500 contrived human biological FFPE samples, consisting of synthetic DNA or RNA variants spiked into a background matrix of FFPE-extracted DNA or RNA; over 500 contrived human biological plasma samples, consisting of synthetic DNA or RNA variants spiked into a background matrix of plasma-extracted cell free DNA or RNA; and residual human biological FFPE and plasma NSCLC samples that were previously characterized using a targeted sequencing workflow. The samples were tested using the HDPCR NSCLC assay on the QuantStudio Absolute Q Digital PCR system, and data analysis was performed with custom analysis algorithms. Results: For the more than 500 contrived FFPE and plasma samples, the HDPCR NSCLC assay had high overall agreement with expectation across a range of mutant allele fractions for both DNA and RNA analytes (≥99% PPA and ≥99% NPA). For a set of N = 25 residual human biological FFPE samples, the assay was also highly concordant (100% PPA and 99% NPA) with a targeted panel sequencing comparator. The hands-on workflow time from isolation start to analysis complete was < 24 hours. Conclusions: The HDPCR NSCLC assay is a robust RUO tool for the sensitive and rapid detection of commonly targeted variants relevant to NSCLC samples. This technology could complement sequencing assays when there is a need for a rapid turnaround time or there are limited amounts of isolated nucleic acid.
Long-term survival in small-cell lung cancer patients: Extension of the SMALLBRAIN study.
Authors: Diaz-Santos Javier , Cantero-Gonzalez Alexandra , Muñoz-Ayllon Marta , Garrido-Almazan Lucia , Gutierrez Calderon Vanesa , Rueda Dominguez Antonio 
Published: June 2022

e20605 Background: Long-term survivors of metastatic Small Cell Lung Carcinoma (SCLC) with overall survival (OS) greater than 12 months are not frequent and have not been deeply studied. Therefore, we conducted the descriptive study SMALLBRAIN to characterize these patients with central nervous system metastases (mCNS), since at least a 20% of SCLC patients has mCNS at the diagnosis. The survival results were reported at the NCCN 2022 Annual Conference, showing no statistically significant survival difference between presenting mCNS at diagnosis or later and no correlation between the mCNS volume and OS. After these results, we have extended our study to metastatic SCLC patients without mCNS to analyze possible differences. Methods: We carried out a systematic search for metastatic SCLC patients with OS > 12 diagnosed and first treatment between January 2016 and April 2020 in our academic medical center in Spain, we excluded those with missing data. The included patients were classified in 3 cohorts: COHORT NA: Stage III at diagnosis with metastatic progression and no mCNS. COHORT NB: Stage IV patients without mCNS. COHORT Y: mCNS during the course of the disease, regardless of onset time. The number of treatment lines received and the survival were analyzed using Kaplan-Meier and multi-variable Cox proportional hazard analysis. Results: A total of 45 patients met study criteria (NA = 5, NB = 11 and Y = 29). The female - male ratio was of 1:3.14 for cohort Y and 1:2.2 for all the patients without mCNS (NA+NB), not statistically significant. The median OS was 24.9 months for cohort NA (range 16 – 64.83), 21.4 months for NB (range 12.30 – 31.83) and 18.6 months for Y (range 12.67 – 60.83), not statistically significant. Only three patients are currently alive, two from cohort NA and one from Y. The median of treatment lines was 3 for all the cohorts with a maximum of 8 for one patient in cohort Y. Best responses were two complete response with later progression in one patient from cohort NA and one from NB. Best response of cohort Y was a partial response. Conclusions: No statistically significant differences were found regarding survival or treatment lines between the population of long-term survivors of metastatic SCLC with and without mCNS. Their infrequency with few living individuals makes their characterization a challenge. These patients are also highly complex, more than 50% received at least 3 lines of treatment. Future research should explore the possibility of extracting long-term SCLC survivors from existing cancer registries of different countries. [Table: see text]
Anlotinib combined with etoposide as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC): Updated results from a phase II trial.
Authors: Shen Bo , Wu Yuan , Shi Lin , Pan Banzhou , Yang Kaihua , Wang Qiong , Zhao Weiqing , Han Zhengxiang , Wang Lifeng , Feng Jifeng 
Published: June 2022

e20610 Background: Existing maintenance treatment strategies for patients with ES-SCLC experiencing no progression after the standard first-line chemotherapy are limited. Anlotinib combined with etoposide as maintenance treatment in ES-SCLC after the standard first-line EP chemotherapy showed encouraging efficacy and good tolerability. This is an update of the phase II study (ChiCTR1800019421). Methods: Patients with histologically confirmed ES-SCLC who have not progressed after the standard first-line EP chemotherapy received anlotinib (12 mg, day 1 to 14 of a 21-day cycle) combined with etoposide (50 mg, QD, day 1 to 14 of a 21-day cycle, up to 6 cycles) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. Results: Between April 2019 and October 2021, we screened 31 patients and enrolled 27 patients in this trial. At data cut-off (January 7, 2022), 20 (74%) patients had discontinued the trial, and 7 (26%) patients remained on treatment. The median follow-up time reached 12.9 months. Among 27 evaluable patients, there was 9 partial response, 17 stable disease and 1 disease progression, resulting in the objective response rate 33.3% and disease control rate 96.3%. The median PFS was 8.9 months (95%CI: 5.4-12.3). The median OS was 13.6 months (95%CI: 9.6-17.6). The most common grade 1-2 adverse events (AEs) were anorexia (9 of 27, 33.3 %), hypertension (8 of 27, 29.6 %) and fatigue (7 of 27, 25.9 %). The most common grade 3-4 AEs were anorexia (4 of 27, 14.8%), hypertension (2 of 27, 7.4%) and hand and foot skin reaction (2 of 27, 7.4 %). Nine patients had to adjust treatment dosage. Conclusions: This updated results have confirmed the combination of anlotinib and etoposide showed significant efficacy and favorable safety profile. The combination may represent a new treatment option as maintenance treatment in patients with ES-SCLC having not progressed after the standard first-line EP chemotherapy. The further exploration is ongoing. Clinical trial information: ChiCTR1800019421.
Patient characteristics and outcomes associated with small cell lung cancer by treatment status in a U.S. Medicare population.
Authors: Ramirez Robert A. , Surinach Andy , Cockrum Paul 
Published: June 2022

e20614 Background: Globally, small cell lung cancer (SCLC) accounts for approximately 10% of lung cancers and is typically diagnosed at an advanced/extensive stage in elderly current or former smokers. The objective of this study was to describe patient characteristics (demographic and clinical) and outcomes (survival) associated with SCLC in the Medicare population by systemic anticancer treatment status (treated vs untreated). Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database. Patients were included if they had a record with a diagnosis of SCLC in the database from 1/1/2007 – 12/31/2017, were ≥65 years of age at diagnosis, and had continuous enrollment for ≥180 days pre-SCLC diagnosis. Patient characteristics and overall survival (OS) were stratified by treatment status. Median OS was estimated using the Kaplan Meier method. Results: 13,516 patients met the study criteria. Overall, 57.7% were female, mean age was 74 years, and 89.5% were white. Nearly three-fourths (73.1%) were diagnosed with stage 4 disease. Just over half (55.4%, N = 6,022) initiated 1L treatment. Older patients were less likely to be treated: 36.3%, 51.1%, and 78.5% of patients 65-74 yrs, 75-84 yrs, and 85+ yrs, respectively, were untreated. Patients diagnosed at stage I-III were more likely to be treated than those diagnosed with stage IV disease (68.2% vs 51.4% treated). Patients with metastasis in the brain and/or liver were also less likely to be treated than patients without metastasis in those sites. On average untreated patients had more comorbid conditions than treated patients (average Charlson Comorbidity Index [CCI] 9.2 vs 9.5). In particular, congestive heart failure (49.3% vs 32.6%), myocardial infarction (25.7% vs 18.9%), renal disease (31.5% vs 18.9%), dementia (13.3% vs 3.5%), hemiplegia/paraplegia (8.0% vs 3.2%), and diabetes with complications (21.1% vs 16.4%) were more common among untreated patients. Median survival among untreated patients was 1.1 months (95% CI: not estimable) versus 9.2 months (95% CI:9.0-9.5 months) among treated patients. Approximately 5% of untreated patients were alive 12 months after diagnosis whereas 40% of treated patients were alive 12 months after initiating 1L treatment. Conclusions: Nearly half of SCLC patients did not initiate systemic anticancer treatment. Those who were untreated were on average older, had more comorbid conditions, were more likely to be diagnosed with stage IV disease, and had shorter survival, affirming the continued need for safe and effective therapies for SCLC.
Neoadjuvant attelizumab combined chemotherapy in limited-stage and resectable small cell lung cancer: A multicentric, single-arm and open study.
Authors: Yan Xiaolong , Duan Hongtao , Shi Liang , Li Hongxia , Tong Liping , Liu Zhe 
Published: June 2022

e20615 Background: Combine chemotherapy and immunotherapy have become the first-line treatment program for extensive small cell lung cancer. The aim of this study is to explore the safety and efficacy of neoadjuvant chemotherapy and immunotherapy in limited-stage small cell lung cancer. Methods: Treatment-naïve patients were enrolled and the patients received the 2-3 cycles of neoadjuvent chemotherapy and atezolizumab (1200mg, D1). surgery was performed within 4-6 weeks after the last treatment. The primary endpoint was surgery patients pathological complete response (PCR). Safety was assessed by adverse events (AEs) and postoperative complications. This trial was registered at the Chinese Clinical Trial Registry (Registration Number: (ChiCTR2100042367). Results: Recruitment started in May 2020. We reported 9 patients with neoadjuvent immunochemotherapy who have completed surgical treatment. Baseline characteristics: 7 males, with an average age of 52.1 years old, all ECOG PS 0-1; 6 current smokers; clinical stages IIB / IIIA / IIIB n = 6 / 1 / 2. There were 1 atezolizumab treatment-related Gr1 AEs (rush) and 4 treatment-related Gr 3-4 AEs. According to Recist 1.1, all patients achieved partial response. 9 patients completed surgery, 3 patients received bilobectomy, and 3 patients underwent pneumonectomy. Surgical methods included robot-assisted thoracoscopic surgery (RATS) /video-assisted thoracoscopic surgery (VATS) (3, 33.3%) and thoracotomy (6, 66.7%). Complete resection (R0) was achieved in 100% of patients (9/9). The mean operation time was 136 min; the mean bleeding volume was 194.4ml, and the mean hospital stay was 8.9 days. The postoperative pathology results showed a PCR (66.7%) in 6 patients and a MPR (88.9%) in 8 patients. Conclusions: Neoadjuvant chemotherapy and atezolizumab therapy significantly improves PCR in small cell lung cancer without unknown AE events and no surgical delay, so this protocol is safe and feasible. Whether the survival benefit is still unknown. Keywords: neoadjuvant therapy, Small cell lung cancer, immunotherapy, surgery, PCR. Clinical trial information: ChiCTR2100042367. [Table: see text]
Clinical characteristics and outcomes of extrapulmonary small cell cancer: A retrospective analysis of the SEER database.
Authors: Abdullah Hafez Mohammad , Ellithi Moataz , Ahmed Mamoon , Ali Lina , Ali Mohammad , Anwer Faiz 
Published: June 2022

e20616 Background: Extrapulmonary small cell cancer (EPSCC) accounts for only 5-10% of small cell carcinoma, with the rest consisting of small cell lung cancer (SCLC). The incidence of this entity has been rising due to better diagnosis, however it is not well described and data is limited. We performed a Surveillance, Epidemiology and End Results (SEER) database analysis to further characterize the biology and clinical aspects of this entity, in comparison to SCLC. Methods: The Surveillance, Epidemiology and End Results (SEER) 18 database was used to obtain data on age, gender, ethnicity, survival, and tumor characteristics of n = 9,712 US patients diagnosed with EPSCC between 2000-2018 and these were compared to n = 118,514 patients with SCLC diagnosed during the same period. Results: Among the EPSCC cohort 58.1 % were males while in the SCLC cohort 50.3% were males. Median age of diagnosis was 65.50 years for EPSCC and 66.81years for SCLC. Among the EPSCC patients, 75.9 % were Caucasians, 9.2 % were African-Americans, and 8.8% were Hispanics. Amongst SCLC patients, Caucasians made up 83.1% of the patients, while African-Americans made up 8.6% and Hispanics made up 4.5 % of the patients. Most common sites for EPSCC were urinary bladder (20.2%), prostate (7%), cervix uteri (6.2%), pancreas (4.5%), rectum (3%), and ovaries (2.6%). Median OS for EPSCC was 8 months (95% CI: 8 - 8), while median overall survival for SCLC was 7 month (95% CI: 7 - 7). Hazard ratio for death for EPSCC: 0.77 (95% CI: 0.75 - 0.79), p < 0.001. The survival at 12 months, 24 months and 60 months was 36%, 22%, and 13 % for EPSCC and 29%, 13%, and 5% for SCLC. There were no significant gender or racial differences in overall survival (OS). Conclusions: EPSCC has better overall and 5-year survival as compared to SCLC. There are no significant differences in survival outcomes in EPSCC patients based on location of primary, gender or race.
Efficacy of lurbinectedin in a clinical trial versus other standard of care in a real-world comparator arm in relapsed/refractory small cell lung cancer patients.
Authors: Ganti Apar Kishor , Prince Patricia , Wang Xue , Estrin Adina , Boccuti Anne , Rengarajan Badri , Naveh Navit , D'Agostino Ralph , Alvord Trevor , Ben-Joseph Rami 
Published: June 2022

e20619 Background: Lurbinectedin monotherapy is currently approved for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy based on the results of a single-arm phase 2 basket trial. The current study established real-world comparator arms (RWCAs) to enable retrospective comparison of the efficacy of lurbinectedin from the trial, notably overall survival (OS) and overall response rate (ORR), to other standard of care treatments. Methods: This exploratory study consisted of two arms, where the 1st arm was the lurbinectedin trial arm (LTA) comprised of data from the SCLC cohort of the trial (NCT02454972) and the 2nd arm was an RWCA sourced from ConcertAI electronic medical records in the US (2010 to 2019). Relevant inclusion and exclusion criteria from the trial were applied to the RWCA to ensure comparability at baseline. Given the absence of Eastern Cooperative Oncology Group performance status (ECOG) for a sizable portion of patients in the RWCA, two RWCA groups were studied, one that excluded patients with reported ECOG > 2 (RWCA1) and the other that excluded patients with reported ECOG > 2 and missing ECOG (RWCA2). Propensity score (PS) weighting was used to further balance measured baseline characteristics between LTA and each RWCA. OS was defined as the time from treatment initiation to death. Weighted cox regression was used to compare OS. ORR was defined as the percentage of patients with a complete or partial response. A weighted two-sample test of proportions was used to compare ORR. Results: This study included 105 patients in LTA and 121 in RWCA1 (74 in RWCA2). After PS weighting, baseline characteristics were mostly similar between LTA and each RWCA. ECOG was balanced between RWCA2 and LTA but was different between RWCA1 and LTA. A numerical median OS benefit of 3.8 and 4.7 months was observed in LTA, compared to RWCA1 and RWCA2, respectively (see table). Probability of survival was greater in LTA compared to RWCAs at 3 and 6 months. ORR was two-fold higher in LTA compared to RWCA1. Consistent findings were seen for LTA compared to RWCA2. Conclusions: Lurbinectedin monotherapy demonstrated improved median OS, lower risk of death at 3 and 6 months, and higher response rate compared to other standard of care treatments in relapsed/refractory SCLC. Future studies with larger sample size powered to detect statistical differences in OS are warranted.[Table: see text]