bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring sex differences in small cell lung cancer: Is this a hormonal issue?
Authors: Duma Narjust , Ho Thanh P. , Durani Urshila , Funni Shealeigh , Inselman Jonathan , Paripati Harshita , Adjei Alex A. , Molina Julian R. , Mansfield Aaron Scott 
Published: March 2020

e20077 Background: Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancers among women and men. Though heavily associated with smoking, its incidence in women is rapidly increasing despite a decline in cigarette exposure. Given the changing demographics of SCLC and hormonal factors associated with other forms of lung cancer, we studied differences between sexes in SCLC. Methods: Utilizing the National Cancer Database, we identified all incident SCLC cases from 2004 to 2014. Patients were classified as limited stage (LS) or extensive stage (ES). Women were stratified by menopausal status (≥55 years = postmenopausal). Kaplan-Meier method and Cox regression were used for overall survival (OS) and multivariable analysis. Results: 161,978 patients were identified. No significant sociodemographic differences were observed between sexes. The majority of patients were non-Hispanic whites (89.1%), followed by non-Hispanic blacks (7.5%). Men were more likely to be diagnosed with ES disease than women (63% vs. 56%). Both sexes initiated treatment within a similar time frame from diagnosis (chemotherapy, median: 18 days, IQR 8-32). Women had better median OS compared to men in both LS (15.2 vs. 12.7 months, HR: 0.85, 95% CI 0.83-0.86, p < 0.0001) and ES (6.4 vs. 5.7 months, HR: 0.88, 95% CI 0.87-0.90, p < 0.0001). No racial or ethnic disparities in OS were observed, overall and when examined within sex and disease stage groups. Differences between sexes in OS were also observed when comparing patients within the same racial/ethnic group (women having better OS). When divided by menopausal status, postmenopausal women with LS and ES had worse OS than premenopausal women (14.7 vs. 22 months, HR: 1.50, 95% CI 1.44-1.56; 6.1 vs. 9.8 months, HR: 1.41, 95% CI: 1.37-1.46, respectively). We also observed worse OS in older men when divided by age ( < 55 years and ≥55 years). In multivariable analysis, older age, postmenopausal status, and Medicaid as primary insurance were associated with worse OS for both LS and ES. Conclusions: In this large cohort, women with SCLC had better OS compared to men. Post-menopausal women had worse OS compared to pre-menopausal women. Since older men had a similar trend of worse survival compared to younger men, age might exert a more significant influence on survival than hormonal status in SCLC. Further studies with data on sexual hormone levels are necessary to better understand their role in women with SCLC.
Radiologic imaging utilization of small cell lung cancer staging and treatment.
Authors: Kikano Elias , Bomberger Thomas , Shinagare Atul B. , Laukamp Kai , Dowlati Afshin , Ramaiya Nikhil H. 
Published: March 2020

e20079 Background: Over the past several decades, first line therapy recommendations for small cell lung cancer (SCLC) have remained relatively unchanged. Additionally, the National Comprehensive Cancer Network (NCCN) guidelines regarding initial evaluation, staging, response assessment, and surveillance of SCLC have also remained relatively static. To evaluate radiologic imaging utilization for SCLC, we reviewed patients imaging data and assessed their association with staging, metastatic sites at presentation, overall survival, and other clinical factors. Methods: Retrospective analysis of patients with a diagnosis of SCLC that received treatment and follow up from 2003 through 2018 was completed. Cross-sectional radiology imaging data including computed tomography of the chest abdomen and pelvis (CT CAP), magnetic resonance imaging (MRI), and positron-emission tomography (PET) was obtained from the picture archiving and communication system (PACS) and clinical data including age, sex, race, smoking history, extensive/limited stage, and metastatic sites at presentation was obtained from the electronic medical record. Results: The average age at diagnosis for all SCLC patients (n = 518) from 2003 to 2018 was 66 with a male to female ratio of 0.89. The mean overall survival of all SCLC patients was 410.2 days with extensive (n = 371) stage = 312.5 days and limited (n = 147) stage = 718.8 days. We found a significantly increased number of patients less than age 66 presented with brain metastasis compared to those greater than age 66 ( P< 0.01). The absolute total number of CT CAP and PET studies was significantly increased in limited stage patients compared to extensive stage ( P< 0.001). However, when accounting for mean overall survival, extensive stage patients received a significantly increased number of CT Brain ( P< 0.05), PET ( P< 0.01), CT CAP, and MRI Brain ( P< 0.001) studies compared to limited stage per year. Conclusions: Overall radiology imaging utilization is significantly different between limited and extensive stage SCLC patients over the past 15 years.
Prognostic impact of paraneoplastic syndromes in patients with small cell lung cancer, real-world data.
Authors: Picard Leblanc Gabrielle , Blais Normand , Tehfe Mustapha , Routy Bertrand , Florescu Marie 
Published: March 2020

e20082 Background: Small cell lung cancer (SCLC) remains an aggressive cancer, with a reported mOS of 15-20 mo when localized (L-SCLC) and 9-11 mo when extensive (E-SCLC). Paraneoplastic syndromes (PNS) are a debilitating condition either related to the embryogenic stem cell origin or to auto-immune antibodies produced against the tumor. These mechanisms may be even more relevant with the use of immunotherapy for first-line treatment of E-SCLC. Methods: We retrospectively reviewed our clinical database of patients diagnosed with SCLC between 2006 and 2017 at CHUM University Center. The primary outcome was to compare OS of patients with and without PNS in L-SCLC and E-SCLC. No patients received immunotherapy. Results: We identified 426 unselected SCLC patients, 39% L-SCLC and 61% E-SCLC. 84 patients (20%) were diagnosed with a PNS: 66 (15%) SIADH, 8 (2%) paraneoplastic Cushing syndromes, 2 (1%) humoral hypercalcemia and 8 (2%) paraneoplastic neurologic syndromes. 25% of patients with PNS vs 14% without PNS had a PS 3-4 and would not have been eligible to a clinical trial. 65% of patients with PNS received chemotherapy vs 63% without PNS. Neurologic PNS were all diagnosed in patients with L-SCLC. PNS affecting the central nervous system (4 limbic encephalitis and 1 cerebellar degeneration) were associated with a poorer prognosis than L-SCLC without PNS (mOS 3,5 mo vs 16,7 mo (p = 0,003)). The 2 patients with Lambert-Eaton myasthenic syndrome had a long survival (29 and 82 mo), but persistence of the neurologic symptoms. 86% of patients with paraneoplastic Cushing syndrome were diagnosed with an E-SCLC and had a worse prognosis than E-SCLC without PNS (mOS 1,1 mo vs 4,63 mo (p = 0,022)). SIADH had a significative poor impact on OS in patients with L-SCLC (mOS 10,1 mo vs 16,7 mo (p = 0,016)), but no impact in survival for patients with E-SCLC (mOS 3,63 mo vs 4,63 mo (p = 0,735)). Conclusions: PNS either in patients with L-SCLC or E-SCLC worsen the overall prognosis, except for Lambert-Eaton myasthenic syndrome. A more systematic detection of these syndromes is suggested before starting immunotherapy as first-line standard treatment for E-SCLC. Furthermore, this real-world unselected clinical cohort shows our E-SCLC patients have a worse prognosis than the clinical trial experience.
Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive small cell lung cancer in China.
Authors: Li Lingyu , Wang Hong , Li Wenqian , Cui Jiuwei 
Published: March 2020

e20083 Background: Atezolizumab plus chemotherapy as a first-line therapy has shown significant survival benefits in patients with extensive small-cell lung cancer (SCLC). While, overprice limited its broad use in clinical. Here, the aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China. Methods: A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients. Utility values were obtained from published studies, and the costs were acquired from real world and literature. Additionally, sensitivity analyses based on a willingness-to-pay threshold (WTP) were performed to identify the uncertain parameters of Markov model. Results: Total costs of atezolizumab group was $183801, while cost of chemotherapy alone group was just $12920 in placebo group. The QLAYs in atezolizumab group was just 1.15 higher than that in placebo group (13.73 QALYs vs. 12.58 QALYs). The ICER between atezolizumab combination with chemotherapy and chemotherapy alone was $148592/QALY in China. The net benefit of placebo group was significantly higher than atezolizumab group. One-way sensitivity analyses highlighted that utilities of the PFS and PD state in placebo group were the most influential parameter. Conclusions: Atezolizumab combination therapy was not more cost-effective than chemotherapy alone therapy at a WTP threshold of $25929/QALYs in China.
The concomitant EGFR T790M/C797S in trans and cis in three osimertinib-resistant lung adenocarcinoma patients.
Authors: Liu Chunling , Li Jidong , Liu Hailong , Du Rong , Fang Nan , Zhang Jingbo , Tang Yu , Wang Jianwei , Wu Qixi 
Published: March 2020

e20105 Background: EGFR C797S mutation is an important cause of Osimertinib resistance. Previous studies showed that patients harboring EGFR C797S in trans with T790M are sensitive to a combination of first- and third-generation EGFR tyrosine kinase inhibitors (TKI). However, patients harboring EGFR C797S in cis with T790M are resistant to combination therapy or each single reagent. Methods: We performed next-generation sequencing on peripheral blood samples from patients with advanced lung adenocarcinoma who had been undergoing targeted therapy. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 14 lung cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq 500 platform. Results: Among 6489 Lung adenocarcinoma patients sample, we identified concomitant trans and cis EGFR T790M/C797S in three patients with very poor prognosis. All three patients were sensitive to the first-generation EGFR TKI, and took Osimertinib when disease progressed. When resistant to Osimertinib, the patients went to genetic testing to find new target therapy. Patient No. 1 was a 66-year-old man with mutations of EGFR exon 19del (25.08%), EGFR T790M (10.08%) / C797S (5.37%) in trans and in cis, TP53 exon8 mutation (12.35%). This patient died 20 days after the genetic testing without any further treatment. Patient No. 2 was a 53-year-old woman who carried gene mutations including EGFR exon 19del (0.51%), EGFR T790M (0.57%) and C797S (0.47%) in trans and in cis. She was treated with the combination of first- and third-generation EGFR TKI, and disease progressed after 50 days. She died half months after the gene test. Patient No. 3 was a 63-year-old woman whose gene mutation included EGFR L858R (77.49%), EGFR T790M (40.94%) and EGFR C797S (5.46%) in trans and in cis, also combined with EGFR amplification. Treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor Anlotinib was attempted, but the patient died within one month after the gene test. Conclusions: We firstly reported three cases with concomitant EGFR T790M/C797S in trans and EGFR T790M/C797S in cis mutation in the word. Physicians tried either the EGFR TKI inhibitor combination therapy or VEGFR inhibitor, but neither of them had an effect on these patients. All three patients had very poor prognosis and died within two months of the gene test, indicating that the concomitant of the cis and trans mutation could be a very important prognostic prediction factor.
Real-world characterization of advanced/metastatic non-small cell lung cancer (aNSCLC) patients (pts) with rapid disease progression (RDP).
Authors: Gutierrez Martin , Molife Cliff , Belli Andrew J. , Hansen Eric , Stefaniak Victoria Jennifer , Winfree Katherine B. , Cui Zhanglin Lin , Batus Marta , Clarke Jeffrey Melson , Narayanan Viraj , Manion Chelsea , Norden Andrew David , Bonomi Philip D. 
Published: March 2020

e20706 Background: Despite advances in therapy, recent observational data shows that aNSCLC pts with RDP continue to have a poor prognosis. This retrospective, observational study characterizes the demographic, molecular, & treatment profile of pts with RDP. Methods: Adult aNSCLC pts receiving first-line (1L) platinum-based (Pt) therapy between 01/2014 - 12/2018 were identified in the COTA Real-World Evidence database and assigned to RDP (n = 280) & non-RDP (n = 1,212) cohorts based on time to progression during 1L Pt therapy (≤ 12 and > 12 weeks, respectively). Results: Of 1,492 eligible pts, the incidence of RDP was 19%. Mean age (±SD) was 64.6 (10.9) and 66.1 (10.2) in the RDP and non-RDP group, respectively (p = 0.04). Data showed RDP patients had higher percentage of stage IV disease at diagnosis (77 v 72, p < 0.01), higher histologic grade G3/G4 (37 v 29, p = 0.01), and PD-L1 negative (< 1% expression) status (p = 0.01). Table shows molecular profiling across cohorts. No notable difference in treatment patterns across 1L and 2L was observed. Conclusions: This study identifies stage IV disease at diagnosis, higher grade, & PD-L1 negative ( < 1% expression) as potential risk factors for RDP. A better understanding of this poor prognosis cohort may offer an opportunity to better optimize therapies & outcomes. [Table: see text]
Treatment and outcomes for patients (pts) with selected advanced/metastatic cancers by place of care.
Authors: Xu Yihua , Hess Lisa M. , Molife Cliff , Cuyun Carter Gebra , Zhu Yajun Emily , Bunniran Suvapun , Loy Bryan A. , Churchill Collin , Nair Radhika 
Published: March 2020

e20717 Background: Place of care may be an important factor affecting treatment & economic outcomes for pts in advanced stages of cancer. This retrospective observational study compared treatment patterns, healthcare resource use & costs, and overall survival (OS) for pts treated for selected cancers in the hospital outpatient department (HO) vs community oncology practices (CP) including physician offices & freestanding ambulatory centers. Methods: Claims data from a large national health plan were used to identify adult pts with newly diagnosed advanced/metastatic non small cell lung cancer (aNSCLC), metastatic breast (mBC) or metastatic colorectal cancer (mCRC) between 07/2012 & 12/2016, who initiated anticancer therapy in HO or CP settings. Pts enrolled in Medicare Advantage Prescription Drug (MAPD) or commercial plans for ≥ 6 months prior & ≥ 30 days after start of first line (1L) (index date) were included. OS was evaluated among pts enrolled in MAPD and costs were evaluated among pts enrolled ≥ 6 months pre- & post-index, by cancer type & by place of care. Outcome analyses were adjusted using multivariable models. Results: Among 8,333 eligible pts, there were 4,618, 2,304 & 1,411 pts with aNSCLC, mCRC & mBC, respectively and each cohort was evenly split by place of care. No notable differences in baseline characteristics or the most commonly used 1L, 2L or 3L regimens were observed by place of care for the 3 cancers. For aNSCLC pts, mean 1L treatment duration was shorter (96 v 102 days, P = 0.02) and time between 1L & 2L was longer (125 v 106 days, P = 0.04) in the HO than the CP setting, respectively. For mBC, mean 1L treatment duration was longer in the HO setting (156 v 190 days, P < 0.01). Adjusted total all cause healthcare costs were higher in HO than CP for mBC ( P < 0.01) & mCRC ( P < 0.01), but no significant difference in median OS was observed between HO & CP settings for the 3 cancer types. Conclusions: This study showed no major differences between HO & CP settings in baseline characteristics, the first 3 lines of therapy, or adjusted median OS for aNSCLC, mCRC, or mBC cohorts. However, total costs were higher in the HO setting for mCRC & mBC pts. These findings may be useful for healthcare decision & policy makers but warrant further evaluation.
Can texture analysis of pre-immunotherapy CT imaging predict clinical outcomes for patients with advanced NSCLC treated with Nivolumab?
Authors: Spieler Benjamin Oren , Saravia Diana , Lopes Gilberto , Azzam Gregory , Kwon Deukwoo , Dal Pra Alan , Yechieli Raphael , Diwanji Tejan , Mihaylov Ivaylo 
Published: March 2020

e20720 Background: Targeted therapies are ineffective in most NSCLC patients and response rates remain < 20% for patients with advanced NSCLC on immuno-monotherapy. Predictive models that distinguish responders from non-responders to immunotherapy could help guide clinical practice. Texture analysis is a data-mining tool used to identify intensity patterns in diagnostic imaging. We hypothesized that texture features on pre-immunotherapy CT imaging can be associated with clinical outcomes for patients with advanced NSCLC treated with Nivolumab. Methods: In an IRB-approved database containing 159 patients with advanced NSCLC treated with Nivolumab monotherapy, 20 patients with the longest overall survival (OS) and 20 with the shortest were selected for retrospective analysis. Patient characteristics were compared using paired t-tests. The last pre-immunotherapy PET CT for each patient was transferred to MIM software for segmentation. All FDG-avid intrathoracic tumors were delineated on the CT scan per RTOG contouring guidelines. Ninety-two texture features within each tumor were analyzed for association with the primary endpoint, OS. OS time was dichotomized to less than 1 year vs. more than 1 year. A univariate logistic regression model was used to estimate odds ratio (OR), 95% confidence interval and p-value for each feature. Multiple testing adjustments were performed using false discovery rate. Results: Eleven out of 92 texture features showed significant association with OS time (p-values from 0.009 to 0.044), of which 7 exhibited large effect (OR < 0.5 or > 1.5). Fifteen additional texture features trended toward statistical significance with p-values from .05 to .10. In all, 26 out of the 92 texture features showed significant association or trended toward significance with duration of OS. Conclusions: This preliminary study suggests that texture features on pre-immunotherapy CT imaging may help in predicting OS duration for patients with advanced NSCLC treated with Nivolumab monotherapy. We are in the process of validating a multivariate predictive model. Future directions include expansion of this study across the full database, survival analyses and correlation of texture features with tissue biology.
Personalizing cancer treatment using gene activity scores with the NIH Medical Genetics Summaries.
Authors: Malheiro Adriana J. , Dean Laura Charlotte , Kattman Brandi L. 
Published: March 2020

e22000 Background: Oncology professionals need to access a wide range of genetic tests, including tests for cancer biomarkers, predisposition to hereditary cancers, and pharmacogenetic tests. While pharmacogenetic testing is fundamental to personalized medicine, the adoption of testing has been slow, partly due to a lack of readily accessible information about new developments, such as gene activity scores. Methods: Medical Genetics Summaries (MGS) was created to bridge the translation gap between genetic test results and personalized treatment plans. MGS is a free, regularly updated, peer-reviewed pharmacogenetics resource. The complete set of summaries can be browsed online or saved as PDF (www.ncbi.nlm.nih.gov/books/n/gtrbook). Excerpts of the summaries can be found via PubMed (www.pubmed.gov) and MedGen (www.ncbi.nlm.nih.gov/medgen). Results: Of the 45 drug-gene interactions included so far in MGS, 10 are commonly used cancer drugs. These include capecitabine (Xeloda) and fluorouracil (Adrucil), which are both fluoropyrimidines—antimetabolite drugs used in the treatment of colon cancer and breast cancer. The DPYD gene encodes the rate-limiting enzyme for the breakdown of fluoropyrimidines. Patients with specific variations in the DPYD gene (e.g., DPYD*2A, DPYD*13) have decreased or absent enzyme activity. In these patients, the standard recommended dose of fluoropyrimidine can cause life-threatening bone marrow suppression and neurotoxicity. MGS presents the dosing recommendation for each DPYD phenotype, which are clearly defined using the recently assigned DPYD activity scores, from authoritative professional guidelines such as the National Comprehensive Cancer Network (NCCN) and the Clinical Pharmacogenetics Implementation Consortium (CPIC), in addition to the FDA. MGS also provides an overview of the drug (drug class, mechanism of action, adverse events), an introduction to the gene(s) and significant alleles, and guidance on genetic testing—along with links to the relevant tests in the NIH Genetic Testing Registry (GTR, www.ncbi.nlm.nih.gov/gtr). Conclusions: This presentation will demonstrate how NIH precision medicine resources, with a focus on MGS, can simplify the process of ordering and interpreting pharmacogenetic tests and efficiently tailor care for your patient.
Salvage chemotherapy using irinotecan and temozolamide in pediatric and adult populations with relapsed Ewing sarcoma.
Authors: Salah Samer , To Yat Hang , Ismaeel Taleb , Khzouz Omar , Sultan Iyad Yasin , Yaser Sameer , Alnsour Anoud Zaid , Abuhijlih Ramiz , Shahin Omar , Aldouri Rasha , Lewin Jeremy 
Published: March 2020

e22500 Background: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing Sarcoma (ES), although studies are largely limited to the paediatric population. We aimed to compare the tolerability and efficacy of IT between paediatric and adult patients. Methods: We retrospectively reviewed paediatric (< 18 years) and adult patients treated with salvage IT chemotherapy at two institutions from March, 2010 to June, 2018. Toxicities were graded according to common terminology criteria of adverse events (CTCAE v. 4.03) and compared using the Chi Square test. Responses were interpreted by Response Evaluation Criteria in Solid Tumors (RECIST). The Kaplan-Meyer method was used to estimate progression free survival (PFS); survival comparisons were carried out by the Log-rank test. Results: Fifty-three patients were included ( n= 16 paediatric; n= 37 adult). Median age was 20 (range, 5 – 45 years). A total 236 IT cycles were delivered (median = 4, range:1-7). IT was given as second-line ( n= 34; 64%) or ≥third-line ( n= 19; 36%). There was no difference in ≥grade 3/4 haematologic toxicity between paediatric and adult patients (31% vs. 35% respectively; p= 0.76), whilst febrile neutropenia was observed in two (4%) patients (one adults and one paediatric). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 19 (44%) had disease progression and 12 (28%) had stable disease. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.1 months, p = 0.001). Superior PFS for the paediatric population was observed in both, the second-line (6.2 vs. 2.2 months; p= 0.060) and ≥third-line setting (7.4 vs. 1.2 months, p= 0.014). Conclusions: IT is an effective salvage regimen for ES, with favourable toxicity and equally observed objective responses in paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in a larger prospective study.