bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune-checkpoint inhibitors among privately insured cancer patients: Utilization pattern and out-of-pocket cost.
Authors: Zhao Hui , Xu Ying , Giordano Sharon H. , Shih Ya-Chen T. 
Published: May 2020

e19252 Background: Immune-checkpoint inhibitors (ICI) is a form of immunotherapy that “releases the brakes” on the immune cells to restore antitumor immunity and promote tumor cell death to treat cancer. In March 2011, the United States Food and Drug Administration (FDA) approved ipilimumab, the 1st ICI, to treat advanced-stage melanoma. Since December 2014, FDA successively approved another six ICIs: nivolumab, pembrolizumab, avelumab, durvalumab, cemiplimab, and atezolizumab. Beside melanoma, the treatment indications for these agents have been expanded to renal cell carcinoma, microsatellite instability (MSI)-high malignancies, small-cell lung cancer, non-small-cell lung cancer, and cutaneous squamous cell carcinoma. No study had examined the patterns and out-of-pocket (OOP) costs of ICI among cancer patients (pts) with private insurance. Methods: We used the IBM MarketScan Commercial Claims and Encounters database to document the uptake of ICI from 2011 to 2017. Using the Healthcare Common Procedure Coding System (HCPCS) codes, and national Drug code, we identified ICI claims among pts 18 to 64 years old. OOP cost for ICI was computed as sum of coinsurance, copayment, and deductible. To determine whether financial burden was higher for pts with high-deductible (HD) plans, we dichotomized pts’ insurance plan as HD vs. non-HD. Summary statistics was used to describe the patterns of ICI use. We used Wilcoxon Rank Sum test to compare the OOP by HD status. Results: The study cohort included 7,855 pts with 62,636 ICI claims of ipilimumab, nivolumab, pembrolizumab, avelumab, durvalumab, and atezolizumab between 2011 and 2017. The median age was 57 years and about 56.9% pts were male. Approximately 90% of pts used ICI as monotherapy, and the median number of claims per patient was 4. The most commonly used ICI was nivolumab (55.4%), accounting for about 90% of claims after 2014, followed by lpilimumab (24.6%), pembrolizumab (18.5%). Among the ICI pts, 17.2% enrolled in HD plans and 82.8% had non-HD plans. The median OOP for both HD and non-HD groups was $0, whereas the 3rd quartile of OOP was significantly higher for pts in HD plans ($556 vs. $26, P < 0.01). In addition, approximately 18.7% of pts (17.3% of pts in non-HD and 25.6% in HD plans) paid over $500 OOP per patient for ICI. Conclusions: The use of ICI was dramatically increased as more ICI agents were approved since 2015. Although more than 50% of pts had $0 OOP, possibly due to the out-of-pocket max provision in private insurance, pts with HD plans are especially susceptible to high financial burden of ICIs.
Real-world data of a cohort of patients with soft tissue sarcoma in a single institution of Colombia.
Authors: Pino Luis Eduardo , Triana Ivan Camilo , Ospina Serrano Aylen Vanessa , Segovia Javier , Hennessey Diana Carolina 
Published: May 2020

e19259 Background: Soft Tissue Sarcomas (STS) are a group of neoplasm with huge histological diversity and biological behaviors. They have a low prevalence and lack of data, especially in Colombia where there is no specific report of this disease. The objective of this study is to describe clinical characteristics and outcomes of patients with soft tissue sarcoma at Fundación Santafe, a university hospital located in Bogotá. Methods: This is an observational study of a cohort of soft tissue sarcoma patients treated at a single institution with a follow-up of 4 years (2015 - 2019). Clinical, molecular and epidemiological variables were registered, and overall survival was calculated for stage IV sarcomas. For the survival analysis a Kaplan Meier model was used. Results: Twenty-four patients were included. The histologies reported were: Pleomorphic sarcoma 25.0%, Ewing's sarcoma 20.8%, liposarcoma 16.7%, chondrosarcoma 8.3%, leiomiosarcoma 8.3%, synovial sarcoma 8.3%, soft part alveolar sarcoma 8.3%, and dermatofibrosarcoma protuberans 4.3%. OSm for the whole stage IV group was: 30.22m, according to subtypes OSm was: Ewing's sarcoma 37.13 OSm, liposarcoma 11 OSm, chondrosarcoma 12.3 OSm. Only 3 of the cases (2 Ewing's sarcoma and 1 alveolar sarcoma) had multigenic platform information. In these cases, main mutations in BCL2, SOX9, SATB2 and TFE3 were described. In two of the cases PDL1 expression was done with a negative result ( < 1%) (pleomorphic sarcoma and Ewing's sarcoma). Ifosfamide and anthracyclines was the most frequent chemotherapy regimen used, but in two of the cases checkpoint inhibitors were initiated. Conclusions: This real-world cohort of STS have a similar clinical and epidemiological distribution to historic cohorts, but our OSm for Ewing's sarcoma stage IV is longer than reported, even with a case of complete remission after consolidation with autologous bone marrow transplant. Other histologies had a worse prognosis with a less than 12 m OSm. Genomic data were scarce and useless for directed therapies or immunotherapy as usual in STS. [Table: see text]
Landscape of targetable alterations discovered by next generation sequencing demonstrates the role a community hospital can play in precision-guided oncology: Experience from Lenox Hill Hospital.
Authors: Vojnic Morana , Steinberg Jordan , Odintsov Igor , Ziemba Yonah , Hill Lindsay K , Vele Oana , Brunckhorst Keith R. , Hasanovic Adnan 
Published: May 2020

e19279 Background: Next generation sequencing (NGS) has become standard of care in aiding diagnosis and treatment of advanced solid cancers, and in conducting clinical trials at large centers. It is imperative that this is expanded to other hospitals that care for the majority of cancer patients. We analyzed NGS reports from our hospital to assess the number of patients who can benefit from approved or investigational targeted therapies. Methods: We analyzed NGS data for 511 solid tumor samples sequenced between January 1, 2018 and December 31, 2019. NGS was performed by GenPath Dx (77%), Caris Life Sciences (16%) or Foundation Medicine (7%). Results: The majority of samples represented advanced stage malignancies and 21% were stage I or II. They originated from the following primaries: 195 lung (37%), 150 gastrointestinal (29%), 64 primary brain (12%), 20 gynecological (4%), 14 skin (3%), 13 head and neck (3%) and 11 sarcomas (1%). 72 samples had mutations in EGFR (14%), 170 in TP53 (33%), 124 in KRAS (24%), 28 in BRAF (6%), and 3 in RET (0.6%). 34/107 (32%) early stage samples harbored an actionable mutation (20 EGFR mutations, 1 MET exon 14 skipping, 4 KRAS G12C, 7 BRAF V600E, 1 FGFR3 amplification and 1 CD74/NRG1 fusion). In contrast, only 58/317 (18%) advanced stage samples had a targetable mutation (p-value = 0.02, χ² test). 76% of EGFR-mutated samples were lung adenocarcinomas, and 19% were primary brain tumors; 54% of these are targetable by FDA-approved EGFR inhibitors. KRAS mutations were found in gastrointestinal (54%), lung (37%) and pancreatic (5%) malignancies. 17 patients had a KRAS G12C mutation and, therefore, could benefit from one of the KRAS G12C inhibitors in early clinical trials. Four samples harbored crizotinib-sensitive mutations (2 MET amplifications and 2 MET exon 14 skipping mutations). Regarding gene fusions, one glioblastoma sample had a PTPRZ-MET fusion and one lung adenocarcinoma sample harbored a CD74-NRG1 fusion. Conclusions: We identified 92/511 samples (18%) with clinically actionable mutations; distributed in 32% early stage and 18% advanced stage disease, indicating that actionable mutations are present at an increased frequency in early stage solid malignancies in our data set and trials to investigate targeted therapy in such settings should be considered. Furthermore, we show that a community-based hospital can be a site for future clinical trials of small molecule inhibitors and bring precision-guided medicine to additional patients.
Molecular profiles and treatment recommendations for invasive lobular carcinoma in a real-world prospective breast cancer registry.
Authors: Lesnikoski Beth-Ann , Crozier Jennifer A. , Srkalovic Gordan , Robinson Patricia A. , Osipo Clodia , Banda Kalyan , Kling Heather M. , Yoder Erin , Audeh William ,   FLEX Investigators Group
Published: May 2020

e19291 Background: Invasive lobular carcinoma (ILC), the second most common histological breast cancer type, comprises 10-15% of breast tumors. Although ILC is thought to have a low risk of relapse, patient survival data vary. ILC treatment guidelines mirror those for invasive ductal carcinoma (IDC); however, these were extrapolated from trials that included predominantly IDC. The FLEX Registry captures data from real-world breast cancer patients; the current sub-study evaluated molecular profiles and treatment recommendations in ILC. Methods: The FLEX Registry (NCT03053193) includes stage I-III primary invasive breast cancer patients who receive 70-gene signature (70-GS)/80-gene signature (80-GS) testing and consent to full transcriptome and clinical data collection. This sub-analysis includes 335 ILC patients and 2,179 IDC patients enrolled from 2017 to present. 70-GS stratified tumors by risk of distant metastasis [High (HR), Low (LR), Ultralow (UL) Risk], and 80-GS classified tumors by molecular subtype (Luminal, HER2, or Basal type). Genomic and clinical data were compared for ILC and IDC using chi-square or Fisher’s exact test. Results: ILC represented 13% of FLEX cases (n = 335/2752); 81% were lymph node-negative, 99% ER-positive, and 94% HER2-negative. Clinical risk assessment (MINDACT criteria) classified 61% of ILC and 53% of IDC as low risk (p = 0.03). 70-GS risk distribution in ILC (18% UL, 51% LR, 31% HR) differed from IDC (13% UL, 34% LR, 53% HR; p < 0.01). Discordance between 70-GS and clinical risk was greater in ILC (43%) than IDC (30%, p < 0.01). 80-GS results also differed between ILC (98% Luminal, 1.6% HER2, 0.3% Basal) and IDC (85% Luminal, 3% HER2, 11% Basal; p < 0.01). Inclusion of chemotherapy (CT) in treatment plans was associated with 70-GS risk (p < 0.01); treatment plans that disagreed with 70-GS results were associated with discordant clinical risk (p < 0.05). Treatment plans disagreed with 70-GS in 15% of ILC and 12% of IDC total cases (p = 0.08), and more frequently in HR cases (25% in ILC, 14% in IDC; p < 0.01). Conclusions: The FLEX Registry includes patients with ILC consistent with real-world breast cancer frequencies. ILC demonstrated genomic risk and subtype profiles distinct from IDC. Treatment plans largely agreed with 70-GS results; however, discordance was more frequent in HR ILC than IDC. Future studies will evaluate clinical outcomes; however, these results demonstrate the added value of molecular profiling in ILC and the utility of real-world registry data in evaluating uncommon breast tumor types. Clinical trial information: NCT03053193 .
Examination of PD-1/PD-L1 inhibitor use and adverse events in a real-world setting.
Authors: Irwin Debra E. , Brady Brenna L. 
Published: May 2020

e19294 Background: Immune checkpoint blockade through PD-1 and PD-L1 inhibition is an effective treatment for multiple cancers. This study used administrative claims to examine potential adverse events (AEs) associated with real-world PD-1 or PD-L1 inhibitor use. Methods: Adult patients newly initiating a PD-1 (pembrolizumab or nivolumab) or PD-L1 (atezolizumab, avelumab, or durvalumab) inhibitor from September 1, 2016 to August 30, 2018 were selected in the MarketScan Commercial and Medicare Supplemental Database. Patients were grouped by use of PD-1 or PD-L1 inhibitor; the study period consisted of 90 days baseline and 60 days follow-up around drug initiation. Patients who used both PD-1 and PD-L1 inhibitors during follow-up were excluded. Clinical characteristics were examined during baseline, while AEs were investigated over follow-up. Results: A total of 6,430 patients qualified for the analysis. The majority of the sample (N = 5,956; 93%) received PD-1 inhibitors. Compared to the PD-1 cohort, the PD-L1 cohort was older (64±10 vs. 61±12 yrs) and more likely to be male (61% vs. 56%), p < 0.05. PD-L1 patients were significantly more likely to have history of chronic pulmonary disease (28% vs. 23%) or myocardial infarction (4% vs. 3%) but less likely to have liver disease (2% vs. 0.6%) compared to PD-1 patients, p < 0.05. Lung cancer was the most common diagnosis in both groups (PD-1: 47%; PD-L1: 62%, p < 0.001). The PD-L1 cohort was more likely to have evidence of bladder cancer (36% vs. 5%), while the PD-1 cohort was more likely to have a melanoma (19% vs. 0.8%) or renal cell carcinoma diagnosis (10% vs. 7%), p < 0.05. Over half of the PD-1 (65%) and PD-L1 (61%) patients had metastatic cancer diagnosis during the study period. Incident AEs occurring in > 5% of the sample included dyspnea (PD-1: 13%; PD-L1: 14%), nausea/vomiting (PD-1: 11%; PD-L1: 8%, p < 0.05), anemia (PD-1: 11%; PD-L1: 12%), fatigue (PD-1: 10%; PD-L1: 12%), abdominal pain (PD-1: 7%; PD-L1: 7%), cough (PD-1: 7%; PD-L1: 10%, p < 0.05), back pain (PD-1: 7%; PD-L1: 10%, p < 0.05), constipation (PD-1: 6%; PD-L1: 8%), arthralgia (PD-1: 6%; PD-L1: 6%), pyrexia (PD-1: 5%; PD-L1: 8%, p < 0.01), and edema (PD-1: 6%; PD-L1: 5%). Conclusions: This study assessed real-world AEs associated with PD-1/PD-L1 inhibitor use in the 60 days following first treatment. Results showed AEs are common soon after starting therapy. Although, PD-1 and PD-L1 inhibitors target the same pathway, slightly different AE profiles exist for the two classes. More longitudinal analyses of real-world AEs are needed to better understand potential impacts of prolonged therapy.
Access to molecular testing and targeted molecular therapy among Mexican patients with lung adenocarcinoma.
Authors: González-Gutiérrez Adriana , Salazar-Mejía Carlos Eduardo , Dorsey-Trevino Edgar , Gonzalez Vela Jose Luis , González-Guerrero Juan Francisco , Hernández-Barajas David , Vidal-Gutiérrez Oscar , Oyervides Victor 
Published: May 2020

e19296 Background: Precision medicine has led to important changes in the treatment paradigm for patients with lung adenocarcinoma (LA) with mutations in EGFR or rearrangements of ALK or ROS1. The objective of this study is to describe the proportion of patients with LA who had access to molecular testing and targeted molecular therapy at an oncology referral center in Northeast Mexico. Methods: A retrospective study was performed with information gathered from electronic health records of the Hospital Universitario “Dr. José E. González” in Monterrey, Mexico from 2014 to 2019. Patients with LA were identified based on ICD-10 codes (C34) and diagnosis was confirmed with histopathological reports. Results: A total of 316 cases of lung cancer were identified, of which, 194 (64%) were LA, and of those, 117 (60%) had access to molecular testing. Mutations in EGFR were detected in 47%; 38% in men and 59% in women. Rearrangements in ALK were observed in 6.4%, whereas no alterations in ROS1 were seen. Access to molecular testing increased from 2014 to 2019, with a rate of 42% to 67%, respectively. Among patients that were candidates to receive targeted molecular therapy only 37% had access in 2014 versus 66% in 2019. Conclusions: The frequency of mutations in EGFR among our patients with LA showed a high discrepancy with previous studies conducted in countries with a predominantly white population. In Latin America, reports range from 14% to 34% in Argentina and Mexico, respectively. In our study, we identified a higher proportion of mutations in EGFR when compared to what previously reported; however, limited access to molecular testing may bias our results. Despite the advances in treatment for patients with LA, the availability of molecular testing and personalized treatment remains a challenge for developing countries.
Analysis of bleeding risk with concurrent treatment of VEGFR tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors.
Authors: George Tiffany L. , Patel Sandip H. , Wang Tzu-Fei , Mori-Vogt Sherry , Folefac Edmund , Yin Ming 
Published: May 2020

e19305 Background: Tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor receptor (VEGFR) may interfere with the coagulation system making patients susceptible to both hemorrhage and thromboembolism. Some cancer patients require dual treatment with VEGFR TKIs and factor Xa inhibitors. However, the safety of such combination treatment (e.g. bleeding risk) has not been well characterized in the literature. Methods: This retrospective study identified metastatic cancer patients who received VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib, cabozantinib, tivozanib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs]- rivaroxaban or apixaban) from 2001 to 2018 at the Ohio State University. We assessed bleeding risks of dual therapy vs factor Xa inhibitors alone, using the same patients as self-controls. We defined bleeding based on criteria from the International Society on Thrombosis and Haemostasis. Fisher’s exact test was used to compare distribution of bleeding severities and the Cox model was used to analyze bleeding risk. Results: A total of 86 patients were included for analysis, with a median age of 56 (range, 34-88). The patient population was predominantly of male gender (69.7%), Caucasian race (89.3%) and renal cell cancer type (48.9%). As some patients had been on both LMWH and DOAC at different time periods, we found that 81 patients received concurrent TKI and LMWH; 19 patients had concurrent TKI and DOAC. Overall, 25 patients developed 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment, and 15 patients developed 17 clinically significant bleeding events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days. We found a statistically higher bleeding risk with concurrent treatment (HR = 2.23, 95% CI, 1.13–4.42, p = 0.02) compared with Xa inhibitor alone. In a stratified analysis, concurrent VEGFR TKI plus LMWH or DOAC both showed a strong trend for elevated bleeding risk. Although there were increased bleeding events with concurrent treatment, there was no significant difference in the proportion of major bleeding (27.6% vs 23.5%, p = 0.76). Median time to first bleeding event was 56 days for concurrent therapy and 72 days for Xa inhibitor alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with significantly increased bleeding risk when compared with factor Xa inhibitors alone in metastatic cancer patients.
Real-world evidence: A retrospective-cohort study of castration-resistant advanced prostate cancer (CRAPC) patients treated with abiraterone 1000 mg or 250 mg.
Authors: Smolje Leonel , Niewiadomski Dario , Acuna Claudia Lorena , Gonzalez Cesar , Gonzalez Liliana D , Ares Sandra L. , Muino Marcelo , Garcia Gerardi Carlos , Gil Deza Ernesto , Morgenfeld Eduardo L. , Rivarola Edgardo G. J. , Gercovich Felipe G. 
Published: May 2020

e19315 Background: The efficacy of Abiraterone 250 mg with food was established ten years ago (Ryan JCO 2010). Recent publications (Szmulewitz JCO 2018) have concluded that 1000 mg on an empty stomach or 250 mg with food have similar results. This paper focuses on our experience with patients treated with either scheme at Instituto Oncológico Henry Moore (IOHM). Methods: Between July 2013 and December 2019, CRAPC patients were treated with Abiraterone 1000 mg on an empty stomach (Group A) or 250 mg with breakfast (Group B), according to the decision of the attending physician. Both groups received 5 mg of Prednisone twice a day. All cases from Group B were included and they were matched in a 1:2 ratio with Group A by two criteria: age at diagnosis and interval between diagnosis and Abiraterone. We studied: A) response rate of PSA at 12 weeks, B) time to progression, C) post-Abiraterone survival and D) overall survival. Results: We included 99 patients in the study: 66 in Group A and 33 in Group B. The table below shows population characteristics and results. Conclusions: 1) Abiraterone 1000 mg on an empty stomach or 250 mg with food both have similar outcomes. 2) In Argentina, the monthly cost of Abiraterone 1000 mg per patient is equivalent to USD 5,300. This cost can be reduced by 75% with Abiraterone 250 mg with food without losing efficacy. [Table: see text]
Machine learning imputation of Eastern Cooperative Oncology Group performance status (ECOG PS) scores from data in CancerLinQ discovery.
Authors: Agrawal Smita , Narayanan Babu , Chandrashekaraiah Prajwal , M Sai Vinod , Nandi Sourav , Vaidya Vivek , Sun Ping , Cabrera Claudia , Svensson David , Khosla Sajan , Stepanski Edward , Komatsoulis George Anthony 
Published: May 2020

e19318 Background: ECOG PS is a prognostic indicator of outcomes, and scores of 0-1 (good ECOG PS) are often required for clinical trial enrollment. Patients treated in non-trial settings often lack ECOG PS scores limiting the ability of Real World Data from these patients to be used in external control arms (ECAs) or to provide optimal specificity for clinical effectiveness research. Machine Learning can be used to impute ECOG PS scores from other clinical data at various points during treatment. Methods: We developed a series of models using logistic regression (LR) or XGBoost (XGB) that impute ECOG PS at initial diagnosis, metastatic diagnosis and final evaluation using a curated Non-Small Cell Lung Cancer cohort of 31,425 patients with at least one ECOG PS score. Results: AUC-ROC values of up to 0.81 could be obtained for imputing a patient’s final ECOG PS, with lower AUC values when imputing ECOG PS at initial and metastatic diagnosis using large numbers (i.e. thousands) of features. We developed more interpretable models with 110 or 40 features with reduced but still satisfactory AUC, with accuracy of predicting good ECOG PS scores of around 80%. Key features were obtained from lab tests, physical exams, comorbidities, medications, age and metastatic status. The table below shows the results of several of these models. Where the models misclassify ECOG PS, the error was rarely greater than 1 grade. Conclusions: ECOG PS is subjective, suggesting that ML based cohort assignment will be sufficiently accurate to support their use in research. Further work will be required to assess if the ML predicted cohorts have different outcomes. [Table: see text]