bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a novel EHR-based tumor progression outcome to support biomarker discovery.
Authors: Kehl Kenneth L. , Hassett Michael J. , Stafford Katherine A. , Xu Wenxin , Johnson Bruce E. , Schrag Deborah 
Published: May 2020

e19297 Background: Obtaining clinical outcomes for analysis has historically been a critical barrier to cancer genomics research. EHRs could constitute an important data source to bridge this gap, but EHRs rarely capture structured outcomes such as cancer progression. Novel, robust methods are needed to capture clinically relevant outcomes from EHRs. Methods: Among patients with lung adenocarcinoma whose tumors were sequenced via the Dana Farber Cancer Institute/Brigham and Women’s PROFILE study from 2013-2018, imaging reports following first palliative-intent systemic therapy were annotated using natural language processing (NLP) models trained to capture cancer progression according to the structured “PRISSMM” framework. NLP-based cancer progression and imaging report frequency were jointly modeled using inverse-intensity weighted generalized estimated equations, censored at six months, to explore associations between alterations in lung cancer biomarkers (ALK, EGFR, ROS1, BRAF, KRAS, SMARCA4) and progression. Among patients with KRAS mutations who received immunotherapy, we also analyzed the association between STK11 mutations and progression. The novel outcome generated by the model – imaging report-based progression (iPROG) – corresponded to the difference in the mean log odds of progression per inverse-intensity weighted report associated with a given biomarker; it was reported as adjusted mean probability and in exponentiated form as an odds ratio (OR). Results: Among 690 patients with lung adenocarcinoma, associations between tumor mutations and the iPROG outcome are listed in the Table. Conclusions: A deep NLP model applied to EHR data can capture a novel cancer progression outcome, which is associated with known prognostic markers in lung cancer. Application of this method to large “real world” datasets, with attention to interactions between treatment and genomics, could speed biomarker discovery. [Table: see text]
Real-world burden of myelosuppression in patients with small cell lung cancer (SCLC): Retrospective, longitudinal data analysis.
Authors: Epstein Robert S. , Krenitsky JoAnn , Weerasinghe Roshanthi K. , Parrish Amy S. , Sanborn Rachel E. , Salimi Tehseen 
Published: May 2020

e19300 Background: Myelosuppression is a common side effect of chemotherapy (CT) that can compromise patient (pt) and economic outcomes. To evaluate the overall burden of myelosuppression, a longitudinal, patterns of care analysis was conducted among pts with SCLC treated with CT in routine clinical practice. Methods: Data were obtained from Providence St. Joseph Health electronic medical records between Jan 2016 and Dec 2019. Hematologic adverse events, treatment patterns, and hospital-based healthcare resource utilization and costs were assessed during the 12 months from first diagnosis of SCLC in pts who had CT-induced grade 3/4 myelosuppression in 1st or 1st/2nd/3rd-line (1/2/3L) treatment settings. Descriptive statistics were utilized to summarize key findings. Costs of care were calculated from actual treatment costs for inpatient, outpatient, and emergency room services after first diagnosis and treatment with CT. Professional billing was not included due to variability in physician employment by the system. Results: 347 pts were eligible for analysis; mean age (SD) was 66 (9.0) years, 49% were female, and 89% were Caucasian. Prominent comorbidities included chronic obstructive pulmonary disease (52%), diabetes (23%), and peripheral vascular disease (20%). 264 pts (76%) received 1L treatment only, while an additional 83 pts (24%) had both 1L and 2/3L treatment. Of 339 evaluable pts with longitudinal laboratory data, grade 3/4 cytopenias were reported as follows: 45%, neutropenia; 41%, anemia; and 25%, thrombocytopenia. 43% and 15% of pts received red blood cell or platelet transfusions, respectively. 49% of pts received prophylaxis (6%) or treatment (43%) with G-CSF, and 4% of pts were treated with erythropoiesis-stimulating agents. Average total costs of care (post initial-diagnosis and treatment) for pts without grade 3/4 hematologic events (n = 110) were $67,802 per pt throughout the 12 months’ follow-up. On average, annual per pt costs for those with grade 3/4 hematologic events were $131,047 for neutropenia, $95,954 for anemia, and $90,053 for thrombocytopenia. Conclusions: A large and meaningful proportion of pts had grade 3/4 myelosuppression with annual incremental associated costs per pt ranging from $22,251 for pts with thrombocytopenia to $63,245 for pts with neutropenia. Despite the availability of protocols of care and various rescue treatments, CT-induced myelosuppression places a significant real-world burden on pts and the healthcare system.
Real-world treatment attrition rates in advanced esophagogastric cancer.
Authors: Tsang Erica S , Lim Howard John , Renouf Daniel John , Davies Janine Marie , Loree Jonathan M. , Gill Sharlene 
Published: May 2020

e19301 Background: Over the last decade, multiple agents have demonstrated efficacy for advanced esophagogastric cancer (EGC). Despite the availability of later lines of therapy, there remains limited real-world data about the treatment attrition rates between lines of therapy. We sought to characterize the use and attrition rates between lines of therapy for patients with advanced EGC. Methods: We identified patients who received at least one cycle of chemotherapy for advanced EGC between July 1, 2017 and July 31, 2018 across 6 regional centers in British Columbia (BC), Canada. Clinicopathologic, treatment, and outcomes data were extracted by chart review. Patients who continued on treatment were censored at the date of last contact. Results: Of 245 patients who received at least one line of therapy, median age was 65.7 years (IQR 58.2-72.3) and 186 (76%) were male, ECOG PS 0/1 (80%), gastric vs. GEJ (36% vs. 64%). Histologies included adenocarcinoma (78%), squamous cell carcinoma (8%), and signet ring (14%), with 31% HER2 positive. 72% presented with de novo disease, and 25% had received previous chemoradiation. There was a high level of treatment attrition, with patients receiving only one line of therapy (n = 122, 50%), two lines (n = 83, 34%), three lines (n = 34, 14%), and four lines (n = 6, 2%). Kaplan-Meier survival analysis demonstrated improved survival with increasing lines of therapy (median overall survival 7.7 vs. 16.6 vs. 22.8 vs. 40.4 months, p< 0.05). On multivariable Cox regression, improved survival was associated with better baseline ECOG and increased lines of therapy ( p< 0.05). Conclusions: The steep attrition rates between therapies highlight the unmet need for more efficacious earlier-line treatment options for patients with advanced EGC. [Table: see text]
The impact of home hospice care on patients with hematologic disorder in Taiwana population-based cohort study.
Authors: Chang Yuehshih , Lai Chien-Hong , Wang Cheng-Hsu 
Published: May 2020

e19304 Background: The aim of the study is to examine the effect of home hospice care on quality of end-of-life (EOL) care for patients with hematologic malignancies in Taiwan between 2002 and 2011 by using the Taiwanese National Health Insurance Research Database. Methods: We enrolled patients with hematologic malignancies and lung cancer from the Longitudinal Cohort of Diabetes Patients database. For realizing the impact of home hospice care, those patients were divided into two groups, inpatient hospice care and home hospice care. Results: In Taiwan, 18.44 % patients with hematologic malignancies received hospice care and the ratio was similar with patients with lung cancer. Among those patients, 28.64% patient were able to receive home hospice care. The mean probability of survival was longer in the home-hospice group. Considering those indicators for the quality of hospice, blood transfusion and antibiotic use were significantly more frequent in the home hospice group. But the total cost for the last month for home hospice group was cheaper than inpatient hospice group. Conclusions: Hospice care for patients with hematologic disorder still need improvement. Receiving home hospice care in Taiwan did not decrease the survival life so to enroll the suitable patients for home hospice care are reasonable.
Study on deep vein thrombosis (DVT) risk factors at the time of cancer diagnosis in patients from the multicenter, prospective Cancer-Venous Thromboembolism (VTE) Registry.
Authors: Ohashi Yasuo , Ikeda Masataka , Kunitoh Hideo , Sasako Mitsuru , Okusaka Takuji , Mukai Hirofumi , Fujiwara Keiichi , Nakamura Mashio , Saito-Oba Mari , Kimura Tetsuya , Ibusuki Kei , Sakon Masato 
Published: May 2020

e19323 Background: Although the incidence of VTE is known to be high in cancer patients, many details of the frequency, risk factors, and management of VTE in patients with cancer remain unclear, especially in Asian populations. Methods: The multicenter, prospective, Cancer-VTE Registry study (UMIN000024942) aimed to clarify the actual status of VTE in cancer patients. The study enrolled patients diagnosed with colorectal, lung, stomach, breast, gynecological, or pancreatic cancer in Japan. Patients underwent VTE screening before initiating cancer treatment and were observed for 1 year. Registry objectives included the assessment of VTE prevalence and risk factors for VTE before initiating cancer treatment, real-world treatment of VTE, and frequency of new-onset events during the observation period. DVT screening was waived for those with a normal D-dimer level. Using a multivariate logistic regression model, we examined risk factors for DVT in cancer patients prior to initiating cancer treatment. Results: Of the 9726 patients enrolled, 3661 patients underwent DVT screening and 549 subjects were diagnosed with DVT. The risk factors for DVT among patients who underwent DVT screening (n=3661) are shown in the Table. Conclusions: The risk of DVT before initiating cancer treatment was clarified, and the factors strongly influencing DVT risk included age, sex, VTE history, D-dimer concentration, and hemoglobin concentration. [Table: see text]
Regorafinib outcomes from the population-based South Australian mCRC registry (SAmCRCR).
Authors: Price Timothy Jay , Piantadosi Cynthia , Townsend Amanda Rose , Padbury Rob , Roy Amitesh Chandra , Maddern Guy , Moore James , Karapetis Christos Stelios 
Published: May 2020

e19344 Background: Regorafinib has been shown to improve survival over BSC alone in large randomized trials. The median survival in the CORRECT study was 6.4 months and 12 month survival 24.3%. In Australia regulators have limited the use of regorafenib and patients are required to self-fund. Understanding the potential benefit of regorafenib in a real world non trial setting would be informative for consumers when considering self funding. Methods: The SAmCRCR collects all mCRC patients prospectively. The Registry was analysed for patients who had received regorafinib between February 2006 and December 2018. Survival was analysed using Kaplan Meier method. Results: Only 53 patients have received regorafenib therapy since February 2006. The median age was 66 (range 34-82). 66% were male, 66% had stage IV at diagnosis, 53% had liver only, 13% liver and lung and 6% lung only involvement. 75% were left sided. K/RAS was available in 35/53 patients, 49% WT. BRAF in 8/53, 25% MT. MSI measured in 14, and MSI-H 21%. Prior lines of treatment received: one 4%, two 9%, three 23%, four 26%, > four 37%. Prior biological use: bevacizumab 72%, anti-EGFR 100% (for RAS WT). Median survival from diagnosis was 3.3 years (95% CI 2.8-3.8 years). From start of regorafinib median survival was 7.1 months (95% CI 4.8-9.4 months) and12 month survival 28%. Conclusions: The outcome for those patients who do access regorafinib is in keeping with that reported from large randomized trials and thus clinicians can quote these outcomes when discussing access to regorafinib in the community.
Real-world outcomes among patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors versus immunotherapy or chemotherapy in first-line setting.
Authors: Simmons Daniel , DerSarkissian Maral , Shenolikar Rahul , Wang Min-Jung , Lax Angela , Muthukumar Aruna , Laliberté François , Duh Mei Sheng 
Published: May 2020

e19345 Background: While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the NCCN-recommended first-line (1L) therapy for non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutation (EGFRm), many pts initiate immunotherapy (IO) + chemotherapy (chemo) prior to receiving EGFRm test results. This study assessed clinical outcomes associated with initiating EGFR-TKI vs other therapies in stage IV EGFRm NSCLC. Methods: A retrospective study was conducted in adult pts with stage IV EGFRm NSCLC who initiated 1L EGFR-TKI, IO (+ chemo), or chemo alone from 5/2017-12/2018, using data from Flatiron Health. Treatment patterns were characterized with respect to timing of EGFRm test results. Kaplan-Meier analysis was used to assess the median duration of therapy (mDoT) and time to next therapy (mTTNT), as proxies for progression-free survival. Adjusted hazards ratios (HR) and 95% confidence intervals (CI) representing the effect of 1L therapy on the risk of discontinuing treatment or death (DoT) and risk of initiating second-line therapy or death (TTNT) were reported from multivariable Cox proportional hazards models controlling for differences in demographics, smoking history, histology, cancer stage, ECOG score, NCI index, and year of and time from diagnosis to 1L initiation, across treatment arms. Results: Among 593 study pts, mean age was 67.5 years and 65.4% were female. EGFR-TKI was used as 1L therapy for 77.2% of pts (n=458), IO in 13.3% (n=79) and chemo alone in 9.4% (n=56). 7.2% of EGFR-TKI pts, 54.4% of IO pts, and 57.1% of chemo pts initiated 1L before receiving EGFRm test results. Compared to pts on IO and chemo alone, pts on EGFR-TKI had longer mDoT (EGFR-TKI: 8.7 months [mo]; IO: 4.8 mo; chemo alone: 3.0 mo, p<0.01) and mTTNT (EGFR-TKI: 12.3 mo; IO: 6.5 mo; chemo alone: 4.0 mo, p<0.01). After adjustment, pts on EGFR-TKI vs pts on IO or chemo alone had significantly lower risk of discontinuing therapy or death (DoT) and initiating second-line therapy or death (TTNT) (see Table). Conclusions: A substantial number of stage IV EGFRm NSCLC pts initiated IO or chemo alone in 1L and EGFR-TKI was associated with better clinical outcomes than IO or chemo alone, highlighting the importance of adhering to NCCN-recommended therapy for these pts. [Table: see text]
Characterization of first-line use of cyclin dependent kinase 4/6 (CDK4/6) inhibitors in metastatic breast cancer among Florida health care systems.
Authors: Mahtani Reshma L. , Raez Luis E. , Unzaga Jessica , García Jorge J , Paranjpe Krupa , Arias Irene , Castrellon Aurelio Bartolome 
Published: May 2020

e19347 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered standard of care based on the compelling data across all landmark trials. Commission on Cancer (CoC) as well as the Quality Oncology Practice Initiative (QOPI) describe standards for cancer care; some of which include utilizing data for continuous quality improvement as well as using nationally recognized guidelines to drive treatment selection. Reducing unwarranted variations in care through tracking and reporting adherence to nationally-recognized guidelines can be one way to focus on improving quality metrics. We evaluate first-line real-world treatment patterns of HR+/HER2- mBC patients in three health care systems in south Florida and compare with national standards. Methods: A retrospective analysis utilizing pharmacy and medical claims data (commercial and governmental payers) was performed. The data source was the IQVIA anonymized patient longitudinal open claims data for patients treated at the south Florida health systems. Patients age ≥18 years with HR+/HER2- mBC were included. First-line treatment was defined as the first claim for a medication after the mBC diagnosis. Results: Characterization of treatment patterns in three cancer centers in south Florida showed an increased utilization of CDK4/6 inhibitors as compared to the national average across all groups (see table). Conclusions: These data provide a baseline assessment of the utilization of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- mBC. These data are reassuring with respect to the appropriate treatment in south Florida patients. However, we anticipate that treatment patterns may vary in other geographic areas given the national data trends. We would recommend this data be evaluated in other systems to identify potential areas of improvement. Limitations of this evaluation are consistent with any methodology using claims data which include possible coding errors and missing data which may or may not be systematic. [Table: see text]
Naloxegol for patients with cancer pain diagnosed with opioid induced constipation (OIC): NACASY observational study.
Authors: Davies Andrew , Tack Jan , Fernandez Ana , Chambers Jonathan , Sanz Juan Luis ,   on behalf of NACASY Study Group
Published: May 2020

e19350 Background: Opioids have been the cornerstone of analgesic treatment for severe chronic pain. OIC is the most commonly reported adverse effect associated with opioids, and compromises patient satisfaction and adherence to analgesic treatment and also quality of life. Naloxegol is a PEGylated derivative of the µ-opioid receptor antagonist naloxone indicated for the treatment of opioid-induced constipation (OIC) in adult patients who have had an inadequate response to laxatives. This real-world (RW) study (NCT03638440) aims to evaluate safety and efficacy of Naloxegol in patients with cancer pain diagnosed with OIC. Methods: This is a single-arm, multinational, prospective, RW observational study in adult subjects receiving treatment with opioids for at least 4 weeks, diagnosed with OIC that receive naloxegol in routine clinical practice. This study will recruit patients from 25 European hospitals. Data for efficacy are collected through the patient's diary during a 4-week period. Results: One hundred fifty-two patients, median age 66 years, 54% women, have been included in this analysis. Main cancer locations were lung (26%), breast (21%), prostate (10%), pancreas (9%) and head and neck (9%), and 67% had metastasis, mainly in bone (37%). Most frequent opioid treatments were fentanyl (29%), oxycodone (22%), and morphine (15%). Most frequent previous laxatives were osmotic (61%) and stimulant (27%) laxatives. Over 109 patients with at least one BFI score available after baseline, change in BFI score was ≥12 points in 61% of patients and 33% had BFI score <30 points after 4 weeks of treatment. There were statistically significant differences between baseline and final visit in BFI overall score as well as in the score of each of the three questions. Most common adverse reactions to naloxegol were abdominal pain (7.9%), diarrhea (2.6%), flatulence (1.3%) and nausea (1.3%), most of them grade 1-2. Eight patients had adverse reactions leading to study discontinuation: abdominal pain (5), diarrhea (2), intestinal perforation (1) and fatigue (1). Only one patient died due to an adverse reaction: intestinal perforation. Conclusions: Preliminary results show a promising efficacy of naloxegol in this RW treatment study. Toxicity profile was as expected. RW evidence seems to be a useful methodology to assess the real-life use of naloxegol and its efficacy in cancer patients.
Factors related to drug pipeline success for oncology companies using stock performance as a surrogate.
Authors: Ferris Matthew J. , Sun Kai , Savard Corey , Suresh Tejas , Mishra Mark Vikas 
Published: May 2020

e19405 Background: Developing oncology drugs demands substantial investment despite high uncertainty of success and ultimate market value. High drug costs have become subject to recent controversy. We sought to analyze factors influencing success in bringing new drugs to market using stock performance as a surrogate. Methods: Stock screeners and lists of initial public offerings (IPOs) captured small and mid-cap drug companies with share price ≥ $1.00 on major US indices. Share price was obtained from IPO to 03/09/2019. Company websites provided: headquarters (HQ) location, number/nature of drug programs (oncology vs. not, immunotherapy, gene editing, RNA-targeted, CAR-T). Funding to physicians and teaching hospitals (CMS funding) was acquired via CMS.gov Open Payments, and categorized into contributions < or ≥ $100,000. Stock performance was considered good (+ ≥25%), average (+/- 25%), or poor (- ≥25%). Univariate and multivariate associations were assessed for all companies; a subset analysis included only oncology-focused companies. Results: 420 companies were included. 101 companies (24%) had good, 76 average (18%), and 243 poor (58%) performance. Associated with performance in univariate analysis: IPO price ( P < 0.001), time from IPO ( P < 0.001), number of drug programs ( P = 0.019), and CMS funding ( P = 0.00013), with a strong trend for diverse pipelines that included both oncology and non-oncology programs ( P = 0.069). On multivariable analysis, IPO price was inversely associated ( P < 0.0001), while CMS funding ( P < 0.0001) and greater number of drug programs ( P = 0.0025) were positively associated with performance. Within the sub-analysis of oncology companies, 178 were included. 44 (24.7%) had good, 30 (16.9%) average, and 104 (58.4%) poor performance. The following were associated with performance on univariate analysis: IPO price ( P < 0.001), time from IPO ( P < 0.001), HQ location ( P = 0.009), diverse pipelines (P = 0.016), and CMS funding ( P < 0.001). On multivariable analysis, IPO price was inversely associated ( P < 0.0001), while California HQ location ( P < 0.01), diverse pipelines ( P = 0.028), and CMS funding ( P = 0.0002) were positively associated with performance. Conclusions: The majority of included companies had lackluster stock performance suggestive of low potential for drug success and high probability of financial disaster during development. Diverse pipelines and academic collaboration seem to be strongly related to success. This is the first study to demonstrate association between CMS funding and pharmaceutical stock performance.