bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early mortality in metastatic cancer: A SEER population data analysis.
Authors: Globus Opher , Sagie Shira , Lavine Noy , Barchana Daniel Itshak , Urban Damien 
Published: June 2021

e18789 Background: Overall survival from cancer has continuously improved over the last thirty years. This is due, in part, to advances in systemic treatment of some cancers resulting in clinically significant increases in long-term survival. Despite these improvements in long-term survival, many patients die quickly after a diagnosis of metastatic cancer, possibly being denied the opportunity to benefit from these recent advances in cancer treatment. To identify the scope and predictors of early mortality in de novo metastatic cancer, we analyzed population-based data, focusing on patients with early mortality. Methods: Using the Survival, Epidemiology and End Results (SEER) Database we analyzed adult patients who presented with de-novo metastatic solid malignancies diagnosed between 2008-2016. We defined early mortality as 1- and 2-month mortality. Factors associated with early mortality were analyzed including primary site of cancer and demographics. Correlations between categorical variables were analyzed with chi squared tests and survival data was derived from life tables using STATA I/C 12.1. Results: Of 519,553 patients identified, 273,976 (53%) were males, 411,041 (79%) were white, 213,325 (41%) had lung cancer, 65,679 (13%) colorectal cancer and 49,139 (10%) pancreatic cancer. One - and two - month cancer specific mortality was 12.4% and 22.5% respectively for the entire cohort. Mortality from cancer in the first two months after diagnosis decreased only marginally between 2008 and 2016 (23.4% and 21.6 %, respectively). Cancers with the highest 2-month cancer specific mortality rates were liver (39.5%), pancreatic (36.3%), lung (26.8%), gastroesophageal (23.7%), and urothelial (21.2%). Cancers with the lowest 2-month mortality rate were breast (10.4%) and prostate cancer (5%). Patients who presented with liver metastases had a clinically significant higher 2- month cancer specific mortality rate (29% vs. 18% p < 0.001), brain metastases were associated with a milder increase in 2-month cancer specific mortality (25%vs 21% p < 0.001) and bone metastases were not associated with a clinically significant difference in 2-month cancer specific mortality (22% vs 21%, p = 0.047). Other factors associated with early mortality included increasing age, low income, and living in a rural area. Conclusions: Over 21% of newly diagnosed metastatic cancer patients die within 2 months of their diagnosis, with little improvement over the last decade, rendering this an urgent unmet need in cancer care. Further research is urgently required to better identify the causative and treatable factors of early mortality in cancer patients.
Cancer therapy related dysphonia: Analysis of real-world FAERS data.
Authors: Wang Shuai , Kaur Anahat , Viteri Malone Mariuxi Alexandra , Elrafei Tarek N. , Steinberg Lewis , Kumar Abhishek 
Published: June 2021

e18794 Background: Dysphonia is a rare and under-reported adverse event. It is associated with the use of several cancer drugs. Dysphonia has been included as possible side effect on packet insert (PI) for some medications, like regorafenib, lenvatinib and axitinib. However, dysphonia has not been reported on multiple other drugs. We aimed to conduct a more comprehensive study to generate signal for dysphonia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of dysphonia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 41840 cases of dysphonia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 2996 cases. Dysphonia was reported as side effect of 30 medications. Some of the most common medications were regorafenib (n=463), cabozantinib (290), lenvatinib (178), axitinib (176) and palbociclib (126) as noted in Table. Dysphonia was not listed as adverse reaction on PI for cabozantinib, palbociclib, sorafenib and oxaliplatin. However, it has been reported for regorafenib, lenvatinib and axitinib. Median age at diagnosis was 66 years (interquartile range 59-73). Dysphonia was reported more commonly in males (51.5%) as compared to females (46.2%). Reactions were reported to the FDA more commonly by consumers (53.3% cases) as compared to healthcare professionals (44.5% cases). Conclusions: This study demonstrates signal of developing dysphonia in patients receiving certain cancer directed medications based on FAERS database. It is worth noting that some of the suspect medications identified in this study do not have dysphonia listed as known adverse effect on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and development of dysphonia. Detailed description of five drugs used for oncologic indications with highest reported cases of dysphonia as adverse effect.[Table: see text]
Incidence and severity of systemic allergic reactions (SAR) reported with chemotherapeutic drugs.
Authors: Thomas Beulah Elsa , Murugan Anju , Varayathu Hrishi , Sangi Lalram , Rani Sonia , Somayaji Shalaka , Mathew Smruthy Ann , Mathew Hephzibah Sara , Gupta Sunny Kumar , Kumar Dr Goutham , Tripathi Priyank , Mufti Suhail Sayeed , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah 
Published: June 2021

e18802 Background: SAR, a known adverse event of cancer therapy has variable severity. Despite the availability of many approved grading tools, there is still a lack of a globally applicable grading system. To address this, World Allergy Organization (WAO) created a uniform 5-grade classification system which was modified recently to be applicable for all SAR’s. This study aims to understand the incidence and severity of chemotherapy induced SAR and overall response rate (ORR) of rechallenged drugs in a tertiary cancer center. Methods: A retrospective single centered analysis of 103 patients with chemotherapy induced SAR was carried out. Patients were stratified based on age, gender, drugs given, dose number and severity of reaction. We used Modified WAO Grading System for assessing the severity. Descriptive statistics was applied to decipher the data. ORR is defined as the proportion of patients who have a partial or complete response to rechallenged drugs using RECIST Criteria for solid tumors and Lugano Classification for lymphoma. Results: Among 103 patients who reported SAR, 63.1% were female and 64.1% patients were less than 60 years of age. Among the 22 drugs, median dose number was high for Oxaliplatin (6) and Carboplatin (5). SAR was more observed with Paclitaxel (20.39%), Carboplatin (17.48%) and Rituximab (13.59%). However, carboplatin and rituximab had more incidence of grade 1 SAR(25.92% and 29.63% respectively). Grade 1 SAR (39.80%) were reported the highest followed by grade 3 (29.13%), grade 5 (13.59%), grade 2 (11.65%), and grade 4 (5.83%). Cetuximab precipitated the most grade 5 reactions (33.33%). Among patients exhibiting SAR with Paclitaxel, 42.86% were switched to alternatives, Nab-paclitaxel (28.57%) being preferred the most. Carboplatin was changed to cisplatin in 16.66% patients and Nanosomal docetaxel lipid suspension replaced docetaxel in 42.86% patients who reported SAR with carboplatin and docetaxel respectively. Rituximab was rechallenged the most (11.65%) off which one patient had reaction. ORR was observed to be 62.5% and 50% among rechallenged Paclitaxel and Rituximab respectively. The incidence of SAR is depicted in the below table. Conclusions: The study inferred that most SAR reactions occurred with Paclitaxel and Carboplatin. Oxaliplatin and Carboplatin presented with delayed SAR. Grade 1 and grade 3 reaction were relatively more. Cetuximab reported the most grade 5 reactions. ORR of rechallenged drugs should be monitored in further larger studies.[Table: see text]
Impact and predictors of readmission in hypercalcemia of malignancy: Findings of a nationwide analysis.
Authors: Baral Binav , Salazar Miguel , Prado Victor , Gauto Estefania , Upadhyay Shristi , Shrivastava Trilok , Chhabra Navika , Rosen Fred R. 
Published: June 2021

e18809 Background: Hypercalcemia of malignancy (HCM) is common in cancer. It is a sign of advanced malignancy and associated with poor outcomes. Although a well-known phenomenon, treatment options are limited and recurrence leading to readmissions is common, increasing morbidity and mortality. We attempt to explore the mortality, healthcare resource utilization, 30-day readmission rate and independent predictors of readmission for HCM. Methods: We queried the 2017 National Readmission Database (NRD) of adults readmitted within 30 days after index admission for HCM with a concomitant diagnosis of solid tumors. T test was used for continuous variables and chi square test was used for categorical variables. Multivariate regression was used to identify predictors for unplanned readmissions. Results: A total of 14,323 patients with solid tumors were admitted with HCM. The 30-day readmission rate was 24.9%. Common causes for readmission were sepsis, respiratory failure, hypercalcemia, distant metastases and AKI. At 30 days, readmitted patients were less likely to be discharged compared to patients admitted initially due to hypercalcemia (27.4 vs 30.8%; P<0.01). Readmitted patients had a higher in-hospital mortality at 30 days (1.5 vs. 0.1%; P<0.01), more incidence of chemotherapy induced pancytopenia (3.8 vs 2.5%; P<0.01), mechanical ventilation (5.8 vs 4.7%; P=0.05) and venous thromboembolism (8.3 vs 5.9%; P<0.01). Total economic burden of readmission was $251 million in total charges and $62.6 million in total costs. Adjusting for age and comorbidities, independent predictors of readmission were anemia of chronic disease, iron deficiency anemia and obesity. Conversely, predictors for lower odds of readmission were disposition to skilled facility and discharge with home health care services (Table). Conclusions: Nationally, HCM has a high rate of readmissions with increased morbidity and mortality making it a consequential healthcare burden. Among causes of readmission, potentially targetable include AKI and sepsis while among readmission predictors, iron deficiency anemia and anemia of chronic disease warrant further attention. Similarly, negative predictors highlight the importance of proper disposition planning and supportive care in malignancy.[Table: see text]
Patient and caregiver experience with an online, open-access, standardized, evidence-based, cancer drug and supportive care educational platform.
Authors: Gilreath Jeffrey A , Stuart James A. , Wilds Brandon , Lo Mimi , Greenly Anthony , Liu Haopeng , Stenehjem David D. 
Published: June 2021

e18811 Background: An open-access, web-based platform was developed to provide standardized, evidence-based information, that is cancer regimen-specific and supportive care focused. Online content was provided in the English language only for more than 200 anti-neoplastic regimens. A survey was conducted to determine reasons adult patients and their caregivers seek internet-based cancer drug information, and to evaluate if there is an unmet need for improved oncology therapy education. Methods: Between February 2020 and January 2021, patients and caregivers completed an online anonymous, English language survey deployed on the website www.chemoexperts.com. Results: A total of 1,021 website users responded. The majority of users were from North America (75%). Female respondents comprised 65% of the population and users self-identified as being a patient (67%), or family member/caregiver (33%). The mean age of respondents was 60.7 years (+ 16.2). Roughly two-thirds (66.4%) had a college degree. The majority of respondents reported they were either currently receiving (59.6%), or planning to receive (27.4%) treatment, however patients of all education levels, and in all phases of treatment (before, during, and after) sought online drug information. Clinical drug information education was reportedly provided by a doctor (68.9%), nurse (40.9%), physician assistant or nurse practitioner (23.8%), or pharmacist (15%), while 23% did not receive any education from clinical staff. Modes of education received by participants included printed material (73.9%), teaching in person (52.3%), and/or other internet sites (27.5%). Reasons for visiting the website were reported as follows: seeking additional information (92%), did not know what questions to ask (12%), looking at treatment alternatives (10%), forgot to ask questions (5%), not enough information given (11%), not enough time to ask questions (5%), and afraid to ask questions (2%). Respondents could mark all reasons. Among content sections, the percentage of users reported the side effect section as being the most useful. However, section usefulness varied based upon age, phase of treatment, and baseline education level. Overall, 86% reported finding the information they were looking for on the website. Conclusions: The majority of respondents received education from a health care provider, but not all. It is possible that the current pandemic prevented some patients from receiving education when in-person teaching was not available. However, many patients and caregivers still use the internet to seek additional drug information. These data highlight a continued unmet need for patients using online sources when searching for cancer drug and supportive care information. Further work is required to determine whether supplemental online, education can improve outcomes while reducing adverse effects.
Does the precision oncology medicine development pathway deliver value for health systems?
Authors: Henderson Raymond , French Declan , Stewart Elaine , Smart Dave , Idica Adam , Clark Jordan , Eckstein Markus , Lawler Mark 
Published: June 2021

e18818 Background: While there is increasing evidence that precision cancer medicines (PCMs) can be more effective than “one-size-fits-all” (OSFA) oncology medicines, questions persist as to their cost, availability, and overall patient benefit. We determined whether using a PCM approach to medicines discovery/development delivers medicines within cost constraints of health systems. R&D costs of developing a medicine are a subject of debate, with average estimates ranging from $314 million (M) - $2.8 billion (B). Methods: Data on oncology medicines approved (2011-2020) by the US Food and Drug Administration (FDA) were analyzed, employing two approaches to estimate R&D costs to bring the medicine to market: (i) Securities and Exchange Commission (SEC) data were compiled from 10-K and 10-Q financial performance filings on the medicine’s development cost through its R&D lifetime. (ii) Employing a base figure of $100,271 (the estimated cost per patient in a phase III clinical trial), costs were calculated, based on data from clinicaltrials.gov. Trial data were split into clinical trial phases and probability of trial success calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and if appropriate an orphan drug tax credit (ODTC) was subtracted from the total. Results: 19 PCMs and 11 OSFA oncology drugs listed by the National Cancer Institute which had complete data were analyzed from 22 companies (Table). Initial costs from SEC data suggest a 50% reduced development spend for PCM, ($605M; range = $181M-$1.1B) (Clinical Trial Modelling Analysis: $604M ($63M-$2.29B)), compared to an OSFA oncology drug development spend ($877M; $333M-$3.34B) (Modelling Analysis: $597M ($41M-$1.64B)). Once preclinical costs were added total R&D costs capitalized and ODTC subtracted, there was an 83% increase in costs, from $2.44B ($614M-$5.23B) (Modelling Analysis: $3.1B ($209M-$11.52 B)) for PCMs to $4.46B ($1.59-$14.9B) (Modelling Analysis: $3.92B ($282-$12.74B) for OSFA oncology drugs. SEC data are more accurate, as they capture real data, rather than modelling assumptions. Conclusions: Our results provide an estimate of the R&D spend required to bring an oncology medicine to market. R&D cost of a PCM is below the top range of prior estimates published, while R&D cost of an OSFA oncology medicine is almost twice the cost of a PCM, emphasizing the potential for PCM treatments to deliver care at greater value to patients and health systems.[Table: see text]
Prevalence-adjusted trends in U.S. healthcare spending on colorectal cancer, 1996-2016.
Authors: Stukalin Igor , Ahmed Newaz Shubidito , Fundytus Adam Michael , Singh Siddharth , Ma Christopher 
Published: June 2021

e18819 Background: Colorectal cancer is rising in prevalence and associated with high healthcare costs. We estimated trends in the US healthcare spending in patients with colorectal cancer between 1996 and 2016. Methods: We used data on national healthcare spending developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. Corresponding US age-specific prevalence of colon cancer was estimated from the Global Burden of Diseases Study. Prevalence-adjusted, temporal trends in the US healthcare spending in patients with colorectal cancer, stratified by age groups ( < 20, 20-44, 45-64, >65) and by type of care (ambulatory, inpatient, emergency department, pharmaceutical prescriptions, nursing care and government administration) were estimated using joinpoint regression, expressed as annual percent change (APC) with 95% confidence intervals. Results: Overall, annual US healthcare spending on colorectal cancer increased from $8.85 billion (95% CI $8.17 billion, $9.53 billion) in 1996 to $10.5 billion (95% CI $9.35 billion, $11.7 billion) in 2016, with total costs increasing by 0.9%/year (95% CI 0.1%, 1.6%). After adjusting for colorectal cancer prevalence, the absolute per capita spending decreased from $8848 to $8427 and there has been no significant change over time (APC 0.3%, 95% CI, -0.2%, 0.8%). However, spending in patients > 65 decreased significantly by 1.3%/year (95% CI -2.2%, -0.5%). Inpatient care was the largest contributor to total colorectal cancer-related expenditures: in 2016, 65.9% (95% CI 59.5%, 71.0%) and 19.7% (95% CI 14.8%, 25.8%) of the total cost were spent on inpatient care and ambulatory care, respectively. Between 1996-2016, increases in the price and intensity of care (defined by the cost per encounter) was the largest positive driver of changing healthcare spending, accounting for $5.02 billion ($2.60, $7.33 billion). Conclusions: After adjusting for rising prevalence, US healthcare spending on colorectal cancer has not changed significantly since 1996, while the per capita cost continues to decrease, primarily in patients > 65 years old. Inpatient care accounts for the majority of colorectal cancer-related expenditures.
U.S. budget impact analysis of biosimilar versus originator intravenous rituximab for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
Authors: James Elizabeth , Trautman Holly , McBride Ali , Choudhry Azhar , Thompson Stephen 
Published: June 2021

e18820 Background: Rituximab-abbs is an anti-CD20 monoclonal antibody and an important immuno-oncology agent for the treatment of B-cell malignancies NHL (diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma [FL]) and CLL. It is also indicated for patients with RA, GPA, and MPA. Rituximab-abbs was the first rituximab biosimilar approved in the US and is expected to reduce drug acquisition costs. This budget impact model (BIM) estimated the impact of replacing a share of originator rituximab (IV-R-REF) use with rituximab-abbs (IV-R-BIOSIM) for NHL (DLBCL and FL), CLL, RA, GPA, and MPA. The objective was to project incremental annual cost differences between IV-R-BIOSIM and IV-R-REF for a hypothetical 1-million-member US healthcare insured (Medicare) population. Methods: An illustrative BIM estimated changes in 1-year drug and administration costs for an increased IV-R-BIOSIM uptake from 17.5% to 22.0%. Values for epidemiology, market share distribution, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Dosing was based on a mean patient body surface area of 1.8 m2. Annual dose counts per patient were: 10 untreated FL with maintenance; 8 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 6 CLL, and 4 for RA, GPA, or MPA. All treatments were assumed to infuse over 3 hours. Drug acquisition and administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. Patient cost share was based on 2020 Medicare Part B 20% cost-share for office visits and drug products. Univariate sensitivity analyses were conducted. A scenario analysis was performed to project 2-year costs for extended FL maintenance treatment. Results: Estimated total annual plan incremental savings for a 1-million-member payer after the utilization shift were $312,379, equating to $0.31 per enrolled member per year (PMPY). Per-patient incremental drug cost savings with IV-R-BIOSIM for 1-year were $5,474–$12,924 (Table). The model was most sensitive to IV-R-REF cost and proportion of patients with RA. Conclusions: This analysis estimated annual savings of over $310,000 ($0.31 PMPY) for a 1-million-member US payer following a 4.5% utilization shift from IV-R-REF to IV-R-BIOSIM, demonstrating that IV-R-BIOSIM may confer considerable economic benefits vs originator rituximab.[Table: see text]