bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of reimbursement (R) for next generation sequencing (NGS) on patients' tumors in the context of a personalized medicine program.
Authors: Brown Thomas D. , Tameishi Mariko , Liu Xiaoyu , Scanlan James , Beatty J. David , Drescher Charles , Pagel John M. , Gold Philip Jordan , Alexander Shlece , Summers Lauren K. , Brindle Madeleine , Varghis Nina , Yates James , Fondren Kathleen N. , Birchfield George Richard , Dong David Edwin , Benkers Tara L. , Wahl Tanya A. , Ramsey Scott David , Berry Anna Belinda 
Published: September 2018

6506 Background: R policies for NGS testing vary widely among private and public insurers. While drug costs are the greatest challenge in personalized or precision medicine, cost and R are substantial barriers to genomic profiling with NGS. We examined variation in coverage and R for a cohort of cancer patients (pts) treated at a tertiary oncology center. Methods: An Institutional Review Board approved prospective registration protocol was activated with the objective of establishing a centralized longitudinal clinical, molecular phenotypic, and research data repository for pts diagnosed with cancer. Based on provider assessment of medical necessity, mutations in 68 cancer associated genes were analyzed. Evaluation of R for NGS was performed from Sept, 2014 through Jan, 2017, with use of CPT code 81455. R was analyzed based on: payer type; pt age; localized vs. metastatic disease; and actionability of data. Results: 588 pts with evaluable analytic cases, and NGS testing, with R results shown in the table below. For groups with >= 10 pts: R frequency was highest in managed care programs, either private or Medicare, and least frequent in non-HMO Medicare (p<.001). In pts receiving R, payments by private HMOs were highest (p<.02). NGS results with labelled drug indications were associated with less frequent R (26% vs. 35%; p<.05), and lower payments (mean of $358 vs. $567; p<.02) compared to other NGS results. Younger age was associated with more frequent R (38% in pts <60 years, 24% in pts >= 60 years; p<.005). Neither cancer diagnosis nor stage were significantly associated with R. Conclusions: One third of pts received some R for NGS testing. R was more frequent and higher in managed care programs, both private and Medicare. R was more likely for younger age pts, while actionable NGS results were associated with lower R. These data demonstrate the need for rational, transparent, and consistent R policies, along with a value-based R model for NGS across all payer groups. [Table: see text]
The impact of positive SWOG treatment trials on population survival.
Authors: Unger Joseph M. , LeBlanc Michael Leo , Blanke Charles David 
Published: September 2018

6513 Background: Recently, tremendous prominence has been given to the investigation of the impact of different research processes as part of the Cancer Moonshot. More than half a century ago, the National Cancer Institute (NCI) established a network of publicly-funded cancer cooperative research groups to systematically advance the science of clinical trial research and the evaluation of new treatments for efficacy and safety. Our objective was to examine the extent to which positive NCI-sponsored cancer treatment trials have benefited cancer patients in the U.S. population. Methods: We used study data from SWOG, an NCI-sponsored Network cooperative research group. We identified all treatment trials over SWOG’s 60-year history (1956-2016) for which the new experimental therapy provided a statistically significant improvement in overall survival. We assumed the new, proven treatments from these trials established new standards for care in the treatment community. Twenty-three treatment trials were identified from a variety of difference cancer types. We estimated population life-years gained from the trials through 2015 by mapping the impact of the new treatments onto the U.S. cancer population, using an area-under-the-survival-curve approach that combined trial-specific hazard function and hazard ratio results with SEER and life-table data. Calculations were age-adjusted. Dollar return on investment was estimated as the ratio of total investment by the National Cancer Institute in the SWOG treatment trial program divided by the estimate of life-years gained. Results: In total, 12,361 patients were enrolled to the 23 positive trials from 1965-2012. We estimated that 3.34 million years of life were gained through 2015. Estimates were greater than 2 million life years gained under 95% of model simulations. The dollar return on investment was $125 per life year gained. Conclusions: SWOG treatment trials have had a substantial impact on population survival for cancer patients over 60 years. The National Cancer Institute’s investment in its cancer cooperative group research program has provided exceptional value and benefit to the American public.
Cancer drug assessment: What is driving high clinical added value in France?
Authors: Fernandez Judith , Grande Mathilde , Dahmani Bachir , Stanel Sorin , Galbraith Margaret , Albin Nicolas , Belorgey Chantal , Guillevin Loic , d'Andon Anne 
Published: September 2018

6526 Background: Concerns about the increase of cancer drug prices emphasized the need to base pricing decisions on clinical added value (CAV). In France, the CAV assessment is done by the National Authority for Health (HAS) on a 5-point scale based on clinical data. The magnitude of the CAV is partly used by the economic committee for healthcare products to determine drugs prices: a major to moderate CAV leads to the highest prices. Recognizing the importance of presenting clear statements, we analyzed which criteria are taking into account for CAV appraisal. Methods: A retrospective and descriptive study analysis of all new hematology/oncology cancer indications assessed by HAS between 2010 and 2015 has been conducted. For each appraisal, information regarding the level of evidence and clinical effect has been collected. Results: 78 new cancer indications (58 drugs) have been assessed: 20 had a major to moderate CAV (25%), 32 a minor CAV (41%) and 26 no CAV (33%). The percentage of major to moderate CAV was higher when a comparative pivotal trial was conducted (25%, 16/62 vs. 20%, 4/16). Among the 62 comparative trials, 58 had a superiority design (94%) supporting a major to moderate CAV in 27% (16/58) of the cases. Overall survival (OS) was measured in 91% of the pivotal trials (n = 71) and in 24% (n = 19) as a primary outcome. A higher proportion of major to moderate CAV were observed in trials using OS as a primary endpoint (31%, 6/19) than progression free survival (PFS) (23%, 9/39) or response rate (25%, 5/20).When a major to moderate CAV was obtained, a median absolute gain of 4 and 8 months for OS and PFS respectively were observed. All non-inferiority or non-conclusive designs led to no or minor CAV whatever the quantity of clinical effect. Conclusions: CAV is assessed in a two-step process where clinical effect is taken into account when level of evidence is appropriate. Consequently, there is not a unique profile of outcomes supporting a major to moderate CAV but a combination of several key elements such as study design, primary endpoint, and statistical significance. HAS appraisals remain multi-factorial, and medical need add a nuance to HAS expectations in terms of level of evidence.
Communication about immunotherapy: Barriers and information to discuss.
Authors: Gillespy Kristen , Dixon Margie D , Pentz Rebecca D. 
Published: September 2018

6543 Background: Since immunotherapy is a promising new therapeutic approach to cancer treatment, improving physician/patient communication about this approach is important. No communication guidelines exist. To begin to fill this gap, we identified provider and patient preferences for information, and identified barriers to communication about immunotherapy. Methods: We qualitatively interviewed 15 oncology professionals who offer immunotherapy treatment about the information they deemed important to communicate to patients and the communication barriers. After a discussion about immunotherapy options with a provider, we interviewed 18 oncology patients about the information that was most useful to them and their impressions of immunotherapy. We captured impressions on two 1-5 scales with 5 being ‘very positive impression’ and ‘very likely to be cured’ and by picking words from a list of positive and negative terms like ‘effective’ and ‘risky.’ All open-ended questions were qualitatively coded. We reached saturation of themes with 18 patients. Results: Patients identified 4 useful topics to discuss: treatment options, benefits, treatment logistics, and side effects. Providers identified 3 topics important topics to convey: side effects, realistic view of benefit and treatment logistics. The most frequently provider-identified barrier to communication was patients’ baseline misconceptions about immunotherapy’s effectiveness. Supporting this, patients’ impressions were very positive (average of 4 on impressions scale and 3.9 on potential to be cured scale.) The most frequently chosen word patients chose to describe immunotherapy treatment was ‘hopeful’ (10/18 55%). Conclusions: There is largely agreement on the important topics to discuss about immunotherapy, though half of the patients thought a discussion of treatment options would be useful and only one physicians mentioned options. Of note, communication is hampered by patients’ preconceptions about immunotherapy’s effectiveness. Communication guidelines should identify techniques to effectively overcome this barrier.
Temporal trends in the intensity and duration of oncologic care among colorectal cancer (CRC) patients (pts).
Authors: Chen Leo , Spinelli John Joseph , Cheung Winson Y. , Kennecke Hagen F. 
Published: September 2018

6552 Background: Substantial advances in therapy of CRC pts occurred between 2000 and 2012 contributing to a significant increase in overall survival. The objective of this study is to quantify the change in treatment (tx) intensity as measured by clinic and tx visits at a network of medical and radiation oncology clinics. Methods: Electronic scheduling records of stage I-IV CRC patients referred between 2000-2012 to the six oncology centers comprising the British Columbia Cancer Agency were reviewed and stratified by tx phases: I and II (adjuvant first 6 months, continued), III and IV (palliative first 6 months, continued), and V (last 6 months of life). Clinic Visit Intensity (CVI), Chemo Tx Intensity (CTI), number of chemo agents and number of cycles (CC), Radiotherapy (Rx) courses (RC) and fractions (RF) were measured, and trends by referral year were modelled using zero inflated negative binomial regression. Mean duration of visit for chemo tx (CHD) and clinic visits (CVD) were modelled using linear regression. Sex, age at diagnosis, stage, income, and community size were included in models if terms were significant. Results: 15,157 pts were included across 10 cohorts. CTI and CC increased significantly in tx phases II-V with later year of referral, while phase I results were stable or decreased, likely due to the substitution of oral for intravenous regimens. Rx increased only in advanced phases. Mean duration of scheduled time showed significant increases. Conclusions: CRC pts referred in 2012 vs 2000 receive significantly greater intensity and duration of care in tx phases II-V. Results have significant implications for resource allocation and the patient experience. [Table: see text]
Global Cancer Institute multidisciplinary tumor boards as a tool to improve patterns of clinical practice for breast and gynecologic cancer in resource-limited settings.
Authors: St. Louis Jessica , Bukowski Alexandra , Rodrigues Angelica Noguelra , Moreno Joel , Ferreyra Mayra , Lopes Andre , De La Serna Frances , Tindwa Chakou Halfani , Mollah Obayedullah Baki , Villarreal-Garza Cynthia , Duarte Carlos , Hambardzumyan Vahagn , Salman Pamela , Soria Tannia , Goss Paul E. 
Published: September 2018

6556 Background: Multidisciplinary tumor boards (MTBs) are commonly practiced in high-income countries (HICs) to ensure adherence to guidelines through a team approach to patient care. The Global Cancer Institute (GCI) established online MTBs in 2012 to facilitate live telemedicine discussions of breast and gynecologic case scenarios between specialists in low- and middle-income countries (LMICs) and expert specialists in HICs. GCI MTBs aim to improve clinical knowledge and patterns of practice for specialists in LMICs through an interactive online forum. Methods: In each monthly MTB, three patient case scenarios are presented by specialists in LMICs for live discussion with an expert panel of specialists based in HICs. Guideline or clinical trial-based discussions are held for each case scenario. Best practices for clinical care in limited resource settings are also discussed. Links to clinical practice guidelines, clinical trials, and resources are provided to all MTB attendees. For educational purposes, each MTB is live streamed and uploaded to a private YouTube channel for viewing by community oncologists and trainees worldwide. Results: The GCI MTBs program has recruited over 500 LMIC participants from 48 hospitals in 24 countries across Latin America, Eastern Europe, Africa, and Asia. 17 expert breast cancer specialists and 13 expert gynecologic cancer specialists provide multidisciplinary guidance. To date, 130 breast cancer case scenarios and 80 gynecologic cancer case scenarios have been presented. For breast MTBs, 73% of case scenarios were invasive ductal carcinomas. Common subtypes presented were ER/PR+ (63%), HER2+ (30%), and triple negative disease (28%). 56 cases involved advanced disease management (43%). For gynecologic MTBs, common gynecologic cancer case scenarios were cervical (74%) and ovarian (15%). 37 cases involved advanced disease management (46%). Conclusions: GCI MTBs are a useful educational tool for specialists in LMICs to improve patterns of clinical practice and engage in multidisciplinary discussions. GCI continues to expand its MTBs to cancer facilities in LMICs.
Difference in cardiovascular disease incidence by sociodemographic factors in adolescent and young adult (AYA) cancer survivors.
Authors: Keegan Theresa , Kushi Lawrence H. , Li Qian , Brunson Ann , Malogolowkin Marcio H. , Wun Theodore 
Published: September 2018

6565 Background: AYA cancer survivors are at increased risk of developing cardiovascular disease (CVD) compared to AYAs without a history of cancer. In AYA cancer survivors, few population-based studies have focused on CVD risk and none have considered whether the occurrence of CVD differs by sociodemographic factors. Methods: Analyses focused on 64,918 patients aged 15-39 y at diagnosis for one of 14 first primary cancers during 1996-2010 and surviving > 2 years after diagnosis, with follow-up through 2013. Data were obtained from the California Cancer Registry and State hospital discharge data. CVD included coronary artery disease, heart failure, and stroke. We estimated the cumulative incidence of developing CVD, accounting for death as a competing risk, stratified by race/ethnicity, neighborhood socioeconomic status (SES) at diagnosis, health insurance status at diagnosis/initial treatment and cancer type. We examined the impact of CVD on mortality using multivariable Cox proportional hazards regression with CVD as a time-dependent covariate. Results: Overall, 2374 (3.7%) patients developed CVD, and 7690 (11.9%) died over the follow-up period. Survivors of acute myeloid leukemia (12.6%), acute lymphoid leukemia (11.1%), central nervous system cancer (9.0%) and non-Hodgkin lymphoma (6.0%) had the highest incidence of CVD at 10-years. Incidence was significantly higher among Blacks (6.7%) at 10-years than non-Hispanic Whites (3.0%), Hispanics (3.7%) and Asian/Pacific Islanders (3.7%) (p < 0.001). AYA survivors with public or no insurance (vs private) had a higher 10-year incidence of CVD (5.8% vs 2.9%; p < 0.001), as did survivors residing in low (vs high) SES neighborhoods (4.1% vs 2.7%; p < 0.001). These sociodemographic differences in CVD incidence were apparent across most cancer sites. The risk of death was increased by five-fold or higher among AYAs who developed CVD. Conclusions: AYA cancer survivors who were uninsured or publicly insured, of Black race/ethnicity, or who resided in lower SES neighborhoods are at increased risk for developing CVD and experiencing higher mortality. The proactive management of CVD risk factors in these subgroups may improve patient outcomes.
Differences in mortality among patients with acute leukemia admitted on weekends as compared to weekdays.
Authors: Parikh Kaushal , Shah Mahek , Mehta Dhruv , Liu Delong 
Published: September 2018

6576 Background: The association between weekend admissions and patient outcomes has been widely reported for several acute illnesses. However, this is the first study using a nationwide database to focus on outcomes of weekend admissions for acute leukemia. Methods: We used the 2002-2012 Nationwide Inpatient Sample Databases to identify patients admitted with a diagnosis of acute leukemia. Admissions were identified as weekend or weekday admissions and rates of mortality, in-hospital complications, existing comorbidities, and demographic differences were assessed. Adjusted logistic regression models were used to analyze mortality and complication outcomes. Results: Out of a total of 71,392 patients included in the analysis, 12,234 (17.1%) patients were admitted over the weekend. While there has been a general decline in admissions and mortality in acute leukemia from 2002-2012, mortality was 18.8% for weekend admissions and 16.3% for weekday admissions (p < 0.001). Weekend admissions independently predicted higher mortality (adjusted odds ratio 1.128, 95% confidence interval, 1.06 to 1.20; p < 0.001). These patients were also less likely to receive an early bone marrow biopsy than their weekday counterparts (45% vs 26.5%; p < 0.001). Bone marrow biopsy was independently associated with a reduced in-hospital mortality (aOR 0.395, 95% CI 0.373 to 0.417; p < 0.001). Admissions to teaching hospital were also associated with a lower mortality (aOR 0.890, 95% CI 0.845 to 0.936; p < 0.001). Weekend admissions were also more likely to have in-hospital complications than weekday admissions (52.4% vs 50.5%; p < 0.001). Conclusions: There was a significantly increased mortality among acute leukemia patients admitted on a weekend. Our study suggests that patients admitted over the weekend may be clinically sicker or receive inferior care than weekday admissions. We also conclude that patients admitted to teaching hospitals have a better outcome and emphasize the importance of availability of resources and early presentation to tertiary care centers.
Financial impact of flat dosed (FD) monoclonal antibodies (MABs) at a single institution in 2016.
Authors: Kane Michael P. , Silk Ann W. , Lee Fuwing , Auriemma Paul , Mehnert Janice M. 
Published: September 2018

6617 Background: Immuno-oncology (I/0) agents represent an important, accelerated breakthrough in cancer therapy. Like other MABs, these agents have been adjusted after FDA approval to have a flat-dose. Purportedly, flat dosing simplifies prescribing, dispensing, inventory and billing. Nivolumab (N) and Pembrolizumab (P) achieved FDA approval in several malignancies. Original studies determined the dosing of N @ 3 mg/kg q2-weeks and P @ 2 mg/kg q3-weeks. Based on simulations from population pharmacokinetics models, the FDA approved a FD of N 240 mg in melanoma, RCC and NSCLC. The financial impact of this FD methodology in our patient population was compared with weight based dosing (3mg/kg) of N with a cap of 240 mg versus flat dosing. The potential impact of this change was also evaluated for P, including if a 50 mg vial of P was still available. Methods: Applicable dispensed doses (N & P) and patients’ weights for 2016 were mined from the electronic health record. Wholesale Acquisition Costs at end of year were used for financial comparison. Results: see table. Conclusions: Weight based dosing with a cap (N 240mg; P 200mg) versus flat dosing would have saved $198,567 and $80,037, respectively. Additionally, $760,351 would have been saved if 50 mg vials of P were available. With the current drug pricing structure, wide-scale adoption of flat dosing for I/O mABs may result in higher drug costs. Labeling I/O mABs with both weight-based and FD options and ensuring the availability of proper vial sizes, particularly multi-dose vials, to fit the population and dosing schema would restrain the costs of care. [Table: see text]
Price trajectories assessment for Medicare Part B generic anti-cancer drugs.
Authors: Gordon Noa , Ben-Aharon Omer , Stemmer Salomon M. , Greenberg Dan , Goldstein Daniel A. 
Published: September 2018

6624 Background: Patented anti-cancer drugs launch prices have increased in recent years with subsequent increases after launch. Recently, large price increases of generic drugs were at the center of public attention in the United States. Our aim was to assess price changes with time for Medicare part B anti-cancer generic drugs and to understand how drug characteristics and market structure influence price trajectories. Methods: We included all Medicare part B anti-cancer drugs with price reported in both 2006 and 2016. Patent expiration dates were attached using the Medicare Drug Patent Expiration engine and drugs with a patent expiration date later than 2006 were excluded. Generic manufacturers' FDA approvals for each drug were extracted from the FDA Orange Book. For each drug we extracted the Average Sales Price (ASP) history from October 2006 to October 2016, published by the Center for Medicare and Medicaid services (CMS). Prices were adjusted for inflation, using information obtained from the United States Department of Labor. For each drug we calculated the cumulative ASP change during the follow-up period. Data were analyzed using IBM SPSS Statistics software. Results: We identified 31 anti-cancer generic drugs that met the inclusion and exclusion criteria. During the follow-up period, 15 (48%) drugs had increases in price (median 139%, range 18-2632%). Seven (23%) drugs increased by more than 200% (Table 1). Both gradual price and acute price increases were observed. Some of the drugs which had substantial price increases had no market competition market. Conclusions: Generic drug prices may change substantially with time. Gradual or rapid price increases may be due to lack of generic drug competition, substitution shortages or marketing reasons. New regulations may be needed to prevent further increases in generic drug costs, while balancing the need to maintain financial incentives for drug production and competition. [Table: see text]