bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of germline polygenic risk for thyroid autoimmunity with overall survival in the I-SPY2 Trial.
Authors: Fergus Kirkpatrick B , Middha Pooja , Quandt Zoe , Shieh Yiwey , Basu Amrita B , Sayaman Rosalyn , Pohlmann Paula R , Yee Douglas , Shatsky Rebecca Arielle , Isaacs Claudine , Campbell Michael J. , Hirst Gillian L. , Brown Swigart Lamorna , van 't Veer Laura , Ziv Elad , Esserman Laura 
Published: June 2024

10600 Background: Germline genetic variation influences immune activity and risk of autoimmunity, and has been hypothesized to play a role in response to cancer therapeutics and survival. Prior studies of breast cancer have reported associations between genetic variation in thyroid autoimmunity and overall survival (OS). Here, we aim to investigate the association between a polygenic risk score for hypothyroidism (PRS-H) and response to therapy in women with early-stage breast cancer, and hypothesize that high PRS-H will be associated with better treatment response and survival. Methods: This study includes 1,368 women aged 18 years and above with stage II-III breast cancer of size > 2.5cm by clinical exam, with germline data available. It is an approved biomarker analysis of the I-SPY 2 trial, which is a phase II, adaptive, randomized platform trial across multiple sites studying novel cancer therapeutics across multiple arms for use as neoadjuvant chemotherapy for early-stage breast cancer. The outcome of survival is defined as alive at the most recent follow-up. Using the Cox proportional hazards model, we evaluate the association between a previously published PRS-H and overall survival. Models are adjusted for age at screening, immunotherapy status, and five principal components. Results: Among 1,368 early-stage breast cancer women, 33% (n=447) had pCR, and 85% (n=1,157) were alive at the last follow-up. Additionally, 16% (n=219) of women received immunotherapy. We observe a significant association between PRS-H and OS (HR = 0.78, 95% CI 0.66-0.92, p=0.004). Individuals in the top 10th percentile of the PRS-H (highest genetic risk) have improved survival (log rank p=0.04). Conclusions: Germline genetic variation in thyroid autoimmunity proclivity is associated with improved overall survival in our cohort of women with early-stage breast cancer receiving neoadjuvant chemotherapy. Our findings suggest that the genetic risk for autoimmunity may be important for long-term survival. We will expand this analysis to include the entire I SPY 2 population when all patients have completed genotyping. We plan to further characterize the role of germline autoimmunity profiles and survival. Clinical trial information: NCT01042379 .
State mandatory paid medical leave policies and cancer stage at diagnosis in US adults.
Authors: Kohut-Jackson Abigail , Barnes Justin Michael , Chino Fumiko , Zheng Zhiyuan , Han Xuesong , Johnson Kimberly J. , Yabroff Robin , Johnston Kenton J 
Published: June 2024

11008 Background: Since 2012, several states implemented mandatory paid medical leave policies. Mandatory paid medical leave may alleviate time and financial burdens, enabling patients to undergo screening and/or timely diagnostic workup for new cancer-related symptoms. These policies have been associated with increased cancer screening. We investigated whether state mandatory paid medical leave policies were associated with stage at cancer diagnosis. Methods: Adults ages 18-64 years diagnosed with cancer from 2010-2019 were identified from the Surveillance, Epidemiology, and End Results program. Differences-in-differences (DID) analyses using the updated method of accounting for heterogeneity in policy enactment compared proportions of stage I and IV cancer diagnoses from pre- to post-policy implementation in states with vs. without paid medical leave policies. Analyses adjusted for age, sex, race, ethnicity, rurality, cancer site, county-level income, and time-varying state Medicaid eligibility levels. Since some cities enacted city-wide policies prior to state-wide implementation, cases from affected states between the time of city and state policy enactment were excluded. Sensitivity analyses were conducted excluding counties with cities that enacted paid leave policies. The plausibility of the parallel trends assumption was assessed by comparing stage at diagnosis between state groups in the pre-policy period and was satisfied for all reported results. Results: A total of 1,052,307 adults with cancer were identified. 39.8% and 19.7% of patients were diagnosed with stage I and IV cancers, respectively. In adjusted DID analyses, there was a 1.34 percentage point (PP) increase in stage I diagnoses and a 2.05 PP decrease in stage IV diagnoses associated with mandatory paid medical leave policy implementation (Table). Results were similar in sensitivity analyses. In subgroup analyses, policy-associated stage shifts were seen in males, Hodgkin lymphoma, and liver and lung cancers, with less clear patterns for cervix and pancreas cancers. Conclusions: State mandatory paid medical leave was associated with increased early-stage cancer diagnoses and decreased late-stage diagnoses. Paid leave policies may promote earlier detection of non-screenable cancers by enabling employees to promptly seek care for new cancer-related symptoms. Policies that improve opportunities to seek medical care may facilitate earlier cancer detection and ultimately contribute to better patient outcomes. [Table: see text]
Impact of trial eligibility criteria on enrollment to KRASG12C inhibitor trials in patients with non-small cell lung cancer.
Authors: May Michael S. , Wooster Margaux , May Benjamin , Shu Catherine A. , Henick Brian S. , Stoopler Mark , Smith-Marrone Stephanie , Saqi Anjali , Mansukhani Mahesh M. , Riely Gregory J. , Hershman Dawn L. , Herzberg Benjamin 
Published: June 2024

11012 Background: Clinical trials of novel therapies should enroll a population that reflects patients (pts) who might receive the drug upon FDA approval. In 2017 ASCO proposed modifications to common eligibility criteria (EC) to increase the generalizability of trial findings. Despite this, barriers to trial enrollment in the recent era of molecularly-targeted therapies are not well-characterized. We examined a cohort of non-small cell lung cancer (NSCLC) pts with KRAS G12C mutations to determine whether EC for trials of KRAS G12C inhibitors allowed enrollment of patients seen as part of routine care at an academic medical center. Methods: We extracted EC for Phase I-III trials among six KRAS G12C inhibitors: sotorasib, adagrasib, LY3537982 , divarasib, JDQ443 and RMC-6291. We retrospectively reviewed pts with NSCLC and G12C mutations detected on universal, NGS-based testing of NSCLCs at Columbia University Irving Medical Center (CUIMC) from 2020 to 2023. We defined dates of disease progression and evaluated pts for clinical trial eligibility for each line of treatment. Pts were deemed trial-eligible if they met all EC, borderline if they had 1 laboratory value < 20% from cutoff, or ineligible. The association between baseline factors including self-reported race, sex, and age with rates of eligibility were evaluated with chi-squared tests. Results: EC criteria for 14 trials were characterized. EC were similar across trials regardless of agent or phase and did not substantially change over time; 1 Phase III trial had expanded EC from the Phase I/II trials. Of 1172 patients with NSCLC, we identified 185 pts with G12C mutations (15%), including 69 pts with advanced or metastatic disease. Of these, 19% (13/69) would have been eligible for any G12C trial, 15% (10/69) were borderline, and 67% (46/69) were ineligible. 9% (6) would have qualified for only 1 of the trials. The most common reasons for ineligibility were poor performance status (54% [30/56]), excluded comorbidities (25% [14/56]), and renal dysfunction (27% [15/56]). Among patients who received therapy after FDA accelerated approval (N = 22), only 23% (5) would have been eligible for the related Phase III trial. Conclusions: Our findings suggest that most patients with KRAS G12C mutations would not have been eligible for relevant trials, including > 75% of patients who received KRAS G12C inhibitors off-trial after accelerated FDA approval. EC did not expand after early phase trials demonstrated evidence of safety. These data should guide sponsor and FDA considerations in the development of trial protocols for targeted therapies, as fewer barriers to trial participation would enable trials to be completed more quickly and would improve the generalizability of trial results.
Mind the gap: Estimating the opportunity lost due to the gap between FDA and EMA cancer drug approvals.
Authors: Gage Samantha , Eteshola Elias , Hadfield Matthew James , Hamze Dany , Khaki Ali Raza , Mishra Sanjay , Rooney Michael Kevin , Masse Gabrielle , Hilal Talal , Jain Sandeep Kumar , Rubinstein Sam , Lythgoe Mark , Warner Jeremy Lyle 
Published: June 2024

11030 Background: Drug regulators operate on their own timelines to assess the safety and efficacy of new drugs and/or extensions to existing indications, such that there are delays between regulators. During such a gap, patients in the “early” domain have access to the approved drug, while those in the “late” domain do not, outside of compassionate use. Our study aimed to quantify the “opportunity lost” for new therapies approved by FDA and EMA, assuming patients in the late domain receive standard-of-care (SOC) therapy – which is presumably inferior to the new drug – during the gap. Methods: Anticancer drugs approved by both FDA and EMA were identified through the HemOnc knowledgebase. Inclusion criteria included: 1) drugs approved in both domains based on the same randomized clinical trial (RCTs) for the same indication; 2) a primary time-to-event endpoint; and 3) a quantitated median time-to-event for the primary endpoint. For each included trial, the approval gap between FDA and EMA in days and the ratio of approval gap to median control arm time-to-event duration was calculated. A ratio ≥2 implies that, on average, no late domain patients starting treatment in the first half of the gap would be expected to have access to the new drug prior to an event. Results: Of 60 eligible RCTs, 59 had calculable median event durations. 25 (42%) had a primary overall survival endpoint; the most common surrogate endpoint was progression-free survival (PFS; 29/59; 49%). The median (interquartile range [IQR]) approval gap was 186 (124-271) days, with FDA being the first approver in 56/59 (95%) cases. The median (IQR) ratio of approval gap to median control arm event duration was 0.63 (0.35-1.11). Drugs with ratio ≥2 (Table) were targeted or immunotherapies; 7/8 (88%) were approved with PFS endpoint; 5/8 (62.5%) were approved for second line or later. Conclusions: Our study shows that FDA approves most drugs prior to EMA and a nontrivial number of patients may experience progression or death events while awaiting access to anticancer therapies already approved in another domain. The analysis does not take into consideration scenarios in which the new therapy is inferior to SOC or delays in patient access (due to slow uptake; regulatory barriers [in Europe/UK]; or patient affordability [in US]). Further regulatory collaboration (e.g., Project Orbis) between FDA and EMA could help to reduce and potentially ameliorate this differential in access to new cancer drugs in the future. [Table: see text]
Assessing the true cost of cancer screening: Comparing hospital prices to claims remittance data for common cancer screening tests at top-ranked US hospitals.
Authors: Alford Mason , Triana Austin , Baker Katherine , Trivedi Yash , Mullangi Samyukta , Van Horn Larry 
Published: June 2024

11055 Background: Patients in the United States often lack information about the price of common cancer screening services across hospitals and payers. Recent legislation in the US, including the 2021 Hospital Price Transparency Final Rule and the No Surprises Act of 2022, require hospitals to post payer-specific negotiated prices for all services, creating a unique opportunity to understand variation in hospital pricing. While there has been much study regarding the wide variations in prices for healthcare screening services, little is known about the relationship between the prices for screening made publicly available by hospitals and the actual claims remittance recorded for those same services. Methods: We extracted payer-specific prices for four common cancer screening tests among 20 top-ranked US hospitals: colonoscopy, low-dose helical computed tomography (CT) scan, mammography, and prostate-specific antigen (PSA). Additionally, we extracted the cash prices published by these same hospitals and determined the median cash price for each screening service. To evaluate price variation for these screening tests, we determined the median and inter-quartile range (IQR) across all payers for these 20 hospitals. We compared this hospital pricing data to the 835 claims remittance data from December 1, 2021 to January 15, 2022. Results: Across 20 top US hospitals, the median hospital price for colonoscopy was $1597 (IQR $1780) and median claims price was $806 (IQR $788). The median hospital price for low-dose CT was $315 (IQR $472) and median claims price was $126 (IQR $83). The median hospital price for mammogram was $300 (IQR $351) and median claims price was $72 (IQR $83). The median hospital price for PSA was $85 (IQR $113) and median claims price was $29 (IQR $10). For all four screening tests, the median cash price was greater than the median negotiated price by an average of 27%. Conclusions: For common cancer screening tests, the distribution of hospital prices is wider than the actual prices reflected in claims data for the same screening services. Median cash prices published by hospitals were greater than the median negotiated rates for all cancer screening services, consistent with trends observed among large academic centers in metropolitan areas. Policies that improve precision in price estimates may help improve adherence in the United States for uninsured patients by providing more accurate information about prices for common cancer screening services. [Table: see text]
Prospective iterative data visualization (DV) study to enhance health literacy in prostate cancer (PC).
Authors: Spratt Daniel Eidelberg , Bingham Patrick , Eckardt John Randall , Moneer Shelby , Pagano Matthew , York Kirsten 
Published: June 2024

11061 Background: Methods used to visualize and present comparative effectiveness research (CER) impact patient (pt) and caregiver (CG) understanding and ultimately treatment decisions. Evidence-based approaches to optimize DV and comprehension in PC are lacking. We studied the presentation and DV of CER with key stakeholders aiming to overcome health disparity/inequity barriers related to understanding of CER DV. Methods: A panel representing pt and advocate, industry, and health care provider viewpoints provided qualitative feedback on multiple CER DV methods and generated a survey for US PC pts and CGs. Respondents were identified by a market research agency (buzzback, n=192) or a pt advocacy group (ZERO Prostate Cancer, n=58). Respondents first reported on comfort with and understanding of scientific data on PC using a Likert scale, then evaluated a randomly assigned graphic (1 of 2 versions each depicting the same information) for each of 4 topics. For efficacy and prostate-specific antigen (PSA) data, figures showed superiority of treatment over placebo; for safety, figures positively or negatively represented outcomes. For quality of life (QoL), overall QoL and specific QoL domains were illustrated. For each graphic, respondents first suggested their own key takeaway, then selected the best from 4 options, and reason for selection. Graphics were then assessed side by side with better key takeaway selected to create an overall story. Results: Respondents (pts, n=199; CGs, n=51) enrolled between Aug and Sep 2023; 54% were non-White; 52% had an annual income <$75,000/yr; 45% had no college degree. Some respondents reported being uncomfortable/neutral toward PC scientific data (26%) or found data difficult to understand (35%) or overwhelming (29%). >70% identified correct takeaways for Efficacy and PSA. Figures with numerical data showing a difference between treatment groups (Efficacy, PSA) more effectively communicated key takeaways than those without (Safety, QoL). Figures representing pts without toxicity (positive reporting) versus pts with toxicity (negative reporting) were better understood (62% vs 37%) and communicated (67% vs 33%). Respondents (~55-60%) chose the correct key takeaway for QoL figures, not containing quantitative data, and were divided as to which version best communicated the key takeaway. There were no consistent, robust patterns of differences in accuracy of interpretation based on respondent characteristics, especially for top performing Efficacy and PSA graphics. Conclusions: This is one of the first prospective multistakeholder studies in PC to explore comprehension and preferences from a diverse group of pts and CGs. Figures showing a difference between treatments were more accurately interpreted than those conveying parity. We provide a benchmark for best practices for CER DV for pts and CGs to assist in their education and optimize shared decision-making.
Trends in pharmaceutical industry payments to US cancer centers, 2014-2021.
Authors: Mitchell Aaron Philip , Chakraborty Nirjhar , Brown Meredith , Persaud Sonia , Gallagher Grace B , Trivedi Niti U. , Bach Peter Brian 
Published: June 2024

11065 Background: US National Cancer Institute-designated comprehensive cancer centers (NCICCCs) receive federal funding to support their public missions. However, these institutions also receive substantial funds (both research and non-research) from the pharmaceutical companies, which have private, for-profit goals. The amount of industry money received by NCICCCs, with respect to their federal funding, is poorly understood. The goal of this study was to examine trends in industry payments to US cancer centers. Methods: NCICCCs were identified (N=51). Industry payments to each NCICCC from 2014-2021 were obtained from Open Payments, and NIH grant funding from NIH RePORT. Given our interest in NCICCCs, we focused on the subset of industry payments (those designated as being related to a cancer drug, both research and non-research) and NIH grant funding (grants awarded by the NCI specifically, as opposed to other institutes) that were likely to be cancer-related (we also measured overall industry payments and overall NIH funding). In order to capture both industry payments and grant funding broadly, we manually identified teaching hospitals and research universities affiliated with each NCICCC and included payments and grants to these as well. All amounts were inflation-adjusted to 2021 dollars. Results: Oncology-related industry payments increased from $320 million in 2014 to $896 million in 2021. NCI funding increased slightly during the same period, from $2,481 million to $2,691 million. Overall industry payments increased from $1,811 million in 2014 to $3,015 million in 2019 (exceeding NCI funding in that year), though overall industry payments subsequently declined to $1,977 million in 2021. Non-research (as opposed to research) payments were the minority of industry payments; the year with the greatest proportion of non-research payments was 2019, at 39%. NCI funding exceeded oncology-related industry payments at all NCICCCs except for two: City of Hope ($1,137 million oncology-related industry payments vs. $311 million in NCI funding) and MD Anderson ($1,040 million vs. $1,001 million). Conclusions: Oncology-related industry payments to NCICCCs has increased substantially more than NCI funding in recent years. Although most industry payments are research-related, a substantial portion are not. A small number of NCICCCs receive comparable or greater amounts of money from industry than they receive in grant funding from the NCI. These trends raise concerns regarding the influence of industry payments and the ability of these institutions to maintain their public missions.
Cost trends in standard-of-care cancer treatments, 2017-2021.
Authors: Wang Judy J. , Persaud Sonia , Tabatabai Sara , Chakraborty Nirjhar , Dey Pranam , Trivedi Niti U. , Mitchell Aaron Philip 
Published: June 2024

11073 Background: Financial burden of cancer care in the United States is substantial. Prior studies have explored price trends at the level of individual cancer drugs but not that of clinical indications, which can be impacted not only by changes in drug prices but also changes in standard-of-care. This study evaluates temporal trends in the cost of providing the contemporary best guideline-concordant therapy for each cancer indication. Methods: We analyzed trends in the cost of the standard-of-care treatments for the 20 most prevalent cancer types, using NCCN Guidelines to identify the standard-of-care (SOC) treatment for each indication. Our primary comparison of interest was the cost of providing the SOC treatment regimen for each indication in 2021 vs. 2017. All solid tumor treatment indications present in the NCCN Guidelines at both study time points, 7/1/2017 and 7/1/2021, were included. Indications that involved radiotherapy or stem cell transplant among the treatment options were excluded. Costs of all recommended treatment options for each included indication were calculated using Medicare reimbursement rates. We included costs of the antineoplastic agents themselves as well as necessary supportive medications. Costs were inflation-adjusted to 2021 USD. We identified the SOC treatment for every indication at both time points by referring to NCCN Evidence Blocks and identifying the regimen(s) with the highest scores (prioritizing Efficacy, then Safety, then Quality, then Consistency, in that order). If multiple SOC treatments for a single indication had identical scores, we chose the least-costly treatment. Results: 83 clinical indications across 16 solid tumor cancer types (bladder, brain, breast, colon, kidney, liver, lung, melanoma, oropharyngeal, ovary, pancreas, prostate, rectal, soft tissue, stomach, and uterus) were included. Median SOC cost was $8,364 (IQR = $3,838, $15,783) in 2017, compared to a median of $4,290 (IQR = $1,438, $14,947) in 2021. 57 indications (68.7%) had lower SOC costs in 2021 vs 2017, with median change of -$935 (IQR = -$4,432, +$452), representing a 31% decrease (IQR = -50%, 8%). Gastric cancer perioperative chemotherapy had the biggest absolute cost decrease at $65,612 (-90%), while extensive stage small cell lung cancer had the biggest absolute increase at $37,213 (706%). 45 indications (54.2%) had the same SOC regimen across this study period, of which 75.6% saw price drops. Of the 38 indications with new SOCs, 60.5% had lower costs. Conclusions: Majority of the best SOC treatments decreased in cost over a 4 year period. Although introduction of newly approved drugs can cause large price increases for some indications, more commonly the financial cost of delivering the standard-of-care treatment for a given cancer trended down due to slower-than-inflation price increases and new generic entrants.