bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of polygenic risk score for clinically significant prostate cancer in a screening program: The BARCODE 1 study results.
Authors: Eeles Ros A. , Bancroft Elizabeth Kathryn , McHugh Jana Kathlyn , Saunders Edward , Brook Mark , McGrowder Eva , Wakerell Sarah , James Denzil , Page Elizabeth , Osborne Andrea , Kinsella Netty , Sohaib Syed Aslam , Cahill Declan , Hazell Stephen , Withey Sam , Rafi Imran , Kumar Pardeep , James Nicholas D. , Benafif Sarah , Kote-Jarai Zsofia ,   BARCODE1 Study Group and Collaborators
Published: June 2024

10500

Background: Incidence of prostate cancer (PCa) is increasing, but there is no internationally agreed population screening program. Studies using an age-based PSA approach show a high rate of false-positive results as well as over-diagnosis of indolent PCa. Genome wide association studies identify common germline variants to calculate a polygenic risk score (PRS) associated with PCa risk. The BARCODE1 study used PRS to target PCa screening to those at higher risk based on genotype. Methods: European men aged 55-69yrs were recruited via Primary Care in the UK. PRS was constructed by summing weighted risk alleles for 130 PCa risk variants using germline DNA from saliva samples via mailed kits. Men with a PRS > 90th centile were invited for PCa screening using MRI and 12-core transperineal biopsy (including MRI fusion to target additional lesions where identified) irrespective of PSA result. Results: Invitation letters were sent to 40,292 men. 8,953 (22%) expressed an interest; 8,014 were eligible and sent a saliva kit. 6,644 consented; 6,393 were genotyped; 251 failed QC. A total of 6,142 participants had PRS calculated: 745 (12.1%) had a PRS > 90th centile and were invited to screening. 558/745 participants attended screening (121 declined, 66 excluded on health grounds). 551 underwent MRI and 468 had prostate biopsy resulting in 187 (40.0%) diagnoses of PCa, overall PCa detection rate 2.8%. Mean age at diagnosis 64.1yrs (range 57-73; median 64). Using NCCN criteria (2023) 103/187 (55.1%) of cancers were Intermediate or High Risk; 40/187 (21.4%) were Intermediate Unfavourable/High/Very High Risk. 119/187 (63.6%) men had a PSA <3.0ug/L; PPV of biopsy for PSA > 3.0ug/L was 49.6%. PPV of MRI (presence of PI-RADS 3-5 lesion) 60.4%. PPV of PRS alone 40%. 103/187 (55.1%) had Gleason >7; compared with 360/1014 (35.5%) p < 0.001 in the PSA directed ERSPC study. Conclusions: A population PCa screening program using PRS risk-stratification enriches for clinically significant PCa requiring treatment. It detects a high proportion of clinically significant disease compared with PSA or MRI based screening programs and MRI missed a significant proportion (17-67%) of cancers found on biopsy. This is the first study to assess if this approach will be useful in population screening programs. Clinical trial information: NCT03857477 . [Table: see text]
Association of a polygenic risk score with risk of abnormal ultrasound findings and ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
Authors: Phillips Sarah , Landy Rebecca , Bodelon Clara , Machiela Mitchell J. , Temkin Sarah M. , Wentzensen Nicolas
Published: June 2024

10542

Background: Several susceptibility loci have been identified in genome-wide association studies (GWAS) of single nucleotide polymorphisms (SNPs) that are associated with ovarian cancers. Polygenic risk scores (PRS) combining certain loci have shown limited performance at predicting ovarian cancer risk. However, the utilization of PRS with ovarian cancer screening tests, like transvaginal ultrasound (TVU), warrants further evaluation. This study investigated the association between a polygenic risk score and ovarian cancer risk and abnormal TVU screening in a large-scale randomized controlled ovarian cancer screening trial. Methods: A polygenic risk score was constructed using weighted sums of risk alleles of 15 ovarian cancer SNPs identified in previous GWAS to evaluate the association with abnormal TVU screening results and ovarian cancer outcomes in female participants of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Complete genotyping information, TVU results, and ovarian cancer outcomes were available for 15722 females (mean age 62.2 years +/- 5.3) with European ancestry, including 116 ovarian cancer cases. Abnormal TVU was defined as ovarian volume or cyst volume > 10 cm3, any solid/cystic component within a cystic ovarian tumor, or any solid area or papillary projection extending into the cavity of a cystic ovarian tumor. Polygenic risk scores were categorized as quartiles and odds ratios (OR) were calculated to assess risk of ovarian cancer or abnormal TVU result using the lowest PRS quartile as reference category. Results: TVU screening results were abnormal for 732 (732/15722, 4.66%) participants and normal for 14990 (14990/15722, 95.3%) participants at trial baseline. PRS within the fourth quartile demonstrated increased risk of ovarian cancer with reference to the lowest quartile (OR 1.77, 95% confidence interval: 1.04-3.08). Similarly, women in the highest quartile of the PRS had increased odds of an abnormal TVU screening result (OR 1.46, 95% confidence interval: 1.17-1.83) compared to women in the lowest PRS quartile. Conclusions: A polygenic risk score including 15 loci previously shown to be associated with ovarian cancer risk showed an association with increased ovarian cancer risk in the PLCO trial. Furthermore, the PRS was also associated with abnormal ultrasound results. Our findings support further evaluation of polygenic risk scores and transvaginal ultrasound for ovarian cancer risk stratification and screening approaches.
Risk of subsequent primary cancers among adult cancer survivors.
Authors: Warkentin Matthew T. , Cheung Winson Y , Brenner Darren R , O'Sullivan Dylan E.
Published: June 2024

10554

Background: Improvements in early detection and clinical management of cancers have led to a significant increase in long-term cancer survivors who may be at an elevated risk of developing a subsequent primary cancer (SPC). As the largest and most comprehensive analysis in Canada, we assessed the risks and patterns of SPC development among 134,693 adult cancer survivors with 852,661 person-years of follow-up. Methods: We used data from the Alberta Cancer Registry (ACR) to identify all first primary cancers (FPC) occurring between 2004 and 2015 to allow for adequate follow-up until December 31, 2020. A SPC was considered as the next primary cancer occurring in a different organ/site. We estimated incidence rates (IR) and standardized incidence ratios (SIR) for SPC development with 95% confidence intervals (CI). IRs were estimated as the observed number of SPC divided by the person-years of follow-up. SIRs were estimated as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the general population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up among the adult cancer survivors. Results: The risk of developing a SPC up to fifteen years after an initial cancer was 16.1% for males and 12.3% for females. These risk estimates varied considerably by initial cancer site. Survivors of initial head and neck cancers had a fifteen-year cumulative incidence of 21.3% and a 2.5-fold relative risk of SPC development. Overall, both males (SIR=1.50) and females (SIR=1.64) had an increased risk of developing a SPC. Both male and female survivors of a FPC were at a significantly increased relative risk of developing a screen-detectable SPC (breast, cervical, colorectal, lung). There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors of early-onset cancers diagnosed between ages 18 to 39. Conclusions: Cancer survivors of nearly every FPC site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and this highlights the need to develop evidence-based guidelines for cancer screening in the growing population of long-term cancer survivors.[Table: see text]
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.
Characterizing the authorship of phase 3 randomized clinical trials in oncology, 1960-2023.
Authors: Warner Jeremy Lyle , Bakow Brianna R. , Brown Alaina J. , Choe Jennifer Hsing , Fan Elaine , Ganta Teja , Glover Michael , Hadfield Matthew James , Hilton C. Beau , Khaki Ali Raza , Kothari Shalin , Lythgoe Mark , Nagpal Seema , Nguyen Ryan Huu-Tuan , Noyd David H , Riaz Irbaz Bin , Rooney Michael Kevin , Sethi Tarsheen Kaur , Singhi Eric Kumar , Rubinstein Sam
Published: June 2024

11079

Background: Phase 3 randomized clinical trials (RCTs) inform the standard of care in cancer treatment yet have a mixed track record of success. In this study, we sought to 1) determine the overall success rate of phase 3 RCTs; 2) assess whether authorship patterns differ between successful (positive) and unsuccessful (negative) trials; and 3) explore if individual authors have distinct track records of success. Methods: The HemOnc knowledgebase (KB) was queried for initial publications of phase 3 RCTs of systemic anticancer therapy; those without primary outcome described were excluded. RCTs were labeled positive if the primary endpoint was met per HemOnc standard criteria (P value ≤ 0.05 or hazard ratio upper bound ≤ 1 for any experimental arm[s]) and negative if they did not meet these criteria or if the experimental arm was statistically inferior. Trial metadata and author information were extracted from the HemOnc KB. Author positive publication rate (PPR) was defined as % of publications reporting a positive result divided by total number of eligible publications. Prolific authors were defined as those with 6+ eligible publications. Author count for manuscripts reporting positive vs negative results was evaluated with the Mann-Whitney U test; other statistics were descriptive. Results: 3328 studies met criteria as of February 5, 2024; these were associated with 3305 initial publications between 1960-2023, involving 25,412 unique authors. 1474 (44.3%) of the studies were positive. Publications reporting positive trial results had, on average, 3 more authors, median (interquartile range) of 18 (12-23) vs 15 (11-20), p<0.0001. The mean (±SD) PPR for n=1967 prolific authors was 47.7% (±22.3%). The PPR was not related to individual author output; mean PPR for non-prolific authors was 48.0% (SD not reported). Differences in PPR were apparent by the disease under study and the years of publication (Table). Among the 46 prolific authors who had a PPR 2+ SD above the mean, 26 (55%) were from China followed by Italy with 3 (6%). Conclusions: Despite known positive publication bias, the success rate of published phase 3 RCTs remains <50%. Publications reporting positive results had significantly more authors; this finding requires further study including adjustment for trial sample size. Significant variation in PPR amongst fields could be due to watershed therapeutic advances, differential selection of primary endpoints, and/or selective reporting of results. Finally, a signal for geographic association of outlier PPRs suggests the need for further investigation. [Table: see text]
Effects of prehab or rehabilitation on upper extremity disability and quality of life after breast cancer surgery.
Authors: Wood Kelley C , Bertram Jessica , Love Kim , Kendig Tiffany , Lightner Ashley N , Mayo Stacye , Canavan Lynn DiDonato , Pergolotti Mackenzi
Published: June 2024

11090

Background: Growing evidence and NAPBC guidelines support the need for physical and/or occupational therapy (PT/OT) to optimize recovery from surgery. Research is needed to better understand the benefits of prehab (PT/OT before surgery and continuing afterward). We performed a retrospective study to understand the effect of participating in prehab or rehab-only on outcomes after surgery. Methods: Outpatient medical record data was extracted for cases who attended prehab (n=328) or rehab-only (n=306). Outcomes were upper extremity disability (Quick-DASH) and HRQOL (PROMIS measures of physical functioning, social role functioning, and global health [physical and mental]). Outcome time points included the post-surgery PT/OT assessment (T1, M=4 weeks), and PT/OT re-assessment (T2, M=15 weeks). We used linear mixed-effect models to examine the effect of prehab on T1/T2 outcomes while controlling for covariates (age, PT/OT, payer, and time), and to examine changes in outcomes from T1 to T2 for both groups. Results: Attending prehab was associated with better outcomes at T1 (upper extremity disability, p<.001; physical functioning, p<.001; social role functioning, p<.001; and physical health p<.001) and T2 (upper extremity disability, p=.025; physical functioning, p=.045; and social role functioning, p=.028; Table). From T1 to T2, each group improved significantly: upper extremity disability (prehab: M∆=8.92, p<.001; rehab-only: M∆=17.65, p<.001), physical functioning (prehab: M∆=1.89, p<.001; rehab-only: M∆=3.51, p<.001), social role functioning (prehab: M∆=1.61, p=.009; rehab-only: M∆=3.66, p<.001), and physical health (prehab: M∆=1.73, p<.001; rehab-only: M∆=3.50, p<.001). There was no significant effect of prehab on mental health and improvement from T1 to T2 was non-significant for both groups (p>0.05). Conclusions: In this study, attending outpatient prehab PT/OT services was associated with less upper extremity disability and greater HRQOL after breast cancer surgery. After post-surgery PT/OT, prehab and rehab-only cases each improved significantly; and upper extremity disability, physical functioning and social role functioning remained better among prehab cases. Although more research is needed, these findings support the integration of PT/OT in routine care and suggest that early PT/OT may optimize outcomes. [Table: see text]
Disparities in stereotactic radiosurgery practice patterns for treatment of brain metastases: A large national cancer database study.
Authors: Taparra Kekoa A. , Shih Jonathan , Patel Manali I. , Pollom Erqi L.
Published: June 2024

11094

Background: Brain metastases (BM) portend high mortality rates. While whole brain radiation therapy (WBRT) is a commonly used treatment strategy for BM, stereotactic radiosurgery (SRS) has less neurocognitive toxicity with comparable survival. The objective of this study was to compare treatment practice patterns for SRS vs WBRT using a large national hospital database. Methods: The National Cancer Database (NCDB) was queried for patients ≥18 years treated with radiotherapy (RT) for a BM diagnosis between 2004-2017 and with known follow-up. 12 cancers were included based on highest prevalence including: breast, colorectal, kidney/bladder, liver, lung, lymphoma, melanoma, oral cavity, pancreas, prostate, and thyroid. Patients were grouped by first course RT modality (SRS vs WBRT) confirmed by fraction number (SRS: 1-5; WBRT: 5-15). Multivariable logistic regression assessed predictors of SRS as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). Analyses were adjusted for patient and cancer characteristics. Results: Of 88,539 patients with BM, 17,734 (18%) received SRS. Median age was 64 years. Most patients were White (84%), diagnosed in 2011-2017 (58%), with a higher income (55%), more education (55%), and Medicare/Medicaid (58%). The most common cancer treated with RT for BM was lung (86%). Patients were less likely to be treated with SRS if they were Hispanic (aOR=0.85; 95%CI=0.76-0.96), lower income (aOR=0.90; 95%CI=0.86-0.95), lower education (aOR=0.87; 95%CI=0.83-0.91), with Medicare/Medicaid (aOR=0.83; 95%CI=0.79-0.87) or no insurance (aOR=0.46; 95%CI=0.41-0.51), at a Midwest hospital (aOR=0.74; 95%CI=0.71-0.78; vs Northeast), and at a community (aOR=0.28; 95%CI=0.25-0.30; vs academic) or comprehensive community cancer program (aOR=0.50; 95%CI=0.47-0.52). Patients were more likely to be treated with SRS if they were older (aOR=1.01; 95%CI=1.01-1.01), diagnosed in 2011-2017 (aOR=2.39; 95%CI=2.30-2.49; vs 2004-2010), lived farther from the hospital (aOR=1.09; 95%CI=1.07-1.11), and received chemotherapy (aOR=1.41; 95%CI=1.35-1.47). SRS was most often used to treat BM from primary colorectal cancer (aOR=1.99; 95%CI=1.65-2.40), endometrial cancer (aOR=1.52; 95%CI=1.08-2.10), kidney/bladder cancer (aOR=3.09; 95%CI=2.68-3.55), and melanoma (aOR=2.74; 95%CI=2.39-3.14), while less often used to treat BM from lymphoma (aOR=0.18; 95%CI=0.11-0.30), vs breast primary cancers. Conclusions: In one of the largest BM studies with nearly 90,000 US patients, disparities in SRS treatment patterns were identified. On adjusted analysis, SRS was less likely to be used for patients who were of Hispanic ethnicity, lower income, lower educational attainment, without private insurance, and treated at community centers. The data highlight populations with cancer and BM who may benefit from increased access to SRS.
Real-world assessment of treatment-related symptoms and associated burden among African American and Caucasian patients receiving chemotherapy in the US.
Authors: Galaznik Aaron , Rusli Emelly , Holt Tracy , Kramer Mordecai , Trask Peter
Published: June 2024

11102

Background: In the treatment of breast cancer, research has identified racial differences in the ability to receive the full dose of prescribed chemotherapy which may be due in part to cancer-treatment symptom burden. In clinical trials, evaluation by race is challenging due to enrollment disparities, with African Americans (AA) accounting for 7% of trial participants, but comprising 12% of the US total population. The objective of this study is to evaluate treatment-related symptoms and treatment burden among patients treated with chemotherapy through an electronic remote symptom monitoring system, and explore whether there were any racial differences. Methods: Patients (pts) diagnosed with multiple myeloma, breast, ovarian, or lung cancer in academic cancer practices were enrolled in Carevive’s Patient Reported Outcomes Mobile Platform (Carevive PROmpt) between September 2020 and June 2023. A total of 1000 pts received chemotherapy alone or in combination. PRO-CTCAE-derived weekly surveys assessed severity, frequency, and interference for 16 symptoms: anxiety, constipation, cough, decreased appetite, diarrhea, fatigue, general pain, insomnia, mouth/throat sores, muscle pain, nausea, numbness and tingling, rash, sadness, shortness of breath, and vomiting. The GP5 assessed weekly overall burden from treatment. Results: The mean age of pts was 60.9 (SD=12.8) years, with 75% female, and 20% AA. At the time of enrollment, fatigue was reported by roughly 48% of AA and Caucasian (C) pts. Muscle pain was noted in 38% of AA pts, followed by general pain (33%), and anxiety (30%), with constipation, decreased appetite, insomnia, nausea, and numbness/tingling occurring in over 20% of pts. A different pattern was observed in C pts, with anxiety occurring in 38%, followed by cough, decreased appetite, general pain, insomnia, muscle pain, nausea, and numbness/tingling present in 20% of pts. The proportion of pts at least “somewhat” bothered by the side effects of treatment were similar (44% AA, 45% C). Conclusions: This study enabled evaluation of symptom burden in cancer in a population closer in racial representation to the real world than in clinical trials; with AA representation being three-fold that seen in clinical trials. Consistent with a qualitative study of AA breast cancer pts, fatigue was identified as the most frequent symptom among those treated with chemotherapy either alone or in combination in the real world. Racial differences in the proportions of pts reporting pain (muscle or general) and anxiety suggest that treating physicians should consider these symptoms to ensure they do not interfere with patients’ ability to receive full chemotherapy courses. Additionally, the levels of anxiety reported in patients highlights the importance of considering concomitant psycho-oncology treatments in cancer therapy.
Evaluating the feasibility of a Mobile Audio Companion (Elly) to reduce anxiety and to improve patient-reported outcomes among patients with cancer.
Authors: Nguyen Tyra , Nikravesh Nima , Monette Tailyr , Luna-Lupercio Bianca , Salvy Sarah-Jeanne , Freedland Stephen J. , Asher Arash , Irwin Scott A. , Shirazipour Celina H. , Gresham Gillian
Published: June 2024

11120

Background: Anxiety is one of the most commonly reported symptoms among cancer patients, and is a known risk factor for reduced health-related quality of life and other negative patient-reported outcomes (PROs). Mobile health applications (apps) are tools that can be used flexibly in patients’ preferred environments with the potential to reduce anxiety and improve quality of life. The current study sought to examine the feasibility and preliminary efficacy of a mobile audio companion app, Elly, to improve anxiety and other critical PROs among cancer patients. Methods: This was a single-site, single-arm pilot study conducted over 6-months. Adults 18 years or older with a diagnosis of cancer of any type, received treatment within 6 months of consent, and had access to an iPhone were eligible. The primary outcome was change in mean anxiety t-scores (NIH PROMIS anxiety short form (8a)) administered electronically via REDCap at baseline, 1 (primary timepoint), 3, and 6 months. Secondary outcomes included changes in NIH PROMIS depression, loneliness, social support, and perceived stress scores from baseline to 6 months. Changes in NIH PROMIS T-scores at each time point were calculated and analyzed using paired t-tests. Results: Of 53 patients who consented for the study, 38 patients (72%) were included in the analysis ( Mage: 52.8 years, SD: 11.7, 84.2% female). Most participants reported a history of breast cancer (50%), followed by ovarian (16%), hematologic (11%), and other cancer types (24%) Phone incompatibility and technological challenges were the most common reasons for screen-fails (n=15). All participants downloaded and used the app at least once, with an average of 154 app usage events across participants recorded over the study period (median: 64, range 11-1186 times). The mean baseline anxiety T-score was 63.5 (SD: 2.1). Anxiety levels decreased among participants over time, with a mean difference in anxiety T-scores of -1.9 at 30 days, -3.3 at 90 days, and -3.0 at 6 months from baseline, which was statistically (p<0.05) and clinically significant. Participants also reported improvements in perceived stress, depression symptomatology, social support, and loneliness, although statistical significance was not reached. Conclusions: Mobile apps, such as Elly, may feasibly be used to support patient-reported anxiety as well as other PROs, especially among those who present with high levels of anxiety at baseline. Efforts to increase access to mobile health apps and provide technical support for patients should be made increase equity across the cancer survivor population. Larger, multi-center randomized controlled trials are needed to build on these findings.