bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving feasibility and timeliness of hereditary cancer risk assessment with a brief patient-administered digital tool and rapidly available telehealth genetic counseling.
Authors: Daley Ashley , He Wenjun , Iverson Gabrielle , Petersen Jenna , Hila Andi , Johnson Kiley , Caleshu Colleen
Published: June 2024

10614

Background: Multiple guidelines recommend hereditary cancer risk assessment for all adults, yet it rarely is performed. This is largely due to the time-consuming nature of such assessments and difficulty with access to genetic counseling for those at high risk. We designed a care model to address these issues that is suitable for both oncology and non-oncology settings. It includes a brief patient-administered and clinically validated digital hereditary cancer risk assessment tool, followed by immediate online self-scheduling features for telehealth genetic counseling, with appointments available within 48 hours. The digital tool uses a guideline-based algorithm to assess whether genetic testing for hereditary cancer risk is indicated. Here we aim to evaluate the effectiveness and timeliness of this model. Methods: We conducted a retrospective chart review of consecutive patients that engaged with this model from May 2021 to August 2023 at 32 obstetrics and gynecology clinics. We also used nationwide data from the National Society of Genetic Counselor's (NSGC) Professional Status Survey. To assess timeliness of genetic counseling appointments in this care model, we compared the time from scheduling the appointment to the start of the appointment to wait times at health systems for comparable non-urgent cancer genetic counseling appointments, from the NSGC data. Effectiveness was assessed via rates of completion of the tool and scheduling of genetic counseling. Results: 2538 patients (98% female, mean age 37 years, 3.9% with a personal history of cancer) initiated the care model and 95% (2415/2538) completed the risk assessment tool. A quarter (26% (628/2415)) met criteria for germline genetic testing. The median time to complete the tool was 2.7 minutes (IQR 2.9). At the end of the tool, patients could click a button to schedule an appointment with a genetic counselor to discuss hereditary cancer risk and genetic testing. 44% (274/628) booked an appointment. The median time from scheduling to genetic counseling appointment was 2.8 days (IQR 4.9 days), which is shorter than the median wait time for comparable genetic counseling appointments at health systems in the nationwide NSGC dataset (21 days (IQR 53 days); p<< 0.01). Conclusions: The tool completion rate, rate of patients meeting criteria, and uptake of genetic counseling indicate the model is effective. Timeliness was improved by this model, with the digital tool assessing risk in ~3 minutes, compared to previous reports of ~30 minutes for manual hereditary cancer risk assessment. In addition, the timeliness of genetic counseling appointments was markedly better than the current standard of care. These findings suggest that this care model can support physicians in providing timely guideline-recommended hereditary cancer risk assessment to their patients.
Contribution of mammography to breast cancer detection among pathogenic germline BRCA carriers by age and mutated gene.
Authors: Goldvaser Hadar , Bernstein-Molho Rinat , Michaelson-Cohen Rachel , Moss Lior , Gekhtman David , Sklair-Levy Miri , Rabinovitch Rachel , Tomer Ariela , Miller Yahelli , Moore Pnina , Levy-Lahad Ephrat , Lieberman Sari
Published: June 2024

10615

Background: Healthy carriers of pathogenic germline BRCA 1/2 (gBRCA) may choose between risk reducing mastectomy and intensive screening surveillance. Current international guidelines recommend both annual breast MRI and annual mammography. The aim of this study was to investigate the added contribution of annual mammography in gBRCA carriers to the annual breast MRI. Methods: A retrospective study from 2 large centers comprising gBRCA carriers who were diagnosed with breast cancer between 2000-2022 and were aware of their gBRCA status prior breast cancer diagnosis. Collected data included age at diagnosis, mutated gene and mode of breast cancer diagnosis (MRI, mammography, ultrasound [US], or other means [including clinical or incidental findings]). Data on pregnancy and breastfeeding at the time of breast cancer diagnosis were also collected. Differences in the mode of diagnosis were analyzed by age (≤40y vs. >40y) and mutated gene (BRCA1 vs. BRCA2). Results: The cohort included 200 gBRCA carries: 134 (67%) BRCA1, 62 (31%) BRCA2 and 4 (2%) with both BRCA1 and BRCA2 mutations. The median age at the time of breast cancer diagnosis was 41 (24-88). Most cancers (68%) were diagnosed by MRI, followed by mammography (14.5%), US (7%) and other means (10.5%). While MRI was the most common diagnosis modality in both age groups, the distribution of mode of diagnosis was significantly different in younger women (≤40y) where breast cancer detection was more commonly by US or following clinical findings, compared to older women, p< 0.001 (see Table). Five women were pregnant and 9 women were breastfeeding at the time of breast cancer diagnosis, all age 40 or younger. Four (80%) of pregnant carriers and 5 (55.6%) of breastfeeding carriers were diagnosed by US. There was no difference in mode of diagnosis between BRCA1 to BRCA2 carriers, p=0.974. There were only 16 women under age 30 that were diagnosed with breast cancer, 2 (12.5%) of whom were diagnosed with mammography. Conclusions: MRI is the most common modality for breast cancer diagnosis in gBRCA carriers who were aware if there gBRCA prior breast cancer diagnosis. Annual mammography also has a meaningful role in this population. We did not identify a subgroup in which it could be omitted. The increased utility of US among younger women is attributed to reduced utilization of MRI/mammography during pregnancy and breastfeeding. This finding strengthens the role of US screening in gBRCA carriers who are not eligible for other methods of imaging. [Table: see text]
Beyond the binary: A transformative implementation science initiative to improve LGBTQ+ cancer care.
Authors: Maingi Shail , Schabath Matthew B. , Dewald Ilona , Storey Janet , Dooyema Samuel , Carter Jeffrey D. , Heggen Cherilyn , McKinnon Kelly
Published: June 2024

11010

Background: Patient, provider, and system-level barriers contribute to significant disparities in care of LGBTQ+ persons, including delays in screening and diagnosis, and poorer outcomes. This implementation science initiative was designed to identify and address root causes of disparities in care for LGBTQ+ patients (pts) and drive sustainable change to improve health equity in LGBTQ+ cancer care. Methods: In 2023, a steering committee of 3 expert oncologists and 5 LGBTQ+ cancer pts convened to develop survey instruments and a point-of-care LGBTQ+ Cancer Care Toolkit. Next, LGBTQ+ pts with cancer (N = 817) and oncology providers (OPs) from 2 academic and 5 community-based practices (N = 115) completed surveys to reveal alignments and discordances in beliefs, perceptions, and practices regarding cancer care. OPs participated in audit-feedback (AF) sessions to critically assess system-specific practice gaps, prioritize areas for improvement, and develop action plans for improving LGBTQ+ cancer care. Results: Provider-reported top challenges in care included: unsure how sexual orientation/gender identity (SOGI) affect treatment considerations (35%), unsure how to discuss SOGI (30%), and systemic barriers that limit inclusion (29%). While most providers (84%) were at least moderately comfortable treating LGBTQ+ pts, these data suggest they overestimated the level of comfort of their pts. For example, only 24% of pts reported feeling safe disclosing their LGBTQ+ identity, while 65% of providers thought pts felt safe. Additionally, while most providers (73%) thought it was important to know a pt’s gender identity, only 46% thought it was important to know sexual orientation, and only 3% of providers reported routinely discussing SOGI with new pts. Patients and providers were not concordant in several other key areas, including the experience of pts’ partners, measures of inclusivity, and supportive care services offered, such as fertility preservation. Survey data also revealed systemic barriers to equitable care, such as EMR documentation of SOGI. In AF sessions, teams reviewed survey outcomes, and developed action plans for improvement, including integrating the toolkit, updating EMR documentation, developing LGBTQ+ education, and adopting measures of inclusivity. Notably, following the intervention, there were considerable gains in provider confidence and knowledge, and ~70% of providers committed to discussing SOGI with their pts at first introduction. Conclusions: Through this QI initiative, teams identified patient-, provider-, and systemic-level barriers that affect LGBTQ+ cancer care in their own practices and implemented action plans to address key challenges. The sustainable changes implemented in this QI initiative represent key opportunities for improvement that can be implemented in clinics across the country to improve equitable LGBTQ+ cancer care.
Improving delivery of smoking cessation assistance for patients with cancer: Results of the Beyond ASK quality improvement.
Authors: Mullett Timothy W. , Burris Jessica L , Reilly Eileen M , Shelton Rachel C , Warren Graham W. , Ostroff Jamie S.
Published: June 2024

11011

Background: Smoking by cancer patients and survivors causes adverse health outcomes, and quitting smoking after a cancer diagnosis can improve survival. However, assistance with smoking cessation is not regularly provided to cancer patients. Reported are results of the national 2023 Beyond ASK quality improvement initiative to increase and sustain delivery of smoking cessation assistance across participating sites. Methods: In 2023, American College of Surgeons Commission on Cancer (CoC) accredited sites were invited to participate in the Beyond ASK quality improvement initiative to increase evidence-based smoking cessation assistance delivery to cancer patients who report current smoking. Participating sites were required to monitor and periodically report on provider performance (e.g., assist rate = number of patients assisted with smoking cessation / number of patients who smoke), resource utilization, barriers, and facilitators. Educational resources, webinars, toolkits, and online data collection were facilitated by CoC. Results: Among 306 participating programs who completed the Beyond ASK initiative (94% of baseline programs), high rates of asking patients about and documenting smoking status were maintained at 88-92% from the baseline to final survey. During the 12-month project period, overall rates of assisting with smoking cessation increased from 53% to 67%. Referral to state quitlines increased from 31% to 49%, and referral to ‘in house’ smoking cessation programs increased from 15% to 28%. Rates of providing brief in office counseling more than tripled from 20% at baseline to 66% at final. The most frequently reported components that contributed to programs’ success were educational webinars (30.6%), structured data collection (28.2%), and smoking cessation toolkit (21.2%). The leading logistical barriers were extracting clinical data from the EHR and making changes to the clinical workflow, reported by 36.5% and 28.2% of respondents, respectively. Overall, 95.3% of respondents “agreed” or “strongly agreed” that identifying patients who smoke and assisting patients with cessation was sustainable. Conclusions: Increasing smoking cessation assistance through a national accreditation organization is feasible with substantial improvements in assisting patients. Results support delivery of smoking cessation as an achievable national quality component of cancer care.
The toxicity swimmer plot: A novel approach for evaluating patient-level toxicity following immune checkpoint inhibitor (ICI) therapy on the Checkmate 214 trial.
Authors: Viray Hollis , Huang Hui , Mantia Charlene , Jegede Opeyemi , Atkins Michael B. , McDermott David F. , Regan Meredith M.
Published: June 2024

11014

Background: Treatment with ICIs creates the possibility of prolonged disease control or remission but also creates the possibility of prolonged toxicity even after treatment is discontinued. Treatment-free survival (TFS) with and without toxicity has previously been described as an integral piece of a partitioned survival analysis in advanced renal cell carcinoma (aRCC). Prior analyses have reported further partition of TFS as mean duration of TFS with and without treatment-related adverse events (TRAEs), but this metric fails to provide more granular information regarding individual patients experiencing toxicity during TFS. We present a novel extended swimmer plot that characterizes patient-level toxicity data within TFS using the example of the Checkmate 214 trial to complement analyses of the population average experience. Methods: Data were analyzed from the Checkmate 214 trial which randomized 1096 patients with aRCC to receive either first-line (1L) nivolumab plus ipilimumab (n = 550) or sunitinib (n = 546). The minimum follow-up from protocol therapy initiation was 42 months. Patients’ overall survival was partitioned into 3 survival states: time on 1L protocol therapy, TFS, and survival after subsequent therapy initiation. With a re-defined time origin relative to cessation of 1L protocol therapy, we generated swimmer plots highlighting the TFS period and documenting each patient’s experience with and without grade 2+ and grade 3+ TRAEs during TFS. The swimmer plot was sorted by duration of TFS and duration of TFS with grade 2+ TRAEs in order to illustrate patterns of individuals’ experiences. Results: The 42-month mean TFS was 7.8 months (with grade 2+ TRAEs: 3.2 months) for patients treated with nivolumab plus ipilimumab and 3.3 months (1.6 months) for patients treated with sunitinib. In the respective treatment groups, TFS with grade 2+ TRAEs was experienced by 32% and 25% of patients and comprised of 13% and 9% of patients for whom it was the entire TFS period. These percentages were consistent regardless of TFS duration. TFS with grade 3+ TRAEs was experienced by 15% and 3% of patients, respectively. For most patients having TFS with TRAEs, the TRAEs persisted from the protocol therapy period, but 7% and 1% of patients in the respective treatment groups had new-onset grade 3+ TRAE during TFS. A swimmer plot will be presented as a visual presentation of this study’s results. Conclusions: We describe a novel extension of swimmer plots for presenting patient-level information and illustrating patterns in toxicity duration relative to TFS by incorporating individual toxicity data into a swimmer plot of partitioned survival. This approach allows for a more comprehensive understanding of toxicity trends and risk of prolonged toxicity after treatment is discontinued.
Assessing patient engagement levels in clinical cancer research: Development of a novel evaluation tool and comparison between eastern and western countries.
Authors: Gatellier Laureline , Tombal Bertrand F. , Serckx Béatrice , Charvat Hadrien , Katsui Keiko , Majima Yoshiyuki , Higashijima Jin , Suzuki Kazuyuki , Klingmann Ingrid , Nakamura Kenichi , Matsuda Tomohiro
Published: June 2024

11018

Background: Patient Public Involvement and Engagement (PPIE) is essential in healthcare and cancer research. Currently, there is no objective method to assess at which stage of a clinical trial PPIE is effectively implemented. In this study, we developed a simple method for objectively assessing PPIE with an international scale. Methods: A novel, simple scoring method was developed to evaluate the PPIE implementation in cancer research. It follows the EUPATI Patient Engagement Roadmap and assesses PPIE at eight steps: defining research priorities, fundraising, protocol, informed consent, ethical review, investigator meeting, study results reporting, and application. PPIE level was self-rated by investigators on a five-level engagement scale: no engagement, considered, informed, actively involved, and co-creation. It was submitted to 124 Japanese and 203 European principal investigators (PI) of non-commercial sponsor cancer research clinical trials, conducted between January 2018 and December 2022, identified from publicly available databases (EudraCT, UMIN, jRCT). Results: The questionnaire was answered by 66 (53.2%) and 45 (22.2%) of the Japanese and European PIs, respectively. Overall, the PPIE implementation was low in both regions, with a “no engagement” rate of 61.7% in Europe and even lower, 78.5%, in Japan. Forty percent of the European PIs actively engaged patients (“actively involved” and “co-creation”) in at least one research step, versus only 16.7% of the Japanese PIs. The percentage of PIs answering “no engagement” in all eight steps was 47.0% in Japan and 11.1% in Europe. PPIE was the highest for the informed consent domain, with 73.3% of the European and 20.3% of the Japanese PIs reporting some level of engagement. Similarly, 55.6% of the European and 18.8% of the Japanese PIs involved PPIE in the ethical review domain. PPIE was notably low in the earlier steps of the research. Conclusions: Our innovative PPIE scoring method allowed us to objectively assess PPIE in cancer clinical trials and compare its implementation among different countries. This 2018-2022 snapshot revealed low (EU) to very low PPIE (Japan) levels, especially in the research design. Future assessments should help to monitor the enhancement of PPIE in cancer research on an international scale.
Improving clinical trial performance using adult-learning methods.
Authors: Burke Matthew M. , Kubitschek Trees Carolyn , Maan Mukta , Levonyak Mark , Johnson Lindsay , Koeppen Nicholas , Barrera Victoria , Nemeth Agnes , Reddy Sree , Coleman Robert L. , Franson Paula J.
Published: June 2024

11025

Background: Timely and efficient accrual to oncology treatment trials is among the most vital components of clinical research. However, more than 80% of trials fail to reach enrollment targets, compromising outcome interpretation and cost. We hypothesized that a novel and customized application of adult-learning methods would enhance clinical trial screening and randomization. Methods: In collaboration with a multinational sponsor, Vaniam Group (VG) introduced a structured set of interventions to sites in 3 global randomized trials. Sites choosing to “opt in” formed the experimental group (EG). EG received tailored interventions: interactive Trial Educational Discussions (iTEDs: 30-min virtual meetings), and/or interactive Trial Acceleration Meetings (iTAMs: 4-hr live workshops of 10-30 investigators), and standard study support. Adult-learning techniques including the Socratic Method, case studies, and teach-back were used. Control group (CG) comprised sites receiving only standard study support. Primary endpoints were screening rate (SR) and randomization rate (RdR) compared atbaseline (6 mos prior to intervention) and 6 mos post-intervention (M6). Nonparametric statistical analyses compared between-group (Mann–Whitney U test) and within-group (Wilcoxon Signed-Rank test) differences. Results: Trial 1, a phase 3 placebo-controlled adjuvant trial had been open for 45 mos (54% enrolled) prior to intervention. At baseline, SR and RdR were similar between groups ( P>0.05). At M6, SR increased 100% and RdR increased 37% in the EG; in the CG, SR did not change and RdR decreased 7%. For both endpoints, EG performed better than CG ( P=0.018, P=0.014). Trial 2, a phase 3 neoadjuvant trial had been open for 49 mos (86% enrolled) with a projected 18 mos to completion. At M6, SR increased 3% in the EG, but decreased 39% in the CG. RdR increased 15% in the EG but decreased 33% in the CG. While changes in performance were not significant between groups ( P >0.05), study met its target enrollment goal with no further delays. Trial 3, a phase 2 recurrence trial was 30% behind enrollment with a projected 51 mos to completion. At M6, increases in SR were recorded in both EG and CG at 116% and 18%, respectively. RdR increased in both EG and CG (90% and 50%, respectively), augmented by protocol amendment. Despite increases in both groups, SR and RdR were significantly enhanced by VG intervention ( P=0.009 and P=0.015). Conclusions: Our novel, site-focused intervention strategy structured upon adult-learning methods significantly enhanced clinical trial performance, as measured by SR and RdR. Future work will expand these findings to different trial designs and outcome measures such as endpoint fidelity and cost. [Table: see text]
Supplemental Nutrition Assistance Program (SNAP) policy changes and mammography use in the United States.
Authors: Kazmi Ali , Hussaini S. M. Qasim , Chino Fumiko , Yabroff Robin , Barnes Justin Michael
Published: June 2024

11033

Background: The Supplemental Nutrition Assistance Program (SNAP) alleviates food insecurity among low-income households, which has been linked to healthcare access. Several states increased SNAP eligibility by implementing policies that eliminate asset tests and/or broaden income eligibility criteria. This study investigates the associations of SNAP policy changes on mammography use within the past year among low-income females eligible for breast cancer screening. Methods: Income-eligible females ages 40-79 years were identified from the 2006-2019 Behavioral Risk Factors Surveillance System. 28 and 22 states adopted SNAP asset test elimination and income increase policies, respectively. Difference-in-differences analyses compared changes in the percentage of mammography within one year from pre- to post-SNAP policy adoption (asset test elimination or income eligibility increase) between states that did and did not adopt policies expanding SNAP eligibility. The samples were limited to females with household income < 130% and <200% federal poverty level for analyses of asset test elimination and income eligibility increase policies, respectively, to correspond to typical eligibility criteria. Results: A total of 171,684 and 294,647 income-eligible females were included for the asset test elimination and income eligibility increase policy analyses, respectively. Overall, 58.4% reported mammography within 1 year. Adoption of asset test elimination policies was associated with a 2.11 percentage point (95% CI = 0.07 to 4.15, P=0.043) increase in mammography, particularly for non-metropolitan residents (4.14 percentage points, 95% CI = 1.07 to 7.21, P=0.008), those with household income <$25,000 (2.82 percentage points, 95% CI = 0.68 to 4.97, P=0.01), and those residing in states in the South (3.08 percentage points, 95% CI = 0.17 to 5.99, P=0.038) or in states that did not expand Medicaid under the Affordable Care Act (3.35 percentage points, 95% CI = 0.36 to 6.34, P=0.028). There was no significant association between state-level policies broadening SNAP income eligibility and mammography use (-1.07 percentage points, 95% CI = -2.64 to 0.49, P=0.18). Conclusions: This nationwide study suggests that policies eliminating the asset test for SNAP eligibility were associated with increased mammography use within one year, with the most pronounced positive impact observed in Southern states, non-expansion states, non-metropolitan areas, and households with the lowest incomes. Findings highlight the role that states policies have to both meet essential needs and promote health among vulnerable populations.
Relationship between receipt of combined axillary dissection and nodal irradiation and age.
Authors: Myers Sara , Partridge Ann H. , Warren Laura Elizabeth , Greenup Rachel Adams , Mittendorf Elizabeth A. , King Tari A. , Kantor Olga
Published: June 2024

11043

Background: Combined axillary lymph node dissection and regional nodal irradiation (ALND+RNI) is the greatest risk factor for breast cancer-related lymphedema (BCRL), a lifelong ailment that negatively impacts quality of life. As disability from BCRL may be particularly profound for adults <45 yo with longer life expectancy, we examined the association of age and other sociodemographics with receipt of ALND+RNI to further our understanding of patients at greatest risk for BCRL. Methods: The National Cancer Database (NCDB) was used to examine age-based differences in receipt of ALND+RNI in patients with stage I-III breast cancer treated from 2018-2020. Cohort characteristics were compared by age (<45 yo, 45-64 yo, and 65 yo). Multivariable regression examined the association between age and ALND+RNI adjusting for relevant factors. Sensitivity analyses explored associations between covariates and combined ALND+RNI by age group. Results: Of 155,010 patients, 5.4% were <45 yo, 47.2% were 45-64 yo, and 47.4% were 65 yo. Clinical and pathological node (cN, pN) positive disease, and receipt of ALND, RNI, and ALND+RNI were more common in patients <45 yo (Table). Age <45 yo was independently associated with ALND+RNI (<45 yo OR 1.40; 45-64 yo OR 1.26 vs 65, p<0.001). Residing in areas with a high proportion of high-school graduates (%HSG), Hispanic ethnicity but not race, and lower income were also associated with ALND+RNI in adjusted analyses (all p<0.05). Medicare (p=0.02 vs private insurance) was inversely associated with ALND+RNI. Among clinical factors, pN+ was the greatest risk factor for receipt of ALND+RNI (all p<0.001 vs pN0). Higher cT, cN1 and cN2 categories, lobular tumors, mastectomy, not receiving endocrine therapy, and having chemotherapy were also associated with ALND+ RNI (all p<0.05). Sensitivity analyses showed that while sociodemographics influenced receipt of ALND+RNI for women 45 yos, only clinical factors were significant for ALND+RNI for <45 yo. Among 45-64 yo, high %HSG (p<0.001) and low household incomes (p<0.01) were associated with ALND+RNI. In the 65 yo cohort, high %HSG (p=0.028), and Asian race (p=0.011) were more likely to receive ALND+RNI while Medicare patients were less likely to have ALND+RNI (p=0.012). Conclusions: Our findings suggests that clinical factors predominate in axillary treatment decisions for younger patients; while sociodemographic factors are more prominent for those 45 yo. Given their higher odds of receiving ALND+RNI, BCRL screening may be especially important in patients <45 yo. Further studies are needed to understand the interplay between age and sociodemographics on receipt of ALND+RNI. [Table: see text]
Association of frailty assessed by a ten-item frailty index (FI-CGA-10) with health-related quality of life in older adults with cancer.
Authors: Nishijima Tomohiro F. , Shimokawa Mototsugu , Nyrop Kirsten A. , Arimizu Kohei , Esaki Taito , Morita Masaru , Toh Yasushi , Muss Hyman
Published: June 2024

11047

Background: A 10-item frailty index based on a comprehensive geriatric assessment (FI-CGA-10) is a recently developed measure of frailty in the geriatric oncology setting [Oncologist, 26, e1751 (2021)]. Our objective was to investigate the association between frailty defined by the FI-CGA-10 and health-related quality of life (HRQOL) in older adults with cancer. Methods: This study included 1015 consecutive older adults with cancer who underwent a CGA before cancer treatment decision at a geriatric oncology service in Japan from February 2020 through September 2023. Fitness and frailty level was evaluated using the FI-CGA-10 that assesses 10 domains: cognition, mood, communication, mobility, balance, nutrition, base and instrumental activities of daily living, social support, and comorbidity. Deficits in each domain were scored as 0 (no problem), 0.5 (minor problem), and 1.0 (major problem). FI-CGA-10 scores (range 0-1) were calculated by dividing the sum of the scores for each domain by 10 and then categorized as fit (<0.2), pre-frail (0.2–0.35), and frail (>0.35). HRQOL was measured by the EQ-5D-5L index score and visual analogue scale (VAS) at the CGA consultation. The minimally important difference (MID) values for the EQ-5D-5L Japan-based index and VAS scores are 0.048 and 7, respectively. Associations between EQ-5D-5L and FI-CGA-10 scores were analyzed by Pearson’s correlation and linear regression models adjusting for covariates (age, sex, cancer type, and stage). Results: Median age was 80 years, 60% were male, and 68% had gastrointestinal cancer. The mean +- SD of the FI-CGA-10 score was 0.35 +- 0.19. The FI-CGA-10 negatively correlated with the EQ-5D-5L index (Pearson’s r = -0.69; 95% CI -0.72 to -0.66; P<.001) and VAS (r = -0.47; 95% CI -0.52 to -0.42; P<.001) scores. After adjusting for the covariates, each 0.1 unit increase in FI-CGA-10 score was associated with 0.070 decrease in EQ-5D-5L index (95% CI -0.075 to -0.066; P<.001) and 4.9 decrease in VAS scores (95% CI -5.5 to -4.4; P<.001). Using the three-level classification, 22% of patients (n = 221) were categorized as fit, 38% (n = 384) as pre-frail, and 40% (n =410) as frail. Overall, the fit group had the highest EQ-5D-5L index and VAS scores followed by the pre-frail and frail groups (table). The score differences between the frailty categories were statistically significant and clinically meaningful according to the MID values. Conclusions: This study demonstrated that frailty assessed by the FI-CGA-10 cross-sectionally correlated with HRQOL measured by the EQ-5D-5L in older Japanese adults with cancer. The observed association further supports construct validity of the FI-CGA-10 as a CGA-based frailty measure. [Table: see text]
Overlapping and non-overlapping indications for checkpoint inhibitors in the US.
Authors: Paul Jeddeo , Mitchell Aaron Philip , Kesselheim Aaron S , Rome Benjamin N
Published: June 2024

11057

Background: Since the first checkpoint inhibitor was approved in 2014, this class of cancer drug has revolutionized the treatment of several malignancies. As of January 2024, 11 checkpoint inhibitors have been approved by the US Food and Drug Administration (FDA), each with its own particular indications. We assessed the overlap of approved indications, which has implications for competition and price negotiation by payers. Methods: In this cross-sectional study, we evaluated the FDA-approved indications for 11 checkpoint inhibitors as of January 2024. Indications were defined by cancer tissue type (or mutation status for non-tumor-type indications), stage, and line of treatment (first-line, second-line, third-line, or fourth-or-greater-line). Non-overlapping indications were defined as those with only a single drug approved; for overlapping indications, we tabulated the number of approved drugs. Results: The 11 FDA-approved checkpoint inhibitors were associated with 43 distinct indications, ranging from 2 (retifanlimab, toripalimab, and tremelimumab) to 35 (pembrolizumab) indications per drug. Fifteen (43%) indications were non-overlapping. Pembrolizumab had 11 non-overlapping indications (e.g., certain breast, cervical, and urothelial cancers); all other drugs had between 0 and 2 non-overlapping indications (Table). Among the 28 overlapping indications, 15 (54%) had approvals for 2 drugs, 9 (32%) had approvals for 3 drugs, 3 (11%) had approvals for 4 drugs, and 1 (3%; non-small cell lung cancer) had approvals for 7 of the 11 drugs. Conclusions: Checkpoint inhibitors are FDA-approved for a total of 43 different indications, but most indications were included on the labeling of 3 or fewer drugs in this class. Over 1 in 3 indications had only 1 approved drug, most commonly pembrolizumab. This limited overlap of indications suggests that manufacturers may avoid seeking approval for indications that already have multiple approved drugs of the same class, which may decrease competition and lead to sustained high drug prices. To provide patients with better information about the checkpoint inhibitor most appropriate for their cancer, the NIH could fund, and the FDA could encourage, more direct comparative effectiveness trials. [Table: see text]
Accelerating cancer research trial startup in the community setting: A quality-improvement study.
Authors: Claes Jason Joseph , Maher James F. , Thompson Wayne , Benoit Lisa , Cook Billie , Newbury Patrick , Adams Alyssa , O'Connor Melinda , Ohlhaut Emma , Wirthlin Chelsea
Published: June 2024

11066

Background: There is a large variation in activation times for cancer clinical trials, delaying the opportunity for patients to benefit from cutting edge treatments. Academic medical centers typically take longer to activate a clinical trial as compared to community settings. Some academic medical centers have adopted quality improvement processes to reduce clinical trial start-up time. Our center, TriHealth Cancer & Blood Institute (TCBI) in the SW Ohio community has also adopted quality improvement processes to further reduce startup time within our oncology research group. Methods: This study encompassed July 2022-June 2023, with baseline data drawn from January 2021 to December 2021 prior to the study period which revealed a mean clinical trial start-up time of 116 days. The research group used a swim-lane process to define the typical process & stakeholders for clinical activation time at our institution prior to the study time. Our group identified three major areas with significant lag-time - contracts, budgets, & IRB/ICF - with the overarching root cause for delays due to lack of organizational process & expertise in these major areas. Using Plan-Do-Study-Act (PDSA), we instituted interventions, which included utilizing a central IRB, identifying a responsible member with extensive research budgeting to review research study budgets, & identified a responsible member with extensive contracts review & negotiations working with Central Legal throughout the contracts negotiation process with sponsor(s). Results: During this 12-month study time, our center demonstrated a 44% reduction in trial start up time (141 days to 79 days), while at the same time doubling the number of active trials. This process change resulted in sustainability that carried into 2023, further reducing start-up time to 70 days. In 2021, we opened 6 studies and after adoption of these process improvements (2022) we doubled the number of studies by 117%, while opening 67% more in 2023 than in 2021. The ability to open more studies has allowed us to shift patient enrollment to more investigational trials while increasing treatment enrollment from 2022 to 2023 by 24%. Through process improvement, more treatment studies are open & available for our community. Conclusions: By implementing interventions to streamline clinical trial activation time, our center was able to significantly & sustainably reduce the time required to start a clinical trial in our community health system in a 12-month period, resulting in our ability to initiate more clinical trials. As a result, more treatment trial patients were able to be enrolled in these clinical trials at TCBI, with the hope of improved outcomes. We anticipate that further adoption of just-in-time studies may help to decrease this activation time further. [Table: see text]
Cost-effectiveness of a circulating tumor fraction molecular biomarker for treatment response monitoring.
Authors: Rivers Zachary , Aggarwal Charu , Matrana Marc Ryan , Feliciano Josephine Louella , Mitra Akash , Nimeiri Halla , Ben-Shachar Rotem , Eng Cathy , Kircher Sheetal Mehta
Published: June 2024

11082

Background: Clinical validation studies have demonstrated that molecular biomarkers quantifying ctDNA changes in circulating tumor fraction (TF) predict survival outcomes and may be used for treatment response monitoring (TRM). While clinical utility studies to determine the impact on outcomes of molecular biomarker-driven treatment decisions versus standard of care imaging are ongoing, cost-effectiveness has not been evaluated. Here we evaluate the cost-effectiveness of a molecular biomarker, Tempus xM, used for TRM. Methods: xM quantifies changes in TF from baseline and on-treatment liquid biopsies. We use a patient-level Markov simulation to compare xM-guided treatment (intervention) to diagnostic imaging-guided treatment (control) over 24 weeks of therapy. In both arms xM and imaging is assessed at 12 weeks and treatment decisions are made based on xM (intervention) or diagnostic imaging (control). Imaging and xM concordance (Table) was based on a retrospective, real-world (RW) study of 51 patients tested with xM that received rw-imaging that evaluated the association of xM with rw-outcomes in advanced pan-cancer patients treated with immune checkpoint inhibitors (ICIs) +/- chemotherapy (CT). We assume non-responders discontinue ICIs and switch to CT and responders remain on ICIs. Appropriate (inappropriate) therapy was defined as treatment decisions concordant (discordant) with xM results. Costs were calculated from Medicare’s perspective in 2023 USD. Control patients do not accrue the cost of xM. Sensitivity analyses were conducted. Results: Intervention patients saved $4,400 ($63,424 vs. $67,824 in controls) by preventing use of ineffective therapy (4.3 weeks avoided vs 0.2 weeks in controls), a savings of $1076 per week of ineffective therapy avoided. In all sensitivity analyses, xM-guided therapy remained cost effective (Table). The timing of therapy intervention and the cost of therapy had the largest impact on savings. Conclusions: This model demonstrates that xM-guided treatment is cost-saving compared to imaging alone during 24 weeks of treatment. Future work will incorporate variable clinical uptake and long-term outcomes by expanding the time horizon and including treatment discontinuation due to toxicities and mortality. [Table: see text]
Cost-effectiveness of short-course radiotherapy versus long-course chemoradiation in organ preservation for locally advanced rectal cancer.
Authors: Dornisch Anna , Cui Christina , Luo William Yu , Sherer Michael Vincent , Murphy James Don
Published: June 2024

11089

Background: Short-course radiation therapy (SCRT) has previously been found to be cost-effective compared to long-course chemoradiation (LCRT) for patients with locally advanced rectal cancer undergoing operative management. However, non-operative management protocols have recently become a standard treatment option for patients diagnosed with locally advanced rectal cancer achieving a complete clinical response after total neoadjuvant therapy (TNT) as surgery has significant impacts on quality of life. Recent data suggests higher rates of local regrowth and a correspondingly lower rate of organ preservation with SCRT-TNT compared to LCRT-TNT. With this study, we evaluated the cost-effectiveness of SCRT versus LCRT in the setting of non-operative management for locally advanced rectal cancer. Methods: We built a microsimulation model to simulate 5-year outcomes for 1 million hypothetical patients aged 65 years with locally advanced rectal cancer treated with TNT including either SCRT or LCRT. Patients achieving a complete clinical response with TNT opted for a non-operative management approach, undergoing surgery only with subsequent local progression. Patients not achieving a complete clinical response went directly to surgery. The model incorporated costs, quality of life (measured by health utility), and probabilities of disease progression and death. We extracted probabilities of disease progression and death and health utilities from published literature. We assessed costs from the healthcare payer perspective. We measured cost-effectiveness with incremental cost-effectiveness ratio (ICER), with ICERs under $100,000 per quality-adjusted life-year (QALY) considered cost-effective. One way and probabilistic sensitivity analyses were used to test model uncertainty. Results: We found that compared to SCRT, LCRT increased overall cost by $10,457 and improved effectiveness by 0.16 QALYs resulting in an ICER of $67,200/QALY. The model was most sensitive to assumptions about risks of local recurrence in the non-operative setting, the health utility of non-operative management, and the costs of LCRT and SCRT. The model was not sensitive to assumptions about costs of diagnostic evaluation (i.e. flexible sigmoidoscopy) and probability of distant recurrence. Probabilistic sensitivity analysis demonstrated that LCRT was cost-effective in 91% of iterations. Conclusions: Long-course chemoradiation could represent a cost-effective strategy compared with short-course radiotherapy in the non-operative management of patients with locally advanced rectal cancer. The ongoing ACO/ARO/AIO-18.1 trial testing the hypothesis that LCRT-TNT will increase organ preservation rates relative to SCRT-TNT will help confirm these findings.
Systemic anti-cancer therapy and cost at end of life: A SEER Medicare analysis.
Authors: Adelson Kerin B. , Cheng Lee , Huang Yu-Ting , Niu Jiangong , Zhao Hui , Nortje Nico , Xiang Jenny Jing , Giordano Sharon H. , Canavan Maureen
Published: June 2024

11092

Background: Systemic anticancer therapy (SACT) administered near the end of life (EOL) is associated with higher costs, driven by pharmaceuticals and associated acute care use that occurs when patients continue treatment in lieu of transition to hospice. Since 2015 overall rates of systemic therapy at the EOL have remained stable, while some chemotherapy has been replaced by costly immunotherapy. It is not known whether immunotherapy is associated with the same impact on total cost of care (TCOC) as chemotherapy. We evaluated the relationship between type of SACT vs no SACT within 30 days of death on categories of cost. Methods: We identified patients from the SEER-Medicare database diagnosed between 2005 and 2019 with solid tumors (ST) and liquid tumors (LT) who died from 2015-2020. We assessed differences in Medicare cost within 30 days of death by subtype of SACT: combination chemo-immunotherapy (CI), immunotherapy only (IO), chemotherapy only (CO) and no SACT. Dependent variables were TCOC (including all Medicare claims), as well as cost of drugs, hospitalizations, emergency department (ED), and hospice normalized and adjusted for inflation. Results: 6.2% (27,317/440,349) of ST decedents and 12.7% (7,544/59,449) LT decedents received SACT at EOL. See table. Among ST patients who received SACT, the mean TCOC was $26,282 (standard deviation (SD) $26,700) and was highest among patients receiving CI, $27,973 (SD: $26,285) vs. $17,642 (SD: $29,798) for patients without SACT ( p <.001). Among LT patients who received SACT, the mean TCOC was $26,282 (SD $26,700) and was highest among CI patients $33,632 (SD: $26,283) vs. $24,689 (SD: $39,735) for patients with no SACT ( p<.001). We observed higher cost for drugs, hospitalizations (except for LT patients receiving CI vs. no SACT), ED and lower hospice costs for patients receiving each SACT subgroup compared with no SACT. All results except those noted in table were significant (p <.001). Conclusions: Receipt of SACT within 30 days of death was associated with significantly higher Medicare costs. Higher TCOC in those who received SACT is only partially explained by drug costs; most acute care costs were also significantly higher among patients who received any type of SACT including CI, IO, CO than among those who did not. [Table: see text]
Enhancing the patient journey to clinical trial enrollment with navigation to optimize accrual: A pilot study for a pragmatic multicentre, stepped wedge, cluster randomized controlled trial (The CTN Pilot Trial).
Authors: Akingbade Emmanuel , Fatima Rija , Delisle Megan , Abdel-Nabi Rhonda , Hossami Mahmoud , Touma Kayla , Nassar Renee , Sharma Depen , Luginaah Anthony , Hamm Caroline M.
Published: June 2024

11093

Background: Clinical trials are essential to the advancement of clinical therapies, yet accrual rates remain disappointing. Multiple challenges lead to less than 5% of cancer patients enrolled onto clinical trials. The Clinical Trials Navigator (CTN) program was established to assist patients and health care professionals identify appropriate clinical trials for patients. Methods: Between March 2019 to January 2024, a novel navigator-assisted clinical trials search program was offered to Canadian patients. Three non-medical navigators were trained to receive referrals, review medical information, and search five different clinical trial search engines. Eligibility criteria was scrutinized. A second review of the clinical trial list was conducted by two physicians. The final curated list of clinical trials was provided to patients and their oncologist. Results: A total of 373 patients were referred to the CTN program during the study period. A unique clinical trial search was performed for each patient yielding a median of only one potentially eligible trial per patient. Clinical trial enrolment occurred in 3.2% of patients in our database which translates to a 19% rate of successful enrolment of those referred to a trial by the CTN. Most patients (78%) were referred to clinical trial sites that conducted more than 100 clinical trials at any time. Compared to the Canadian cancer statistics, lung, lymphoma, pancreatic and brain cancers were overrepresented in referrals to the CTN program while prostate cancer was underrepresented. Type of cancer played a significant role in the likelihood of a successful referral (p < 0.01). Lung cancer was the most frequently reported cancer that resulted in referrals and breast cancer showed a lower frequency of referrals. The cancer type, stage and number of lines of prior therapy were not significantly associated with the patient enrollment onto a clinical trial. An increase in survival of referred patients from last analysis from 3.0 months to 5.3 months. Conclusions: The CTN program is a successful tool to identify clinical trials for cancer patients and can improve clinical trial accrual, as almost one fifth of patients (19%) who were referred to a clinical trial were enrolled. Ongoing iterative changes to the program to improve these metrics are underway and efforts to improve implementation of the CTN program across Canada are ongoing.