tbuckley/cabot-search huggingface dataset:
Geographic distribution and accessibility of clinic trials for advanced-stage pancreatic cancer in the United States: A focus on rural and minority health disparities.
Authors: Wade T. Swenson, Emily Westergard, Abigail P Swenson, Zachary Schroeder
Journal: Journal of Clinical Oncology (2024)

11048 Background: Our research delves into the geographical distribution and accessibility of clinical trials for metastatic pancreatic cancer patients in the U.S., spotlighting the challenges faced by rural communities and minority groups. Prior research indicated nearly half of these patients would have to commute over an hour to reach a trial site. [1] Our study provides a refreshed perspective on this issue, offering a more comprehensive analysis. Methods: Utilizing the ClinicalTrials.gov portal, we identified active interventional clinical trials for metastatic pancreatic cancer patients as of November 25, 2022. We obtained distinct zip codes linked to these trials and, using 2020 census data, gauged the proportion of the U.S. populace residing within specific distances from these sites. Our analysis encompassed factors like urbanity, ethnicity, and other socio-economic parameters. We also developed illustrative maps to visually represent the U.S. clinical trial accessibility landscape. Results: The majority of Americans diagnosed with metastatic pancreatic cancer have clinical trials within their reach. A significant 65.7% of the U.S. populace resides within a 30-mile radius of a relevant clinical trial site. However, a closer look reveals pronounced disparities based on urban-rural demarcations and racial lines, with American Indians facing the most pronounced accessibility challenges. Conclusions: Our data underscores the uneven geographical spread of these trials. This skewed distribution poses accessibility hurdles for specific demographics, especially those in rural areas and certain racial groups. Our findings underscore the pressing need for strategic initiatives to rectify these disparities, ensuring clinical trials are within reach for every individual, irrespective of their location or background.
Recent trends in incidence, survival and mortality of female breast in the US: A Surveillance, Epidemiology, and End Results (SEER) database study 2010-2020.
Authors: Samia Asif, Meghana Kesireddy
Journal: Journal of Clinical Oncology (2024)

e23078 Background: We examined epidemiological trends and patient characteristics including age, race, incidence and survival in female breast cancer (BC) using the updated largest population-based cancer registry in the US. Methods: Female patients diagnosed with breast cancer between 2010-2020 were identified in SEER registries. We incorporated SEER 22 registries to calculate incidence, race, disease characteristics and overall survival. Results: Incidence Rate (IR) for BC has been increasing by 0.4%/year and mortality rates (MR) have declined 1.3%/year during 2010-2020 for all patients. 5-&amp;10-year overall survival (OS) has increased by 0.1 and 0.2% respectively. For ages &lt; 50 years,IR increased by 0.9% vs 0.4% for those 65 and above. No statistically significant change in IR was noted for ages 50-64y. For ages &lt; 50 and between 50-64y, MR overall decreased by 1.4%/y each vs by 1.1%/y for those 65+. However, no statistically significant change in MR was noted for women &lt; 50y between 2016-2020. IR increased by 1.6%/year in Asian/Pacific Islanders (API), 1.1%/y in Hispanics (H),0.6% in Blacks (B) and 0.4% in Non-Hispanic White (NHW) and. MR declined 1.5%/y in B, 1.2%/y NHW, 1% H and by 0.3% in API.IR for HR+/HER2- BC increased by 1.9%. No statistically significant change in IR was noted for triple negative or HER2+ only BC. IR for HR+/HER2+ BC increased overall during this time period by 1.4%; however, IR increased by 3.6% between 2010-2016 and decreased by 2.9% after 2016. 5y-OS was 91% in 2015 (CI 90.7-91.3) for all women, improved from 89.7% in 2010 (CI 89.4-90.0). 5yOS was 90.7% vs 91.3% vs 91.0% for &lt; 50, 50-64 and 65+ age groups. When compared to 2010 and 2005, 5yOS was consistently improved across all age groups. 5yOS in B was 82.5% (CI 81.6-83.4) vs 92.1% (CI 91.8-92.5) in NHW. This discrepancy existed across all age groups: for &lt; 50, 50-64 and 65+y, 91.6 vs 92.5 vs 92.1% for W women vs 82.7 vs 82.9 vs 82.0% for their B counterparts. 5yOS for localized, regional and distant disease at diagnosis for all women was 99.2%, 86.7% and 31.5%. 5yOS for B vs W females was 95.9 vs 99.7% localized, 78.3 vs 88% regional and 23.4 vs 33.0% for distant disease. Conclusions: Epidemiological trends show improved OS in BC among all groups. B females and patients with advanced stage have worse outcomes. Greater increase in IR was noted for women &lt; 50 years of age. Greater IR increase was noted in H and API women but decline in MR was smallest in these women. IR for HR/HER2 + BC increased initially followed by a decline. 5r survival in B women was lower compared to NHW across all age groups. 5y survival for B women was worse, irrespective of stage at diagnosis. We hypothesize underlying disease biology may be a potential factor for worse outcome in B women.
Insights from C-CAT repository: A novel approach to identifying appropriate patient populations for anticancer drug development using the clinicogenomic nationwide database in Japan.
Authors: Rui Kitadai, Takafumi Koyama, Yusuke Okuma, Taro Shibata, Takashi Kohno
Journal: Journal of Clinical Oncology (2024)

11159 Background: The integration of Comprehensive Genomic Profiling (CGP) with real-world data (RWD) provides crucial insights for anticancer drug development to achieve precision oncology, therefore, the current global trend to construct as the national projects, yet its clinical impact remains underexplored. The therapeutic efficacy of each line of anti-cancer drug in various cancer types and the relationship between genetic alterations and the effect of anticancer drugs is needed to guide the direction of future drug development promptly and precisely. Methods: A comprehensive analysis was conducted on data from Japan's Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository between June 2019 and December 2023. Five genomic profiling assays for CGP testing were reimbursed by nation-wide insurance in Japan. Utilizing the clinicogenomic repository of C-CAT, registered data of therapeutic efficacy of anticancer drug including cytotoxic agents, molecular-targeted agents, and immune checkpoint inhibitors were evaluated in association with genetic alterations. Data on anticancer drug of patients (pts) with recurrent or metastatic disease were included in the analysis. Results: The C-CAT registry data encompassed 60,256 pts across 32 tumor organ sites, classified ontology by the OncoTree over 4.5 years. Of these patients, 30,234 were male, and 30,017 were female, with 5 classified as unknown. In terms of age, 31,919 pts were &lt; 65. The most registered origins were colorectal (n=10,110), pancreas (n=8,069), biliary tract (n=5,030), breast (n=3,744), esophagus/stomach (n=3,734), prostate (n=3,701), ovarian/fallopian tube (n=3,521), lung (n=3,427), and soft tissue (n=2,568). TP53mutations (58.3%, n=35,102) were most prevalent, followed by KRAS (25.8%, n=15,521), APC (19.9%, n=11,919), NOTCH3 (14.1%, n=8,502), and PIK3CA (13.0%, n=7,861). The frequency of BRCA1/2mutation was 4.1% (n=2,479). Overall response rate (ORR) for the first-, second-, third-, and fourth-lines treatment were 35.7%, 23.3%, 19.4%, and 19.2%, respectively. Pts treated with cisplatin or carboplatin in the first-line treatment, who had TP53 mutations, showed a better ORR than those without (44.0% vs. 38.9%, p &lt; 0.001). Similarly, pts with BRCA1/2mutation showed a better ORR than those without (53.9% vs. 41.4%, p &lt; 0.001) in the first-line treatment. Conclusions: This study was the first to report the relationship between genetic alterations and the therapeutic effect of anticancer drugs in each line. This approach based on big data analysis potentially accelerates drug development in the appropriate patient population by identifying significant associations between specific genetic mutations and improved outcomes with certain chemotherapy regimens in various cancers.
Real-world treatment patterns and outcomes of zanubrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL).
Authors: Margaret Krackeler, Bryant Chee, Arthur K Orchanian, Lisa Y. Law, Alfredo R. Lopez, Susan Buchanan, Gregory A. Maglinte, Raymond Liu, Zheng Zhu, Lori C. Sakoda, Jahan Tavakoli
Journal: Journal of Clinical Oncology (2024)

11158 Background: Zanubrutinib (zanu) is a next-generation selective Bruton’s tyrosine kinase inhibitor (BTKi) with superior efficacy over first generation ibrutinib (ibru) in CLL/SLL patients (pts). Herein we present real-world treatment patterns based on a formulary change from ibrutinib to zanubrutinib in pts with CLL/SLL in an integrated community oncology practice. Methods: We retrospectively analyzed CLL/SLL pts 18 years and older who received at least 3 months of zanubrutinib from October 1, 2018 to September 15, 2023 at Kaiser Permanente Northern California. Treatment patterns, treatment-emergent adverse events (TEAEs: AEs reported during BTKi use), treatment-limiting adverse events (TLAEs: AEs leading to BTKi discontinuation), and mortality were reported. Results: A total of 281 pts received zanu (median age: 71 years; 64% male); 190 pts switched from ibru (ibru-zanu), and 91 pts received zanu only. Most pts were White (75%) followed by Black (10%). Compared with ibru-zanu pts, zanu-only pts were older (median age 74 vs 69 years) and had more comorbidities but were comparable in sex, race, and insurance type. The primary reasons for switching to zanu were formulary change (73%) and progression (15%). Median follow-up time after initiation of first BTKi was longer in the ibru-zanu group (Table). Similar TEAE rates were seen with use of both BTKi therapies, with lower TLAE rates with zanu (Table). Most common TLAE were atrial fibrillation and fatigue for ibru, and cytopenias and rash/bruising for zanu. Cardiac TLAE and non-TLAE rates overall were higher with ibru than zanu, and the rates decreased while on zanu after switching from ibru (Table). Dose modification occurred in 34 pts on ibru and 50 pts on zanu (18 ibru-zanu pts, 32 zanu-only pts), with reductions primarily for grade 1-2 AEs. Of the 281 pts who received zanu, 79% remain on treatment at the end of data collection; 13 pts died (8 from infection, including 5 from COVID), with no reports of treatment-related deaths. Conclusions: In the real-world setting post-formulary change, zanu is effective and safe in pts with or without prior ibru use. Zanu use had lower cardiotoxicity and TLAE rates than ibru though data was limited by a difference in follow-up time. Similar results were seen in zanu-only pts despite being older and having more comorbidities, with discontinuation most often due to grade &lt;3 AEs. [Table: see text]
Cognitive symptoms in patients with cancer receiving PD-1/PD-L1 checkpoint inhibitors: Insights from a cross-sectional pilot study.
Authors: GeeSu Yang, Upendra P. Hegde
Journal: Journal of Clinical Oncology (2024)

12094 Background: Cancer-related cognitive impairment is common with traditional therapeutic modalities, affecting memory, psychomotor speed, attention, and executive function of up to 75% of adults with cancer. Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as novel and efficacious treatments due to their ability to penetrate the blood-brain barrier and improve survival rates. However, they come with significant short- and long-term complications, including neurological toxicities. Despite their benefits, the impact of ICIs on cognitive function is not well understood. This study aims to examine the frequency and severity of cognitive impairment and the factors correlated among adults with cancer receiving ICIs. Methods: We collected questionnaire data on cognitive function using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) and other concurrent symptoms, as well as saliva samples of a subset of inflammatory cytokines from patients treated with PD-1/PD-L1 checkpoint inhibitors between 2022 and 2023. Sample characteristics were described using mean, frequency, and percentage. To analyze the relationship among symptoms and demographics, we used Pearson’s correlation and the Mann-Whitney U test. Saliva cytokines were analyzed using ELISA assays. This study is IRB approved. Results: Twenty-three patients (male: n=11, female: n=12) have received ICIs for an average of eight months, with a mean age of 70.87±11.63 years. 78.3% had melanoma/skin cancer, 8.7% had head and neck cancer, and 13% had other malignancies. Pembrolizumab was administered to 47.8%, and Nivolumab to 26.1%. The mean scores of FACT-Cog for perceived cognitive impairment (PCI) and perceived cognitive abilities (PCA) were 60.87±13.06 (maximum: 72) and 22.30±6.70 (maximum: 28), respectively. 26.1% of participants (n=6) reported lower scores than the cut-off in both PCI (cut-off: ≤55.1) and PCA (cut-off: ≤19.5). Lower FACT-Cog PCI scores were significantly correlated with older age ( r=-.511, p&lt;.05), greater fatigue ( r=-.483, p&lt;.05) and pain ( r=-.558, p&lt;.01). Participants with PCA and PCI scores below the cut-off showed higher mean concentrations of IL-1β (mean±SE: 188.22±133.72 vs. 80.99±14.73pg/mL), CRP (6659.47±3027.58 vs. 3910.71±1022.41pg/mL), and IL-6 (109.24±56.07 vs. 30.22±6.26pg/mL) compared to those with scores above the cut-off, although the results were not significant. This suggests that increased inflammatory cytokines may be associated with cognitive impairment. Conclusions: This preliminary study suggests that some patients may experience cognitive impairment during ICI treatment. As cancer patients are more at risk for cognitive impairment before treatment, a longitudinal study is warranted to confirm cognitive function both pre- and post-immunotherapy, along with objective measures of cognitive performance.
Implementing financial toxicity and health-related social risks screening and referral.
Authors: Bridgette Thom, Emeline Mariam Aviki, Fumiko Chino
Journal: Journal of Clinical Oncology (2024)

11006 Background: Financial toxicity (FT), or cancer-related economic hardship, is associated with delayed/skipped care, reduced quality of life, and worse mortality. Screening for FT and health-related social risks (HRSR) as part of assessment for social determinates of health is currently being integrated into clinical care, but there is limited research on outcomes after patients screen positive for FT or HRSR. Methods: We conducted FT and HRSR screening for patients receiving treatment for breast, gynecologic, gastrointestinal, or thoracic cancer at an urban comprehensive cancer center. Screening included the 11-item Comprehensive Score for Financial Toxicity (COST) tool (scored 0-44, lower scores = worse FT) and a HRSR checklist to identify food, housing, medicine, and transportation insecurity. A COST score ≤20 or any endorsed HRSR was considered a positive screen, and financial/assistance counseling referral was offered. Multivariable logistic regression assessed associations of accepting referral, after controlling for demographic and clinical characteristics. Data were collected 09/2022-08/2023. Results: 28,606 patients completed screening, of which 32% (n = 9106) screened positive. Median COST was 16.0. Identified HRSR were: 23% food, 25% housing, 21% medicine, and 24% transportation insecurity. Of positive screens, 51% (n = 4683) requested some form of financial counseling. Associations with accepted referral include: higher FT (β = 1.15, 95% CI: 1.13, 1.16), younger age (β = 1.01, 95% CI: 1.008, 1.02), more essential needs (β = 1.19, 95% CI: 1.13, 1.25), non-White race/ethnicity (β = 1.70, 95% CI: 1.49, 1.93), and stage 3 (β = 1.29, 95% CI: 1.08, 1.53) or stage 4 (β = 1.26, 95% CI: 1.07, 1.49) diagnoses (vs. stage 0/1). Needs of patients who requested counseling included concerns relating to out-of-pocket expenses (68%), non-medical expenses (39%), health insurance coverage (23%), and paying for prescription medication (18%; not mutually exclusive). Of financial counseling sessions with available dispositions (n = 2336/4683, 50%), outcomes (not mutually exclusive) included general counseling (29%), referral to specific assistance programs (e.g., copay assistance, reduced cost care program; 15%), and insurance navigation (15%). One-third of patients requesting counseling did not respond to contact attempts; 21% reported no longer being interested in counseling upon contact. Conclusions: Screening for FT and HRSR was feasible, and one-third of patients were identified as at risk for FT or having an unmet essential need. Patients known to have worse FT outcomes (those with later-stage disease, younger age, higher FT, minoritized groups) were more likely to accept financial counseling; however, only one-half of those at risk accepted help. Future work will focus on improving workflows to ensure assistance meets patient needs, including addressing patient stigma around requesting help.
Patients’ voices matter: Translating pretreatment patient-reported outcomes into high and low health-related quality of life provides a new clinical aspect on prognosis and survival in patients with previously untreated diffuse large B‐cell lymphoma.
Authors: Peiqing Yu, Will Liao, Avrita Campinha-Bacote, Peter Trask, Sandhya Balasubramanian, Andrea Knapp, Huang Huang
Journal: Journal of Clinical Oncology (2024)

e23165 Background: Patient-reported health-related quality of life (HRQoL) measures collected prior to treatment initiation have been shown to be prognostic of disease outcomes and survival in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), including progression-free survival (PFS) and overall survival (OS), However, these HRQoL measures are usually expressed as numbers from a scale (e.g. from 0 to 100), which limit their ease of clinical utility compared to binary scales (i.e. high vs. low). Using HRQoL measures collected from the phase 3 study GOYA, we aim to convert these measures into binary scales by identifying optimal cutoffs and demonstrate their clinical utility in differentiating patient risks in DLBCL. Methods: HRQoL data from the physical functioning (PF2), global health status (QL2), and fatigue (FA) scales from the EORTC QLQ-C30 questionnaire and the lymphoma subscale (LYMS) from the FACT-LYM questionnaire were used in this analysis. The optimal cutoff points were identified using statistical metrics that evaluate the prognostic value and goodness-of-fit for each assessed cutoff point. The top performing binary HRQoL scale was further assessed in its clinical utility as an addition to the Internal Prognostic Index (IPI), a standard risk classification tool in DLBCL based on 5 binary measures of patient baseline characteristics, to evaluate whether adding the HRQoL scale would potentially improve the risk classification. Results: As shown in the table, while all binary scales can clearly differentiate patient overall survival (demonstrated by the hazard ratios), PF2 numerically exhibited the best performance, and was further assessed as an addition to IPI. After adding PF2 to the base OS model containing only IPI, we observed improvements in model performance metrics, including the concordance index and the goodness-of-fit. In addition, among patients classified as high risk by IPI (n = 185, 3-yr OS: 65% [95% CI 68-72%]), those with low HRQoL (n = 102, 3-yr OS: 56% [95% CI 47-67%]) had a substantially worse OS, suggesting that further refinement of patient-risk defined by IPI may be feasible with HRQoL measures. Conclusions: Our work highlights the potential of the binary HRQoL scales to provide additional prognostic value to IPI, and suggests that patient reported outcomes may be useful in further refining patient risk classification in addition to IPI in untreated DLBCL. [Table: see text]
Unintentional weight loss, body composition, and all-cause mortality among United States adults with cancer.
Authors: Thomas Lucido, Aayush Visaria, Benjamin Bates
Journal: Journal of Clinical Oncology (2024)

e22527 Background: While unintentional weight loss (UWL) is a common presenting symptom of malignancy, weight changes also occur regularly in patients with diagnosed cancer.UWL is often characterized by considerable muscle and fat loss and can lead to cachexia, which may increase risk of mortality. This nationally representative study aims to assess the association between UWL and mortality among adults with history of cancer and characterize differences in body composition. Methods: This was a retrospective cohort study of the National Health and Nutrition Examination Survey 1999-2018 linked to the 2019 National Death Index. We identified adults with self-reported history of cancer, excluding non-melanoma skin cancer. Weight change was determined as the difference between current weight and self-reported weight 1 year prior to interview. We categorized weight change into: UWL (unintentionally losing &gt; 5% of weight), intention weight loss (IWL) (intentional loss &gt; 5% weight), no weight change (NWC) (≤5% weight change), weight gain (WG) ( &gt; 5% weight gain). We estimated risk of all-cause mortality using gender-stratified multivariable Cox regression, adjusting for demographics (age, race, income, education, insurance status), sociobehavioral factors (smoking, alcohol, nutrition, physical activity, self-reported health), comorbidities, and albumin. We additionally identified participants with cancer who had whole-body dual x-ray absorptiometry scans (2011-2018) and assessed body composition measurements including total lean mass, lean-to-fat ratio, subcutaneous fat mass, and visceral fat mass by weight change category using multivariable linear regression. Results: Among 3,153 participants (mean age 62 years, 55% women, 82% non-Hispanic White), the top four primary cancers were breast (21%), prostate (14%), melanoma (11%), and cervical (11%). Approximately 9% of men and 11% of women experienced UWL. Adults with UWL were more likely to have lower socioeconomic status, more functional limitations, and higher comorbidity burden. Across a median 7 years (IQR, 3-11y) follow-up, 22% of females and 34% of men died. Both men and women experiencing UWL had more than 2 times the risk of all-cause mortality compared to NWC (adjusted HR [95% CI]; men: 2.02 [1.47, 2.78]), women: 2.43 [1.78, 3.34]). Participants with UWL had less subcutaneous fat mass (-113g, 95% CI [-242, 16]) and visceral fat mass (-65g, 95% CI [-146, 16]) compared to NWC, though not statistically significance. Conclusions: UWL in patients with history of cancer is independently associated with more than 2 times the risk of all-cause mortality in both men and women. UWL was associated with proportional loss of both subcutaneous and visceral fat mass. Further longitudinal studies examining UWL’s impact on body composition changes and downstream outcomes by cancer type and stage are needed.