bluuebunny/crossref_metadata_2025 huggingface dataset:
Inpatient healthcare utilization in the first year following a childhood cancer diagnosis: A population-based analysis.
Authors: Ohlsen Timothy James Daeeun , Doody David , Noyd David H , Desai Arti D , Leisenring Wendy M. , Mueller Beth A , Chow Eric Jessen
Published: June 2024

11138

Background: Children with cancer may require substantial healthcare resources during treatment, including inpatient care. Hospital utilization patterns at the population level, and factors associated with higher utilization, are not well-described. Methods: We conducted a retrospective cohort analysis of Washington State (WA) cancer registry data (1992-2013) linked to state birth (1974-2013), death (1992-2013), and hospital discharge (1992-2013) records to identify all WA children diagnosed with cancer <20 years. We examined hospitalization frequency and total inpatient bed days in the year after cancer diagnosis. To evaluate factors associated with outcomes of interest, we constructed multivariable negative binomial regression models of children with ≥1 inpatient admission, calculating incidence rate ratios (IRR). Covariates included rural residence (binary; census tract rural-urban commuting area codes), high neighborhood deprivation (binary; state-normative census block group Area Deprivation Index [ADI]), sex, race/ethnicity, diagnosis age, birth year, and cancer type (per International Classification of Childhood Cancer). Due to differences in utilization by cancer type, we also examined children in subanalyses with acute lymphoblastic leukemia (ALL), lymphomas, and solid (including central nervous system [CNS]) tumors. Results: 2,231 children (mean diagnosis age 7.2 years; 68% diagnosed since 2000) had 12,833 inpatient encounters. In the year after diagnosis, children had a median of 4 (IQR 2-8) hospitalizations/year at-risk, and 21 (IQR 8-54) inpatient days (median length of stay 4 days [IQR 2-6]). In multivariable analysis, high ADI (IRR 1.11, 95% CI 1.01-1.21), but not rural residence (IRR 0.95, 95% CI 0.85-1.05), was associated with greater hospitalization frequency. Female sex was associated with lower frequency (IRR 0.94, 95% CI 0.88-1.00). In analysis of total inpatient days, high ADI (IRR 1.15, 95% CI 1.02-1.29) and Hispanic ethnicity (IRR 1.31, 95% CI 1.13-1.51) were independently associated with greater inpatient days. In subanalysis of patients with ALL (N=497), associations between inpatient days and ADI (IRR 1.18, 95% CI 0.99-1.40) and Hispanic ethnicity (IRR 1.01, 0.84-1.23) were no longer significant. For lymphoma (N=259), associations were similar but also no longer significant (ADI IRR 1.14, 95% CI 0.78-1.71; Hispanic IRR 1.26, 95% CI 0.79-2.10). Among patients with solid/CNS tumors (N=1,151), associations with Hispanic ethnicity remained significant (IRR 1.46, 95% CI 1.19-1.80), but not ADI (IRR 1.11, 95% CI 0.95-1.30). Conclusions: Children with cancer spend considerable time inpatient during the year after diagnosis. Disparities in hospital utilization mirror some known disparities in childhood cancer survival. Initiatives to alleviate systemic disadvantages may reduce inpatient utilization for some groups.
Incorporating precision oncology in everyday clinical practice: First two years of comprehensive genomic profiling (CGP) testing experience in Croatia.
Authors: Čerina Dora , Šuto Pavičić Jelena , Njavro Antonela , Librenjak Niksa , Tomaš Ilijan , Šeparović Robert , Plestina Stjepko , Bajić Žarko , Dedic Plavetic Natalija , Vrdoljak Eduard
Published: June 2024

11151

Background: Despite increased availability of modern technologies and evolution of tailored treatment, which has already significantly changed the outcomes in some cancer types, applicability of precision medicine in everyday clinical practice is still emerging and is one of the hot topics. Croatia is among first ones in the World to have entered into force a country-level based project of precision oncology throughout the CGP analysis in everyday clinical work, fully covered by Croatian health insurance. Hence, here we would like to present our data from everyday clinical practice and analyze the penetration of CGP given the opportunity and challenges we had. Methods: The study was observational and retrospective in nature, conducted on a country level among all patients on whose tumor specimens CGP was performed between January 1, 2020 and December 31, 2021. Eligible patients for the CGP analysis were those with metastatic disease, with at least 6-12 months of life-expectancy, with ECOG performance status ≤ 2, and after the recommendation from the multidisciplinary team. The analysis was performed in accredited laboratory (Foundation Medicine Inc., Cambridge, MA, USA), through FoundationOneCDx for solid tumors, FoundationOne Liquid in case of insufficient tissue or FoundationOneHeme for sarcomas. Results: There was total of 481 patients with CGP results. Median age was 61 years (IQR 49-69) and 58% of patients were women, while 42% were men. Most commonly tested were gastrointestinal (29.1%) and reproductive tumors (28.9%) with colorectal (19.1%) and uterine cancer (11.2%) as the most prevalent. At least one clinically relevant genomic alteration was found in 48.7% of patients. The most frequent mutations were those of KRAS (27.2%), PIK3CA (12.9%), AR (10.6%), NRAS (10.4%) and PTEN (9.1%) genes. Currently clinically not relevant mutations were found in 51.8% of patients with TP53 gene mutation as the most common (42.8%). According to the Croatian cancer registry, there was around 26 000 cancer related deaths during the investigated period defining population of at least more than 10 000 potentially eligible patients for the CGP analysis. Conclusions: Our results have shown that almost 50% of tested patients could have potential treatment benefit based on the detection of clinically relevant genomic alteration. Unfortunately, taking into consideration country level insurance eligibility criteria for CGP testing and number of potentially eligible cancer patients, we could say that only less than 5% of patients with metastatic disease were tested within first two years and that penetration of CGP is rather low, resulting with a significant number of patients underserved.
Medicare reimbursement trends of biological reference agents and their biosimilars.
Authors: Albaugh John , Indurlal Puneeth
Published: June 2024

11155

Background: Biosimilars have the potential to reduce healthcare costs for payers and provide savings to patients by introducing competition and driving down prices. Centers for Medicare and Medicaid Services’ (CMS) Average Sales Price (ASP) is used as an index price to determine Medicare drug reimbursement (MCR) in the United States and is published on a quarterly basis. We studied the trends of ASP and MCR reimbursement rates for reference and biosimilar agents. Methods: Using publicly available quarterly CMS data, we evaluated and compared the trends of MCR for 7 reference and 25 biosimilar agents for a period of 2 years before and 5 years after launch. We evaluated the MCR for filgrastim, pegfilgrastim, bevacizumab, trastuzumab, rituximab, infliximab, epoetin-alfa, and their respective biosimilars. Results: On average, the published MCR for all reference agents increased by 9.2% (range: 0.6% to 16.8%) over the 2-year period prior to the biosimilar launch. Over the 5-year period following the launch of the first biosimilar, reference agents’ MCR fell 32.7% (range: -8.0% to -78.0%) while biosimilar agents’ MCR fell 50.3% (range: -3.7% to -90.5%) over the same period, with a median follow-up period of 16 quarters. Biosimilar MCR rates fell at an accelerated rate compared to reference agents. 76% (19 of 25) of the biosimilars that entered the market had an initial MCR below, and 20% (5 of 25) above, that of the reference agent. 16 of 18 successive biosimilars for reference agents launched with a MCR above that of the first biosimilar. Despite the fall in MCR, reference agents’ rates in the most recent quarter were 2x higher than their corresponding biosimilar agents, except for pegfilgrastim, which had a precipitous fall in MCR (87%) after biosimilar launch to a price lower than 5 of its 6 biosimilars. Conclusions: Biosimilars, with lower Medicare reimbursement at launch, and an accelerated decline in ASP post-launch, deliver on the goal of driving lower healthcare costs and increased savings. Biosimilar competition breaks the price increase trends with reference agents and contributes to a decrease in reference agent drug reimbursement. The effects of manufacturer rebates, payer policies, 340b programs, and discounts on ASP and Medicare reimbursement are also areas of active investigation.
Real-world outcomes in patients with biomarker-selected early-stage non-small cell lung cancer.
Authors: Abu Rous Fawzi , Sussell Jesse , Ngiam Celina , Zhang Qing , Majda Thomas , Sheinson Daniel , Ogale Sarika , Bara Ilze , Schulze Katja , Gadgeel Shirish M.
Published: June 2024

11156

Background: Extensive literature has assessed the prognostic value of Lung driver mutations (LDMs) in advanced non-small cell lung cancer (aNSCLC). However, their role in predicting outcomes in early-stage cases (eNSCLC) is less defined due to limited data on biomarker-selected eNSCLC. Study variations have led to diverse findings on the prognostic value of individual LDMs in eNSCLC. Methods: We retrospectively analyzed patients with resected stage I-IIIa NSCLC diagnosed between 2011-2023 using the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine lung clinico-genomic database, which consolidates data from approximately 280 US cancer clinics (~800 sites of care). We allocated patients to five cohorts classified by early-stage LDM status: ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+ and wild-type (WT - negative for the listed biomarkers). The clinical attributes and treatment patterns for this cohort were described by our group in a previous abstract; here we analyze recurrence-free and overall survival (RFS and OS) by cohort, using the Kaplan-Meier method. We used Cox regression for multivariate analysis, controlling for demographic and clinical characteristics including age, race, insurance status, stage, histology, and smoking status. Results: The sample contained 1,595 stage I-IIIa patients with known LDM status. Of these, 2.8%, 20.4%, 10.7%, 19.3%, and 46.8% were ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+, and WT. Median OS and RFS were shorter in the WT group compared to any LDM group; results can be found in the table. These differences in OS and RFS persisted in multivariate analysis; hazard ratios (HR) were all statistically significant (p<0.05) and can be found in the table below. Conclusions: In this real-world analysis, patients with eNSCLC LDM-positive tumors had improved OS and RFS relative to WT patients. Differences in OS between WT and LDM+ patients are likely due to frequent receipt of targeted therapy (TT) following progression to advanced disease. However, the small fraction of patients that received adjuvant TT within 6 months of surgery (described in our previous abstract) is not likely to explain observed differences in RFS; thus the differences may be due to innate characteristics of these LDMs. [Table: see text]
Biomarker testing and targeted therapy use among patients with non-small cell lung cancer in the United States: An analysis using a physician notes real-world database.
Authors: Videna Vernon , Iwanyckyj Dave , Otalora Fernando , Jardim Melanie
Published: June 2024

11175

Background: Biomarker testing informs treatment decisions by identifying patients who would clinically benefit from targeted regimens, leading to improved patient outcomes. However, the use of guideline-recommended biomarker testing in patients with advanced non-small cell lung cancer (NSCLC) is inconsistent. This study investigates the rates of biomarker testing in patients with NSCLC using a qualitative, real-world database. Methods: Natural language processing (NLP) was used to search and analyze the Amplity Insights database, consisting of transcribed, de-identified, records of physician-patient interactions obtained from patient medical records across the United States. This was a retrospective analysis of patients with a diagnosis of NSCLC (October 2003 - November 2023). Patient characteristics, biomarker testing, and treatment use were summarized and described. Results: 61,018 patients with NSCLC (mean [standard deviation] age of 69.8 [10.5] years) were identified. Among these, 50.6% were female and 87.9% identified as white. Among records with staging information, 26.6% had early-stage disease (stage 0-II) and 73.4% had late stage (stage III-IV) disease. In total, 13.4% (n=8,151) of all patients received biomarker testing. 13.3% (n=879) and 22.4% (n=2,402) of patients with stage III and IV, respectively, had biomarker testing performed; rates were higher in patients who were receiving care from an oncologist (16.8%, 31.0%, respectively). Among patients who had a confirmed actionable mutation (n=6,387), 35.9% received an appropriately matched targeted therapy and 10.1% received a nonindicated targeted therapy without harboring the indicated mutation. Of these, 40.7%, 22.7%, and 37.7% of patients harbored EGFR or ALK mutations, or were PD-L1 positive, respectively, and 35.8%, 17.8%, and 40.2% received the appropriate indicated treatment, respectively, based on testing. ALK-, EGFR-, and PD-L1-targeted therapies were taken by 12.1%, 9.4%, and 1.9% of patients, respectively, without evidence of the indicated biomarkers. Conclusions: These findings suggest that biomarker testing may be underutilized and that many patients may not be benefitting from treatment with precision therapies, highlighting the need for additional educational strategies to optimize precision oncology and elevate patient outcomes.
Impact on biomarker documentation in community oncology by optimizing clinical decision support.
Authors: Rubin Daniel , Handy Victoria , Gilmore Steven , Ginsburg Aimee , Dickens Andrea , Howell Josh , Hough Shannon
Published: June 2024

11182

Background: Timing of biomarker results is critical to informing the selection of appropriate precision medicine-based treatment options for patients. Prior studies have demonstrated that low rates of biomarker testing may be driven by poor documentation. Our clinical decision support (CDS) tool aims to provide community oncology clinicians with a clear picture of the ever-growing available treatments. Evaluation of CDS data revealed an excess of biomarker results documented as “unknown” thought to be related to results availability. Methods: During treatment selection in the CDS tool, providers answer various prompts related to the patient’s disease, staging, treatment intent, and biomarker results. Prompts are aligned with NCCN guidelines for the respective cancer type. Changes were implemented to ease providers’ documentation of biomarker results. For adjuvant (adjNSCLC) and metastatic NSCLC (mNSCLC), prompts were relocated to align with when biomarker results were likely to be available. For metastatic castrate resistant prostate cancer (mCRPC), some biomarkers are only needed after a patient has received prior docetaxel and hormone therapy, thus prompts were moved to that scenario. Re-prompting of biomarker status for subsequent therapy was also implemented if the initial response was “unknown.” We report changes in percentage of known biomarkers specifically in adjNSCLC, mNSCLC, and mCRPC. Descriptive statistics were used to describe the rates of known biomarkers, and a chi-square test was used to analyze differences from pre and post changes. Results: In this evaluation, 85,493 biomarkers were documented. In adjNSCLC and mNSCLC, biomarker prompt changes increased documentation of known biomarkers from 69% to 78% and 59% to 79% pre- to post-implementation. In adjNSCLC, ALK and PD-L1 recording increased by ≥10% (P<0.00001). For mNSCLC, documentation increased for all known biomarkers (P<0.00001), including ≥15% increases for 8 of 10 biomarkers. In mCRPC, known biomarker documentation improved from 34% pre-implementation to 61% post-implementation. BRCA1/2, MSI, MMR, TMB, and PSMA biomarker recording increased by ≥20% (P<0.00001) after prompt changes. Selected biomarkers are shown in the table. Conclusions: Adjusting prompts in a CDS tool to align with the availability of biomarkers in clinical practice increased the documentation of known biomarker results for adjNSCLC, mNSCLC, and mCRPC. Based on these findings, similar changes are being implemented for other cancer types in the CDS tool. [Table: see text]
Disparities in frontline treatment and overall survival in the era of targeted tyrosine kinase inhibitor therapy for chronic myeloid leukemia: 2004-2021.
Authors: Vardell Victoria , Tantravahi Srinivas Kiran
Published: June 2024

11187

Background: The treatment of chronic myeloid leukemia (CML) was revolutionized in 2001 with the introduction of the BCR::ABL tyrosine kinase inhibitor (TKI), imatinib. In 2006, dasatinib was approved, followed by nilotinib in 2007. Two other TKIs, bosutinib & ponatinib were approved in 2012, followed by the allosteric ABL myristoyl inhibitor asciminib in 2021, providing multiple options for patients (pts) who have refractory disease. In this study we examine how survival has improved in CML pts with the availability of multiple TKI’s and identify disadvantaged socioeconomic & demographic groups which continue to have disparate survival. Methods: The National Cancer Database was used to identify CML pts diagnosed (dx) from 2004-2021. Demographic, treatment, & overall survival (OS) were compared by era of TKI availability, with pts dx from 2004-2005 considered to be treated in the imatinib era, 2006-2011 for dasatinib & nilotinib, 2012-2020 with access to bosutinib & ponatinib, and 2021 for asciminib. Results: Of 44,993 CML pts identified, 55.8% were male & 82.5% were White, with median age of 58 years. The portion of pts who were untreated (due to contraindication or early death) decreased by each time period, from 17.8% in the imatinib era to only 7.8% in 2021. The rate of upfront transplant decreased from 2.5% from 2004-2005, to 0.8% in 2021. For dx 2004-2005 median OS was 11.5 yrs (95% CI 10.6-12.5). This increased to 13.6 yrs (CI 13.1-14.1), with age-adjusted hazard ratio (HR) of 0.86 (CI 0.81-0.91) for pts dx 2006-2011, with median OS unreached for 2012-2020, HR 0.67 (CI 0.63-0.71, p<0.001); referenced to 2004-2006. Survival at 1-, 5- & 10-yrs was improved for each subsequent time period of dx, with 5-yr OS of 65%, 71%, & 76%, respectively, p<0.001. On multivariate cox regression adjusted for yr of dx, features associated with reduced OS included age (HR 1.06 [95% CI 1.05-1.06], p<0.001 for each yr), Black race (HR 1.11 [95% CI 1.05-1.18], p<0.001), increased comorbidity index (HR 1.94 [95% CI 1.84-2.04], p<0.001 for index ≥2), uninsured (HR 2.20 [95% CI 2.01-2.41], p<0.001), or insured through Medicaid (HR 2.40 [95% CI 2.23-2.58], p<0.001). Conclusions: Survival for CML pts has significantly improved during the last 20 yrs with the availability of each additional TKI, likely related to increased treatment options for pts with resistance or intolerance. Additional TKI options, particularly approval of ponatinib for patients with T315I mutation, have a secondary benefit of decreasing the utilization of allogenic transplant. Though survival has improved for all pts, pts from traditionally underserved populations, including pts who are underinsured or from racial minority groups, have reduced OS. Continued advances in treatment & efforts to improve access to care for underserved populations is vital to achieve equitable survival outcomes in CML.
Informal caregiving for older adults on systemic treatment for hepatocellular carcinoma.
Authors: Wu Meng , Watman Deborah , Perez Sasha , Chen Yingtong , Woodrell Christopher D.
Published: June 2024

12059

Background: Hepatocellular carcinoma (HCC) disproportionately affects older adults who are often supported by informal or unpaid family caregivers (CGs). Despite rising incidence of advanced HCC worldwide, little is known about the experiences and unmet supportive needs of patients (pts) and their informal CGs, particularly in the context of contemporary first-line immunotherapy-based treatment. Methods: As part of two cross-sectional descriptive studies conducted in parallel at a single academic center, we interviewed non-dyadic older pts on systemic HCC treatment and family CGs and examined themes of informal caregiving. Eligible CGs were ≥18 years old and identified by pts; eligible pts were ≥60 years old and on systemic treatment for BCLC stage B or C HCC. CGs completed the Zarit Burden Interview (ZBI). Participants completed semi-structured interviews focused on pt and CG experiences and needs, which were transcribed and analyzed using an inductive approach by at least two investigators. Results: Transcripts (n=16) from 11/2021-11/2023 of interviews with CGs (n=8) and pts (n=8) were analyzed. CGs were 87.5% female. Their median ZBI score was 20/88, indicating little or no burden, although scores ranged from 2-64; higher scores indicate greater burden. Four themes emerged: CG tasks, sources of burden, sources of support, and views of palliative care. CG tasks included coordinating medical appointments and transport, attending appointments, advocating for pt interests, and helping with household chores. Two sources of burden most commonly identified were logistics of medical visits and supporting pts through physical and emotional symptoms. CGs recognized multiple sources of support, including spouses, family, friends, church groups, and therapists. Pts were 87.5% male, median aged 70, 25% Black, 50% non-Hispanic white, and 25% Hispanic. Their responses about caregiving, in contrast to the CGs interviewed, showed strong themes of independence. Representative quotes include, “I don’t need any help,” “I am independent..so far,” and “I live alone, I’ve got my own place, I do the best I can for myself.” Some shared that the support of CGs is more spiritual or emotional, “I feel stronger because you’re there,” which was needed mostly with new diagnoses or disease progression. Conclusions: Levels of burden varied among CG participants; pt participants felt independent for the most part while receiving their treatments, consistent with improved functional status and quality of life experienced by those receiving combination therapy. The task of juggling logistics for numerous medical visits between multiple subspecialties emerged as a major challenge. Strategies to optimize care coordination, including increased use of navigation for those with advanced HCC, may help pts and their CGs live better as they live longer on improved treatments.
Effect of palliative care on economic burden in lung cancer admissions: Insights from the NIS database.
Authors: Turk Ekrem , Olafimihan Ayobami Gbenga , James George Lina , Aryal Badri , Oh Youjin , Deenadayalan Vaishali , Batra Kunnal
Published: June 2024

12081

Background: Lung cancer (LC) remains the leading cause of cancer mortality globally, presenting substantial challenges in symptom management and quality of life (QoL) for affected patients. Despite the crucial role of palliative care (PC) in alleviating suffering and enhancing QoL, its integration into LC treatment is inconsistent, attributed to healthcare provider perceptions and systemic barriers. This study examines the utilization of PC consultations in LC admissions using the National Inpatient Sample (NIS) database, seeking to identify patterns of use and opportunities for improved care integration. Methods: The study queried the NIS database from 2016 to 2020 for adult hospitalized patients with a primary diagnosis of LC using ICD-10 codes. The primary outcome examined was the impact of PC consultations on length of stay (LOS), total hospital charges (THC), and healthcare utilization, with inpatient mortality as a secondary outcome. Baseline characteristics were assessed using t-tests and chi-square tests, while multivariable logistic regression analysis adjusted for age, gender, race, Charlson index, insurance type, and household income was employed to evaluate the outcomes. Results: Among 584,055 LC patients, 50.4% was female and 14.6% had a PC consult. These patients were typically older (68.4 vs. 70.6 years, p <0.001), more likely to be male (51.1% vs. 49.3%, p < 0.001) and African American (13.3% vs. 11.9% p < 0.001), and had Medicaid coverage (11.1% vs. 9.7%, p < 0.001) compared to their counterparts . PC was more frequently consulted in non-teaching hospitals (16.3% vs 14.1%, p < 0.001). Patients with PC consults also had a higher Charlson Comorbidity index 6.4 vs. 4.9 (p < 0.001). The overall inpatient mortality rate was 7.4%, with a significantly higher rate in patients with PC (32%) versus without (3.2%) (p < 0.001). While PC was associated with a longer LOS (7.6 vs. 5.9 days, p < 0.001), it resulted in lower THC ($74,399 vs. $84,233, adjusted difference: $6,874 p < 0.0001) and increased discharges with home health care and to nursing homes. Conclusions: PC consultations in LC patients are associated with reduced THC despite a slight increase in LOS. This finding emphasizes the economic and therapeutic value of PC in the treatment of LC, advocating for its earlier and broader integration. By addressing both symptom management and healthcare costs, palliative care can play a significant role in enhancing the comprehensive care of lung cancer patients, highlighting the need for overcoming existing barriers to its adoption. [Table: see text]
Novel screening approach for cancer cachexia using metagenomic gut microbiome profiling in patients with advanced non-small cell lung cancer.
Authors: Hakozaki Taiki , Salazar Eder Mendez , Kobayashi Takayuki , Fukuoka Shota , Koyama Shohei , Nishikawa Hiroyoshi , Motooka Daisuke , Nakamura Shota , Okuma Yusuke , Hosomi Yukio , Takeyama Haruko , Hosokawa Masahito , Routy Bertrand
Published: June 2024

12090

Background: Cancer cachexia (CC) is a multifactorial syndrome involving immune-metabolic crosstalk across multiple organs and has been associated with a negative clinical impact in patients with non-small cell lung cancer (NSCLC) amenable to immune checkpoint inhibitors (ICIs). In parallel, the gut microbiome (GM) has emerged as a key contributor to ICI response. In this study, we aimed to evaluate the association between CC and GM composition and its metabolic potentials. Methods: We collected fecal samples from 139 patients with advanced NSCLC treated with ICI. In addition to 16S rRNA sequencing for all patients, shotgun metagenomic microbiome profiling was performed for 69 patients to estimate the species-level composition and functional capacity of the GM. Cancer cachexia was diagnosed according to the international consensus based on the body weight changes over the previous six months. Survival time was calculated using the Kaplan-Meier method. GM diversity indices, differential abundance, and functional profiles based on the MetaCyc database were compared between the patients with and without CC. Results: Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group compared to the non-cachexia group [4.5 vs. 11.5 months (p < 0.001) and 10.8 vs. 44.9 months (p < 0.01), respectively]. Both GM profiling techniques revealed a significant difference in beta diversity between both groups (p < 0.01). In addition, metagenomic analyses revealed the distinct characteristics of GM at the species level between the groups. The CC group showed an overrepresentation of the commensal bacteria, such as Escherichia coli, Ruthenibacterium lactatiformans, Hungatella hathewayi,and Eggerthella lenta, whereas the non-CC group showed an enrichment of Parabacteroides distasonis, Eubacterium rectale,and Roseburia inulinivorans. Moreover, functional analysis revealed the significantly different metabolic potentials of GM in the CC group. The CC group showed an enrichment of pathways, such as D-arabinose degradation II, L-lysine degradation, and octan oxidation. Finally, the clustering of patients based on significant metabolic pathways or gene reactions provided a high predictive ability to discriminate between patients with and without CC. Conclusions: The shotgun metagenomic approach allowed for the characterization of the altered gut microbes and their metabolic potentials in patients with CC. Stratification based on the GM profiles may be useful as a novel screening method for CC, which is progressive and may involve more multistage pathology than identified by the conventional approach.
Sleep apnea and glymphatic dysfunction as a mediator of executive dysfunction and neurodegenerative risk in cancer related cognitive impairment (CRCI).
Authors: Kushman Sophie , Topalian Alique Gabrielle , Shatz Rhonna
Published: June 2024

12091

Background: Cancer survivors often experience cognitive changes, formally known as Cancer-Related Cognitive Impairment (CRCI), during or after treatment. CRCI commonly consists of executive dysfunction, which includes impairments in short-term memory, sustained attention/inhibitory control, cognitive flexibility, processing speed, and top-down processing. CRCI may be impacted by comorbidities and can increase neurodegenerative disease risk. Sleep disorders and disruptions (SDs) impair executive function in the general population. SDs may contribute to CRCI by impeding progression to deep sleep stages associated with enhanced glymphatic flow (GF) and clearance of inflammatory byproducts, leading to ventriculomegaly (VM- enlarged ventricles). VM is associated with cognitive impairment in other disorders, such as normal pressure hydrocephalus. Using data from the University of Cincinnati Cancer Cognitive Registry, we investigated relationships between the incidence and type of SD in CRCI, SDs and executive dysfunction, and evidence of altered GF in SD as measured by Evans Indices (EIs). SDs are known to be prevalent in CRCI patients. We hypothesize that evidence of impaired GF as measured by EIs will be present and associated with SDs and executive dysfunction. Identifying modifiable contributors to CRCI and their mechanisms of action are critical steps towards increasing quality of life in survivors. Methods: 174 patients referred for CRCI between 10/2021-10/2023 underwent assessments for CRCI and sleep hygiene with a cognitive battery, subjective questionnaires, and nocturnal polysomnography. Retrospective data gathered from Epic was entered into a REDCap registry. MRIs were analyzed in McKesson to calculate EIs. Results: Our data demonstrated the presence of SDs in 84% of patients and obstructive sleep apnea in 45%. Measures of apnea severity (apnea-hypopnea index-AHI) and GF (EIs) inversely correlated with executive function scores. This implicates sleep-related GF as a potential mediator of CRCI. Conclusions: CRCI and accompanying increased neurodegenerative risk may be the result of restricted cerebral spinal fluid exchange due to SDs in conjunction with systemic inflammation from cancer and its treatment. Sleep assessments should be routine in CRCI evaluations. Longitudinal assessments will help determine the relationship of SDs and their treatment to the course of CRCI and risk of neurodegenerative disease.
Mental healthcare utilization and psychosocial outcomes among patients with recently diagnosed cancer: A National Health Interview Survey report.
Authors: Parmet Tamar , Sannes Timothy S. , Kilbourn Kristin
Published: June 2024

12096

Background: Individual's diagnosed with cancer (IWC) often experience heightened psychosocial distress. Studies suggest 25-50% of IWC experience some form of psychosocial distress (Mehnert-Theuerkauf et al., 2023). Further, research shows that an individual's risk of developing a new mental disorder increases by 30% during the first year after being diagnosed with cancer (Hu et al., 2023). Although many IWC experience distress, literature depicts the underutilization of psychosocial services, with estimates suggesting that fewer then 10% of IWC receive support for their distress (Forsyth et al., 2013). This is concerning as research in rodents and humans shows that unaddressed distress can lead to faster growing tumors and rapidly advancing disease (Eckerling et al., 2021). The present study aimed to characterize mental healthcare utilization among Americans recently diagnosed with various types of cancer. We also aimed to illustrate prevalence of anxiety and depression in this population. Methods: Data from the 2022 National Health Interview Survey was used in this report. A total of 667 recently diagnosed IWC were included in the final analytic sample. Cancer type was divided into five subcategories: blood cancers (n=76), breast cancer (n=193), gynecologic cancer (n=87), colorectal cancer (n=72), lung cancer (n=62), and prostate cancer (n=177). Participants’ mental healthcare utilization at the time of the survey and within the last 12 months was assessed. The General Anxiety Disorder-7 (GAD-7) was used to measure participants’ anxiety levels and the Personal Health Questionnaire Depression Scale (PHQ-8) was used to assess depressive symptoms. Results: Over 28% of recently diagnosed IWC reported moderate-severe levels of anxiety on the GAD7, and 43% of participants reported high levels depression on the PHQ8. One-way ANOVA demonstrated significant differences in PHQ8 (F(5, 666)=3.332, p=0.006) and GAD7 (F(5,666)=3.35, p=0.005) scores across cancer groups. Post Hoc testing found that participants coping with colorectal cancers reported the highest levels of anxiety and depression compared to other cancer types. Of newly diagnosed patients, only 1.2% of patients reported currently receiving psychosocial support from a mental health professional, and only 13.6% reported receiving therapy from a mental health professional in the last year. Conclusions: Consistent with many studies, psychosocial distress among recently diagnosed IWC was very common, yet mental health care utilization remained low. These results indicate that efforts to target newly diagnosed IWC with psychosocial support interventions remains challenged. As such, our results underscore the importance of developing novel means of reaching IWC, and particularly colorectal cancer, as these individuals continue to struggle with significant levels of psychosocial distress.
Efficacy of mammography screening in women aged 40–49 years: An updated systematic review and meta-analysis.
Authors: Reis Pedro Cotta Abrahão , Oliveira João Pedro , Vellaichamy Swathi , Cagnacci Renato
Published: June 2024

e22513

Background: The screening of women aged over 50 through mammography has proven to significantly reduce breast cancer mortality in randomized controlled trials (RCTs). Despite prior trials and meta-analyses, new trials have been published and debates persist regarding the effectiveness of mammography screening for women aged 40–49. Therefore, we conducted an updated meta-analysis to assess the impact of mammography screening on reducing breast cancer mortality within this age group. Methods: In adherence to PRISMA guidelines, we systematically searched Pubmed, Cochrane, and Embase libraries for RCTs evaluating the efficacy of mammography screening in lowering breast cancer mortality among patients aged 40–49. Exclusion criteria encompassed non-RCTs, studies lacking reports on breast cancer mortality for individuals aged 40–49, and secondary analyses of included trials. Data extraction was carried out based on the latest available follow-up. We synthesized the relative risk (RR) for breast cancer mortality along with their corresponding 95% confidence intervals (95% CI). Employing a random-effects model, statistical analysis was conducted using RevMan 5.4 version, with an evaluation of I2 statistics for heterogeneity. Results: From 797 initial studies, 10 RCTs were included, comprising 163,634 women in the intervention group and 206,130 in the control group. Median follow-up ranged from 14 to 30 years. In individual studies, statistical significance was only reached in one trial (Table). Breast cancer mortality in the intervention group was significantly lower than in the control group RR 0.86 [95% CI 0.77–0.95]; p = 0.004; I2 = 0%. Conclusions: Despite limited data availability for this age group in certain recent publications with extended follow-up periods, raised questions about the design and reported results in some trials, the comprehensive findings of this meta-analysis suggest that mammography screening retains its effectiveness in reducing breast cancer mortality among women aged 40–49 years. [Table: see text]
Psilocybin, peyote, mescaline, and lysergic acid diethylamide (LSD) use in a nationally representative population by cancer history.
Authors: Baral Amrit , Pan Yue , Caban Martinez Alberto J. , Pinheiro Paulo S. , Hlaing WayWay M. , Vidot Denise Christina
Published: June 2024

e22518

Background: Classic psychedelics (Peyote, Psilocybin, Mescaline, and LSD) are re-emerging in the oncology toolbox. Peyote is the oldest known psychedelic, yet underexplored in clinical research. Preclinical studies suggest its extract stimulates lymphocyte proliferation, kills tumor cells, and may regulate sleep. This study aims to estimate the prevalence of classic psychedelic use among a US-representative sample of adults with and without a history of cancer. Methods: Data ( N= 208,220, weighted N: 239,589,661) from adults >18y in the 2015 - 2019 National Surveys on Drug Use and Health (52.8% female, 68.4% non-Hispanic White, 45.6% aged ≥50y) were analyzed to estimate lifetime classic psychedelic use among those with no cancer history, past history (diagnosed > 1y ago), or recently (≤1y ago) diagnosed. Weighted prevalence of psychedelic use, 95% confidence intervals, and adjusted (sex, race, income, education) odds ratio were calculated using logistic regression analysis in SAS. Results: Overall, 6.2% had a cancer history and 14.0% reported lifetime classic psychedelics use. LSD was the most prevalent in the sample (10.6%, 95% CI:10.4-10.8) compared to Psilocybin (9.6%, 95% CI: 9.4-9.9), Mescaline (3.1%, 95% CI:3.0-3.2), and Peyote (2.3%, 95% CI:2.2-2.4). Psychedelic use was lowest in adults with past cancer diagnosis (12.3%, 95% CI:11.4-13.1) vs recently diagnosed [14.0% (95% CI:12.0-16.0] and cancer naive (14.1%, 95% CI:13.8-14.4). Each classic psychedelic was used more often among recent cancer diagnosed adults than past diagnosed (p < 0.05). Specifically, LSD (11.1%, 95% CI:9.3-12.9 vs 9.3%, 95% CI:8.5-10.0), Psilocybin (8.3%, 95% CI:6.6-10.0 vs 7.3%, 95% CI: 6.7-8.0), Mescaline (5.4%, 95% CI:4.0-6.8 vs 4.6%, 95% CI: 3.9-5.2), and Peyote (3.7%, 95% CI: 2.5-5.0 vs 2.9%, 95% CI: 2.5-3.4) use was higher in recently diagnosed cancer patients than past diagnosed. There were no significant differences in age, except among Peyote. Among 18-to-34-year-olds, recent cancer patients had 3-fold greater odds (aOR:3.55, 95%CI: 1.11-11.31) of using peyote vs cancer naïve. In ≥50-year-olds, those with past cancer diagnosis had 21% lower odds (aOR:0.79, 95% CI:0.63-0.97) of using peyote vs cancer naïve. Conclusions: Results suggest differential psychedelic use by cancer history and age. These findings, while limited by temporality of diagnosis and initiation of psychedelic use, underscore the need to investigate reasons and long-term impact of specific psychedelic use with more rigor among adults with a cancer history.
Impact of obesity on breast cancer clinicopathological characteristics in underserved community dweller women of Chicagoland: An experience from a US safety-net hospital.
Authors: Proskuriakova Ekaterina , Aryal Barun Babu , Shrestha Dhan , Valencia Stephanie , Kovalenko Iuliia , Adams Megan , Boxwala Mubaraka , Verda Larissa , Khosla Paramjeet Grewal
Published: June 2024

e22519

Background: Breast cancer (BC) continues to pose a significant public health challenge, with its incidence and disproportionate impact on underserved populations in the United States. The relationship between obesity and clinicopathological characteristics at presentation remains a critical area of investigation. Safety-net hospitals catering to diverse, underserved, and often marginalized communities provide a unique setting to explore these associations, shedding light on potential disparities and informing targeted interventions. This study seeks to address a critical gap in knowledge on obesity and BC characteristics in underserved populations in the United States. Methods: In this retrospective study, 927 BC patients were included. Analysis was conducted to assess the association between body mass index (BMI), age of diagnosis, tumor clinicopathologic characteristics, and molecular types. The analysis was stratified by menopausal status at diagnosis. Results: The average age at diagnosis was 57.52 ± 12.40 years; 60.2% were postmenopausal women. Patients were categorized based on BMI into underweight/normal, overweight, and obese categories. One-way ANOVA analysis revealed no significant difference in mean age at presentation between BMI groups (p = 0.08). A significant association was found between BMI and menopausal status (p < 0.05). Disease stage at presentation was significantly associated with BMI (p < 0.05). Further investigation into BMI categories and tumor characteristics revealed a significant correlation in postmenopausal women, with obesity linked to tumor size and lymph node status (p < 0.05). No significant associations were observed between HER-2 status, ER/PR status, and obesity in either premenopausal or postmenopausal groups. In the subgroup analysis focusing on ethnic groups, African American patients (with an average BMI of 32.8 ± 8.2 kg/m2) demonstrated a higher prevalence of obesity at BC diagnosis in both pre and post-menopausal females compared to other ethnic groups (p < 0.05). Conclusions: Obesity was associated with the disease stage and menopause status at diagnosis. In postmenopausal patients, obesity was associated with tumor size and lymph node disease status. Additionally, ethnic variations were evident, with African American patients displaying a higher prevalence of obesity. We need further investigations to tailor interventions addressing diverse demographic factors in BC management.
Implementation of video assisted point-of-care germline genetic education and testing for patients with peri-diagnostic pancreatic cancer.
Authors: King Daniel , Mitnick Nathan , Mann Aman , Kauff Noah D.
Published: June 2024

e22530

Background: Germline genetic testing is universally recommended for patients with exocrine pancreatic cancer (PC). Pretest consultation with a genetics professional is recommended to ensure patients are informed about risks, benefits, and limitations of testing. This is a resource intensive process and is associated with a suboptimal testing rate (~30%). Prior work demonstrates that video-assisted pre-test education does not increase patient anxiety compared to traditional pre-test genetic counseling in peridiagnostic ovarian cancer patients. In this report, we assess the feasibility of using a similar video assisted, streamlined genetic education and testing approach in peridiagnostic PC patients. Methods: As part of a pilot quality improvement initiative, patients with a diagnosis of exocrine PC seen in a single academic practice were offered streamlined, video-assisted genetic education followed by germline testing. Patient eligibility for this pilot included: new diagnosis or radiographic suspicion of PC; English language proficiency; and no prior germline testing. After this approach was presented by the medical oncology team, eligible patients viewed a 9-minute educational video describing the goals, pros, and cons of germline genetic testing. After watching the video, patients were given the option to proceed with testing that day. Patients with pathogenic mutations were referred for formal post-test genetic counseling, and patients with variants of uncertain significance (VUSs) were referred on a case-by-case basis. Following IRB approval, we conducted a retrospective review of the experience of all patients presenting to this pilot site from April-Dec 2023. Results: During the study period, 56 new patients with exocrine PC presented to the pilot site. 50 patients were eligible for participating in the pilot program. All patients, except one who declined on the basis of transferring care, consented to testing (49/50; 98%). Median patient age was 71, 49% were female. Race distribution was: White (30), Asian (6), Black (4), Other (2), Declined (7). Median time from patient diagnosis to testing was 11 days. One patient had a germline ATM mutation, and this patient was seen for formal posttest counseling 18 days after testing was initiated. Seven patients had VUSs. Six new patients presenting during the study period were not eligible for this pilot, all due to limited English proficiency. All 6 of these patients underwent genetic testing after translation service assisted counseling by either the primary oncology or cancer genetics team. Conclusions: Video assisted point-of-care genetics education and testing led to nearly universal uptake of genetic testing in peridiagnostic PC patients. This workflow was feasible, timely, and optimized use of genetic counseling resources.
Co-occurrence of germline pathogenic variants in a Brazilian cohort of patients with breast cancer.
Authors: Souto Andreza Karine de Barros Almeida , Santana Thaiana Aragao , Oliveira Leandro Jonata Carvalho , Bulcao Marcela Lima , Farias João Paulo Gonzaga de , de Bustamante Fernandes Carolina , Christtanini Koyama Fernanda , Tiaki Uehara Daniela , Rego Fernanda Orpinelli Ramos do , Testa Galindo Layla , Ferrari Bruno Lemos , Mano Max S. , Dienstmann Rodrigo , Zalis Mariano , Garicochea Bernardo
Published: June 2024

e22532

Background: The estimated prevalence of germline pathogenic variants (PV) or likely pathogenic variants (LPV) in high and moderate penetrance genes is around 7-10% among women with breast cancer (BC). The emergence of next-generation sequencing (NGS) technology allowed multi-gene panel testing (MGPT) analysis at a lower cost. However, the detection of incidental findings with unknown significance (VUS) and challenges with variant interpretation increase substantially with MGPT. The effect of co-existing PV/LPV in two or more genes is still understudied. Here, we present the prevalence of concurrent germline LPV/PV in a cohort of Brazilian women with BC who underwent a MGPT in a single reference laboratory. Methods: Retrospective observational study using a laboratory cohort (Oncoclínicas Precision Medicine). This study includes women with BC who performed a germline MGPT (able to call SNVs, indels and CNVs) from 2019 to 2023. All patients were tested in a single reference laboratory (OC Precision Medicine) and originated from several Brazilian centers within the Oncoclínicas network. Two distinct germline NGS assays were used: breast and ovarian cancer (BOC) panel (36 genes) and a pan-cancer (PC) panel (105 genes). Results: In the overall cohort, 2,651 women with BC were included in this analysis. The median age at genetic testing was 51 years. 1,867 pts (70.4%) underwent a PC panel testing and the remaining 784 pts (29.6%) a BOC panel.Overall, 314 (12%) pts carrier of LP/PV in high- and/or moderate-penetrance genes. Two or more heterozygous LP/PV were found in 35 pts (1.32%), including 8 pts (1.02%) in the BOC panel and 27 pts (1.44%) in the PC panel subgroups. There were no differences in age of onset of BC in single vs co-occurring double mutants. The most frequent co-existing PV/LPV were found in BRCA2 (11) / BRCA1 (8) / PALB2 (4) / TP53 (3) and MUTYH (7) / CHEK2 (3) in the high and moderate penetrance genes, respectively. Six pts (0.23%) had a double heterozygous involving high and/or moderate penetrance genes. Interestingly, there was a case with four heterozygous variants in TP53, MUTYH, MUTYH and APC. Conclusions: In times of rapid incorporation of MGPT in the clinical practice, our real-world data showed that a small proportion of BC patients could be carriers of two or more germline heterozygous LP/PV in cancer genes. However, this represents a challenging scenario for patient and family management, especially in a co-occurrence of high and moderate penetrance genes.