bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating genetic features and clinical characteristics of young women diagnosed with breast cancer by the age of 35.
Authors: Kurian Christine Jane , Abou Hussein Ahmed K. , Mattie Kristin , Hunter Krystal , Grana Generosa 
Published: June 2024

10580 Background: Breast cancer in young women tends to be more aggressive with a unique distribution of molecular phenotypes compared to the general population. We evaluated the clinical characteristics and germline genetic test results in this cohort. Methods: We performed a single center retrospective review of 167 women diagnosed with breast cancer by 35, treated at our institution between the years 2013 to 2023. We reviewed medical records under Institutional Review Board approval for demographics, family history, tumor characteristics, surgical interventions performed, germline genetic test results, and number of pathogenic mutations identified. We used both descriptive and comparative quantitative statistics (student’s t test, Mann Whitney U Test and Chi Square tests) to compare data between patients with a pathogenic mutation and those without a pathogenic mutation. Results: Germline genetic testing was performed in 92.2% of individuals. The majority (81.4%) had no pathogenic mutation, whereas 15.6% had a pathogenic mutation implicated in hereditary breast cancer, and 3.0% had a pathogenic mutation not implicated in hereditary breast cancer. Our population was diverse - 60.4% white, 25.1% black, 7.8% Hispanic, and 6.5% Asian. Most patients had tumors that were high grade (56.3%), had a bilateral mastectomy performed (57.4%), did not have recurrence (87.4%), had exposure to oral contraceptives prior to diagnosis (59.9%), and had a family history of breast cancer (52.1%). 3.5% of patients were pregnant at the time of diagnosis. 26 patients were found to have pathogenic mutations implicated in hereditary breast cancer including BRCA1 (10), BRCA2 (10), CHEK2 (2), TP53 (2) and 88.5% of these patients underwent bilateral mastectomy. A higher proportion of patients with a pathogenic mutation were found to be progesterone receptor (PR) negative (56.8% vs 34.9; p = 0.029), undergo bilateral mastectomy (80.8% vs 53.2%; p = 0.009), be stage 1 at diagnosis (50.0% vs 19.1%; p < 0.001), have invasive ductal carcinoma (80.8% vs 59.6%; p = 0.040), and have a family history of breast cancer (73.1% vs 48.9%; p = 0.024) compared to those with no pathogenic mutation. While not statistically significant, a higher proportion of patients with pathogenic mutations experienced recurrence (19.2% vs 11.3%; p = 0.330). Conclusions: Our study showed that breast cancer diagnosed in young women has a more aggressive disease biology with 56.3% of the cohort found to have grade 3 disease. A higher proportion of those who had a pathogenic mutation implicated in hereditary breast cancer were found to be PR negative, underwent bilateral mastectomy, and had a family history of breast cancer. As our study was an exploratory observational study, further prospective multi-center studies are needed to help corroborate our findings and to better elucidate the potential clinical significance.
Association of germline HSD3B1 (c.1100) genotype with tumoral and clinical outcomes in breast and endometrial cancers.
Authors: Hwang Justin , Nazari Shayan , Elliott Andrew , Vanderwalde Ari M. , Lange Carol A , Geller Melissa Ann , Ryan Charles J. , Nabhan Chadi , Sharifi Nima , Antonarakis Emmanuel S. 
Published: June 2024

10587 Background: A germline single-nucleotide polymorphism in HSD3B1 results in adrenal-permissive (c.1100 C) and adrenal-restrictive (c.1100 A) phenotypes with respect to androgen synthesis. In pre- and post-menopausal patients with breast cancer (n=3548 and 7871) and endometrial cancer (n=1588 and 8439), we annotated samples as adrenal permissive (CC/AC) or restrictive (AA) based on HSD3B1 variant status and then examined tumoral characteristics and clinical outcomes. Methods: We utilized tumors from the Caris Life Sciences Precision Oncology Alliance database and inferred germline HSD3B1 c.1100 genotype using variant allele frequencies (VAFs): c.1100 C VAF of 0% defined the AA genotype, VAF of 40-60% defined the AC genotype, and VAF of 100% defined the CC genotype. We explored associations of each HSD3B1genotypes with other genomic (WES) and transcriptomic (RNA-seq) features, as well as with survival outcomes. To performed consider menopausal status we used the patient’s age at the time of biopsy (>55 indicating post-menopausal). Results: In breast cancer (BC) and endometrial cancer (EC), the permissive HSD3B1genotype had greater mRNA expression of the estrogen receptor ( ESR1) and co-alterations of the TP53 (p<0.0001). In post-menopausal ECs, the permissive genotype was associated with increased alterations in the PI-3-kinase pathway ( PTEN, PIK3CA, PIK3R1, p<0.0001). In pre-menopausal HER2+ BCs, the restrictive genotype was associated with worse survival (HR=1.40, 95% CI = 1.05-1.85, p=0.027) and exhibited increases in hallmark GSEA signatures including epithelial-to-mesenchymal transition. Post-menopausal basal BCs with the permissive genotype had numerically higher PD-L1 protein expression (50% vs 13%) and less PI-3-kinase alterations ( PTEN, PIK3R1, p<0.01). Post-menopausal clear cell ECs with the restrictive genotype exhibited worse survival (HR=1.60, 95% CI=1.07-2.38, p=0.03) and were 3-fold more likely to be TMB-high or MSI-high (p<0.05). Distinctly, post-menopausal endometrioid ECs of the restrictive genotype were less likely to be TMB- or MSI-high (p<0.05). Conclusions: Breast and endometrial cancers can be classified as adrenal-permissive or -restrictive based on HSD3B1 c.1100 genotype. This classification distinguishes clinical outcomes and tumoral features, particularly when stratifying by menopausal status. Importantly, these genotypes are differentially associated with druggable pathways (PI-3-kinase) and markers of immune sensitivity (PD-L1, TMB, MSI). [Table: see text]
Patient-reported fatigue and risk of treatment-related adverse events (AEs) in patients receiving systemic therapy in cancer clinical trials.
Authors: Unger Joseph M. , Vaidya Riha , Fisch Michael Jordan , Jones Salene M. W. , Henry Norah Lynn , Hershman Dawn L. 
Published: June 2024

11015 Background: Fatigue in patients with cancer is common and negatively impacts quality of life. Patient-reported outcomes (PROs) assess a patient’s direct report of their symptoms and well-being; research has highlighted their potential to predict cancer outcomes. We examined whether fatigue prior to treatment was associated with AEs. Methods: We analyzed 18 phase II and III cancer treatment clinical trials with baseline fatigue data conducted by SWOG between 1988-2018. The Common Terminology Criteria for Adverse Events was used. Symptomatic AEs were defined as those aligned with the NCI’s PRO-CTCAE; laboratory-based or measurable AEs were designated as objective (hematologic v nonhematologic). Thirteen symptomatic and 14 objective AE categories were examined. Fatigue was derived from multiple scales (e.g., FACT, EORTC QLQ-C30 and PROMIS-Fatigue 7a). Each measure was mapped to a 5-point Likert scale. Binary categories were compared (e.g., < some vs. > = some fatigue). Generalized estimating equations were used with a binomial distribution and logit link, adjusting for age, sex, race, and BMI, with clustering by study. Results: We examined N = 8,040 patients receiving systemic therapy. Among 18 trials (prostate, 5; lung, 3; colorectal, 2; lymphoma, 2; breast, 2; bladder, 1; melanoma, 1; ovarian, 1, pancreas, 1), n = 108,059 AEs were examined. Patient fatigue was present at levels of “a little” or greater in 75.8%, “some” or greater in 42.8%, and “quite a lot” or “very much” in 17.7%. Patients with some or greater fatigue were nearly twice as likely to have severe or worse toxicity (OR = 1.92, 95% CI, 1.53-2.40, p < .001) or life-threatening toxicity (OR = 1.93, 95% CI, 1.44-2.59, p < .001) and nearly threefold more likely to have fatal toxicity (OR = 2.76, 95% CI, 1.37-5.53, p = .004). Similar patterns were seen at a threshold of “quite a lot”. A dose response pattern was evident; patients reporting quite a lot/very much compared to no fatigue were > 5 times more likely to experience fatal toxicity (OR = 5.63, p = .002). These patterns were consistent in symptomatic, objective hematologic, and objective non-hematologic AEs. Conclusions: Baseline fatigue was highly predictive of subsequent risk of AEs. These findings suggest that in an era of precision medicine, patient-reported fatigue may be an important component of determining toxicity risk and could aid in treatment decision making.[Table: see text]
Post-market study requirements and associations with timely submission and regulatory action for oncology drugs receiving accelerated approval, 2011-2023.
Authors: Kurian Martin , Ferrell William J. , Perez Ernesto Ulloa , Hubbard Rebecca , Joffe Steven , Lynch Holly Fernandez , Mamtani Ronac , Parikh Ravi Bharat 
Published: June 2024

11028 Background: For oncology drugs receiving accelerated approval (AA), the Food and Drug Administration (FDA) enforces Postmarketing Requirements (PMRs) to verify clinical benefit prior to regular approval. Although previous work has characterized the rigor and timeliness of confirmatory studies, the association between specificity and scope of PMR statements and the timeliness of PMR submission and ultimate approval status is not well understood. Methods: We identified 161 oncology indications granted AA between January 2011 and July 2023 using FDA’s Cancer AA database. We linked indications to 181 corresponding PMR statements using the Drugs@FDA database. We analyzed PMR statement scope and specificity based on the presence or requirement of eight characteristics: target population, comparator (active or placebo-controlled), randomization, multicenter trial, blinding (double-blind or open-label), enrollment target, follow-up duration, and endpoints. We used chi-square and t-tests to analyze associations between PMR characteristics and two primary outcomes: indication approval status (regular vs. withdrawn) and PMR timeliness (on time vs. late). We defined “late” submissions as PMRs submitted or withdrawals occurring after an expected PMR Final Report submission date. Ongoing PMRs were excluded from the timeliness analysis unless expected dates occurred before August 2023. Results: Among 181PMR statements, 98% percent specified target population, 81% endpoint (44% overall survival), 63% use of randomization, 54% comparator (40% active; 14% placebo-controlled), 30% follow-up duration 26% enrollment targets, 24% multicenter trial, and 13% double-blinding (and 8% open-label). Among AAs converted to regular approval, 82% of PMRs were submitted on time vs. 24% on-time for withdrawn AAs (p=0.001). Regular approval PMRs were submitted 10.2 months ahead of expected dates, whereas withdrawn AAs were submitted 14.5 months behind expected dates (p<0.001). Compared late PMR submissions, on-time PMR submissions had lower enrollment (400 vs. 665, p=0.01), less blinding (19% vs. 40%, p=0.03), more frequent use of a single trial for both AA and PMR (38% vs. 8%, p=0.001), and primary endpoints other than overall or progression-free survival (36% vs. 5%, p<0.001). Compared to late PMR submissions, on-time PMR submissions more often followed PMR statements that specified follow-up duration (39% vs. 13%, p=0.006) and non-survival primary endpoints (30% vs. 8%, p=0.01). Conclusions: There is marked variability in the contents of PMR statements for oncology AA drugs. Several characteristics of PMRs – including smaller enrollment size, surrogate endpoints, and single trials for AA and PMR – are associated with timely submission. These findings inform the specificity and scope of future FDA PMRs for oncology AA indications.
Association of characteristics of cancer, patient, and county with telemedicine services use: Impact of the waiver of reimbursement restrictions on telemedicine.
Authors: Tak Hyo Jung , Goldsweig Andrew M , Lee Min Sok , Verhoeven Dana , Horner Ronnie D 
Published: June 2024

11058 Background: Telemedicine services have great potential to improve access to care of cancer patients who are vulnerable in health status and may experience financial hardship due to the cost of their care. However, very little is known about how the Centers for Medicare and Medicaid Services’ waiver of reimbursement restrictions on telemedicine and characteristics of cancer affected their use of telemedicine services. We examined the changes in frequency of telemedicine use before and after the waiver and, after the waiver, the determinants of telemedicine use across medical provider types. Methods: We used the 5% Surveillance, Epidemiology and End Results registry file linked to Medicare data among patients who had a newly diagnosed cancer in 2019 and were enrolled in Medicare Parts A and B during 2019-2020, and Area Health Resources File. Our outcomes were binary variables of telemedicine services use in outpatient (OP), office-based clinics (OB), and emergency department (ED), respectively, and for detailed provider types in OB. Primary independent variables included the ten most frequently observed cancer sites (reference: all other sites), sequence of cancer, stage of diagnosis, and quarter of diagnosis in 2019. Analysis was by a multilevel mixed effects logistic regression model, adjusting characteristics of cancer, patient and county. Results: Among eligible patients (n = 14,226), telemedicine services use for all provider types increased from 4.3% in pre-waiver period to 40.3% (5.2% in OP, 39.3% in OB, and 0.2% in ED) in post-waiver period. Telemedicine services use varied by primary cancer site, but was higher for those with a cancer recurrence (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.16-1.60) and advanced cancer stage (OR 1.24, 95% CI 1.03-1.48). For visits to oncologists, cancer characteristics such as recurrence (OR 1.67, 95% CI 1.34-2.08), advanced stage (OR 5.52, 95% CI 4.12-7.40) and diagnosis in the last quarter in 2019 (OR 1.39, 95% CI 1.20-1.61) were associated with greater use of telemedicine. Patients of older age and minority race/ethnicity and in non-Northeast regions were less likely to use telemedicine, while women, patients with dual eligibility for Medicaid, and those living in a county with high median household income and high availability of hospital beds were more likely to use telemedicine. Conclusions: Cancer patients used telemedicine services more frequently after the waiver and their cancer characteristics were most strongly associated with that use, implying their greater need for, and benefit from, telemedicine. Disparities in telemedicine use related to individual and county-level socio-demographics and medical supply suggest health policy changes to improve equitable access to telemedicine and efficient cancer care planning.
Inpatient burden and clinical outcomes of cytokine release syndrome in patients with cancer: A National Inpatient Sample study.
Authors: Makhani Sarah , Azhar Waqas , Shah Ejaz , Hussain Mohammad Junaid , Goel Ruchika 
Published: June 2024

11067 Background: Cytokine release syndrome (CRS) is a potentially life-threatening complication commonly seen in patients receiving chimeric antigen receptor (CAR)-T cell therapy, allogeneic stem cell transplant, or immunotherapies. This study aims to evaluate the inpatient burden outcomes of CRS leading to hospitalization in patients diagnosed with cancer. Methods: Hospitalizations for cytokine release syndrome (CRS) were identified using ICD-10 coding from the 2020 National Inpatient Sample (NIS), the largest all-payer inpatient database in the US. Only CRS patients with a co-diagnosis of cancer (identified using the Clinical Classification Software (CCS) coding) were included in this study. The underlying severity of illness index was used to verify CRS grading. Sampling weights were applied to generate nationally representative estimates. Results: In 2020, there were 4,765 hospitalizations coded with CRS. 27.2% of these admissions had a co-diagnosis of cancer (n=1,295) and were included in the final analysis. The top co-diagnoses in the patients with CRS without cancer were COVID-19 infection and sepsis. Hematologic malignancies had the highest incidence amongst cancer types (75.7%), the distribution was as follows: 29.6% with diffuse large B-cell lymphoma, 19.9% with acute lymphoblastic leukemia, 12.8% with multiple myeloma, 12.2% with acute myeloid leukemia, and 7.7% with mantle cell lymphoma. The most common procedures in oncology patients hospitalized with CRS were CAR-T cell therapy (29.3%), chemotherapy (28.6%), stem cell transplant (8.5%), or Blinatumomab bispecific antibody (5.4%). 11.4% of patients with CRS received tocilizumab. Of those that received tocilizumab, 10% were CRS grade 2, 56.7% were grade 3, 33.3% were grade 4. 51.7% of tocilizumab was given in the first 48 hours of admission. A minority of CRS patients required critical care interventions: 12.0% requiring intubation, 5.8% requiring vasopressor support, and 2.7% received dialysis. Overall, 10.4% of all oncology admissions with CRS resulted in death during hospitalization (n=135). Of these deaths, 92.6% were in the extreme severity of illness and 63.0% were CRS grade 4. Those with CRS who died during hospitalization had a significantly longer length of stay (24.6 vs 13.6 days, p<0.001). The overall median hospital charges of a CRS-related admission were $531,692. Conclusions: This study represents the inpatient burden of CRS-related admissions in patients diagnosed with cancer. CRS admissions are commonly seen in patients with hematologic malignancies, those undergoing CAR-T cell or immunotherapies (bispecific antibodies). CRS poses a significant healthcare burden, with average hospital charges being greater than 0.5 million US dollars per admission. About 1 in 10 patients with CRS died during hospitalization with higher mortality likely with severe CRS grades and longer length of stay.
Health-related quality of life (HRQoL) and symptoms in LIBRETTO-431 patients with RET fusion-positive advanced non-small-cell lung cancer (NSCLC).
Authors: Zhou Caicun , Novello Silvia , Garrido Pilar , Dooms Christophe Alfons , Alatorre Alexander Jorge Arturo , Reinmuth Niels , Gilligan Adrienne M. , Payakachat Nalin , Cocks Kim , Worthy Gill , Goto Koichi 
Published: June 2024

11068 Background: LIBRETTO-431 (NCT04194944), a randomized phase 3 trial, compared first-line selpercatinib to platinum-based chemotherapy +/- pembrolizumab (pembro). Selpercatinib, a highly selective and potent CNS penetrant RET inhibitor, is approved for the treatment of advanced RET fusion+ NSCLC. This analysis reported NSCLC symptoms and HRQoL from LIBRETTO-431. Methods: This analysis used data (cut-off date: May 01, 2023) from the intent-to-treat (ITT) pembro subpopulation [selpercatinib (n=129); chemotherapy + pembro (control, n=83)] to assess time to confirmed deterioration (TTCD) of NSCLC symptoms (cough, dyspnea, pain, fatigue, poor appetite using NSCLC-Symptom Assessment Questionnaire [SAQ]). TTCD of NSCLC symptoms were defined as time from randomization to the first score that met the pre-specified meaningful within-patient change thresholds, confirmed at next assessment. TTCD was compared between treatment arms using log-rank test and Cox proportional hazards model. Changes of NSCLC-SAQ total score (meaningful important difference [MID] ≥2 points) and HRQoL (using EORTC QLQ-C30 Physical Function (MID ≥6 points) and Global Health Status (GHS)/QoL (MID ≥5 points)) up to 1 year were evaluated and compared between the arms using a growth curve model and mixed model for repeated measures. Results: Selpercatinib significantly (p <.05) delayed TTCD of all individual symptoms with hazard ratio ranging from 0.41 (cough and pain) to 0.57 (dyspnea), compared to control (Table). Selpercatinib also showed a significant and clinically meaningful difference in the mean NSCLC-SAQ total score (difference = -2.0, p <.001) and physical function (difference = 8.1, p =.003) at 1 year, compared to control. GHS/QoL was improved in both arms with no difference in the mean scores between the arms at 1 year. Conclusions: Selpercatinib significantly delayed TTCD of NSCLC symptoms and improved physical function compared to control in this patient population after 1 year of treatment. The findings were consistent with the favorable efficacy of selpercatinib compared with platinum-based chemotherapy + pembro and further support 1L use of selpercatinib in this population. [Table: see text]
Access barriers and cost of varenicline for smoking cessation: A national comparative analysis of Medicare standalone part D and Medicare Advantage plan.
Authors: Jiang Changchuan , Wang Qian , Hong Arthur S , Mullins Megan A , Xing Jiazhang , Wang Tianci , Hu Xin , Nipp Ryan David , Yabroff Robin , Liao Joshua , Han Xuesong , Shih Ya-Chen Tina 
Published: June 2024

11080 Background: Smoking cessation is a critical part of cancer prevention and control. Oral varenicline is the most cost-effective medication for smoking cessation, yet seniors enrolled in Medicare Part D Prescription Drug Plans (PDPs) can potentially face costs and access barriers to varenicline in the forms of prior authorization and quantity limits. Although over half of Medicare beneficiaries are now insured and receiving drug benefits through Medicare Advantage, it remains unclear how costs and access barriers compare between PDPs and MA drug plans (MADPs). This study compared plan-level costs and prevalence of prior authorization and quantity limit policies between PDPs and MADPs for oral varenicline. Methods: We used 2023 Q3 MA and PDP data from the Center for Medicare and Medicaid Services, excluding employer-sponsored and Supplemental Need Plans (including dual-eligible plans) and plans with <10 enrollees. We focused on two generic varenicline forms: 0.5mg and 1mg tablets. To compare medication quantities, we calculated the plan-level median (IQR) cost for 30-day supply, based on the average unit cost. Price benchmarks were defined based on average wholesale acquisition cost (WAC) from Micromedex Red Book. T-test and Chi-squared tests were used to compare costs and prevalence of prior authorization and quantity limits. Results: Across 3512 MADPs and 813 PDPs, median costs for a 30-day supply of varenicline were similar (0.5mg tab: $375.32 vs. $376.87, p=0.64; 1mg: $371.88 vs. $376.87, p=0.49, respectively). Median costs for both PDPs and MAPDs were higher than benchmarks; p<0.01 for all). For both varenicline dosages, MAPDs had higher rates of prior authorization (27.1% vs 16.2%, p<0.01) and quantity limits (48.0% vs 30.4%, p<0.01) than PDPs. Conclusions: Varenicline prices in both PDPs and MAPDs were much higher than benchmarks. Compared to PDPs, MAPDs used more prior authorization and quantity limit to control cost. This can create access barriers to this cost-effective medication, burdening patients, physicians, health systems, and pharmacies. [Table: see text]