tbuckley/cabot-search huggingface dataset:
Impact of age on clinical trial availability for AYAs with cancer: A time-trend analysis.
Authors: Jessica Sheth Bhutada, Nupur Mittal, David R. Freyer, Michael Roth
Journal: Journal of Clinical Oncology (2024)

1534 Background: Low participation of adolescents and young adults (AYAs, age 15-39 yrs at diagnosis) in cancer clinical trials (CCT) limits their access to novel therapies and hinders the ability to study disease biology and age-specific toxicities. Patient age may be an important barrier as younger and older AYAs may be excluded depending on the trial’s focus. In 2017, the American Society of Clinical Oncology and Friends of Cancer Research issued a joint statement encouraging removal of age as a CCT eligibility criterion unless there is specific biological rationale. To evaluate the impact of this statement, we undertook this analysis of CCT availability for AYAs. Our primary objective was to compare the number of CCT available for AYAs, overall and by tumor types, from 2019-2023 vs previously published data from 2007-2018. The availability of early phase trials and study sponsor was also assessed. Methods: We identified CCT registered on ClinicalTrials.gov from January 2019 to July 2023 enrolling patients with 10 malignancies relevant for AYAs (Hodgkin lymphoma, anaplastic large cell lymphoma, melanoma, extracranial germ cell tumors [GCT], medulloblastoma, thyroid cancer, Ewing sarcoma, osteosarcoma, rhabdomyosarcoma [RMS], and synovial sarcoma). Trials were categorized as adult (≥18 yrs), transitional (patients &lt; or ≥18 yrs), or pediatric (&lt;18 yrs). Transitional trials with an age range 12-18 to &lt;40 yrs were defined as AYA specific trials. Early phase included phase 1 and 1/2 trials; late phase included phase 2/3 and 3 trials. Trial availability from 2007-2018 was identified from a prior analysis by deRojas et al in 2019 (PMID:32337483). The proportion of trials in each category was compared between 2007-2018 and 2019-2023 using z-tests. Results: There were 1071 eligible trials registered on Clinicaltrials.gov: 840 (78%) adult, 226 (21%) transitional, and 5 (0.5%) pediatric. Four trials were AYA-specific. Compared to the prior 10 years, the proportion of transitional trials did not change overall (19% vs 21%, p=0.24) or within any disease. Whereas the proportion of trials available at age 17 has not significantly changed overall (20% vs 21%; p=0.48) or within any disease, the proportion of trials available at age 18 significantly increased (95% vs 98%; p&lt;0.001) in aggregate and specifically for Ewing sarcoma (93% vs 100%; p=0.003), GCT (96% vs 99%; p=0.002), medulloblastoma (86% vs 98%; p=0.006), RMS (87% vs 98%; p=0.007) and thyroid cancer (92% vs 98%; p=0.01). Time trends for transitional trials by phase and sponsor are summarized (Table). Conclusions: Availability of transitional trials for AYAs has not increased, particularly for those &lt;18 yrs. The 18-yr-old age limit continues to be an obstacle in CCT availability and enrollment. [Table: see text]
Disparities uncovered: LGBTQ+ patients report on their cancer care journey.
Authors: Shail Maingi, Matthew B. Schabath, Ilona Dewald, Janet Storey, Samuel Dooyema, Jeffrey D. Carter, Cherilyn Heggen, Kelly McKinnon
Journal: Journal of Clinical Oncology (2024)

1516 Background : In the U.S, LGBTQ+ people face higher cancer rates and worse outcomes than the general population. Few studies have described the experiences of LGBTQ+ people and their caregivers during treatment. As part of an implementation science initiative aimed at improving care for LGBTQ+ patients, we conducted a large survey (n=817) to understand treatment experiences of this population. Here we report our findings which provide insight into how stigma and incorrect assumptions may contribute to medical mistrust and worse experiences. Methods: In 2023, 817 diverse LGBTQ+ cancer patients from academic and community-based settings, as well as patient advocacy groups, completed web-based surveys evaluating their care experiences during cancer treatment. Participants included patients with gastric (n=165), breast (n=238), ovarian (n=218), prostate (n=56), and colorectal cancers (n=140), including 83 gender non-conforming patients. Results: Most LGBTQ+ patients (80%) reported not receiving appropriate preventative cancer screening, with top barriers including provider did not mention cancer screening tests (40%) and did not have a healthcare provider (28%). Additionally, only 24% felt at least moderately comfortable disclosing their LGBTQ+ status. Inclusive measures that helped patients feel most comfortable included care teams sharing/displaying their own pronouns (39%), making public statements of support (43%), or wearing personal items indicating acceptance (39%). Of those who did disclose their identity, only 50% of gender-expansive patients reported consistently being referred to by the correct names and pronouns. Importantly, patients reported that only 34% of their partners/caregivers felt welcome at appointments, and only 4% felt respected by the care team. Few patients reported receiving key supportive care services, including counseling/support groups (23%), quality-of-life related care, such as sexual function counseling (23%), and LGBTQ-specific resources/education (19%). Furthermore, less than half of LGBTQ+ patients discussed with HCPs how cancer treatment affects fertility (41%), fertility preferences (26%), or fertility preservation (14%), even though only 22% of patients reported not being eligible for fertility services. Interestingly, many of these gaps in care differed based on cancer type. For example, prostate, colorectal, and gastric patients were more likely to report not feeling safe disclosing their LGBTQ+ status (80%, 69%, and 54% respectively), while breast cancer patients were more likely to report having discussed fertility prior to starting treatment (64%). Conclusions: This study offers insights into experiences of LGBTQ+ patients and confirms disparities in care are real and pervasive. Ongoing education and inclusion efforts can help create a safe and welcoming environment, enabling equitable care and improved outcomes.
Antitumor mechanisms of OncoTherad (MRB-CFI-1) nanoimmunotherapy involving monoamine oxidases: Clinical implications in BCG-unresponsive non-muscle invasive bladder cancer.
Authors: Wagner José Fávaro, Gabriela Cardoso de Arruda Camargo, Gabriela Oliveira, Monaliza Ávila, Isadora Manzato Roberto, João Carlos Cardoso Alonso
Journal: Journal of Clinical Oncology (2024)

e14597 Background: Bacillus Calmette-Guérin (BCG) immunotherapy has been the gold standard treatment for non-muscle invasive bladder cancer (NMIBC) for nearly half a century. However, many high-risk patients experience recurrence, including those who progress and eventually become unresponsive to BCG. The emergence of new immunotherapeutic agents has revolutionized the treatment of various tumor types, including urothelial carcinoma. In this context, our research group has developed OncoTherad (MRB-CFI-1) immunotherapy, which has shown promising results in cancer treatment, particularly in NMIBC. Given the inherent complexity of the immune response, patient selection and the development of biomarkers to guide the identification of individuals who will derive the greatest benefit from a specific immunotherapy remain crucial. Over the past years, several studies have demonstrated the upregulation of monoamine oxidases (MAOs) in tumor progression and metastasis. Therefore, the objectives of this present study were to characterize the effects of OncoTherad (MRB-CFI-1) on the modulation of MAOs (MAO-A and MAO-B) in the bladder of patients with BCG-unresponsive NMIBC. Methods: A total of 40 bladder biopsies from patients with BCG-unresponsive NMIBC treated with OncoTherad (MRB-CFI-1) were collected and analyzed from Paulínia Municipal Hospital (HMP). These samples were then divided into two groups (n=20 per group): Group 1 (biopsy before OncoTherad treatment) and Group 2 (biopsy after OncoTherad treatment). Subsequently, the samples underwent immunohistochemical analyses for MAO-A and MAO-B. The retrospective anonymous study was approved by the local ethics committee (Clinical Trial: RBR-6swqd2). Results: Our results demonstrated high immunoreactivities for both MAO-A and MAO-B in the bladder tumor microenvironment prior to OncoTherad (MRB-CFI-1) treatment, confirming that the pattern reported in literature studies can also be observed in NMIBC. Total immunoreactivities for MAO-A did not differ statistically between bladder biopsies of Groups 1 and 2, indicating that this treatment does not interfere with the action of MAO-A in bladder tissue. In contrast, immunoreactivities for MAO-B were significantly lower (p&lt;0.05) in the Group 2 when compared to Group 1 suggesting that this immunotherapy reversed the immunosuppressive state and tumor progression induced by MAO-B. Conclusions: Taken together, our results support the use of MAO-B as a biomarker for clinical response to OncoTherad (MRB-CFI-1) immunotherapy.
Treatment-related adverse events of PD-1 versus PD-L1 inhibitors commonly used in lung cancer therapy: Analysis of real-world FAERS data.
Authors: Dawood Findakly, Kavitha Beedupalli
Journal: Journal of Clinical Oncology (2024)

e14598 Background: With the increasing utilization of immune checkpoint inhibitors (ICIs) in the dynamic landscape of cancer treatment, understanding immune-related adverse events (AEs) has become crucial for optimizing patient outcomes and therapeutic selection. In this study, we utilized the FDA Adverse Event Reporting System (FAERS) database to assess AEs reported with commonly used PD-1 and PD-L1 inhibitors in lung cancer therapy. Methods: We conducted a retrospective FAERS public database review to assess anti-PD-1 inhibitors (Pembrolizumab and Nivolumab) and anti-PD-L1 inhibitors (Atezolizumab and Durvalumab) reported AEs from January 2017 through September 30, 2023. We assessed disproportionality signals by calculating the reporting odds ratio (ROR) with a 95% confidence interval (CI). Significance was determined when the lower limit of the 95% CI exceeded 1. Results: In our analysis of 134,184 reported AEs, anti-PD-1 therapies had higher rates of cardiac AEs (ROR = 1.08; 95% CI: 1.03-1.14; P = 0.0015), vascular AEs (ROR = 1.23; 95% CI: 1.17-1.30; P &lt; 0.0001), respiratory AEs (ROR = 1.30; 95% CI: 1.25-1.34; P &lt; 0.0001), gastrointestinal AEs (ROR = 1.04; 95% CI: 1.01-1.08; P = 0.0117), hepatobiliary AEs (ROR = 1.12; 95% CI: 1.07-1.17; P &lt; 0.0001), and renal and urinary AEs (ROR = 1.06; 95% CI: 1.01-1.11; P = 0.0195) compared to anti-PD-L1 therapies. Conversely, anti-PD-L1 therapies had higher rates of endocrine AEs (ROR = 1.31; 95% CI: 1.25-1.38; P &lt; 0.0001), skin and subcutaneous tissue AEs (ROR = 1.43; 95% CI: 1.37-1.49; P &lt; 0.0001), and musculoskeletal and connective tissue AEs (ROR = 1.33; 95% CI: 1.26-1.39; P &lt; 0.0001) compared to anti-PD-1 therapies. Conclusions: Our study provides insights into the adverse event profiles of selected anti-PD-1 and anti-PD-L1 therapies in a real-world clinical setting. Further prospective studies are essential to enhance our understanding of the comparative safety profiles of these agents, guiding personalized treatment decisions and, ultimately, advancing patient outcomes.
Constructing adverse event timelines for patients receiving CAR-T therapy using large language models.
Authors: Jordan Guillot, Brenda Miao, Arvind Suresh, Christopher Williams, Travis Zack, Jeffrey Lee Wolf, Atul Butte
Journal: Journal of Clinical Oncology (2024)

2555 Background: Chimeric antigen receptor T (CAR-T) therapy is associated with a high risk of severe adverse events often only detailed in clinical notes. Monitoring them demands significant time and effort for manual chart review. Recent developments in large language modeling (LLMs) show promise for large-scale information extraction from clinical text. We performed a pilot study to evaluate the capability of the GPT-4 LLM to extract adverse events documented in the progress reports. Methods: We extracted progress notes within 30 days of any CAR-T administration from the UCSF deidentified clinical data warehouse. GPT-4, accessed through a HIPAA compliant Microsoft Azure Studio API, was used to extract CAR-T adverse events resulting in clinical intervention. A random sample of adverse events from 10% of patient notes were evaluated by a clinical reviewer (JG, PharmD). Topic modeling using BERTopic was used to cluster all adverse events to identify trends over time. Results: We identified 4183 clinical notes written within 30 days of CAR-T administration from 253 patients (39.1% women, 60.9% men). Mean age was 60.6 (SD:17.7). Manual validation of clinical notes from 10% of patients with CAR-T therapies (n=25) demonstrated that GPT4 was able to extract CAR-T related adverse events with 64% accuracy. We used BERTopic to cluster all extracted adverse events into 19 topics. Clusters with key terms “hyponatremia, leukocytosis, encephalopathy, toxicities, and neurologic” occurred most often (n=277), and primarily documented 12.9 days after CAR-T administration (Table). Conclusions: Although limited by use of de-identified data and absence of prompt engineering, this pilot supports the further investigation of LLMs for extraction of adverse events from unstructured clinical text. [Table: see text]
National and state models for relationships between social vulnerability and mammography rates.
Authors: Ismail Aijazuddin, Abdurahman Alloghbi, Ammar Sukari
Journal: Journal of Clinical Oncology (2024)

1573 Background: Health disparities arise from the confluence of medical and non-medical factors that affect measures of prevention, treatment, and outcomes. One crucial preventative measure is mammography rate. Neighborhood-level analysis using tools such as the CDC’s Social Vulnerability Index (SVI) may identify correlates of disparity in mammography access and utilization. Such investigation may reveal drivers of disparity in communities with lower screening. Methods: Self-reported mammography rates among women aged 50-74 were obtained from the CDC’s 2018 PLACES dataset at the Census Tract level and merged with the CDC’s 2018 SVI release. Data were available for 72,075 Census Tracts across all states and Washington, D.C. National univariate and multivariate regressions were performed between mammography rates and percentiles for SVI percentiles. State-specific multivariate regressions were performed for each state's Census Tracts. Results: In the national analysis, significant correlations with non-negligible effect size (correlation coefficient &gt; 0.20 or &lt; -0.20) were found between mammography rate and the following: Theme 2 - Household Composition &amp; Disability (R = -0.22, p &lt; 0.0001), Mobile Homes (R = -0.36, p &lt; 0.0001), Civilians with a Disability (R = -0.24, p &lt; 0.0001), and Minority Status (R = 0.25, p &lt; 0.0001). The national multivariate model achieved Multiple R of 0.54 and Significance F &lt; 0.001. The variables with the most negative associations (lower mammography rates with increased vulnerability) were Income (coefficient = -4.05, p &lt; 0.001) and Speaks English Less than Well (coefficient = -2.33, p &lt; 0.001). Across the state multivariate models, mean Multiple R was 0.70 (95% CI 0.67-0.73), with Significance F &lt; 0.05 in all states (Table). The variables with the most negative mean coefficients across models were Income (-3.20) and No High School Diploma (-2.98); the most positive was Minority status (6.11). Conclusions: Neighborhood-level social determinants correlate meaningfully with mammography rates. Although lower income, limited English proficiency, and lower educational attainment are most strongly associated with lower mammography, the effect sizes vary across geographies, and additional factors have meaningful influence in certain states. The stronger performance of most state-specific models than the national model reinforces this finding. It demonstrates the need for further analysis at the level of state and within narrower geographies. Ultimately, targeted interventions should address those disparities that are most relevant to specific neighborhoods. [Table: see text]
A United Kingdom prospective, multicentre, observational cohort study investigating tolerance of anti-cancer systemic therapy in the elderly: The TOASTIE study.
Authors: Helen Clare Dearden, Michael Rowe, Adam Peters, Maria Rohan, Alexandra Marsh, Abigail Louise Gee, Kieran Zucker, Gemma Quesne, Jonathan Heseltine, Rachel Prichard, Deborah Scott, Conor ONeill, Clair Brunner, Joni Howells, Veronica Conteh, Avinash Aujayeb, Xiangfei Yan, Lisa Jane Rodgers, Sally Martin, Mark Baxter
Journal: Journal of Clinical Oncology (2024)

1521 Background: Older adults have a higher risk of developing chemotherapy (CTx) related toxicity. The Cancer Aging Research Group (CARG) score was developed and validated in the USA to predict risk of severe CTx induced toxicity in older adults; subsequent validation studies have had varying results. The TOASTIE study sought to evaluate the CARG score prospectively in a United Kingdom (UK) population. Methods: This multicentre, prospective, observational study recruited patients aged ≥65 years commencing first-line neo-adjuvant, adjuvant or palliative CTx for any solid organ malignancy. Those receiving non-CTx agents were excluded. Baseline demographics and established frailty measures were recorded, including Eastern Cooperative Oncology Group performance status (ECOG PS), Rockwood Clinical Frailty Scale (CFS), Geriatric-8 (G8) score and Charlson Co-morbidity Index (CCI). CARG score was calculated after initial Oncology consultation. Follow-up data including CTCAEv5 toxicity and hospital admissions were collected retrospectively. Results: 19 centres recruited 330 patients between Nov 2019 - Dec 2022. Median age was 73 years (range 65-92) and 51.9% were male. 54.9% had a primary tumour of gastrointestinal origin, 48.7% received CTx with palliative intent and 70.8% received doublet therapy. At baseline, 85% patients had an ECOG PS 0 or 1, with median CFS 3 (range 0-8), G8 score 12 (range 6-16) and CCI 6 (range 2-12). Follow-up data was available for 314 (92.6%) patients; the median CTx cycles received was 4 (range 1-16) with 124 (39%) patients dose reduced at cycle one. Treatment delays occurred in 83 (26.4%) patients and 123 (39.2%) stopped treatment early, with 60 (48.8%) cases due to treatment-related toxicity. 69(22.3%) patients experienced a CTCAE grade ≥3 toxicity and 84 (27%) requiring hospital admission. CARG score was available for 313 patients; 107 (34.2%) low risk, 167 (53.4%) medium risk and 39 (12.5%) high risk. Increasing CARG risk groups had increased toxicity rates (low 19.6%, medium 22.2%, high 28.2%) however this was non-significant with no evidence of robust predictive performance (Table). The performance of CFS and ECOG PS was superior to CARG. Conclusions: In this UK older patient population, baseline frailty was prevalent. CARG score was unable to robustly discriminate or predict risk of high-grade toxicity. ECOG showed superior, albeit limited, ability to predict and discriminate toxicity risk. This study highlights the need for development of further tools predictive of toxicity in this population. [Table: see text]
Real world study of racial disparities associated with toxicities of sacituzumab govitecan.
Authors: Shista Priyadarshini, Justin Petucci, Avnish Katoch, Vasant Honavar, Monali K. Vasekar
Journal: Journal of Clinical Oncology (2024)

1572 Background: Sacituzumab govitecan (SG) is approved in the treatment of metastatic hormone receptor positive and triple negative breast cancer (BC). The efficacy of SG across racial subgroups is known but no real-world data compares the racial differences in toxicities. We aim to expand knowledge about racial disparities regarding SG toxicities and any ineffective treatment or drug failure. Methods: We utilized TriNetX, a multi-health care organization electronic health record database, to identify African American (AA) and Caucasian (C) cohort for outcome comparison. Inclusion criteria required a C50 ICD-10-CM diagnosis code and at least one SG treatment. Age, gender, and race-controlled Cox proportional-hazard (CPH) model was used to analyze the time until the first pause or cessation of SG (defined as first deviation from the approved 21-day SG cycle). Several measures of deviation were noted 0, ±1 and ±3 days. Association between race and toxicity outcomes (controlled for age and gender) for anemia, neutropenia, thrombocytopenia, nausea and inpatient encounters were evaluated using multiple logistic regression (MLR). The odds (OR) and hazard (HR) ratios with corrected p-values are reported as an effect size and significance estimation. Results: 823 patients met the inclusion criteria (545 C, 116 AA &amp; 162 unknown). The mean age (in years) at the initiation of 1st SG treatment was 58.22 ± 12.7 for C and 58.19 ± 12.18 for AA. AA had a 1.26 times higher hazard of SG treatment pause/cessation as compared to C. Blacks experienced an 88% increase in the odds of having a delay longer than 7-days between 2 doses of 1st cycle SG. Males were found to have an 80% increase in the pause/cessation rate as compared to females. The median number of SG treatments was 6 (3 cycles) for both AA and C. SG was noted as 4 th chemo line (median) among all races. When compared to C, AA had decreased odds for neutropenia, increased odds for anemia and increased odds for hospitalization. Hazard Ratio and corrected p-values for outcomes comparing the AA and C cohorts. Conclusions: Survival analysis indicates that AA and male patients have an increased SG treatment pause/cessation rate. While the result is sensitive to specific conditions used to calculate the deviation, an increased odds of delay in treatment is also found using logistic regression modeling. Additionally, AA experience increased odds for anemia and late-stage hospitalization. These findings highlight the impact of race on BC outcomes, treatment toxicities and the need for further research to enhance treatment outcomes in diverse populations. [Table: see text]