bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectrum and characteristics of germline PALB2 pathogenic variants among patients with early-onset breast cancer in China.
Authors: Li Jing , He Peng , Cai Qindong , Chen Lili , Wang Yali , Cai Weifeng , Qiu Yibin , Guo Wenhui , Chen Minyan , Lin Yuxiang , Wang Chuan , Fu Fangmeng
Published: June 2024

e22536

Background: Partner and localizer of BRCA2 ( PALB2) plays a critical role in homologous recombination repair and recognized as a breast cancer predisposition gene. Early age at onset of breast cancer is considered a hereditary high-risk factor. However, limited information is available about early-onset breast cancer in China. The objective of this study was to investigate the spectrum and characteristics of germline PALB2 pathogenic variants among this population. Methods: A total of 1556 patients with BRCA1/2-negative early-onset breast cancer were included. Peripheral blood samples were collected and all coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing. Results: The prevalence of germline PALB2 pathogenic variants was approximatel 0.77% in entire cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations, four nonsense mutations and one missense mutation. Except for PALB2 c.1056_1057del, which was detected twice, all other variants were detected once. In comparison to non-carriers, PALB2 carriers were more likely to be 30 years old or younger (25% vs. 14.4%), have a positive family history of breast or ovarian cancer (16.7% vs. 6.3%), exhibit metastatic lymph nodes (75% vs. 50.9%), belong to human epidermal growth factor receptor-2 (HER2) -negative and hormone receptor (HR) - positive subtype (75% vs 54.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%). Conclusions: The prevalence of the germline PALB2 pathogenic variants is approximately 0.77% in BRCA1/2 mutation-negative early-onset breast cancer patients in China. Our findings contribute additional insights into the spectrum and characteristics of PALB2 pathogenic variants in Chinese early-onset breast cancer patients, providing valuable information for this population. Key words: PALB2, Germline mutation, Genetic sequencing, early-onset breast cancer, China. [Table: see text]
The value of blinded independent central review (BICR) in recent trials in non-small cell lung cancer (NSCLC).
Authors: Edelman Martin Joseph
Published: June 2024

e23000

Background: Progression free survival (PFS) is an endpoint that has been increasingly used to obtain approval of new cancer drugs and strategies. However, there are a number of issues that can complicate assessment of PFS. One of these is the potential for investigator bias. This has been addressed by the use of blinded independent central review (BICR). However, BICR increases costs and complexity. Methods: The current study evaluated the results of BICR versus investigator assessment (IA) for phase III randomized clinical trials in thoracic oncology with initial publication from 1.01.2013-12.31.2023. Trials were included if they involved targeted agents, antibody drug conjugates or immunotherapy. Studies with < 100 pts or comparing only cytotoxic chemotherapy or maintenance strategies were excluded. Studies with cytotoxic chemotherapy as part of therapy or within the control arm were included. A search of clinicaltrials.gov with the terms “phase III”, “non-small cell lung cancer” for completed studies was done, supplemented by a bibliographic search. Publications were then reviewed for whether a BICR was utilized and whether both BICR and IA were reported. Hazard Ratios (HR) for PFS between IA vs BICR were compared. Results: 49 randomized phase III trials were identified of which 34 describe BICR of which 21 reported both IA and BICR results. Six studies evaluated immunotherapy and enrolled 3337 pts, 15 evaluated targeted agents and enrolled 6531 pts. All immunotherapy studies were significantly positive for the experimental arm and 14 of 15 of the targeted therapies were positive. PFS data was reported for 17 of the studies (not reached for experimental arms in 2 and not reported in 2 others). HRs were directionally similar in all studies, though were lower (more favorable) in IA vs BICR in 5 of 6 immunotherapy studies and 11 of 15 targeted therapy studies. The mean % difference for immunotherapy studies was 8.9% and the median 10%, range 2-23.5%. For the positive targeted therapies studies the mean/median differences were 14.6%/15.6%, range 1.5-42%. The largest % differences were seen at the lowest HRs (e.g..19 vs .27; 42%). For immunotherapy studies, the median PFS difference was 0.2 and 0.28 months for the control and experimental arms, respectively. For targeted therapy studies, median PFS differences were 0.4 and 0.95 months for the control and experimental arms, respectively. The studies were performed in multiple countries including the United States, European Union, China and Japan. Conclusions: Despite a wide range of agents and settings, no trial for which information is publicly available comparing BICR to IA has demonstrated any qualitative difference in outcome nor more than a marginal numerical difference.
Heterogeneity in methods for estimating renal function in anticancer drug development.
Authors: Karol Alexander B. , Fujiwara Yu , Paredes Rodrigo , Argulian Anna , Joshi Himanshu , Galsky Matt D.
Published: June 2024

e23002

Background: Accurate assessment of renal function is critical in oncology clinical trials. Many anti-cancer agents are renally excreted or cleared, and impaired kidney function can significantly impact drug safety and efficacy. In an effort to modernize renal eligibility criteria the American Society of Clinical Oncology–Friends of Cancer Research Organ Dysfunction Working Group recommended that if renal toxicity and clearance are not of direct treatment-related concern, then patients with impaired renal function should be included in trials (Lichtman, JCO, 2017). However, a diversity of approaches are available to determine renal function. Methods: We systematically searched the clinicaltrials.gov database to review renal eligibility criteria for phase III clinical trials. These trials evaluated systemic anti-cancer therapies in adult patients between October 28th 2013, and October 28th 2023. Studies were excluded if they did not include eligibility criteria related to renal function. The demographics of the trials and methods used for estimating renal function were recorded. Results: 436 trials met criteria for review and 231 trials, enrolling 111,424 patients, met our inclusion criteria. Systemic therapies explored included: immunotherapy (98 trials, 42%), targeted therapy (110 trials, 48%), chemotherapy (17 trials, 7%) or other regimens (6 trials, 3%). Renal function exclusion criteria are shown in the Table. Among studies that estimated renal function with a formula, 140 (61%) studies used Cockcroft-Gault, 3 (1%) used Modification of Diet in Renal Disease, 9 (4%) used an institutional standard, 10 (4%) used a heterogenous combination of estimation equations, and 69 (30%) trials did not specify the estimation approach. Conclusions: In phase III clinical trials involving adult cancer patients, there is substantial heterogeneity in methodologies utilized for determining renal function as related to trial eligibility. Harmonization of approaches to estimate renal function in oncology trials may improve trial accessibility, generalizability, and comparability. [Table: see text]
Precision oncology clinical trials: A systematic review of phase II clinical trials with biomarker-driven, adaptive design.
Authors: Lee Hee Yeon , Ha Hyerim , Kang Jin Hyoung , Park Hye-Sung
Published: June 2024

e23005

Background: Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. Methods: We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Results: Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Table. Precision Oncology Trials led to the FDA approval. Conclusions: Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape. [Table: see text]
Uptake of recommendations for broadening clinical trial eligibility criteria for patients with brain metastasis and leptomeningeal disease in lung cancer clinical trials: A systematic review.
Authors: Riano Ivy , Velez Maria Antonia , Pomares-Millan Hugo , Velazquez Manana Ana I.
Published: June 2024

e23007

Background: Brain metastasis (BM) in patients with lung cancer are relatively frequent (~20%). Clinical trials (CTs) often exclude patients with BM due to concerns about life expectancy, functional status, and toxicity. Restrictive eligibility criteria deter patients with BM from receiving investigational treatments that may be beneficial. In 2017, ASCO, Friends of Cancer Research (FoCR), and the US FDA recommended to expand eligibility criteria to assist in design more representative trials. We examined the uptake of these guidelines in BM/leptomeningeal disease (LMD) inclusion criteria among registered lung cancer CTs. Methods: We extracted eligibility criteria of US-based, phase I/II/III interventional CTs for patients with metastatic lung cancer registered in ClinicalTrials.gov between 10/2012 to 01/2024. CTs registered one year within ASCO/FoCR/FDA published their recommendations were excluded. For each trial, two independent reviewers screened eligibility criteria and classified patients with BM as fully included (active/untreated disease), partially included (treated/stable disease), or excluded, and LMD as included or excluded. Discrepancies were resolved by a third reviewer. Fisher’s exact tests and odds ratio (OR) were obtained by logistic regression. Results: Among 307 CTs, patients with BM were partially included in most CTs (228, 74.3%), excluded in 9 (2.9%) and not mentioned in 35 trials (11.4%). Patients with active BM were included in 35 trials (11.4%). The use of steroids was accepted in 69 trials (22.5%). Only 18 trials (5.8%) included patients with LMD. Most patients with LMD were excluded (135, 44.0%) or not mentioned as criterion (154, 50.2%). A statistically significant difference was observed in the inclusion of patients with BM pre- vs post-recommendations ( p= 0.046). Yet, there was not significant difference in trials with active BM and LMD pre- vs post-recommendations. CTs including patients with active BM or LMD were more likely to appear in CTs explicitly measuring central nervous system outcomes (OR = 4.3; p= 0.002; OR = 14.3; p= 7e-5, respectively). Conclusions: Although existing recommendations to broaden CTs eligibility criteria to include patients with BM showed a significant change, patients with active BM and LMD remained excluded from lung cancer trials. Designing CTs including patients with active BM/LMD is likely to improve patient accrual, increase access to clinical trials and further characterize the investigational drug’s safety and efficacy in this patient population. Exclusion criteria should be clearly justified, and expected toxicity should be reflected in the rationale. As new targeted therapies emerge in lung cancer realm, eligibility criteria should be modernized to fit patients who will be using novel therapies once they are available.
MetaAnalysisOnline.com: A new easy-to-use bioinformatic tool for the meta-analysis of clinical trials.
Authors: Gyorffy Balazs , Fekete Janos Tibor
Published: June 2024

e23012

Background: A meta-analysis is a formal, quantitative study design in epidemiology and clinical medicine that systematically assesses and consolidates previous research findings to derive comprehensive conclusions on a specific topic. Here, we aimed to establish a new tool for the visualization options useful for conducting a meta-analysis specifically designed for oncology trials. Methods: A meta-analysis can be based on binary data, continuous data, or time-to-event data. The most crucial statistical models, including the random effect model and the fixed effect model, are outlined alongside their respective statistical methods. Furthermore, we implemented graphical representations such as the forest plot, funnel plots, and Z-scope plots. While the forest plot effectively illustrates heterogeneity and pooled results, a funnel plot can reveal potential publication bias, and a Z-score plot shows the robustness of the used sample number. Results: The models and visualization options outlined have been integrated into a new, online web portal which can be accessed without the need for registration. The web application operates on an Ubuntu server running Apache and enables users to conduct meta-analyses using results typically used in oncology trials including binary (total and event numbers), continuous (mean and standard deviation data), and time-to-event data (hazard rate and CI data). Study results from common spreadsheet applications like Excel can be directly input into the system. The online platform utilizes the meta and metafor packages in the R programming environment (R version 4.2.2) for calculations and plots. The Shiny user interface is powered by shinyjs, shinydashboard, and rhandsontable R packages. The portal generates a forest plot to summarize meta-analysis results, a funnel plot for visual detection of potential bias, and a Z-score plot showing the sufficiency of the cumulative sample number. The analysis results of the tool were validated using IBM SPSS v28. The new bioinformatic tool is available at www.metaanalysisonline.com and requires no programming knowledge or command line use. Conclusions: Our platform aims to provide a user-friendly meta-analysis tool for epidemiological studies and oncology clinical trials, offering a swift and reproducible way to integrate the results from multiple studies.
Reduced time to efficacy signals in advanced cancer trials using Chauhan weighted trajectory analysis.
Authors: Chauhan Utkarsh , Mackey Daylen , Mackey John Robert
Published: June 2024

e23028

Background: As Kaplan-Meier (KM) analyzes single unidirectional endpoints, most advanced cancer randomized clinical trials (RCTs) are powered for a 10 endpoint of either progression free survival (PFS) or overall survival (OS). This disregards efficacy information carried by stable disease (SD), partial response (PR), and complete response (CR) that may precede progressive disease (PD) and death. Chauhan Weighted Trajectory Analysis (CWTA), a generalization of KM, permits simultaneous evaluation of multiple rank ordered endpoints. We hypothesized that using CWTA with all efficacy inputs could expedite RCT efficacy signals. Methods: We performed 100-fold simulations of RCTs in advanced cancer and determined the time to first significant efficacy signal (p < 0.05) for KM PFS and OS (logrank test) and CWTA (weighted logrank test). RCTs were stochastically generated at defined sample size (SS) allocated 1:1 to control or intervention and run for 60 months. Rank ordered health statuses were CR = 0, PR = 1, SD = 2, PD = 3, and Death = 4. All patients we assigned SD at time 0 and, each month, were capable of response (PR then CR), maintained SD, or irreversible exacerbation to PD or Death. Event probabilities were modified between groups as defined by a hazard ratio (HR). We modeled a control group CR rate of ~10% and a PR rate of ~50% to reflect first-line advanced cancer RCTs with a dropout rate of 10% over 60 months. At increments of SS and HR, we determined the mean and standard deviation of time-to-efficacy signals. Results: CWTA markedly reduced the time-to-efficacy signals when compared to KM PFS (23% to 67%) and KM OS (43% to 82%) (Table 1). Conclusions: CWTA, by incorporating the entirety of the cancer trajectory including disease response, progression, and death, meaningfully expedites the efficacy signals of cancer treatments compared to KM PFS and OS. We have previously reported CWTA increases trial power and reduces sample size requirements (Chauhan U, Zhao K, Walker J, Mackey JR; 2023. DOI: 10.3390/biomedinformatics3040052). Using CWTA rather than KM reduces trial duration, cost, and numbers of patients needed to evaluate therapies in advanced cancer, while reducing the regulatory risk inherent in powering a trial for a single KM primary endpoint. [Table: see text]
Compliance with Centers for Medicare & Medicaid Services (CMS) 2021 price transparency requirements among proton therapy centers.
Authors: Feder Noah Maxwell , Cargill Kasey , Wilhite Tyler , Skinner Heath Devin , Mowery Yvonne Marie , Wilke Christopher
Published: June 2024

e23034

Background: Since 2019, the Centers for Medicare & Medicaid Services (CMS) has required hospitals to publish gross charges for all goods and services provided. In 2021, CMS amended this requirement to include publishing standard charge files, which include cash and payer-negotiated prices for all goods and services provided. This was enacted in an attempt to reduce healthcare prices by reducing information asymmetry and generating competition among both insurers and hospitals. Since complex proton therapy is one of the most expensive modalities of cancer treatment, we aimed to determine proton therapy center compliance with CMS price transparency requirements. Methods: We searched for online standard charge files for the 44 proton therapy centers in the United States. To assess compliance with the nine CMS price transparency criteria, we obtained prices for proton therapy using keyword searches and billing code 77525, the CPT code for the per fraction technical charge billed for complex proton treatment delivery. Results: Out of 44 operating proton therapy centers, 5 (11.4%) are free-standing private practice centers that are not affiliated with a hospital system, and thus not required to publish standard charge files per CMS policy. Of the 39 centers required to publish, 39 (100%) published their standard charge files free of charge with appropriately named files, thus meeting Criteria 1-3. Twenty-seven (69.2%) centers met Criteria 4 by including data on complex proton therapy (CPT code 77525) and Criteria 5a by including the gross charge for the service. One (2.6%) center partially met Criteria 4. Seventeen (43.6%) centers included negotiated prices for commercial insurers, thus meeting Criteria 5b, while 3 (7.7%) partially met this criterion. Twenty-two (56.4%) centers met Criteria 5c and 5d by including the deidentified minimum and maximum negotiated commercial prices, respectively. Twenty-six (66.7%) centers met Criteria 5e by listing the cash price for complex proton therapy, which is typically paid out-of-pocket by patients. One (2.6%) center partially met Criteria 5c-e. In total, 17 (43.6%) out of 39 proton therapy centers were in complete compliance with the 2021 CMS price transparency requirements. Conclusions: In summary, 17 out of 39 eligible proton centers were fully compliant with the 2021 CMS price transparency requirements in regard to complex proton radiation therapy. This suggests that deficiencies exist among hospital compliance and the CMS review process used to identify non-compliance. Future directions are aimed at expanding this analysis to include evaluation of proton center compliance with other billing codes, such as simple and intermediate proton treatment delivery. [Table: see text]
COVID vs. non-COVID oncology patient cohorts: Demographics and cancer variables.
Authors: Sajith Bilja Kurian , Cesario Sandra K. , Fadol Anecita P. , Fredland Nina M. , Dello Stritto Rita A. , Day Lakeisha R. , Reddy Dereddi Raja , Nates Joseph ,   D3CODE Team
Published: June 2024

e23046

Background: This study aimed to compare demographics and cancer-specific variables in oncology patients hospitalized with (n = 551) and without COVID-19 (n = 3674) during the first year of the pandemic. Methods: We analyzed prospectively collected data from March 2020 to February 2021 at a major US cancer center, comparing age, sex, cancer category, race, metastasis, treatments within one month prior to admission, and smoking history. Results: The study found no significant difference in mean age between COVID and non-COVID cohorts (60.7% vs. 60.9%; p = 0.830). Significant differences (p = 0.002) in cancer categories were noted between COVID and non-COVID cohorts. Hematological cancers had the highest hospitalization rates in both groups (38.8% vs 29.2%). Statistically significant racial differences were observed between COVID and non-COVID cohorts (p < 0.001). Whites had the highest hospitalization rates in both groups, yet COVID-related admissions were lower for Whites (COVID cohort: 51.2% vs non-COVID cohort: 61.9%) and Asians (COVID cohort: 2.7% vs non-COVID cohort: 5.9%) compared to non-COVID admissions, while higher for Blacks (COVID cohort: 15.4% vs non-COVID cohort: 14%) and Hispanics (COVID cohort: 28.3% vs non-COVID cohort: 15.7). Significant differences (p < 0.001) were noted in metastasis prevalence between COVID and non-COVID hospitalizations, with rates of 81.3% and 86.0%, respectively. Conversely, non-metastatic cancer was more prevalent in COVID hospitalizations (18.1%) than in the non-COVID cohort (8.7%). In the COVID cohort, 30.5% received chemotherapy within one month before admission, compared to 43.8% in the non-COVID cohort, showing a significant difference in admission rates (p < 0.001). Similarly, recent immunotherapy (8.0% vs. 10.9%) and recent surgery (3.6% vs. 6.6%) were associated with higher hospitalization rates in the non-COVID cohort (p = 0.046 and p = 0.010, respectively). We observed significant differences (p < 0.001) in the smoking history of the COVID and. non-COVID cohorts. While 2.5% of COVID patients were current smokers, 5.4% of non-COVID patients were, more than double the COVID rate. In the COVID cohort, 36.3% were former smokers, slightly lower than the 37.6% in the non-COVID cohort. Additionally, 59.3% of COVID patients were never smokers, compared to 56.3% in the non-COVID group. Conclusions: COVID-related admissions were lower for Whites and Asians compared to non-COVID admissions, while higher for Blacks and Hispanics. Lower rates of metastasis were noted in COVID cohort. Lower rates of hospitalizations among patients who received chemotherapy, immunotherapy, and surgery were observed in the COVID cohort. The smoking prevalence was higher in the non-COVID group, former smoking rates were similar across cohorts, and a higher proportion of COVID patients were never smokers.
Exploring outcomes in hospitalized patients with COVID-19 based on nutritional status: Comparing those with and without a cancer diagnosis.
Authors: Bhinder Muhammad Mujtaba , Davis Elaine A. , Welch Christine A. , Kamran Amir Shahzad
Published: June 2024

e23068

Background: This study explores how nutritional status impacts COVID-19 outcomes, particularly in patients with cancer. Obesity is known to heighten risk of adult respiratory distress syndrome in COVID-19, malnutrition and its associated effects related to the immune response, respiratory compromise, debility, and other adverse outcomes has not been well defined in this patient population. Methods: In this retrospective cohort study, we examined data from the Charleston Area Medical Center’s (CAMC) COVID-19 Registry, involving 5,479 adult, symptomatic, PCR-positive COVID-19 hospitalized patients (3/1/20 to 1/20/24). Low nutritional status (LNS) was defined as Body Mass Index (BMI) < 18.5 kg/m² or serum albumin < 3.5g/dL). Demographics, comorbidities, lab values, treatments, and outcomes were assessed. Propensity score matching (3:1) non-cancer patients vs those with an active cancer diagnosis was undertaken using sex, age, and BMI. SAS 9.4 was utilized for the analysis. The groups were compared using Chi-square/Fisher’s Exact tests for categorical variables and t-tests for continuous variables. Multivariate analysis was utilized to determine predictors of adverse outcomes. Results: A cohort of 1,146 non-cancer and 382 active cancer patients were included in the study. The LNS subgroup had a higher frequency of active cancer (29.2% vs 19.3%, p < 0.001), higher rates of diabetes (27.0% vs17.8%, p = 0.03) and chronic kidney disease (18.8% vs 11.7%, p = 0.02). They had greater frequencies of abnormal ferritin levels (57.8% vs 42.7%, p < 0.001), CRP levels > 3 mg/L (96.6% vs 90.3%, p < 0.001), and elevated procalcitonin levels > 0.05 ng/mL (71.2% vs 50.1%, p < 0.001). LNS patients had a higher mortality rate (22.3% vs 9.7%, p < 0.001), a higher need for mechanical ventilation (19.3% vs 9.5%, p < 0.001), and intensive care unit (ICU) admission (35.7% vs 19.5%, p < 0.001. Predictors of mortality included LNS (OR = 2.2, 95%CI [1.5-3.2], p < 0.001), an active cancer diagnosis (OR = 1.7, 95% CI [1.2-2.6], p = 0.003), chronic kidney disease (OR = 1.8 95%CI [1.3-2.5], p = 0.004) and concurrent bacterial pneumonia (OR = 4.9 95%CI [3.3-7.2], p < 0.001). Conclusions: In patients with COVID-19, those with LNS had higher rates of co-morbid conditions including active cancer, higher rates of elevated inflammatory markers, mechanical ventilation, ICU admission, and mortality. Predictors of mortality included concurrent bacterial pneumonia, cancer diagnosis and chronic kidney disease, with LNS increasing the risk of mortality by more than two-fold. These results support the recommendation of early nutritional assessment and a multi-disciplinary approach to aggressive nutritional support in the COVID-19 patient population particularly in those with a concurrent high-risk condition such as cancer.
Influence of aging, comorbidities, and chemotherapy on dementia in patients with metastatic cancer.
Authors: Shour Abdul Rahman , Rhodes Heather X. , Wen Zhi , Anguzu Ronald , Sheku Tejan Yusuf , N’jai Alhaji U. , Dedo Sika A. , Edet Precious Patrick , Puthoff David , Onitilo Adedayo A.
Published: June 2024

e23097

Background: Studies highlight cognitive decline in cancer survivors, exploring treatment-linked neurodegeneration risks. Yet, the effects of aging (age), comorbidities, and chemotherapy on dementia in metastatic patients are unclear. Methods: US Trauma Quality Program (2017-2019) for 17,940 metastatic cancer patients was analyzed. Our outcome was dementia diagnosis in metastatic cancer patients (no/yes). Independent variables were patient’s age (younger adults aged 18-55 years and seniors ≥56 years), any comorbid condition (yes/no), and received chemotherapy (yes/no). Covariates included sex, payment type, verification level, injury intent, mechanism, injury place, and Injury Severity Score. We used Stata.v18 for descriptive statistics, chi-square, and logistic regression with statistical significance at p≤0.05. Results: Of the 17,940 patients, 7.9% had dementia. Seniors had higher dementia rate than younger adults (98.9% vs. 1.1%; p < 0.001). Most dementia patients had comorbidities (89.4%, p < 0.001). Chemotherapy recipients had a lower dementia rate than those untreated (8.9% vs. 91.1%; p < 0.001). In the adjusted analyses, seniors than younger adults (OR: 4.51, 95% CI: 2.38 - 8.56) and any comorbidities (OR: 1.33 ,95% CI: 1.07 - 1.65) exhibited higher odds of dementia. Notably, chemotherapy recipients had decreased odds of dementia than those untreated (OR: 0.42, 95% CI: 0.34 - 0.53). Conclusions: Metastatic cancer patients of older age and comorbidities had increased risk of dementia. Chemotherapy remarkably lowered this risk. This should guide clinicians in managing dementia risk. [Table: see text]
Investigating disparities in enrollment of patients in lung cancer clinical trials that led to FDA approval for immunotherapies between 2015 and 2023: A comparison with the US population.
Authors: Le Nhu Tuyet , Nguyen Ryan Huu-Tuan
Published: June 2024

e23104

Background: Registrational clinical trials have led to the FDA approval of numerous immunotherapy (IO) agents in the treatment of non-small cell lung cancer (NSCLC) since 2015. Given the historical lack of adequate representation of the US population with cancer in clinical trials, we aimed to analyze disparities in race and ethnicity reporting and enrollment in lung cancer clinical trials that led to FDA-approved immunotherapies between 2015-2023. Methods: The FDA archives and database were queried to review all FDA drug approvals for IO approved to treat NSCLC between 2015 to 2023. Enrollment data were obtained from FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. The enrollment incidence ratio (EIR) and enrollment mortality ratio (EMR) were calculated as the proportion of patients of a particular race among clinical trial participants in approval studies divided by the estimated proportion of patients of that particular race diagnosed or dying of lung cancer, respectively, among the US population. Results: Among 27 trials with a total of 15,878 subjects, distribution by race shows that 77.5% were White, 16.7% Asian, 8.8% Hispanic, 1.63% Black, 0.33% American Indian Alaska Native (AIAN), and 0.07% were Native Hawaiian and Other Pacific Islander (NHOPI). 67.4% were males while 32.6% were females. The EIR for Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic patients was 0.99, 0.13, 3.56, and 0.85 respectively. The EMR for Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic patients was 0.99, 0.12, 4.23, and 0.96 respectively. Racial demographics were reported in 65% of journal manuscripts, 65% of ClinicalTrials.gov pages, and 92% of FDA labels while ethnicity demographics were reported in 0% of journal manuscripts, 42% of ClinicalTrials.gov pages, and 15% of FDA labels. Conclusions: Black, AIAN and female patients are severely underrepresented in lung cancer trials that lead to approval for IO based therapy. Asian patients were overrepresented. Less than half of the trials reported data on ethnicity. Further research is needed to see if regulatory initiatives to increase clinical trial diversity result in more equitable clinical trial enrollment in pivotal trials.
Comparing emergency department and oncology urgent care for non-emergent acute care.
Authors: Hong Arthur S. , Charania Sadaf , Bazzell Angela F. , Courtney D. Mark , Sweetenham John W. , Halm Ethan A.
Published: June 2024

e23107

Background: Adults with cancer often visit the emergency department (ED) during treatment for commonly anticipated issues (e.g. pain, nausea). Some providers have created oncology urgent care clinics (OUCC) to manage these non-emergent issues. Evidence suggests that they are associated with lower ED use. Little is known about the care delivered at OUCCs, and how it compares to ED care. We compared visits from our OUCC to ED visits at our comprehensive cancer center. Methods: We studiedvisits from Jan 1 – June 30, 2023. To limit selection bias, we excluded ED visits if patients were referred by an outpatient clinician, including phone triage. Triage nurses document a validated Emergency Severity Index (ESI, version 4) as part of usual care in the ED, but not the OUCC. The ESI ranks high-severity (level 1 – “patient dying”; 2 – “shouldn’t wait”) to lower-severity (level 5), with the three lower levels distinguished by vital signs and clinical resources needed to stabilize a patient. Two clinicians reviewed OUCC visits and recorded ESIs. We assessed inter-rater reliability of OUCC ESI coding. We used multivariate, mixed-effects methods (visits clustered to patient) to model two outcomes: care escalation (OUCC to ED/inpatient; ED to inpatient) and length of stay (LOS). We excluded visits with ESI at the extremes (1 and 5). We adjusted for sex, age, comorbidities, cancer type and stage, date/time of arrival, and ESI. We then used marginal effects methods to report adjusted outcomes, stratified by ESI. Results: We analyzed 904 OUCC visits (580 patients) and 4,115 ED visits (2,866 patients). Over half (55.5%) of ED arrivals occurred after business hours. Median patient age was 67 (IQR 57 - 74), 48% were female, and 58% non-Hispanic white. Cancer types included 18% hematologic, 17% GI/colorectal, 12% breast, and 7% lung; 11% were advanced-stage. Unweighted inter-rater reliability for ESI was high for a subset of 164 OUCC visits (k = 0.81, 95% CI: 0.72 - 0.89). Although OUCC had a sizable portion of level 2 visits, ED had significantly higher severity. At each ESI level, adjusted rates of care escalation were significantly higher for ED than OUCC (overall aOR 5.6, 95% CI: 4.4 - 7.2), and LOS was longer for ED than OUCC (5.2 hours longer, 95% CI 4.8 – 5.6). Conclusions: The severity of OUCC visits was high, though patient self-referred ED visit severity was higher. OUCC may be more efficient than the ED for managing non-emergency care in this population. Future work should further investigate the quality of care delivered at each site, including cost of care. [Table: see text]
CGP-based IO biomarker assessment and treatment utilization across a major US health system.
Authors: Dowdell Alexa K. , Meng Ryan , Weerasinghe Roshanthi K. , Vita Ann , Bapat Bela , Hanes Douglas , Schroeder Brock , Champagne Maude , Fox John Leonard , Wong Cliff , Poon Hoifung , Bifulco Carlo B. , Piening Brian
Published: June 2024

e23109

Background: Immune checkpoint inhibitors (IO) have become a powerful precision therapy option to treat advanced stage cancer with biomarkers such as PD-L1, tumor mutational burden (TMB), and microsatellite instability (MSI) associated with improved patient response rates. Despite this, many patients do not receive genomic testing for all IO biomarkers. Providence, a large US community health system, developed a pathologist-directed testing protocol where comprehensive genomic profiling (CGP) was routinely used at time of diagnosis for advanced cancer patients. Methods: Advanced cancer patients who received CGP (ProvSeq 523) and IHC testing for PD-L1 between 2019-2023 were included in the study. Patients were required to be treated at Providence and were assessed for presence of IO biomarkers and subsequent therapy selection. Real world data were curated from patient charts and genomic laboratory data by employing a novel natural-language processing (NLP) approach to accelerate abstraction. Results: The study included 2,502 patients (53% female, median age 68y, 83% white). Top 3 tumor types tested were lung (40%), colorectal (9%), and breast (8%). Overall, 58% (N = 1,455) of patients had presence of ≥1 IO biomarker, with 46% (N = 1,155) being PD-L1 positive, and 27% (N = 682) being TMB-H. In PD-L1 negative patients (N = 1,347; 54%), 300 (22%) were TMB-H and 18 (1%) were MSI-H. 53% (N = 767) of patients who harbored an actionable IO biomarker received IO-based therapy. Fewer patients with an IO biomarker received chemotherapy compared to patients without an IO biomarker (23% vs 35%, p < 0.001). Patients who possessed ≥2 IO biomarkers received an IO precision therapy 68% of the time vs 47% in patients with 1 IO biomarker (p < 0.001). In PD-L1 negative patients, 26% (N = 78) of TMB-H patients received IO monotherapy compared to 5% (N = 49) of TMB-L patients. Conclusions: IO biomarker presence is associated with increased precision therapy use. CGP identified many TMB-H patients for IO monotherapy that would have been missed with PD-L1 testing alone. More than half of patients eligible for IO therapy don’t receive it; ongoing analyses will evaluate the impact of pathology-directed reflex testing on IO as well as targeted therapy approaches. [Table: see text]
Mapping disparities in head and neck cancer care: Geospatial analysis of social vulnerability and healthcare access in the US.
Authors: Black Christopher M. , Zheng Dandan , Goodnight Bradley , Habila Magdiel , Merchant Sanjay , Cassese Marie , Fortman Alexander , Walbert Harold , Sieling Fred , Hanna Glenn J.
Published: June 2024

e23112

Background: Ensuring equitable access to head and neck (H&N) cancer care across the US is vital for optimal patient outcomes. This study explores the impact of social vulnerability on disparities in access to H&N multidisciplinary specialist care by US region and metro status. Methods: Oncologists and a subset of H&N cancer specialist practice locations were extracted from the National Provider Index, American Society of Clinical Oncology, and US News and World Report. Travel time using the fastest transportation mode from population-weighted county centroids to the nearest H&N cancer specialist (surgical, radiation, or medical oncologist) was computed using Travel Time API. Cancer data were obtained from United States Cancer Statistics and Surveillance, Epidemiology, and End Results (SEER). Regression analysis assessed impact of aspects of social vulnerability from the Social Vulnerability Index (SVI) on travel time. A disparity index incorporating travel time, county-level H&N cancer incidence, and SVI was developed to quantify disparities at the county-level. Results: In total, 18,241 medical, 6,387 radiation, and 2,564 surgical oncologists were identified, of which 346 medical, 308 radiation, and 453 surgical oncologists self-identified as H&N specialists. Regression analysis indicated that low household income and lack of insurance within counties significantly increased travel time ( p < .001) after controlling for US region, metro status, cancer rate, and other county-level factors. The disparity index identified counties with highest and lowest disparity (Table 1). Conclusions: Key findings highlight specific counties with higher vulnerability, primarily rural counties in the West and Southeast, and underscores the influence of social vulnerability on access to care. After accounting for US region and metro status, aspects of social vulnerability still predict travel time, with low household income and lack of insurance being the most impactful. Identified disparities in care may provide targets for interventions and policies aimed at reducing access inequalities, such as outreach programs and allocation of resources to underserved areas. [Table: see text]
Access to cancer center information for patients with limited English proficiency from NCI Cancer Center websites.
Authors: Fuchs Jeffrey William , Fuchs Joseph Robert , Theros Jonathan S , Liu Yingzhe , Sun Zequn , Mohindra Nisha Anjali
Published: June 2024

e23124

Background: Patients with Limited English Proficiency (LEP) can experience health disparities in cancer care and clinical trial participation. This study sought to assess the availability of information on interpreter services, clinical trials, and second opinions from National Cancer Institute – Designated Cancer Center (NCI-DCC) websites for patients with LEP. Methods: The public facing websites of all 65 adult NCI-DCCs were reviewed from January 1, 2023 to May 15, 2023 to assess availability of English and translated, non-English information on interpreter services, second opinion programs, and clinical trials. Data abstraction was conducted through predefined criteria for website inspection and search bars. Three authors independently abstracted websites for content, with constant comparison until consensus was achieved. Chi-square tests were used to ascertain any significant association between the proportion of LEP populations served by the centers ( > 5%) and their likelihood to provide translated information. Results: 92.3% of NCI-DCCs and their affiliated flagships hospitals provide information on interpreter services for patients with LEP. This information was translated into a non-English language approximately half of the time. All NCI-DCC center webpages provide information on clinical trials and 38.5% provide information regarding second opinions. There was no difference in the availability of translated information on interpreter services or second opinion programs based on percentage of LEP population. However, there was an association between higher LEP population and the provision of translated clinical trial pages. Conclusions: The majority of NCI-DCCs provide information on their webpages related to interpreter services and clinical trials. Half of these centers provide this information in a non-English language and there was an association between higher percentage of LEP populations in the NCI-DCC state and translated clinical trial pages. Future work should identify optimal methods to provide cancer related information to patients with LEP with the goal of improving clinical trial participation for LEP populations. [Table: see text]
Oncofertility: The unmet need.
Authors: Venkitaraman Balasubramanian
Published: June 2024

e23143

Background: Breast cancer incidence has been increasing across the globe and it has become most common cancer among women in Indian population also. The age trend of breast cancer incidence has shown change, with increasing number of women in the young age group( < 35 years) developing breast cancer.With increasing incidence of breast cancer among young women, the question of fertility in these young women becomes a significant issue. Most of these patients are in a state of shock when they are detectedwith cancer. It becomes the utmost responsibility of the treating oncologist to discuss about fertility issueswith the patient. This study was done to determine the prevalent knowledge, practice and attitude among oncologist across various parts in India with respect to fertility issues. Methods: We performed an online survey among oncologist spread across the country. The survey included questions aimed to identify their knowledge and attitude towards fertility preservation in young breast cancer patients and what they actually practice. Also demography details of the oncologist were recorded to identity and socioeconomic or cultural variations affecting their practice behaviour. Their response was graded and analysis done using SPSS software. Results: A total of 123 oncologists had completed the survey. Among the responders majority were surgical oncologist (68.3%) followed by medical and radiation oncologist with majority doing Institution based practice. Most of the oncologists were aware of the literature available for onco fertility discussion with patient. 84.91%responders had the knowledge that this discussion should be initiated at the time of diagnosis of disease. There were no significant disparity among respondents with respect to location and site of practice in terms of knowledge 88.68% were comfortable in discussing these issues with the patients; however, majority of responders felt that very few patients came out to discuss options of onco fertility (less than 25% of patients). Most of the responders were aware of the facilities available for appropriate referrals In practice, 63.4% said they had offered information, however patient has declined to take any further step . 22.76% of responders had actually successfully referred at least one patient for fertility consultation. Conclusions: There seems to be a positive trend in terms of fertility conservation among oncologist, however study has identified a lack of willingness among young Indian breast cancer patients to seek such treatments.
Adherence and persistence of encorafenib in combination with cetuximab among patients with BRAF metastatic CRC in the United States (US) based on two claims databases.
Authors: Parikh Aparna Raj , Vieira Maria Cecilia , Silver Michelle , Rava Andrew , Rau Reina , Li Benjamin
Published: June 2024

e23146

Background: The BRAF V600E mutation (BRAF-m) occurs in approximately 7% of patients with metastatic CRC (mCRC). Encorafenib (enco) in combination with cetuximab (cetux) was approved in April 2020 as the first targeted regimen for the treatment of adult patients with mCRC with BRAF-m. The purpose of this study is to analyze the post-approval real-world persistence and adherence to treatment with enco in combination with cetux or with panitumumab (pani), an alternative EGFR, in mCRC, based on two claims databases in the US. Methods: This was a retrospective cohort study in the IQVIA PharMetrics Plus database and the Merative MarketScan Commercial Database (2013-2022). Adults ≥18 years old with ≥1 claim for enco (first claim for enco on/after its date of approval in April 2020) with concurrent EGFR (cetux or pani), ≥2 ICD-9/10 codes for malignancy of the colon or rectum ≥30 days apart in the 1 year before index date, and ≥1 day of pharmacy and medical continuous enrollment during the index date were included. Patients were excluded if they had a record of melanoma or non-small cell lung cancer during the year before index date, were enrolled in a clinical trial any time after the CRC diagnosis date or did not have a treatment regimen starting on or after CRC diagnosis date (-14 days). Index date was the date of first treatment of enco + EGFR during the identification period (4/1/2020-3/31/2022). Patient demographics and disease characteristics were assessed at baseline, adherence (measured as at least 80% of days covered) and persistence (measured as time to discontinuation by Kaplan-Meier method) were estimated during the follow-up period. Results: 205 patients were included. Median (Q1 [1st quartile], Q3 [3rd quartile]) age at index was 59 (50, 64) years and 51.7% were female. Metastases were present in 3 or more sites in 62.9% of the patients, in 1 or 2 sites in 35.6%. The 2011 Modified Quan Charlson Comorbidity Index was 0 for 44.9% of the patients, 1-2 for 38.5%, and 3 or more for 16.6%. Most patients received cetux as their EGFR combined with enco (76.1%). Adherence to enco + EGFR was high (87.8%); enco + cetux vs. enco + pani: 89.7% vs. 82.6%. Median (Q1, Q3) proportion of time on cetux while on enco was 87% (78%, 95%) and median (Q1, Q3) proportion of time on pani while on enco was 85% (71%, 91%). Median (95% confidence interval) time to enco regimen discontinuation during follow-up was 6.1 (5.3–7.7) months. Conclusions: This up-to-date study provides current real-world evidence on the use of enco + EGFR in mCRC BRAF-m patients in the US. The results show high levels of adherence to the treatment, suggesting high tolerability to encorafenib, and persistence consistent with clinical trial evidence.