bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adapting a prescreening program from VHIO to match molecular alterations in over 10,000 patients' tumors with targeted agents and immunotherapies in early clinical trials.
Authors: Aguilar Susana , Vivancos Ana , Nuciforo Paolo , Gonzalez-Zorelle Jenifer , Pedrola Anna , Viaplana Cristina , Felip Enriqueta , Tabernero Josep , Garralda Elena , Dienstmann Rodrigo 
Published: June 2024

e23071 Background: VHIO's Molecular Prescreening Program (MPP) began in 2010 to catalyze precision medicine at the institution. Over the last decade, this program has provided access to advanced molecular diagnostics to more than 10,000 cancer patients (pts) and is critical in matching targeted therapeutic approaches to clinical trials (CTs). Here we report the clinical utility of our program given the evolving molecular testing landscape and trends in drug development. Methods: We assess the adoption and impact of the VHIO’s MPP in CTs recruitment. All tests were developed in-house: a. from 2010 to 2014 we used formalin fixed paraffin embedded tumor samples to test for hotspot mutations (Sequenom, 20 oncogenes) plus FISH/IHC of selected markers; b. from 2015 to 2017 we moved to a amplicon-based NGS panel (MiSeq, 61 genes), a copy number alteration (CNA) panel (Nanostring, 44 genes) and a fusion + gene expression assay (Nanostring, 26 genes) with additional FISH/IHC in selected cases, including PDL1 and MSI status; c. since 2019, we use a custom capture-based NGS assay for mutations (mut), CNA and Tumor Mutation Burden (TMB) estimation (NextSeq, 435 genes); d. since 2022, we run a liquid biopsy panel in-house (Guardant360, technology transfer). Results: We found a stepwise increase in the MPP adoption, from 207 pts in 2010 to 1,965 pts in 2023, representing almost a tenfold increase. Most common tumours analysed were colorectal, lung, breast, gynaecologic, pancreato-biliary, and gastric. The number of CTs requiring biomarker match has increased from 13 in 2010 to more than 201 in 2023, the most frequent in the last year being HER2 (33), PDL1 (20), EGFR (17), RAS (15) and FGFR (9), MSI (9) and ALK (7). In 2023, 1,230 patients had broad tissue NGS panel, 1,235 were tested with IHC, 373 with fusions + expression assay and 991 with liquid biopsy. Inclusion rate in CTs with biomarker match has fluctuated between 13% and 19% in the past 5 years. Overall, close to 50% of these trial recruitments are with genomically-informed enrichment strategies and not mandatory inclusion criteria. On average, 20% of the patients were still enrolled in unmatched trials after molecular testing. Conclusions: The success of VHIO's MPP is related to agile innovation and clinical deployment of new technologies in a timely manner, critical for the development of new drugs in CTs. Biomarker matched trials evolved from a “few targets/ large populations” scenario to a complex situation with “many targets/ small populations”. Many pts benefit from enrichment strategies in Phase 1 CTs. The impact of the recent implementation of liquid biopsy and ongoing development of genomic + transcriptomic signatures will be closely monitored.
Outcomes of pericardial complications among patients with solid and liquid cancer: Analysis of National Inpatient Sample database.
Authors: Shah Nagma , Hajiabbasi Maryam , Bhatt Navin , Song David 
Published: June 2024

e23073 Background: Pericardial complications (PC) are common in malignancy as sequelae of metastasis, direct toxicity of radiation or chemotherapy, or pericardial infection/inflammation due to malignancy. The goal of this study was to assess the cardiovascular outcomes of pericardial complications among patients with solid and liquid cancer. Methods: The National Inpatient Sample from the years 2015 to 2018 was queried to assess cardiovascular outcomes in the setting of pericardial complications (acute pericarditis, chronic constrictive pericarditis, chronic adhesive pericarditis, hemopericardium, cardiac tamponade and other unspecified pericarditis) for patients that have any solid or liquid malignancy. Outcomes included in-hospital mortality, acute kidney injury (AKI), heart failure (HF), cardiogenic shock (CS), myocardial infarction (MI), sudden cardiac arrest (SCA), mechanical circulatory support (MCS), major adverse cardiovascular and cerebrovascular events (MACCE), and stroke. Outcomes were assessed using chi-square analysis using STATA. Results: A total of 1,183,619 cancer patients with PC (n = 20,410.00; 1.7%) and without PC (n = 1,163,209.60; 98.3%) were included. The mean age of patients with and without PC was 58 and 59 years, respectively. The average length of stay in the hospital was 14 and eight days in patients with and without PC, respectively. The most common complications were electrolyte disorders (51.2%, p = 0.000) and arrhythmias (40.4 %, p = 0.000) for patients with and without PC. Patients with PC had higher incidence of in-hospital mortality (11.7% vs 5.1%, p = 0.000), AKI (37.8% vs 22.1%, p = 0.000), HF (25.7% vs 15.5%, p = 0.000), CS (2.7% vs 0.4%, p = 0.000), MI (3.6% vs 2.0%, p = 0.000), SCA (3.2% vs 1.0%, p = 0.000), MCS (0.7% vs 0.1%, p = 0.000), and MACCE (17% vs 7.9%, p = 0.000) compared to cancer patients without PC. There was no difference in outcomes in terms of stroke (1.2% vs 1.2%, p = 0.879). The yearly trend was stable for length of stay among both groups while adjusted total hospital cost was progressively increasing from 2015 to 2018, with a greater net increase in those with PC. Yearly trends of complications were stable among both cohorts. Conclusions: Pericardial complications are prevalent in up to 1.7% of cancer patients, and they are associated with worse cardiovascular outcomes as compared to patients without pericardial complications. Patients with PC also have a higher incidence of in-hospital mortality.
Overestimation of survival in individuals with cancer treated in the real world with new cancer drugs: A population-based cohort study.
Authors: Niraula Saroj 
Published: June 2024

e23076 Background: Oncologists and individuals with cancer often rely on outcomes from pivotal randomized controlled trials (RCTs) for real-world treatment decisions. However, stringent inclusions and standardized protocols limit their applicability. This study quantifies overall survival (OS) disparities for novel cancer drugs between real-world and pivotal RCTs. Methods: Ethics approvals were secured, and data on frequently used targeted cancer drugs for solid cancer treatment in all individuals with cancer in Manitoba, Canada from inception to June 30, 2023, collected using pharmacy database and the Manitoba Cancer Registry. Evidence consistently indicates similar cancer outcomes in Manitoba to most high-resource countries. This analysis includes six common immunotherapies and monoclonal antibodies. Kaplan-Meier Method was used to plot survival probabilities, and descriptive statistics to elucidate variable differences. Comparison between survival outcomes in pivotal RCTs and real-world scenarios was expressed as "Overestimation Quotient or OQ" (OS in RCT over OS in the real world for same indication). Results: A total of 941 individuals diagnosed with cancer were evaluated across eight indications. The observed median OS in the real world for included indications was 11.9 months, ranging from 6.6 to 37.6 months— a duration significantly shorter than the median OS reported in pivotal Randomized Controlled Trials (RCTs) (31.35 months, range 9.2 to 72.1) (P < 0.001). This translated to a median difference of 15.6 months (range 2.6 to 59.9) per indication and an "Overestimation Quotient" ranging from 1.5 to 5.9. Notably, the observed OS was even inferior in the real-world setting compared to the control group used in pivotal RCTs in half of the indications (Table 1). Conclusions: In routine practice, new cancer drugs offer starkly inferior survival compared to that reported in pivotal RCTs used for approval of those drugs, with the difference in survival ranging from a few months to several years, translating up to six-fold difference. Our results highlight potential for alarming misinformation influencing treatment decisions in clinics. We trust that oncologists will consider our findings during treatment discussions in clinics. [Table: see text]
The integration of big data analytics in examining the effects of mental illness screening on mortality and burden of illness among patients with cancer.
Authors: Mohan Minu , Epstein Joel Brian , Alam Naheed , Haniff Shaniza , Pili Roberto , Poolakkad Sankaran Satheesh Kumar 
Published: June 2024

e23083 Background: Cancer patients receiving cancer care in US hospitals undergo notable psychological suffering, characterized by manifestations of multiple psychiatric disorders and a further doubling of healthcare spending each year. The psychological burden of illness (BOI) frequently accompanies the physical obstacles of the disease, hence increasing the intricacy of cancer care. Analysis was conducted on cancer patients admitted to hospitals in the US in 2017 for the treatment of prostate (PC), cancers of the lip, oral cavity, and pharynx (CLOP), lung (LC), and leukemia. The aim was to understand better and compare the differences in mental illness screening (MIS) and its impact on these patients. Methods: We employed generalized linear models to examine the association between MIS and outcomes––BOI, such as cost, total charge, length of stay (LOS), and in-hospital mortality after controlling for clinical and patient variables. Results: Among 224,540 LC, 178,470 patients underwent MIS. This was 151,285 vs. 58,125 among PC; among CLOP, 35,770 vs. 18,495; for leukemia, this was 53,019 vs.18,759. In the adjusted analysis, MIS among the LC cohort was associated with lower length of stay—(coefficient, 0.96, 95% CI, 0.92-0.98), lower total charges, (0.94, 0.92-0.96), and lower mortality (aOR, 0.77, 95% CI, 0.73-0.82). In the LC cohort, when compared to Whites, Blacks (1.11, 1.05-1.17) and Others (Native Americans, Asians, and Others (1.1, 1.02-1.20) had longer LOS. Compared to high-income neighborhoods, low-income neighborhoods showed higher LOS (1.09, 1.03-1.153), and compared to "Central" counties of metro areas of ≥ 1 million population, Not metropolitan or micropolitan counties had a lower LOS (0.86, 0.80-0.92). Private insurance holders had lower total charges than Medicare beneficiaries (0.84, 0.81-0.88). Females, when compared to males, had a lower total charge (0.96, 0.94-0.98), and when compared to Whites, Hispanics (1.35, 1.25-1.45), and Others (1.28, 1.19-1.37) had a higher total-charges. And compared to Whites, Others had a higher in-hospital mortality (aOR, 1.16, 95% CI, 1.03-1.31). Further, the analysis was stratified into surgical and non-surgical cohorts in the LC cohort. Compared to LC, none of the other solid or liquid cancer cohorts, MIS showed no beneficial association with BOI or mortality. Conclusions: The LC cohort showed a positive association between MIS and BOI and in-hospital mortality. To provide holistic treatment for all cancer patients, including MIS as a standard practice is advantageous. This study can offer helpful information for future research on the impacts and implementation of routine mental illness screening among patients with cancer.
National Comprehensive Cancer Network guideline compliance in an oncology value-based care program serving Medicare members.
Authors: Thompson Edward , Hastings Kevin , Cullum Robert , Reddy Shirisha , Brito Rogelio Alberto , Byrd Brooke , Avalos-Reyes Elisea , Johnson Kjel Andrew 
Published: June 2024

e23095 Background: Value-based care (VBC) focuses on improving patient health outcomes while reducing the overall cost of healthcare. National Comprehensive Cancer Network (NCCN) cancer treatment guidelines standardize and improve quality of care. While studies have shown that compliance to NCCN guidelines improves survival, little information exists regarding the impact of compliance in VBC arrangements. This study aimed to evaluate compliance to NCCN regimen guidelines in Medicare members being treated for cancer under a VBC arrangement. Methods: This is a cohort study of individuals receiving care, in a single state, enrolled in a VBC contract within a large national insurer from February 2023 to October 2023. Medicare members with bladder, colon, lung, melanoma, breast, hepatocellular, rectal, pancreatic, multiple myeloma, gastric, ovarian, esophageal, lymphoma, kidney, leukemia, head and neck, biliary tract and uterine cancer with at least one oncology claim within the contract year were included. NCCN compliance was a quality measure of the VBC. NCCN regimen compliance was identified from pharmacy and medical claims and defined as concordant if the entire prescribed treatment regimen matched an NCCN regimen (Level 1 and 2a); members not receiving an NCCN recommended regimen were deemed to be non-concordant. Results: This study included 561 patients, the mean [SD] age was 75.7 [8.2] years and 286 [51.0%] members identified as male. The total population captured through the automated prior authorization platform yielded 100% NCCN compliance. Conclusions: In this study, individuals receiving chemotherapy participating in a shared savings VBC demonstrated 100% compliance to NCCN guidelines.
Childhood Cancer in Cameroon and Kenya: Preliminary findings of an implementation effectiveness study for early detection of childhood cancer.
Authors: Noh Hayle , Denburg Avram , Gupta Sumit , Barwick Melanie , Githanga Jessie Nyokabi , Pondy Ongotsoyi Angele Hermine , Afungchwi Glenn Mbah , King'e Maureen , Landis Fongang Che , Ward Nathan 
Published: June 2024

e23096 Background: Early childhood cancer detection reduces mortality, particularly in LMIC contexts where an improved understanding of early warning signs and symptoms (EWSS) and integration of vital referral pathways into existing health systems are crucial to improved childhood cancer outcomes. Our project seeks to adapt and implement a Ghanaian-developed EWSS intervention for Kenya and Cameroon using implementation science frameworks to move beyond the common but ineffective train-and-hope approach. Cameroon operates on a three-tiered sub-sector health system, with the intermediate level consisting of regional delegations that support districts1. In Kenya a six-tiered health system delivers primary care (1-2), mid-level care (3-4), advanced care with centers of excellence (5-6) 2. Health system contexts will inform implementation planning and execution. Methods: Health system stakeholders convened in each country to launch their EWSS initiative. Two-day meetings were collaboratively led by local stakeholders and the research team, guided by The Implementation Roadmap3, a multi-implementation framework resource. They discussed l) local barriers to childhood cancer detection, 2) referral pathways, 3) leadership and operational implementation teams, 4) sustainable EWSS training, and 4) target settings. Results: Stakeholders endorsed the EWSS program and identified individuals to form implementation teams to plan and execute implementation reflective of health system organization and realities. Both countries engaged in an evidence-based implementation planning process, reviewed EWSS core components and training logistics, and endorsed a sustainable tiered training model targeting clinicians and oncologists across system levels and institutional providers. Training content will be adapted for country, region, and county contexts. Both countries endorsed and identified district childhood cancer champions to facilitate training and coordinate timely referrals. Common implementation barriers identified included high healthcare worker turnover, transportation logistics for in-person training, and remuneration options for trainees. Conclusions: Health system leaders in Kenya and Cameroon endorsed an evidence-based EWSS implementation and sustainment approach and identified adaptations responsive to the health system contexts. Implementation will be locally led to ensure effectiveness, sustainability, and appropriate cultural EWSS adaptation. Moving forward, local implementation teams will work with researcher-facilitators to implement EWSS toward improved cancer detection rates.
A comparative analysis of needs and role of patient navigation among early-phase cancer clinical trial participants and non-participants at a single cancer center.
Authors: Doroshow Deborah Blythe , Sheng Tianxiang , Aryeh Brittany , Conner Robert , Loehle Julia , Lucas Natalie , Padilla Melissa , Pappalardo Rachel , Fromm Katherine , Smith Cardinale B. 
Published: June 2024

e23127 Background: Early phase clinical trials (EPCTs) assess the safety and toxicity of novel anticancer agents and represent opportunities for patients (pts) to try novel therapies when standard therapies have become ineffective. However, EPCT participants represent a vulnerable population with high financial toxicity and symptoms related to their cancer and previous treatments. EPCTs often require frequent visits and additional procedures which may be burdensome. Pt navigators perform needs assessments and provide guidance to pts as they move through the health care system. Navigation, which has a high level of acceptance among pts with cancer, can improve time from diagnosis to treatment, decrease pt anxiety, and improve participation of minoritized individuals in clinical trials. We hypothesized that EPCT participants would have higher navigation needs than those of non-EPCT participants with cancer. Methods: Utilizing a needs assessment conducted in person or by telephone, pts with cancer treated at Mount Sinai are assessed for 26 individual and systemic social drivers of health (SDoH) barriers by pt navigators at their trial screening visit. EPCT participants were defined as pts participating in a study in the Early Phase Trials Unit. Descriptive characteristics were assessed for all participants regarding demographic characteristics and SDoH barriers. Welch's T-test was used to compare differences in navigation encounters, SDoH barriers and navigator interventions between the EPCT and non-EPCT pt groups. Results: From February to December 2023, 31 EPCT pts and 1145 non-EPCT pts completed the assessment. Median age was 58.9 and 62.4 years, respectively. Racial and ethnic self-identification included 13% vs. 20% Black pts and 19% vs. 20% Hispanic pts. EPCT pts had a mean 5.29 navigation encounters per pt compared to 4.11 in non-EPCT pts (p = 0.27). Pts in the EPCT group were found to have an average of 3.81 SDoH barriers identified, in contrast to 1.7 in the non-EPCT group (p < 0.001). The most common barriers identified in EPCT pts were institutional, knowledge, and psychosocial; in non-EPCT pts, transportation barriers were most common. Furthermore, based on the identified barriers, EPCT pts required an average of 17.23 interventions, compared to 4.57 among those not in the EPCT group (p < 0.001). Interventions most frequently involved coordination with the primary team and education for pts in both groups. Conclusions: EPCT pts had more navigation encounters, SDoH barriers identified, and resultant interventions than non-EPCT pts. Participants in EPCTs are a vulnerable pt population for whom navigation is particularly warranted. [Table: see text]
Molecular and genomic testing in Native American patients with metastatic lung and colorectal cancers: A retrospective chart review.
Authors: Popuri Niveditha , Phan Minh Duc , Nipp Ryan David , Doescher Mark Philip , Janitz Amanda , Dvorak Justin , Buckner Sheryl , Anderson-Buettner Amber , Rhoades Dorothy Alison 
Published: June 2024

e23136 Background: The Native American (NA) population has the poorest cancer survival of all racial groups in the U.S. A long history of research misconduct has caused many tribal communities to hold unfavorable views toward genomic data collection. Routine molecular and genomic testing is standard of care for most metastatic lung and colorectal cancers but the frequency of such testing in NA patients is unknown. Many NA patients have limited financial resources and must rely on coverage for health care from an Indian Health Service, Tribal Health Service, or Urban Indian Health (ITU) program. However, ITU programs do not operate their own cancer treatment services and must refer their patients elsewhere for such care. Methods: A Native American Navigation program (NANP) was established at the Stephenson Cancer Center (SCC) in Oklahoma to promote cancer health equity and provide high-quality cancer care by facilitating access to care for ITU patients from across the state. The NANP interfaces with ITU programs to obtain approvals for care as well as to coordinate clinical and supportive services, such as transportation or food assistance. We conducted a retrospective chart review of patients referred from an ITU program to the SCC NANP in Oklahoma from 1/2014 to 6/2023. Among patients with metastatic colorectal cancer (CRC), we investigated the frequency of testing for KRAS, NRAS, BRAF as well as MSS/MSI. In patients with metastatic non-small cell lung cancer (NSCLC), we identified the frequency of EGFR, ALK, ROS1, and PD-L1 testing. Results: A total of 305 NA patients were referred to SCC for colorectal and lung cancers. Of these, 68 patients had metastatic disease and qualified for molecular and genomic testing per National Comprehensive Cancer Network guidelines. The mean age of our cohort was 63 with a male-to-female ratio of 1.6:1. Most (85.3%) patients eligible for testing had testing for at least one biomarker. In patients with metastatic CRC, 100% received MSS/MSI as well as KRAS testing and the frequency of NRAS and BRAF testing was 69.6% and 84.8% respectively. In patients with metastatic NSCLC, the frequency of EGFR, ALK, and ROS1 testing was 95.8%, 87.5%, and 79.1%, with PD-L1 testing frequency being 83.3%. Conclusions: The overall frequency of molecular and genomic testing in these navigated NA patients (85.3%) was comparable to the range reported in the general population (66-90%). By facilitating access to cancer care, programs such as the NANP may help NA patients receive appropriate testing to guide treatment. Larger studies are needed to further assess the role of navigation programs in reducing cancer disparities by facilitating access to appropriate molecular and genomic testing for NA patients with metastatic cancers.