tbuckley/cabot-search huggingface dataset:
Prevalence of HTLV-1 and 2 infection in the blood donor population of Colombia during 2012 to 2022.
Authors: Jaime Molina, Ivan Camilo Triana, Javier Segovia
Journal: Journal of Clinical Oncology (2024)

e22528 Background: The HTLV-1 and 2 virus are oncogenic retrovirus with a global distribution. Viral infection is primarily associated with two conditions: HTLV-1-associated myelopathy and adult T-cell lymphoma. Although Colombia is an endemic country for the virus, data on its incidence, prevalence, and the population characterization of infected individuals are limited. Methods: This is a descriptive observational study of a retrospective cohort from a blood donor population of Fundación Hematológica de Colombia from 2012 to 2022, to determine the seroprevalence of HTLV-1 and 2 in this population. Demographic and clinical variables such as age and gender were described to characterize the seropositive population and identify specific populations, such as women of childbearing age who are seropositive for the virus. Results: During the study 1,553,478 patients were recruited, of which 3,484 were seropositive, representing a global prevalence of 0.22% over 10 years. The annual incidences were as follows: from 2012 to 2013, 0.22%; from 2014 to 2015, 0.26%; 2016 to 2017, 0.23%; 2018 to 2019, 0.25%; 2020 to 2021, 0.15%; and in 2022, 0.12%. Among the seropositive individuals, 58% were women, and 42% were men. In the donor population studied, the order of prevalences by city was as follows: Bogotá with 48%, Ibagué 13%, Barranquilla 7%, Pasto 5%, Villavicencio 4%, Pereira 3%, Soacha 3%, Tunja 2%. The average age for seropositive women and men was 22 years. 54% of seropositive women were within the reproductive age. Conclusions: Our cohort has a higher seroprevalence compared to North America. In Colombia, the two cities with the highest prevalence are the capital of the country and the city of Ibagué in our study. From a public health perspective, it is noteworthy that approximately 1100 seropositive women for HTLV-1 and 2 are in reproductive age and could potentially transmit the oncogenic virus through vertical transmission or breastfeeding. With our results it would be in the interest of public health agencies to report positive results to women of child bearing age and positive donors to begin health counseling as soon as possible.
Molecular characteristics of dedifferentiated liposarcoma with broad rhabdomyosarcomatous differentiation.
Authors: Wanming Hu, Zhouyu Wang, Minghui Ge, Ningning Luo, Dong-sheng Chen, Xin-ke Zhang
Journal: Journal of Clinical Oncology (2024)

e23530 Background: Dedifferentiated liposarcoma (DDLPS) with broad rhabdomyosarcomatous differentiation has a worse prognosis compared with other types of DDLPS. Therefore, it is of importance to recognize its molecular characteristics in order to investigate individualized treatment strategies. Methods: We conduct next-generation sequencing (NGS) including DNA and RNA sequencing analysis in 5 DDLPS patients with broad rhabdomyosarcomatous differentiation and perform comparative analysis between well-differentiated and dedifferentiated components from the patients. Results: In the ten samples, several somatic copy-number variations (CNVs) including the gain of 12q are considered as frequent molecular alterations. IGFN1, FGFR4, BLM, RICTOR, RUNX1 and TOP1 mutation is the high-frequency single-nucleotide variations (SNVs). Novel BEST3/CD63/LGR5/CENPL-MDM2 and ERBB3-TAFA2 fusion genes are identified in this subtype of tumor. The comparative analysis between well-differentiated and dedifferentiated components recognized two categories of molecular variations: shared variations, such as FGFR4 and BLM mutation, ERBB3-TAFA2 fusion, and MYC amplification that are associated with tumorigenesis, and dedifferentiated-specific variations including GRIN2A, FOXP1 and TP53 mutation, CERS4-PTPRB and TRIO-TERT fusion, and ESR1 amplification, which are related with malignant progression. After surgery, the patient received adjuvant therapy. The mean follow-up of the patients was 30 months, and the mean recurrence-free survival (RFS) was 9.6 months. Conclusions: This NGS analysis disclosed the possible progression mechanisms and therapeutic targets in DDLPS with broad rhabdomyosarcomatous differentiation and provided insights contributing to the refinement of management in this tumor. [Table: see text]
Mind the gap: Estimating the opportunity lost due to the gap between FDA and EMA cancer drug approvals.
Authors: Samantha Gage, Elias Eteshola, Matthew James Hadfield, Dany Hamze, Ali Raza Khaki, Sanjay Mishra, Michael Kevin Rooney, Gabrielle Masse, Talal Hilal, Sandeep Kumar Jain, Sam Rubinstein, Mark Lythgoe, Jeremy Lyle Warner
Journal: Journal of Clinical Oncology (2024)

11030 Background: Drug regulators operate on their own timelines to assess the safety and efficacy of new drugs and/or extensions to existing indications, such that there are delays between regulators. During such a gap, patients in the “early” domain have access to the approved drug, while those in the “late” domain do not, outside of compassionate use. Our study aimed to quantify the “opportunity lost” for new therapies approved by FDA and EMA, assuming patients in the late domain receive standard-of-care (SOC) therapy – which is presumably inferior to the new drug – during the gap. Methods: Anticancer drugs approved by both FDA and EMA were identified through the HemOnc knowledgebase. Inclusion criteria included: 1) drugs approved in both domains based on the same randomized clinical trial (RCTs) for the same indication; 2) a primary time-to-event endpoint; and 3) a quantitated median time-to-event for the primary endpoint. For each included trial, the approval gap between FDA and EMA in days and the ratio of approval gap to median control arm time-to-event duration was calculated. A ratio ≥2 implies that, on average, no late domain patients starting treatment in the first half of the gap would be expected to have access to the new drug prior to an event. Results: Of 60 eligible RCTs, 59 had calculable median event durations. 25 (42%) had a primary overall survival endpoint; the most common surrogate endpoint was progression-free survival (PFS; 29/59; 49%). The median (interquartile range [IQR]) approval gap was 186 (124-271) days, with FDA being the first approver in 56/59 (95%) cases. The median (IQR) ratio of approval gap to median control arm event duration was 0.63 (0.35-1.11). Drugs with ratio ≥2 (Table) were targeted or immunotherapies; 7/8 (88%) were approved with PFS endpoint; 5/8 (62.5%) were approved for second line or later. Conclusions: Our study shows that FDA approves most drugs prior to EMA and a nontrivial number of patients may experience progression or death events while awaiting access to anticancer therapies already approved in another domain. The analysis does not take into consideration scenarios in which the new therapy is inferior to SOC or delays in patient access (due to slow uptake; regulatory barriers [in Europe/UK]; or patient affordability [in US]). Further regulatory collaboration (e.g., Project Orbis) between FDA and EMA could help to reduce and potentially ameliorate this differential in access to new cancer drugs in the future. [Table: see text]
Progress Tracker Breast Cancer Registry: A Breast Cancer Canada initiative.
Authors: Shaniah Leduc, Amanda Williams Gibson, Michelle Liane Dean, Kimberly Carson, Doris Howell, Omar Farooq Khan
Journal: Journal of Clinical Oncology (2024)

e23018 Background: Significant gaps exist in the collection of real-world evidence and validated patient-reported outcome measures (PROMs) data from individuals with breast cancer. Variations in treatment and surveillance care across regional jurisdictions present knowledge gaps across diverse populations which remain difficult to study. The PROgress Tracker Breast Cancer Registry, a large, prospective Canadian PROMs cohort study aims to identify care gaps through the lived patient experience to inform patient-centered care and new research directions. Methods: PROgress Tracker is a real-world, longitudinal, non-interventional PROMs registry directed by Breast Cancer Canada, a registered non-profit patient-led organization, and data managed by University of Calgary’s POET program. Launched in October 2023, this registry aims to enroll up to 50,000 adult Canadian participants with a histologic diagnosis of in-situ or invasive breast cancer (stage 0 through IV) within 10 years. A volunteer-led peer-to-peer support model, based in regional and provincial hubs across Canada, facilitates participant recruitment, engagement, and retention. Individuals who self-identify for study inclusion provide informed consent, demographic and socioeconomic profile, and clinical information on their breast cancer diagnosis. Every three months (and up to 10 years) a bilingual digital platform to reduce barriers to access is used to provide all PROgress Tracker participants 8 validated PROMs to capture evolving measures of self-efficacy for wellbeing, symptoms and overall global functioning. Based on treatment, up to 10 additional PROMs to assess the immediate adverse effects and long-term impacts of treatment are collected. PROgress Tracker has the additional capacity to link to external ethics-approved studies to investigate clinical outcome and healthcare utilization metrics for participants consenting to additional studies. Results: In progress. Conclusions: PROgress Tracker represents Canada’s first national PROMs breast cancer registry. Its unique design and implementation by a patient-led research organization helps fill gaps in current knowledge through longitudinal follow up of patients prior to, during, and after cancer care, and from the time from diagnosis through active treatment, long-term survivorship, and/or palliative care. The PROgress Tracker Registry will comprehensively gather the validated real-world data information rarely collected in in the traditional clinical or trial-based research setting using a novel self-enroll design and digital process. Such information is crucial to support evidence-based decision making to inform patient-centered healthcare change. This allows comparison across Canadian jurisdictions, is scalable to other jurisdictions around the world and further explores the utility of electronic PROMs data capture within a diverse patient population.
Radon exposure in Colombian never smoker patients with non-small cell lung cancer: A pilot study.
Authors: William Armando Mantilla, Mariana Borras, Alberto Ruano, Isabel Munevar, Lucia Viola, Jairo Andrés Zuluaga, Luis Leonardo Rojas Puentes, Andrés Felipe Cardona Zorrilla, Luis J Tellez
Journal: Journal of Clinical Oncology (2024)

e22521 Background: Lung cancer (LC) is the leading cause of cancer-related death globally, with 1.8 million deaths estimated in 2022. In Colombia, up to 74% of patients with LC are diagnosed with stage IV which negatively impacts survival, with 6,000 estimated deaths in 2022. The most critical strategy for reducing LC is the reduction of tobacco exposure; however, up to 38% of LC cases are not related to tobacco. Among other risk factors different from tobacco smoke; indoor radon, a radioactive gas found naturally in closed spaces, stands out and could be the most important one. In Latin America, information on the influence of radon on the incidence of LC is scarce. This study aims to establish the prevalence of Radon exposure in Colombian never-smoker LC patients. Methods: This is a Pilot study. Adult patients with de novo NSCLC diagnosis ( &lt; 6 mo) were included. Past smokers (≥100 cigarettes in life or ≥1 cigarette daily for 6 mo) or patients with a change in place of living in the last 10 years were excluded. Sociodemographics, clinical, and molecular information were obtained and included in an eCRF using REDCap®, Radon measurement was done using a DTPA-type detector (Alfa-track). The detector was located in the patient's home, (60-140 cm from the floor at the point of least ventilation of the space to be measured), for 90 days, Subsequently an automated count quantification was carried out using the Radosys® system at a certified lab (Universidad Santiago de Compostella Radon Lab). The Radon levels were reported in Bq/m3, using the average value observed during the measurement period (The threshold was 20 Bq/m3). Results: Between February 2022 to May 2023, 30 patients were included in the study, 86.7% were women, 73% had stage IV disease at inclusion, 53% had a driver mutation, with EGFR being the most frequent (62,5%) followed by ALK (31.3%). The mean Radon levels were 25.6 Bq/m3 (5 – 48). No patient had Radon levels ≥100 Bq/m3. Conclusions: In this pilot study, we didn´t find high radon exposure among never-smoker NSCLC patients. 2 other studies on indoor Radon concentrations have been done in Colombia, with only one demonstrating high radon levels (≥100 Bq/m3) in Bogotá. These differences could be explained by the type of house, rainfall adjustment, or underlying rock composition in our study. It´s important to increase the sample size for a definitive conclusion and to explore other risk factors in non-smoker patients as the quality of air or occupation, among others. [Table: see text]
Shareable artificial intelligence to extract cancer outcomes from electronic health records.
Authors: Kenneth L. Kehl, Justin Jee, Karl Pichotta, Pavel Trukhanov, Christopher Fong, Michele Waters, Chelsea Nichols, Ethan Cerami, Deb Schrag, Nikolaus Schultz
Journal: Journal of Clinical Oncology (2024)

11000 Background: Clinical outcomes such as response, progression, and metastasis represent crucial data for observational cancer research, but outside of clinical trials, such outcomes are usually recorded only in unstructured notes in electronic health records (EHRs). Manual EHR annotation is too resource-intensive to scale to large datasets. Individual cancer centers have trained artificial intelligence natural language processing (AI/NLP) models to extract outcomes from their EHRs. However, due to concerns that models trained on protected health information (PHI) might encode private data, such models usually cannot be exported to other centers. Methods: EHR data from Dana-Farber Cancer Institute (DFCI) and Memorial-Sloan Kettering (MSK) collected through the AACR Project GENIE Biopharma Collaborative were used to train and evaluate Bidirectional Encoder Representations from Transformers (BERT)-based NLP models to extract outcomes from imaging reports and oncologist notes annotated with the Pathology, Radiology/Imaging, Signs/Symptoms, Medical oncologist, and bioMarkers (PRISSMM) framework. Document-level outcomes included the presence of active cancer; response; progression; and metastatic sites. ‘Teacher’ models trained on DFCI EHR data were used to label imaging reports and discharge summaries from the public MIMIC-IV dataset. ‘Student’ models trained to use MIMIC documents to predict teacher labels were transferred to MSK for evaluation. Results: Teacher models were trained at DFCI on 30,332 imaging reports for 2609 patients and 32,173 oncologist notes for 2917 patients with non-small cell lung, colorectal, breast, prostate, pancreatic, or urothelial cancer. The models were used to label 217,642 imaging reports and 141,377 discharge summaries from MIMIC for student model training. These DFCI-trained student models were evaluated at MSK, demonstrating high discrimination (AUROC &gt; 0.90) across outcomes. Conclusions: This privacy-preserving “teacher-student” AI/NLP framework could expedite linkage of genomic data to clinical outcomes across institutions, accelerating precision cancer research. [Table: see text]
The predictive value of the MASCC score in patients with febrile neutropenia.
Authors: Zackary Anderson, Keegan Plowman, Mohammed Ahsan, Mark Rasnake, Michal J. Kubiak, Joel Scott Grossman
Journal: Journal of Clinical Oncology (2024)

e23059 Background: Febrile neutropenia (FN) is a life-threatening complication in patients receiving cytotoxic chemotherapy. Guidelines classify FN as a one-time oral temperature of greater than 38.3°C or sustained temperature greater than 38°C for ≥ 1 hour with an absolute neutrophil count (ANC) of less than 500 cells/μL or an ANC expected to decrease to less than 500 cells/μL within a 48-hour period. This condition has a high rate of hospitalization and mortality. Currently, the Multinational Association of Supportive Care in Cancer (MASCC) risk score is used to classify patients as high or low risk. The current study outlines the predictive role of MASCC scoring in risk stratifying patients with FN at our institution. Methods: This is a single-center, retrospective observational study. IRB approval was obtained for this study. Electronic medical record data was reviewed to record mortality, length of stay (LOS), and antimicrobial use as primary outcomes with age at time of admission, sex, race, type of malignancy, any confirmed infection diagnosis, MASCC risk score, and subspecialist consultation as predictors of outcomes. Results: 220 records of possible FN episodes were screened, 160 were excluded leaving a total of 60 patients for review. The median age was 72.5 with 28 males and 32 females. Overall mortality rate was 10%.33 patients (55%) did not have an identifiable source of infection. Among the 27 patients with confirmed infection, 7 were associated with COVID-19, 12 had gram negative rod (GNR) sepsis and 8 were other bacterial infections. Patients with GNR sepsis had the highest mortality risk in which 4 of the 12 (33%) died. LOS was also significantly longer in patients with GNR sepsis. Lower MASCC scores were associated with identification of GNR sepsis. Of the patients with MASCC score of &lt; 24, significantly more patients 7/20 (35%) developed GNR sepsis compared to 5/40 (12.5%) of those with MASCC score of 24 or greater (p = .004). Patients with GNR sepsis received a mean 5.7 days of broad spectrum antibiotics compared to 3 days in those without, (p &lt; 0.001). Those with no identified infection had significantly lower LOS (4.5 days) compared to the groups with GNR sepsis (11.1 days) or other bacterial infections (10.1 days). Conclusions: Febrile neutropenia is a complication of cytotoxic chemotherapy that warrants special attention due to high mortality rates. We found lower MASCC scores were associated with GNR sepsis and that in the setting of FN these patients had higher mortality rates and longer LOS. This highlights the importance of risk stratification with MASCC index scoring as early recognition and treatment of high risk patients could lead to improved patient outcomes.
CAR T-cell therapies: Measuring the growing need for increasing long-term safety protocols.
Authors: Yacoub Faroun, Daniel F. Winkelman, Nicholas Gambone, Patrick Angelastro
Journal: Journal of Clinical Oncology (2024)

e23047 Background: The CAR T-Cell market has grown significantly over the last five years with six products in the U.S. market covering a range of cancer types (DLBCL, FL, MCL, MM, ALL). The number of transplant centers certified for CAR T-Cell administration has also grown from 142 centers in Q4 2020 to 200 in Q4 2023. The FDA is currently investigating the safety of CAR T-Cell therapies due to the threat of secondary malignancies. CAR T-Cell patients are treated at advanced treatment centers but after they have completed therapy, they are often referred back to their original specialist for long-term monitoring. The purpose of this research is to measure if referring Oncologists have the information required to safely manage CAR T-Cell patients. Methods: This study followed market research best practices. The study was based on a survey of the BrandImpact panel of Oncologists who refer patients and a CAR T-Cell Panel of Oncologists who administer CAR T-Cell therapies. Results: The majority of referring Oncologists (61%) report they could use more information about CAR T-Cell therapies. When asked on an unaided basis what type of information they require, the most common request was for additional safety information (57%). At the same time, one-third of Oncologists treating CAR T-Cell patients at the advanced centers feel that there needs to be improved knowledge of the long-term safety aspects of CAR T-Cell therapies. When they resume monitoring CAR T-Cell patients, they would like to better understand the relevant long-term side effects and how they differ from the short-term side effects. Conclusions: Oncologists who refer CAR T-Cell patients report that they need more information; mainly around safety/side-effects. Of the Oncologists administering CAR T-Cell therapies, one-third feel there needs to be improved knowledge of the long-term safety issues. Consideration should be given to improving the level of educational information provided on this topic to improve CAR T-Cell patient outcomes. [Table: see text]
Precision oncology clinical trials: A systematic review of phase II clinical trials with biomarker-driven, adaptive design.
Authors: Hee Yeon Lee, Hyerim Ha, Jin Hyoung Kang, Hye-Sung Park
Journal: Journal of Clinical Oncology (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]