tbuckley/cabot-search huggingface dataset:
Clinical and histological profiling of triple-negative breast cancer at Chihuahua´s state cancer center: An observational study.
Authors: Victor Baylon Valdez, Luisa F Gonzalez-Gonzalez, Enrique Jose Zamudio Lozoya, Patricio Ochoa-Elizondo, Paolo Mendoza-Muraira, Regina Martinez-Garcia Lascurain, Rafael Martinez-Sanciprian, Valeria Bates Rodriguez, América Susana Mares García, Gustavo Gil Reza Bravo, Rene Lazaro Gonzalez Mendoza
Journal: Journal of Clinical Oncology (2024)

e22529 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This subtype is associated with a poorer prognosis and higher recurrence rates compared to other breast cancer subtypes. Understanding the histopathological and clinical characteristics of TNBC is crucial for improving early detection, clinical management, and treatment outcomes. In this context, a descriptive analysis was conducted to explore the association between TNBC and histological grade, histopathological type, and clinical stage at the State Cancer Center. Methods: A retrospective, single-center study was conducted at Chihuahua's State Cancer Center, where medical records of patients aged ≥ 18 years old diagnosed with TNBC between January 2018 and December 2022 were retrospectively reviewed. Data related to weight, histological grade, histopathological type, and clinical stage at TNBC diagnosis were collected. Frequency analysis was performed to determine the distribution of these characteristics in the TNBC patient population. Additionally, the association between histological grade and clinical stage at diagnosis was examined using appropriate statistical tests. Results: During the study period, 753 patients were diagnosed with breast cancer. Of these, 84 (11%) were diagnosed with triple-negative breast cancer and were included in the study. The mean age was 49 ± 13 years, with a mean BMI of 28 ± 5. The most common histologic subtype in this group was invasive ductal carcinoma, accounting for 78 (93%) of the TNBC cases. At the time of diagnosis, 19 (23%) were diagnosed with stage IIA, 17 (20%) with stage IIIA, 9 (11%) with stage IV, and 4 (5%) were detected in situ. Overall, the majority were identified as grade 3 tumors (44; 52%). Finally, within the stage IIA group, the majority were grade 3 tumors (58%). Conclusions: As seen in other cohorts, we found a similar frequency of TNBC among patients with breast cancer in our facility in the northwest of Mexico. The distribution of clinical stages highlights the varying degrees of disease progression at the time of diagnosis, with a considerable portion presenting at advanced stages. Moreover, these insights underscore the urgent need for improved screening strategies and early detection methods.
Hematologic parameters as predictors of overall survival in metastatic solid tumor and aggressive lymphoma.
Authors: Dan Morgenstern Kaplan, Asaad Trabolsi, Thomas Plate, Gil Hevroni, Leticia Campoverde, Rachel Kronenfeld, Alyssa Mercadel, Wei Zhao, Gerald A. Soff
Journal: Journal of Clinical Oncology (2024)

e23053 Background: Aggressive cancer is associated with an increased rate of thrombosis. In addition to body mass index (BMI), the Khorana score has identified several hematologic parameters associated with an increased risk of thrombosis. In this study, we assessed the relationship of these parameters with overall survival. Methods: Using data from our tumor registry, we selected patients with aggressive lymphomas (AL), glioblastoma multiforme (GBM), metastatic prostate (MP), metastatic lung (ML), and metastatic colorectal (MCRC) cancer from 2018 to 2023. Laboratory data were extracted from our electronic medical record, with a timeframe of 90 days before and 30 days after first contact, but prior to initiating treatment. We analyzed the relationship of hemoglobin (Hgb), white blood cell (WBC) count, platelet (Plt) count, and body mass index (BMI), with overall survival (OS). Each cancer type was analyzed as a separate group and multivariable analysis was controlled by sex and age at diagnosis. Dichotomizing the variables from categories of the Khorana score, we evaluated the relationship of such variables and OS using Kaplan-Meier Analysis and Cox Proportional Hazards Models. Patients were censored at two years of follow-up. Data analysis was done using R (version 4.3). Results: Of 2,362 patients, 55% were male, and median age was 63 years. (Cancer types: 622 ML, 604 AL, 453 GBM, 281 MCRC, 203 MP, and 199 MB). An initial, pre-treatment Hgb &lt; 10 g/dL was associated with a shorter OS in patients with ML, MCRC, MP, and AL patients. Plt ≥350 x 10 9 /L was associated with a shorter OS in ML and MCRC patients. WBC &gt; 11 x 10 9 /L was associated with a shorter OS in ML, AL, and MCRC, and a BMI ≥35 was associated with a shorter OS only in GBM patients (Table). Conclusions: While not in all cancer types, the hematologic parameters of the Khorana score that predict thrombosis correlate with a reduced overall survival. This effect was significant for different parameters in different cancers. The increased hazard ratio is beyond that which would be expected from thrombosis-related mortality. Our study is limited to data from our single institution and the retrospective nature of the study. [Table: see text]
Intra-read analysis of radiologists in the setting of blinded independent central review of oncology studies.
Authors: Amir Elbahnasawi
Journal: Journal of Clinical Oncology (2024)

11179 Background: This study explored the outcome of an analysis completed on the Intra-reader variability of radiologists when assessing the imaging endpoint surrogates of Date of Progression (DOP) and Best Overall Response (BOR) within the context of Blinded Independent Central Review (BICR) in Oncology clinical trials. The analysis encompassed 55,000 test cases derived from 217 clinical trials involving 138 readers. Methods: Data collection and parsing were executed through a Python script, enabling a manual analysis of the results. The analysis posited that Intra-read variability serves as a valuable tool when seeking to exclusively observe the consistency of readers in a specific re-read setting. Results: The data analysis yielded significant insights, revealing that 89.81% of readers demonstrated substantial and above agreement in DOP determinations, while 72.38% achieved the same in BOR determinations. This suggests a higher level of consistency in DOP compared to BOR determination. Notably, 11 DOP and 20 BOR inconsistencies were observed. This prompted further investigation which led to 5 of the 138 readers being flagged based on discrepancies against their own prior or subsequent reads. The kappa values for these 5 readers ranged from 0.33 to 0.59, consistently indicating fair and moderate agreement. Conclusions: This analysis underscored the role of Intra-read variability in identifying inconsistent readers within the landscape of BICR in Oncology clinical trials. The re-read inconsistency is not a universal requirement, and its application is recommended primarily for complex oncology clinical trials or those with indications known to have elevated adjudication metrics. The study emphasized the potential for targeted retraining strategies based on Intra-read analysis outcomes, contributing to the ongoing refinement of reader proficiency. Future directions may involve further exploration of specific retraining strategies or assessing the effectiveness of exclusively using Intra-read variability as a metric for reader performance.
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: Susana Aguilar, Ana Vivancos, Paolo Nuciforo, Jenifer Gonzalez-Zorelle, Anna Pedrola, Cristina Viaplana, Enriqueta Felip, Josep Tabernero, Elena Garralda, Rodrigo Dienstmann
Journal: Journal of Clinical Oncology (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.
Cancer screening and first-time visits to oncology services during and after COVID-19 pandemic in Uruguay.
Authors: Lucia Beatriz Delgado, Natalia Camejo, Cecilia Castillo, Nicolas Vacca, Bruno Camargo, Gabriel David Krygier
Journal: Journal of Clinical Oncology (2024)

e23016 Background: On March 13, 2020, Uruguay confirmed the first cases of COVID-19 and the same day the government declared a Public Health Emergency that was extended until April 4, 2022. The measures implemented to mitigate the transmission included, among others, postponing screening studies and in-person consultations. Added to these measures was the fear of going to health centers and the consequences of the economic crisis, with the increasing difficulties in traveling and facing the co-payments necessary to access health services. This study aims to evaluate the impact of the COVID-19 pandemic on cancer screening and first time- visits to oncology services during the public health emergency and following its lifting. Methods: We compare the number of PAP test, mammograms and fecal immunochemical test (FIT) reported by the same comprehensive health providers during 3 periods: pre-pandemic (2018-2019), public health emergency period (March 13, 2020- April 4, 2022) and post-public health emergency (April 5 2022-June 30,2023). Cancer screening data was obtained from the screening registry of the Honorary Commission to Fight Cancer (CHLCC) and first oncology visits from the Oncology Electronic Health Record (HCEO). Health providers that report PAP, mammograms, and FIT cover around 90%, 30%, and 40% of health system users, respectively, and those that use HCEO, 40%. Results: After two years of COVID-19 public health emergency, the number of reported PAP smears test, mammography and fecal occult blood test, decreased by 26%, 46% and 33% respectively (Table 1). The reduction was greater during the first months of the pandemic and during the peak of the first wave (April-June 2021: PAP -50%, mammography -58%, occult blood test: -70%). Likewise, the number of first-time visits to oncology services decreased by 37%, reaching a 56% decline during the first wave. As shown in Table 1, these declines continued after the health emergency was lifted. Conclusions: Our results show an important decline of cancer screening and first-time visits to oncology services during the pandemic in Uruguay. After emergency was lifted, reported PAP test showed a partial recovery but mammography, occult fecal blood test and first-time visits to oncology services remain well below pre-pandemic levels. [Table: see text]
Utility of automated data transfer for cancer clinical trials.
Authors: Ivy Altomare, Addison Shelley, Yichen Lu, Paul M. Salcuni, Nicole Graves, Abhishek Maiti, Ramaswamy Govindan
Journal: Journal of Clinical Oncology (2024)

e23011 Background: The burden of data collection on site staff for cancer clinical trials is steadily increasing, and inefficiencies in data entry into electronic data capture (EDC) systems lead to poor data quality and delays in reporting. Software that facilitates automated transfer of mapped structured data from the electronic health record (EHR) to the study EDC system can help to address these challenges. We examined the impact of multi-site usage of an embedded point and click EHR-to-EDC tool on study data capture across multiple cancer clinical trials. Methods: We conducted a retrospective analysis of usage of an EHR-to-EDC tool among research teams at 3 Academic Medical Centers (AMCs) for 4 industry-sponsored Phase 1 cancer clinical trials from the start of use of the tool at each AMC to a cutoff date of 12/31/23. We assessed the types and volume of structured data accessible via FHIR APIs and amenable for transfer (“mapped”) across protocols, the volume of data transferred per protocol, and the time for data transfer, defined as time from case report form (CRF) launch to submission in EDC and time spent in the software application overall. Descriptive statistics were generated for all study metrics. Results: During the 10 month observation period, the EHR-to-EDC tool was used by 8 users to transfer data for 25 patients enrolled across the 4 protocols. Table 1 shows the percentage of total CRF forms mapped and breakdown of proportion of mapped fields per protocol. Overall, 8,597 individual data points (87% labs, 10% vitals and 3% concomitant medications) were pushed for 718 unique CRF submissions. The average number of individual data points and unique CRF submissions per patient were as follows: 400 and 36 (Study A), 420 and 36 (Study B), 251 and 16 (Study C), 270 and 21 (Study D). The average total time spent in the tool per CRF submission was 2.16 minutes (range 1.17-7.00 minutes, inclusive of potential inactive time, application launch and data search). The average time to complete a CRF was 46 seconds (range 15-65 seconds). Conclusions: Use of EHR-to-EDC software facilitated efficient automated transfer of a high volume of study data due to EDC-required repeat use of mapped CRF forms. The impact appeared consistent across protocols, with dozens of unique CRF submissions and hundreds of individual data points pushed per patient for each study. Time for CRF completion was low and uniform across users. This study supports the growing adoption of EHR-to-EDC technology among sites and sponsors, and highlights the evolving potential to further improve and facilitate clinical trial data entry, as tool capabilities are developed beyond structured fields to enable unstructured data capture and transfer. [Table: see text]
Impact of chemotherapy-induced peripheral neuropathy permanence on patients' preference to discontinue chemotherapy.
Authors: Yerial Jun, Xueting Tao, Ciao-Sin Chelsea Chen, Jennifer J. Griggs, Kelley M. Kidwell, Daniel Louis Hertz
Journal: Journal of Clinical Oncology (2024)

12046 Background: Chemotherapy-induced peripheral neuropathy (CIPN) diminishes patients’ functional ability and quality of life; approximately 40% of patients experience CIPN symptoms 3 years after treatment. Due to the absence of effective CIPN treatments, ASCO guidelines recommend discontinuing chemotherapy in patients experiencing intolerable CIPN symptoms. Little is known about patient’s preference to continue or discontinue chemotherapy when experiencing CIPN, and whether the potential permanence of CIPN symptoms affects this decision. The objective of this prospective observational study was to determine the effect of CIPN symptom permanence on patients’ preference to discontinue chemotherapy. Methods: Patients receiving taxane and/or platinum chemotherapy for breast or colorectal cancer were enrolled in a prospective observational clinical study. Patients reported their CIPN severity using the EORTC CIPN20 patient-reported outcome questionnaire at the start of each treatment cycle. At the same time, patients were asked if they would prefer to continue or discontinue chemotherapy treatment under the hypothetical scenario that their current CIPN symptoms would be temporary or permanent. A generalized linear mixed effects model was used to determine the effect of CIPN severity, permanence, and other clinical variables on a patient’s decision to discontinue (vs. continue) chemotherapy treatment. Results: A total of 66 patients completed data collection at least one time, of whom 55 (83%) had breast cancer, 12 (18%) had metastatic disease, and 52 (79%) received a taxane. The odds a patient would prefer to discontinue chemotherapy treatment if their CIPN symptoms would be permanent (vs. temporary) were nearly 30 times greater (odds ratio (OR)=30.15, 95% confidence interval (CI): 15.73-57.79, p&lt;0.001, Table). There was a statistical trend toward preferring to discontinue chemotherapy treatment as CIPN symptom severity increased (OR=1.09, 95% CI: 1.00-1.19, p=0.063). Conclusions: The potential for CIPN symptoms to be permanent has a huge effect on whether patients want to continue or discontinue chemotherapy treatment. Additional data is needed on the incidence and predictors of permanent CIPN. More importantly, shared decision-making tools that convey the risk of permanent CIPN, and the potential risk of discontinuing chemotherapy treatment, are needed to facilitate patient-centered treatment decisions so that each patient with cancer achieves their personal treatment goals. [Table: see text]
Historic redlining, modern neighborhood structures, and mortality in children, adolescents, and young adults with cancer.
Authors: Kristine Karvonen, Annie Vu, Katherine Lin, Joseph Gibbons, Jason Mendoza, Eric Jessen Chow, Lena E. Winestone, Scarlett L. Gomez
Journal: Journal of Clinical Oncology (2024)

11037 Background: Historic redlining, referring to the Home Owners Loan Corporation (HOLC) program’s racially biased risk monitoring maps in the 1930’s, has indelible impacts on modern day neighborhood characteristics and health outcomes. The impact of redlining, a form of structural racism, on children, adolescents, and young adults with cancer (CAYACs) is unknown. This retrospective cohort study evaluates the association between redlining and mortality in CAYACs. Methods: Using the California Cancer Registry, we identified cases &lt;25 years old diagnosed with first primary malignant cancer between 2000-2019. Using merged HOLC maps and U.S. Census data we determined case redlining status (A “Best”, B “Still Desirable”, C “Declining”, D “Hazardous”, and N “Not graded”) by residence at diagnosis. We defined residents of D neighborhoods redlined-exposed and residents of A or B neighborhoods unexposed or referent. Kaplan Meier methods and multivariable Cox proportional hazard models were applied to calculate overall survival. Additional models accounted for census tract-level neighborhood SES (nSES, a composite measure incorporating seven SES domains), neighborhood racial and ethnic composition (or typology) and racialized economic segregation (via index of concentration at the extremes). Results: In total 8,210 cases were HOLC-graded, the median age was 16 years, 46% were female, and 48% had solid tumors. Overall survival at 5 years was inferior for D cases vs. A or B cases (OS 80.2%, 95% CI: 78.5-81.7 vs. OS 88.2, 95% CI: 84.0-91.3). Adjusting for individual clinical characteristics (age, sex, year of diagnosis, and cancer stage), D cases experienced greater mortality (HR 1.32, 95% CI: 1.12-1.55) compared to A or B cases. Additional adjustment for insurance and nSES attenuated the relationship (HR 1.17, 95%CI: 1.00-1.36 and HR 1.07, 95% CI: 0.92-1.24 respectively). Similar patterns were observed in models adjusting for racialized economic segregation (HR 1.07, 95% CI: 0.92-1.24) and typology (HR 1.10, 95% CI: 0.94-1.28) in place of nSES. Conclusions: In this population-based study, redlined-exposed CAYACs experienced greater mortality compared to unexposed CAYACs. Adjusting for insurance and contemporary nSES attenuated the association between redlining and mortality. Findings suggest current neighborhood attributes may be downstream manifestations of structural racism with survival implications for CAYACs.