tbuckley/cabot-search huggingface dataset:
Genomic and phenotypic adaptations of <i>Rattus tanezumi</i> to cold limit its further northward expansion and range overlap with <i>R. norvegicus</i>
Authors: Ming-Yu Zhang, Rui-Dong Cao, Yi Chen, Jian-Cang Ma, Cheng-Min Shi, Yun-Feng Zhang, Jian-Xu Zhang, Yao-Hua Zhang
Journal: Molecular Biology and Evolution (2024)

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.
Differences in baseline ctDNA value between Hispanic and non-Hispanic White patients with soft tissue sarcoma (STS): A single-center retrospective analysis.
Authors: Waleed Ikram, DIana Zamora, Jonathan Braat, Han Dinh, Chelsea Azevedo, Shyamal Patel, Jason T. Wiseman, Miguel Gonzalez Velez
Journal: Journal of Clinical Oncology (2024)

e23533 Background: Circulating tumor DNA (ctDNA) has shown promise as a biomarker for cancer detection and tracking in multiple malignancies like melanoma, colon and lung. Due to the heterogeneity of sarcoma, there has been limited research on ctDNA as a tool for measuring minimal residual disease (MRD). Differences in baseline in ctDNA for STS in racial minorities have been poorly studied. To identify potential racial differences in the efficacy of this tool, this study compares the quantitative values of baseline ctDNA between non-Hispanic white (NHW) and Hispanic (H) patients with soft tissue sarcoma (STS). Methods: The medical records of 33 STS patients who had ctDNA analysis from Natera™ were examined retrospectively at Dignity Health Cancer Institute.There were 19 H patients and 14 NHW patients in the group. All Black (B), Asian (A), and Other (O) racial groups were excluded due to lower numbers. GraphPad Prism software was used to examine the baseline ctDNA levels. Using continuous measures for statistical analysis, we conducted descriptive statistics and determined the mean, standard deviation, and median ctDNA levels for each group. The ctDNA levels were compared between groups using a two-tailed t-test with a significance level of p &lt; 0.05. Results: The average ctDNA levels were 416.675 (standard deviation = 1349.394) in NHW and 300.305 (standard deviation = 1000.543) in H. The median levels were 0 for both groups. The statistical analysis showed that there was no significant differences in the baseline ctDNA levels between the two groups (p = 0.73). Furthermore, the gender distribution among NHW and Hs in the cohort was comparable, with a p-value of 1.00. Conclusions: This study establishes that there is no substantial differences in baseline levels of ctDNA between H and NHW patients with STS. These findings indicate that ctDNA levels in these populations can be equally utilized for diagnostic and monitoring reasons in clinical settings. Nevertheless, to gain a comprehensive understanding of the racial disparities in ctDNA utility and its implications in customized treatment for STS, it is necessary to conduct more extensive research with larger sample sizes and incorporate additional variables.
Primary human papillomavirus testing vs cotesting: clinical outcomes in populations with different disease prevalence
Authors: Shrutikona Das, Nicolas Wentzensen, George F Sawaya, Didem Egemen, Alexander Locke, Walter Kinney, Thomas Lorey, Li C Cheung
Journal: JNCI Journal of the National Cancer Institute (2024)

Implementation of primary human papillomavirus (HPV) testing has been slow in the United States perhaps because of concerns of decreased sensitivity compared with concurrent HPV and cytology testing ("cotesting"). We used the National Breast and Cervical Cancer Early Detection Program and the Kaiser Permanente of Northern California cohort to quantify potential trade-offs with primary HPV compared with cotesting in 4 US populations with differing precancer or cancer prevalence. In all settings, cotesting required more lab tests and more colposcopies compared with primary HPV testing. Additional cervical intraepithelial neoplasia grade 3 or cancer immediately detected from cotesting vs primary HPV decreased with decreasing population-average cervical intraepithelial neoplasia grade 3 or cancer prevalence from 71 per 100 000 screened among never or rarely screened individuals in the National Breast and Cervical Cancer Early Detection Program (prevalence = 1212 per 100 000) to 4 per 100 000 screened among individuals with prior HPV-negative results in Kaiser Permanente of Northern California (prevalence = 86 per 100 000). These data suggest that cotesting confer an unfavorable benefit-to-harm ratio over primary HPV testing.
Modeling any potential change in size, cost or patient benefit, resulting from incorporation of ctDNA, or other “optimizing diagnostic,” as part of a novel “SMARTer” oncology registration trial design.
Authors: Floyd Taub, Suzin Mayerson Wright, Dexiang Gao
Journal: Journal of Clinical Oncology (2024)

e23027 Background: One limitation in speeding more effective new cancer therapies to patients, and saving lives, is the time and expense of clinical trials. A second limitation is cancer is often a chronic disease, sequentially treated with multiple therapies; unlike in most registration trials, patient progress through a series of therapies. Building on previously published Sequential Multiple Assignment Randomized Trial (SMART) design, herein we model a new design to enhance registration (“SMARTer”). An “optimizing diagnostic” (often a ctDNA test) is used to determine, soon after initial use, if the new therapy is working. Those failing it are switched to the Standard of Care (SOC) for analysis they remain in the “new therapy first” arm, which is compared to the SOC arm. The aim is for all patients who benefit from the new therapy to remain on it, and, in contrast, if they are doomed to fail it, switch to SOC promptly to receive benefit from SOC early in the therapy path. Methods: To determine the value of the “new therapy first” arm we compared it to SOC by modeling assumptions of the accuracy of the optimizing test and the level of benefit of SOC after new therapy. The benefits of a new therapy first and switching, vs. SOC, was compared to a standard new therapy vs SOC “head-to-head”, without switching. Six scenarios, varying the effectiveness of the therapies, each with 16 combinations of sensitivity and specificity, were modeled. Results: Surprisingly, a good optimizing test reduces the number of patients by as much as 84% (from 710 to 114 in total) when new therapy alone had a 40% response rate and SOC a 30% rate (see table). When new therapy alone was no better than SOC, a study of 104 patients was sufficient to document that using the new therapy first added to patient benefit and could save lives, assuming independent mechanisms. Conclusions: SMARTer design thus significantly increases chances of approval, better mimics patients’ real world therapy path, and would reduce both time and cost significantly. An Optimizing Diagnostic, predicting appropriateness of a second dose/round of therapy based on the benefit of the first dose/round, thus facilitates clinical trials in a manner analogous to a Companian Diagnostic predicting the appropriateness of starting the first dose of a new therapy. [Table: see text]
Disparities in cancer care utilization in patients with brain tumors: A nationwide analysis.
Authors: Shahzaib Ahmad, Saad Javaid, Nouman Aziz, Hadin Darain Khan, Mirza Rehan Yousaf, Haseeb Ur Rehman, Muhammad Ahsan Hanif Chaudhary, Mohammad Arfat Ganiyani, Muhammad Abbas Khokhar, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2024)

e23142 Background: Brain tumors are highly aggressive and are associated with poor prognosis. Minority populations still experience inequities in the delivery of cancer care, despite concerted efforts to reduce such disparities. We studied disparities in receipt of cancer care for patients with primary brain tumor. Methods: National Inpatient Sample 2017-2020 was queried to identify the patients admitted with brain tumor. Results of the study were reported in accordance with the STROBE guidelines. We divided the cases into two groups i.e., the patients undergoing curative cancer care (CC) and palliative care (PC). We performed descriptive analysis and analyzed predictors of getting PC or CC using logistic regression analysis. Results: Among 144,355 patients hospitalized for primary brain tumor, 33,645 (23.3%) received PC. Mean age of PC group was 60±20.1 years, while the CC group had mean age of 52.9±21.3 years ( P &lt; 0.01). Compared to patients &lt; 45 years, the patients with age 46-64 years and ≥65 years were more likely to receive PC (OR = 1.9, 95% CI 1.6-2.4 and OR = 2.23, 95% CI 1.8-2.8, P &lt; 0.01, respectively). The proportion of Black patients in the PC group was more compared to the CC group (10.4% vs 7.6%). However, the proportion of White patients in the PC group was lower than the CC group (74.8% vs 77.9%), P &lt; 0.001. Black patients were more likely to receive PC (OR = 1.5, 95% CI 1.3-1.7, p &lt; 0.01), while no difference was observed in other ethnic or racial groups. Compared to CC group, PC group had a higher percentage of patients with Medicare (50.9% vs 35.9%), Medicaid (14.4% vs 13.8%) and a lower percentage of patients with private insurance (31.9% vs 47.0%) p &lt; 0.01. Patients with private insurance were less likely to receive PC (OR = 0.7, 95% CI 0.6-0.8, p &lt; 0.01). PC group had a higher percentage of low-income group patients compared to the CC group ($1-$49,999: 22.5% vs 20.6% and $50,000-$64,999: 25.3% vs 24.2%, P &lt; 0.01). Patients in teaching hospitals had decreased odds of PC (OR 0.8, 95% CI 0.7-0.9, P = 0.01) compared to non-teaching hospitals. Patients with major depressive disorder (OR 1.3, 95% CI 1.1-1.4, P &lt; 0.01), electrolyte disorders (OR 1.6, 95% CI 1.5-1.8, P &lt; 0.01), and atrial fibrillation (OR 1.3, 95% CI 1.1-1.5, P = 0.01) had increased odds of receiving PC. Conclusions: The patients who underwent PC were older, more likely to be Black, and of low-income groups. Patients in teaching hospital had a decreased likelihood of undergoing PC. The health care disparities should be addressed to achieve a better quality of care across all groups. [Table: see text]
Diffuse Midline (H3 K27M-Mutant) Glioma in Adults – Resection Fails to Matter
Authors: Patrick T Grogan, Michael A Vogelbaum
Journal: Neuro-Oncology (2024)

Journal Article Accepted manuscript Diffuse Midline (H3 K27M-Mutant) Glioma in Adults – Resection Fails to Matter Get access Patrick T Grogan, MD, PhD, Patrick T Grogan, MD, PhD Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael A Vogelbaum, MD, PhD Michael A Vogelbaum, MD, PhD Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL, USA Corresponding author: Michael A. Vogelbaum, MD, PhD, Moffitt Cancer Center, Department of Neuro-Oncology, 12902 Magnolia Drive, CSB 6th floor, Tampa, FL, USA, E-mail: Michael.Vogelbaum@Moffitt.org, Telephone: 813-745-4251 https://orcid.org/0000-0002-9833-2374 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae099, https://doi.org/10.1093/neuonc/noae099 Published: 03 June 2024 Article history Received: 27 May 2024 Published: 03 June 2024
Implementation of a hepatitis B screening program in patients receiving systemic anti-cancer therapy: A Canadian single center retrospective review.
Authors: Jennifer Leigh, Ranjeeta Mallick, Stephanie Yasmin Brule, Lisa Rambout, Jennifer Newton, Dominick Bosse, Sara Moore, Joanna Gotfrit
Journal: Journal of Clinical Oncology (2024)

e23242 Background: Cancer patients receiving non-endocrine anti-cancer therapies are at risk of hepatitis B virus (HBV) reactivation (HBVr). Medical society guidelines recommend HBV screening prior to treatment, but real-world uptake is slow and variable. The Ottawa Hospital Cancer Centre implemented a screening pilot program for all patients receiving FOLFOX based regimens or FOLFOXIRI between January and April 2023 which included incorporating HBV screening tests into treatment plan builds and specifying pharmacy and nursing pre-treatment checks. Methods: Charts were retrospectively reviewed, and patient and disease characteristics were collected. The primary endpoint was to identify the proportion of patients who underwent screening prior to treatment start. Univariate analyses assessed the association between baseline characteristics and failure to screen. We also reviewed quality metrics including time from consult to testing, time to result, number of duplicate screens, and treatment delays due to testing. Results: Baseline demographics of the 42 patients included can be found in Table 1. 32 patients (76.2%) completed screening and 5 (15.6%) had a positive screen. The majority of patients screened (78.1%) completed screening prior to first treatment as intended, however 38.1% were drawn on day of treatment. 9.52% of patients had duplicate screening inadvertently. All patients who tested positive were referred to Infectious Diseases. Of those, 1 received antivirals for chronic HBV, and 4 had resolved HBV and were recommended for monitoring. There were no treatment delays due to pending screening and no HBVr. Receipt of prior systemic therapy was significantly associated with failure to screen (55% vs 95%, OR 17.1 (95% CI 1.92-153), p = 0.011). Factors including age, sex, primary disease site, therapy intent, and regimen received were not significantly associated with screening completion or HBV positivity. Conclusions: The results of this pilot highlights the importance of building HBV screening into standardized treatment plans and engaging all team members to ensure high levels of screening. Prior systemic therapy receipt was associated with failure to screen, and thus programs should include education on the necessity of screening as recommended by medical guidelines. The prevalence of HBV in this population may also be higher than previously expected, which should be explored in future research. [Table: see text]
Bevacizumab combination therapy versus standard chemotherapy for ovarian cancer in shorter and longer followup duration: A systematic review and meta-analysis of randomized controlled trials.
Authors: Muhammad Zain Farooq, Obaid Ur Rehman, Eeshal Fatima, Hiba Imran, Umar Akram, Amna Badar Ahmad, Zain Ali Nadeem, Laveeza Fatima, Ahmad Hussain, Manar Ala Mabrouk, Michael Vishal Jaglal
Journal: Journal of Clinical Oncology (2024)

e23296 Background: Bevacizumab is an anti-angiogenesis drug commonly added to standard chemotherapy regimens in the treatment of ovarian cancer. However, its comparative efficacy and safety in shorter and longer followup duration leaves a research gap that needs to be addressed. This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer in shorter and longer follow up duration. Methods: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (95% CIs). We assessed the quality of included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). Results: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had low risk of bias while five had some concerns. Bevacizumab was associated with a progression free survival benefit for &lt; 36 months (HR 0.59, 95% CI 0.45 to 0.76, p &lt; 0.0001, I 2 = 90%) and &gt; 36 months (HR 0.66, 95% CI 0.55 to 0.80, p &lt; 0.0001, I 2 = 80%), and an overall survival benefit for &lt; 36 months (HR 0.87, 95% CI 0.78 to 0.98, p = 0.02, I 2 = 0%) but not for &gt; 36 months (HR 0.98, 95% CI 0.89 to 1.09, p = 0.77, I 2 = 30%). There was no difference in deaths between intervention and control groups &lt; 36 months (RR = 0.95, 95% CI 0.86 to 1.04, p = 0.26, I 2 = 10%) or &gt; 36 months (RR 1.02, 95% CI 0.97 to 1.06, p = 0.50, I 2 = 0%). Bevacizumab reduced disease progression &lt; 36 months (RR 0.82, 95% CI 0.72 to 0.92, p = 0.0008, I 2 = 82%) but not at &gt; 36 months (RR 0.83, 95% CI 0.58 to 1.19, p = 0.30, I 2 = 94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. Conclusions: Bevacizumab may improve progression free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months. Future studies should explore the long-term effectiveness of bevacizumab in diverse patient populations and focus on individual patient-tailored treatment approaches to optimize outcomes.
Disrupting how we recruit to cancer clinical trials.
Authors: Nina A. Bickell, Benjamin May, Ihor Havrylchuk, Jimmy John, Sylvia Lin, Radhi Yagnik, Ariana Tao, Grace C. Hillyer, Bruce Rapkin, Nicholas Tatonetti
Journal: Journal of Clinical Oncology (2024)

11072 Background: Traditional methods to identify eligible patients for cancer clinical trials rely heavily on manual review, a time-consuming bottle neck limiting access to novel treatments, particularly for underserved populations. This study presents an automated informatics platform designed to simplify and streamline patient identification and trial matching. Methods: Our platform leverages three tools: 1. Parser:Extracts and categorizes trial data based on cancer type, stage, and receptor status from the National Cancer Institute's ClinicalTrials.gov database, storing it in a structured JSON format; 2. Screener: Utilizes Epic Clarity electronic health record data to identify upcoming patients approaching treatment decision points, times when clinical trials are more relevant. Patients are classified as "newly diagnosed" or "potentially progressed" based on progress notes and imaging reports. Eligibility criteria, including stage and receptor status, are assessed using regular expressions; 3. Matcher: Pairs eligible patients with relevant trials based on compatible cancer stage and receptor status. One Cancer Center (CC) is prospectively using the platform to identify patients. The 2 nd CC is refining the code using retrospective data. Accuracy was measured comparing automated to manual review by experienced trained abstractors. Results: Implementation across two cancer centers yielded: 1. Reduced manual review burden: Between June 2023 – Jan 2024, of 674 breast cancer patients seen at CC #1, 371 were new patients (N=371) and thus, at a treatment decision point; 3 did not undergo imaging. Of the 300 established patients undergoing imaging studies, the algorithm identified 50/300 (17%) scans as “positive,” and 61 (20%) with mixed disease progression/ regression, requiring manual review and trial matching. 189 scans were read as “negative”: 96% True Negatives; 4% were False Negatives. Automated screening reduced manual review from 300 to 111 patients, significantly alleviating workload on healthcare personnel. 2. Variable staging accuracy: While receptor status classification proved effective, stage accuracy varied between centers, highlighting a need for further refinement in this area. 3. Accurate receptor status classification: The system achieved high accuracy in demonstrating reliable assessment of this vital factor. Conclusions: This automated informatics platform demonstrates significant potential to streamline case identification for cancer clinical trials and thus, foster broader access to novel therapies. Its adaptability makes it suitable for implementation across diverse healthcare settings, empowering wider participation in advancements in cancer care. Ongoing efforts to refine the staging module are underway. Clinical trial information: NCT05146297 . [Table: see text]
Knowledge, attitudes, and current practices toward lung cancer palliative care management in China: A national survey.
Authors: Mengting Chen, Huiqing Yu, Junhui Zhang, Hong Yang, Liejun Yang, Ling Tian, Sixiong Wang
Journal: Journal of Clinical Oncology (2024)

11143 Background: To demonstrate the status and differences in knowledge, attitudes, and practices (KAP) of lung cancer palliative care (LCPC) management, and to measure patient controlled analgesia (PCA) in cancer pain management in of China. Methods: A questionnaire on LCPC management was used in this study, which involved a total of 2093 participants from 706 hospitals in China. Seven major components make up the questionnaire, including chi-square tests or Fisher exact probabilities to measure the differences in KAP between hospitals grades. Comparing distributions of ordered data between groups was done using the Kruskal-Wallis H test or the Mann-Whitney U test. Multiple choice questions use multiple response cross analysis. Correlation was evaluated by the Spearman correlation coefficient. Results: 84.2% participants believed that anti-tumor therapy is equally important as palliative care. The satisfaction rate of participants from grade 3 hospitals, which was significantly higher than that of grade 2 and grade 1 hospitals (χ²=27.402, P=0.002). The most common symptoms requiring LCPC was pain. The major barriers toward to LCPC were “Patients and families are concerned about the safety of long-term use of palliative care related drugs”. The most common reasons for the use of PCA treatment were 31.1% participants thought “Patients with systemic application of large doses of opioids or adverse reactions to opioids that cannot be tolerated”. The top three barriers toward PCA treatment of cancer pain were (i) worry about adverse reactions of drug overdose, (ii) worry about opioid addiction, and (iii) increase of patients' economic burden. In the past 24 months, 33.9% of the participants had not participated in online or offline training related to palliative care of lung cancer. Conclusions: Chinese healthcare workers are in need of training for lung cancer palliative care and, in particular, for controlling cancer pain symptoms.