tbuckley/cabot-search huggingface dataset:
Predictive factors for academic oncology career placement.
Authors: John X. Wei, John Yan, Santiago Beltran, Enrico Castellucci
Journal: Journal of Clinical Oncology (2024)

9039 Background: Oncology is a discipline that has witnessed rapid expansion with new therapeutics and practices. Following this trend, training programs are increasingly valuing the cultivation of academic oncologists who will contribute to these developments through research. This study aims to explore characteristics of fellowship programs in the US promoting academic careers in oncology (initial academic position). Methods: A sampling of graduated fellow profiles available on the public websites of US hematology-oncology programs was conducted. To minimize over-representation from programs, even sampling of all available graduated fellows by year was done with a maximum of 10 per program. Characteristics including demographics, educational background, google scholar publication count during fellowship (divided into quartiles), program characteristics, and initial job (academics vs private practice) were collected. Academics was defined as working for an institution associated with a medical school. Logistic regression modeling was utilized to identify characteristics associated with higher odds of initial academic placement. Results: Between 2007 and 2023, 564 graduated fellows were identified, making up 39% of programs, with a majority favoring more recent years. Fellows graduating from NCI cancer center-associated programs and those of academic programs had significantly higher odds of obtaining an initial academic position (OR 1.60, 95% CI 1.08-2.38, p &lt;0.05; OR 2.25, 95% CI 1.22-4.30, p &lt;0.05). The strongest association was noted with scholarly productivity. Fellows of the highest quartile of productivity during their fellowship years (OR 9.70, 4.94-19.80, p &lt;0.001) had the highest odds of obtaining an initial academic position. Characteristics without significant association included type of medical school (US vs IMG) and gender. Conclusions: Our data shows several characteristics associated with higher odds of initial academic placement, but most prominently, fellows of the highest quartile of research productivity were more than nine times likely than those of the lowest quartile of research productivity to obtain an academic position after fellowship. Our study is limited by its observational nature, but the magnitude and significance of association is worth investigating further and can shed light on the value of fellowship academic initiatives to foster research development. Select variables of a logistic regression model examining characteristics associated with obtaining an initial academic position after fellowship. Gender and Medical School status not included. [Table: see text]
Young adults (YA) with non-small cell lung cancer (NSCLC): Snapshot of the oncogenic drivers and immune landscapes.
Authors: Aaron Pruitt, Robert Hsu, Nishant Gandhi, Coral Olazapasti, Estelamari Rodriguez, Dwight Hall Owen, Jinesh Gheeya, Jun Zhang, Muhammad Furqan, Jaclyn LoPiccolo, Andrew Elliott, Ari VanderWalde, Stephanie Rock, Patrick C. Ma, Balazs Halmos, Zhonglin Hao
Journal: Journal of Clinical Oncology (2024)

8538 Background: Approximately 5% of NSCLC occurs in patients 50 years or younger (median age:71) representing distinct clinicopathological features. Reports characterizing genomic alterations are scarce. Using a large real-world (RW) dataset, we characterize oncogenic drivers, and immune landscapes to better understand YA with NSCLC. Methods: 42,326 NSCLC specimens were analyzed using next-generation sequencing of DNA (DNA-592 panel or whole exome) or RNA (whole transcriptome) at Caris Life Sciences (Phoenix, AZ). YA (&lt;=50 years) were categorized into three groups (years): 18-30 (A1, n=61), 31-40 (A2, n=277) &amp; 41-50 (A3, n=1,549); vs &gt;50 (A4, n=40,439). Composition of tumor microenvironment (TME) was estimated from bulk RNA sequencing using QuanTIseq method. RW survival on Osimertinib (Osi-OS) was obtained from insurance claims and calculated from initiation of Osi treatment to last contact and was compared between ages 18-50 and &gt;50 years. Hazard ratio (HR) was calculated using the Cox proportional hazards model. Statistical significance was determined using Chi-square, Fisher’s Exact, Mann-Whitney U and log-rank tests and corrected for multiple comparisons where applicable (q&lt;0.05). Results: Consistent with previous reports, NSCLC in YA was more prevalent in females, non-smokers and was associated with adenocarcinoma histology. Among driver alterations, ALK(IHC+), ROS1, RET and NTRK1 fusion were enriched and KRAS mutations were reduced in YA. Interestingly, while the prevalence of KRAS G12D from transition (non-smoker related) and EGFR E746_A750 decreased with age, KRAS G12C from transversion increased with age in YA. YA were also associated with improved Osi-OS (HR: 0.79, median Osi-OS=37.4 months vs 32 months in &gt;50 years old, p=0.019). High tumor mutation burden (&gt;=10 mut/Mb), the prevalence of mutations in TP53, KMT2D, NF1, RBM10, NFE2L2 and NOTCH1 increased while GNAS decreased with age. The expression of immune checkpoint genes such as PDCD1LG2(A1/A4: 0.63, A3/A4: 0.89), LAG3(A2/A4: 0.73, A3/A4: 0.89) and IFNG (A1/A4: 0.32, A3/A4: 0.75) were reduced, while M2 macrophage (A2/A4: 1.2) and neutrophil (A2/A4: 1.2) were increased in YA (all q&lt;0.05). Conclusions: We report an increased prevalence of RET and NTRK1 fusions in YA and key differences in distributions of frequent KRAS and EGFR mutations in YA (vs A4) along with decreased expression of immune related genes in the tumor microenvironment. The implications are under active investigation. [Table: see text]
Loss of heterozygosity (LOH) in <i>KEAP1/STK11</i>-mutated lung adenocarcinoma to characterize a new subgroup of hard-to-treat patients with unmet need in the real-world setting.
Authors: Louisa Hempel, Laura Amanda Boos, Luis Fábregas-Ibáñez, Gabriele Gut, Marta Nowak, Martin Zoche, Andreas Wicki
Journal: Journal of Clinical Oncology (2024)

8641 Background: Recent research suggests that loss of heterozygosity (LOH) in KEAP1/STK11 mutated lung adenocarcinoma (LUAD) may present a new immunological and biological aggressive subtype unresponsive to current standard of care treatment options. Currently, there is limited data on the clinical impact of LOH in KEAP1/STK11 co-alterations in real-world settings. Methods: From November 1 st , 2021, to October 1st, 2023, patients with LUAD and mutations detected by FoundationOne CDx in any of the genes KEAP1, STK11, KRAS were enrolled in the study. Clinical data, including overall survival (OS), duration of response to different treatment lines (DOR), and real-world progression-free survival (rwPFS) according to the treatment lines, were retrospectively assessed in patients who had given informed general consent. Multivariate Cox regression models included patient characteristics, selected two-way interactions, OS, LOH, PD-L1 status and rwPFS for patients with STK11, KEAP1, KRAS mutations. Results: A total of 104 patients were included, 63 (60.6%) males with a median age of 64.4 years; [range: 38-90]). 23 (22.1%) patients with STK11/KEAP1/KRASmutations, 15 (14.4%) patients with KEAP1/LOH mutations, 10 (10.4%) patients with STK11/KRAS mutations and six (5.8%) patients with STK11/KEAP1. In the KEAP1/LOH mutated subgroup, median OS (mOS) was 14 months (ms), whereas in the subgroup with KEAP1/KRASmutations mOS was 13 ms. Across all groups mOS was 14 ms. Compared to Keynote 189 with a PFS of 8.8 ms, rwPFS for the first treatment line (rwPFS1) was shorter in patients with KEAP1/LOH status and KRAS/STK11 mutations at 3.5 ms and 3 ms respectively. Additionally, DOR and rwPFS for further treatment lines were analyzed according to PD-L1 and TMB status, as well as the treatment lines patients received. Conclusions: Patients with mutations on STK11/KEAP1/KRAS or with LOH presented an mOS inferior to what is currently expected from historic data for metastatic LUAD, with a worse prognosis and shorter rwPFS1 for the subgroup of K EAP1/LOH, KEAP1/KRAS and KRAS/STK11. Surprisingly, the percentage of patients carrying concurrent mutations of interest was much higher in the analyzed population than previously described, emphasizing the importance of broad NGS panel testing, including STK11 and KEAP1 mutations. Our findings based on real-world data indicate that in addition to the already known STK11/KEAP1/KRASconcomitant mutations, KEAP1/LOH mutations define a new subset of hard-to-treat genetic alterations. These patients represent a subgroup associated with primary therapy resistance, highlighting a new unmet need for tailored therapeutic strategies. Furthermore, our data emphasizes the benefit of upfront panel sequencing, including STK11/KEAP1 mutations and LOH, to identify at-need patients.
Safety and efficacy of osimertinib in patients with NSCLC and uncommon tumoral <i>EGFR</i> mutations: A systematic review and meta-analysis.
Authors: Jonathan N. Priantti, Maysa Vilbert, Francisco Cezar A Moraes, Isabella Michelon, Caio Castro, Natasha B. Leighl, Ludimila Cavalcante, Yu Fujiwara, Alfredo Addeo, Jair Bar, Alessio Cortellini, Amin Nassar, Abdul Rafeh Naqash
Journal: Journal of Clinical Oncology (2024)

8642 Background: Osimertinib is broadly used for advanced EGFR-mutant NSCLC patients. However, the activity of osimertinib is not fully characterized in tumors harboring uncommon EGFR mutations, which represents about 10% of EGFR-mutated NSCLC cases. Hence, we conducted a systematic review and meta-analysis to assess the efficacy and safety of osimertinib in patients with NSCLC and uncommon tumoral EGFR mutations. Methods: PubMed, Embase, and the Cochrane Library were searched for eligible studies. Uncommon EGFR mutations were defined as any mutation other than the exon 19 deletion, L858R and T790M mutations, and exon 20 insertion, except when in compound. Efficacy was assessed by objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Heterogeneity was examined with I 2 statistics and random-effect model was used for a meta-analysis. Results: Nine studies comprising 331 patients were included. Median follow-up ranged from 12.6 to 22.0 months (mos). Median age in each study ranged from 51 to 72 years old (table). Overall, 62% (205/331) of patients were female and 77% (256/331) of patients had an ECOG PS ≤1. About 78% (258/331) of patients received Osimertinib in a 1 st line setting. Uncommon tumoral EGFR mutations included G719X in 40% (131/331) of patients, L861X in 27% (91/331), and S768I in 15% (49/331). Pooled analysis showed an overall ORR of 49.5% (95% CI, 42.2 – 56.9), a DCR of 90.2% (95% CI, 86.2 – 94.3), a median OS of 24.5 mos (95% CI, 11.9 – 24.5), a median PFS of 9.5 mos (95% CI, 8.2 – 11.0), and a median DOR of 17.4 mos (95% CI, 7.9 – 22.7). Intracranial (i) efficacy had an iORR of 50.3% (95% CI, 30.3 – 70.3), an iDCR of 92.8% (95% CI, 76.2 – 100), and a median iPFS of 6.1 mos (95% CI, 4.5 – 6.6). In a subgroup analysis according to EGFR mutation, overall ORR was significantly different in patients with tumoral G719X, S768I and L861 mutations (ORRs of 28.8%, 33.3%, and 67.7%, respectively, p for subgroup differences &lt; 0.01). Overall, osimertinib was well tolerated with a frequency of all-grade AEs of 86.2% (95% CI, 61.2 – 100) and ≥ G3 of 18.0% (95% CI, 1.2 – 34.7). Conclusions: This systematic review and meta-analysis suggests that patients with NSCLC with uncommon tumoral EGFR mutations may benefit from osimertinib treatment. Patients harboring tumoral L861 mutation achieved a significantly higher ORR compared to the modest ORR in G719X, S768I cases. [Table: see text]
Decision making in oncology: Unleashing the power of artificial intelligence—Beyond the question of feasibility.
Authors: Ernesto Gil Deza, Carlos Garcia Gerardi, Lourdes Gil Deza, Mariana Abal, Leonel Smolje, María del Huerto Jaunarena, Flavio A Tognelli, Gabriela Norese, Gaston Martin Reinas, Daniela Gercovich
Journal: Journal of Clinical Oncology (2024)

9021 Background: This study examines how consulting artificial intelligence (Chat GPT, Bard) or electronic tools (Apps, Journal or Guidelines) affects the decision-making process in Oncology Fellows. Methods: In the OSCE IOHM-USAL 2023, Oncology Fellows (2022 and 2023 cohorts) individually answered stations I and II, both spontaneously and after AI consultation. Group responses for stations III and IV were also gathered. Sign tests compared pre- and post-consultation responses in stations I and II while the impact of AI in stations III and IV was individually assessed on a five-point scale (0= Null and 5= Extremely useful). Results: 15 Oncology Fellows participated in OSCE 2023- 14 Females. Median age: 30 (r=28-36). A) Stations I - II Cases: Case1: 70 y. Non smoker. PS 0. Stage IV NSCLC. PS 0. EGFR mutated E746 _A750. PDL1 90%. Case 2: 52 y. Postmenopausal Stage II Luminal B Her2 negative Breast cancer (pT2, pN1, M0). Case 3: 35 yo. Advanced colon cancer. Stage IV. BRAF p(V600E) c.1799 A&gt;C. No Micorsatellite Instability. B) Station III (Ethics Committee), the following cases were addressed: 4. “BRCA1: Insured, not excluded”. 5. “Smoke vs. oath? Tough choice” 6. “Follow Lynch path, or HMO exit”. In all three cases, 3/15 students reported finding AI useful in the discussion. C) Station IV (Tumor board), the following cases were addressed: 7. “Postmenopausal NOS IBC (pT1c pNmic Luminal B Her2 negative)”. 8. “Oncology emergency in a 22 y male patient testicular tumor pending pathology”. In Case 7, 3/15 students reported finding AI useful in the discussion. In Case 8, 4/15 students reported finding AI useful. Conclusions: 1. A study of 15 oncology fellows found no appreciable influence of AI on clinical decision-making. 2. Analysis of eight cases (individual/collective) identified anchor value, optimistic denial, and confirmation bias in reasoning and processing. 3. Fellow training in critical AI analysis and outcome evaluation is imperative. [Table: see text]
Letter to editor：“Prognosis and conditional nomogram of cervical spine fracture in patients with severe spinal cord injury: a multicenter retrospective study”
Authors: Yanfei Yang, Yu Zhang, ShuXin Zhao, Rui Zhang
Journal: International Journal of Surgery (2024)

aDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China bDepartment of Spinal Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China Yanfei Yang, Yu Zhang, ShuXin Zhao These authors have contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Rui Zhang. E-mail address: [email protected] (R. Zhang). This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0/
Dual-stream multi-dependency graph neural network enables precise cancer survival analysis
Authors: Zhikang Wang, Jiani Ma, Qian Gao, Chris Bain, Seiya Imoto, Pietro Liò, Hongmin Cai, Hao Chen, Jiangning Song
Journal: Medical Image Analysis (2024)

Histopathology image-based survival prediction aims to provide a precise assessment of cancer prognosis and can inform personalized treatment decision-making in order to improve patient outcomes. However, existing methods cannot automatically model the complex correlations between numerous morphologically diverse patches in each whole slide image (WSI), thereby preventing them from achieving a more profound understanding and inference of the patient status. To address this, here we propose a novel deep learning framework, termed dual-stream multi-dependency graph neural network (DM-GNN), to enable precise cancer patient survival analysis. Specifically, DM-GNN is structured with the feature updating and global analysis branches to better model each WSI as two graphs based on morphological affinity and global co-activating dependencies. As these two dependencies depict each WSI from distinct but complementary perspectives, the two designed branches of DM-GNN can jointly achieve the multi-view modeling of complex correlations between the patches. Moreover, DM-GNN is also capable of boosting the utilization of dependency information during graph construction by introducing the affinity-guided attention recalibration module as the readout function. This novel module offers increased robustness against feature perturbation, thereby ensuring more reliable and stable predictions. Extensive benchmarking experiments on five TCGA datasets demonstrate that DM-GNN outperforms other state-of-the-art methods and offers interpretable prediction insights based on the morphological depiction of high-attention patches. Overall, DM-GNN represents a powerful and auxiliary tool for personalized cancer prognosis from histopathology images and has great potential to assist clinicians in making personalized treatment decisions and improving patient outcomes.
Modifiable risk factors for mild cognitive impairment among cognitively normal community-dwelling older adults: A systematic review and meta-analysis
Authors: Christo Y.Y. He, Zhixing Zhou, Mandy M.P. Kan, Dorothy H.Y. Chan, Athena C.T. Wong, Kenny H.Y. Mok, Freddy M.H. Lam, Sam C.C. Chan, Chelsia K.C. Cheung, Michael.K.C. Yeung, Arnold Y.L. Wong
Journal: Ageing Research Reviews (2024)
Engagement With a Mobile Chat-Based Intervention for Smoking Cessation
Authors: Yajie Li, Tzu Tsun Luk, Yee Tak Derek Cheung, Shengzhi Zhao, Yingpei Zeng, Henry Sau Chai Tong, Vienna Wai Yin Lai, Man Ping Wang
Journal: JAMA Network Open (2024)

Importance Determining how individuals engage with digital health interventions over time is crucial to understand and optimize intervention outcomes. Objective To identify the engagement trajectories with a mobile chat-based smoking cessation intervention and examine its association with biochemically validated abstinence. Design, Setting, and Participants A secondary analysis of a pragmatic, cluster randomized clinical trial conducted in Hong Kong with 6-month follow-up. From June 18 to September 30, 2017, 624 adult daily smokers were recruited from 34 community sites randomized to the intervention group. Data were analyzed from March 6 to October 30, 2023. Intervention Chat-based cessation support delivered by a live counselor via a mobile instant messaging app for 3 months from baseline. Main Outcomes and Measures Group-based trajectory modeling was used to identify engagement trajectories using the participants’ weekly responses to the messages from the counselor over the 3-month intervention period. The outcome measures were biochemically validated tobacco abstinence at 3-month (end of treatment) and 6-month follow-ups. Covariates included sex, age, educational level, nicotine dependence, past quit attempt, and intention to quit at baseline. Results Of 624 participants included in the analysis, 479 were male (76.8%), and the mean (SD) age was 42.1 (16.2) years. Four distinct engagement trajectories were identified: low engagement group (447 [71.6%]), where participants maintained very low engagement throughout; rapid-declining group (86 [13.8%]), where participants began with moderate engagement and rapidly decreased to a low level; gradual-declining group (58 [9.3%]), where participants had high initial engagement and gradually decreased to a moderate level; and high engagement group (58 [5.3%]), where participants maintained high engagement throughout. Compared with the low engagement group, the 6-month validated abstinence rates were significantly higher in the rapid-declining group (adjusted relative risk [ARR], 3.30; 95% CI, 1.39-7.81), gradual-declining group (ARR, 5.17; 95% CI, 2.21-12.11), and high engagement group (ARR, 4.98; 95% CI, 1.82-13.60). The corresponding ARRs (95% CI) of 3-month validated abstinence were 4.03 (95% CI, 1.53-10.59), 5.25 (95% CI, 1.98-13.88), and 9.23 (95% CI, 3.29-25.86). Conclusions and Relevance The findings of this study suggest that higher levels of engagement with the chat-based smoking cessation intervention were associated with greater biochemically validated tobacco abstinence. Improving engagement with digital interventions may increase intervention benefits. Trial Registration ClinicalTrials.gov Identifier: NCT03182790
Multivitamin Use and Mortality Risk in 3 Prospective US Cohorts
Authors: Erikka Loftfield, Caitlin P. O’Connell, Christian C. Abnet, Barry I. Graubard, Linda M. Liao, Laura E. Beane Freeman, Jonathan N. Hofmann, Neal D. Freedman, Rashmi Sinha
Journal: JAMA Network Open (2024)

Importance One in 3 US adults uses multivitamins (MV), with a primary motivation being disease prevention. In 2022, the US Preventive Services Task Force reviewed data on MV supplementation and mortality from randomized clinical trials and found insufficient evidence for determining benefits or harms owing, in part, to limited follow-up time and external validity. Objective To estimate the association of MV use with mortality risk, accounting for confounding by healthy lifestyle and reverse causation whereby individuals in poor health initiate MV use. Design, Setting, and Participants This cohort study used data from 3 prospective cohort studies in the US, each with baseline MV use (assessed from 1993 to 2001), and follow-up MV use (assessed from 1998 to 2004), extended duration of follow-up up to 27 years, and extensive characterization of potential confounders. Participants were adults, without a history of cancer or other chronic diseases, who participated in National Institutes of Health–AARP Diet and Health Study (327 732 participants); Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (42 732 participants); or Agricultural Health Study (19 660 participants). Data were analyzed from June 2022 to April 2024. Exposure Self-reported MV use. Main Outcomes and Measures The main outcome was mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. Results Among 390 124 participants (median [IQR] age, 61.5 [56.7-66.0] years; 216 202 [55.4%] male), 164 762 deaths occurred during follow-up; 159 692 participants (40.9%) were never smokers, and 157 319 participants (40.3%) were college educated. Among daily MV users, 49.3% and 42.0% were female and college educated, compared with 39.3% and 37.9% among nonusers, respectively. In contrast, 11.0% of daily users, compared with 13.0% of nonusers, were current smokers. MV use was not associated with lower all-cause mortality risk in the first (multivariable-adjusted HR, 1.04; 95% CI, 1.02-1.07) or second (multivariable-adjusted HR, 1.04; 95% CI, 0.99-1.08) halves of follow-up. HRs were similar for major causes of death and time-varying analyses. Conclusions and Relevance In this cohort study of US adults, MV use was not associated with a mortality benefit. Still, many US adults report using MV to maintain or improve health.