tbuckley/cabot-search huggingface dataset:
Integration of a focused podcast curriculum (PC) to improve hematology oncology fellow (HOF) knowledge: A multi-center cluster randomized controlled trial.
Authors: Vivek Patel, Karine Tawagi, Samantha Ann Armstrong, Daniel Hausrath, Inas Abuali, Sean Taasan, Agrima Mian, Nathaniel R. Wilson, Daniel Egert, Ericson Stoen, Aleena Itani, Giuliana Berardi, Yurhee Lee, Pranali Santhoshini Pachika, Ronak Mistry
Journal: Journal of Clinical Oncology (2024)

9041 Background: Several studies demonstrate widespread use of medical podcasts as learning resources. Utility of integration of educational podcasts in fellowship curricula remains unknown. Here we describe a multicenter cluster randomized trial comparing a supplemental PC with standard curriculum (SC) to SC alone for HOF. Methods: HO fellowship programs in the United States were eligible. One HOF from each program was invited via email to participate as a local PI. The trial protocol was reviewed by program directors for approval. Programs were cluster randomized to novel PC with SC (intervention) or SC alone (control). Permuted block randomization stratified by program size was performed using STATA. The PC arm was given access to a website developed by the study team with links to podcasts episodes (PE) covering 4 topics: breast oncology, myeloma, bleeding disorders, and HIT. Written show notes (SN) were provided as separate links. PE and SNs were previously developed employing an inductive approach and released by The Fellow on Call and Two Onc Docs podcasts and are freely available. Pre and post qualitative surveys (QS) and knowledge assessments (KA) were administered via REDCAP. QS utilized a 7-point Likert score. KAs were peer reviewed by expert disease-specific faculty. QS and KA links were included on the PC website. To maintain blinding, the SC arm was given a separate website with these links. HOF participation was voluntary. To improve enrollment, at minimum, QS completion was required; KA was optional. Baseline data was obtained from October to November 2023. Post data cut off will be June 2024. Power calculation was based on mean difference in comfort level and knowledge. Assuming a mean improvement by 0.5 points for QS, a total sample size of 210 HOF, 11 clusters in each arm would provide at least 80% power assuming a standard deviation (SD) of 1, intracluster correlation coefficient (ICC) of 0.05, and coefficient of variation of cluster sizes of 0.7. For improvement in KA by 10%, a total sample size of 60 HOF would provide the same power assuming SD of 15%. We therefore planned to recruit 30 HO programs to account for non-response rates. IRB review deemed the study exempt. Results: Baseline characteristics from 28 randomized programs are presented below. Conclusions: This is the first randomized education trial in graduate medical education of its kind with a priori power calculations. Our innovative use of HOF as local PIs may have led to increased participation in KAs. Recruited sites will serve as a consortium for future multicenter education research. Interim analysis will be presented at ASCO 2024. [Table: see text]
Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor treatment (HARMONi-A): A randomized, double-blind, multi-center, phase 3 trial.
Authors: Li Zhang, Wenfeng Fang, Yuanyuan Zhao, Yongzhong Luo, Runxiang Yang, Yan Huang, Zhiyong He, Hui Zhao, Mingjun Li, Kai Li, Qibin Song, Xiaobo Du, Yulan Sun, Wei Li, Fei Xu, Zhiyu Wang, Kunning Yang, Yun Fan, Wenting Li, Yu Xia
Journal: Journal of Clinical Oncology (2024)

8508 Background: Ivonescimab (AK112/SMT112) is a anti-PD-1/VEGF bispecific antibody. Previous phase I/II clinical studies have shown potential efficacy of ivonescimab in NSCLC patients with EGFR mutations who had failed prior EGFR-TKIs therapies. This phase 3 study aimed to evaluate and confirm the efficacy and safety of ivonescimab combined with chemotherapy versus chemotherapy alone in this population. Methods: Patients were randomized 1:1 to receive ivonescimab (20 mg/kg) plus pemetrexed (500 mg/m 2 ) and carboplatin (AUC 5) or placebo plus chemotherapy once every 3 weeks for four cycles, with stratification according to the third-generation EGFR-TKI (received vs not received) and brain metastases (presence vs absence), followed by maintenance therapy of ivonescimab and pemetrexed or placebo and pemetrexed. The primary endpoint was progression-free survival (PFS) in intention-to-treat (ITT) population assessed by independent radiographic review committee (IRRC) per RECIST v1.1. Here we report the results of the first planned interim analysis. Results: Total 322 patients were randomized (161 to the ivonescimab plus chemotherapy arm, 161 to the placebo plus chemotherapy arm). 86.3% versus 85.1% of patients had received the third generation EGFR-TKIs treatment, 21.7% versus 23.0% of patients had brain metastases. As of March 10, 2023, median follow up time was 7.89 months. PFS was significantly improved in the ivonescimab plus chemotherapy arm (HR 0.46 [0.34, 0.62], P &lt; 0.0001). Median PFS (95%CI) by IRRC were 7.06m (5.85, 8.74) in the ivonescimab arm versus 4.80m (4.21, 5.55) in chemotherapy arm. The prespecified subgroup analysis showed PFS benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including in patients who progressed on the third-generation EGFR-TKIs therapy (HR 0.48, 95% CI 0.35-0.66), those with brain metastases (HR 0.40, 0.22-0.73), those with EGFR mutation of deletion 19 (HR 0.48, 0.32-0.73), and individuals with T790M mutation positive (HR 0.22, 0.09-0.54). The ORR were 50.6% and 35.4%, respectively. Grade ≥3 TEAEs occurred in 99 (61.5%) patients versus 79 (49.1%) patients, the most common grade ≥3 TEAEs were chemotherapy related adverse events. Grade ≥3 immune-related adverse events occurred in 10 (6.2%) patients versus 4 (2.5%). Grade ≥3 VEGF blocking related adverse events occurred in 5 patients (3.1%) versus 4 patients (2.5%). Conclusions: Ivonescimab plus chemotherapy significantly improved PFS while maintaining a manageable safety profile in patients who had failed EGFR-TKIs treatments. Clinical trial information: NCT05184712 .
Development of a professional oncology navigation training and credentialing program: ACS Leadership in Oncology Navigation (ACS LION).
Authors: Bonny Morris, Arif Kamal, Elizabeth Franklin, Elizabeth Calhoun, Jennifer Balistreri, Shanthi Sivendran
Journal: Journal of Clinical Oncology (2024)

9045 Background: Navigation by trained professionals is a key component to improving cancer outcomes in the US, helping to ensure every cancer patient has access to timely, quality, and culturally competent care. Due to limited standardized training and lack of sustainable funding for navigation, patients are not receiving the comprehensive care they deserve. The new Center for Medicare (CMS) 2024 physician fee schedule pathway for reimbursement of non-clinical patient navigation (PN) offers a pathway to create sustainable oncology navigation. Methods: The American Cancer Society developed the Leadership in Oncology Navigation (ACS LION) training and credentialing program with the goal of increasing access to high quality, standardized navigation training in compliance with Medicare requirements and in alignment with the Oncology Navigation Standards of Professional Practice. The program includes 10 learning modules and associated quizzes and a final summative assessment that is remotely live-proctored to demonstrate learning comprehension. This mixed methods analysis includes program descriptive data and paired t-tests of pre- and post-course comprehension and qualitative thematic analysis of open-ended survey responses. Results: The ACS LION program was piloted among 11 organizations nationally, including both academic health systems and community-based organizations. Of the 79 participants, 23% were Black and 14% were Hispanic. 18% of participants had less than one year of experience and 29% had more than 5 years of experience in navigation. 28% held clinical job titles. 51% had organization-specific in-service training and only 11% had taken an external standardized training program. Compared with pre-course scores, the program was significantly associated with higher post-course self-reported comprehension of 9 CMS required PN competencies (p&lt;0.001; p=0.08 for professionalism and ethical conduct). Qualitative analysis revealed 4 themes: learner experience, practicality, comprehensiveness, and role delineation. Post-program ratings averaged 4.5 out of 5.0, including overall learning experience, meeting a need, would recommend to others, and enhanced their professional experience. Conclusions: Pilot participants from diverse racial, ethnic, and work experience backgrounds found ACS LION to be comprehensive, engaging, and provided either critical foundational knowledge for less experienced navigators or enhanced their existing knowledge for experienced navigators, providing practical tools and resources. Pilot results informed the course that was launched nationally on Jan 1, 2024. Webinars, learning collaboratives, refresher courses, and re-credentialing will continue to be developed and offered as part of ACS LION and ACS commitment to advancing high quality professional navigation.
Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019
Authors: Pojsakorn Danpanichkul, Kanokphong Suparan, Priyata Dutta, Chuthathip Kaeosri, Banthoon Sukphutanan, Yanfang Pang, Narathorn Kulthamrongsri, Methasit Jaisa-Aad, Cheng Han Ng, Margaret Teng, Masahito Nakano, Asahiro Morishita, Naim Alkhouri, Ju Dong Yang, Vincent L Chen, Donghee Kim, Michael B Fallon, Luis Antonio Diaz, Juan Pablo Arab, Christos S Mantzoros, Mazen Noureddin, Jeffrey V Lazarus, Karn Wijarnpreecha
Journal: Metabolism (2024)
Training of clinical oncologists in Africa: Results of a regional survey.
Authors: Franklin Kenechukwu Okwunze, Abdu Adem Yesufe, Aalaa Mahmoud Hassan Abdou, Olasubomi Jimmy Omoleye, Wah Praise Senyuy, Surbhi Grover, Chidinma Pamela Anakwenze
Journal: Journal of Clinical Oncology (2024)

9026 Background: Africa grapples with a significant human resource shortage in cancer care. The vast majority of practicing oncologists are clinical oncologists, performing the roles of both medical and radiation oncologists. Building a sustainable oncology workforce depends on robust training pipelines. However, the distribution and characteristics of oncology training programs across the continent have not been described. Methods: A cross-sectional study was conducted to outline the landscape of postgraduate clinical oncology training in Africa. A semi-structured electronic questionnaire designed to collect data on locations and capacity of training centers, components of training curriculum, and administration of training programs was distributed via e-mail between February and May 2023 to board-certified clinical oncology consultants practicing in Africa. Participants were identified through the personal contacts of the co-authors. Results: Responses were received from 31 oncologists practicing in 24 countries. We identified 74 centers in 16 countries (67%) with ongoing clinical oncology training, and Egypt, South Africa, and Tunisia accounted for two-thirds of all training centers identified. Duration of training ranged from 4 to 8 years. Each year, about 230 residents commence training, and 198 graduate from training and join the workforce. More than half of the countries with available data require an internship and passing an entrance examination before commencing training. Almost all countries require trainees to pass an exit examination and submit a thesis before completing training. We obtained data on training components in 19 (26%) centers, and all centers provide training in chemotherapy administration and radiotherapy techniques. However, marked variations were observed in the exposure to modern radiotherapy techniques, with 10 (53%) centers including IGRT and 5 (26%) including IMRT. More than three-quarters of respondents reported that most trainees find jobs in the government service after completing training. Conclusions: Clinical oncology training programs in Africa are relatively limited in number. Moreover, there is a wide variation in the existing programs in terms of training duration and components of curriculum. There is tremendous potential for expansion to countries without training, which can be facilitated by partnerships with existing training programs on the continent. Furthermore, regional coordination and accreditation is vital to ensure uniformity.
Results of a phase III clinical trial with anti-PDL1 treatment in combination with chemotherapy for extensive stage small cell lung cancer.
Authors: Shun Lu, Xiang Rong Dai, Benjamin Xiaoyi Li, Zhiwei Chen
Journal: Journal of Clinical Oncology (2024)

8095 Background: In China, small cell lung cancer (SCLC) accounts for over 15% of lung cancers. The morbidity of SCLC has been continuously increasing. SCLC is invasive, fast-growing cancer that distinctly differs from other cancers. Approximately 70% of cases present with metastasis at diagnosis and the median overall survival rate is about 8 to 11 months with a 5-year survival rate of less than 5%. Although being sensitive to chemotherapy and radiotherapy, SCLC patients are liable to relapse and often present with drug resistance. Here we study the combination of Socazolimab, an anti-PDL1 antibody, carboplatin and etoposide to treat extensive stage small cell lung cancer. Methods: The study is a randomized, double-blinded, placebo-controlled multicenter Phase III clinical trial. Patients who have extensive-stage SCLC are eligible to the trial. Patients are randomly assigned to the study group (Socazolimab + carboplatin + etoposide) or control group (placebo + carboplatin + etoposide) at 1:1 ratio, with a treatment cycle of every 3 weeks. There are 4 cycles of chemotherapy followed by Socazolimab or placebo alone until termination events occurred or for up to 2 years. The primary endpoint is overall survival (OS). The major secondary endpoint is progression free survival (PFS). Results: There were a total of 498 patients recruited for the study with average age of 61.9 amount which 449 patients were diagnosed with stage IV SCLC. All the analysis was based on intent-to-treat (ITT). The median baseline performance status score was 1.0. The median OS of study group and control group are 13.90 months (95% CI: 12.22-15.34) and 11.58 months (95% CI: 10.64-12.81) respectively, with a P-value of 0.0316. The 24 month survival rate of study group and control group are 20.7% (95% CI:14.8-27.3) and 5.9 %(95% CI: 0.8-18.9). The median PFS of the two groups are 5.55 months (95% CI:5.06-5.82) and 4.37 months (95% CI: 4.27-4.70) with a P-value &lt; 0.0001. The treatment related adverse event were similar in both groups. Conclusions: These results show that Socazolimab plus chemotherapy continued to provide clinically meaningful improvements in OS for patients with extensive stage small cell lung cancer. Clinical trial information: NCT04878016 .
Repotrectinib in tyrosine kinase inhibitor (TKI)-naïve patients (pts) with advanced <i>ROS1</i> fusion-positive (<i>ROS1+)</i> NSCLC in the phase 1/2 TRIDENT-1 trial: Clinical update, treatment beyond progression and subsequent therapies.
Authors: Alexander E. Drilon, Rafal Dziadziuszko, David Ross Camidge, Jessica Jiyeong Lin, Benjamin Besse, Sang-We Kim, Ki Hyeong Lee, Benjamin J. Solomon, Misako Nagasaka, Koichi Goto, Juergen Wolf, Adrianus Johannes De Langen, Parneet Kaur Cheema, Nong Yang, Vamsidhar Velcheti, Yasir Y Elamin, Yuanfang Xu, Christophe Calvet, Felipe Ades, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2024)

8522 Background: Repotrectinib, a next-generation ROS1 TKI, has demonstrated durable clinical activity in the pivotal phase 1/2 TRIDENT-1 trial (NCT03093116). We report updated efficacy with a median follow-up of 33.9 months (mo) [~10 mo of additional follow-up], the first analyses of progression patterns, treatment beyond progression, and an update on subsequent anticancer therapies. Methods: Recommended phase 2 dose was 160 mg QD for 14 days, then 160 mg BID. Phase 2 primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), intracranial ORR (icORR), and safety. Treatment beyond BICR-assessed progression and sites of progression (per investigator) were also assessed. Safety assessments included all treated pts. Results: As of 15 Oct 2023, median follow-up in the TKI-naïve cohort (n = 71) was 33.9 (range, 24.0–76.5) months (mo). cORR was 79% (95% CI, 68–88); median DOR was 34.1 (95% CI, 27.4–not estimable [NE]) mo and 70% (95% CI, 57–83) of responders maintained a response of ≥ 24 mo. Median PFS was 35.7 (95% CI, 24.6–NE) mo and 63% (95% CI, 51–75) of pts were progression-free at 24 mo. Of 9 pts with measurable baseline brain metastases, icORR was 89% (95% CI, 52–100). Results for pts who received repotrectinib beyond progression are shown in the table. Of pts with disease progression per investigator (n = 37), the most common sites were lung (49%) and lymph nodes (35%). Of 42 (59%) pts who discontinued repotrectinib for any reason, 11 (26%) received single-agent TKI as the first subsequent anticancer therapy, 10 (24%) received chemo with/without immunotherapy (IO), and 2 (5%) received IO alone. Among all pts who received ≥ 1 dose of repotrectinib (n = 565), grade ≥ 3 treatment-emergent adverse events occurred in 323 (57%) pts and treatment-related adverse events in 162 (29%) pts. Treatment-emergent dizziness occurred in 63% of pts and was mostly grade 1-2. Conclusions: With a median follow-up of ~3 years in TRIDENT-1, repotrectinib continued to demonstrate durable clinical activity in ROS1 TKI-naïve pts. Progression patterns and treatment beyond progression were described for the first time. Clinical trial information: NCT03093116 . [Table: see text]
Outcome of chemo-immunotherapy for extensive-stage small-cell lung cancer according to potential clinical trial eligibility: 3-year outcomes from prospective cohort study.
Authors: Motohiro Tamiya, Daichi Fujimoto, Akito Hata, Hirotaka Matsumoto, Jun Sugisaka, Toshihide Yokoyama, Yoshihiko Taniguchi, Junji Uchida, Satoshi Hara, Go Saito, Satoru Miura, Hidekazu Suzuki, Satoshi Ikeda, Ryota Hiraoka, Masaaki Yanai, Nobuyuki Yamamoto, Hiroaki Akamatsu
Journal: Journal of Clinical Oncology (2024)

8087 Background: Chemo-immunotherapy is the standard 1st-line therapy for patients with extensive-stage small-cell lung cancer (ES-SCLC). Our large previous real-world prospective analysis showed outcomes of chemo-immunotherapy for these patients according to potential clinical trial eligibility with a minimum follow-up period of 1 year. However, long-term outcomes have not been studied in the real-world setting. Methods: We conducted a 32-hospital prospective cohort study of consecutive patients with ES-SCLC who received carboplatin and etoposide with atezolizumab as 1st-line therapy between September 2019 and September 2020. Patients who met eligibility criteria for pivotal phase 3 clinical trials were considered “trial-eligible.” We present 3-year outcomes from this study. Results: In total, 207 patients with ES-SCLC were analyzed. The median (range) time from the start of treatment to data cutoff (September 30, 2023) was 42.2 (35.8.-48.2) months. The median age was 72 years, and 64 patients (31%) were elderly (≥75 years). Most patients (89%) had a performance status (PS) of 0 or 1. As a result, 132 (64%) were categorized as trial-eligible patients. The 3-year PFS and OS probability of all patients was 6.1 % (95%CI:3.5-10.4%) and 20.9 % (95%CI:15.6-27.3%), respectively. Patients achieving 3-year OS included significantly higher proportions of trial-eligible patients (30 out of 132 versus 5 out of 75, respectively; p = 0.002). Kaplan-Meier estimates of the 3-year OS rate were 26.7% for the trial-eligible group and 9.5 % for the trial-ineligible group. Conclusions: This is the first real-world study to show the long-term efficacy of chemo-immunotherapy for ES-SCLC by using the largest prospective cohort of its kind. Additionally, this study demonstrated that trial eligibility was associated with long-term efficacy. Our study suggests that long-term clinical outcomes among trial-eligible patients may not translate to ineligible patients.
Charge-guided masking of a membrane-destabilizing peptide enables efficient endosomal escape for targeted intracellular delivery of proteins
Authors: Yan Zhao, Haolin Jiang, Hang Chen, Jiazhen Yu, Luyao Wang, Wen Zhou, Juanjuan Du
Journal: Acta Pharmaceutica Sinica B (2024)

Intracellular delivery of biologicals such as peptides, proteins, and nucleic acids presents a great opportunity for innovative therapeutics. However, the endosome entrapment remains a major bottleneck in the intracellular delivery of biomacromolecules, largely limiting their therapeutic potential. Here, we converted a cell-penetrating peptide (CPP), low molecular weight protamine (LMWP), to endosomal escape peptides (EEPs) by masking LMWP with a pH-responsive counter-ionic peptide. The resulting masked CPPs (mLMWP and mLMWP2) effectively promoted the escape of peptide/protein cargoes from endosomes into the cytoplasm. Consequential lysosome repair and lysophagy were initiated upon the endolysosomal leakage. Minimal reactive oxygen species (ROS) elevation or cell death was observed. Based on mLMWP2, we constructed an intracellular protein delivery system containing an antibody as a targeting module, mLMWP2 as an endosomal escape module, and the desired protein cargo. With the HER2-targeting delivery system, we efficiently translocated cyclization recombination enzyme (Cre) and BH3-interacting domain death agonist (BID) into the cytosol of HER2