bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revolutionizing global hematology-oncology education: Assessing the two-year impact of a digital platform on socioeconomic equity and inclusivity against gender disparities.
Authors: Leyfman Yan , Wilkerson William B. , Cortiana Viviana , Gambill Jade , Menon Gayathri P. , Joshi Muskan , Heller Elizabeth Jean , Smith Keira , Coloma Helena S. , Balasubramanian Maduri , Zahid Emad B. , Van de Kieft Alexandra , Chorya Harshal , Abbas Rabab H. , Ghazal Jenna Fadi , Bowers Blaise , Azeez Ahmed , Park Chandler H. 
Published: July 2024

e21000 Background: Social media has transformed the global exchange of knowledge, with 77.4% of cancer patients relying on it as a primary source of information especially in resource-limited areas. Given that a third of social media posts contain misinformation that can have negative ramifications, MedNews Week (MNW) was developed as a digital platform featuring presentations by global authorities to enhance global oncology education through its freely accessible programming. In light of the gender disparity in speakers at scientific symposia, where females represent <30%, MNW strived to combat gender inequity by featuring them in equal proportion to males. The goal of this study was to evaluate the ability of MNW’s virtual oncology education platform to combat socioeconomic (SE) education inequity while promoting gender inclusivity. Methods: From January 2022 to 2024, MNW hosted 36 distinguished global oncology leaders as Keynote Speakers (Mean H-index=50.09). Data on viewership and outreach were collected from MNW's social media accounts. A mixed-method approach was employed to determine audience and speaker demographics, and engagement. Results: MNW achieved a Healthcare Social Score amongst the top 0.07 percentile of global healthcare influencers on Twitter. Over the past year, MNWoncology programming experienced a 10.5-fold increase in mean attendance, reaching 743,991 people in 95 countries globally, with 23 classified as low-to-middle SE status. In 2023, MNW followers exhibited a female predominance (48.8%), mainly from non-healthcare fields (60.0%). MNW showcased gender parity among oncology keynote speakers, with female lecturers drawing similar attendance as males (p=0.89, two-tailed unpaired t-test). Conclusions: MNW has established a growing digital platform, while removing financial barriers to effectively engage lay audiences, particularly in underserved regions. MNW's commitment to empowering female speakers exemplifies its dedication to inclusivity in a historically imbalanced field. This underscores MNW's success in fostering inclusivity, by driving engagement of those traditionally underserved, and positively impacting oncology education globally. [Table: see text]
Empowering tomorrow's oncologists: Establishing an oncology student interest group to propel careers in cancer care.
Authors: Singh Abhishek , Jain Nidhi , Chauhan Aditya , Obulareddy Sri Usha Jeevani , Seetharaman Kala 
Published: July 2024

e21014 Background: In cancer care, smaller academic community hospitals play a crucial role in serving local and underserved populations. However, these institutions often need help providing comprehensive mentorship opportunities for internal medicine residents interested in pursuing careers in oncology. Limited resources, smaller clinical teams, and a focus on delivering patient care often precede research and scholarly activity. To help with this goal, ASCO has a program known as OSIG, which stands for Oncology Student Interest Group, which provides resources for medical students and residents to meet regularly, network with academic faculty, learn about cancer care, and learn about opportunities in oncology. Methods: This observational study employed a cross-sectional survey design to investigate the perceived benefits of establishing an oncology interest group among internal medicine residents. The survey aimed to collect quantitative and qualitative data on residents' opinions regarding the potential advantages, challenges, and overall impact of initiating an ASCO affiliated oncology-focused student interest group [OSIG] within an academic community hospital internal medicine residency program in Worcester, MA. Results: Of the total strength of 75 residents, a total of 17 residents were surveyed for this project, with 7 [41%] female, and 10 [59%] male residents. 6 [35%] PGY1, 2 [11%] PGY2, and 9 [52%] PGY3 residents participated in the survey. 15 [88%] residents were 'very likely' interested in a career in oncology. 16 [94%] residents replied that participating in the oncology interest group meetings enhanced their understanding of cancer care and treatment options. 17 [100%] replied that networking with oncology professionals was 'very important' for their career development. 15 [88%] replied that the support provided by the OSIG helped find them mentorship opportunities 'to a large extent'. 15 [88%] replied that the oncology interest group could assist in clarifying their career goals within oncology by 'a lot'. The survey included two questions with room for subjective answers aboutpotential challenges or concerns, and additional thoughts, suggestions, or comments. Conclusions: The results indicate that residents recognize the potential of an ASCO-affiliated interest group to significantly enhance their understanding of cancer care and treatment options, providing a valuable supplement to their internal medicine training. The prospect of networking with established oncologists by spurring collaboration among residents, attending national and local conferences in the field is deemed crucial for career development, as is the belief that mentorship opportunities within the interest group could play a pivotal role in shaping future careers in oncology.
A multicenter, single-arm, open-label phase II study to evaluate the efficacy and safety of YH003 in combination with pembrolizumab and nab-paclitaxel in the first-line treatment of patients with unresectable/metastatic mucosal melanoma.
Authors: Chen Yu , Zhang Xiaoshi , Ding Ya , Jiang Yu , Chen Jing , Pu Xingxiang , Ren Xiubao , Zhang Weizhen 
Published: July 2024

e21520 Background: Mucosal melanoma therapy remains a formidable challenge especially in Asia. Although several therapies are available for skin type of melanoma, the efficacy of mucosal melanoma is not satisfactory. YH003, a humanized agonistic anti-CD40 monoclonal antibody specifically recognizes and agonizes CD40 to enhance immune responses, has demonstrated good safety and promising antitumor activity in Phase I clinical studies in patient with ocular melanoma. Here, we report the results of the phase II study of YH003 in combination with pembrolizumab and nab-paclitaxel in the first-line treatment of patients with unresectable/metastatic mucosal melanoma. Methods: Patients with unresectable/metastatic mucosal melanoma were enrolled and received 0.3 mg/kg YH003, 200 mg pembrolizumab and 200 mg/m2 of nab-paclitaxel iv, every 21 days. The treatment continued for 12 months if subject was deriving an ongoing clinic benefit. The primary endpoint was overall Response Rate (ORR) by investigator’s assessment per RECIST 1.1. Results: A total of 20 patients were enrolled and had at least 1 evaluable post-treatment tumor assessment, the unconfirmed ORR was observed in 7 patients (35.0%), with 7 partial responses (PR). 7 patients (35.0%) had stable disease (SD), and the Disease Control Rate (DCR) was 70.0%. The mOS was not reached, mPFS was 4.11 months. The grade 3 or above TEAE that occurred in the 20 patients were 30.0% (6/20). There is no significant safety signal from the study. Conclusions: The results of the phase II study have shown that YH003 in combination with pembrolizumab and nab-paclitaxel, as 1L treatment in patients with unresectable/metastatic mucosal melanoma have promising antitumor activity and response durability and well tolerated. Clinical trial information: NCT05420324 .
Risk score stratification of cutaneous melanomas based on whole slide images using deep learning.
Authors: Bossard Céline , Salhi Yahia , Quereux Gaelle , Khammari Amir , Salhi Sanae , Lavoine Eric , Chetritt Jérôme 
Published: July 2024

e21573 Background: Predictive and prognostic biomarkers represent the cornerstone of clinical oncology. Improving the prognostication of melanoma is needed to select patients for effective adjuvant therapies. Taking into account that tumor tissue contains a large amount of clinically relevant hidden information that is not fully exploited, we applied a weakly-supervised deep-learning approach on H&E-stained whole-slide image (WSI) to directly predict 5-year survival outcomes in melanoma patients. Methods: We designed a deep neural (DL) network that extracts features from no-padding patches of WSI (tiles of size 512x512 pixels) using a self-supervised learning framework as well as from the tumor region. These features are then fed along with survival information into the deep learning fusion network assigning a survival risk score to each WSI. The model was trained and validated on 195 cases of primary melanoma diagnosed between 2015 and 2017 originating from the IHP Group and the French RICMel melanoma database. Performance was evaluated using a cross-validation and cross-testing framework as well as on an external set of 238 cases from the TCGA database. Concordance index (c-index) was used as a metric to assess the performance of the proposed algorithm. Results: For the prediction of survival, the proposed pipeline yielded c-index of 0.76 and 0.66 for the IHP Group cohort and TCGA dataset respectively. Furthermore, the model is able to significantly discriminate between the 2 groups of patients, with a good and a poor prognosis in terms of overall survival (p-value < 0.001 for IHP and p-value = 0.01 for TCGA). Also, the proposed score is statistically significant when added to a multivariate cox model incorporating the classic prognosis factors (p-value < 0.005) and allows to reach a c-index of 0.81 over the discovery cohort. Conclusions: This infrequent weakly-supervised deep-learning approach to HE images analysis has the advantage of leaving the feature selection entirely to the deep network, and so discover new morphological biomarkers. By this way, it could have in the near future the potential to accelerate and improve the clinical decision-making process in the field of melanoma. Also, these findings will undoubtedly open room for substantial applications with economic and treatment delay fallouts.
The efficacy and safety of ruxolitinib as an add-on therapy to corticosteroids for patients with severe checkpoint inhibitor pneumonitis.
Authors: Xu Yan , Huang Hui , Gao Xiaoxing , Liu Xiaoyan , Chen Ruxuan , Chen Minjiang , Zhao Jing , Zhong Wei , Gao Junzhen , Wang Mengzhao 
Published: July 2024

e24121 Background: Although immune checkpoint inhibitors (ICIs) have improved survival of patients with malignancies, they also bring forth the immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) stands out as a prominent complication following ICI therapy, while a substantial proportion of CIP cases present with severe manifestations, often leading to life-threatening outcomes. The management of severe and refractory CIP is challenging. This study was aimed to evaluate the efficacy and safety of ruxolitinib as an add-on therapy to corticosteroids for patients with severe CIP. Methods: In this investigator-initiated, multicenter, randomized, open-label, phase 2 trial, cancer patients with CTCAE grade (G) 3 or G4 CIP after ICIs therapy were enrolled. CIP patients were randomly assigned in a 1:1 ratio (randomized block method) to corticosteroids administration (the initial dosage was more than prednisone 1mg/kg/d or equivalent) or corticosteroids with add-on ruxolitinib administration (5mg twice a day for 2 weeks, followed by 5mg once a day for 2 weeks). The primary end point was the proportion of patients with a prednisone daily dosage of no more than 10mg and improvement to G1 CIP at week 8. Results: From April 2023 to Jan 2024, 19 patients were enrolled. There were 17 cases of G3 CIP and two cases of G4 CIP. Eleven cases were assigned to corticosteroids group (C group), and 8 cases were assigned to corticosteroids with add-on ruxolitinib administration group (R group). Fourteen patients completed 8 weeks of follow-up. Five cases (5/6, 83.3%) in the R group and three cases (3/8, 37.5%) in the C group improved to G1 CIP and received ≤prednisone 10mg daily at week 8. One patient in the R group and three cases in the C group failed to taper to 10mg/d prednisone or had G2-3 CIP. Two patients in the C group died from CIP. Two cases in R group and three cases in C group were still under follow-up. The G3 or higher treatment-related AEs (TRAEs) occurred in three patients, including one case of aspiration pneumonia in C group and two cases of COVID-19 (one in each group). Conclusions: Corticosteroids with add-on ruxolitinib administration could improve clinical responsiveness for severe CIP patients. The safety profile was controllable and favorable. Ruxolitinib could provide a valuable promising therapeutic option for cancer patients with severe CIP. Clinical trial information: NCT05899725 .
Positive baseline thyroid autoantibodies as a predictive biomarker for thyroid immune-related adverse events: A systematic review and meta-analysis.
Authors: Ponvilawan Ben , Wannaphut Chalothorn , Tselovalnikova Tatiana , Bansal Dhruv 
Published: July 2024

e24124 Background: Thyroid dysfunction is one of the most common immune-related adverse events (irAE) by immune checkpoint inhibitors (ICI). Given the known relationship between antithyroid autoantibodies (ATA), including antithyroid peroxidase (TPO Ab) and anti-thyroglobulin (Tg Ab), and autoimmune thyroid disease, they could also play a role as a predictive biomarker for thyroid irAE (T-irAE). We performed this meta-analysis to evaluate the association of positive baseline thyroid autoantibodies and T-irAE. Methods: Eligible studies were screened using Ovid Medline and Embase databases with search terms related to ATA and thyroid irAE. Studies must be case-control or cohort studies with patients who received ICI and report the numbers of patients who have thyroid dysfunction and do not have thyroid dysfunction by the pre-ICI treatment statuses of ATA, TPO Ab, or Tg Ab. The pooled odds ratio (OR) and the associated 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method. Subgroup analysis by types of ICI (anti-PD1, anti-PD-L1, or combination treatment) and study region were also performed. The presence of publication bias was assessed by direct visualization of funnel plots. Results: After two rounds of screening, 19 case-control and five retrospective cohort studies were included in the meta-analysis. Patients who had positive baseline ATA had increased odds of developing T-irAE, hypothyroidism, and hyperthyroidism (pooled OR 10.95, 95% CI 6.65-18.02, I2= 38%; 6.82, 95% CI 2.99-15.56, I2= 27%; and 7.59, 95% CI 2.51-22.96, I2= 42%; respectively). Positive pre-treatment TPO Ab and Tg Ab were also independently associated with higher odds of hypothyroidism (pooled OR 5.01, 95% CI 2.87-8.75, I2= 4%, and 18.73, 95% CI 9.04-38.80, I2= 0%, respectively) and hyperthyroidism (pooled OR 2.94, 95% CI 1.57-5.52, I2= 25%, and 8.36, 95% CI 1.18-59.31, I2= 82%, respectively). The associations did not significantly differ between the types of ICI utilized and the study region. Visualization of funnel plots did not reveal a presence of publication bias. Conclusions: Pre-ICI treatment statuses of ATA, TPO Ab, and Tg Ab are associated with both hypothyroidism and hyperthyroidism. Thyroid autoantibodies as a baseline predictive tool can be helpful for early detection of T-irAE in patients who receive ICI therapy.
Screening for ocular toxicities of immunotherapy in a real-world population.
Authors: Barr Logan C. , Rullo Jacob , Baetz Tara D. 
Published: July 2024

e24125 Background: Nivolumab, Pembrolizumab, and Ipilimumab have revolutionized the treatment of melanoma. However, patients receiving these treatments risk immunotherapy-related adverse events (IRAEs). IRAEs can occur in any organ system, are treated with steroids or immunosuppressive medications, and may require treatment delay or discontinuation. Ocular IRAEs, which are caused by off-target reactions with ocular immune mechanisms, are often identified after significant damage to the eye. Ocular IRAEs are rare in the literature with an approximate prevalence of 3.3%. After observing intraocular inflammation (uveitis) with uveal depigmentation (pigment release) in some patients receiving immunotherapy, we hypothesized that the rate of such events in a real-world population may be higher than previously reported. We predict ophthalmic screening and early intervention may prevent severe and potentially permanent ocular IRAEs. Methods: Patients starting immunotherapy for melanoma were referred to an ocular screening clinic at the Cancer Centre of Southeastern Ontario (Queen’s University, Kingston, Canada) for baseline ocular assessments. Repeat assessments occurred every three months (single agent) or at every cycle (dual immunotherapy). Intake visits included examination by an attending ophthalmologist, including examination for uveitis and anterior chamber free pigment under high-powered field. Intraocular inflammation (IOI) was defined as the presence of endothelial deposits and/or anterior chamber cell and/or pigment that was not present at baseline. Ocular findings were monitored alongside other IRAEs during treatment. Results: 28 patients (17 male, 11 female) receiving adjuvant (46.4%) or palliative (53.6%) immunotherapy for melanoma were evaluated. 9 of these patients received dual immunotherapy (Ipilimumab/Nivolumab) and 19 received single agent immunotherapy. IOI was identified in 11 patients (39.2%), while only 4 presented with symptoms. None of the patients had overt signs of anterior segment inflammation such as erythema, conjunctival injection, and chemosis. IOI developed in 54.5% of dual immunotherapy-treated patients. Patients with ocular IRAEs were treated with topical/systemic steroids or other immunosuppressive medications. None required discontinuation of immunotherapy. The development of IOI was more common in metastatic patients whose cancer was responding to immunotherapy, and many of these patients sustained IRAEs in other organ systems. Conclusions: Our findings suggest IOI related to ocular IRAEs are quite common and develop in a third of patients receiving immunotherapy for melanoma. Ocular screening for IOI identified early, often asymptomatic toxicities that could progress to permanent visual disability. Further evaluation of dedicated ocular screening is indicated in patients receiving immunotherapy.
Immune-related adverse events associated with nivolumab: Analysis of the FAERS database in the United States.
Authors: Liu Yi , 朱 亚宁 
Published: July 2024

e24126 Background: To describe the risk of nivolumab adverse events (AEs) and to provide a reference for the safe clinical to use this drug. Methods: Nivolumab AE reports from January 2014 to December 2023 were collected from the FDA Adverse Event Reporting System, with a total of 133,12811 background patients (3,853,1848 occurrences of adverse events) included in the analysis, of which the number of patients in the target drug population was 60,625 (16,512 occurrences of adverse events). The number of patients in the target drug population was 60625 (161512 adverse events). Signals were detected using the Reporting Odds Ratio (ROR) method in conjunction with the Proportional Reporting Ratio (PRR), with signal judgment thresholds typically using a ≥ 3, and the lower limit of the 95% confidence interval for the ROR being greater than 1, The ROR and PRR (using a ≥ 3, and the lower limit of the 95% confidence interval for the ROR being greater than 1) were compared to the PRR. When ROR and PRR (using a ≥ 3, PRR ≥ 2 and chi-square ≥ 4 as thresholds) were used in combination, signal crossover between the two methods was defined as a positive risk signal. The preferred system organ classification (SOC) and preferred terminology (PT) of the current version of the MedDRA dictionary were used to classify AEs, and the top 30 PTs in terms of AE signal intensity were selected for analysis. Results: A total of 161,512 reports of AE with nivolumab as the first suspected drug were collected, involving 5174 PTs. A total of 995 positive PT signals were calculated using the combined ROR and PRR assay. The top 5 risk signals induced by nivolumab were immune-mediated small bowel colitis (ROR (95% CI) 114.42 (103.26-126.79), PRR (Chi-Square) 114.04 (40959.8)), pituitary gland inflammation (ROR (95% CI) PRR (Chi-Square) 88.60 ( 79.17-99.15)PRR(Chi-Square)88.37(26256.6)), fulminant type 1 diabetes mellitus (ROR(95% CI)213.73(183.24-249.30),PRR(Chi-Square)213.33(34295.5)) immune-mediated pneumonias (ROR(95% CI) 114.08 (99.42-130.89),PRR(Chi-Square) 113.87 (22764.4)), immune-mediated hepatitis (ROR(95% CI) 86.09 (75.08-98.71),PRR(Chi-Square) 85.94 (17262.8)).The top 5 SOCs were systemic diseases and various reactions at the site of administration in 25447 cases (15.76%), gastrointestinal disorders in 25447 cases(15.76%), gastrointestinal disorders 16,282 cases (10.08%), various types of injuries, poisoning and operational complications 12,510 cases (7.57%), respiratory, thoracic and mediastinal disorders 11,572 cases (7.16%), as well as benign, malignant, and tumors of undetermined nature (including cystic and polypoid) 10,486 cases (6.49%). Conclusions: The risk signal of autoimmune diseases caused by nivolumab is relatively strong, and it is recommended that clinicians should pay attention to the possible autoimmune diseases of various systems during the use of the drug.