bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical modeling of routine biological parameters kinetics in order to predict durable benefit for first-line immunotherapy in metastatic or unresectable melanoma.
Authors: Forestier Jessica , Daumas Alice Julie , Richard Marie-Aleth , Gaudy-Marqueste Caroline , Benzekry Sebastien , Malissen Nausicaa 
Published: July 2024

e21549 Background: PD1, CTLA4 and LAG3 blockade have shown remarkable efficacy in melanoma patients. Predictive biomarkers are needed to predict response, prevent unneeded toxicity and reduce costs. Despite collective efforts, no biomarker is robust or accessible enough for routine use. Our objective was to evaluate mathematical modeling-based kinetic markers derived from routine biological parameters as early predictors of durable benefit for first-line immunotherapy in advanced melanoma. Our secondary objective was to assess if these modeling could predict progression-free survival (PFS). Methods: We retrospectively included all consecutive, treatment-naïve, metastatic or unresectable melanoma patients treated with PD1 blockade alone or in combination with CTLA4 or LAG3 blockade between April 2020 and 2022 in our department. Clinical, biological and radiological data were collected. The primary endpoint was durable clinical benefit (DCB) defined as partial or complete response at 6 months or stable disease of at least 6 months. 11 simple blood markers and their on-treatment kinetics were considered. 4 empirical mathematical models (constant, linear, double exponential and hyperbolic) were fitted to the data, allowing to reject the constant null hypothesis for all of them. The association of the best-models coefficients with DCB and PFS was assessed using logistic and Cox regression. To do so, the data was truncated at 1, 2 and 3 months and the model coefficients were retrieved using Bayesian estimation with a population prior identified on the full-kinetics dataset. This study was approved by our local IRB. Results: 61 patients were included with 24 months median follow-up. DCB was observed for 57% of them. A low model-based value at baseline using 1 month truncated data was significantly associated with DCB for neutrophils (OR = 4.54[1.69-12.5], p < 0.0001) and - neutrophils/lymphocytes ratio (NLR) (OR = 3.03 [1.47-6.67], p = 0.003). Model-based results increased AUC versus baseline raw data: 0.755 versus 0.699 for neutrophils and 0.76 versus 0.7 for NLR. An elevated model-based at baseline using 1 month truncated data was significantly associated with PFS for neutrophils (HR = 1.56 [1.25-1.96], p < 0.0001), AST (HR = 1.71 [1.24-2.35], p < 0.0001), LDH (HR = 2.0 [1.44-2.77], p < 0.0001), CPR (HR = 1.75 [1.14-2.67], p = 0.01) and ALT (HR = 1.37 [1.05-1.78], p = 0.02). At 1 month, the kinetics parameters on creatinine (HR = 1.38 [1.05-1.82], p = 0.02), albumin (HR = 0.68 [0.48-0.97], p = 0.03) and monocytes (HR = 1.49 [1.02-2.18], p = 0.04) were significantly associated with PFS. Conclusions: Modeling the kinetics of routine biological parameters shows potential ability to predict DCB. Perspectives include model improvement, kinetics machine learning integrative model development as well as a toxicity prediction.
Cutaneous melanoma during pregnancy: Management and real-world outcomes.
Authors: Hickman Ashley , Smith Katherine Emilie Rhoades , Nelson Corrine K. , Rose Carl H. , McWilliams Robert R. , Kottschade Lisa A. , Markovic Svetomir , Yan Yiyi , Hieken Tina J. , Block Matthew Stephen 
Published: July 2024

e21554 Background: Pregnancy associated melanoma (PAM) occurs in 1% of female patients with melanoma and affects 1 in 2200 pregnancies. Antepartum evaluation of melanoma must incorporate both maternal and fetal factors, and currently there is lack of standardization. Our study aimed to review the incidence of antepartum melanoma at our institution and highlight patterns in management and treatment during this high-risk scenario. Methods: After IRB approval, the Mayo Clinic electronic medical record was searched with key words “melanoma” and “pregnancy”. 25 patients with melanoma during pregnancy were identified from 1987-2023. 6 patients were excluded as skin changes noted during pregnancy were not formally diagnosed as melanoma until after delivery. Abstracted data included demographic information, disease characteristics, staging (per AJCC guidelines at time of diagnosis), and clinical outcomes. Survival data were calculated. Results: 19 patients were included. Diagnosis occurred at an average maternal age of 30 years (range 24-38 years) and a mean gestational age of 20 weeks (range 6-35 weeks). All patients had a term delivery. 4 patients underwent labor induction at 37 weeks for staging/treatment. 60% of patients had a delay in imaging or treatment attributed to pregnancy, including 1 patient who was upstaged with metastatic disease based on postpartum imaging. 82% of stage I-III patients underwent wide local excision during pregnancy; however, 35% of sentinel lymph node sampling was delayed until postpartum. 3 stage II/III patients received adjuvant therapy (interferon or sargramostim) after delivery. Adjuvant immunotherapy was discussed with 2 patients in the postpartum period but ultimately not given due to the time lapse between surgery and delivery. 1 patient with stage IV disease diagnosed at a gestational age of 20 weeks was evaluated with MRI PET scan then treated with vemurafenib monotherapy during pregnancy. Workup and outcomes were reviewed by stage (Table 1). 7 of 19 patients had subsequent pregnancies, and 1 had recurrence of melanoma during a second pregnancy (stage II followed by stage IV). Due to a low number of censoring events, median progression free survival and overall survival were not reached. Conclusions: Melanoma diagnosed during pregnancy can be safely and effectively staged with sentinel lymph node surgery, MRI imaging (PET-MRI vs standard), and CT imaging with shielding without a need for early induction of labor nor a delay in cancer care. Furthermore, we report a patient with stage IV disease treated with vemurafenib during and immunotherapy after pregnancy, indicating that treating stage IV PAM with systemic therapy is a consideration. [Table: see text]
Toripalimab (anti-PD-1) plus recombinant human endostatin as adjuvant therapy in patients with resected stage III melanoma: Interim analysis of an open-label phase II trial.
Authors: Hu Xianglin , Xu Yu , Sun Yang-bai , Yang Ling-ge , Zheng Bi-qiang , Sun Zheng-Wang , Chen Yong , Yan Wangjun , Wang Chun-Meng 
Published: July 2024

e21557 Background: Patients with completely resected stage III melanoma are under high risk of disease recurrence. Recurrence-free survival (RFS) remains unsatisfactory despite there is adjuvant anti-PD-1 monotherapy following surgery, with the 1-year RFS about 70% and 2-year RFS about 49% in our country. It's urgent to explore combined regimens with anti-PD-1 to further improve the RFS. Here we report the interim efficacy and safety results of toripalimab (a PD-1 inhibitor) plus recombinant human endostatin (an angiogenesis inhibitor) as combined adjuvant therapy for patients with resected stage III melanoma. Methods: This prospective single-center, single-arm, open-label phase II trial screened adult patients with stage III melanoma who had undergone complete tumor resection within the previous 13 weeks for eligibility. Toripalimab was administrated in intravenous drip to patients at 3 mg/kg every 2 weeks in a 4-week cycle (day 1 and day 15 of each cycle), for up to 13 cycles or until disease recurrence, unacceptable toxicity or decease. Recombinant human endostatin was administrated in a continuous intravenous infusion at a dose of 210 mg from day 1 to day 3 for each 4-week cycle, for up to 6 cycles or until disease recurrence, unacceptable toxicity or decease. The primary endpoints were the 1-year and 2-year RFS. Results: By the data cut-off on Jan 25, 2024, 43 eligible patients with resected stage III melanoma between October 2021 and December 2023 were enrolled. In ITT population (n = 43), patients' median age was 56 (IQR 52~69) years. There were 25 (58%) male and 18 (42%) female; 27 (63%) with acral melanoma and 16 (37%) with cutaneous melanoma. With a median follow-up of 14 months, the 1-year and 2-year RFS rates were 83% and 71%, respectively. For security, 33 (77%) patients experienced at least one adverse event (AE), including 27 grade 1-2 AEs and 6 grade 3~4 AEs. One patient discontinued the combined therapy due to immunotherapy-associated myocarditis. Conclusions: Toripalimab in combination with recombinant human endostatin as adjuvant therapy could further improve disease-free survival in Chinese patients with completely resected stage III melanoma, with a manageable toxicity profile. Clinical trial information: 05907512 .
A randomized trial of topical cannabis balms for the treatment of aromatase inhibitor–associated musculoskeletal syndrome (AIMSS).
Authors: Zylla Dylan M. , Idossa Dame , Borrero Maria , Napurski Char , Dahmer Stephen , Cowger Jordan , Gilmore Grace , Luo Xianghua , Blaes Anne Hudson 
Published: July 2024

e24129 Background: Aromatase inhibitors (AIs) are commonly used for postmenopausal women with hormone receptor positive breast cancer. Nearly 2 of 3 women on AIs complain of AIMSS leading to poor adherence. Preclinical and clinical pilot data suggest topical cannabinoids can reduce inflammation in arthritis. Methods: We conducted a randomized controlled trial assessing the feasibility and acceptability of two different topical medical cannabis balms for AIMSS. Women with stage 1-3 breast cancer with AIMSS [scoring 4 or higher on at least one of the four screening Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affectations of the Hands (M-SACRAH) questions] were eligible. Patients with skin lesions, use of any cannabis in prior 4 weeks, acupuncture, or plans to increase doses of other analgesics were excluded. Women were randomized 1:1 to cannabidiol (CBD) (2210mg CBD/ < 0.3% THC) vs delta-9-tetrahydrocannabinol (THC) (375mg THC/ < 20mg CBD) predominant balm. Participants enrolled in the Minnesota Medical Cannabis Program and were dispensed balms at state-registered dispensaries. 125cc of balm was applied 3 times daily to hands for 2 weeks. M-SACRAH, brief pain inventory (BPI), and NCI Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) measures were captured weekly. Results: 20 women were enrolled from one academic and one community oncology practice in Minnesota over a 10-month period. Reasons patients with AIMSS did not enroll included patient/clinician not interested, AIMSS not meeting M-SACRAH severity, and patient already using cannabis. Adherence to study protocol through week 2 was 85%. Mean age was 54 years, 85% White/15% Asian, 45% received adjuvant chemotherapy, and 50% reported no lifetime cannabis use. Participants reported improvement in M-SACRAH, BPI, and PRO-CTCAE pain scores from baseline to week 2 (Table 1). No skin toxicity was reported by patients. One patient discontinued balm due to greasy texture. Conclusions: Conducting a randomized trial of topical cannabis using state approved dispensaries is feasible. Both THC and CBD predominant topical balms are well tolerated and appear to reduce AIMSS severity in this pilot study of breast cancer survivors. Further confirmatory studies are warranted. Clinical trial information: NCT05935891 . [Table: see text]
Breaking barriers for cancer clinical trials: A multi-tiered interventional approach to boost racial and ethnic minority participation in early-phase studies.
Authors: Erfani Hadi , Thomas Jacob Stephen , Hanna Diana L. , Martynova Anastasia , Chow Lydia D. , Nieva Jorge J. , Kim Stephanie , Umayam Rebecca , Levano Jessica , Baezconde-Garbanati Lourdes , Tsui Jennifer , Hughes Halbert Chanita , El-Khoueiry Anthony B. 
Published: July 2024

TPS1639 Background: Racial and ethnic minority populations are underrepresented in cancer clinical trials. The USC Norris Comprehensive Cancer Center (USC NCCC) has multiple clinical trial recruitment sites, including the Los Angeles General Medical Center (LAG), the largest safety-net hospital in the western USA. LAG partners with USC to provide cancer care to the underserved minority population of LAC, including clinical trials. As a result, between 2015-2022 a total of 120 LAG patients were accrued to phase I clinical trials; enrolled subjects were 66% Hispanic, 21% Asian, 4% Black, and 9% other. An interventional study was designed to further enhance the referral and participation of racial and ethnic minority patients from other Los Angeles County (LAC) safety-net facilities. The study is funded by the Stand up to Cancer Diversity in Early Development Clinical Trials Research Grants Program. Methods: This interventional study has 3 specific aims. First, to identify barriers to referral for minority and underserved patients: Qualitative interviews will be conducted with key stakeholders in the LAC safety net system which will uncover barriers to referring minority and underserved patients. A screening tool developed by the NCI to characterize barriers will be used. Second, to implement a multi-component program to enhance the referral of patients to early-phase clinical trials. The intervention addresses system-level, provider-level, and patient-level factors to improve the process, with a demonstration site compared to a non-demonstration site. Key features include a streamlined referral process for healthcare professionals with a singular centrally operated email managed by a specialized facilitator, weekly meetings to assign trials to prospective patients, and facilitation of approval and scheduling for referrals. We will educate providers regarding trials and exchange feedback on the referral process. We will extend resources to patients to assist with financial and transportation limitations. We will compare change in referral and enrollment rates at baseline and after the intervention for both the demonstration site and non-demonstration site. Third, to explore the impact of remotely conducted clinical trials: A clinical trial (NCT05340309) administers study drug subcutaneously and uses telemedicine visits, wearable sensors, and a smartphone app for monitoring. This pilot trial will be analyzed to determine the model’s impact on barriers to enrollment. The above interventions may provide a model that can be adapted in other healthcare delivery settings to optimize referral and enrollment of racial and ethnic minorities.
A new model to enhance enrollment of diverse participants to therapeutic clinical trials.
Authors: Ryan Patricia Y. , Brain Julia M. , Pai Sara I. , Lyerly H. Kim , Harris Jennifer Lynn 
Published: July 2024

TPS1640 Background: Disparities in United States clinical trial participation are well described, with the inclusion of only 8% Black, 6% Asian, and 1% Hispanic participants in phase III oncology trials supporting US FDA filings in 2020. The FDA, Cancer Moonshot, and ASCO-ACCC have issued guidance, sponsored initiatives, and developed strategies to raise awareness around the importance of equality, diversity, and inclusion at centers with current clinical research capabilities. Centers with ongoing research capability are typically large academic or private practice sites located in urban areas. There is an urgent need to expand clinical trial offerings to rural communities as geographic constraints disproportionally limit people of color and people of low socioeconomic status from accessing innovative drugs offered only through clinical trials. An additional contributing factor to low enrollment of diverse participants is a lack of racial, ethnic, gender, and geographic diversity amongst clinical trial investigators, who may be more relatable and, thus, effective at recruiting underrepresented patients to clinical trials. Lastly, to provide high quality care for their patients, clinical investigators must have ability to identify and select trials which address the specific needs of the patients within their practice. We hypothesize that a tool which improves identification and inclusion of an expanded investigator pool will result in improved diversity of clinical trial participation. Methods: We have developed a bi-directional matching software program that allows healthcare providers to define their areas of interest and match them to available pharmaceutical company clinical trial opportunities. The software, Golgi-CONNECT, will be piloted with up to 500 oncology-focused healthcare providers across a diverse geographic landscape and up to 6 pharmaceutical companies of varying sizes to evaluate the functionality and usability of the application. Additionally, HCP-reported barriers to clinical trial conduct, inclusive of financial, infrastructure, training, mentoring and lack of support staff will be collected.
Neuro-oncology anywhere: A decentralized approach to clinical trials in brain tumors and beyond.
Authors: Neth Bryan , Webb Mason , Galloway Taylor , Flickinger Lynn M , Chan Katrina , Steinmetz Sue , Breen William , Kizilbash Sani Haider , Campian Jian Li , Uhm Joon H. , Ruff Michael W. , D'Andre Stacy D. , Burns Terry C. , Stricker John L , Geyer Susan Michelle , Alden Eva , Stricker Nikki , Sener Ugur 
Published: July 2024

TPS1647 Background: The majority of patients with primary and secondary central nervous system (CNS) malignancy develop cognitive impairment, fatigue, and mood-related symptoms. Radiotherapy has been shown to contribute to symptom burden often limiting quality of life and functional status. The development of interventions mitigating neurocognitive toxicity requires an accurate assessment of function and symptom burden. Formal neuropsychological evaluation is resource and time intensive, and often challenging to incorporate in routine clinical practice. There is a critical need to accurately assess cognition without causing undue burden to cancer patients while evaluating the efficacy of interventions that can be scaled and implemented at a population level. Methods: To adequately assess the neurocognitive function and related symptoms in patients with CNS malignancy we have designed an open-label decentralized clinical trial that will randomize patients who received intracranial radiation for primary or metastatic brain tumors in a 1:1 allocation to a therapy targeting radiation-related toxicity (metformin shipped to patient home) plus health promotion with a wearable device vs. health promotion with a wearable device alone. Participants will be stratified based on tumor type (glioblastoma vs. other glioma vs. brain metastases vs. meningioma) and age (<70 vs. 70+ years). Participants will be provided a wearable device for monitoring health status. Participants will undergo serial remote cognitive assessments with the Mayo Test Development Through Rapid Iteration, Validation and Expansion platform (Mayo Test Drive). Remote reported symptom collection via patient surveys and remote neurologic examination by telehealth will also be incorporated. Cognitive assessments and symptom surveys will be designed for completion on a smartphone, tablet, or computer device. Health data will be collected from the wearable device, including the number of steps per day and sleep quality/duration. Participants receiving metformin will utilize device apps to report medication adherence and adverse events. Study-related laboratory assessments will be completed remotely and transmitted electronically. This decentralized clinical trial will provide real-world cognitive and quality-of-life data for patients with primary and metastatic brain tumors while providing preliminary data on the effectiveness of device-based health promotion with or without metformin for treating radiation-related cognitive decline. Results gained from this study will guide future trials in neuro-oncology and other fields. This study is expected to open in March 2024.
Tislelizumab plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy for elderly patients with inoperable locally advanced esophageal squamous cell carcinoma: A multicenter, randomized, parallel-controlled, phase II clinical trial.
Authors: Zhang Wencheng , Zhang Ke , Wang Qifeng , Cao Jianzhong , Fan Chengcheng , Shen Wenbin , Xiao Qin , Ge Xiaolin , Liu Xiao , Zhang Tian , Chen Xi , Dong Jie , Li Zewei , Zheng Zhunhao , Yan Cihui , Pang Qingsong , Wang Ping 
Published: July 2024

TPS4183 Background: There is few high-level prospective randomized studies and international consensus guideline on treatment in elderly patients with inoperable locally advanced esophageal squamous cell carcinoma (LAESCC). Double-agent intravenous chemotherapy concurrent with radiotherapy is the standard of care for LAESCC. However, it’s based on clinical trials that only enrolled patients ≤ 75 years old and infeasible in elderly patients. Oral S-1 plus concurrent radiotherapy for elderly ESCC showed tolerable toxicity and survival benefit compared with radiotherapy alone. While, the 3-year overall survival (OS) rate is limited about 40%. Therefore, it urgently needs find new treatment strategies to further improve the efficacy in elderly ESCC patients. Tislelizumab, the antii-PD-1 antibody, has recently been proved in the first- and second-line standard treatment for advanced ESCC. It shows mild toxicities and might be well-tolerated in the elderly. Here, we conducted the first clinical trial to assess the efficacy and safety of tislelizumab plus concurrent chemotherapy (CCRT) versus CCRT for elderly patients with inoperable LAESCC. Methods: The study is an open label, multicenter, parallel-controlled, investigator-initiated phase II clinical trial in elderly patients with inoperable LAESCC. We plan to enroll 136 elderly patients with LAESCC who will be randomly divided into two groups: tislelizumab combined with CCRT group (tislelizumab + radiotherapy + S-1) and CCRT group (radiotherapy + S-1). Tislelizumab is given intravenously on the first day of CCRT at the dose of 200 mg once every 3 weeks (Q3W). Radiotherapy is delivered at 50.4 Gy/1.8 Gy/28 fraction (5 times per week). S-1 is orally given at the dose of 40-60 mg from day1 to day14 and day 22 to 35. We will evaluate the efficacy and safety during the treatment and follow-up period until disease progression, death or the end of the trial. Considering the median progression free survival (PFS) is 16 months in elder receiving CCRT in history studies, we expect the median PFS would be 28 months at the hazard ratio of 0.57. The final sample size consists in 136 patients by 1:1 randomized in the two groups with 80% power and one-sided alpha and calculating for a 10% dropout rate. The primary endpoint is PFS. Secondary endpoints include OS, objective response rate, duration of objective response and severity of adverse events. Fresh or archival tumor tissues and peripheral blood samples will be used in the exploratory studies. This trial started on October 10, 2023 and has enrolled 19 patients till February 1, 2024. Clinical trial information: NCT06061146 .