bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the risk of immune checkpoint inhibitor-related toxicity among patients with melanoma and their history of cannabis use.
Authors: Waris Imtisaal , Raiker Rahul , Siva Nanda , Goswami Sanya , Pakhchanian Haig , Kamran Amir Shahzad
Published: July 2024

e21539

Background: With cannabis use rising due to better availability for recreational and medicinal uses, there is a need for studies examining cannabinoids interactions. Immune Checkpoint Inhibitors have been increasing in popularity among metastatic cancer patients like those with melanoma. The biological impact of cannabis is mediated in part by the CB1 and CB2 receptors present in the endocannabinoid system that is present in the immune system. ICI therapy also targets the immune system through manipulating PD-1/PD-L1 receptors to induce cancer cell death. Therefore, concurrent cannabis use with ICI therapy could have potentiating effects on toxicities and negatively impact efficacy. There is limited information in the literature examining this and therefore the goal was to examine the impact of ICI toxicity risk among melanoma patients on any form of ICI therapy. Methods: A retrospective cohort study was conducted using TriNetX, a multicenter database comprised of ~100 million patients across 84 healthcare organizations. Adults ( > 17 years) from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Patients were then stratified by history of those with and without cannabis use disorder. ICI toxicity categories were determined a priori and included cardiac, nephrological, gastrointestinal, endocrine, respiratory, ocular, hematological, hepatological, musculoskeletal, and neurological toxicities. 1:1 propensity score matching was conducted to control for comorbidities and demographics. Adjusted hazard ratios (aHR) with 95% CI were calculated at 1-year follow-up after therapy initiation for ICI toxicities between the cohorts. aHR was estimated using the Cox proportional hazard model. Results: A total 14589 melanoma patients who underwent ICI therapy were identified where 2.3% had history of cannabis use. Matching revealed two balanced cohorts of 344 patients. Melanoma patients with a history of cannabis use did not have any significant differences with controls for cardiotoxicity (aHR[95%CI] = 0.94[0.54,1.6]), Nephrotoxicity (0.86[0.51,1.5]), GI toxicity (1.44[0.95,2.2]), endocrine toxicity (1.2[0.82,1.8]), respiratory toxicity (0.93[0.55,1.6]), ocular toxicity (0.63[0.25,1.6]), hematologic toxicity (1.04[0.7,1.6]), neurotoxicity (1.04[0.6,1.7]), liver toxicity (1.41[0.78,2.5]), or musculoskeletal toxicity (1.53[0.62,3.8]). Conclusions: With cannabis use rising due in part to recreational use and in part to medical marijuana, the implications of use must be a topic of research. Cannabis use among melanoma patients did not provide any significant differences in risk of developing ICI-therapy-related toxicities. Additional studies are needed to validate this finding.
CD44 and CD271 expression and chemoresistance in BRAF V600E/K mutation–positive melanoma.
Authors: Hyde Erin , Reed Madison J , Baer Robert W.
Published: July 2024

e21542

Background: Melanoma stem cells (MSC) are thought to play a role in cellular proliferation, migration, and chemotherapeutic resistance. We investigated native expression of several putative MSC biomarkers in human BRAF V600E/K mutation positive melanoma cell lines of different phases—radial growth phase (WM35), vertical growth phase (WM278)—and metastatic (LM-Mel-45, LM-Mel-71) cell lines. We examined cell viability of select cell subpopulations during in vitro treatment with BRAF and MEK inhibitor monotherapy and combination therapy. Methods: Using flow cytometry, we assessed surface expression of putative MSC biomarkers: CD44, CD271, CD133, CD186, and CD20. We sorted each cell line by CD44 and CD271 expression with a predetermined hierarchical gating strategy and compared 4 chemotherapy conditions: control, BRAF inhibition with 1.25 µM dabrafenib, MEK inhibition with 0.125 µM trametinib, and combination therapy. Cells (25,000) were collected directly into chemotherapy treated media and incubated for 72 hours. Cell viability was measured by MTT assay. Statistical analysis used mixed-effects ANOVA and Tukey HSD. Results: No significant expression of CD133, CD186, or CD20 was found in any cell line. Over 99% of live cells were CD44+ in all 4 cell lines. Only WM35 and LM-Mel-71 had both CD44+/CD271+ and CD44+/CD271- subpopulations. CD271 expression was restricted to CD44+ cells. Among live cells, the CD44+/CD271+ subpopulation was 31.2% for WM35 and 14.4% for LM-Mel-71. For WM35, cell viability in CD44+/CD271+ cells was greater than CD44+/CD271- cells for all treatments (p < 0.001). For LM-Mel-71 cells, CD271 expression did not affect cell viability within any treatment (p = 0.64). For chemotherapeutic treatments, cell viability in CD44+/CD271- subpopulation was higher in LM-Mel-45 cells than WM278 (p < 0.03) or LM-Mel-71 (p < 0.002), but not WM35 cells (p > 0.05). Trametinib monotherapy and combination therapy had similar cell viability in all 4 cell lines (p > 0.05). Conclusions: To our knowledge, our study is the first to show differences in phenotypic expression of CD44 and CD271 across nonmetastatic and metastatic melanoma cell lines and suggests co-expression of CD44 and CD271 confers increased chemotherapeutic resistance to in vitro BRAF and MEK inhibitor treatment in radial growth phase but not metastatic melanoma. More research is needed to better understand the role of CD44 and CD271 co-expression in melanoma initiation, progression, and chemotherapeutic resistance. CD271 remains a potential immunotherapeutic drug target in the treatment of BRAF V600E/K mutation positive melanoma.
Peripheral blood biomarkers in immune checkpoint inhibition therapy in metastatic melanoma.
Authors: Ghelani Ghanshyam H. , Mandava Anupa , Bou Zerdan Maroun , Mehta Radhika , Sivapiragasam Abirami
Published: July 2024

e21543

Background: Immune checkpoint inhibitors are extensively employed in the management of various solid cancers. Our study aims to assess the potential prognostic and predictive value of peripheral blood biomarkers, as well as their correlation with adverse events. Methods: In this study, we conducted a retrospective analysis of data retrieved from a cohort of 23 patients diagnosed with metastatic melanoma at a single institution between 2015 and 2019. Specifically, we focused on analyzing the neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil+monocyte-to-absolute lymphocyte+eosinophil ratio (ANMC/ALEC) from complete blood count (CBC), and lactate dehydrogenase (LDH) level from peripheral blood to assess their correlation with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs). Results: Our findings revealed that NLR values less than 0.34 and ANMC/ALEC ratio less than 3.45 were associated with improved PFS and OS, as well as a lower incidence of immune-related adverse events, which supports our initial hypothesis. However, these results were not statistically significant due to the low power of our study. On the other hand, high NLR values were significantly associated with higher pre-treatment LDH levels (P-value = 0.037), which is a well-established adverse prognostic factor in melanoma. Additionally, high ANMC/ALEC ratios were also found to be associated with high LDH levels, although this relationship was not statistically significant (P-value = 0.133). Conclusions: The results of our study suggest that patients with lower pre-treatment NLR and ANMC/ALEC ratios have better PFS and OS, as well as lower incidence of irAEs. Conversely, those with high NLR and high ANMC/ALEC ratios exhibited lower PFS and OS, as well as higher incidence of irAEs. High NLR and ANMC/ALEC ratios were also found to be associated with higher pre-treatment LDH levels, which have previously been demonstrated to be an adverse prognostic factor in melanoma. [Table: see text]
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 .
Apatinib and camrelizumab plus hepatic arterial infusion with oxaliplatin and 5-fluorouracil vs. apatinib and camrelizumab as the first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A randomized multi-center clinical trial.
Authors: He MinKe , Du Zefeng , Lai Zhicheng , Kan Anna , Shi Ming
Published: July 2024

TPS4194

Background: The combination of immune checkpoint inhibitors and antiangiogenic drugs has been approved as the first-line treatment for advanced hepatocellular carcinoma (HCC). However, the survival benefit is still limited, especially in patients with high-risk features (Vp4, and/or bile duct invasion and/or tumor occupancy of ≥50% of the liver). Hepatic arterial infusion chemotherapy (HAIC) plus apatinib (an antiangiogenic drug) and camrelizumab (a PD-1 antibody) showed encouraging antitumor activity for these patients in a previous phase 2 study. Herein, we investigated the efficacy and safety of apatinib and camrelizumab plus HAIC compared with apatinib and camrelizumab as the first-line treatment for HCC with portal vein tumor thrombus (PVTT). Methods: In this randomized, open-label, phase 3 trial, eligible patients are ≥18 years with HCC confirmed by radiology, histology, or cytology. Other eligibility criteria were as follows: with PVTT, ECOG PS 0/1, no history of systemic therapy, not amenable to curative treatment approach, Child-Pugh A class liver score, and ≥1 measurable lesion by RECIST v1.1. A total of 214 patients (anticipated) will be randomized (1:1) to receive apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) plus HAIC with FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 20 hours via hepatic artery Q4W) or apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) until disease progression or intolerable toxicity. Stratification will be by patients with or without high-risk features. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, objective response rate per RECIST 1.1 and mRECIST, disease control rate per RECIST 1.1 and mRECIST, time to progression, duration of response, time to response, and safety. Whole-Exome Sequencing and RNA Sequencing of tumor biopsy samples were performed for predictive biomarker exploration. Clinical trial information: NCT05198609 .
Phase 1 study to evaluate safety and preliminary efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in patients with locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC).
Authors: Abi-Jaoudeh Nadine , Valerin Jennifer Brooke , Imagawa David K , Preise Dina , Sacks Zachary , Cohen Yaniv , Rothman Julia , Brook Keren , Morag Eyal , Scherz Avigdor Joshua , Krasnopolskaya Inna , Alpert Genia , Chung Vincent , Melstrom Laleh Golkar , Kessler Jonathan
Published: July 2024

TPS4204

Background: Pancreatic cancer is the third most common cause of cancer death. Surgery offers the best survival rates however only a minority of patients are eligible. Approximately 15-20% of patients are deemed unresectable due to vascular involvement LA. Conversion of unresectable tumors, due to vascular involvement to resectable, is an unmet clinical need. Methods: A novel approach was developed to destroy the tumor encasing the artery combining padeliporfin, a photosensitive drug, locally activated by laser light illumination. The effectiveness of the strategy was confirmed in an orthotopic mouse model. A proof-of-concept study using 12 non-tumor pigs demonstrated an acceptable safety profile. A phase I dose escalation trial (NCT5918783) will be performed to evaluate the safety and maximal tolerated dose (MTD) of laser light dose of padeliporfin VTP. VTP will be delivered through an endovascular fiber integrated in a standard angioplasty balloon. The balloon will be advanced under fluoroscopy to the encased vascular segment of the superior mesenteric artery (SMA) and inflated. Following IV administration of padeliporfin, it will be activated by the laser light. Part A will be a classic 3+3 dose-escalation design to determine the MTD of laser light. The identified MTD will be applied in the Part B for preliminary efficacy evaluation. The primary objectives are to determine safety and MTD and/or recommended phase 2 laser light dose of VTP treatment. Secondary objectives are: rate of surgical conversion; evaluation of the pattern of disease progression (local regional and/or metastatic disease) after VTP based on CT. Standard of care surgery can be performed after 14 days post VTP. Key inclusion criteria: patients with histologically/cytologically confirmed stage III unresectable LA-PDAC in the head/uncinate process of the pancreas, with SMA solid tumor contact ˃180° with measurable disease per RECIST 1.1 and ECOG 0-1. Key exclusion criteria: metastatic disease, other malignancy, photosensitive skin diseases or porphyria, concurrent investigational therapy within past 30 days, medically uncontrolled moderate or severe ascites, previous radiation to pancreas, SMA variants. Recruitment begins in April 2024. Conversion of unresectable locally advanced pancreatic cancer to surgery is a critical unmet need. This phase I trial explores a novel approach to treat the tumor encasement enabling surgery. Clinical trial information: NCT5918783 .
Randomized pilot study assessing the safety and tolerability hyperthermic intraperitoneal chemotherapy (HIPEC) at completion of interval cytoreductive surgery or chemotherapy the day prior to interval cytoreductive surgery for patients with stage III/IV ovarian cancer undergoing neoadjuvant chemotherapy.
Authors: Backes Floor Jenniskens , Calo Corinne , Chambers Laura
Published: July 2024

TPS5638

Background: A recent randomized phase III trial demonstrated an improvement in recurrence free and overall survival when heated intraperitoneal chemotherapy (HIPEC) was given at the time of interval cytoreductive surgery (iCRS) for advanced ovarian cancer. While there is rationale for HIPEC’s mechanism of effect, it remains unclear whether the observed benefit is because the chemotherapy schedule is not interrupted perioperatively (typically at least 6-8 weeks). We hypothesize that administration of the same agent and similar dose the day before surgery, will not increase toxicity and may improve feasibility for closing the gap between treatment cycles, while also limiting length of surgery and time under anesthesia. The primary objective of this study is to assess the feasibility, safety, and tolerability of IV Cisplatin the day prior to iCRS compared to HIPEC to determine if this is an acceptable alternative. Methods: This is a single institution randomized Pilot Study (NCT05415709). Patients with newly diagnosed stage III or IV epithelial (serous, mucinous, or endometrioid) ovarian, fallopian tube, or peritoneal cancer are eligible if they achieve a partial or complete response to 3-4 cycles of neoadjuvant carboplatin/paclitaxel +/- bevacizumab and are deemed to have disease amenable to a complete or optimal iCRS. Patients are scheduled for iCRS within 3-4 weeks following the third or fourth cycle and randomized 1:1 to IV Cisplatin (75 mg/m2) given the day prior to iCRS or HIPEC with Cisplatin (100 mg/m2) given intraoperatively over 90 min at 40°Celsius at the completion of surgical debulking. 15 patient per arm are planned (N=30); currently 7 patients have completed study interventions. No formal power calculation was required for this feasibility and safety study. Frequency and severity of adverse events (AEs) and tolerability of the regimens will be collected and summarized by descriptive statistics for each group. Patients who are able to receive planned treatment will be summarized as percentage for each treatment group. Accrual is anticipated to complete in June 2025. As an exploratory secondary endpoint, we plan to explore changes to the gut microbiome before and after HIPEC and examine correlative patterns with response and toxicity. Clinical trial information: NCT05415709 .
Biomarker-driven radiation therapy dose reduction after transoral robotic surgery for the treatment of HPV-positive oropharyngeal cancer.
Authors: Bates James Edward , Stokes William A. , McDonald Mark William , Rudra Soumon , Stallings Madison Miller , Lockney Natalie A , Mannion Kyle , Saba Nabil F. , Schmitt Nicole C. , Gross Jennifer H , Steuer Conor Ernst , Kaka Azeem , Topf Michael , Patel Mihir R.
Published: July 2024

TPS6119

Background: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is a highly curable cancer with a considerable burden of treatment-related toxicities. Transoral surgery (TOS) is a treatment option for patients with early-stage disease; however, adjuvant radiotherapy (RT) is often recommended and can add to these late toxicities. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive marker of tumor recurrence, and undetectable post-operative ctHPVDNA is associated with improved recurrence-free survival. We hypothesize that patients with undetectable post-TOS ctHPVDNA without high risk pathologic factors can safely undergo de-escalation of adjuvant RT to 36 Gy, and this reduction will improve long-term swallowing function. Methods: We opened a multi-institutional phase II study (NCT05387915) including patients with pT1-2, N0-1, M0 HPV-related OPSCC who had TOS resection of their primary site and at least ipsilateral neck dissection. Pertinent inclusion criteria include a <10 pack-year smoking history, or a <30 pack-year smoking history if >10 years since last tobacco consumption, and pathologic findings of one or more intermediate risk factors: close margin (1 – 4 mm), perineural invasion, 2 – 4 positive lymph nodes or a single lymph node >3 cm. Patients with high risk factors (positive margin, extranodal extension, 5 or more positive lymph nodes) are excluded. Patients must have a detectable pre-operative ctHPVDNA and a post-operative ctHPVDNA drawn 7-14 days after TOS; if negative, patients receive 36 Gy of adjuvant RT in 15 fractions of 2.4 Gy delivered daily; if positive, they receive care per the discretion of the treating radiation oncologist. If the final surgical margins at the site of the primary tumor are >2mm, patients are eligible for omission of the primary tumor post-operative bed from the radiation volume. Our primary endpoint is 1-year swallowing function as measured by the composite MD Anderson Dysphagia Index (MDADI) score. Secondary endpoints include overall/progression-free survival and other quality of life metrics. The study is powered to detect an 8.5-point improvement in MDADI composite score at one year over the historical control from ECOG 3311 Arm B. With an alpha of 0.05 and a power of 0.90 we require 27 evaluable patients. Accounting for dropout and patients lost to follow-up, we aim to enroll 35 total patients. Since accrual began in June 2022, we have enrolled 18 patients as of January 2024. We recently opened the study at a second institution and are in the process of opening at a third institution. Clinical trial information: NCT05387915 .
HERD: A multi-centre prospective cohort study to facilitate early detection of relapse in radically treated, high risk head and neck squamous cell carcinoma.
Authors: Forster Martin , Mithra Sanjena , Ng Tony , Rosenfeld Nitzan , Sawyer Elinor , Reis Ferreira Miguel , Sinkus Ralph , Shmueli Karin , Coolen Ton , Roshan Amit , Mustapha Rami , Ng Kenrick , Gomes Camila , Petkar Imran , Guerrero Urbano Teresa , Connor Steve , Arora Asit , Fry Alastair , Berin Michelle , Brew-Graves Chris
Published: July 2024

TPS6128

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the 7th most common cancer worldwide with more than 660,000 cases diagnosed annually. Many patients present with locally advanced disease, which despite aggressive multi-modality treatment remains associated with poor survival. Approximately 50% of patients relapse within 2 years, mostly occurring in the first year after treatment. Biomarkers predicting relapse are lacking and there remains no consensus on surveillance, with strategies differing according to local guidelines and recurrence too often detected when not amenable to salvage surgery (estimated to improve survival outcomes in relapsed HNSCC by up to 73%). We hypothesize that risk of relapse relies on a dynamic interplay between the immune profile, tumor microenvironment (TME; elucidated by radiology and tissue-based laboratory imaging), genomic background and clinicopathological characteristics. Our primary objectives are to develop and validate a multi-analyte based risk prediction tool and risk-stratified follow up strategy to enhance detection of early relapse and improve survival. Methods: This multi-center study is prospectively collectingsamples across multiple platforms including imaging, blood, saliva, stool, urine, and tissue from patients with newly diagnosed high risk locally advanced HPV-negative HNSCC planned for radical treatment (either surgery or (chemo)radiotherapy). We aim to recruit 200 patients in 2 stages, including discovery and validation cohorts. Three mechanistic (hypothesis-driven) meta-covariates and five working platform meta-covariates will be analysed to test recurrence prediction. Each meta-covariate represents an integrated risk score from covariate subsets. The 3 hypotheses are H1) combining magnetic resonance parameters of hypoxia and stromal composition with TME changes; H2) capturing the interactions between genomic mutations, immune cells and exosomes within the TME H3) understanding the relationship between micro-organisms and TME. The technical platforms include exosomal analyses, multi-parametric MRI including novel elastography (MRE) and quantitative magnetic susceptibility mapping (QSM) techniques, comprehensive circulating tumour and cell-free DNA analyses to aid detection of minimally residual disease, tissue immune profiling, somatic mutation testing and microbiome analysis. Regression Analysis will be performed by machine-learning with advanced mathematical and Bayesian statistical modelling. Accrual began in October 2023. Clinical trial information: NCT05097625 .
Left Turns in Brown Study
Authors: Ruiz Sandra
Published: July 2024

In Left Turns in Brown Study Sandra Ruiz offers a poetic-theoretical inquiry into the interlacing forms of study and mourning. Drawing on Black and Brown activism and theory, Ruiz interweaves poetry, memoir, lyrical essay, and vignettes to examine study as an emancipatory practice. Proposing “brown study” as key for understanding how Brownness harbors loss and suffering along with the possibility for more abundant ways of living, Ruiz invites readers to turn left into the sounds, phrases, and principles of anticolonial ways of reading, writing, citing, and listening. In doing so, Ruiz engages with a panoply of hauntings, ghosts, and spectral presences, from deceased teachers, illiterate ancestors, and those lost to unnatural disasters to all those victims of institutional and colonial violence. Study is shared movement and Brownness lives in citation. Conceptual, poetic, and unconventional, this book is crucial for all those who theorize minoritarian literary aesthetics and think through utopia, queer possibility, and the entwinement of forms.
Surprises as a bait to work harder – Four cases in the Louros Archive
Authors: Marinis Christos P.
Published: July 2024

This brief paper discusses the author’s personal impressions from the process of recording, archiving, and categorising the N. Louros Archive during the summer of 2023, as well as the surprises that served as a motivation to continue this effort with increasing enthusiasm. Four cases of primary material with relevant photographs are indicative. Thus, the value of the Louros archive is emphasized for the history of medicine and other scientific fields, encouraging researchers to engage in a fruitful dialogue with related and unrelated sciences. Finally, a brief reference is made to the difficulties encountered during the project.