tbuckley/cabot-search huggingface dataset:
Effectiveness of online activities to reinforce multidisciplinary management of advanced soft tissue sarcoma and extend education globally.
Authors: Elizabeth Jean Heller, Keira P. Smith, Lyn Brook, Eden Maack, Amy J. Karfonta
Journal: Journal of Clinical Oncology (2024)

e21013 Background: Soft tissue sarcoma is a heterogeneous group of rare tumors. The multidisciplinary team is integral to optimize patient care and prolong survival. Online video platforms provide a convenient and costless method to deliver content, but their ability to reach and teach clinicians has not been studied extensively. We investigated usage and pre/post-survey data from viewers of a continuing medical education (CME)/nursing continuing professional development (NCPD) Virtual Tumor Board (VTB) video activity. Methods: We developed Virtual Tumor Board: Multidisciplinary Management of Advanced Soft Tissue Sarcoma, for oncologists, pathologists, nurse practitioners, physician assistants, and nurses. The VTB discussed strategies to optimize treatment outcomes of patients with soft tissue sarcoma using case studies. It was made accessible on August 10, 2023, on the i3 Health website, YouTube, and VuMedi. Viewers can receive CME/NCPD. Responses were analyzed, with Fisher’s exact test used to compare responses. Results: At the 5-month follow-up, the VTB has been viewed 1,547 times: 459 views on i3 Health, 988 views on YouTube, and 150 views on VuMedi, representing viewers from across the US and internationally. Baseline assessment data revealed gaps in knowledge in areas addressed by the VTB. For learners who completed the assessments (N=422), the mean score for all topics combined rose by 56% (33% vs 89%). The activity resulted in significant gains in knowledge and competence, with P &lt; 0.001 for all learning gains (Table).Upon completion, 92% of learners self-reported that knowledge acquired from this activity would be utilized to improve the outcomes of their patients, and 91% self-reported that, based on the information learned during the activity, they felt more confident in treating patients with soft tissue sarcoma. Conclusions: Over 1,500 viewers from both rural and urban areas have viewed this lecture, primarily on YouTube. Learners of i3 Health’s accredited activities have grown from 100,000 YouTube viewers in 2021 to over 600,000 by the end of 2023. In 2023, viewership extended to 60 countries, including 30 countries classified as low-to-middle income by The World Bank. The post-activity knowledge gains and improvements in competence show significant impact and the educational benefits of online video viewing. [Table: see text]
Combined EORTC FDG-PET/CT and RECIST 1.1 response criteria and prediction of pathological response to neoadjuvant nivolumab and ipilimumab for clinical stage III melanoma.
Authors: Milton Jose De Barros E Silva, Monique Celeste Tavares, Joao Paulo S. N. Lima, Daniel Garcia, Jose Augusto Rinck Jr, Andre Molina, Matheus Lobo, Clovis Antonio Lopes Pinto, Rafaela Brito De Paula, Alexander Christopher Jonathan van Akkooi, João Pedreira Duprat Neto
Journal: Journal of Clinical Oncology (2024)

9590 Background: Accurate identification of pathological response to neoadjuvant therapy for clinical stage III melanoma before surgery may allow us to better tailor the treatment. RECIST 1.1 has shown poor concordance rates with pathological responses and EORTC FDG-PET/CT response criteria using SUV max is susceptible to internal and external variables leading to difficulty in determining accuracy appropriately. Methods: We conducted a multicenter retrospective analysis of patients with clinical stage III melanoma treated with neoadjuvant nivolumab 3mg/kg + ipilimumab 1mg/kg(N3+I1) for two cycles who did baseline and pre-operative 18F-FDG-PET/CT. RECIST 1.1 and EORTC PETCT criteria were used to classify patients in terms of response. The pathological results were correlated to the image findings. Results: Between Jan 2019 and Jan 2024, 37 patients with clinical stage III melanoma treated with neoadjuvant N3+I1 were identified. Gender: 25 males (67%), median age (years): 58 (range: 31-78), BRAFV600 mut: 25(67%), positive nodes on baseline exam:1=30 (81%), 2=4(11%), and 3 or more =3(8%). Stage AJCC 8th edition: IIIB=23 (62%), IIIC=12 (32%), IIID=2(6%). Among them, 34 had baseline and post-neoadjuvant therapy PET-CT. Twenty-one (62%) had major pathological response (MPR) and 13(38%) had non-MPR. Using objective response and non-objective criteria to capture MPR and non-MPR, respectively, we found the following results: RECIST 1.1 (sensitivity= 48%, specificity=100%, accuracy=68%), EORTC-PET (sensitivity=90%, specificity=69%, accuracy=82%). Combining RECIST 1.1 and EORTC-PET/CT analysis, we found that: double objective responders (CR/PR and CMR/PMR, n=10) had 100% specificity to MPR and double progressors (PD/PMD, n=9) had 95% specificity to non-MPR. The only patient classified as double progressor that did not have non-MPR presented an intense inflammatory response with fever, pain and erythema leading to an increase in the size and number of lymph-nodes. No viable cells were found in the pathological report. Conclusions: Using combined RECIST 1.1 and EORTC-PET/CT response criteria may help to predict pathological response in patients with clinical stage III melanoma who undergo to neoadjuvant nivolumab and ipilimumab.
The impact of adjuvant radiation therapy on disease-specific survival in stage I and II Merkel cell carcinoma: A SEER database analysis.
Authors: Marcus Curlin, Aubriana McEvoy, George Ansstas
Journal: Journal of Clinical Oncology (2024)

9593 Background: Merkel Cell Carcinoma (MCC) is a rare, cutaneous neuroendocrine tumor associated with poor prognosis. Adjuvant radiation therapy (RT) is commonly used for the treatment of locoregional disease, but the impact on survival remains controversial. Previous studies from the Survival, Epidemiology, and End Results (SEER) database have shown an overall survival benefit to adjuvant RT without controlling for important prognostic differences in comparison groups such as age. To better control for these variables, we examined the impact of postoperative adjuvant radiation therapy on stage I and II disease-specific survival using the SEER database. Methods: SEERStat was used to obtain and analyze the outcomes of 2423 histologically confirmed MCC patients treated with surgery monotherapy or surgery with postoperative radiation therapy between 2004 and 2020 in the 17-registry (November 2021) SEER database. We compared the 5-year disease-specific survival (DSS) between the surgery monotherapy and adjuvant RT groups for stage I (n=1697) and stage II (n=726) MCC patients. Results: Patients treated with surgery and adjuvant RT were younger than those who received surgery monotherapy (median age 72 versus 77, respectively). Adjuvant RT was not associated with an increase in disease-specific survival. In contrast, adjuvant RT was associated with a statistically significant decrease in 5-year DSS among stage I patients (82.8% for those treated with RT versus 87.5% for those treated with surgery monotherapy, p = 0.023). Additionally, RT was not associated with a significant increase in DSS among stage II patients (77.0% versus 74.4% for patients treated with surgery monotherapy, p=0.490). Conclusions: This study demonstrates that there is no statistically significant disease-specific survival benefit from adjuvant radiation therapy for stage I and II MCC in the SEER database. Interestingly, in stage I patients we find a significant negative association between adjuvant RT and DSS. Younger patients are more likely to receive adjuvant RT, which likely contributes to higher overall survival previously reported from the SEER database, but the explanation for decreased DSS in patients who received RT remains unclear. Further studies regarding the effect of radiation therapy on local disease control and tumor microenvironment are needed to establish the appropriate role of RT in stage I-II MCC patients. [Table: see text]
EVICTION study: ICT01, an anti-Butyrophilin 3A monoclonal antibody activating γ9δ2 T cells in combination with pembrolizumab in checkpoint inhibitor refractory melanoma.
Authors: Stephane Champiat, Martin Wermke, Cecile Vicier, Johann S. De Bono, Emiliano Calvo, Jorge Ramón, Evan Thomas Hall, Elena Garralda, Vladimir Galvao, Emanuela Romano, Antoine Italiano, Esma Saada, Benoit You, Aude De Gassart, Maelle Mairesse, Emmanuel Valentin, Patrick Brune, Daniel Olive, Katrien Lemmens, Paul Frohna
Journal: Journal of Clinical Oncology (2024)

9534 Background: γ9δ2 T-cell tumor infiltration is associated with a favorable prognosis making these cells a new potential target for immunotherapy. The anti-BTN3A mAb ICT01 selectively activates γ9δ2 T cells and is being studied in the phase1/2a EVICTION Trial (NCT04243499). In preclinical studies, ICT01 induces upregulation of PD-1 on γ9δ2 T-cells and combination with pembrolizumab leads to enhanced cancer cell killing, providing scientific rationale to evaluate this combination. Here we present interim results from EVICTION of ICT01 in combination with pembrolizumab in patients with checkpoint inhibitor (CPI) refractory melanoma. Methods: EVICTION evaluated ICT01 (20 µg to 200 mg, Q3W) plus pembrolizumab (200mg IV Q3W) in a dose escalation solid tumor basket design that resulted in an ongoing expansion cohort of patients with CPI refractory melanoma (2 dose levels, 7 and 200 mg ICT01). Patients are selected based on higher baseline γ9δ2 T cells. Efficacy evaluations by i/RECIST 1.1 are conducted every 8 weeks. Disease Control Rate (DCR) as primary efficacy endpoint is defined as the sum of complete response (CR), partial response (PR) and stable disease (SD, minimum week 16). Baseline and on-treatment blood and biopsy specimens are collected for correlative translational work. Results: ICT01 plus pembrolizumab has a favorable safety profile with first-dose Grade 1/2 infusion related reactions (IRR) and cytokine release syndrome (CRS) as most common adverse events (in 38% and 19% of patients respectively, 5%and 2% Grade 3) among all doses and indications. To date, 35 CPI refractory melanoma patients have been enrolled, of which 65% have received 2+ prior lines of CPI. Currently 21 patients are evaluable at week 16 with a DCR of 42% (including 3 PR) and a 6-month progression free survival of 38%. In the circulation, full BTN3A receptor occupancy on immune cells was achieved at 7 mg dose, with down-modulation of BTN3A observed at doses greater than 20 mg. Clinical response was related to baseline tumoral BTN3A expression, sustained elevation of IFNg levels, and tumor microenvironment remodeling, including increased PD-L1 expression and CD8 T cells proliferation and activation. Conclusions: ICT01 in combination with pembrolizumab has a favorable safety profile and promising efficacy data. Patient selection based on BTN3A tumor expression will be further evaluated as an enrichment strategy. Clinical trial information: NCT04243499 .
Continuous intrathecal infusion of nivolumab in advanced melanoma with leptomeningeal disease.
Authors: Matthieu Faillot, Lauriane Goldwirt, Fanelie Jouenne, Nora Kramkimel, Barouyr Baroudjian, Adrien Ortiz-Carle, François Nataf, Bastien Oriano, Helene Staquet, Raphael Bacquet, Sélim Aractingi, Stéphane Goutagny, Samia Mourah, Celeste Lebbe, Philippe Decq
Journal: Journal of Clinical Oncology (2024)

9522 Background: The prognosis of melanoma patients with leptomeningeal disease (LMD) remains poor (median OS of 3.5 months). Intrathecal (IT) drug administration could bypass the blood-cerebrospinal fluid (CSF) barrier and has been explored in many cancers using chemotherapies or monoclonal antibodies. According to a recent phase I trial (PMID36997799), nivolumab IT delivery appears safe while its efficacy remains to be further investigated. Methods: We retrospectively reviewed melanoma patients with LMD treated with continuous IT administration of nivolumab (after decision in multidisciplinary tumor boards) at 2 institutions from February 2021 to October 2023. Patients received 10 to 13.5 mg/day of IT nivolumab delivered through a catheter (cath) connected to an implanted pump. Nivolumab concentrations were monitored in spinal CSF via an independent access port. All patients were enrolled in the MelBase cohort. Results: 11 patients (5 females, median age 52) were treated with continuous IT nivolumab with median (IQR) time to follow-up of 2.5 (1.1-6.3) months (m). Nivolumab was delivered through a spinal (n=10) and ventricular (n=1) cath. All patients had progressed on systemic immunotherapy (ipilimumab + nivolumab n=10, nivolumab n=1). Five patients had symptomatic LMD. All patients were ECOG 0 or 1 except one patient ECOG 3 (due to neurological deficit). Primary tumors were cutaneous (n=8), mucosal (n=1) and unknown (n=2). Tumors were BRAFV600 (n=10) and NRASQ61-mutated (n=1). All but 3 patients had stable extracranial disease. Concomitant systemic therapies were the following: corticosteroids (n=5), intravenous nivolumab (first 3 months of IT therapy) (n=1), and targeted therapies (n=4). The median duration of IT treatment was 1.5 (0.5-2.7) m. The median overall survival (OS) was 2.5 (1.1-NA) m. OS at 3, 12 and 19 m were 36.4 % (16.6-79.5), 27.3 % (10.4-71.6) and 13.6 % (10.4-71.6), respectively. Three patients had prolonged survival (19 m n=2, 12 m n=1). Treatment-related adverse events (all reversible) occurred in 5 patients: hemorrhage on cath path (n=1, grade 2), immune-mediated meningoencephalitis (n=1, grade 3), intracranial hypotension syndrome (n=3, grade 2). Steady state was obtained after 3 weeks of continuous IT infusion. Pharmacokinetics data are summarized in Table. Conclusions: Survival data are slightly inferior to those previously published. However 3 patients had prolonged survival (&gt;=1 year). Median nivolumab concentrations in CSF were comparable to through plasma concentrations at steady state after 3mg/kg IV infusion. High plasma concentrations suggest rapid clearance of nivolumab from the CSF, possibly related to reverse transcytosis of immunoglobulins. [Table: see text]
First-line treatment preferences for advanced melanoma among oncologists and patients in the US: A discrete choice experiment.
Authors: Michael A. Postow, Gabriela Burgos, Marc DeCongelio, Jennell Palaia, Flavia Ejzykowicz, Divya Patel, Lisa Rosenblatt, Kushal Modi, Zander Pittman, Ryan Honomichl, Neelanzana Paudel, Cody Barnett, Jennifer L. Hay
Journal: Journal of Clinical Oncology (2024)

9539 Background: NCCN guidelines recommend nivolumab + ipilimumab, nivolumab + relatlimab, and anti-PD-1 monotherapy as category 1 preferred first-line (1L) treatments (txs) for advanced melanoma. These immunotherapies (IOs) however differ in administration, efficacy, and safety. Given these differences, this study examines oncologists (oncs) and patients (pts) preferences when choosing 1L tx. Methods: Pts with self-reported unresectable or metastatic melanoma and oncs completed an online cross-sectional survey. A discrete choice experiment assessed preferences for three efficacy attributes, three safety attributes, and dosing schedule. Attributes (shown in table) were identified via literature and qualitative research. Each attribute had two or three levels based on clinical trial data of recommended IOs. Participants completed 12 tasks; each task showed two tx options with varying levels for each attribute. Hierarchical Bayesian modeling was used to estimate preference weights for each level and relative importance estimates, based on the range between levels, were computed. Results: 75 oncs (male 76%; mean age 46 years; community-based 51%) and 62 pts (male 68%; mean age 43 years) were analyzed (pt recruitment ongoing; target n = 75). For both oncs and pts, improvements in safety attributes was more important than improvements in efficacy attributes (pts: 50.3 vs. 33.9; oncs: 48.6 vs. 40.9). For safety, a decrease in risk of discontinuation due to treatment-related adverse events (TRAEs) was most important in oncs (24.7); while for pts, lower risk of grade 3/4 TRAEs was most important (22.6). For efficacy, an increase in overall survival (OS) was most influential for oncs (21.0); pts had similar estimates within efficacy. Dosing schedule was third most important for pts (15.8), while it was among the least important for oncs. Conclusions: Oncs and pts prioritize minimizing the risk of serious AEs when efficacy differences are minimal in 1L advanced melanoma tx choice. These findings highlight that oncs and pts value an IO with an efficacy benefit while ensuring a favorable risk-benefit profile. This information can inform tx counseling and selection discussions among oncs and pts. [Table: see text]
Long-term overall survival after isolated liver perfusion with melphalan in patients with isolated liver metastases of uveal melanoma (SCANDIUM trial).
Authors: Axel Nelson, Amir Shafazand, Charlotta All-Eriksson, Christian Cahlin, Nils Elander, Hildur Helgadottir, Jens Folke Kiilgaard, Sara Kinhult, Ingrid Ljuslinder, Jan Erik Mattsson, Magnus Rizell, Malin Sternby Eilard, Gustav J. Ullenhag, Jonas A Nilsson, Lars Ny, Per Lindner, Roger Olofsson Bagge
Journal: Journal of Clinical Oncology (2024)

9532 Background: Uveal melanoma is a rare subtype of melanoma characterized by frequent metastases to the liver. The median survival for patients with liver metastases is less than one year, and there are few systemic treatment options available, providing only small survival benefits. Patients with liver metastases of uveal melanoma were in the SCANDIUM trial randomized to a one-time treatment with isolated hepatic perfusion (IHP) with high dose melphalan and investigator´s choice. We have previously reported that IHP gave significantly superior response rates and progression-free survival compared to best alternative care Furthermore, the primary endpoint, overall survival (OS) rate at 24 months was numerically higher for the IHP treated group (46.5% vs 29.5%), but the difference was not statistically significant. Here we present extended OS follow-up. Methods: In this randomized, controlled, phase III trial, treatment naïve Swedish patients with isolated liver metastases from uveal melanoma were between 2013 and 2021 randomly assigned in a 1:1 ratio to receive a one-time treatment with IHP or best alternative care (control group). No crossover from the control group to the IHP group was allowed. Results: A total of 87 patients were randomized and assigned to either IHP (43 patients) or control (44 patients). In the IHP group, 41 (89%) patients received IHP. In the control group, the first-line treatment was chemotherapy (49%), immunotherapy (39%) or localized treatment interventions (9%). The overall response rate was 40% in the IHP group, with a median duration of response of 13.7 months (95% CI, 11.6-18.3, n=17). At a minimum follow-up of 36 months, the 3-year OS rate was 18.6% (95% CI, 10.0-34.8%) in the IHP group compared to 9.1% (95% CI, 3.6-23.1%) in the control group (p=0.23, fisher exact test), and the 5-year OS rate was 16.3% (95% CI, 8.3-32.1%) compared to 6.8% (95% CI, 2.3-20.3%). The median OS in the IHP group was 21.4 months (95% CI, 19.0-30.4 months) compared to 17.3 months (95% CI, 13.8-22.3 months) in the control group (p=0.11, log-rank test). Conclusions: This extended analysis from the SCANDIUM trial supports long-term efficacy of a one-time treatment with IHP compared to best alternative care in patients with isolated liver metastases of uveal melanoma. Clinical trial information: NCT01785316 .
Clinical and epidemiological profile of patients with atypical melanomas treated with immunotherapy.
Authors: Andre Luiz Cicilini, Thamilyn Saruwatari, Monique Celeste Tavares
Journal: Journal of Clinical Oncology (2024)

e21532 Background: Atypical melanomas, such as acral lentiginous, uveal, mucosal, spitzoid, desmoplastic, meningeal, and primary occult site, represent less than 5% of melanoma cases. Due to their different biological tumor behavior from cutaneous melanomas, their treatment is still challenging. Currently, checkpoint inhibitors are the main treatment based on extrapolations or data from small surveys. Methods: This study aims to describe the epidemiological profile, clinical and pathological characteristics, and treatment of patients with atypical melanomas treated with immunotherapy. It is an observational, descriptive, retrospective study that analyzed 72 medical records of patients with atypical melanomas, ECOG 0-1, &gt; 18 years old, treated with immunotherapy (neo, adjuvant, and palliative lines), between January 2015 and December 2023 at the A.C. Camargo Cancer Center, São Paulo, Brazil. Results: We gathered 72 patients, 61% male and 39% female, with an average age of 58.89 (±13.63) years; 57% were white, 15% African-descendant (black and brown), 8% Asian, and 20% not specified. Regarding primary site, 26% were acral, 24% mucosal, 24% occult primary site, 15% uveal, 8% desmoplastic, 1% amelanocytic, 1% spitzoid, and 1% cauda equina meningeal. Regarding staging, (3%) were stage I, (15%) stage II, (25%) stage III, (47%) stage IV, and (10%) unknown. LDH: 372.5 (±360) mg/dL. Metastases: lymph node 29%; hepatic 23%; pulmonary 21%; bone 18%; central nervous system 15%; peritoneal carcinomatosis 5%; stomach 3%; cauda equina 3%; adrenal 1%; in transit 1%; intestine 1%; bone marrow 1%; parotid 1%. BRAF mutations were present in 23% of cases (variants V660E, V600K, V660R, and G469R); NRAS 6% (codons 13 and 61); KIT 1% (exon 11) and NTRAK 1% (S701F). In relation to treatment, 5 received neoadjuvant anti-pd1 + anti-ctla4 combination, 13 adjuvant with anti-pd1+/- anti-ctla4. About 50 patients received systemic treatment for metastatic disease anti-pd1+/- anti-ctla4. Overall survival: 26 (±14.8) months. Conclusions: Atypical melanoma primary occult site is the most prevalent, with the majority diagnosed at stage IV, with high LDH levels and lymph nodes as the main sites of metastases. Twenty-three percent had a BRAF gene mutation. The majority were treated palliatively with first-line immunotherapy, with median survivals of 14.8 months.