Browsing by Author "Denu, Ryan"

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    Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study
    (Elsevier, 2024-01-16) Nassar, Amin H.; El-Am, Edward; Denu, Ryan; Alaiwi, Sarah Abou; El Zarif, Talal; Macaron, Walid; Abdel-Wahab, Noha; Desai, Aakash; Smith, Caleb; Parikh, Kaushal; Abbasi, Muhannad; Farhat, Elias Bou; Williams, James M.; Collins, Jeremy D.; Al-Hader, Ahmad; McKay, Rana R.; Malvar, Carmel; Sabra, Mohamad; Zhong, Caiwei; El Alam, Raquelle; Chehab, Omar; Lima, Joao; Phan, Minh; Pria, Hanna Ferreira Dalla; Trevino, Alexandra; Neilan, Tomas G.; Kwan, Jennifer M.; Ravi, Vinod; Deshpande, Hari; Demetri, George; Choueiri, Toni K.; Naqash, Abdul Rafeh; Medicine, School of Medicine
    Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.
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    Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study
    (BMJ, 2025-03-03) Nassar, Amin H.; Abou Alaiwi, Sarah; El Zarif, Talal; Denu, Ryan; Macaron, Walid; Abdel-Wahab, Noha; Freeman, Dory; Vasbinder, Alexi; Hayeck, Salim; Anderson, Elizabeth; Goodman, Rachel S.; Johnson, Douglas B.; Grynberg, Shirly; Shapira, Ronnie; Kwan, Jennifer M.; Woodford, Rachel; Long, Georgina V.; Haykal, Tarek; Dent, Susan; Kojima, Yuki; Yonemor, Kan; Tandon, Ankita; Trevino, Alexandra; Akhter, Nausheen; Yang, Eric H.; Hui, Gavin; Drakaki, Alexandra; El-Am, Edward; Kozaily, Elie; Al-Hader, Ahmad; Farhat, Elias Bou; Babu, Priyanka; Mittra, Arjun; Li, Mingjia; Jones, Nicholas; Baena, Javier; Juarez Herrera, Mercedes; Foderaro, Simone; Aboubakar Nana, Frank; Kim, Chul; Sackstein, Paul; Parikh, Kaushal; Desai, Aakash P.; Smith, Caleb; Cortellini, Alessio; Pinato, David J.; Korolewicz, James; Lopetegui-Lia, Nerea; Funchain, Pauline; Choudhary, Arrush; Asnani, Aarti; Navani, Vishal; Meyers, Daniel; Stukalin, Igor; Ocejo Gallegos, Jesus Antonio; Trent, Jonathan; Nusrat, Sanober; Malvar, Carmel; McKay, Rana R.; Neilan, Tomas G.; Choueiri, Toni K.; Naqash, Abdul Rafeh; Medicine, School of Medicine
    Background: Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited. Methods: This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results: Among 110 pts, median age at ICI initiation was 65 (IQR: 59-75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients. Conclusions: Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis.