PMID- 37166798 OWN - NLM STAT- MEDLINE DCOM- 20230515 LR - 20230719 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 6 IP - 5 DP - 2023 May 1 TI - Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers. PG - e2312824 LID - 10.1001/jamanetworkopen.2023.12824 [doi] LID - e2312824 AB - IMPORTANCE: Patients with recurrent or unresectable skin cancers have limited treatment options. Diffusing alpha-emitter radiation therapy (DaRT), a novel solid tumor management strategy using alpha-particle interstitial brachytherapy, may address this challenge. OBJECTIVE: To evaluate the feasibility and safety of using DaRT to manage recurrent or unresectable skin cancers. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study of patients who received a 2-week to 3-week treatment course and were followed up for 24 weeks after treatment during 2021 and 2022 at 2 sites in the US. Patients with malignant skin tumors or soft tissue tumors were recruited if they had limited treatment options for tumors recurrent after prior surgery or external beam radiotherapy or unresectable tumors. INTERVENTION: Patients underwent DaRT to deliver a physical dose of 10 Gy (equivalent weighted dose of 200 CGE) to the tumor. MAIN OUTCOMES AND MEASURES: Feasibility of the DaRT procedure was evaluated based on the ability of investigators to successfully deliver radiation to the tumor. Patients were followed up for adverse events (AEs) for 24 weeks and for tumor response by physicians' physical examination and imaging 12 weeks after device removal. RESULTS: This study included 10 participants with recurrent or unresectable skin cancer (median [IQR] age, 72 [68-75] years; 6 males [60%]; 4 females [40%]). Six patients (60%) had recurrent disease, and 4 (40%) had tumors that were deemed unresectable. Tumors were located on the nose, chin, eyelid, scalp, neck, trunk, and extremities. Median (range) tumor volume before treatment was 2.1 cm3 (0.65-12.65 cm3). The mean (SD) prescription dose coverage of the gross tumor volume was 91% (2.8%) with all tumors having coverage of 85% or more. No device-related grade 3 AEs were noted. Common AEs were grade 1 to 2 erythema, edema, and pruritus. At 12 weeks following treatment, there was a 100% complete response rate. Nine of 10 complete responses (90%) were confirmed by CT imaging. CONCLUSIONS AND RELEVANCE: This cohort study suggests the feasibility and preliminary safety of DaRT in the management of recurrent or unresectable skin cancers. The favorable safety profile and high response rates are promising. A US trial for marketing approval based on this pilot study is under way. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04377360. FAU - D'Andrea, Mark A AU - D'Andrea MA AD - University Cancer Centers, Houston, Texas. FAU - VanderWalde, Noam A AU - VanderWalde NA AD - West Cancer Center, Germantown, Tennessee. FAU - Ballo, Matthew T AU - Ballo MT AD - West Cancer Center, Germantown, Tennessee. FAU - Patra, Pradeep AU - Patra P AD - West Cancer Center, Germantown, Tennessee. FAU - Cohen, Gil'ad N AU - Cohen GN AD - Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Damato, Antonio L AU - Damato AL AD - Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Barker, Christopher A AU - Barker CA AD - Memorial Sloan Kettering Cancer Center, New York, New York. LA - eng SI - ClinicalTrials.gov/NCT04377360 GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230501 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 SB - IM MH - Male MH - Female MH - Humans MH - Aged MH - *Brachytherapy/adverse effects MH - Cohort Studies MH - Prospective Studies MH - Pilot Projects MH - Feasibility Studies MH - *Skin Neoplasms/radiotherapy PMC - PMC10176125 COIS- Conflict of Interest Disclosures: Dr Ballo reported receiving personal fees from Novocure outside the submitted work. Dr Cohen reported receiving support from Alpha Tau Medical research outside the submitted work. Dr Damato reported receiving grants from Alpha Tau Medical outside the submitted work. Dr Barker reported personal fees from Regeneron and grants from Elekta, Amgen, Merck, Physical Sciences Incorporated, EMD Serono, and Regeneron outside the submitted work. No other disclosures were reported. EDAT- 2023/05/11 13:18 MHDA- 2023/05/15 06:42 PMCR- 2023/05/11 CRDT- 2023/05/11 11:33 PHST- 2023/05/15 06:42 [medline] PHST- 2023/05/11 13:18 [pubmed] PHST- 2023/05/11 11:33 [entrez] PHST- 2023/05/11 00:00 [pmc-release] AID - 2804784 [pii] AID - zoi230395 [pii] AID - 10.1001/jamanetworkopen.2023.12824 [doi] PST - epublish SO - JAMA Netw Open. 2023 May 1;6(5):e2312824. doi: 10.1001/jamanetworkopen.2023.12824.