Intraperitoneal radioimmunotherapy (RIT) for desmoplastic small round cell tumor (DSRCT).

Abstract

TPS9595 Background: DSRCT, a rare sarcoma of adolescents and young adults arises from serosal surfaces typically the peritoneum. It is characterized by t(11;22)(p13;q12) chromosomal translocation; and is lethal in >80% of patients despite aggressive surgery and chemoradiotherapy. Disease recurrence often presents as multifocal peritoneal implants, making it uniquely suited for intraperitoneal (IP) targeting. Since DSRCT is radiosensitive, we hypothesize that improving local control with targeted radiotherapy may reduce relapse and enhance survival. IP RIT, by virtue of prolonged residence time, and slow/incomplete transfer to the circulation, may selectively target IP disease while minimizing organ toxicity. The anti-4Ig-B7H3 murine monoclonal antibody 8H9 binds to 96% of primary DSRCT with restricted reactivity to normal tissue (Med Pediatr Oncol 39:547). 131I-8H9 targets DSRCT xenografts and has proven safe at 80mCi when injected intrathecally (J Neurooncol 97:409). 124I-8H9, a novel positron-emitting radioimmunoconjugate is ideally suited for quantitative imaging and pharmacokinetic (PK) studies. Methods: We have initiated a phase I study to test the safety of IP RIT using 131I-8H9 in patients with DSRCT (clinicaltrials.gov NCT01099644). Cohorts of 3-6 patients are treated with 131I-8H9 at escalated doses from 30mCi/m2-60mCi/m2 as a single IP injection. An IP tracer dose of 2mCi124I-8H9 is given prior to 131I-8H9 to acquire high-resolution PET images and data on 8H9 tumor targeting and biodistribution. PK is also studied using serial blood draws. Patients are monitored for toxicity clinically and biochemically. Response to treatment is assessed using RECIST criteria and via a follow up 124I-8H9 PET scan if tumor targeting is noted on initial imaging. Hematopoietic stem cells are harvested a priori to reverse myelosuppression if any. Three cohorts of patients (n=9) up to 50mCi/m2 have completed therapy thus far without dose-limiting toxicity or myelosuppression. This is the first study of IP RIT in pediatrics, and the first to use PET for IP RIT. Data obtained will be critical in establishing safety of IP 131I-8H9 in children and young adults, and in designing phase II trials to study efficacy of IP RIT for DSRCT.