Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Mar;162(1):69-78.
doi: 10.1007/s11060-022-04235-w. Epub 2023 Feb 28.

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma

Kathryn R Tringale  1 , Suzanne L Wolden  1 , Matthias Karajannis  2 , Sofia Haque  3 , Luca Pasquini  3 , Onur Yildirim  3 , Marc Rosenblum  4 , Jamal K Benhamida  4 , Nai-Kong Cheung  2 , Mark Souweidane  5 , Ellen M Basu  2 , Neeta Pandit-Taskar  6 , Pat B Zanzonico  7 , John L Humm  3   7 , Kim Kramer  8
Affiliations
Clinical Trial

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma

Kathryn R Tringale et al. J Neurooncol. 2023 Mar.

Abstract

Purpose: Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT. This study evaluates predictors of response, patterns of failure, and radiologic events after cRIT.

Methods: Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan-Meier analysis.

Results: All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma patients were NED, associated with improved PFS (p = 0.002) and OS (p = 0.048) in medulloblastoma. Most relapses were multifocal. With medium follow-up of 3.0 years (95% confidence interval, 1.8-7.4), 6 patients remain alive with NED.

Conclusion: For patients with medulloblastoma, remission at time of cRIT was associated with significantly improved survival outcomes. Relapses are often multifocal, particularly in the setting of measurable disease at cRIT initiation. EBRT is a promising tool to achieve NED status at cRIT initiation, with no cases of radiation necrosis.

Keywords: External beam radiotherapy; Intraventricular compartmental radioimmunotherapy; Pediatric brain tumors; Proton beam radiotherapy; Radiation necrosis.

PubMed Disclaimer

Conflict of interest statement

Both Memorial Sloan Kettering Cancer Center (MSK) and Dr. Cheung have financial interest in Y-mAbs, Abpro-Labs and Eureka Therapeutics. Dr. Cheung also reports receiving commercial research grants from Y-mabs Therapeutics and Abpro-Labs Inc. Dr. Cheung was named as inventor on multiple patents filed by MSK, including naxitamab and omburtamab licensed to Ymabs Therapeutics, and others licensed to Biotec Pharmacon, and Abpro-labs. Dr. Cheung is a SAB member for Eureka Therapeutics. Dr. Modak and Dr. Kramer reports consulting and equity in Ymabs, Therapeutics Inc. Omburtamab was licensed to Y-mAbs Therapeutics in 2015. Dr. Karajannis reports grants from Y-mAbs Therapeutics, Inc. (research support) and personal fees from Bayer AG, AstraZeneca, Inc., QED Therapeutics, Inc., CereXis, Inc., Recursion, Inc., Cardinal Health and Medscape (Medical Advisory Board and/or consultant).

Figures

Fig. 1
Fig. 1
Swimmer’s plot demonstrating timing of treatments received and progression events. An arrowhead indicates that the patient was alive at the time of last follow-up. Those without an arrowhead indicate that the patient died at that time. *One patient was lost to follow-up and died of unknown causes. MB medulloblastoma; EP ependymoma; MD measurable disease; CSF cerebrospinal fluid; 8H9, I-131-omburtamab; cRIT compartmental radioimmunotherapy. TTwo patients (both with medulloblastoma) only received a single test dose (2 mCi)
Fig. 2
Fig. 2
Survival outcomes among patients with medulloblastoma (top) and ependymoma (bottom) calculated from the time of pre-cRIT relapse. A Progression-free and B overall survival among patients with medulloblastoma. C Progression-free and D overall survival among patients with ependymoma. Note: one patient with ependymoma was lost to follow-up and was therefore not included in the progression free survival calculation
Fig. 3
Fig. 3
Survival outcomes among patients with medulloblastoma based on disease status at cRIT initiation. A Progression free and B overall survival from cRIT administration among patients with medulloblastoma. cRIT, compartmental radioimmunotherapy
See this image and copyright information in PMC

References

    1. Christopherson K, Rotondo R, Bradley J, et al. Late toxicity following craniospinal radiation for early-stage medulloblastoma. Acta Oncol (Madr) 2014;53:471–480. doi: 10.3109/0284186X.2013.862596. - DOI - PubMed
    1. Oker N, Lang P, Bresson D, et al. Radionecrosis of the frontal lobe as a consequence of malignant ethomid tumor management: incidence, diagnosis, risk factors, prevention, and management. Eur Arch Oto-Rhino-Laryngol. 2014;271(255):3223–3232. doi: 10.1007/s00405-014-3013-7. - DOI - PubMed
    1. Kramer K, Kushner BH, Modak S, et al. Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma. J Neurooncol. 2010 doi: 10.1007/s11060-009-0038-7. - DOI - PMC - PubMed
    1. Kramer K, Humm J, Souweidane M, et al. Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using Intra-Ommaya 131-I-3F8. J Clin Oncol. 2007;25(34):5465–5470. doi: 10.1200/JCO.2007.11.1807. - DOI - PubMed
    1. Kramer K, Pandit-Taskar N, Kushner B, et al. Phase 1 study of intraventricular 131-I-omburtamab targeting B7H3(CD276)-expressing CNS malignancies. J Hematol Oncol. 2022 doi: 10.1186/s13045-022-01383-4. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances