Modified RANO, immunotherapy RANO, and standard RANO response to convection-enhanced delivery of IL4R-targeted immunotoxin MDNA55 in recurrent glioblastoma

Benjamin M. Ellingson, John Sampson, Achal Singh Achrol, Manish K. Aghi, Krystof Bankiewicz, Chencai Wang, Martin Bexon, Steven Brem, Andrew Brenner, Sajeel Chowdhary, John R. Floyd, Seunggu Han, Santosh Kesari, Dina Randazzo, Michael A. Vogelbaum, Frank Vrionis, Miroslaw Zabek, Nicholas Butowski, Melissa Coello, Nina MerchantFahar Merchant

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). Patients and Methods: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. Results: A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P < 0.0001; HR ¼ 0.3) and mRANO (P < 0.0001; HR ¼ 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P ¼ 0.47; central, P ¼ 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P ¼ 0.017), but not central measurements (P ¼ 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 ¼ 0.66, P < 0.0001) and centrally determined reads (R2 ¼ 0.57, P ¼ 0.0007). Conclusions: No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.

Original languageEnglish (US)
Pages (from-to)3916-3925
Number of pages10
JournalClinical Cancer Research
Volume27
Issue number14
DOIs
StatePublished - Jul 15 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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