A phase I/II trial of 5-fraction stereotactic radiosurgery with 5-mm margins with concurrent temozolomide in newly diagnosed glioblastoma: primary outcomes.

Abstract

BACKGROUND:

We sought to determine the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with 5-mm margins delivered with concurrent temozolomide in newly diagnosed glioblastoma (GBM).

METHODS:

We enrolled adult patients with newly diagnosed glioblastoma to 5 days of SRS in a 3 + 3 design on 4 escalating dose levels: 25, 30, 35, and 40 Gy. Dose limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events grades 3-5 acute or late CNS toxicity, including adverse radiation effect (ARE), the imaging correlate of radiation necrosis.

RESULTS:

From 2010 to 2015, thirty patients were enrolled. The median age was 66 years (range, 51-86 y). The median target volume was 60 cm3 (range, 14.7-137.3 cm3). DLT occurred in 2 patients: one for posttreatment cerebral edema and progressive disease at 3 weeks (grade 4, dose 40 Gy); another patient died 1.5 weeks following SRS from postoperative complications (grade 5, dose 40 Gy). Late grades 1-2 ARE occurred in 8 patients at a median of 7.6 months (range 3.2-12.6 mo). No grades 3-5 ARE occurred. With a median follow-up of 13.8 months (range 1.7-64.4 mo), the median survival times were: progression-free survival, 8.2 months (95% CI: 4.6-10.5); overall survival, 14.8 months (95% CI: 10.9-19.9); O6-methylguanine-DNA methyltransferase hypermethylated, 19.9 months (95% CI: 10.5-33.5) versus 11.3 months (95% CI: 8.9-17.6) for no/unknown hypermethylation (P = 0.03), and 27.2 months (95% CI: 11.2-48.3) if late ARE occurred versus 11.7 months (95% CI: 8.9-17.6) for no ARE (P = 0.08).

CONCLUSIONS:

The per-protocol MTD of 5-fraction SRS with 5-mm margins with concurrent temozolomide was 40 Gy in 5 fractions. ARE was limited to grades 1-2 and did not statistically impact survival.

• Authors: Melissa Azoulay, Steven D Chang, Iris C Gibbs, Steven L Hancock, Erqi L Pollom, Griffith R Harsh, John R Adler, Ciara Harraher, Gordon Li, Melanie Hayden Gephart, Seema Nagpal, Reena P Thomas, Lawrence D Recht, Lisa R Jacobs, Leslie A Modlin, Jacob Wynne, Kira Seiger, Dylann Fujimoto, Melissa Usoz, Rie von Eyben, Clara Y H Choi, Scott G Soltys
• Journal: Neuro-oncology (Neuro Oncol) Vol. 22 Issue 8 Pg. 1182-1189 (08 17 2020) ISSN: 1523-5866 [Electronic] England
• PMID: 32002547 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antineoplastic Agents, Alkylating
• Temozolomide

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents, Alkylating (therapeutic use)
• Brain Neoplasms (radiotherapy, surgery)
• Chemoradiotherapy
• Female
• Glioblastoma (radiotherapy, surgery)
• Humans
• Male
• Middle Aged
• Radiosurgery
• Temozolomide (therapeutic use)