A phase I/II trial of 5-fraction stereotactic radiosurgery with 5-mm margins with concurrent temozolomide in newly diagnosed glioblastoma: primary outcomes
| Autor: | D.K. Fujimoto, Jacob Wynne, Iris C. Gibbs, Griffith R. Harsh, Lawrence Recht, Ciara Harraher, Seema Nagpal, Clara Y.H. Choi, Steven D. Chang, Reena Thomas, Rie von Eyben, Gordon Li, Leslie A. Modlin, Lisa R Jacobs, Melanie Hayden Gephart, Kira Seiger, Melissa Azoulay, Erqi L. Pollom, Steven L. Hancock, Scott G. Soltys, Melissa Usoz, John R. Adler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
hypofractionated Cancer Research medicine.medical_specialty Hypofractionated Radiation Therapy medicine.medical_treatment Oncology and Carcinogenesis Urology Clinical Investigations Antineoplastic Agents Radiosurgery Rare Diseases 80 and over Temozolomide Medicine Humans Oncology & Carcinogenesis Progression-free survival Adverse effect Aged Cancer Intention-to-treat analysis business.industry Brain Neoplasms glioblastoma Neurosciences Evaluation of treatments and therapeutic interventions Common Terminology Criteria for Adverse Events Chemoradiotherapy Middle Aged prospective medicine.disease Alkylating Brain Disorders Brain Cancer Oncology 6.1 Pharmaceuticals Female Radiation Dose Hypofractionation Neurology (clinical) newly diagnosed business Glioblastoma Progressive disease medicine.drug |
| Zdroj: | Neuro Oncol Neuro-oncology, vol 22, iss 8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|