Randomized Phase II Trial of Re-Irradiation and Concurrent Bevacizumab versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma (NRG Oncology/RTOG 1205): Initial Outcomes and RT Plan Quality Report

Tsien, Christina; Pugh, Stephanie L.; Dicker, Adam P.; Raizer, Jeffrey J.; Matuszak, Martha M.; Lallana, Enrico C.; Huang, Jiayi; Algan, Özer; Taylor, N. Jane; Portelance, Lorraine; Villanó, John L.; Hamm, John; Oh, Kevin; Ali, Arif; Kim, M.M.; Lindhorst, Scott; Mehta, Minesh P.

doi:10.1016/j.ijrobp.2019.06.539

Cited by 40 publications

(42 citation statements)

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“… 19 The role of bevacizumab with RT remains to be determined, and preliminary results from the prospective Radiation Therapy Oncology Group trial 1205 indicate that the addition of hypofractionated RT to bevacizumab improves PFS, but not OS. 20 …”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes in Patients with Recurrent Glioblastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry

Saeed

Khairnar

Sharma

et al. 2020

Advances in Radiation Oncology

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Purpose As a means of limiting normal tissue toxicity, proton-beam therapy (PBT) is an emerging radiation modality for glioblastoma (GBM) reirradiation. However, data for recurrent GBM treated with PBT reirradiation is limited. Therefore, we analyzed treatment patterns, toxicities, and clinical outcomes of patients with recurrent GBM treated with PBT reirradiation using the multi-institutional Proton Collaborative Group registry. Methods and Materials Prospectively collected data for patients with recurrent GBM who underwent PBT while enrolled in Proton Collaborative Group study 01-009 (NCT01255748) were analyzed. We evaluated overall survival (OS), progression-free survival (PFS), and toxicity. Toxicities were scored per the Common Terminology Criteria for Adverse Events, version 4.0. Descriptive statistics were used to report patient, tumor, and treatment characteristics. Multivariable analyses (MVA) for toxicity were conducted using logistic regression. The Kaplan-Meier method was used to calculate OS and PFS. MVA for OS and PFS was conducted using Cox proportional-hazards models. The SAS statistical software was used for the analysis. Results We identified 45 recurrent patients with GBM who underwent PBT reirradiation between 2012 and 2018. The median time between initial GBM diagnosis and recurrence was 20.2 months. The median follow-up time from PBT reirradiation was 10.7 months. Median PFS was 13.9 months (95% confidence interval [CI], 8.23-20.0 months) and median OS was 14.2 months (95% CI, 9.6-16.9 months) after PBT reirradiation. One patient experienced an acute grade 3 toxicity, 4 patients experienced late grade 3 toxicity (no grade ≥4 toxicities). MVA revealed that prior surgery was associated with a 91.3% decreased hazard of death (hazard ratio: 0.087; 95% CI, 0.02-0.42; P < .01). No explanatory variables were associated with PFS or grade 3 toxicities. Conclusions This is the largest series to date reporting outcomes for PBT reirradiation of patients with recurrent GBM. Our analysis indicates that PBT is well tolerated and offers efficacy rates comparable with previously reported photon reirradiation.

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Section: Discussionmentioning

confidence: 99%

Clinical Outcomes in Patients with Recurrent Glioblastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry

Saeed

Khairnar

Sharma

et al. 2020

Advances in Radiation Oncology

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“…Survival benefits have been reported following fractionated SRT and concurrent bevacizumab [ 12 , 55 , 60 , 64 – 68 ]. Gutin et al [ 55 ] observed a median overall survival time of 12.5 months and 1-year survival rate of 54% in twenty patients who received 30 Gy in 5 fractions to the recurrent tumor with SRT; median progression-free survival time and 6-month rates were 7.4 months and 65%, respectively.…”

Section: Survival Outcomes and Toxicitymentioning

confidence: 99%

“…In a small retrospective study comparing hypofractionated SRT (25 Gy in 5-Gy fractions) plus bevacizumab or the alkylating agent fotemustine, median survival times and 12-month survival rates were 11 months and 30% for patients treated with SRT and bevacizumab and 8.3 months and 5% for those treated with SRT and fotemustine (p = 0.01); respective median progression-free survival times were 6 and 4 months (p = 0.01). In a recent multi-institutional, prospective randomized phase II trial (NRG Oncology/Radiation Therapy Oncology Group (RTOG) trial 1205) designed to evaluate the safety and efficacy of reirradiation for recurrent GBM with modern radiation techniques, a similar survival of 10.1 months has been observed following hypofractionated SRT (35 Gy/10 fractions) and concurrent bevacizumab [ 68 ].…”

Section: Survival Outcomes and Toxicitymentioning

confidence: 99%

Current status and recent advances in reirradiation of glioblastoma

et al. 2021

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Despite aggressive management consisting of maximal safe surgical resection followed by external beam radiation therapy (60 Gy/30 fractions) with concomitant and adjuvant temozolomide, approximately 90% of WHO grade IV gliomas (glioblastomas, GBM) will recur locally within 2 years. For patients with recurrent GBM, no standard of care exists. Thanks to the continuous improvement in radiation science and technology, reirradiation has emerged as feasible approach for patients with brain tumors. Using stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT), either hypofractionated or conventionally fractionated schedules, several studies have suggested survival benefits following reirradiation of patients with recurrent GBM; however, there are still questions to be answered about the efficacy and toxicity associated with a second course of radiation. We provide a clinical overview on current status and recent advances in reirradiation of GBM, addressing relevant clinical questions such as the appropriate patient selection and radiation technique, optimal dose fractionation, reirradiation tolerance of the brain and the risk of radiation necrosis.

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“…Thus, the survival in this prospective trial compares favorably to those series. Moreover, the one prospective trial of reirradiation in recurrent GBM for bevacizumab-naïve patients, Radiation Therapy Oncology Group (RTOG) 1205, failed to show an incremental benefit of radiation given via 35 Gy in 10 fractions when added to bevacizumab in this population [30].…”

Section: Discussionmentioning

confidence: 99%

Repeat radiation with bevacizumab and minocycline in bevacizumab-refractory high grade gliomas: a prospective phase 1 trial

et al. 2020

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Introduction There are no effective treatments for gliomas after progression on radiation, temozolomide, and bevacizumab. Microglia activation may be involved in radiation resistance and can be inhibited by the brain penetrating antibiotic minocycline. In this phase 1 trial, we examined the safety and effect on survival, symptom burden, and neurocognitive function of reirradiation, minocycline, and bevacizumab. Methods The trial used a 3 + 3 design for dose escalation followed by a ten person dose expansion. Patients received reirradiation with dosing based on radiation oncologist judgment, bevacizumab 10 mg/kg IV every two weeks, and oral minocycline twice a day. Symptom burden was measured using MDASI-BT. Neurocognitive function was measured using the COGSTATE battery. Results The maximum tolerated dose of minocycline was 400 mg twice a day with no unexpected toxicities. The PFS3 was 64.6%, and median overall survival was 6.4 months. Symptom burden and neurocognitive function did not decline in the interval between treatment completion and tumor progression. Conclusions Minocycline 400 mg orally twice a day with bevacizumab and reirradiation is well tolerated by physician and patient reported outcomes in people with gliomas that progress on bevacizumab.

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Randomized Phase II Trial of Re-Irradiation and Concurrent Bevacizumab versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma (NRG Oncology/RTOG 1205): Initial Outcomes and RT Plan Quality Report

Abstract: HFRT should be limited to small volume recurrences especially in previously non-irradiated treatment areas at least 6 months following completion of previous RT. Due to treatment plan complexity, future re-irradiation GBM trials should require real time RT review.

Cited by 40 publications

References 0 publications

Clinical Outcomes in Patients with Recurrent Glioblastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry

Clinical Outcomes in Patients with Recurrent Glioblastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry

Current status and recent advances in reirradiation of glioblastoma

Repeat radiation with bevacizumab and minocycline in bevacizumab-refractory high grade gliomas: a prospective phase 1 trial

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