In summary, the overall prognosis of glioblastoma (GBM) patients remains poor. Although clinical gains have been achieved in the past, these have been modest, with a majority of patients succumbing to local disease progression within 2 years. New strategies for treatment need to be identified which enhance local control above the current treatment regimen in order to achieve further clinical gains in this disease. Favorable early experience with magnetic resonance spectroscopy imaging (MRSI) demonstrates that metabolic imaging can identify active tumor beyond standard MRI as well as high risk regions at risk for local failure. There is also clinical evidence that limited field dose escalation with either simultaneous integrated boost (SIB) or stereotactic radiosurgery (SRS) is feasible and safe. Coupling these findings provide the rationale for this proposed Phase II trial designed to define efficacy and toxicity of the novel treatment approach of whole brain volumetric 3D MRSI guided dose-escalated radiation therapy (RT) in newly diagnosed GBM patients.
This phase II study will investigate efficacy and safety of volumetric 3D MRSI-directed treatment for newly diagnosed GBM patients. This study will enroll 48 patients in order to obtain at least 40 patients receiving RT and temozolomide. Depending on the size and number of HTVs, a patient will receive either simultaneous integrated boost (SIB) with IMRT (Group 1) or SRS boost followed by IMRT 1 week later (Group 2). Duration of enrollment will be 2 years and minimum follow-up will be 2 years. The duration of treatment and follow-up will occur as follows: * Six weeks of RT with concurrent Temozolomide treatment; * 3D MRSI at week 3 and at the end of RT; * 28 day break; * Adjuvant treatment with Temozolomide administered daily on days 1-5 of each cycle, for up to 12 cycles (one cycle = 28 days) which will include standard gadolinium enhanced MRI and 3D MRSI prior to cycle 1, 5, 9, and post cycle 12 of adjuvant Temozolomide; * Active follow-up at least every three months for one year after the end of adjuvant Temozolomide treatment; * After one year follow-up for survival will occur every three months for one year.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1
IMRT treatment will consist of 60 Gy in 30 fractions to PTV 60
Concurrently during radiation therapy. Adjuvant therapy administered daily on days 1 - 5 for 12 cycles. One cycle = 28 days: * Concurrent during Radiation Therapy: 75 mg/m\^2 orally for 6 weeks; * Post-radiation, adjuvant therapy: 150 mg/m\^2 - 200 mg/m\^2 orally daily on days 1 - 5 of each cycle.
FACT-Br Quality of Life (QOL) questionnaire to be completed by study patients as protocol specific timepoints
Patients will undergo SRS boost in a single fraction dose prior to IMRT treatment: HTV Maximum dimension vs. Prescribed Dose to HTV: ≤ 20 mm = 21 Gy; 21 mm - 30 mm = 18 Gy; 31 mm - 40 mm = 15 Gy.
Treatment shall consist of 60 Gy in 30 fractions to planning target volume (PTV) 60 and 75 Gy in 30 fractions to PTV 75.
Three Dimensional Magnetic Resonance Spectroscopy Imaging (MRSI) during pre-treatment, week 3 during radiation therapy, end of radiation therapy; will include standard gadolinium enhanced MRI prior to cycle 1, 5, 9, and post cycle 12 of adjuvant temozolomide therapy, per protocol.
University of Miami
Miami, Florida, United States
Rate of Overall Survival (OS) in Study Patients
The efficacy of 3D MRSI-guided, dose escalated radiation in newly diagnosed glioblastoma (GBM) patients as measured by overall survival (OS). Overall survival (OS) is defined as the time elapsed from the start of study treatment until death. Surviving patients (including patients lost to follow up) will be censored at the date of last contact.
Time frame: Up to 2 years
Rate of Progression-Free Survival (PFS) in Study Patients
Rate of progression-free survival in study participants. Progression-free survival (PFS) is defined as the time elapsed from the start of study treatment to the date of documented progression events. For progression-free patients (without progression events), PFS will be censored at the last date of documented PF status.
Time frame: Up to 2 years
Rate of Grade 3 or Higher Toxicity as a a Consequence of Study Therapy.
Rate of Grade 3 of Higher Toxicity in study participants as a consequence of study therapy.
Time frame: 2 years
Change in Quality of Life From Baseline in Study Participants
Change in quality of life during radiation and across the longitudinal progression-free interval compared to baseline. Change of quality of life will be assessed and scored via the FACT-Br behavioral questionnaire.
Time frame: Up to 2 years
Patterns of Failure in Study Participants Post-Protocol Therapy
Patterns of Failure will be assessed by determining the number of failures that arise in-field compared to the number that arise out-of-field. In-field failure will be defined as those where greater than 80% of the recurrence volume was encompassed by the 95% prescription isodose line. In addition, we will also describe failures by three types: unifocal, multifocal and diffuse (multicentric including leptomeningeal dissemination).
Time frame: Up to 2 years
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