A Phase II Trial of Accelerated Radiotherapy UsingA Phase II Trial of Accelerated Radiotherapy Using
Weekly Stereotactic Conformal Boosts forWeekly Stereotactic Conformal Boosts for
Supratentorial Glioblastoma Multiforme.Supratentorial Glioblastoma Multiforme.
Robert Cardinale, M.D.
Princeton Medical Center, Princeton, NJ
Medical College of Virginia Hospitals, Richmond, VA
Comprehensive radiotherapeutic strategy
SRT boost trial at MCV was well tolerated
Study FeaturesStudy Features
Unlike radiosurgery/brachytherapy trials:
- Patients with gross total resection
- Entire resection cavity is included in
- Strict dose homogeneity requirement
- Technique uses shaped conformal
- Large target sizes (post-op diameter up to 60
To assess the feasibility, toxicity, and
efficacy of four weekly stereotactic
radiotherapy boosts given during a 50 Gy
course of EBXRT for GBM patients
• Histologically confirmed GBM (gross total
• Boost GTV < 60 mm
• Performance status 0-1, Neurologic function
• Adequate bone marrow reserve
• Mutifocal disease
• Tumors of the brainstem or within 10 mm of
the optic chiasm
RT ScheduleRT Schedule
1 2 3 4 5 6
IIIII IIIII IIII* IIII* IIII* III*
I = standard EBXRT (pre-op tumor volume plus
edema), 2 Gy x 25 fractions
* = SRT boost, 5-7 Gy x 4 fractions
4 SRT Boosts: weeks 3-64 SRT Boosts: weeks 3-6
GTV: Postoperative residual enhancing lesion
plus entire resection cavity
PTV: GTV + 5 mm
Dose: Maximum PTV Diameter Dose/fx
≤40 mm 7 Gy
>40 mm 5 Gy
SRT planning: sites pre- certified, MRI, conformal
fields, strict homogeneity requirement
BCNU: 80 mg/m2
i.v. for 3 days,
beginning within one month after the
completion of RT then q 8 weeks for a
total of 6 cycles
A sample size of 76 pts (Dixon-
Simon method) assuming 10%
ineligibility rate was used to
compare survival with 1027 pts. in
the RTOG- RPA class database
(p<0.05- one sided)
80 pts enrolled from June, 2001 - June, 2004
4 patients ineligible, 76 analyzed
Age (median) 58
Gender (male, female) 63%, 37%
Performance Status (0, 1) 64%, 36%
Subtotal resection 35%
Gross total resection 41%
Oncology GroupOverall Survival – Gross Total ResectionOverall Survival – Gross Total Resection
RTOG 0023 (__) vs. Historical control (---)RTOG 0023 (__) vs. Historical control (---)
MONTHS FROM REGISTRATION
0 3 6 9 12 15 18 21 24
17 vs. 12 mos.
Brain 3 0 1
Skin (within the field) 6 2 0
Eye 2 0 0
Subcutaneous Tissue 2 0 0
Other 9 1 0
Worst toxicity per patient 9 3 1
Grade (RT late) 1 2 3
(13%) (4%) (1%)
Significant toxicity included: one grade 4 acute (lethargy) and
one grade 3 late (necrosis). Ten patients experienced grade 4
Pattern of First FailurePattern of First Failure
in relation to boost volumein relation to boost volume
Within target volume 64%
Within target volume plus adjacent 25%
Beyond adjacent 4%
Re-operation in 28 patients (43%)
Quality AssuranceQuality Assurance
Per protocol/minor deviation: 90%
Significant deviations: 10%
4 had inadequate target coverage
4 had optic chiasm dose > 55 Gy
Per Protocol: 83%
Unacceptable Deviation: 1%
This accelerated, SRT boost trial:
Resulted in no significant survival
benefit, patients with gross total
resection trended toward improved outcome
Leading Participating Institutions:
Mass. General Hospital - A. Chakravarti, M.D., Ph.D.
Medical College of Wisconsin - A. Choucair, M.D.
McGill University - L. Souhami, M.D.
Univ. of California, Davis - A. Chen, M.D.
Virginia Mason Medical Center - H. Pham, M.D.
Mike Gillin, Ph.D.
Minesh Mehta, M.D.
Minhee Won, M.A.
Brian Berkey, M.S.
Rupert Schmidt-Ullrich, M.D.