1018 Single dose versus fractionated stereotactic radiotherapy for meningiomas

266

I. J. Radiation

Oncology

* Biology

l

Physics

Volume

45, Number

3 Supplement

1999

accelerator using a pair of opposed lateral fields. Radiotherapy was given in conventional fractionation (50 Gy/25 fx) (n = 597) or hypofractionated (30 Gy/lO fx) (n = 50). Patients were grouped according to the RTOG-RPA prognostic classification system. Class 1 (n = 60 patients): 5 65 years: KPS 2 70, controlled primary disease and no extracranial metastases; class 3 (n = 324 patients): KPS < 70; class 2 (n = 263): all other patients. Actuarial survival was calculated from the first day of radiotherapy using the product limit method of Kaplan and Meier. The log-rank test was employed to test for statistically significant differences. For multivariate analysis we used a proportional hazards model. Results: Median survival was 3.5 months for all patients. 13 patients were still alive and censored at the date of last follow-up. Median survival was 8.7 months (class l), 5.2 months (class 2) and 2.0 months (class 3), respectively (p < 0.0001). Classes (1 vs. 3 and 2 vs. 3), number of brain metastases (1 vs. > 1) and neurosurgical resection (yes vs. no) were analyzed simultaneously in a multivariate analysis. A better prognosis was found in class 1 patients compared with class 3 patients (RR 0.67. 95% C.I. 0.55-0.8), in class 2 patients patients compared with class 3 patients (RR 0.8, 95% C.I. 0.71.0.92), in patients with solitary brain metastasis compared to patients with multiple brain metastases (RR 0.86, 95% C.I. 0.78-0.96) and patients with postoperative radiotherapy compared to patients with primary radiotherapy (RR 0.76, C.I. 0.68-0.84). Conclusion: corroborates on survival. prognosis.

i 0 i 7 Lesser

Our analysis of patients with brain metastases treated the RTOG-RPA prognostic classification system. Patient In addition patients with solitary lesions and patients

INITIAL RESULTS OF A PHASE II TRIAL DIAGNOSED GLIOBLASTOMA (GBM).

G’: Kleinberg

La, Grossman

Sa, Piantadosi

with postoperative or primary whole brain radiotherapy and disease characteristics had a highly significant impact with postoperative radiotherapy had a more favourable

OF RSR13,

S’, O’Neill

A NEW

A3, Pearlman

RADIOENHANCER,

J’, Phillips

P5. Herman

IN NEWLY T6, Gerber

M7

Wake Forest University School qf Medicine, Winston-Salem, NC, USA’; The Johns Hopkins Oncology Center, Baltimore, MD, USA’; Universit)~ of Alabama at Birmingham, Birmingham, AL, USA’; H. Lee Mofjtt Cancer Center, Tampa, FL, USA4; University of Pennsylvania, Philadelphia, PA, USA’; University of Texas Health Science Center, San Antonio, TX, USA6; Allos Therapeutics, Inc., Denver; CO, USA7 Purpose: To determine survival, safety, pharmacodynamics and pharmacokinetics of RSR13 100 mg/kg per day along with cranial radiotherapy in the treatment of glioblastoma. RSR13, an allosteric modifier of hemoglobin (Hgb), is a novel radioenhancing agent which noncovalently binds to Hgb, thereby reducing oxygen binding affinity and increasing tissue oxygen release in capillaries. Materials and Methods: In this 50 patient multi-institution phase II trial, patients with newly diagnosed GBM (Karnofsky Performance Status ~60) received daily RSRI 3 100 mg/kg IV over l/2 hour along with standard cranial radiotherapy (60 Gy/30 fractions). Supplemental oxygen by nasal cannula (4 L/mm) was given during RSR13 infusion and continued until after the radiotherapy (RT) treatment. RT was given within 30 minutes of the end of the RSR13 infusion. Although accrual is complete. only 32 patients have been followed for at least a month after treatment and are currently evaluable for toxicity, pharmacodynamic and pharmacokinetic outcome. All patients are evaluable for survival. The pharmacodynamic endpoint was ~50. the partial pressure of oxygen at which hemoglobin is 50% saturated. Pharmacokinetic assessment included plasma and red blood cell RSR13 concentrations. Results: 25132 (78%) patients completed the planned RSR13 dosing. Four patients discontinued the study drug for the following reasons: allergic reaction to RSR13, hypoxemia, pulmonary embolism and sepsis. Three other patients had 5 to 8 RSR13 doses held during treatment for a bacterial infection, azotemia with nausea/vomiting, and a deep venous thrombosis but then resumed RSRl3 dosing and completed the study. 4/32 patients developed transient self-limited nonoliguric renal dysfunction without any signs of tubular injury. This generally occurred only when patients were on concurrent medications that affect renal blood flow such as antihypertensives working through the renin-angiotensin system or chronic NSAIDs. When the concurrent medications were discontinued and/or creatmme normalized, RSR13 dosing was safely resumed. The mean RSRI 3 concentration at end infusion was 571 i67 ugiml in plasma and 559% 116 ug/ml in red blood cells where RSRl3 is bound to hemoglobin. The mean peak shift in p50 was 11.5022.54 mmHg; a shift of 43% from baseline indicating an increased tendency towards oxygen unloading. With median follow-up of 5.5 months, the 6 month survival (195% confidence interval) by lifetable analysis is 842 12%. Conclusion: These preliminary results confirm that daily RSR13 administration is safe and that the desired pharmacodynamic effect can be reliably achieved. Further survival follow-up is needed to determine whether a phase III study of RSR13 with cranial radiotherapy for GBM should proceed.

10

i 8

SINGLE DOSE MENINGIOMAS

Lo SS. Cho KH. University

Hall WA,

of Minnesota

VERSUS Gerbi

Hospital

FRACTIONATED

BJ, Higgins and Clinic,

PD, Unger Minneapolis,

STEREOTACTIC J, Levitt MN,

RADIOTHERAPY

FOR

SH USA

Purpose: To evaluate the efficacy of stereotactic radiotherapy (SRT) in patients with meningiomas by comparing two different regimens, single dose and fractionated radiotherapy. Method and Materials: Between 1992 and 1998, 59 patients (16 male and 43 female) were treated with SRT. Thirty nine patients were treated with single dose radiosurgery (SRS). The remaining twenty patients with tumors adjacent to vital stmctures or of large sizes were treated with fractionated stereotactic radiotherapy (FSRT). 48 and 11 had benign and atypical or malignant meningioma respectively. The median dose for the SRS group was 1400 cGy (800-4500 cGy), and the median dose for the FSRT group was 5400 cGy (4000-6000 cGy) delivered in a median of 30 fractions (I 80.250 cGy/fraction). The median

Proceedings

treatment volumes for the SRS and the FSRT was 24.7 months (4.1-81 .O months).

of the 41st Annual

groups

were

ASTRO

267

Meeting

14.5 and 30 ml respectively.

The median

follow-up

for the 59 patients

Results: The 5 year progression free survival for 59 patients was 86.3%. 9 patients developed recurrence; 6 had atypical or malignant meningioma and 3 had benign tumors. Eight patients in the SRS group developed recurrence and only one in the FSRT group did so. Six had local recurrence (within or at the margin of treatment volume) and three had regional recurrence (outside of treatment volume). The 5 year local control (LC) for benign versus atypical or malignant meningiomas were 97.1% vs. 45.7% (p=O.O004). The 5 year LC were 84.4% for the SRS and 92.9% for the FSRT group (p=O.65). For the 48 patients with benign meningioma, the 5 year LC were 100% for the SRS (31 patients) and 90.9% for the FSRT groups (17 patients). Tumor grade (benign vs. atypical or malignant) was an independent prognostic factor predicting LC. Two patients in the SRS group (one with optic nerve meningioma had progressive vision loss and one had brain necrosis) and one in the FSRT group (one with chiasmal meningioma had progressive visual deterioration) developed late complications. Conclusion: Our preliminary data suggests that SRT is effective in patients with benign meningomas associated with minimal toxicities. For patients with meningiomas of large sizes or adjacent to vital structures such as optic chiasm and brainstem. FSRT offers comparable outcome to SRS without increased risk of toxicities. A longer follow up is required to determine the long term efficacy and toxicity of these treatment modalities. For atypical or malignant meningioma, the outcomes are suboptimal and innovative therapy is necessary to improve the outcome.

10

19

Kossow Dept. Dept.

THE DOSE RESPONSE RELATIONSHIP ARTERIOVENOUS MALFORMATIONS RJ’. Cho KHi,

qf Therapeutic of Neurological

Hall WA].*,

Gerbi

Radiology-Radiation Surgery University

Purpose: To determine linac based stereotactic

BJ’,

Higgins

FOR THE TREATMENT USING STEREOTACTIC PD’

Oncology University of Minnesota Hospital

if a dose response radiosurgery.

relationship

OF INTRACRANIAL RADIOSURGERY

exists

of Minnesota Hospital & Clinic, Minneapolis, for cerebral

arteriovenous

& Clinic, MN’

Minneapolis,

malformations

MN,

(AVMs)

USA’;

treated

with

Materials & Methods: Sixty-five patients with intracranial AVMs underwent stereotactic radiosurgery (SRS) from January 1991 to June 1998 at the University of Minnesota. All patients were treated using a 6 MV linear accelerator. Fifty-two patients who had follow up imaging studies were able to be evaluated for this analysis. The mean maximum diameter of the lesions was 3.1 cm (range 0.8 to 7.0 cm). The mean dose was 1440 cGy (range 800 to 2000 cGy) prescribed to the 40.90% isodose surface. The mean follow up interval was 29.5 months. Results: Failure was defined as the inability rate for patients who received a dose of less 1500 cGy or greater had a failure rate of only exact test (p=O.O071). The dose was the only on both univariate and multivariate analysis. necrosis. Conclusion: obliteration.

A dose response

1020 Saunders Marie

LOW DOSE INFLUENCE MI’,

Curie

appears

to exist for AVMs,

and a dose of 1500 cGy is adequate

HYPER-RADIOSENSITIVITY - IS IT h CLINICAL THE RADIATION SCHEDULES USED IN THE

Shah N’, Joiner Research

relationship

to achieve complete obliteration of the AVM at 3 years of follow up. The failure than 1500 cGy was 3 1.6% (6/19); whereas those patients who received a dose of 3.0% (l/33). The difference in failure rates was statistically significant by Fisher’s factor among variables evaluated which influenced the outcome, i.e. failure rate, One patient died of hemorrhage post treatment, and two developed radiation

Wing,

REALITY TREATMENT

to achieve

complete

AND CAN IT OF GLIOMAS?

MC* Middlesex,

United

Kingdom’;

Gray

Laboratory

Cancer

Research

Trust,

United

Kingdom”

Introduction: Malignant gliomas remain refractory to innovations of radiotherapy and chemotherapy. Research, initially carried at the Gray Laboratory, in radioresistant cell-lines including glioma have shown an excess of cell kill at doses below 1 Gy relative to that predicted by the linear quadratic model and this phenomenon is called “low dose hyper-radiosensitivity.” Modelling from cell-line and normal tissue data would indicate that if 0.5 Gy per fraction is given three times per day, seven days a week, to a total dose of 73.5 Gy, this would achieve local tumour control equivalent to 140 Gy whilst the late damage would be equivalent to that given to a total dose of 63 Gy at 2 Gy per fraction. This biological data has stimulated clinical investigation into low dose hyper-radiosensitivity at Mount Vernon. Objective: To translate the concept of low dose hyper-radiosensitivity into the clinic studying normal tissue and radioresistant tumour nodules in a phase I study.

and achieve

“proof

of principle”

by

Methods: 1) Normal tissue: Normal skin is irradiated at different dose levels in patients receiving routine radiotherapy for prostate. gynaecological. oesophageal or bronchial carcinomas. The dose levels being investigated currently are: 0.5 Gy versus 1 Gy and 0.5 Gy versus 1.5 Gy. The effect on skin is assessed by measuring basal cell density, erythema and pigmentation and skin conductance, during treatment and in follow up. 2) Tumours: Patients with skin nodules from radioresistant tumours who have failed all other forms of treatment are included in this phase I trial. Currently we are looking towards irradiating patients with multiple skin nodules of malignant melanoma. The skin nodules are ranked by size and randomised to two different fractionation schedules: 1.5 Gy per day versus 0.5 Gy tds, both to a total of 18 Gy, treating 7 days per week. The size of the tumour is measured before, during and after radiotherapy and growth delay curves constructed.