Proceedings of the 40th Annua l A S T R O Meeting

2091 IMPROVED NEUROPSYCHOLOGIC TEST RESULTS IN PATIENTS WITH ARTERIO-VENOUS MALFORMATION (AVM)

AFTER RADIOSURGERY Steinvorth S, Wenz F, Wildermuth S, FuB M, Lohr F, Essig M, Debus J, Wannenmacher M

University of Heidelberg and German Cancer Research Center, Heidelberg, Germany

Purpose/Objective: The purpose of this study was to investigate how radiosurgery changes IQ, attention and memory functions in patients with cerebral AVM in order to clarify whether potential normal tissue effects are balanced by the therapeutic effect of AVM occlusion. Materials & Methods: Seventy-nine patients (m = 42, f= 37, 37.5 -+ 13.7 yrs, 36 patients with history of intracerebral hemorrhage) were studied before, acutely after radiosurgery and during the regular follow-up (subacute phase week 6 - 12, chronic phase month 6 - 18). Radiosurgery was performed using a modified linear accelerator (minimum doses to the target volume: 15 - 22 Gy, median 20 Gy). Estimated whole brain dose was 05 to 2 Gy. Neuropsychological testing included assessment of general intelligence (Wechsler Adult Intelligence Scale), attention (modified Trail Making Test A, Digit Symbol Test, D2 Test, Wiener Determination Machine) and memory (Rey Auditory Verbal Learning Test I-V, Benton Visual Retention Test). During follow-up parallel test versions were used. To quantify the influence of hospitalisation and repeated testing on the test results, a group of 16 patients receiving radiotherapy to the pelvis were included into the study as well. Results:

n 79 35 35 35 14

IQ attention [mean percentile _+ SD] memory [mean percentile -+ SD] day0 95 _+ 13 40_+26 31 _+29 day 1 48 -+ 29 36 -+ 32 mon 3 53 + 29 37 + 36 mon 6 48 + 28 33 -+ 30 mort 12 103 + 14 55 _+25 51 +_32

The pretherapeutic evaluation (day 0) of AVM patients revealed marked deviations from the standard normal population (IQ = 100, attention = 50%, memory = 50%). One year after radiosurgery, there is a marked improvement of 8 points in IQ, of 15% in attention and of 20% in memory test results. The group of AVM patients was divided according to a history of previous intracerebral hemorrhage (n = 36) and no previous hemorrhage (n = 43). There was no difference in pretherapeutic test results between these two patient groups. However, one year after radiosurgery, the patients without history of hemorrhage showed slightly better test results of IQ (3 points) and memory functions (4°/'0) and markedly better scores in attention testing (22%) compared to the patients with previous hemorrhage. The results of the control group (IQ = 99 _+ 11, attention = 37 _+ 31, memory = 44 _+ 37) show that IQ and memory functions are not impaired by hospitalisation and that there is an improvement in attention function of about 10% due to practice effects during repeated testing.

Conclusion: Our data indicate that there is an impairment of neuropsychological functions in AVM patients before therapy, which can not be explained by hospitalisation and stress as shown by the results of the control group. There is a marked improvement in the overall neuropsychological performance of AVM patients one year after radiosurgey, which can not be explained by practice effects alone. Patients without previgus hemorrhage seem to show more improvement than patients with history ofintracerebral hemorrhage.

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2092 RADIATION INDUCED REGIONAL CEREBRAL BLOOD VOLUME (rCBV) CHANGES IN NORMAL BRAIN AND LOW GRADE ASTKOCYTOMA (WHO GRADE II): MONITORED BY DYNAMIC SUSCEPTIBILITY CONTRAST MR IMAGING (DSC-MRI)

Fuss M/ , Wenz F/ , Scholdei IL ~, Essig M. 2, Debus J / , Wannenmacher M)

1 Department of Radiation Ontology, University of Heidelberg, 2 Department of Radiology, German Cancer Research Center (dkfz), Heidelberg

Purpose: Irradiation of patients with brain tumors is limited by the radiosensitivity of normal brain tissue. Capillary vessel damage with consecutive occlusion has been attributed for chronic, late delayed radiation effects. Thus the time dependent occurence and severity of these reactions is of interest for the posttherapentic monitoring by assessment of blood volume. In low grade astrocytoma therapeutic effects are often not visible in conventional MRI because of limited response in tumor volume. DSC-MRI allows a functional in-vivo analysis of regional cerebral blood volume (rCBV). This technique monitors the passage of a contrast agent bolus through the cerebral capillary network. By normalizing to an arterial input fimktion (AIF), DSC-MPd can quantify blood volume and can be used for interpersonel comparison and follow-up studies. Material and methods: We performed DSC-MRI in 71 patients without evidence ofintracerebral disease for assessment of normal rCBV values. In 25 patients with a low grade astrocytoma (histologically WHO grade II, no contrast enhancement in MR:I) and 13 patients with brain metastases rCBV was evaluated before and after percutaneous radiation therapy. Fractionated stereotactic radiotherapy was performed in astrocytoma patients using a linear accelerator (6 MeV/15 MeV) and a multi-leaf collimator (leaf thickness 3mm). Total dose prescribed to the reference point was 60.9 Gy (55.8-66 Gy) at a daily dose of 1.8-2 Gy. The 90% isodose covered the entire target volume. 3D treatment plafis were used to define the prescribed dose in interesting areas. We defined low dose areas (doses<24 Gy) and high dose areas (dose<60 Cry). Whole brain irradiation (WBI) was performed in patients with brain metastases (total dose 30-40 Gy, daily dose 2-3 Gy). Mean follow-up was 19 months in astrocytoma patients and 15 months after WBI. DSC-MRI was performed at an standard 1.5T MR-system (SIEMENS Magnetom) with a modified SD-FLASH sequence. We acquired 55 T2*-weighted gradient echo images before, during and after intravenous bolus Gd-DTPA injection. Absolute ICBV values were calculated as area under the tissue concentration time curve in selected regions of interest (ROI) normalized to the AIF. Results: Normal rCBV was 8.4-+2.9 ml/100g brain tisme in grey matter and 4.2-+ 1.7 ml/100g in white matter (ratio grey/white: 2.1 _+0.6). After WBI rCBV was 6.3_+ 1.2 ml/100g and 3.1_+ 1 ml/100g for grey and white matter (ratio grey/white: 2). This rCBV reduction was measured within 6 months after therapy. After conformal radiotherapy rCBV reduction occured within 12 months limited to the irradiated volume with substantial sparing in low dose areas (30% in high dose areas, 24% in low dose areas). A plateau was reached after 12 months. In low grade astrocytoma reduction ofrCBV (initially 6.5 _+3.7 ml/100g, postherapentic 4.7_+1.3) was measured within 6 months after therapy. This level was stable over 24 months after therapy in patients with no evidence of tumor recurrence whereas in patients with recurrent tumor rCBV increased again to 7.2_+2.8 ml/100g. Conclusion: DSC-MRI is able to quantify radiation induced rCBV changes in normal brain matter and low grade astrocytoma and can be used for follow-up. The maximal decrease ofrCBV was found to be 30% in normal brain as in low grade astrocytoma. In low dose areas the decrease was less pronounced. Time dependent decrease of rCBV is related to fraction size and total dose. Especially in low grade astrocytoma this method can demonstrate the efficacy of radiation therapy and may be used as early predictor of tumor recurrence. Beside clinical outcome this method allows a functional assessment for follow-up examinations when the MRI (TI pre and post Gd, T2) often shows no change after radiation therapy. Initial reduction ofrCBV is no prognostic factor concerning the tendency for malignant transformation and recurrence.