title: Stereotactic radiosurgery XII. Large AVM and the failure of the radiation response modifier gamma linolenic acid to improve the therapeutic ratio.
abstract: Large arteriovenous malformations (AVM) are less likely to be 'cured' by single fraction stereotactically delivered radiation therapy (radiosurgery) and such treatment is attended by higher complication risks. Out of 200 successive AVM patients accepted for curative radiosurgery at St. Bartholomew's Hospital (and all treated by the same 6MV x-ray technique to 17.5 Gy marginal dose) were 62 patients whose target volume exceeded 10 ml. Laboratory data demonstrating that gamma linolenic [omega-6-] acid (GLA) protected rat spinal cord from the damaging effect of single shot radiation prompted this study which employed GLA in conjunction with radiosurgery for large AVM. Without GLA, 41% of large AVM obliterated, but in the GLA treated cohort the obliteration rate was only 5.3% (p < 0.02). The permanent complication rates in the same patient groups were 20% versus 0%, respectively. There was a small skew to smaller volume 'large AVM' in the GLA treated cohort. This fact strengthens the conclusion concerning a difference for AVM obliteration, but could lead to a false conclusion quae GLA modulation of complications. When four patients were censored to minimize this possible bias, the risk for complications in the GLA treated patients was still significantly (p < 0.05), less than in the control group. We therefore conclude: (1) GLA spares AVM from radiation induced obliteration; (2) GLA modifies the response of normal human brain to radiation damage; (3) GLA does not improve the therapeutic ratio for AVM based radiosurgery; (4) GLA may have other uses (notably after radiation accidents and in radiation neuro-oncology, radiation cranial prophylaxis, chemoradiation protocols, whole brain radiation for metastases etc.).
authors: Department of Radiotherapy, St Bartholomew's Hospital, West Smithfield, London, UK.
authors: E C
authors: EC
authors: Sims
authors: P N
authors: PN
authors: Plowman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001165:Arteriovenous Malformations / Q000601:surgery*; D002543:Cerebral Hemorrhage / Q000209:etiology; D002648:Child; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000209:etiology; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods* / Q000592:standards; D012008:Recurrence; D017211:Treatment Failure; D017965:gamma-Linolenic Acid / Q000008:administration & dosage*
chemical_list: D011838:Radiation-Sensitizing Agents; D017965:gamma-Linolenic Acid