Peter Varady, Jason Sheehan, Melita Steiner and Ladislau Steiner
Heading : Chun Po Yen
Subtotal obliteration of cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS) implies a complete angiographic disappearance of the AVM nidus but persistence of an early filling draining vein, indicating that residual shunting is still present; hence, per definition there is still a patent AVM and the risk of bleeding is not eliminated. The aim of this study was to determine the risk of hemorrhage for patients with subtotal obliteration of AVMs.
After GKS for cerebral AVMs, follow-up angiography demonstrated a subtotally obliterated lesion in 159 patients. Of these, in 16 patients a subtotally obliterated AVM developed after a second GKS was performed for the partially obliterated lesion. The mean age of these patients was 35.2 years at the time of the diagnosis of subtotally obliterated AVMs. The lesion volumes at the time of initial GKS treatment ranged from 0.1 to 11.5 cm3 (mean 2.5 cm3). The mean peripheral dose used in the 175 GKS treatments was 22.5 Gy (median 23 Gy, range 15–31 Gy). To achieve total obliteration of the AVM, 23 patients underwent a new GKS targeting the proximal end of the early filling vein. The mean peripheral dose given in these cases was 23 Gy (median 24, range 18–25 Gy).
The incidence of subtotally obliterated AVMs was 7.6% from a total of 2093 AVMs treated and in which follow-up imaging was available. The diagnosis of subtotally obliterated AVMs was made a mean of 29.4 months (range 4–178 months) after GKS. The number of patient-years at risk (from the time of the diagnosis of subtotally obliterated AVMs until either the confirmation of a total obliteration of the lesion on angiography or the time of the latest follow-up angio-graphic study that still visualized the early filling vein) was a mean of 3.9 years, ranging from 0.5 to 13.5 years, and a total of 601 patient-years. There was no case of bleeding after the diagnosis of subtotally obliterated AVMs. Of 90 patients who did not undergo further treatment and in whom follow-up angiography studies were available, the same early filling veins still filled in 24 (26.7%), and the subtotally obliterated AVMs were subsequently obliterated in 66 patients (73.3%). In 19 patients who underwent repeated GKS for subtotally obliterated AVMs and in whom follow-up angiography studies were available, the AVMs were obliterated in 15 (78.9%) and remained patent in four (21.1%).
The fact that none of the patients with subtotally obliterated AVMs suffered a rupture is not compatible with the assumption of an unchanged risk of hemorrhage for these lesions, and implies that the protection from re-bleeding in patients with subtotal obliteration is significant. Subtotal obliteration does not necessarily seem to be a stage of an ongoing obliteration. At least in some cases it represents an end point of this process, with no subsequent obliteration occurring. This observation requires further confirmation by open-ended follow-up imaging.
Chun Po Yen, Jason Sheehan, Melita Steiner, Greg Patterson and Ladislau Steiner
Focal tumors, a distinct subgroup of which is composed of brainstem gliomas, may have an indolent clinical course. In the past, their management involved monitoring of open-ended imaging studies and shunt placement if cerebrospinal fluid diversion was required. Nonetheless, their treatment remains a significant challenge for neurosurgeons. Gamma Knife surgery (GKS) has recently been tried as an alternative to surgical extirpation. In the present study the authors assess clinical and imaging results in 20 patients who harbored focal brainstem gliomas treated with GKS between 1990 and 2001.
There were 10 male and 10 female patients with a mean age of 19.1 years. Sixteen tumors were located in the midbrain, three in the pons, and one in the medulla oblongata. The mean tumor volume at the time of GKS was 2.5 cm3. In 10 cases a tumor specimen was obtained either by open surgery or stereotactic biopsy, securing the diagnosis of pilocytic astrocytoma in five patients and nonpilocytic astrocytoma in five others. In the remaining 10 cases, the diagnosis was based on clinical and neuroimaging findings. The prescription Gamma Knife dose varied between 10 and 18 Gy, except in three patients who were receiving a boost to a site in which external-beam radiation was previously delivered. An average of four isocenters were utilized per GKS.
Patients were followed up for a mean of 78.0 months. The tumors disappeared in four patients and shrank in 12 patients. Of these patients, one experienced transitory extrapyramidal symptoms and fluctuating impairment of consciousness (from somnolence to coma) for 6 months. Another patient whose tumor disappeared 3 years following GKS died of stroke 8 years postoperatively. The rest of the patients either remained stable or improved clinically. Tumor progression occurred in four patients; of these four, one patient developed hydrocephalus requiring a ventriculoperitoneal shunt, two showed neurological deterioration, and one 4-year-old boy died of tumor progression.
Gamma Knife surgery may be an effective primary treatment or adjunct to open surgery for focal brainstem gliomas.
Vincenzo Mingione, Chun Po Yen, Mary Lee Vance, Melita Steiner, Jason Sheehan, Edward R. Laws and Ladislau Steiner
The authors report on a retrospective analysis of the imaging and clinical outcomes following gamma surgery in 100 patients with nonsecretory pituitary macroadenoma.
Between June 1989 and March 2004, 100 consecutive patients with nonsecretory pituitary macroadenoma were treated at the Lars Leksell Center for Gamma Surgery, University of Virginia Health System (Charlottesville, VA). Ninety-two patients had residual or recurrent macroadenoma following one or more surgical procedures. In eight patients, gamma surgery was the primary treatment. Ten patients received conventional fractionated radiotherapy before the gamma surgery. Sixty-nine patients required hormone replacement therapy for one or more deficits before gamma knife treatment. Peripheral doses between 5 and 25 Gy (mean 18.5 Gy) were administered.
Imaging and endocrinological follow-up evaluations were performed in 90 patients; these studies ranged from 6 to 142 months (mean 44.9 months) and 6 to 127 months (mean 47.9 months), respectively. Tumor volume decreased in 59 patients (65.6%), remained unchanged in 24 (26.7%), and increased in seven (7.8%). The minimal effective peripheral dose was 12 Gy; peripheral doses greater than 20 Gy did not seem to provide additional benefit. Of 61 patients with a partially or fully functioning pituitary gland and follow-up data, 12 (19.7%) suffered new hormone deficits following gamma surgery. In patients with endocrinological follow-up data that had been collected over more than 2 years, the rate of new deficits was 25%. No neurological morbidity or death was related to treatment.
Current experience suggests that gamma surgery is an appropriate means of managing recurrent or residual nonsecretory pituitary macroadenoma following microsurgery and a primary treatment in selected patients. To evaluate definite rates of recurrence and new endocrine deficiencies, long-term follow-up studies are needed.
Hung-Chuan Pan, Jason Sheehan, Matei Stroila, Melita Steiner and Ladislau Steiner
Object. The authors conducted a study to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of brain metastases from lung cancer.
Methods. Between February 1993 and May 2003 191 patients underwent treatment for 424 brain metastases from non—small (171 cases) and small cell lung carcinoma (20 cases). Imaging and clinical status were monitored every 3 months following the treatment. Kaplan-Meier survival curves, Cox proportional hazards regression for risk factor analysis, and nonparametric methods for evaluating tumor response were used.
There was no difference in median survival following combined whole-brain radiation therapy (WBRT) and gamma knife surgery (14 months) and GKS alone (15 months). There was also no difference between the median survival rates for either tumor type. In the multivariate analysis, age less than 65 years, Karnofsky Performance Scale score greater than 70, normal neurological status, multiple GKS treatments, and pre-GKS craniotomy were related to longer survival.
Tumor control rates varied according to the volume of the metastases and were as follows: 84.4% (< 0.5 cm3), 94% (0.5–2 cm3), 89.1% (2–4 cm3), 93.4% (4–8 cm3), 85.7% (8–14 cm3), and 87.5% (> 14 cm3). Four lesions required post-GKS craniotomy due to swelling or rapid tumor progression. The rate of tumor shrinkage was higher when a volume was 2 cm3, lower in cystic lesions, lower in tumors with previous WBRT, and lower for margin doses less than 14 Gy.
Conclusions. The risk—benefit ratio of GKS in this series was satisfactory. There was no difference in response rates of the two tumor types, and WBRT did not improve the duration of survival.
Hung-Chuan Pan, Jason Sheehan, Matei Stroila, Melita Steiner and Ladislau Steiner
Object. The authors present data concerning the development of cysts following gamma knife surgery (GKS) in 1203 consecutive patients with arteriovenous malformations (AVMs) treated by the senior author (L.S.). The cyst was defined as a fluid-filled cavity at the site of a treated AVM. Cases involving regions corresponding to previous hematoma cavities were excluded. The incidence of cyst formation was assessed using magnetic resonance imaging studies performed in 196 cases with more than 10 years of follow up, in 332 cases with 5 to 10 years of follow up, and in 675 cases with less than 5 years of follow up. One hundred five cases were lost to follow-up study. The Cox regression method was used to analyze the factors related to cyst formation.
Methods. The incidence of cyst formation in the entire patient population was 1.6 and 3.6% in those undergoing follow-up examination for more than 5 years. Ten of 20 cysts developed between 10 to 23 years, nine between 5 to 10 years, and one in less than 5 years following the treatment. Cyst fluid aspiration, cystoperitoneal shunt placement, or craniotomy were used in three symptomatic cases. Analysis of age, sex, and treatment parameters yielded no significant relationship with cyst formation; however, radiation-induced tissue change following GKS (p = 0.027) and prior embolization (p = 0.011) were related to cyst formation.
Conclusions. Overall, the incidence of cyst formation in patients who underwent GKS for AVM was 1.6%. The development of the cyst was related to the duration of the follow-up period. When cysts are symptomatic, surgical intervention should be performed.