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Jesse Jones, Sunyoung Jang, Christopher C. Getch, Alan G. Kepka and Maryanne H. Marymont

✓ Radiosurgery has proven useful in the treatment of small arteriovenous malformations (AVMs) of the brain. However, the volume of healthy tissue irradiated around large lesions is rather significant, necessitating reduced radiation doses to avoid complications. As a consequence, this can produce poorer obliteration rates. Several strategies have been developed in the past decade to circumvent dose–volume problems with large AVMs, including repeated treatments as well as dose, and volume fractionation schemes. Although success on par with that achieved in lesions smaller than 3 ml remains elusive, improvements over the obliteration rate, the complication rate or both have been reported after conventional single-dose stereotactic radiosurgery (SRS). Radiosurgery with a marginal dose or peripheral dose < 15 Gy rarely obliterates AVMs, yet most lesions diminish in size posttreatment. Higher doses may then be reapplied to any residual nidi after an appropriate follow-up period. Volume fractionation divides AVMs into smaller segments to be treated on separate occasions. Doses > 15 Gy irradiate target volumes of only 5–15 ml, thereby minimizing the radiation delivered to the surrounding brain tissue. Fewer adverse radiological effects with the use of fractionated radiosurgery over standard radiosurgery have been reported. Advances in AVM localization, dose delivery, and dosimetry have revived interest in hypofractionated SRS. Investigators dispensing ≥ 7 Gy per fraction minimum doses have achieved occlusion with an acceptable number of complications in 53–70% of patients. The extended latency period between treatment and occlusion, about 5 years for emerging techniques (such as salvage, staged volume, and hypofractionated radiotherapy), exposes the patient to the risk of hemorrhage during that period. Nevertheless, improvements in dose planning and target delineation will continue to improve the prognosis in patients harboring inoperable AVMs.

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Yannick Grenier, Tadanori Tomita, MaryAnne H. Marymont, Sharon Byrd and Delilah M. Burrowes

✓ The authors report two cases of ischemic stroke secondary to occlusive vasculopathy two decades after radiation therapy (RT) for medulloblastoma. Both patients underwent posterior fossa medulloblastoma partial resection, followed by craniospinal RT in which a cobalt 60 source was used; 40 Gy were given to the whole brain plus a 15-Gy boost to the posterior fossa. Both patients received multiagent chemotherapy, immediately following radiation therapy in the first case and after repeated craniotomy for recurrence 13 years after radiation in the second case. They experienced multiple sequelae from radiation and chemotherapy, including growth retardation and psychomotor delay. However, 20 years after treatment, they remained tumor free and able to work, until they presented with focal neurological deficits and seizures. Computerized tomography and magnetic resonance imaging of the brain in both cases showed no tumor recurrence, but did demonstrate ischemia in a posterior cerebral artery distribution. Cerebral angiography revealed multiple mid-sized arterial wall irregularities as well as focal stenoses consistent with a postirradiation vasculopathy. The pathophysiological mechanisms, radiological appearance, and incidence of this syndrome are reviewed from the literature.

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Ania G. Pollack, MaryAnne H. Marymont, John A. Kalapurakal, Alan Kepka, Vythialingam Sathiaseelan and James P. Chandler

✓ The authors describe an acute facial and acoustic neuropathy following gamma knife surgery (GKS) for vestibular schwannoma (VS). This 39-year-old woman presenting with tinnitus underwent GKS for a small right-sided intracanalicular VS, receiving a maximal dose of 26 Gy and a tumor margin dose of 13 Gy to the 50% isodose line. Thirty-six hours following treatment she presented with nausea, vomiting, vertigo, diminished hearing, and a House—Brackmann Grade III facial palsy. She was started on intravenous glucocorticosteroid agents, and over the course of 2 weeks her facial function returned to House—Brackmann Grade I. Unfortunately, her hearing loss persisted. A magnetic resonance (MR) image obtained at the time of initial deterioration demonstrated a significant decrease in tumor enhancement but no change in tumor size or peritumoral edema. Subsequently, the patient experienced severe hemifacial spasms, which persisted for a period of 3 weeks and then progressed to a House—Brackmann Grade V facial palsy. During the next 3 months, the patient was treated with steroids and in time her facial function and hearing returned to baseline levels. Results of MR imaging revealed transient enlargement (3 mm) of the tumor, which subsequently returned to its baseline size. This change corresponded to the tumor volume increase from 270 to 336 mm3. The patient remains radiologically and neurologically stable at 10 months posttreatment.

This is the first detailed report of acute facial and vestibulocochlear neurotoxicity following GKS for VS that improved with time. In addition, MR imaging findings were indicative of early neurotoxic changes. A review of possible risk factors and explanations of causative mechanisms is provided.

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Timothy R. Smith, Rohan R. Lall, Rishi R. Lall, Isaac Josh Abecassis, Omar M. Arnaout, MaryAnne H. Marymont, Kristin R. Swanson and James P. Chandler

Object

Patients with systemic cancer and a single brain metastasis who undergo treatment with resection plus radiotherapy live longer and have a better quality of life than those treated with radiotherapy alone. Historically, whole-brain radiotherapy (WBRT) has been the mainstay of radiation therapy; however, it is associated with significant delayed neurocognitive sequelae. In this study, the authors looked at survival in patients with single and multiple intracranial metastases who had undergone surgery and adjuvant stereotactic radiosurgery (SRS) to the tumor bed and synchronous lesions.

Methods

The authors retrospectively reviewed the records from an 8-year period at a single institution for consecutive patients with brain metastases treated via complete resection of dominant lesions and adjuvant radiosurgery. The cohort was analyzed for time to local progression, synchronous lesion progression, new intracranial lesion development, systemic progression, and overall survival. The Kaplan-Meier method (stratified by age, sex, tumor histology, and number of intracranial lesions prior to surgery) was used to calculate both progression-free and overall survival. A Cox proportional-hazards regression model was also fitted with the number of intracranial lesions as the predictor and survival as the outcome controlling for disease severity, age, sex, and primary histology.

Results

The median overall follow-up among the 150-person cohort eligible for analysis was 17 months. Patients had an average age of 46.2 years (range 16–82 years), and 62.7% were female. The mean (± standard deviation) number of intracranial lesions per patient was 2.5 ± 2.3. The mean time between surgery and stereotactic radiosurgery (SRS) was 3.2 ± 4.1 weeks. Primary cancers included lung cancer (43.3%), breast cancer (21.3%), melanoma (10.0%), renal cell carcinoma (6.7%), and colon cancer (6.7%). The average number of isocenters per treated lesion was 7.6 ± 6.6, and the average treatment dose was 17.8 ± 2.8 Gy. One-year survival for patients in this cohort was 52%, and the 1-year local control rate was 77%. The median (±standard error) overall survival was 13.2 ± 1.9 months. There was no difference in survival between patients with a single lesion and those with multiple lesions (p = 0.319) after controlling for age, sex, and histology of primary tumor. Patients with primary breast histology had the greatest overall median survival (22.9 ± 6.2 months); patients with colorectal cancer had the shortest overall median survival (5.3 ± 1.8 months). The most common cause of death in this series was systemic progression (79%).

Conclusions

These results confirm that 1-year survival for patients with multiple intracranial metastases treated with resection followed by SRS to both the tumor bed and synchronous lesions is similar to established outcomes for patients with a single intracranial metastasis.