Radiotherapy and radiosurgery for meningiomas.

Meningiomas comprise a histologically and clinically diverse set of tumors arising from the meningothelial lining of the central nervous system. In the past decade, remarkable progress has been made in deciphering the biology of these common neoplasms. Nevertheless, effective systemic or molecular therapies for meningiomas remain elusive and are active areas of preclinical and clinical investigation. Thus, standard treatment modalities for meningiomas are limited to maximal safe resection, radiotherapy, or radiosurgery. This review examines the history, clinical rationale, and future directions of radiotherapy and radiosurgery as integral and effective treatments for meningiomas.

The Rationale for Radiation Therapy in Alzheimer's Disease.

Alzheimer's Disease (AD) represents a major health problem without effective treatments. As the incidence of the disease will continue to rise, it is imperative to find new treatment options to halt or slow disease progression. In recent years, several groups have begun to study the utility of low total dose radiation therapy (LTDRT) to inhibit some of the pathological features of AD and improve cognition in a variety of animal models. These preclinical studies have led to Phase 1 and 2 trials in different centers around the world. In this review, we present and interpret the pre-clinical evidence report some preliminary clinical data from a Phase 2 trial in early-stage AD patients.

Low-Dose Whole Brain Radiation Therapy for Alzheimer's Dementia: Results From a Pilot Trial in Humans.

PURPOSE: We report neurocognitive, imaging, ophthalmologic, and safety outcomes following low-dose whole brain radiation therapy (LD-WBRT) for patients with early Alzheimer dementia (eAD) treated in a pilot trial. METHODS AND MATERIALS: Trial-enrolled patients were at least 55 years of age, had eAD meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) Alzheimer's Criteria with confirmatory fluorodeoxyglucose and florbetapir positron emission tomography findings; had the capacity to complete neurocognitive function, psychological function, and quality-of-life assessments; had a Rosen modified Hachinski score ≤4; and had estimated survival >12 months. RESULTS: Five patients were treated with LD-WBRT (2 Gy × 5 over 1 week; 3 female; mean age, 73.2 years [range, 69-77]). Four of 5 patients had improved (n = 3) or stable (n = 1) Mini-Mental State Examination (second edition) T-scores at 1 year. The posttreatment scores of all 3 patients who improved increased to the average range. There were additional findings of stability of naming and other cognitive skills as well as stability to possible improvement in imaging findings. No safety issues were encountered. The only side effect was temporary epilation with satisfactory hair regrowth. CONCLUSIONS: Our results from 5 patients with eAD treated with LD-WBRT (10 Gy in 5 fractions) demonstrate a positive safety profile and provide preliminary, hypothesis-generating data to suggest that this treatment stabilizes or improves cognition. These findings will require further evaluation in larger, definitive, randomized trials.

Low-risk meningioma: Initial outcomes from NRG Oncology/RTOG 0539.

BACKGROUND: Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation reportedly exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539. METHODS: This phase II trial allocated patients to one of three groups per World Health Organization grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 3. RESULTS: Among 60 evaluable patients, the median follow-up was 9.1 years. The 3-, 5-, and 10-year rates were 91.4% (95% CI, 84.2 to 98.6), 89.4% (95% CI, 81.3 to 97.5), 85.0% (95% CI, 75.3 to 94.7) for PFS and 98.3% (95% CI, 94.9 to 100), 98.3%, (95% CI, 94.9 to 100), 93.8% (95% CI, 87.0 to 100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported one grade 3, four grade 2, and five grade 1 AEs. There were no grade 4 or 5 AEs. CONCLUSIONS: These results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.

Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.

Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.

High dose brachytherapy as monotherapy for intermediate risk prostate cancer.

PURPOSE: We evaluated our retrospective, single institution experience with high dose rate brachytherapy as monotherapy for intermediate risk prostate cancer. MATERIALS AND METHODS: Our cohort included 284 patients with intermediate risk prostate cancer, defined as clinical stage T2b/T2c, Gleason score 7 and/or prostate specific antigen 10 to 20 ng/ml, and 1-year minimum followup. Treatment was 2 high dose rate brachytherapy sessions at 3 fractions of 6.5 Gy each for a mean of 19 days. Prostate specific antigen failure was defined as nadir +2 ng/ml. RESULTS: Mean followup was 35.1 months (median 31.9). Actuarial 5-year cause specific survival and clinical local control were 100%, distant-metastasis-free survival 98.8% and biochemical disease-free survival 94.4%. Clinical stage predicted biochemical disease-free survival. For stage T2a or less 5-year biochemical disease-free survival was 95.1% vs 100% for stage T2b and 77.4% for T2c (p = 0.012). Percent positive biopsy cores and prostate specific antigen nadir were also predictive. International Prostate Symptom Score results remained stable and potency was maintained in 82.6% of patients at 2 years. Pads were used for the first time after brachytherapy in 22 patients (7.7%), mostly for grade 1 incontinence (occasionally or less per week). Excluding patients with prior transurethral prostatectomy, stroke or tremor 2.5% used pads for the first time after treatment. No patient had urethral stricture. Radiation Therapy Oncology Group grade 1 rectal toxicity developed in 12 patients (4.2%) but not beyond grade 1. CONCLUSIONS: High dose rate brachytherapy as monotherapy is safe and effective for patients with intermediate risk prostate cancer. We recommend caution for percent positive biopsy cores exceeding 75% or clinical stage T2c. Excluding such patients the 5-year biochemical disease-free survival rate was 97.5%.

Long-Term Report of a Comprehensive Molecular and Genomic Analysis in NRG Oncology/RTOG 0424: A Phase II Study of Radiation and Temozolomide in High-Risk Grade II Glioma.

PURPOSE: This study sought to determine the prognostic significance of the WHO-defined glioma molecular subgroups along with additional alterations, including MGMT promoter methylation and mutations in ATRX, CIC, FUBP1, TERT, and TP53, in NRG/RTOG 0424 using long-term follow-up data. METHODS: Mutations were determined using an Ion Torrent sequencing panel. 1p/19q co-deletion and MGMT promoter methylation were determined by Affymetrix OncoScan and Illumina 450K arrays. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios were calculated using the Cox proportional hazard model. Multivariable analyses (MVAs) included patient pretreatment characteristics. RESULTS: We obtained complete molecular data to categorize 80/129 eligible patients within the WHO subgroups. Of these, 26 (32.5%) were IDHmutant/co-deleted, 28 (35%) were IDHmutant/non-co-deleted, and 26 (32.5%) were IDHwild-type. Upon single-marker MVA, both IDHmutant subgroups were associated with significantly better OS and PFS (P values < .001), compared with the IDHwild-type subgroup. MGMT promoter methylation was obtained on 76 patients, where 58 (76%) were methylated and 18 (24%) were unmethylated. Single-marker MVAs demonstrated that MGMT promoter methylation was statistically significant for OS (P value < .001) and PFS (P value = .003). In a multimarker MVA, one WHO subgroup comparison (IDHmutant/co-deleted v IDHwild-type) was significant for OS (P value = .045), whereas MGMT methylation did not retain significance. CONCLUSION: This study reports the long-term prognostic effect of the WHO molecular subgroups, MGMT promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and MGMT both serve as strong prognostic indicators, but that MGMT does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond IDH and 1p/19q status.

High-risk Meningioma: Initial Outcomes From NRG Oncology/RTOG 0539.

BACKGROUND: Phase 2 cooperative group meningioma trial assessing the safety and efficacy of risk-adaptive management strategies. This is the initial analysis of the high-risk cohort. METHODS AND MATERIALS: High-risk patients were those with a new or recurrent World Health Organization (WHO) grade III meningioma of any resection extent, recurrent WHO grade II of any resection extent, or new WHO grade II after subtotal resection. Patients received intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique (60 Gy high dose and 54 Gy low dose in 30 fractions). Three-year progression-free survival (PFS) was the primary endpoint. Adverse events (AEs) were scored per NCI Common Terminology Criteria for Adverse Events version 3. RESULTS: Of 57 enrolled patients, 53 received protocol treatment. Median follow-up was 4.0 years (4.8 years for living patients). Two patients withdrew without progression before year 3; for the remaining 51 patients, 3-year PFS was 58.8%. Among all 53 protocol-treated patients, 3-year PFS was 59.2%. Three-year local control was 68.9%, and overall survival was 78.6%. Of 51 patients, 1 patient (1.9%) experienced a late grade-5 necrosis-related AE. All other acute (23 of 53 patients) and late (21 of 51 patients) AEs were grades 1 to 3. CONCLUSIONS: Patients with high-risk meningioma treated with IMRT (60 Gy/30) experienced 3-year PFS of 58.8%. Combined acute and late AEs were limited to grades 1 to 3, except for a single necrosis-related grade 5 event. These results support postoperative IMRT for high-risk meningioma and invite ongoing investigations to improve outcomes further.

Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424.

PURPOSE: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). METHODS AND MATERIALS: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. RESULTS: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P < .001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. CONCLUSIONS: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

Pathology concordance levels for meningioma classification and grading in NRG Oncology RTOG Trial 0539.

BACKGROUND: With advances in the understanding of histopathology on outcome, accurate meningioma grading becomes critical and drives treatment selection. The 2000 and 2007 WHO schema greatly increased the proportion of grade II meningiomas. Although associations with progression-free survival (PFS) and overall survival (OS) have been independently validated, interobserver concordance has not been formally assessed. METHODS: Once mature, NRG Oncology RTOG-0539 will report PFS and OS in variably treated low-, intermediate-, and high-risk cohorts. We address concordance of histopathologic assessment between enrolling institutions and central review, performed by a single pathologist (AP), who is also involved in developing current WHO criteria. RESULTS: The trial included 170 evaluable patients, 2 of whom had 2 eligible pathology reviews from different surgeries, resulting in 172 cases for analysis. Upon central review, 76 cases were categorized as WHO grade I, 71 as grade II, and 25 as grade III. Concordance for tumor grade was 87.2%. Among patients with WHO grades I, II, and III meningioma, respective concordance rates were 93.0%, 87.8%, and 93.6% (P values < .0001). Moderate to substantial agreement was encountered for individual grading criteria and were highest for brain invasion, ≥20 mitoses/10 high-powered field [HPF], and spontaneous necrosis, and lowest for small cells, sheeting, and ≥4 mitoses/10 HPF. In comparison, published concordance for gliomas in clinical trials have ranged from 8%-74%. CONCLUSION: Our data suggest that current meningioma classification and grading are at least as objective and reproducible as for gliomas. Nevertheless, reproducibility remains suboptimal. Further improvements may be anticipated with education and clarification of subjective criteria, although development of biomarkers may be the most promising strategy.

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases.

PURPOSE: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. METHODS: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), and the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. RESULTS: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. CONCLUSIONS: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma.

PURPOSE: To systematically review the evidence for the use of stereotactic radiosurgery or stereotactic fractionated radiation therapy in adult patients with malignant glioma. METHODS: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (1997-2004), ASTRO (1997-2004), and the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. RESULTS: For patients with newly diagnosed malignant glioma, radiosurgery as boost therapy with conventional external beam radiation was examined in one randomized trial, five prospective cohort studies, and seven retrospective series. There is Level I evidence that the use of radiosurgery boost followed by external beam radiotherapy and carmustine (BCNU) does not confer benefit with respect to overall survival, quality of life, or patterns of failure as compared with external beam radiotherapy and BCNU. There is Level I-III evidence of toxicity associated with radiosurgery boost as compared with external beam radiotherapy alone. The results of the prospective and retrospective studies may be influenced by selection bias. Radiosurgery used as salvage for recurrent or progressive malignant glioma after conventional external beam radiotherapy failure was reported in zero randomized trials, three prospective cohort studies, and five retrospective series. The available data are sparse and insufficient to make absolute recommendations. Stereotactic fractionated radiation therapy has been reported as boost therapy with external beam radiotherapy for patients with newly diagnosed malignant glioma in only three prospective studies. As primary therapy alone without conventional external beam radiotherapy for newly diagnosed malignant glioma patients, stereotactic fractionated radiation therapy has been reported in only one prospective study. There were only three prospective series and two retrospective studies reported for patients with recurrent or progressive malignant glioma. CONCLUSIONS: For patients with malignant glioma, there is Level I-III evidence that the use of radiosurgery boost followed by external beam radiotherapy and BCNU does not confer benefit in terms of overall survival, local brain control, or quality of life as compared with external beam radiotherapy and BCNU. The use of radiosurgery boost is associated with increased toxicity. For patients with malignant glioma, there is insufficient evidence regarding the benefits/harms of using radiosurgery at the time progression or recurrence. There is also insufficient evidence regarding the benefits/harms in the use of stereotactic fractionated radiation therapy for patients with newly diagnosed or progressive/recurrent malignant glioma.

Surgery and permanent 125I seed paraspinal brachytherapy for malignant tumors with spinal cord compression.

PURPOSE: To evaluate the functional outcome, predictors of response, and toxicity from spinal surgery and 125I brachytherapy in patients with malignant tumors resulting in spinal cord compression. METHODS AND MATERIALS: Between July 1985 and September 2001, after surgical resection, 30 patients underwent 31 intraoperative paraspinal brachytherapy procedures at Barrow Neurological Institute. Twenty-four (with 25 procedures) had follow-up at our clinic and form the basis for this report. Surgical procedures were based on the location of the impinging lesion: corpectomy or spondylectomy in 13 cases and laminectomy in 12. Permanent 125I seeds in absorbable suture were placed with open exposure after resection. RESULTS: Spinal cord compression was cervical in 4 (16%), thoracic in 14 (56%), and lumbar in 7 (28%) of the 25 cases. One patient underwent two separate procedures at different spinal sites. Of the 25 brachytherapy sites, 22 also received external beam radiotherapy (EBRT): 5, EBRT with a planned brachytherapy boost; 4, brachytherapy and prompt EBRT after recovery; and 13, brachytherapy as salvage for local failure after prior EBRT. Three had no EBRT: 1 had lymphoma treated with chemotherapy, 1 had remote previous EBRT for a childhood tumor, and 1 refused EBRT. The mean follow-up was 19.8 months. The 2- and 3-year actuarial local control rate was 87.4% and 72.9%, respectively. Four sites (16.0%) experienced local failure. The mean time to recurrence for these 4 patients was 20.3 months. Three of the four had failed prior EBRT, with surgery and brachytherapy used for salvage. The 2- and 3-year actuarial overall survival rates were 24.0% and 16.0%, mean 19.2 months. An ambulatory function score was assigned pre- and postoperatively: I, normal ambulation; II, abnormal not requiring assistance; III, abnormal requiring assistance; and IV, unable to ambulate. All patients with score I, 91% of those with score II, 67% of those with score III, and 67% of those with score IV were ambulatory after the procedure; 84% had either normal or improved ambulation postoperatively. Morbidity was restricted to four postoperative events: one cerebrospinal fluid leak, two wound infections treated in situ without removal of seeds or instrumentation, and one pulmonary embolus. No myelopathies or other neurologic sequelae were encountered. CONCLUSION: This is the largest series in the literature exploring surgery and 125I brachytherapy in the treatment of malignant spinal cord compression. We found this to be well tolerated and to result in durable local control and ambulatory function. Our results suggest a benefit to aggressive local therapy in selected patients with spinal cord compression.

Gamma knife radiosurgery for recurrent trigeminal neuralgia.

OBJECT: Pain may fail to respond or may recur after initial gamma knife radiosurgery (GKS) for trigeminal neuralgia (TN). The authors examined their experience with performing a second GKS procedure in these patients. METHODS: Twenty-nine patients underwent repeated GKS for TN at our institution between March 1997 and March 2002. Questionnaires were mailed to patients to assess the degree of their pain relief and the extent of facial numbness. Nineteen patients responded. All patients underwent repeated GKS involving a single 4-mm isocenter directed at the trigeminal nerve as it exited the brainstem (mean maximum dose 23.2 Gy). At a mean follow up of 13.5 months after the second procedure, 10 patients (53%) were pain free and medication free. Four patients (21%) were pain free but elected to continue medication in reduced dose, and two patients (11%) had incomplete but satisfactory pain control and were still taking medication. There was new-onset facial numbness in eight patients (42%), rated as tolerable in all instances. CONCLUSIONS: Patients with facial numbness had a greater likelihood of being pain free than those with no sensory loss. The authors observed no cases of corneal anesthesia, keratitis, or deafferentation pain.

Gamma knife radiosurgery for trigeminal neuralgia associated with multiple sclerosis.

OBJECT: The authors assessed the efficacy and complications from gamma knife radiosurgery (GKS) for multiple sclerosis (MS)-associated trigeminal neuralgia (TN). METHODS: There were 15 patients with MS-associated TN (MS-TN). Treatment involved three sequential protocols, 70 to 90-Gy maximum dose, using a single 4-mm isocenter targeting the ipsilateral trigeminal nerve at its junction with the pons with the 50% isodose. Pain was appraised by each patient by using Barrow Neurological Institute (BNI) Scores I through IV: I, no pain; II, occasional pain not requiring medication; IIIa, no pain but continued medication; IIIb, some pain, controlled with medication; IV, some pain, not controlled with medication; and V, severe pain/no pain relief. With a mean follow up of 17 months (range 6-38 months), 12 (80%) of 15 patients experienced pain relief. Three patients (20%) reported no relief (BNI Score V). For responders, the mean latency from treatment to the onset of pain relief was 13 days (range 1-61 days). Maximal relief was achieved after a mean latency of 56 days (range 1-157 days). Five patients underwent a second GKS after a mean interval of 534 days (range 231-946 days). The mean maximum dose at this second treatment was 48 Gy. The target was unchanged from the first treatment. All five patients who underwent repeated GKS improved. Complications were limited to delayed facial hypesthesias. Two (13%) of 15 patients experienced onset of numbness after the first GKS, as well as two of five patients following a second GKS. The patients found this mild and not bothersome. Each patient who developed hypesthesias also experienced complete pain relief. CONCLUSIONS: Gamma knife radiosurgery is an effective treatment for MS-TN. Radiosurgery carries an acceptable small risk of mild facial hypesthesias, and hypesthesia appears predictive of a favorable outcome.