Daniel R. Pieper

Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery

OBJECT The aim of this study was to examine tumor volume as a prognostic factor for patients with brain metastases treated with Gamma Knife surgery (GKS). METHODS Two hundred fifty patients with 1-14 brain metastases who had initially undergone GKS alone at a single institution were retrospectively reviewed. Patients who received upfront whole brain radiation therapy were excluded. Survival times were estimated using the Kaplan-Meier method. Univariate and multivariate analyses using Cox proportional hazard regression models were used to determine if various prognostic factors could predict overall survival, distant brain failure, and local control. RESULTS Median overall survival was 7.1 months and the 1-year local control rate was 91.5%. Median time to distant brain failure was 8.0 months. On univariate analysis an increasing total tumor volume was significantly associated with worse survival (p = 0.031) whereas the number of brain metastases, analyzed as a continuous variable, was not (p = 0.082). After adjusting for age, Karnofsky Performance Scale score, and extracranial disease on multivariate analysis, total tumor volume was found to be a better predictor of overall survival (p = 0.046) than number of brain metastases analyzed as a continuous variable (p = 0.098). A total tumor volume cutoff value of ≥ 2 cm(3) (p = 0.008) was a stronger predictor of overall survival than the number of brain metastases (p = 0.098). Larger tumor volume and extracranial disease, but not the number of brain metastases, were predictive of distant brain failure on multivariate analysis. Local tumor control at 1 year was 97% for lesions < 2 cm(3) compared with 75% for lesions ≥ 2 cm(3) (p < 0.001). CONCLUSIONS After adjusting for other factors, a total brain metastasis volume was a strong and independent predictor for overall survival, distant brain failure, and local control, even when considering the number of metastases.

Stereotactic radiosurgery for cerebral arteriovenous malformations: evaluation of long-term outcomes in a multicenter cohort.

OBJECTIVE In this multicenter study, the authors reviewed the results following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs), determined predictors of outcome, and assessed predictive value of commonly used grading scales based upon this large cohort with long-term follow-up. METHODS Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed. RESULTS The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1-20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment. CONCLUSIONS GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery.

Hearing preservation in patients with vestibular schwannoma treated with Gamma Knife surgery

OBJECT Hearing loss after Gamma Knife surgery (GKS) in patients with vestibular schwannoma has been associated with radiation dose to the cochlea. The purpose of this study was to evaluate serviceable hearing preservation in patients with VS who were treated with GKS and to determine if serviceable hearing loss can be correlated with the dose to the cochlea. METHODS Forty patients with vestibular schwannoma with serviceable hearing were treated using GKS with a median marginal dose of 12.5 Gy (range 12.5-13 Gy) to the 50% isodose volume. Audiometry was performed prospectively before and after GKS at 1, 3, and 6 months, and then every 6 months thereafter. Hearing preservation was based on pure tone average (PTA) and speech discrimination (SD). Serviceable hearing was defined as PTA less than 50 dB and SD greater than 50%. RESULTS The median cochlear maximum and mean doses were 6.9 Gy (range 1.6-16 Gy) and 2.7 Gy (range 0.7-5.0 Gy), respectively. With a median audiological follow-up of 35 months (range 6-58 months), the 1-, 2-, and 3-year actuarial rates of maintaining serviceable hearing were 93%, 77%, and 74%, respectively. No patient who received a mean cochlear dose less than 2 Gy experienced serviceable hearing loss (p = 0.035). Patients who received a mean cochlear dose less than 3 Gy had a 2-year hearing preservation rate of 91% compared with 59% in those who received a mean cochlear dose of 3 Gy or greater (p = 0.029). Those who had more than 25% of their cochlea receiving 3 Gy or greater had a higher rate of hearing loss (p = 0.030). There was no statistically significant correlation between serviceable hearing loss and age, tumor size, pre-GKS PTA, pre-GKS SD, pre-GKS Gardner-Robertson class, maximum cochlear dose, or the percentage of cochlear volume receiving 5 Gy. On multivariate analysis there was a trend toward significance for serviceable hearing loss with a mean cochlear dose of 3 Gy or greater (p = 0.074). Local control was 100% at 24 months. No patient developed facial or trigeminal nerve dysfunction. CONCLUSIONS With a median mean cochlear dose of 2.7 Gy, the majority of patients with serviceable hearing retained serviceable hearing 3 years after GKS. A mean cochlear dose less than 3 Gy was associated with higher serviceable hearing preservation.

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling

OBJECTIVE To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis. METHODS Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis. RESULTS Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity. CONCLUSION Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.

Successful treatment of glomus jugulare tumours with gamma knife radiosurgery: clinical and physical aspects of management and review of the literature

PurposeTo demonstrate the feasibility of treatment and early outcomes for patients treated with gamma knife radiosurgery (GKR), with or without surgical resection, for glomus jugulare tumours.MethodsBetween January 2007 and November 2008, 10 patients with glomus jugulare tumours were treated with GKR. Eight had prior surgical resection, seven subtotal resection and one total resection. In two cases GKR was the only definitive therapy. Baseline neurological deficits were prospectively recorded and present in 90% prior to GKR. The median tumour size and volume were 4 cc (0.7–10.9 cc). The median marginal tumour dose was 14 Gy (12–16 Gy). Clinical and radiographic outcomes are reported with a median follow-up of 9.7 months.ResultsStereotactic frame placement allowed treatment of all 10 lesions, although 3-point fixation was sometimes required to avoid collisions. No patients developed worsening of symptoms or new neurological complaints after GKR; symptom relief was achieved in 50% of cases. No cases of clinical or radiographic progression were identified. Radiographically, 80% of lesions were stable and 20% showed significant shrinkage.ConclusionsGKR is an excellent option for patients with glomus jugulare tumours after complete or subtotal resection or at recurrence. Appropriately planned frame placement allows successful treatment delivery without difficulty. GKR improved symptoms, prevented neurological progression and achieved radiographic stability or regression in all cases.

Endoscopic vascular decompression.

Objective: This article describes the technique and reports the results of endoscopic vascular decompression (EVD) in patients with trigeminal neuralgia (TGN), hemifacial spasm (HFS), and cochleovestibular nerve compressive syndrome. Study Design: Retrospective case review. Subjects and Methods: This study evaluates the outcome and length of stay (LOS) of 20 patients who underwent EVD for vascular compressive disorders from 2005 to 2007. It also evaluates LOS in 41 patients who underwent traditional microvascular decompression (MVD) by the same surgeons from 1999 to 2004. Results: Eighty-six percent (12 of 14) patients had resolution of their TGN, and 80% (4 of 5) had resolution of their HFS. There were no major complications. The EVD patients had an average LOS of 2.36 days as compared with 4.36 days for the MVD patient group (p < 0.001). Conclusion: Endoscopic vascular decompression for patients with vascular compressive syndromes such as TGN and HFS is a safe and equally effective procedure when compared with the traditional and widely successful MVD surgery, with the added benefit of less morbidity and shorter hospital stays.

Trigeminal neuralgia pain relief after gamma knife stereotactic radiosurgery

OBJECTIVES To report outcomes of patients with medical and/or surgical refractory trigeminal neuralgia (TN) treated with gamma knife stereotactic radiosurgery (GK SRS). METHODS One hundred and forty-nine patients with 152 cases of TN treated with GK SRS were analyzed. All patients, except one, received a dose of 40Gy to the 50% isodose volume. The Barrow Neurological Institute (BNI) pain intensity score was used to grade pain. Actuarial rates of pain relief were calculated. Multiple factors were analyzed for association with pain relief. RESULTS The median follow up was 27 months (4-71 months). Overall 92% of cases achieved a BNI score I-III after GK SRS. Of those who had pain relief after GK SRS, 32% developed pain recurrence defined as a BNI score of IV or V. The actuarial rate of freedom from pain recurrence (BNI scores I-III) of all treated cases at 1, 2 and 3-years was 76%, 69% and 60%, respectively. On univariate analysis age ≥70 was predictive of better pain relief (p=0.046). Type of pain, prior surgery, multiple sclerosis, number of isocenters, treated nerve length, volume and thickness and distance from the root entry zone to the isocenter were not significant for maintaining a BNI score of I-III. Those who achieved a BNI score of I or II were more likely to maintain pain relief compared to those who only achieved a BNI score of III (93% vs 38% at three years, p<0.01). The rate of pain relief of twenty-seven patients who underwent repeat GK SRS was 70% and 62% at 1 and 2 years, respectively. Toxicity after first GK SRS was minimal with 25% of cases experiencing only new or worsening post-treatment numbness. CONCLUSION GK SRS provides acceptable pain relief with limited morbidity in patients with medical and/or surgical refractory TN.

Longitudinal assessment of quality of life and audiometric test outcomes in vestibular schwannoma patients treated with gamma knife surgery.

Objective: To prospectively assess the quality of life (QOL) and hearing acuity in vestibular schwannoma (VS) patients after gamma knife surgery (GKS). Patients: Fifty-nine VS patients. Intervention: GKS. Main Outcome Measures: Prospective follow-up algorithm included 36-item Short Form Health Survey (SF-36), Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), pure-tone average, and speech discrimination hearing scores (Gardner-Robertson and American Academy of Otolaryngology), performed before and after GKS at 1-, 3-, 6-, 12-, and 18-month posttreatment intervals. Results: From December 2006 to November 2008, 59 VS patients were treated with a median follow-up of 15 months. At baseline, mean scores for SF-36, HHI, DHI, and THI were 73, 37, 17, and 23, respectively. Median baseline Gardner-Robertson and American Academy of Otolaryngology hearing acuity scores were 2 and B, respectively. No significant decline in SF-36 health survey was noted after GKS. Mean SF-36 score at baseline was 73, compared with a range of 70 to 77 at predetermined posttreatment intervals. Similarly, no significant changes in DHI, HHI, and THI were noted. Approximately 47% of patients with baseline serviceable hearing maintained serviceable hearing at 12 months. Significant acute and chronic worsening in hearing acuity were noted at 1 and 18 months, respectively. No correlative decline in QOL was noted as assessed by SF-36 or HHI. Conclusion: No significant decline in global QOL occurred after GKS with relatively short follow-up and approximately 50% survey completion. When discussing therapy options with VS patients, anticipated treatment-related QOL outcomes should be considered.

Improved facial nerve outcomes using an evolving treatment method for large acoustic neuromas.

Objective To describe a successful paradigm for the treatment of large acoustic neuromas (vestibular schwannomas). Study Design Retrospective case review. Setting Tertiary referral center. Patients The charts of 2,875 acoustic neuroma patients at Michigan Ear Institute were reviewed to identify 153 patients who underwent surgical resection for large acoustic neuromas (≥3 cm) between 2000 and 2009. Intervention(s) Staged surgical resection or single stage surgery with or without adjuvant stereotactic radiosurgery. Main Outcome Measure(s) Postoperative facial nerve outcomes are reported using the House-Brackmann (HB) facial nerve grading scale and compared with historical controls from a literature review. Rates of adverse outcomes are also reported. Results Seventy-five patients underwent staged surgical resection of their tumors, whereas 78 patients underwent either single stage surgery or surgery with subsequent stereotactic radiosurgery. Eighty-one percent of patients in the staged surgical resection group had a postoperative HB Grade I or II facial nerve function compared with 75% in the single stage surgical group. Overall, 78% of patients in the current study had HB Grade I or II after treatment compared with a mean of 53% in the literature for similar sized tumors. Our methods including the decision to use staged surgery when necessary, dissection of tumor with stimulating dissector-directed intraoperative monitoring, and use of adjuvant stereotactic radiosurgery are described. Conclusion Using the described paradigm, large acoustic neuromas can be successfully treated with either staged or single-stage surgical resection with or without adjuvant radiosurgery to obtain more favorable facial nerve outcomes than historically reported controls while minimizing morbidity for the patient.

Third ventricle, cerebral aqueduct, and fourth ventricle mixed ependymal neurocytoma: a case report and review of the literature

PurposeA case report of an 8-year-old female who underwent interhemispheric transcallosal approach to the third ventricle, cerebral aqueduct, and fourth ventricle for resection of a mixed ependymal neurocytoma and review of the literature was evaluated.MethodsAn Ovid MEDLINE review of the literature was conducted starting in 1946 to current using search terms as described in our keywords.ResultsA total of 16 neurocytoma have been described in the literature as either posterior third ventricle or posterior fossa in origin. Of these lesions, five have been described as mixed glial–neuronal and all of these were located in the fourth ventricle. To our knowledge, this is the first described mixed glial–neuronal tumor located in the posterior third ventricle and aqueduct.