Aditya Iyer

Outcome predictors of gamma knife radiosurgery for renal cell carcinoma metastases.

BACKGROUND Although whole-brain radiation therapy (WBRT) has been a standard palliative management for brain metastases from renal cell carcinoma, its benefit has been elusive because of radiobiological resistance. OBJECTIVE To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from renal cell carcinoma. METHODS We reviewed records from 158 consecutive patients (men = 111, women = 47) who underwent SRS for 531 brain metastases from renal cell carcinoma. The median patient age was 61 years (range, 38-83 years), and the median number of tumors per patient was 1 (range, 1-10). Seventy-nine patients (50%) had solitary brain metastasis. Fifty-seven patients (36%) underwent prior WBRT. The median total tumor volume for each patient was 3.0 cm3 (range, 0.09-47 cm3). RESULTS The overall survival after SRS was 60%, 38%, and 19% at 6, 12, and 24 months, respectively, with a median survival of 8.2 months. Factors associated with longer survival included younger age, longer interval between primary diagnosis and brain metastases, lower recursive partitioning analysis class, higher Karnofsky performance status, smaller number of brain metastases, and no prior WBRT. Median survival for patients with < 2 brain metastases, higher Karnofsky performance status (> 90), and no prior WBRT was 12 months after SRS. Sustained local tumor control was achieved in 92% of patients. Symptomatic adverse radiation effects occurred in 7%. Overall, 70% of patients improved or remained neurologically stable. CONCLUSION Stereotactic radiosurgery is an especially valuable option for patients with higher Karnofsky performance status and smaller number of brain metastases from renal cell carcinoma.

Stereotactic Radiosurgery for Patients with Trigeminal Neuralgia Associated with Petroclival Meningiomas

Background:The management of trigeminal neuralgia in patients with associated skull base meningiomas is complex. Objective:We evaluated the pain management needs and outcomes in patients with petroclival meningiomas associated with medically refractory trigeminal neuralgia. Methods: During a 21-year period, 168 patients underwent stereotactic radiosurgery (SRS) for meningiomas involving the petroclival region. We identified 12 patients (10 females; median age 54 years) who had trigeminal neuralgia in association with an ipsilateral petroclival meningioma. The median tumor volume was 3.8 cm3 (1.0–15.9 cm3). The median prescription dose for tumor margins was 13 Gy (11–16 Gy). Results: Initial pain control [Barrow Neurological Institute (BNI) grades I–IIIb] was obtained in 10 of 12 patients (83%). However, 3 patients with initial adequate relief later developed pain. Follow-up imaging revealed control of tumor growth in all patients at a median follow-up of 68 months. No patient developed any new sensory dysfunction. The tumor shrinkage was not associated with pain relief. At the final follow-up, 5 patients had pain of BNI grade I (2 after surgery), 4 had grade IIIb and 3 had grade IV. Conclusions: SRS provided effective tumor control, but trigeminal neuralgia persisted to varying degrees in most patients. Multimodality pain management strategies were required in most patients with skull base meningiomas associated with trigeminal neuralgia.

Stereotactic radiosurgery after embolization for arteriovenous malformations

We sought to define the long-term benefits and risks of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) patients who underwent prior embolization. Between 1987 and 2006, we performed Gamma Knife® SRS on 120 patients with AVM who underwent embolization followed by SRS. Sixty-four patients (53%) had at least 1 prior hemorrhage. The median number of embolizations varied from 1 to 5. The median target volume was 6.6 cm3 (range, 0.2-26.3 cm3). The median margin dose was 18 Gy (range, 13.5-25 Gy). After embolization, 25 patients (21%) developed symptomatic neurological deficits. The overall rates of total obliteration documented by either angiography or magnetic resonance imaging were 35, 53, 55 and 59% at 3, 4, 5 and 10 years, respectively. Nine patients (8%) had a hemorrhage during the latency interval and 7 patients died due to hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8, 3.5, 5.4, 7.7 and 7.7% at 1, 2, 3, 5 and 10 years, respectively. Permanent neurological deficits due to adverse radiation effects developed in 3 patients (2.5%) after SRS. Using a case-match control technique, we found that embolization prior to SRS was associated with a lower rate of total obliteration (p=0.028) in comparison to radiosurgery alone. In this 20-year experience, we found that prior embolization reduced the rate of total obliteration after SRS and latency interval hemorrhage risks were not affected by prior embolization. In the future, the role of embolization after SRS should be explored.

Skull base chondrosarcoma radiosurgery: report of the North American Gamma Knife Consortium

OBJECT Stereotactic radiosurgery (SRS) is a potentially important option for patients with skull base chondrosarcomas. The object of this study was to analyze the outcomes of SRS for chondrosarcoma patients who underwent this treatment as a part of multimodality management. METHODS Seven participating centers of the North American Gamma Knife Consortium (NAGKC) identified 46 patients who underwent SRS for skull base chondrosarcomas. Thirty-six patients had previously undergone tumor resections and 5 had been treated with fractionated radiation therapy (RT). The median tumor volume was 8.0 cm3 (range 0.9-28.2 cm3), and the median margin dose was 15 Gy (range 10.5-20 Gy). Kaplan-Meier analysis was used to calculate progression-free and overall survival rates. RESULTS At a median follow-up of 75 months after SRS, 8 patients were dead. The actuarial overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. Local tumor progression occurred in 10 patients. The rate of progression-free survival (PFS) after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with shorter PFS. Eight patients required salvage resection, and 3 patients (7%) developed adverse radiation effects. Cranial nerve deficits improved in 22 (56%) of the 39 patients who deficits before SRS. Clinical improvement after SRS was noted in patients with abducens nerve paralysis (61%), oculomotor nerve paralysis (50%), lower cranial nerve dysfunction (50%), optic neuropathy (43%), facial neuropathy (38%), trochlear nerve paralysis (33%), trigeminal neuropathy (12%), and hearing loss (10%). CONCLUSIONS Stereotactic radiosurgery for skull base chondrosarcomas is an important adjuvant option for the treatment of these rare tumors, as part of a team approach that includes initial surgical removal of symptomatic larger tumors.

Does Prior Microsurgery Improve or Worsen the Outcomes of Stereotactic Radiosurgery for Cavernous Sinus Meningiomas

BACKGROUND Stereotactic radiosurgery (SRS) is an important option for patients with cavernous sinus meningiomas. OBJECTIVE To evaluate cranial nerve outcomes in patients who underwent SRS for cavernous sinus meningiomas with or without prior microsurgery. METHODS During a 23-year interval, 272 patients underwent Gamma Knife SRS for cavernous sinus meningiomas (70 men, 202 women; median age, 54 years). In this series, 99 patients underwent prior microsurgical resection. The median tumor volume was 7.9 cm and median marginal dose was 13 Gy. The median follow-up period was 62 months (range, 6-209 months). RESULTS The progression-free survival after SRS was 96% at 3 years, 94% at 5 years, and 86% at 10 years. After SRS, 13 of 91 patients (14%) who underwent prior microsurgery had improvement of preexisting cranial nerve symptoms or signs. In comparison, 54 of 145 patients (37%) without prior microsurgery had improvement of preexisting cranial nerve symptoms or signs. The improvement rate of cranial nerve deficits after SRS in patients without prior microsurgery was 20% at 1 year, 34% at 2 years, 36% at 3 years, and 39% at 5 years. Patients who had not undergone prior microsurgery had significantly higher improvement rates of preexisting cranial nerve symptoms and signs (P = .001). After SRS, 29 patients (11%) developed new or worsened cranial nerve function. CONCLUSION SRS provided long-term effective tumor control and a low risk of new cranial nerve deficits. Improvement in preexisting cranial neuropathies was detected in significantly more patients who had not undergone prior microsurgical procedures.

Role of adjuvant or salvage radiosurgery in the management of unresected residual or progressive glioblastoma multiforme in the pre–bevacizumab era

OBJECT After initial standard of care management of glioblastoma multiforme (GBM), relatively few proven options remain for patients with unresected progressive tumor. Numerous reports describe the value of radiosurgery, yet this modality appears to remain underutilized. The authors analyzed the outcomes of early adjuvant stereotactic radiosurgery (SRS) for unresected tumor or later salvage SRS for progressive GBM. Radiosurgery was performed as part of the multimodality management and was combined with other therapies. Patients continued to receive additional chemotherapy after SRS and prior to progression being documented. In this retrospective analysis, the authors evaluated factors that affected patient overall survival (OS) and progression-free survival. METHODS Between 1987 and 2008 the authors performed Gamma Knife SRS in 297 patients with histologically proven GBMs. All patients had received prior fractionated radiation therapy, and 66% had undergone one or more chemotherapy regimens. Ninety-six patients with deep-seated unresectable GBMs underwent biopsy only. Of those in whom excision had been possible, resection was considered to be gross total in 68 and subtotal in 133. The median patient age was 58 years (range 23-89 years) and the median tumor volume was 14 cm(3) (range 0.26-84.2 cm(3)). The median prescription dose delivered to the imaging-defined tumor margin was 15 Gy (range 9-25 Gy). The median follow-up duration was 8.6 months (range 1.1-173 months). Cox regression models were used to analyze survival outcomes. Variables examined included age, residual versus recurrent tumor, prior chemotherapy, time to first recurrence, SRS dose, and gross tumor volume. RESULTS The median survival times after radiosurgery and after diagnosis were 9.03 and 18.1 months, respectively. The 1-year and 2-year OS after SRS were 37.9% and 16.7%, respectively. The 1-year and 2-year OS after diagnosis were 76.2% and 30.8%, respectively. Using multivariate analysis, factors associated with improved OS after diagnosis were younger age (< 60 years) at diagnosis (p < 0.0001), tumor volume < 14 cm(3) (p < 0.001), use of prior chemotherapy (p = 0.001), and radiosurgery at the time of recurrence (p < 0.0001). Multivariate analysis showed that younger age (p < 0.0001) and smaller tumor volume (< 14 cm(3)) (p = 0.001) were significantly associated with increased OS after SRS. Adverse radiation effects were seen in 69 patients (23%). Fifty-eight patients (19.5%) underwent additional resection after SRS. The median survivals after diagnosis for recursive partitioning analysis Classes III, IV and V+VI were 31.6, 20.8, and 16.7 months, respectively. CONCLUSIONS In this analysis 30% of a heterogeneous cohort of GBM patients eligible for SRS had an OS of 2 years. Radiosurgery at the time of tumor progression was associated with a median survival of 21.8 months. The role of radiosurgery for GBMs remains controversial. The findings in this study support the need for a funded and appropriately designed clinical trial that will provide a higher level of evidence regarding the future role of SRS for glioblastoma patients in whom disease has progressed despite standard management.

Epidemiology and Environmental Risk Factors Associated with Vestibular Schwannoma

OBJECTIVE Vestibular schwannomas (VS) are tumors originating from the eighth cranial nerve. The etiology and environmental risk factors for VS remain unclear. The goal of this study was to explore some potential environmental risk factors associated with vestibular schwannoma (VS). METHODS A hospital-based case-control study with 1:1 matching based on age and sex was designed. A written questionnaire was administered. Multiple conditional logistic regression models were created to determine odds ratio (OR). RESULTS There were 353 matched pairs with an average age at diagnosis of 53 years (SD ± 12), 50% of participants were female, and >90% were white. Multivariate models revealed significantly increased OR with a history of hay fever (OR = 3.91, 95% confidence interval [CI] = 1.35-11.30) and managerial/professional occupations (OR = 4.41, 95% CI = 2.07-9.40). Tobacco use had a decreased association with VS (<20 pack-years OR = 0.10, 95% CI = 0.04-0.28; ≥ 20 pack-years OR = 0.03, 95% CI = 0.01-0.12). CONCLUSIONS The profile of patients with VS includes white race, age 50-60 years, either sex, and working in a professional occupation. Better access to health care and diagnostic imaging likely plays a role in the diagnosis of this tumor. Hay fever is strongly associated with VS. Tobacco use demonstrates an inverse relationship with VS, but the possible biologic mechanism for this is poorly understood, and tobacco remains a significant public health problem.

Volumetric response to radiosurgery for brain metastasis varies by cell of origin

OBJECT The aim of this study was to evaluate the imaging response of brain metastases after radiosurgery and to correlate the response with tumor type and patient survival. METHODS The authors conducted a retrospective review of patients who had undergone Gamma Knife radiosurgery for brain metastases from non-small cell lung cancer (NSCLC), breast cancer, or melanoma. The imaging volumetric response by tumor type was plotted at 3-month intervals and classified as a sustained decrease in tumor volume (Type A), a transient decrease followed by a delayed increase in tumor volume (Type B), or a sustained increase in tumor volume (Type C). These imaging responses were then compared with patient survival and tumor type. RESULTS Two hundred thirty-three patients with metastases from NSCLC (96 patients), breast cancer (98 patients), and melanoma (39 patients) were eligible for inclusion in this study. The patients with NSCLC were most likely to exhibit a Type A response; those with breast cancer, a Type B response; and those with melanoma, a Type C response. Among patients with NSCLC, the median overall survival was 11.2 months for those with a Type A response (76 patients), 8.6 months for those with a Type B response (6 patients), and 10.5 months for those with a Type C response (14 patients). Among patients with breast cancer, the median overall survival was 16.6 months in those with a Type A response (65 patients), 18.1 months in those with a Type B response (20 patients), and 7.5 months in those with a Type C response (13 patients). For patients with melanoma, the median overall survival was 5.2 months in those with a Type A response (26 patients) and 6.7 months in those with a Type C response (13 patients). None of the patients with melanoma had a Type B response. The imaging response was significantly associated with survival only in patients with breast cancer. CONCLUSIONS The various types of imaging responses of metastatic brain tumors after stereotactic radiosurgery depend in part on tumor type. However, the type of response only correlates with survival in patients with breast cancer.

Skull base chondrosarcoma radiosurgery: a literature review.

C hondrosarcomas are relatively slow growing and locally invasive tumors that usually do not metastasize until very late in the natural history. Chondrosarcomas are the third most common primary malignancy of bone after myelomas and osteosarcomas. Primary intracranial chondrosarcomas are rare, with a reported incidence of approximately 0.15% of tumors of the skull base. Cranial chondrosarcomas originate from primitive mesenchymal cells within the cartilaginous matrix of the skull base. The imaging features and clinical presentations of patients harboring either chordomas or chondrosarcomas are similar. Whereas chordomas have a tendency to cause brainstem compression because they arise from the clivus, chondrosarcomas tend to affect the lower cranial nerves, because they frequently originate from the occipitotemporal bone synchondrosis. The most common presenting symptom of chondrosarcoma is diplopia, secondary to an abducens nerve palsy. The ability to distinguish chondrosarcomas from chordomas by imaging alone is often difficult but important, because the prognosis is generally considered better for chondrosarcomas.

Postsurgical management strategies in patients with skull base chondrosarcomas

Chondrosarcomas of the skull base are rare, slow-growing tumors that are often lethal and remain a management quandary. A systematic review was performed to understand postsurgical management options for patients with these tumors. The current standard of care includes surgical resection followed by either adjuvant radiation therapy and/or early radiosurgery. The role of chemotherapy has been limited, but remains under investigation. Overall survival and progression-free survival range between 70 and 100% at 5 years when multimodality approaches are used. Overall survival may be greater for patients who have a shorter interval (<6 months) between diagnosis and radiosurgery, an older age, and either a single or no prior resection. Progression-free survival may be increased for patients older than 40 years of age, who have not had prior radiation therapy, and for those with smaller tumors that do not compress the brainstem.