Ajay Niranjan

Radiosurgery of vestibular schwannomas: summary of experience in 829 cases

OBJECT Management options for vestibular schwannomas (VSs) have greatly expanded since the introduction of stereotactic radiosurgery. Optimal outcomes reflect long-term tumor control, preservation of cranial nerve function, and retention of quality of life. The authors review their 15-year experience. METHODS Between 1987 and 2002, some 829 patients with VSs underwent gamma knife surgery (GKS). Dose selection, imaging, and dose planning techniques evolved between 1987 and 1992 but thereafter remained stable for 10 years. The average tumor volume was 2.5 cm3. The median margin dose to the tumor was 13 Gy (range 10-20 Gy). No patient sustained significant perioperative morbidity. The average duration of hospital stay was less than 1 day. Unchanged hearing preservation was possible in 50 to 77% of patients (up to 90% in those with intracanalicular tumors). Facial neuropathy risks were reduced to less than 1%. Trigeminal symptoms were detected in less than 3% of patients whose tumors reached the level of the trigeminal nerve. Tumor control rates at 10 years were 97% (no additional treatment needed). CONCLUSIONS Superior imaging, multiple isocenter volumetric conformal dose planning, and optimal precision and dose delivery contributed to the long-term success of GKS, including in those patients in whom initial microsurgery had failed. Gamma knife surgery provides a low risk, minimally invasive treatment option for patients with newly diagnosed or residual VS. Cranial nerve preservation and quality of life maintenance are possible in long-term follow up.

RADIOSURGERY AS DEFINITIVE MANAGEMENT OF INTRACRANIAL MENINGIOMAS

OBJECTIVEStereotactic radiosurgery has become an important primary or adjuvant minimally invasive management strategy for patients with intracranial meningiomas with the goals of long-term tumor growth prevention and maintenance of patient neurological function. We evaluated clinical and imaging outcomes of meningiomas stratified by histological tumor grade. METHODSThe patient cohort consisted of 972 patients with 1045 intracranial meningiomas managed during an 18-year period. The series included 70% women, 49% of whom had undergone a previous resection and 5% of whom had received previous fractionated radiation therapy. Tumor locations included middle fossa (n = 351), posterior fossa (n = 307), convexity (n = 126), anterior fossa (n = 88), parasagittal region (n = 113), or other (n = 115). RESULTSThe overall control rate for patients with benign meningiomas (World Health Organization Grade I) was 93%. In those without previous histological confirmation (n = 482), tumor control was 97%. However, for patients with World Health Organization Grade II and III tumors, tumor control was 50 and 17%, respectively. Delayed resection after radiosurgery was necessary in 51 patients (5%) at a mean of 35 months. After 10 years, Grade 1 tumors were controlled in 91% (n = 53); in those without histology, 95% (n = 22) were controlled. None of the patients developed a radiation-induced tumor. The overall morbidity rate was 7.7%. Symptomatic peritumoral imaging changes developed in 4% of the patients at a mean of 8 months. CONCLUSIONStereotactic radiosurgery provided high rates of tumor growth control or regression in patients with benign meningiomas with low risk. This study confirms the role of radiosurgery as an effective management choice for patients with small to medium-sized symptomatic, newly diagnosed or recurrent meningiomas of the brain.

Histological Effects of Trigeminal Nerve Radiosurgery in a Primate Model: Implications for Trigeminal Neuralgia Radiosurgery

OBJECTIVE Stereotactic radiosurgical treatment of the proximal trigeminal nerve is used to relieve the pain of trigeminal neuralgia. The mechanism of the radiosurgical effect is not understood. METHODS Two adult baboons underwent stereotactic magnetic resonance imaging-guided radiosurgery, using a gamma knife. A single 4-mm isocenter was targeted to each proximal trigeminal nerve, just anterior to the pons, to deliver a maximal dose of 80 or 100 Gy (total of four nerves). A nonirradiated baboon brain and nerves served as control specimens. Six months after treatment, magnetic resonance imaging was again performed and the brains and nerves were studied using light and electron microscopy. RESULTS Magnetic resonance imaging indicated a 4-mm-diameter area of contrast enhancement at the target site in each nerve. All irradiated nerves exhibited axonal degeneration and mild edema at the target, with remnants of some myelinated axons. Large and small myelinated and unmyelinated fibers were affected. No inflammation was observed. Nerve necrosis was identified after 100-Gy treatment. The trigeminal ganglion appeared normal. CONCLUSION Radiosurgery at 80 Gy causes focal axonal degeneration of the trigeminal nerve. At higher doses, partial nerve necrosis is observed. We think that these effects influence the physiological features of trigeminal neuralgia.

Prospective staged volume radiosurgery for large arteriovenous malformations: indications and outcomes in otherwise untreatable patients.

OBJECTIVE The obliteration response of an arteriovenous malformation (AVM) to radiosurgery is strongly dependent on dose and volume. For larger volumes, the dose must be reduced for safety, but this compromises obliteration. In 1992, we prospectively began to stage anatomic components in order to deliver higher single doses to symptomatic AVMs > 15 ml in volume. METHODS During a 17-year interval at the University of Pittsburgh, 1040 patients underwent radiosurgery for a brain AVM. Out of 135 patients who had multiple procedures, 37 patients underwent prospectively staged volume radiosurgery for symptomatic otherwise unmanageable larger malformations. Twenty-eight patients who were managed before 2002 were included in this study to achieve sufficient follow-up in assessing the outcomes. The median age was 37 years (range, 13-57 yr). Thirteen patients had previous hemorrhages and 13 patients had attempted embolization. Separate anatomic volumes were irradiated at 3 to 8 months (median, 5 mo) intervals. The median initial AVM volume was 24.9 ml (range, 10.2-57.7 ml). Twenty-six patients had two stages and two had three-stage radiosurgery. Seven patients had repeat radiosurgery after a median interval of 63 months. The median target volume was 12.3 ml. (range, 4.2-20.8 ml.) at Stage I and 11.5 ml. (range, 2.8-22 ml.) at Stage II. The median margin dose was 16 Gy at both stages. Median follow-up after the last stage of radiosurgery was 50 months (range, 3-159 mo). RESULTS Four patients (14%) sustained a hemorrhage after radiosurgery; two died and two patients recovered with mild permanent neurological deficits. Worsened neurological deficits developed in one patient. Seizure control was improved in three patients, was stable in eight patients and worsened in two. Magnetic resonance imaging showed T2 prolongation in four patients (14%). Out of 28 patients, 21 had follow-up more than 36 months. Out of 21 patients, seven underwent repeat radiosurgery and none of them had enough follow- up. Of 14 patients followed for more than 36 months, seven (50%) had total, four (29%) near total, and three (21%) had moderate AVM obliteration. CONCLUSIONS Prospective staged volume radiosurgery provided imaging defined volumetric reduction or closure in a series of large AVMs unsuitable for any other therapy. After 5 years, this early experience suggests that AVM related symptoms can be stabilized and anticipated bleed rates can be reduced.

Dose reduction improves hearing preservation rates after intracanalicular acoustic tumor radiosurgery.

OBJECTIVE To assess the potential for long-term serviceable hearing preservation in intracanalicular acoustic tumor patients who underwent stereotactic radiosurgery. METHODS Between August 1987 and December 1997, 29 patients with intracanalicular acoustic tumors underwent stereotactic radiosurgery at our center using the Leksell gamma knife (Elekta Instruments, Inc., Atlanta, GA). Fifteen assessable patients had serviceable preradiosurgery hearing (pure tone average, < or = 50 dB; speech discrimination score, > or = 50%). We retrospectively analyzed our hearing results and compared hearing preservation in patients who received a minimal tumor dose of 14 Gy or less versus those who received more than 14 Gy to the tumor margin. RESULTS No perioperative patient morbidity or mortality was observed. Serviceable hearing was preserved in 11 (73%) of 15 assessable patients (actuarial rate, 65%). Long-term follow-up demonstrated serviceable hearing preservation in 10 (100%) of 10 patients who received marginal tumor doses of 14 Gy or less but in only one of five patients who received more than 14 Gy. Preradiosurgery Gardner-Robertson class was preserved in 49%, and testable hearing was present in 68% of patients who had any testable hearing at presentation. Five patients demonstrated improvement in hearing (three had serviceable and two had nonserviceable hearing before radiosurgery). No patient developed a facial or trigeminal neuropathy. Seven of 13 patients with preoperative tinnitus continued to experience tinnitus in follow-up. Episodic vertigo continued in 3 of the 11 patients who presented with vertigo. CONCLUSION Gamma knife radiosurgery (using conformal dose planning, small-beam geometry, and < or = 14 Gy to the margin) prevents tumor growth and achieves excellent hearing preservation rates.

Tumor bed radiosurgery after resection of cerebral metastases.

OBJECTVEAdjuvant irradiation after resection of brain metastases reduces the risk of local recurrence. Whole-brain radiation therapy can be associated with significant neurotoxicity in long-term survivors of brain metastases. This retrospective study evaluates the role of tumor bed stereotactic radiosurgery as an alternative method of irradiation after initial resection of brain metastases to prevent local recurrence. METHODSForty patients underwent tumor bed radiosurgery after resection of brain metastases at two separate academic medical centers. The median age was 59.5 years. Twenty patients (67.5%) had single metastases. Resection was complete in 80% and partial in 20% of the patients. At the time of radiosurgery, systemic disease was active in 57.5%, inactive in 32.5%, and in remission in 10% of the patients. The median Karnofsky Performance Scale score was 80% (range, 60–100%). Radiosurgery was performed a median of 4 weeks after tumor resection. The median cavity radiosurgery volume was 9.1 ml (range, 0.6–39.9 ml). The median margin and maximum radiation dose were 16 and 32 Gy, respectively. RESULTSLocal control at the resection site was achieved in 73% of patients at a median follow-up period of 13 months. No variable significantly affected local control. New remote brain metastases occurred in 54% of the patients. Symptomatic radiation effect was seen in 5.4% of the patients. The median survival was 13 months after radiosurgery (range, 2–56 mo). CONCLUSIONTumor bed radiosurgery provides effective local control of the tumor after resection in most patients. These preliminary data support radiosurgery after resection rather than traditional radiation therapy.

Radiosurgery for childhood intracranial arteriovenous malformations.

OBJECTIVEThe optimal management of intracranial arteriovenous malformations (AVMs) in children remains controversial. Children with intracranial AVMs present a special challenge in therapeutic decision-making because of the early recognition of their future life-long risks of hemorrhage if they are treated conservatively. The goals of radiosurgery are to achieve complete AVM obliteration and to preserve neurological function. We present long-term outcomes for a series of children treated using radiosurgery. METHODSThe findings for 53 consecutive children who underwent at least 36 months of imaging follow-up monitoring after radiosurgery were reviewed. The median age at the time of treatment was 12 years (range, 2–17 yr). Thirty-one children (58%) presented after their first intracranial hemorrhaging episodes, two (4%) after their second hemorrhaging episodes, and one (2%) after five hemorrhaging episodes. Nineteen children (36%) presented with unruptured AVMs, and a total of 25 children (47%) exhibited neurological deficits. AVMs were graded as Spetzler-Martin Grade I (2%), Grade II (23%), Grade III (36%), Grade IV (9%), or Grade VI (30%). The median AVM volume was 1.7 ml (range, 0.11–10.2 ml). The median marginal dose was 20 Gy (range, 15–25 Gy). RESULTSResults were stratified according to AVM volumes (Group 1, ≤3 ml; Group 2, >3 ml to ≤10 ml; Group 3, >10 ml). Twenty-eight patients (80%) in Group 1 and 11 (64.7%) in Group 2 achieved complete obliteration. The only patient in Group 3 did not achieve obliteration. Complications included brainstem edema (n = 1) and transient pulmonary edema (n = 1). Four patients experienced hemorrhaging episodes, 30, 40, 84, and 96 months after radiosurgery. Multivariate logistic regression analysis demonstrated that only volume was significantly correlated with obliteration rates (P = 0.0109). CONCLUSIONRadiosurgery is safe and efficacious for selected children with AVMs. The obliteration rates and the attendant low morbidity rates suggest a primary role for stereotactic radiosurgery for pediatric AVMs.

Stereotactic radiosurgery for vestibular schwannomas in patients with neurofibromatosis type 2: an analysis of tumor control, complications, and hearing preservation rates.

OBJECTIVEVestibular schwannomas present significant management challenges in patients with neurofibromatosis Type 2 (NF2). We evaluated the results of gamma knife radiosurgery for the management of these tumors, focusing on tumor response, hearing preservation, and other factors affecting outcomes. METHODSStereotactic radiosurgery was performed to manage 74 schwannomas in 62 patients. Ipsilateral serviceable hearing was present in 35% of tumors before the procedure. The mean tumor volume was 5.7 cm3. The mean margin and maximum dose used were 14 and 27.5 Gy, respectively. Cox regression analyses were performed to identify factors affecting outcomes. RESULTSThe median follow-up period was 53 months, and two patients were lost to follow-up. Actuarial local control rates at were 85, 81, and 81% at 5, 10, and 15 years, respectively. Tumor volume was significant as a predictor of local control. Since 1992, using current radiosurgery techniques (magnetic resonance imaging scan targeting and reduced margin dose to 14 Gy or less), the actuarial serviceable hearing preservation rate is 73% at 1 year, 59% at 2 years, and 48% at 5 years after radiosurgery. Facial neuropathy occurred in 8% of tumors, trigeminal neuropathy occurred in 4%, and vestibular dysfunction occurred in 4%. Radiation dose and tumor volume were predictive of development of new deficits. No radiosurgery-associated secondary tumors or atypical or malignant changes were noted. CONCLUSIONStereotactic radiosurgery is a safe and effective management modality for neurofibromatosis Type 2 vestibular schwannomas. Although results do not seem to be as good as for patients with sporadic unilateral tumors, gamma knife radiosurgery results seem favorable and indicate that radiosurgery should be strongly considered for primary tumor management in selected patients.

Radiosurgery with or without whole-brain radiotherapy for brain metastases: the patients' perspective regarding complications.

Introduction:When cancer spreads to the brain, patients and their families report a much reduced quality of life. Whole-brain radiation therapy (WBRT) and/or radiosurgery (RS) are mainstays of management for patients with metastatic brain cancer. Despite the ubiquity of this problem, little is known about the patients’ perspective regarding management-related complications. To assess the patients’ perspective regarding current therapeutic options, we retrospectively surveyed 200 consecutive patients who underwent radiosurgery with or without WBRT. Methods and Materials:The survey consisted of 10 questions that sought information on quality of life, employment status, side effects (hair loss, fatigue, memory, concentration, mood, or employment), activity level, and satisfaction. Results:We tabulated 104 responses (52%). WBRT was used in 69% (72 of 104); all patients had radiosurgery. After WBRT, the following were noted: hair loss (88%; total regrowth in 24%), excess fatigue (95%), problems with short-term memory (72%), long-term memory (33%), concentration (61%), and depression (54%). Sixty-three percent of patients who had WBRT thought they had side effects after treatment compared with 34% who had radiosurgery only (P <0.001). Only 5% of RS patients reported fatigue. Seventy-six percent and 56% of respondents considered RS or WBRT, respectively, a good treatment of them (P = 0.25). Only 26 patients (27%) were employed at the time of treatment and 16 remained employed (62%). Eighteen percent believed that WBRT delayed other cancer treatments. Conclusions:Patients with brain metastases often report complications of their disease or its treatment. Side effects are most pronounced in those who received WBRT. Radiosurgery had fewer reported side effects and was believed by more patients or families to be effective. Further study of clinical outcomes and quality of life is important to guide our management of patients with these common brain tumors.

Outcome predictors of Gamma Knife surgery for melanoma brain metastases. Clinical article.

OBJECT To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from melanoma, the authors assessed clinical outcomes and prognostic factors for survival and tumor control. METHODS The authors reviewed 333 consecutive patients with melanoma who underwent SRS for 1570 brain metastases from cutaneous and mucosal/acral melanoma. The patient population consisted of 109 female and 224 male patients with a median age of 53 years. Two hundred eleven patients (63%) had multiple metastases. One hundred eighteen patients (35%) underwent whole-brain radiation therapy (WBRT). The target volume ranged from 0.1 cm(3) to 37.2 cm(3). The median marginal dose was 18 Gy. RESULTS Actuarial survival rates were 70% at 3 months, 47% at 6 months, 25% at 12 months, and 10% at 24 months after radiosurgery. Factors associated with longer survival included controlled extracranial disease, better Karnofsky Performance Scale score, fewer brain metastases, no prior WBRT, no prior chemotherapy, administration of immunotherapy, and no intratumoral hemorrhage before radiosurgery. The median survival for patients with a solitary brain metastasis, controlled extracranial disease, and administration of immunotherapy after radiosurgery was 22 months. Sustained local tumor control was achieved in 73% of the patients. Sixty-four (25%) of 259 patients who had follow-up imaging after SRS had evidence of delayed intratumoral hemorrhage. Sixteen patients underwent a craniotomy due to intratumoral hemorrhage. Seventeen patients (6%) had asymptomatic and 21 patients (7%) had symptomatic radiation effects. Patients with ≤ 8 brain metastases, no prior WBRT, and the recursive partitioning analysis Class I had extended survivals (median 54.3 months). CONCLUSIONS Stereotactic radiosurgery is an especially valuable option for patients with controlled systemic disease even if they have multiple metastatic brain tumors.