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Douglas Kondziolka, Oscar Zorro, Javier Lobato-Polo, Hideyuki Kano, Thomas J. Flannery, John C. Flickinger, and L. Dade Lunsford

Object

Trigeminal neuralgia pain causes severe disability. Stereotactic radiosurgery is the least invasive surgical option for patients with trigeminal neuralgia. Since different medical and surgical options have different rates of pain relief and morbidity, it is important to evaluate longer-term outcomes.

Methods

The authors retrospectively reviewed outcomes in 503 medically refractory patients with trigeminal neuralgia who underwent Gamma Knife surgery (GKS). The median patient age was 72 years (range 26–95 years). Prior surgery had failed in 205 patients (43%). The GKS typically was performed using MR imaging guidance, a single 4-mm isocenter, and a maximum dose of 80 Gy.

Results

Patients were evaluated for up to 16 years after GKS; 107 patients had > 5 years of follow-up. Eighty-nine percent of patients achieved initial pain relief that was adequate or better, with or without medications (Barrow Neurological Institute [BNI] Scores I–IIIb). Significant pain relief (BNI Scores I–IIIa) was achieved in 73% at 1 year, 65% at 2 years, and 41% at 5 years. Including Score IIIb (pain adequately controlled with medication), a BNI score of I–IIIb was found in 80% at 1 year, 71% at 3 years, 46% at 5 years, and 30% at 10 years. A faster initial pain response including adequate and some pain relief was seen in patients with trigeminal neuralgia without additional symptoms, patients without prior surgery, and patients with a pain duration of ≤ 3 years. One hundred ninety-three (43%) of 450 patients who achieved initial pain relief reported some recurrent pain 3–144 months after initial relief (median 50 months). Factors associated with earlier pain recurrence that failed to maintain adequate or some pain relief were trigeminal neuralgia with additional symptoms and ≥ 3 prior failed surgical procedures. Fifty-three patients (10.5%) developed new or increased subjective facial paresthesias or numbness and 1 developed deafferentation pain; these symptoms resolved in 17 patients. Those who developed sensory loss had better long-term pain control (78% at 5 years).

Conclusions

Gamma Knife surgery proved to be safe and effective in the treatment of medically refractory trigeminal neuralgia and is of value for initial or recurrent pain management. Despite the goal of minimizing sensory loss with this procedure, some sensory loss may improve long-term outcomes. Pain relapse is amenable to additional GKS or another procedure.

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Hideyuki Kano, Douglas Kondziolka, Aftab Khan, John C. Flickinger, and L. Dade Lunsford

Object

Many patients with acoustic neuromas (ANs) have hearing function at diagnosis and desire to maintain it. To date, radiosurgical techniques have been focused on conformal irradiation of the tumor mass, with less attention to inner ear structures for which there was scant radiobiological information. The authors of this study evaluated tumor control and hearing preservation as they relate to tumor volume, imaging characteristics, and nerve and cochlear radiation dose following stereotactic radiosurgery (SRS) using the Gamma Knife.

Methods

Seventy-seven patients with ANs had serviceable hearing (Gardner-Robertson [GR] Class I or II) and underwent SRS between 2004 and 2007. This interval reflected more recent measurements of inner ear dosimetry during the authors' 21-year experience. The median patient age was 52 years (range 22–82 years). No patient had undergone any prior treatment for the ANs. The median tumor volume was 0.75 cm3 (range 0.07–7.7 cm3), and the median radiation dose to the tumor margin was 12.5 Gy (range 12–13 Gy). At diagnosis, a greater distance from the lateral tumor to the end of the internal auditory canal correlated with better hearing function.

Results

At a median of 20 months after SRS, no patient required any other additional treatment. Serviceable hearing was preserved in 71% of all patients and in 89% (46 patients) of those with GR Class I hearing. Significant prognostic factors for maintaining the same GR class included (all pre-SRS) GR Class I hearing, a speech discrimination score (SDS) ≥ 80%, a pure tone average (PTA) < 20 dB, and a patient age < 60 years. Significant prognostic factors for serviceable hearing preservation were (all pre-SRS) GR Class I hearing, an SDS ≥ 80%, a PTA < 20 dB, a patient age < 60 years, an intracanalicular tumor location, and a tumor volume < 0.75 cm3. Patients who received a radiation dose of < 4.2 Gy to the central cochlea had significantly better hearing preservation of the same GR class. Twelve of 12 patients < 60 years of age who had received a cochlear dose < 4.2 Gy retained serviceable hearing at 2 years post-SRS.

Conclusions

As currently practiced, SRS with the Gamma Knife preserves serviceable hearing in the majority of patients. Tumor volume and anatomy relate to the hearing level before radiosurgery and influence technique. A low radiosurgical dose to the cochlea enhances hearing preservation.

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Jay Jagannathan, Chun-Po Yen, Dibyendu Kumar Ray, David Schlesinger, Rod J. Oskouian, Nader Pouratian, Mark E. Shaffrey, James Larner, and Jason P. Sheehan

Object

This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis.

Methods

A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2–115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75–35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery.

Results

The mean radiographic follow-up duration was 14 months (median 10 months, range 4–37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p = 0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p = 0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40–100).

Conclusion:

Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

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Anil A. Dhople, Jared R. Adams, William W. Maggio, Shahid A. Naqvi, William F. Regine, and Young Kwok

Object

Few long-term studies of Gamma Knife surgery (GKS) for trigeminal neuralgia (TN) exist. The authors report their long-term experience with the use of GKS in a previously reported cohort of patients with TN that has now been followed since 1996.

Methods

One hundred twelve patients with TN were treated with GKS at the University of Maryland between June 1996 and July 2001. Of these, 67% had no invasive operations for TN prior to GKS, 13% had 1, 4% had 2, and 16% had ≥ 3. The right side was affected in 56% of cases, predominantly involving V2 (26%), V3 (24%), or a combination of both (18%) branches. The median age at diagnosis was 56 years, and median age at GKS was 64 years. The median prescription dose of 75 Gy (range 70–80 Gy) was delivered to the involved trigeminal nerve root entry zone. The authors assessed the degree of pain before and after GKS by using the Barrow Neurological Institute (BNI) pain scale.

Results

In total, 102 patients took the survey at least once, for a response rate of 91%. Although not found to alter the conclusions of this study, 7 cases of atypical TN were found and these patients were removed, for a total of 95 cases herein analyzed. The median follow-up was 5.6 years (range 13–115 months). Before GKS, 88% of patients categorized their pain as BNI IV or V (inadequate control or severe pain on medication), whereas the remainder described their pain as BNI III (some pain, but controlled on medication). After GKS, 64% reported a BNI score of I (no pain, no medications), 5% had BNI II (no pain, still on medication), 12% had BNI III, and 19% reported a BNI score of IV or V. The median time to response was 2 weeks (range 0–12 weeks) and the median response duration was 32 months (range 0–112 months). Eighty-one percent reported initial pain relief, and actuarial rates of freedom from treatment failure at 1, 3, 5, and 7 years were 60, 41, 34, and 22%, respectively. Response duration was significantly better for those who had no prior invasive treatment versus those in whom a previous surgical intervention had failed (32 vs 21 months, p < 0.02). New bothersome facial numbness was reported in 6% of cases.

Conclusions

This study represents one of the longest reported median follow-up periods and actuarial results for a cohort of patients with classic TN treated with GKS. Although GKS achieves excellent rates of initial pain relief, these results suggest a steady rate of late failure, particularly among patients who had undergone prior invasive surgical treatment. Despite a higher than expected recurrence rate, GKS remains a viable treatment option, particularly for patients who have had no prior invasive procedures. Patients with recurrences can still be offered salvage therapy with either repeat GKS, microvascular decompression, or rhizotomy.

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Toshinori Hasegawa, Dai Ishii, Yoshihisa Kida, Masayuki Yoshimoto, Joji Koike, and Hiroshi Iizuka

Object

The purpose of this study was to evaluate radiosurgical outcomes in skull base chordomas and chondrosarcomas, and to determine which tumors are appropriate for stereotactic radiosurgery as adjuvant therapy following maximum tumor resection.

Methods

Thirty-seven patients (48 lesions) were treated using Gamma Knife surgery (GKS); 27 had chordomas, seven had chondrosarcomas, and three had radiologically diagnosed chordomas. The mean tumor volume was 20 ml, and the mean maximum and marginal doses were 28 and 14 Gy, respectively. The mean follow-up period was 97 months from diagnosis and 59 months from GKS.

Results

The actuarial 5- and 10-year survival rates after GKS were 80 and 53%, respectively. The actuarial 5- and 10-year local tumor control (LTC) rates after single or multiple GKS sessions were 76 and 67%, respectively. All patients with low-grade chondrosarcomas achieved good LTC. A tumor volume of less than 20 ml significantly affected the high rate of LTC (p = 0.0182). No patient had adverse radiation effects, other than one in whom facial numbness worsened despite successful tumor control.

Conclusions

As an adjuvant treatment after resection, GKS is a reasonable option for selected patients harboring skull base chordomas or chondrosarcomas with a residual tumor volume of less than 20 ml. Dose planning with a generous treatment volume to avoid marginal treatment failure should be made at a marginal dose of at least 15 Gy to achieve long-term tumor control.

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Nicolas Massager, Ouzi Nissim, Carine Delbrouck, Isabelle Delpierre, Daniel Devriendt, Françoise Desmedt, David Wikler, Jacques Brotchi, and Marc Levivier

Object

The purpose of this study was to measure the dose of radiation delivered to the cochlea during a Gamma knife surgery (GKS) procedure for treatment of patients with vestibular schwannomas (VSs), and to analyze the relationship between cochlear irradiation and the hearing outcome of these patients.

Methods

Eighty-two patients with VSs were treated with GKS using a marginal dose of 12 Gy. No patient had neurofibromatosis Type 2 disease, and all had a Gardner–Robertson hearing class of I to IV before treatment, and a radiological and audiological follow-up of at least 1-year after GKS. The dosimetric data of the volume of the cochlea were retrospectively analyzed and were correlated with the auditory outcome of patients.

Results

The mean radiation dose delivered to the cochlear volume ranged from 1.30 to 10.00 Gy (median 4.15 Gy). The cochlea received significantly higher radiation doses in patients with worsening of hearing after GKS. A highly significant association between the cochlear and the intracanalicular dose of radiation delivered during GKS was found.

Conclusions

During GKS for VSs, relatively high doses of radiation can be delivered to the cochlea. Worsening of hearing after GKS can be the consequence of either radiation injury to the cochlea or the irradiation dose delivered into the auditory canal, or both.

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Juan J. Martin, Ajay Niranjan, Douglas Kondziolka, John C. Flickinger, Karl A. Lozanne, and L. Dade Lunsford

Object

Chordomas and chondrosarcomas of the skull base are aggressive and locally destructive tumors with a high tendency for local progression despite treatment. The authors evaluated the effect of stereotactic radiosurgery (SRS) on local tumor control and survival.

Methods

Twenty-eight patients with histologically confirmed chordomas (18) or chondrosarcomas (10) underwent Gamma Knife SRS either as primary or adjuvant treatment. Their ages ranged from 17 to 72 years (median 44 years). The most common presenting symptom was diplopia (26 patients, 93%). In two patients, SRS was the sole treatment. Twenty-six patients underwent between one and five additional surgical procedures. Two underwent an initial trans-sphenoidal biopsy. The average tumor volume was 9.8 cm3. The median dose to the tumor margin was 16 Gy.

Results

No patient was lost to follow-up. Transient symptomatic adverse radiation effects developed in only one patient. The actuarial local tumor control for chondrosarcomas at 5 years was 80 ± 10.1%. For chordomas both the actuarial tumor control and survival was 62.9 ± 10.4%.

Conclusions

Stereotactic radiosurgery is an important option for skull base chordomas and chondrosarcomas either as primary or adjunctive treatment. Multimodal management appears crucial to improve tumor control in most patients.

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Aurelia Kollová, Roman Liščák, Josef Novotný Jr., Vilibald Vladyka, Gabriela Šimonová, and Ladislava Janoušková

Object

Meningioma is the most frequent benign tumor treated with Gamma Knife surgery (GKS); however, the assessment of its efficacy and safety in slow-growing tumors is an ongoing process, requiring analysis of long-term results.

Methods

Three hundred sixty-eight patients harboring 400 meningiomas treated between 1992 and 1999 at Na Homolce Hospital were evaluated. The median patient age was 57 years (range 18–84 years). The median tumor volume was 4.4 cm3 (range 0.11–44.9 cm3). The median tumor margin dose to the 50% isodose line was 12.55 Gy (range 6.5–24 Gy). Descriptive analysis was performed in 331 patients (90%); 325 patients had a follow-up longer than 24 months (median 60 months), and six patients were included because of posttreatment complications. The volume of treated tumors decreased in 248 cases (69.7%), remained the same in 99 (27.8%), and increased in nine (2.5%). The actuarial tumor control rate was 97.9% at 5 years post-GKS. Perilesional edema after radiosurgery was confirmed on neuroim-aging in 51 patients (15.4%). The temporary and permanent morbidity rates after radiosurgery were 10.2 and 5.7%, respectively.

Results

A significantly higher incidence of tumor volume increase was observed in men compared with women and in tumors treated with a margin dose lower than 12 Gy. Significant risk factors for edema included an age greater than 60 years, no previous surgery, perilesional edema before radiosurgery, a tumor volume greater than 10 cm3, a tumor location in the anterior fossa, and a margin dose greater than 16 Gy.

Conclusions

Stereotactic radiosurgery is a safe method of treatment for meningiomas. A minimum margin dose of 12 to 16 Gy seems to represent the therapeutic window for benign meningiomas with a high tumor control rate in a mid-term follow-up period.

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Jay Jagannathan, Jason P. Sheehan, Nader Pouratian, Edward R. Laws, Ladislau Steiner, and Mary Lee Vance

Object

In this study the authors address the efficacy and safety of Gamma Knife surgery (GKS) in patients with adrenocorticotropic hormone–secreting pituitary adenomas.

Methods

A review of data collected from a prospective GKS database between January 1990 and March 2005 was performed in patients with Cushing's disease. All but one patient underwent resection for a pituitary tumor, without achieving remission. Successful endocrine outcome after GKS was defined as a normal 24-hour urinary free cortisol (UFC) concentration posttreatment after a minimum of 1 year of follow up. Patient records were also evaluated for changes in tumor volume, development of new hormone deficiencies, visual acuity, cranial nerve neuropathies, and radiation-induced imaging changes. Ninety evaluable patients had undergone GKS, with a mean endocrine follow-up duration of 45 months (range 12–132 months). The mean dose to the tumor margin was 23 Gy (median 25 Gy).

Normal 24-hour UFC levels were achieved in 49 patients (54%), with an average time of 13 months after treatment (range 2–67 months). In the 49 patients in whom a tumor was visible on the planning magnetic resonance (MR) image, a decrease in tumor size occurred in 39 (80%), in seven patients there was no change in size, and tumor growth occurred in three patients. Ten patients (20%) experienced a relapse of Cushing's disease after initial remission; the mean time to recurrence was 27 months (range 6–60 months). Seven of these patients underwent repeated GKS, with three patients achieving a second remission. New hormone deficiencies developed in 20 patients (22%), with hypothyroidism being the most common endocrinopathy after GKS. Five patients experienced new visual deficits or third, fourth, or sixth cranial nerve deficits; two of these patients had undergone prior conventional fractionated radiation therapy, and four of them had received previous GKS. Radiation-induced changes were observed on MR images in three patients; one had symptoms attributable to these changes.

Conclusions

Gamma Knife surgery is an effective treatment for persistent Cushing's disease. Adenomas with cavernous sinus invasion that are not amenable to resection are treatable with the Gamma Knife. A second GKS treatment appears to increase the risk of cranial nerve damage. These results demonstrate the value of combining two neurosurgical treatment modalities—microsurgical resection and GKS—in the management of pituitary adenomas.