Delayed toxicity from gamma knife radiosurgery to lesions in and adjacent to the brainstem.

The aims of this study were to assess the incidence of, and risk factors for, delayed toxicity following gamma knife stereotactic radiosurgery (GKRS) to lesions in and adjacent to the brainstem. We retrospectively evaluated the delayed toxicity of GKRS following the treatment of 114 lesions in and adjacent to the brainstem in 107 patients. The median tumor volume was 6.2 cm(3) and the median dose to the tumor margin was 16Gy. The mean follow-up was 40 months. Thirteen patients (12%) demonstrated clinical evidence of delayed toxicity, with a median latency to the development of toxicity of 6 months. The actuarial incidence of toxicity at 1 year and 5 years was 10.2% and 13.8%. Larger tumor volume (p=0.02) and larger treatment volume (p=0.04) were associated with an increased incidence of delayed toxicity. Large lesions adjacent to the brainstem have a higher than previously suspected rate of delayed toxicity.

Postoperative radiotherapy in 423 patients with pT3N0 prostate cancer.

PURPOSE: To evaluate the treatment outcome in pT3N0 patients with adenocarcinoma of the prostate treated with an elective course of postoperative irradiation (RT). METHODS AND MATERIALS: During a 22-year period, a total of 423 pT3N0 prostate cancer patients were treated at a single medical center with prostatic fossa RT, which was the only adjuvant therapy given. The patient characteristics were as follows: median age 66 years; Stage pT3aN0 in 296 (70%) and pT3bN0 in 127 (30%); Gleason score 2-4 in 12 (2.8%), 5-6 in 157 (37.1%), 7 in 151 (35.7%), and 8-10 in 100 (23.6%); and the median and mean preoperative prostate-specific antigen (PSA) level was 10 and 15.9 ng/mL, respectively. Radiotherapy consisted of a median dose of 48 Gy delivered to the prostatic fossa and its immediate vicinity. The median follow-up was 7 years. RESULTS: The 5- and 10-year actuarial survival rate was 92% and 73%, respectively, and the 5- and 10-year disease-free survival rate (PSA <0.05 ng/mL) was 69% and 51%, respectively. In multivariate analysis, the Gleason score was the most important predictor for survival (p = 0.00005), and pathologic stage and Gleason score were independently predictive of disease-free survival (p = 0.00007 and 0.0003, respectively). The worst prognostic category was represented by pT3bN0, Gleason score 7-10 patients who had a 5.3 times greater risk of tumor recurrence than those with pT3aN0, Gleason score 2-6. A high (>25 ng/mL) preoperative PSA level was also a predictor of tumor recurrence (p = 0.03). A total of 43 patients (10.2%) developed clinical recurrence. This included 30 patients (7%) with distant metastases alone and 13 (3%) with local recurrence, which included 2 patients who also had distant disease. An additional 88 patients (20%) had PSA elevation (>0.05 ng/mL). This treatment program was well tolerated, with acute toxicity common (62%) but of no clinical significance. No late or severe toxicity was recorded. CONCLUSION: Adjuvant radiotherapy, as given in this study, appears to substantially reduce the expected incidence of local tumor recurrence in pT3N0 prostate cancer patients. The treatment outcome was poor in pT3bN0 and Gleason score 7-10 patients, with >80% showing evidence of clinical or PSA recurrence at 10 years after therapy. This group should be the target of a prospective trial of systemic therapy.

Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery.

PURPOSE: To identify important prognostic factors predictive of survival and tumor control in patients with metastatic melanoma to the brain who underwent gamma knife radiosurgery. METHODS AND MATERIALS: A total of 122 consecutive patients with 332 intracranial melanoma metastases underwent gamma knife radiosurgery over a 5-year period. Of these, 39 (32%) also received whole-brain irradiation (WBI). The median tumor volume was 0.8 cm(3) (range: 0.02-30.20 cm(3)), and the median prescribed dose was 20 Gy (range: 14-24 Gy). Median follow-up was 6.8 months. Univariate and multivariate analyses of survival and freedom from progression were performed using the following parameters: status of systemic disease, intracranial tumor volume, number of lesions, tumor location, Karnofsky performance status, gender, age, and WBI. RESULTS: Overall median survival was 7.0 months from time of radiosurgery and 9.1 months from the onset of brain metastasis. In multivariate analysis, improved survival was noted in patients with total intracranial tumor volume <3 cm(3) (p = 0.003) and inactive systemic disease (p = 0.0065), whereas other parameters studied were of lesser importance (tumor location, p = 0.056, and Karnofsky performance status, p = 0.086), or of no significance (number of lesions, WBI, age, and gender). Freedom from subsequent brain metastasis depended on intracranial tumor volume (p = 0.0018) and status of systemic disease (p = 0.034). CONCLUSIONS: Stereotactic radiosurgery is an effective treatment modality for patients with intracranial metastatic melanoma. Tumor volume and status of systemic disease are good independent predictors of survival and freedom from tumor progression.

Measurements of the relative output factors for CyberKnife collimators.

OBJECTIVE: To determine accurately the relative output factors, defined as the ratio of the nominal dose rate for a given collimator to that of the 60-mm collimator. This is particularly important for radiosurgical treatment of functional disorders, such as trigeminal neuralgia, in which a single large radiation dose is delivered to the target with a small collimator, such as the 5-mm collimator for CyberKnife radiosurgery. Numerous studies on the output factors have been reported for the Leksell gamma knife unit but none for the CyberKnife system. METHODS: Measurements of the relative output factors for all 12 collimators were performed by three different methods: silicon diode, radiographic film, and thermoluminescent dosimetry microcubes. The silicon diode is designed for measurements in small (1-50 MV) photon beams performed in water or air. Film and thermoluminescent dosimetry measurements were performed in a plastic phantom. RESULTS: The measured relative output factors for the three methods were very similar except for the three smallest collimators (5, 7.5, and 10 mm). The measured difference between the above methods was approximately 2%. The mean value of the output factor for the 5-mm collimator was 0.686 +/- 0.024. The uncertainties of the output factors are expected to increase with the decrease of collimator diameter. They range from approximately 1 to 4% of the relative output factor. CONCLUSION: The relative output factor can be measured with an acceptable accuracy even for the smallest (5-mm) CyberKnife collimators. This requires the selection of appropriate dosimetric detectors and measuring procedures. The results obtained with the diode are considered more accurate than with the other two methods.

Dosimetric comparison of CyberKnife with other radiosurgical modalities for an ellipsoidal target.

OBJECTIVE: To compare treatment plans obtained with the CyberKnife (CK) (Accuray, Inc., Sunnyvale, CA) with those of other commonly used radiosurgical modalities, such as the gamma knife (GK), linear accelerator multiple arcs, conformally shaped static fields, and intensity-modulated radiotherapy (IMRT). METHODS: An ellipsoidal simulated target was chosen centrally located in a three-dimensional model of a patient's head acquired with magnetic resonance or computed tomographic imaging. It was 25 mm in diameter and 35 mm long. The aims of treatment plans were 100% target volume coverage with an appropriate isodose line, minimum radiation dose to normal tissue, and clinically acceptable delivery. These plans were evaluated by use of a dose-volume histogram and other commonly used radiosurgical parameters such as target coverage, homogeneity index, and conformity index. RESULTS: All selected treatment modalities were equivalent in providing full target coverage. For dose homogeneity, all modalities except for multiple isocenter plans for GK (homogeneity index, 2.0) were similar (homogeneity index, congruent with 1.25). Dose conformity was essentially equivalent for all treatment plans except for IMRT, which had a slightly higher value (conformity index, congruent with 1.27). There was a substantial variation in the radiation dose to normal tissue between the studied modalities, particularly at the lower dose levels. CONCLUSION: CK plans seemed to be more flexible for a given target size and shape. For a target of limited volume and essentially of any shape, one could obtain similarly good conformal dosimetry with CK and GK. For a regular-shaped but other than spherical target, homogeneous dose distribution could be obtained with all selected modalities except for multiple isocenters, linear accelerator multiple arcs, or GK. Both IMRT and conformally shaped static fields offered good alternative treatment modalities to CK, GK, or linear accelerator multiple arc radiosurgery, with slightly inferior dosimetry in conformity (IMRT).

Fetal radiation doses for model C gamma knife radiosurgery.

OBJECTIVE: To assess fetal radiation doses in a pregnant patient undergoing gamma knife stereotactic radiosurgery (GKRS) and to quantify the components of extracranial radiation doses by means of phantom measurements. METHODS: A patient in her 25th week of pregnancy received GKRS with the Model C gamma knife for a solitary metastatic melanoma of the brain. A single isocenter with the 14-mm collimator and trunnions was used to deliver 20 Gy to the lesion defined to the 80% isodose line. Fetal radiation doses were assessed with phantom measurements before GKRS and then measured during GKRS. In addition, doses to the lateral canthi, thyroid, sternum, and pelvis were monitored with thermoluminescent dosimeters in 20 consecutive patients during their GKRS. Phantom measurements were also performed to identify extracranial radiation doses to these structures. RESULTS: Fetal radiation doses were 0.31, 0.20, and 0.15 cGy to the top, middle, and bottom of the uterus, respectively. These approximately corresponded to 0.01% of the maximum tumor dose of 25 Gy. The mean extracranial doses in 20 patients were 36.9, 5.8, 3.3, and 0.6 cGy to the lateral canthi, thyroid, sternum, and pelvis, respectively. Phantom measurements supported the results obtained from the patient measurements and further refined estimates of doses to extracranial sites. These measurements were also compared with those of a previously reported study with the use of the Model U. CONCLUSION: Measured radiation doses in a pregnant patient to extracranial sites, including those to the fetus, were very low. We think that GKRS is a safe treatment, particularly with the Model C, and could be recommended to carefully selected patients with brain metastases who are in the second and third trimester of pregnancy.

Gamma knife radiosurgery for pituitary adenoma: early results.

OBJECTIVE: In recent years, gamma knife radiosurgery (GKRS) has emerged as an important treatment modality in the management of pituitary adenomas. Treatment results after performing GKRS and the complications of this procedure are reviewed. METHODS: Between 1994 and 2002, a total of 78 patients with pituitary adenomas underwent a total of 84 GKRS procedures in our medical center. This patient group comprised 46 men (59%) and 32 women (41%). All patients were treated for recurrent or residual disease after surgery or radiotherapy, with 83% presenting with extensive tumor involvement. The cavernous sinus was involved in 75 patients (96%), and 22 patients (28%) had hormone-secreting adenomas. This latter subset of patients included 12 prolactinomas (15%), 6 growth-hormone secreting tumors (8%), and 4 adrenocorticotropic hormone-secreting tumors (5%). The median tumor volume was 2.3 cm(3), and the median radiation dose was 15 Gy defined to the 50% isodose line. The mean and median follow-up periods were 41 and 36 months, respectively. RESULTS: GKRS was tolerated well in these patients; acute toxicity was uncommon and of no clinical significance. Late toxicity was noted in three patients (4%) and consisted of VIth cranial nerve palsy. In two patients, there was spontaneous resolution of this palsy, and in one patient, it persisted for the entire 3-year duration of follow-up. Of the 15 patients who presented with cranial nerve dysfunction, 8 (53%) experienced complete recovery and 3 (20%) showed major improvement within 12 months of therapy. Tumor volume reduction was slow, with 30% of patients showing decreased tumor volume more than 3 years after undergoing GKRS. None of the 56 patients with nonfunctioning tumors showed progression in the treated volume, and 4 (18%) of the 22 hormone-secreting tumors relapsed (P = 0.008). Of the four patients with adrenocorticotropic hormone-secreting adenomas, therapy failed in two of them. All six patients with growth hormone-producing tumors responded well to therapy. Of the 12 patients with prolactinomas 10 (83%) had normalization of hormone level and 2 patients experienced increasing prolactin level. Two patients with prolactinomas had three normal pregnancies after undergoing GKRS. CONCLUSION: GKRS is a safe and effective therapy in selected patients with pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus. A radiation dose higher than 15 Gy is probably needed to improve control of hormone-secreting adenomas. Longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.

Study of magnetic resonance imaging-based arteriovenous malformation delineation without conventional angiography.

OBJECTIVE: In this study, we aimed to assess the feasibility of arteriovenous malformation (AVM) delineation for gamma knife radiosurgery without conventional angiography and to correlate factors that may affect AVM delineation. METHODS: A series of 57 consecutive patients with AVMs treated with gamma knife radiosurgery from August 1994 to December 2000 were reviewed. All patients in the study had undergone pretreatment angiography. The mean AVM volume was 2.8 cm(3), with a median of 2.0 cm(3) (range, 0.04-22 cm(3)). All AVMs were delineated on the original frame-based magnetic resonance imaging (MRI) scans by a vascular neurosurgeon without the assistance of angiography and then compared with the actual AVM delineation on the basis of previously performed angiography and MRI. Univariate correlation analysis was used to determine the relationship of AVM coverage, size, diffuseness, previous embolization, and hemorrhage parameters. RESULTS: The study volume or MRI-based volume alone coincided with the actual treatment volume by a mean of 58% for diffuse and 87% for nondiffuse AVMs (P = 0.0005). At AVM volume greater than 2 cm(3), the median percentage of coinciding volume was 63% for embolized AVMs and 82% for nonembolized AVMs (P = 0.0315). Conversely, the study volume overestimated the actual treatment volume by a mean of 57% for AVMs larger than 2 cm(3) versus 25% for AVMs smaller than 2 cm(3) (P = 0.0012). In general, the percentage of the coinciding volume was inversely related to that of the excess volume, whereas both the study volume and the coinciding volume were proportionate to AVM volume at treatment. CONCLUSION: MRI-based AVM delineation without conventional angiography may be feasible only for selected patients, such as those with nondiffuse and large nonembolized AVMs.

The Leksell gamma knife Model U versus Model C: a quantitative comparison of radiosurgical treatment parameters.

OBJECTIVE: We present a quantitative comparison of radiosurgery treatments for cavernous sinus tumors using the Leksell gamma knife Model U versus the Model C with automatic positioning system (APS) (Elekta Instruments, Norcross, GA). METHODS: At our medical center from August 1994 through May 2000, the Model U was used to treat 96 patients (37 men [39%] and 59 women [61%]; median age, 54.5 yr) with benign cavernous sinus tumors: 43 meningiomas (45%), 48 pituitary tumors (50%), and 5 others (5%). From June 2000 through April 2002, the Model C with APS treated 45 patients (20 men [44%] and 25 women [56%]; median age, 51.4 yr) with 15 meningiomas (33%), 29 pituitary tumors (65%), and 1 schwannoma (2%). The two groups had similar treated tumor volumes (Model U mean, 4.3 cm(3); Model C mean, 4.2 cm(3)), equivalent tumor distances from critical structures (optic nerve, chiasm, and pons), comparable distributions in Sekhar tumor grades, and the same median prescribed dose of 15 Gy to the 50% isodose line at the tumor periphery. All planning and treatments were performed by the same radiosurgery team to minimize dosage to adjacent critical tissues and to optimize conformity index. RESULTS: Analysis of multiple treatment parameters showed that the Model C plans were superior. Model C treatments had an improved conformity index (Model U mean, 1.7; Model C mean, 1.6; P < 0.02) and a lower underdosed tumor volume (Model U mean, 0.4 cm(3); Model C mean, 0.1 cm(3); P < 0.004). The total treated volume and the excess treated volume were similar. The Model C group had a reduction in optic chiasm dose (Model C mean dose, 3.8 Gy; Model U mean dose, 5.3 Gy; P < 0.0001). The average number of isocenters was slightly higher for the Model C group (6.7 versus 6 for the Model U), but with a lower mean number of collimator sizes (1 versus 2 for the Model U). Model C plans required a mean of 93 fewer plugs per treatment, thus contributing to an estimated 67.6 minutes saved per treatment session. CONCLUSION: Comparison of radiosurgery treatments using the Leksell gamma knife Model U versus the Model C with APS was performed by quantitative analysis of treatment parameters on a cohort of benign cavernous sinus tumors. Treatment plans using the Model C resulted in better tumor coverage (improved conformity, less underdosed tumor volume) and decreased optic chiasm dose. An estimated average of 1 hour was saved per treatment when using the Model C with APS.

Gamma knife radiosurgery for benign cavernous sinus tumors: quantitative analysis of treatment outcomes.

OBJECTIVE: We review our 8-year experience with gamma knife radiosurgery (GKRS) for the treatment of patients with benign cavernous sinus tumors and present a quantitative analysis of factors relevant to treatment outcomes. METHODS: From 1994 to 2002, a total of 139 patients with benign cavernous sinus tumors were treated in 145 sessions. Their median age was 53 years, and the median follow-up was 3.5 years. The tumors included 57 meningiomas, 76 pituitary tumors (49 nonfunctional adenomas, 15 prolactinomas, 5 adrenocorticotropic hormone-secreting tumors, 6 growth hormone-secreting tumors, and 1 plurihormone-secreting tumor), 4 schwannomas, 1 hemangioma, and 1 paraganglioma. Sekhar tumor grades were as follows: I, n = 28 (20%); II, n = 42 (30%); III, n = 42 (30%); IV, n = 19 (14%); and V, n = 8 (6%). The median tumor volume was 3.4 cm(3), and the median prescribed dose was 15 Gy defined to the 50% isodose line. RESULTS: A total of 136 treated tumors (97.8%) were well controlled by GKRS, with low morbidity. For meningiomas, 29 tumors (51%) were unchanged and 26 (46%) were smaller at a median of 15.2 months. For pituitary tumors, 50 (66%) were unchanged and 25 (33%) were smaller at a median of 20.6 months. Improvement in cranial nerve (CN) function was seen in 19 (36.5%) of 52 patients with pre-GKRS deficits, and 3 patients (2.2%) developed new stable CN deficits after GKRS: 1 patient developed IVth CN palsy at 9 months, and 2 developed persistent VIth CN palsies at 43 and 45 months, respectively, that required surgical correction. Two patients developed transient VIth CN palsies at 48 months that self-resolved after another year. Endocrine function normalized for all 6 treated patients with a growth hormone-secreting tumor at a median of 18 months. One of the 5 adrenocorticotropic hormone-secreting tumors required retreatment after 17 months because of continued cortisol elevation. Thirteen (87%) of 15 prolactinoma patients had normalized prolactin levels within 2 years of the procedure; 2 patients relapsed by endocrine criteria at 18 and 22 months after GKRS. Two patients with normalized prolactin levels completed three normal pregnancies within 3 years of treatment. Six patients (4.3%) with a median tumor volume of 8 cm(3) developed radiation-induced injury at a median of 36 months after GKRS. Five of these patients also underwent external beam radiotherapy and received a median dose of 52.2 Gy in 30 fractions. Quantitative analysis revealed that the radiation dose to critical structures (optic apparatus and pons) is correlated with their distance from tumor margins. Underdosed tumor volume, tumor volume, and total treated volume are correlated with treatment outcomes. CONCLUSION: GKRS is a safe and effective treatment for selected patients with benign cavernous sinus tumors and is an important adjunct for treating postoperative tumor residual and/or recurrent tumor. Continued analysis of treated patients over an extended time is needed to evaluate long-term disease control and potential late GKRS complications.

Survival and pattern of failure in brain metastasis treated with stereotactic gamma knife radiosurgery.

OBJECT: Gamma knife radiosurgery (GKS) has become a well-established treatment modality in the management of selected patients with brain metastasis. The authors review the management patients with these tumors treated at a single center. METHODS: Between 1994 and 2002, 458 consecutive patients with metastatic brain disease underwent GKS. There were 1305 lesions treated in 680 separate sessions. The histological diagnosis was melanoma in 231 (50%), lung cancer in 94 (20.5%), breast cancer in 38 (8.3%), renal cell carcinoma (RCC) in 29 (6.3%), colon carcinoma in 13 (2.8%), unknown primary site in 14 (3.1%), and other in 39 patients (8.5%). The median tumor volume was 0.9 cm3 and the median volume treated was 2.3 cm3. The median radiation dose was 18 Gy prescribed to a median isodose of 60%; the median dose was 20 Gy in melanoma, sarcoma, and RCC. Whole-brain radiotherapy (WBRT) either prior to or following GKS was performed in 114 patients (25%). Follow up ranged from 3 to 84 months with a median of 9 months. The median survival for all patients was 9 months and depended on tumor histology. Survival ranged from 6 months for patients with colon carcinoma, unknown primary tumors, and other tumors to 17 months for those with breast cancer. Median survival in patients with melanoma was 8 months. In multivariate analysis Karnofsky Performance Scale score (< 70 vs > 70), status of systemic disease (yes vs no), histological diagnosis, and total intracranial tumor volume were the only significant factors influencing survival. The number of brain metastases (one-five), WBRT (yes vs no), and age were not significant. Pattern of failure was different in patients with melanoma compared with those with other diagnoses. Cause of death in patients with melanoma was in 50% of the cases due to systemic disease and in 42% due to central nervous system causes, whereas it was 70% for the former and 23% for the latter in patients with other diagnoses. The treatment was well tolerated with significant late toxicity requiring craniotomy for removal of a necrotic focus in only 20 patients (4.7%). CONCLUSIONS: Gamma knife radiosurgery provided an excellent palliation with low incidence of toxicity. A Phase III prospective randomized trial is required to define the role of WBRT in combination with GKS.

Episcleral plaque 125I radiotherapy with episcleral LCF hyperthermia: a prospective randomized trial.

PURPOSE: The purpose of this study was to search for an optimal radiation dose in the treatment of patients with uveal melanoma using 125I episcleral plaque radiotherapy (EPRT) and episcleral hyperthermia (HT). METHODS AND MATERIALS: From 1991-1998, 35 patients with uveal melanoma were enrolled in a phase II prospective randomized trial of 125I EPRT combined with episcleral HT. Two groups were closely matched for pre-treatment patient and tumor characteristics. Group 1: N = 16, and Group 2: N = 19. The median dose to the tumor apex for Group 1 was 80.0 Gy and 60.8 Gy for Group 2. Episcleral HT was given once for 45 min immediately prior to EPRT with a median temperature of 44 degrees C for both groups. The median follow-up was 5.5 years for Group 1 and 5.3 years for Group 2. RESULTS: The median tumor height decreased 1.7 mm for patients of both groups. The 5- and 8-year probability of local recurrence was 33% for Group 1, and 25% for Group 2, p = 0.73. The 5-year probability of DFS was 54% for Group 1 and 67% for Group 2, p = 0.51. The 5- and 8-year overall survival was 68% and 34%, respectively, for Group 1, and 83% and 50%, respectively, for Group 2, p = 0.60. The rate of distant metastasis at 5- and 8-years for Group 1 was 29% and 62%, respectively, and 17% and 17%, respectively, for Group 2, p = 0.18. The incidence of enucleation was 4 (25%) in Group 1 vs. 4 (22%) in Group 2. The incidence of late complications was similar in either treatment group. The ambulatory visual acuity (> 5/200) at last follow-up was slightly better in Group 2 (80%) than Group 1 (64%). CONCLUSIONS: Treatment outcomes were similar despite a 25% difference in radiation dose. In view of these findings and in an attempt to reduce the incidence of late treatment toxicity a still lower radiation dose in combination with HT needs to be studied. The reported outcomes need to be evaluated with caution due to the small number of patients in this study.

Radiotherapy and stereotactic radiosurgery for pituitary tumors.

Based on a review of the literature and our medical center experience, we believe that transphenoidal surgery is the procedure of choice in most patients with pituitary adenomas. Conversely, SRS is a procedure of choice for those with cavernous sinus involvement. Patients with incomplete surgical excision should be considered either for a planned stereotactic treatment or for external beam radiotherapy. The same applies to patients with recurrent tumors. We favor stereotactic treatment in patients who have tumors that are less than 35 mm in diameter and at least 3 mm from the chiasm or optic nerves. Other patients should be considered for three-dimensional conformal radiotherapy. Radiotherapy provides a good treatment alternative in those patients who either refuse surgery or have contraindications to this therapy. Contemporary radiotherapy and SRS for pituitary adenomas is safe and effective treatment. This treatment should be undertaken in medical centers with appropriate expertise and instrumentation.

The CyberKnife stereotactic radiosurgery system: description, installation, and an initial evaluation of use and functionality.

The CyberKnife Stereotactic Radiosurgery System is manufactured by Accuray, Inc. (570 Del Rey Avenue, Sunnyvale, CA 94085; telephone 1-888/522-3740 or 1-408/522-3740; http://www.accuray.com). It is currently available for purchase (capital cost of US $3.2 million plus US $0.5 to 0.75 million for site setup), or in a revenue-sharing plan (US $0.5 to 0.75 million setup cost). [Figure: see text].

Gamma knife radiosurgery for trigeminal neuralgia.

OBJECTIVE: The purpose of this study was to assess outcomes in patients treated with gamma knife radiosurgery for trigeminal neuralgia. METHODS: From 1997 to 2003, a total of 49 patients with trigeminal neuralgia underwent gamma knife radiosurgery. The trigeminal root entry zone immediately adjacent to the pons was targeted by use of a 4-mm collimator to deliver 40 Gy to the 50% isodose line (maximum dose, 80 Gy). Special care was taken to limit radiation dose to the adjacent pons to 12 Gy. Of the 49 study patients, all had undergone previous medical therapy, 8 (16%) had undergone microvascular decompression, 8 (16%) had undergone percutaneous rhizotomy, 2 (4%) had undergone linear accelerator-based radiosurgery, and 5 (10%) presented with multiple sclerosis. The median duration of symptoms was 6 years. There were 29 female patients (59%) and 20 male patients (41%). Facial pain outcomes were assessed by use of the Barrow Neurological Institute pain score. Other outcomes assessed included recurrence of symptoms and treatment toxicity. The median follow-up period was 49 months. RESULTS: At last evaluation, a total of 27 patients (61%) with idiopathic trigeminal neuralgia reported pain relief (scores of IIIb or less). This included 14 patients (32%) who reported complete pain relief when not receiving medications. Significant recurrence of pain after an initial interval of relief was reported by 10 patients (23%). Mean time to pain recurrence was 9.6 months (range, 2-36 mo). Mild to moderate facial numbness was experienced by 13 patients (29%), whereas 8 (18%) reported mild dysesthesias. CONCLUSION: Gamma knife radiosurgery established durable pain relief in 61% of patients with medically refractory idiopathic trigeminal neuralgia. A longer follow-up period is necessary to fully assess the incidence of late complications and recurrences.

Squamous cell carcinoma arising in a second branchial cleft cyst.

The existence of primary branchiogenic carcinoma is controversial. In 1950, Martin et al. established four criteria for the diagnosis of primary branchiogenic carcinoma. In 1989, Khafif et al. proposed new criteria, which are currently most recognized in the literature. A pathologic description of the surgical specimen is analyzed and compared with a critical review of the literature. A case is presented in which imaging established the diagnosis of a benign second branchial cleft cyst 2 years prior to the diagnosis of a branchiogenic carcinoma in the same cyst. This cyst was resected and was found to have squamous cell carcinoma arising from the benign epithelium. This case satisfies the histologic criteria established by Martin and Khafif for a primary branchiogenic carcinoma arising in a previously benign second branchial cleft cyst.

Biochemotherapy for metastatic melanoma with limited central nervous system involvement.

OBJECTIVES: Biochemotherapy outcomes were examined in stage IV melanoma patients with previously treated or active central nervous system (CNS) metastases prior to systemic therapy. PATIENTS AND METHODS: Patients who received biochemotherapy for metastatic melanoma with active or pretreated CNS metastases were compared to patients without evidence of CNS metastases in terms of response, time to progression (TTP), overall survival (OS), and treatment toxicity. RESULTS: Twenty-six (16%) of 159 total patients began biochemotherapy with previously treated or active CNS metastases (group I), compared to 133 (84%) who were radiographically free of CNS involvement (group II). A partial or complete response to biochemotherapy was seen in 13 (50%) group I patients, compared to 56 (42%) group II patients (p = 0.243). The median TTP and median survival were 5.5 and 7.0 months, respectively, for group I patients and 6.0 and 9.9 months, respectively, for group II patients (p = 0.222 and 0.434 for TTP and OS, respectively). Five (19%) group I patients survived longer than 24 months. Gamma Knife radiosurgery or surgical resection of CNS disease prior to biochemotherapy improved survival versus delayed treatment (p = 0.017 and 0.005, respectively). CONCLUSION: Patients with limited CNS metastases and widespread systemic disease can achieve prolonged survival with targeted treatment of CNS lesions and aggressive systemic therapy.