Local control and toxicity outcomes in brainstem metastases treated with single fraction radiosurgery: is there a volume threshold for toxicity?

Gamma Knife Radiosurgery (GKRS) has been reported in the treatment of brainstem metastases while dose volume toxicity thresholds remain mostly undefined. A retrospective review of 52 brainstem metastases in 44 patients treated with GKRS was completed. A median dose of 18 Gy (range 10-22 Gy) was prescribed to the tumor margin (median 50 % isodose). 25 patients had undergone previous whole brain radiation therapy. Toxicity was graded by the LENT-SOMA scale. Mean and median follow-up was 10 and 6 months. Only 3 of the 44 patients are living. Multiple brain metastases were treated in 75 % of patients. Median size of lesions was 0.134 cc, (range 0.013-6.600 cc). Overall survival rate at 1 year was 32 % (95 % CI 51.0-20.1 %) with a median survival time of 6 months (95 % CI 5.0-16.5). Local control rate at 6 months and 1 year was 88 % (95 % CI 70-95 %) and 74 % (95 % CI 52-87 %). Cause of death was neurologic in 17 patients, non-neurologic in 20 patients, and unknown in four. Four patients experienced treatment related toxicities. Univariate analysis of tumor volume revealed that volume greater than 1.0 cc predicted for toxicity. A strategy of using lower marginal doses with GKRS to brain stem metastases appears to lead to a lower local control rate than seen with lesions treated within the standard dose range in other locations. Tumor size greater than 1.0 cc predicted for treatment-related toxicity.

Single-institution retrospective series of gamma knife radiosurgery in the treatment of multiple sclerosis-related trigeminal neuralgia: factors that predict efficacy.

BACKGROUND: Gamma knife radiosurgery (GKRS) has been reported as a treatment option for multiple sclerosis (MS)-related trigeminal neuralgia. OBJECTIVE: To report the outcomes of a single-institution retrospective series of MS-related trigeminal neuralgia. METHODS: Between 2002 and 2010, 35 patients with MS-related trigeminal neuralgia were treated with GKRS. The median maximum dose was 90 Gy. Data were analyzed to determine the response to GKRS and factors that may predict for efficacy. RESULTS: Of the 35 patients, 88% experienced a Barrow Neurological Institute (BNI) pain score of I-III at 3 months after GKRS. Kaplan-Meier estimates of 1-, 2- and 5-year freedom from BNI IV-V pain relapse were 57, 57 and 52%, respectively. Numbness was experienced by 39% of patients after GKRS, though no patients reported bothersome numbness. Several differences were noted between how the MS-related variant responded to GKRS and what has previously been reported for idiopathic trigeminal neuralgia. These include the observations that development of post-GKRS numbness did not predict for treatment response (p = 0.62) and that dorsal root entry zone dose did not predict for freedom from pain relapse (odds ratio 1.01, p = 0.1). Active smoking predicted for freedom from pain relapse (odds ratio 67.4, p = 0.04). CONCLUSION: GKRS is a viable noninvasive treatment option for MS-related trigeminal neuralgia.

Retrospective analysis of imaging techniques for treatment planning and monitoring of obliteration for gamma knife treatment of cerebral arteriovenous malformation.

BACKGROUND: It has been well established that Gamma Knife radiosurgery (GKS) is an effective treatment for brain arteriovenous malformations (AVMs). OBJECTIVE: To evaluate complete obliteration rates for magnetic resonance imaging (MRI)-based GKS treatment planning performed with and without angiography and to conduct a preliminary assessment of the utility of using pulsed arterial spin labeling (PASL) magnetic resonance (MR) perfusion imaging to confirm complete obliteration. METHODS: Forty-six patients were identified who had undergone GKS without embolization with a minimum follow-up of 2 years. One group was planned with integrated stereotactic angiography and MR (spoiled gradient recalled) images obtained on the day of GKS. A second technique avoided the risk of arteriography by using only axial MR images. Beginning in 2007, PASL MR perfusion imaging was routinely performed as a portion of the follow-up MRI to assess the restoration of normal blood flow of the nidus and surrounding area. RESULTS: The overall obliteration rate for the angiography/MRI group was 88.0% (29 of 33). Patients in the MRI-only group had an obliteration rate of 61.5% (8 of 13), with P=.092 with the Fisher exact test, which is not statistically significant. A Kaplan-Meier analysis was also not statistically significant (log rank test, P=.474). Four of 9 patients with incomplete obliteration on angiography also had shown residual abnormal blood flow on PASL imaging. CONCLUSION: This retrospective analysis shows that treatment planning technique used in GKS does not play a role in the eventual obliteration of treated AVMs. PASL may have potential in the evaluation of AVM obliteration.

Gamma knife radiosurgery in the treatment of tumor-related facial pain.

BACKGROUND: Intracranial neoplasms can cause pain similar to trigeminal neuralgia. Literature regarding radiosurgery for this is limited. We present a retrospective review of patients with tumor-related facial pain from benign lesions treated with gamma knife radiosurgery (GKRS) at Wake Forest University. OBJECTIVES: The primary objectives were to determine long-term pain relief and predictive factors for pain alleviation. METHODS: We reviewed 515 patients treated with GKRS for benign meningioma, vestibular schwannoma or trigeminal schwannoma between August 1999 and August 2010. Twenty-one eligible patients had tumor-related facial pain prior to GKRS. The median marginal tumor dose was 12 Gy. Long-term pain relief data were obtained by chart review and telephone interview. RESULTS: The median follow-up for symptom evaluation was 3.8 years. Seventeen of 21 patients (81%) experienced a Barrow Neurological Institute (BNI) score of I-III at 6 months following GKRS. Kaplan-Meier estimates of freedom from BNI IV-V relapse were 66% at 1 year and 53% at 2 years. No pain relapses occurred after 2 years. CONCLUSION: GKRS of benign lesions is a noninvasive option for patients with tumor-related facial pain. Pain relief is modest, with the majority of pain relapses occurring within 2 years and approximately one half of patients maintaining relief beyond 2 years.

Patterns of failure after treatment of atypical meningioma with gamma knife radiosurgery.

Atypical meningiomas have poor local control with emerging literature indicating the use of radiosurgery in treatment. The purpose of this study was to evaluate clinical outcomes including local control and failure pattern after Gamma Knife radiosurgery (GKRS) and factors that may affect these outcomes. Between 1999 and 2008, 24 patients were treated with GKRS as either primary or salvage treatment for pathologically proven atypical meningiomas. Treatment failures were determined by serial magnetic resonance imaging. A median marginal dose of 14 Gy was used (range 10.5-18 Gy). Overall local control rates at 1, 2, and 5 years were 75, 51, and 44%, respectively. With median follow-up time of 42.5 months, 14 of 24 patients experienced a treatment failure at time of last follow-up. Eight recurrences were in-field, four were marginal failures, and two were distant failures. Wilcoxon analysis revealed that the conformality index (CI) was a significant predictor of local recurrence (P = 0.04). CI did not predict for distant recurrences (P = 0.16). On multivariate analysis evaluating factors predicting progression free survival, dose >14 Gy was found to be statistically significant (P = 0.01). There appears to be a dose response using GKRS beyond 14 Gy but given the suboptimal local control rates in this study, higher doses may still be needed to obtain better local control.

Gamma knife stereotactic radiosurgery as salvage therapy after failure of whole-brain radiotherapy in patients with small-cell lung cancer.

PURPOSE: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). METHODS AND MATERIALS: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. RESULTS: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). CONCLUSIONS: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to improve this.

Predictive variables for the successful treatment of trigeminal neuralgia with gamma knife radiosurgery.

BACKGROUND: Gamma Knife radiosurgery (GKRS) has been reported to be an effective modality to treat trigeminal neuralgia. OBJECTIVE: To determine predictive factors for the successful treatment of trigeminal neuralgia with GKRS. METHODS: Between 1999 and 2008, 777 GKRS procedures for patients with trigeminal neuralgia were performed at our institution. Evaluable follow-up data were obtained for 448 patients. Median follow-up time was 20.9 months (range, 3-86 months). The mean maximum prescribed dose was 88 Gy (range, 80-97 Gy). Dosimetric variables recorded included dorsal root entry zone dose, pons maximum dose, dose to the petrous dural ridge, and cisternal nerve length. RESULTS: By 3 months after GKRS, 86% of patients achieved Barrow Neurologic Institute I to III pain scores, with 43% of patients achieving a Barrow Neurologic Institute I pain score. Twenty-six percent of patients reported posttreatment facial numbness; 28% of patients reported a post-GKRS procedure for relapsed pain, and median time to next procedure was 4.4 years. Multivariate analysis revealed that the development of postsurgical numbness (odds ratio [OR], 2.76; P = .006) was the dominant factor predictive of efficacy. Longer cisternal nerve length (OR, 0.85; P = .005), prior radiofrequency ablation (OR, 0.35; P = .028), and diabetes mellitus (OR, 0.38; P = .013) predicted decreased efficacy. The mean dose delivered to the dorsal root entry zone dose in patients who developed facial numbness (57.6 Gy) was more than the mean dose (47.3 Gy) given to patients who did not develop numbness (P = .02). CONCLUSION: The development of post-GKRS facial numbness is a dominant factor that predicts for efficacy of GKRS. History of diabetes mellitus or previous radiofrequency ablation may portend worsened outcome.

Toxicity of gamma knife radiosurgery in the treatment of intracranial tumors in patients with collagen vascular diseases or multiple sclerosis.

PURPOSE: To assess toxicity in patients with either a collagen vascular disease (CVD) or multiple sclerosis (MS) treated with intracranial radiosurgery. METHODS AND MATERIALS: Between January 2004 and April 2009, 6 patients with MS and 14 patients with a CVD were treated with Gamma Knife radiosurgery (GKRS) for intracranial tumors. Treated lesions included 15 total brain metastases in 7 patients, 11 benign brain tumors, 1 low grade glioma, and 1 cavernous malformation. Toxicities were graded by the Radiation Therapy Oncology Group Acute/Late Radiation Morbidity Scoring Criteria. "Rare toxicities" were characterized as those reported in the scientific literature at an incidence of <5%. RESULTS: Median follow-up time was 16 months. Median dose to the tumor margin was 13.0 Gy (range, 12-21 Gy). Median size of tumor was 5.0 cm(3) (range, 0.14-7.8 cm(3)). Of the 14 patients with CVD, none experienced a Grade 3 or 4 toxicity or a toxicity characterized as rare. Of the 6 patients with MS, 3 experienced rare toxicities, and two of these were Grade 3 toxicities. Rare complications included a patient experiencing both communicating hydrocephalus and facial nerve palsy, as well as 2 additional patients with motor cranial nerve palsy. High-grade toxicities included the patient with an acoustic neuroma requiring ventriculoperitoneal shunt placement for obstructive hydrocephalus, and 1 patient with a facial nerve schwannoma who experienced permanent facial nerve palsy. Interval between radiosurgery and high-grade toxicities ranged from 1 week to 4 months. CONCLUSIONS: Our series suggests that patients with MS who receive GKRS may be at increased risk of rare and high-grade treatment-related toxicity. Given the time course of toxicity, treatment-related edema or demyelination represent potential mechanisms.

Repeat gamma knife radiosurgery for trigeminal neuralgia.

PURPOSE: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. METHODS AND MATERIALS: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. RESULTS: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). CONCLUSION: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis.

OBJECT: As a strategy to delay or avoid whole-brain radiotherapy (WBRT) after resection of a brain metastasis, the authors used high-resolution MR imaging and cavity-directed radiosurgery for the detection and treatment of further metastases. METHODS: Between April 2001 and October 2009, 112 resection cavities in 106 patients with no prior WBRT were treated using radiosurgery directed to the tumor cavity and for any synchronous brain metastases detected on high-resolution MR imaging at the time of radiosurgical planning. A median dose of 17 Gy to the 50% isodose line was prescribed to the gross tumor volume, defined as the rim of enhancement around the resection cavity. Patients were followed up via serial imaging, and new brain metastases were generally treated using additional radiosurgery, with salvage WBRT typically reserved for local treatment failure at a resection cavity, numerous failures, or failures occurring at short time intervals. Local and distant treatment failures were determined based on imaging results. Kaplan-Meier curves were generated to estimate local and distant treatment failure rates, overall survival, neurological cause-specific survival, and time delay to salvage WBRT. RESULTS: Radiosurgery was delivered to the resection cavity alone in 57.5% of patients, whereas 24.5% of patients also received treatment for 1 synchronous metastasis, 11.3% also received treatment for 2 synchronous metastases, and 6.6% also received treatment for 3-10 additional lesions. The median overall survival was 10.9 months. Overall survival at 1 year was 46.8%. The local tumor control rate at 1 year was 80.3%. The disease control rate in distant regions of the brain at 1 year was 35.4%, with a median time of 6.9 months to distant failure. Thirty-nine of 106 patients eventually received salvage WBRT, and the median time to salvage WBRT was 12.6 months. Kaplan-Meier estimates showed that the rate of requisite WBRT at 1 year was 45.9%. Neurological cause-specific survival at 1 year was 50.1%. Leptomeningeal failure occurred in 8 patients. One patient had treatment failure within the resection tract. Seven patients required reoperation: 2 for resection cavity recurrence, 3 for radiation necrosis, 1 for hydrocephalus, and 1 for a CSF cutaneous fistula. On multivariate analysis, a preoperative tumor diameter > 3 cm was predictive of local treatment failure. CONCLUSIONS: Cavity-directed radiosurgery combined with high-resolution MR imaging detection and radiosurgical treatment of synchronous brain metastases is an effective strategy for delaying and even foregoing WBRT in most patients. This technique provides acceptable local disease control, although distant treatment failure remains significant.

Use of 3.0-T MRI for stereotactic radiosurgery planning for treatment of brain metastases: a single-institution retrospective review.

PURPOSE: To investigate the efficacy of 3.0-T magnetic resonance imaging (MRI) for detecting brain metastases for stereotactic radiosurgery (SRS) planning. METHODS AND MATERIALS: All adult patients scheduled for SRS treatment for brain metastases at our institution between October 2005 and January 2008 were eligible for analysis. All patients underwent radiosurgery treatment planning 3.0-T MRI on the day of scheduled radiosurgery and a diagnostic 1.5-T MRI in the days or weeks prior to radiosurgery for comparison. Both scans were interpreted by neuroradiologists who reported their findings in the radiology reports. We performed a retrospective review of the radiology reports to determine the number of brain metastases identified using each MRI system. RESULTS: Of 254 patients scheduled for treatment from October 2005 to January 2008, 138 patients had radiology reports that explicitly described the number of metastases identified on both scans. With a median interval of 17 days (range, 1-82) between scans, the number of metastases detected using 1.5-T MRI system ranged from 1 to 5 and from 1 to 8 using the 3.0 T-MRI system. Twenty-two percent of patients were found to have a greater number of metastases with the 3.0 T-MRI system. The difference in number of metastases detected between the two scans for the entire cohort ranged from 0 to 6. Neither histology (p = 0.52 by chi-sq test) nor time between scans (p = 0.62 by linear regression) were significantly associated with the difference in number of metastases between scans. CONCLUSIONS: The 3.0-T MRI system appears to be superior to a 1.5-T MRI system for detecting brain metastases, which may have significant implications in determining the appropriate treatment modality. Our findings suggest the need for a prospectively designed study to further evaluate the use of a 3.0 T-MRI system for stereotactic radiosurgery planning in the treatment of brain metastases.

Clinical experience with radiation therapy in the management of neurofibromatosis-associated central nervous system tumors.

PURPOSE: Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. METHODS AND MATERIALS: Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. RESULTS: Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. CONCLUSIONS: RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors.

Photon spectral characteristics of dissimilar 6 MV linear accelerators.

This work measures and compares the energy spectra of four dosimetrically matched 6 MV beams, generated from four physically different linear accelerators. The goal of this work is twofold. First, this study determines whether the spectra of dosimetrically matched beams are measurably different. This study also demonstrates that the spectra of clinical photon beams can be measured as a part of the beam data collection process for input to a three-dimensional (3D) treatment planning system. The spectra of 6 MV beams that are dosimetrically matched for clinical use were studied to determine if the beam spectra are similarly matched. Each of the four accelerators examined had a standing waveguide, but with different physical designs. The four accelerators were two Varian 2100C/Ds (one 6 MV/18 MV waveguide and one 6 MV/10 MV waveguide), one Varian 600 C with a vertically mounted waveguide and no bending magnet, and one Siemens MD 6740 with a 6 MV/10 MV waveguide. All four accelerators had percent depth dose curves for the 6 MV beam that were matched within 1.3%. Beam spectra were determined from narrow beam transmission measurements through successive thicknesses of pure aluminum along the central axis of the accelerator, made with a graphite Farmer ion chamber with a Lucite buildup cap. An iterative nonlinear fit using a Marquardt algorithm was used to find each spectrum. Reconstructed spectra show that all four beams have similar energy distributions with only subtle differences, despite the differences in accelerator design. The measured spectra of different 6 MV beams are similar regardless of accelerator design. The measured spectra show excellent agreement with those found by the auto-modeling algorithm in a commercial 3D treatment planning system that uses a convolution dose calculation algorithm. Thus, beam spectra can be acquired in a clinical setting at the time of commissioning as a part of the routine beam data collection.

A simple model predicts freedom from biochemical recurrence after low-dose rate prostate brachytherapy alone.

OBJECTIVE: The objective of this study was to describe a simple model that predicts freedom from biochemical recurrence (FFBR) in men with prostate cancer after treatment with low-dose rate prostate brachytherapy (LDRPB) alone. MATERIALS AND METHODS: One hundred thirty-two men were treated with LDRPB alone between September 1997 and April 2001. Sixty-four percent of men had low-risk disease (prostate-specific antigen [PSA] <10, Gleason <7, and T stage or =10, Gleason > or =7, or T stage T2b). The dosimetric quantifier D90 was calculated from a computed tomography scan performed 1 month after LDRPB. The percent positive biopsies (PPB) were determined for all patients. FFBR was estimated using the product limit method. All P values are 2-sided. RESULTS: The median follow-up is 65 months. The median D90 is 138 Gy (range, 47-221 Gy). Fourteen men have developed evidence of biochemical relapse at a median of 27 months (range, 6-42 months). The 5-year FFBR rate for the entire cohort is 88%. On univariate analysis, variables found to be associated with FFBR included: PSA, Gleason score, T stage, risk group, PPB, and D90. Multivariate analysis indicated that D90, PPB, and risk group were independently associated with FFBR. Patients were categorized based on the following 3 adverse prognostic factors: D90 <140 Gy, PPB > or =50%, and intermediate-risk group. Group 1 (0 factors, n = 30), group 2 (1 factor, n = 72), and group 3 (> or =2 factors, n = 30) patients had 5-year FFBR rates of 100% (+/-0%), 92% (+/-6%), and 67% (+/-18%) (P < 0.0001). CONCLUSIONS: We have developed a simple, robust model based on implant quality and disease factors that predicts FFBR in men with prostate cancer treated with LDRPB alone.

Optically guided linac radiosurgery with a Leksell head frame as an adjunct to Gamma Knife treatment.

Because of geometrical limitations in the helmet of the Leksell Gamma Knife(Elekta Corp., Atlanta, GA, USA) certain regions within the cranium cannot be targeted for treatment. We describe a method by which lesions in these regions can be treated with the Varian-Zmed stereotactic radiosurgery system utilizing an infrared optical positioning system attached to a Leksell head frame. We have measured the accuracy of the optical tracking system using a phantom attached to a Leksell frame and have determined that the system can target a linear accelerator radiosurgery beam to an accuracy of within 1 millimeter.

Gamma Knife surgery targeting the resection cavity of brain metastasis that has progressed after whole-brain radiotherapy.

OBJECT: Salvage treatment of large, symptomatic brain metastases after failure of whole-brain radiotherapy (WBRT) remains challenging. When these lesions require resection, there are few options to lower expected rates of local recurrence at the resection cavity margin. The authors describe their experience in using Gamma Knife surgery (GKS) to target the resection cavity in patients whose tumors had progressed after WBRT. METHODS: The authors retrospectively identified 143 patients in whom GKS had been used to target a brain metastasis resection cavity between 2000 and 2005. Seventy-nine of these patients had undergone WBRT prior to resection and GKS. The median patient age was 53 years, and the median prescribed dose was 18 Gy (range 8-24 Gy), with resection cavities of relatively larger volume (> 15 cm3). The GKS dose was prescribed at the 40 to 95% isodose contour (mode 50%). Local recurrence within 1 cm of the treatment volume occurred in four (5.1%) of 79 cases. The median duration of time to local recurrence was 6.1 months (range 2-13 months). The median duration of time to occurrence of distant metastases following GKS of the resection cavity was 10.8 months (range 2-86 months). Carcinomatous meningitis developed in four (5.1%) of 79 cases. Symptomatic radionecrosis requiring surgical treatment occurred in three (3.8%) of 79 cases. The median duration of survival following GKS of the resection cavity was 69.6 weeks. The median 2- and 5-year survival rates were 20.2 and 6.3%, respectively. CONCLUSIONS: When metastases progress after WBRT and require resection, GKS targeting the resection cavity is a viable strategy. In 75 (94.9%) of 79 cases, GKS of the resection cavity in patients in whom WBRT had failed appears to have achieved its goal of local disease control.

Does dose rate affect efficacy? The outcomes of 256 gamma knife surgery procedures for trigeminal neuralgia and other types of facial pain as they relate to the half-life of cobalt.

OBJECT: Gamma Knife surgery (GKS) is a treatment option for patients with refractory typical trigeminal neuralgia (TN), TN with atypical features, and atypical types of facial pain. The Gamma Knife's 201 60Co sources decay with a half-life of 5.26 years. The authors examined whether the decrease in dose rate over 4.6 years between Co source replacements affected the control rates of facial pain in patients undergoing GKS. METHODS: The authors collected complete follow-up data on 239 of 326 GKS procedures performed in patients with facial pain. Patients were classified by their type of pain. The isocenter of a 4-mm collimator helmet was targeted at the proximal trigeminal nerve root, and the dose (80-90 Gy) was prescribed at the 100% isodose line. Patients reported the amount of pain control following radiosurgery by answering a standardized questionnaire. Eighty percent of patients experienced greater than 50% pain relief, and 56% of patients experienced complete pain relief after GKS. Neither dose rate nor treatment time was significantly associated with either the control rate or degree of pain relief. A significant association between the type of facial pain and the pain control rate after GKS was observed (p < 0.001; Pearson chi-square test). In their statistical analysis, the authors accounted for changes in prescription dose over time to prevent the dose rate from being a confounding variable. There was no observable effect of the dose rate or of the treatment duration within the typical period to source replacement. CONCLUSIONS: Patients with facial pain appear to receive consistent treatment with GKS at any time during the first half-life of the Co sources.

Dosimetric quantifiers for low-dose-rate prostate brachytherapy: is V(100) superior to D(90)?

PURPOSE: The purpose of the present report is to describe the relationship between two dosimetric quantifiers (V(100) and D(90)) and freedom from biochemical recurrence (FFBR) in a cohort of men treated with low-dose-rate prostate brachytherapy (LDRPB) alone. METHODS AND MATERIALS: One hundred three men were treated with LDRPB alone between September 1997 and December 1999. All men had histologically confirmed clinically localized prostate cancer. Fifty-nine percent of the cohort had low-risk disease (defined as PSA<10, Gleason <7, and T stage /=10, Gleason>/=7, or T stage T2b). The prescription dose was 144Gy according to the Task Group 43 formalism. LDRPB was performed jointly by a radiation oncologist and a urologist. Dosimetric quantifiers (D(90), V(100)) were calculated from a CT scan performed 1 month after LDRPB. Biochemical recurrence was defined according to the ASTRO Consensus Definition. FFBR was estimated using the product-limit method. Disease-specific and treatment variables were examined as putative covariates for FFBR using the proportional hazards regression method. Univariate and multivariate methods were used. All p values are two sided. RESULTS: The median followup for the entire cohort is 61 months. The median followup of patients at risk for biochemical failure is 66 months. The median D(90) is 129Gy (range 47-221Gy), and the median V(100) is 86% (range 51-99%). Thirteen men have developed evidence of biochemical relapse at a median of 25 months (range 6-42 months). The 5-year estimate of FFBR for the entire cohort is 87% (95% CI 80-94%). On univariate analysis, disease-specific variables found to be significantly associated with FFBR included pretreatment PSA and percent positive biopsies. When considered as a continuous variable, each of the dosimetric quantifiers was associated with FFBR (V(100): p=0.007; D(90): p=0.05). D'Amico risk group classification is highly predictive of FFBR after LDRPB (HR 5.68, p=0.003). Multivariate analysis indicated that each dosimetric quantifier was independently associated with FFBR, but due to the high degree of correlation (Pearson correlation coefficient 0.94, p<0.0001) between the dosimetric quantifiers both could not be included simultaneously in the model. In the two models explored, V(100) was at least as good as D(90) in predicting FFBR. CONCLUSIONS: Dosimetric quantifiers (V(100) and D(90)) are independent predictors of FFBR after treatment with LDRPB alone. In our experience, V(100) seems to be at least equivalent (and perhaps superior) to D(90) for predicting FFBR.

Dosimetry and cancer control after low-dose-rate prostate brachytherapy.

PURPOSE: To describe the relationship between two commonly used dosimetric quantifiers (dose received by 90% of the prostate [D(90)] and volume receiving 100% of dose [V(100)]) and biochemical disease-free survival (bDFS) in a cohort of men treated with low-dose-rate prostate brachytherapy (LDRPB). METHODS AND MATERIALS: The information in this report concerned the first 63 men treated with LDRPB alone at our institution between September 1997 and September 1998. All men had histologically confirmed, clinically localized prostate cancer. All men were treated with(125)I. The prescription dose was 144 Gy according to the Task Group 43 formalism. LDRPB was performed jointly by a radiation oncologist and urologist. Dosimetric quantifiers (D(90), V(100)) were calculated from a CT scan performed 1 month after LDRPB. Biochemical recurrence was defined according to the American Society for Therapeutic Radiology and Oncology consensus definition. Biochemical relapse-free survival (bRFS) was estimated using the product-limit method. D(90) and V(100) were examined as putative covariates for bRFS using the proportional hazards regression method. All p values are two-sided. RESULTS: The median follow-up for the entire cohort was 62 months. The median D(90) was 122 Gy (range, 57-171Gy), and in 16 (25%) of 63 patients, the calculated D(90) was >140 Gy. The median V(100) was 81% (range, 51-97%). Nine men developed evidence of biochemical relapse at a median of 19 months (range, 6-38 months). The 5-year estimate of bRFS was 85% (95% confidence interval, 80-90%). The 5-year estimates of bRFS according to D(90) were as follows: D(90) > or =140 Gy, 86%; D(90) <140 Gy, 84% (p = not statistically significant). No threshold value of D(90) was predictive of the 5-year estimates of bRFS until the D(90) was <80 Gy (D(90) > or =80 Gy, 89%; D(90) <80 Gy, 50%; p = 0.02). The 5-year estimates of bRFS according to V(100) were as follows: V(100) > or =85%, 87%; V(100) <85%, 84% (p = not statistically significant). No threshold value of V(100) was predictive of the 5-year estimates of BRFS unless the dosimetry was particularly poor. The 5-year BRFS was 89% if the V(100) was > or =65% compared with 40% if the V(100) was <65% (p = 0.006). CONCLUSION: The dosimetric or quantifiers described in this report did not predict for bRFS after LDRPB unless the dosimetry was very poor. This finding is not in complete agreement with those of previous reports. Possible reasons for this observation are (1) the study in underpowered, (2) inherent measurement error, (3) dosimetric quantifiers are poor surrogates of the dose received by the cancer, and (4) length of follow-up. Additional work in the area of quality assessment after LDRPB is required.

Cancer control after low-dose-rate prostate brachytherapy performed by a multidisciplinary team with no previous prostate brachytherapy experience.

OBJECTIVES: To describe the biochemical disease-free survival observed in the first cohort men treated by a multidisciplinary team of clinicians with no previous experience in low-dose-rate prostate brachytherapy (LDRPB). METHODS: The information in this report concerns the first 63 men treated with LDRPB alone at our institution between September 1997 and September 1998. All men had histologically confirmed, clinically localized prostate cancer. All men were treated with iodine 125 according to published methods. The prescription dose was 144 Gy according to the Task Group 43 formalism. LDRPB was performed jointly by a radiation oncologist and urologist. Three definitions of biochemical recurrence were used: the American Society for Therapeutic Radiology and Oncology consensus definition; prostate-specific antigen level greater than 0.4 ng/mL at last follow-up; and prostate-specific antigen level greater than 0.2 ng/mL at last follow-up. Biochemical relapse-free survival was estimated using the product-limit method. Putative covariates for biochemical relapse-free survival were examined using the proportional hazards regression model. All P values are two-sided. RESULTS: The median follow-up for the entire cohort was 62 months. Of the 63 men, 45 (71%) had more than 60 months of follow-up. The median pretreatment prostate-specific antigen level was 6.68 ng/mL (range 1.1 to 23), and most men (44 of 63; 70%) had nonpalpable disease. The institutionally assigned Gleason score was less than 7 in 54 men (86%). Nine men developed evidence of biochemical relapse at a median of 19 months (range 6 to 38). The 5-year estimate of biochemical relapse-free survival was 85% (95% confidence interval 80% to 90%), 80% (95% confidence interval 74% to 86%), and 70% (95% confidence interval 64% to 76%) according to the three definitions given above. CONCLUSIONS: The biochemical results achieved in the first cohort of men treated with LDRPB by a previously inexperienced multidisciplinary team of clinicians are similar to the results reported from centers with extensive LDRPB experience.