Results of three or more Gamma Knife radiosurgery procedures for recurrent trigeminal neuralgia.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN. METHODS: The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III). RESULTS: A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up. CONCLUSIONS: The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of long-term pain relief, recurrence, and adverse effects.

Recommendations on the practice of calibration, dosimetry, and quality assurance for gamma stereotactic radiosurgery: Report of AAPM Task Group 178.

The American Association of Physicists in Medicine (AAPM) formed Task Group 178 (TG-178) to perform the following tasks: review in-phantom and in-air calibration protocols for gamma stereotactic radiosurgery (GSR), suggest a dose rate calibration protocol that can be successfully utilized with all gamma stereotactic radiosurgery (GSR) devices, and update quality assurance (QA) protocols in TG-42 (AAPM Report 54, 1995) for static GSR devices. The TG-178 report recommends a GSR dose rate calibration formalism and provides tabulated data to implement it for ionization chambers commonly used in GSR dosimetry. The report also describes routine mechanical, dosimetric, and safety checks for GSR devices, and provides treatment process quality assurance recommendations. Sample worksheets, checklists, and practical suggestions regarding some QA procedures are given in appendices. The overall goal of the report is to make recommendations that help standardize GSR physics practices and promote the safe implementation of GSR technologies.

Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases.

BACKGROUND: The diagnosis-specific graded prognostic assessment scale (ds-GPA) for patients with melanoma brain metastasis (BM) utilizes only 2 key prognostic variables: Karnofsky performance status and the number of intracranial metastases. We wished to determine whether inclusion of cumulative intracranial tumor volume (CITV) into the ds-GPA model for melanoma augmented its prognostic value. OBJECTIVE: To determine whether or not CITV augments the ds-GPA prognostic scale for melanoma. METHODS: We analyzed the survival pattern of 344 melanoma patients with BM treated with stereotactic radiosurgery (SRS) at separate institutions and validated our findings in an independent cohort of 201 patients. The prognostic value of ds-GPA for melanoma was quantitatively compared with and without the addition of CITV using the net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metrics. RESULTS: The incorporation of CITV into the melanoma-specific ds-GPA model enhanced its prognostic accuracy. Addition of CITV to the ds-GPA model significantly improved its prognostic value, with NRI > 0 of 0.366 (95% CI: 0.125-0.607, P = .002) and IDI of 0.024 (95% CI: 0.008-0.040, P = .004). We validated these findings that CITV improves the prognostic utility of melanoma ds-GPA in an independent cohort of 201 melanoma cohort. CONCLUSION: The prognostic value of the ds-GPA scale for melanoma BM is enhanced by the incorporation of CITV.

Improving the Prognostic Value of Disease-Specific Graded Prognostic Assessment Model for Renal Cell Carcinoma by Incorporation of Cumulative Intracranial Tumor Volume.

BACKGROUND: We tested the prognostic value of cumulative intracranial tumor volume (CITV) in the context of a disease-specific Graded Prognostic Assessment (ds-GPA) model for renal cell carcinoma (RCC) patients with brain metastasis (BM) treated with stereotactic radiosurgery (SRS). METHODS: Patient and tumor characteristics were collected from RCC cohorts with new BM who underwent SRS. Univariable and multivariable logistic regression model was used to test the prognostic value of CITV, Karnofsky Performance Score (KPS), and the number of BM. Net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to assess whether CITV improved the prognostic utility of RCC ds-GPA. RESULTS: In univariable logistic regression models, CITV, KPS, and the number of BM were independently associated with RCC patient survival. In a multivariable Cox proportional hazard model, the association between CITV and survival remained robust after controlling for KPS and the number of BM (P = 0.042). The incorporation of the CITV into the RCC ds-GPA model (consisting of KPS and number of BM) improved prognostic accuracy with NRI >0 of 0.3156 (95% confidence interval [CI], 0.0883-0.5428; P = 0.0065) and IDI of 0.0151 (95% CI, 0.0036-0.0277; P = 0.0183). These findings were validated in an independent cohort of 107 SRS-treated RCC BM patients. CONCLUSION: CITV is an important prognostic variable in SRS-treated RCC patients with BM. The prognostic value of the ds-GPA scale for RCC brain metastasis was enhanced by the incorporation of CITV.

Survival Patterns of 5750 Stereotactic Radiosurgery-Treated Patients with Brain Metastasis as a Function of the Number of Lesions.

BACKGROUND: The number of brain metastases (BMs) plays an important role in the decision between stereotactic radiosurgery (SRS) and whole-brain radiation therapy. METHODS: We analyzed the survival of 5750 SRS-treated patients with BM as a function of BM number. Survival analyses were performed with Kaplan-Meier analysis as well as univariate and multivariate Cox proportional hazards models. RESULTS: Patients with BMs were first categorized as those with 1, 2-4, and 5-10 BMs based on the scheme proposed by Yamamoto et al. (Lancet Oncology 2014). Median overall survival for patients with 1 BM was superior to those with 2-4 BMs (7.1 months vs. 6.4 months, P = 0.009), and survival of patients with 2-4 BMs did not differ from those with 5-10 BMs (6.4 months vs. 6.3 months, P = 0.170). The median survival of patients with >10 BMs was lower than those with 2-10 BMs (6.3 months vs. 5.5 months, P = 0.025). In a multivariate model that accounted for age, Karnofsky Performance Score, systemic disease status, tumor histology, and cumulative intracranial tumor volume, we observed a ∼10% increase in hazard of death when comparing patients with 1 versus 2-10 BMs (P < 0.001) or 10 versus >10 BMs (P < 0.001). When BM number was modeled as a continuous variable rather than using the classification by Yamamoto et al., we observed a step-wise 4% increase in the hazard of death for every increment of 6-7 BM (P < 0.001). CONCLUSIONS: The contribution of BM number to overall survival is modest and should be considered as one of the many variables considered in the decision between SRS and whole-brain radiation therapy.

Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries.

With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140-178 days irrespective of the number of SRS(s) (interquartile range 60-300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).

Stereotactic Radiosurgery Treatment of Trigeminal Neuralgia: Clinical Outcomes and Prognostic Factors.

BACKGROUND: Stereotactic radiosurgery (SRS) is a minimally invasive surgical option for the treatment of trigeminal neuralgia (TN). Here we review our institutional experience to identify prognostic factors associated with pain relief after SRS. METHODS: 263 patients with TN treated at the University of California, San Diego/San Diego Gamma Knife (2001-2013) were followed for more than 6 months. Univariate and multivariate Cox proportional hazard models analysis of factors associated with outcome was performed. RESULTS: Of the 263 patients, 229 (87%) presented with classical idiopathic TN, 31 (12%) presented with atypical TN, and 4 (1%) presented with secondary TN. 143 (54%) had undergone prior treatment. Most patients were treated with 85 (52%) or 90 Gy (42%). 79% of the SRS treated patients experienced a favorable response (defined as Barrow Neurological Institute Pain Scale <3 pain relief), with a median time to relief of 2.5 months. In a multivariate analysis, diagnosis of classical TN, previous percutaneous procedures, and age older than 70 years were associated with favorable responses; classical TN was associated with sustained pain relief. Dose prescription >85 Gy and prior SRS were associated with bothersome facial numbness posttreatment. For patients presenting with classical TN, diagnosis of multiple sclerosis (MS) did not decrease the likelihood of pain relief after SRS. CONCLUSIONS: Excellent TN pain relief was achieved with the delivery of 85 Gy in a single-shot, 4-mm isocenter SRS targeting the dorsal root entry zone. Patients with classical TN, with age older than 70 years, or who underwent previous percutaneous procedures were more likely to benefit from SRS. SRS is efficacious in patients with classical TN despite concurrent diagnosis of MS.

Anniversary Paper: the role of medical physicists in developing stereotactic radiosurgery.

This article is a tribute to the pioneering medical physicists over the last 50 years who have participated in the research, development, and commercialization of stereotactic radiosurgery (SRS) and stereotactic radiotherapy utilizing a wide range of technology. The authors have described the evolution of SRS through the eyes of physicists from its beginnings with the Gamma Knife in 1951 to proton and charged particle therapy; modification of commercial linacs to accommodate high precision SRS setups; the multitude of accessories that have enabled fine tuning patients for relocalization, immobilization, and repositioning with submillimeter accuracy; and finally the emerging technology of SBRT. A major theme of the article is the expanding role of the medical physicist from that of advisor to the neurosurgeon to the current role as a primary driver of new technology that has already led to an adaptation of cranial SRS to other sites in the body, including, spine, liver, and lung. SRS continues to be at the forefront of the impetus to provide technological precision for radiation therapy and has demonstrated a host of downstream benefits in improving delivery strategies for conventional therapy as well. While this is not intended to be a comprehensive history, and the authors could not delineate every contribution by all of those working in the pursuit of SRS development, including physicians, engineers, radiobiologists, and the rest of the therapy and dosimetry staff in this important and dynamic radiation therapy modality, it is clear that physicists have had a substantial role in the development of SRS and theyincreasingly play a leading role in furthering SRS technology.

Linear accelerator and gamma knife-based stereotactic cranial radiosurgery: challenges and successes of existing quality assurance guidelines and paradigms.

Intracranial stereotactic radiosurgery has been practiced since 1951. The technique has expanded from a single dedicated unit in Stockholm in 1968 to hundreds of centers performing an estimated 100,000 Gamma Knife and linear accelerator cases in 2005. The radiation dosimetry of small photon fields used in this technique has been well explored in the past 15 years. Quality assurance recommendations have been promulgated in refereed reports and by several national and international professional societies since 1991. The field has survived several reported treatment errors and incidents, generally reacting by strengthening standards and precautions. An increasing number of computer-controlled and robotic-dedicated treatment units are expanding the field and putting patients at risk of unforeseen errors. Revisions and updates to previously published quality assurance documents, and especially to radiation dosimetry protocols, are now needed to ensure continued successful procedures that minimize the risk of serious errors.

Functional stereotactic radiosurgery involving a dedicated linear accelerator and gamma unit: a comparison study.

OBJECT: The purpose of this work was to investigate the targeting and dosimetric characteristics of a linear accelerator (LINAC) system dedicated for stereotactic radiosurgery compared with those of a commercial gamma knife (GK) unit. METHODS: A phantom was rigidly affixed within a Leksell stereotactic frame and axial computerized tomography scans were obtained using an appropriate stereotactic localization device. Treatment plans were performed, film was inserted into a recessed area, and the phantom was positioned and treated according to each treatment plan. In the case of the LINAC system, four 140 degrees arcs, spanning +/-60 degrees of couch rotation, were used. In the case of the GK unit, all 201 sources were left unplugged. Radiation was delivered using 3- and 8-mm LINAC collimators and 4- and 8-mm collimators of the GK unit. Targeting ability was investigated independently on the dedicated LINAC by using a primate model. Measured 50% spot widths for multisource, single-shot radiation exceeded nominal values in all cases by 38 to 70% for the GK unit and 11 to 33% for the LINAC system. Measured offsets were indicative of submillimeter targeting precision on both devices. In primate studies, the appearance of an magnetic resonance imaging-enhancing lesion coincided with the intended target. CONCLUSIONS: Radiosurgery performed using the 3-mm collimator of the dedicated LINAC exhibited characteristics that compared favorably with those of a dedicated GK unit. Overall targeting accuracy in the submillimeter range can be achieved, and dose distributions with sharp falloff can be expected for both devices.

A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases.

PURPOSE: Data collected from 10 institutions were reviewed to compare survival probabilities of patients with newly diagnosed brain metastases managed initially with radiosurgery (RS) alone vs. RS + whole brain radiotherapy (WBRT). METHODS AND MATERIALS: A database was created from raw data submitted from 10 institutions on patients treated with RS for brain metastases. The major exclusion criteria were resection of a brain metastasis and interval from the end of WBRT until RS >1 month (to try to ensure that the up-front intent was to combine RS + WBRT and that RS was not given for recurrent brain metastases). Survival was estimated using the Kaplan-Meier method from the date of first treatment for brain metastases until death or last follow-up. Survival times were compared for patients managed initially with RS alone vs. RS + WBRT using the Cox proportional hazards model to adjust for known prognostic factors or Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class. RESULTS: Out of 983 patients, 31 were excluded because treatment began after 6/1/98; 159 were excluded because brain metastases were resected; 179 were excluded because there was an interval >1 month from WBRT until RS; and 45 were excluded for other reasons. Of the 569 evaluable patients, 268 had RS alone initially (24% of whom ultimately had salvage WBRT), and 301 had RS + up-front WBRT. The median survival times for patients treated with RS alone initially vs. RS + WBRT were 14.0 vs. 15.2 months for RPA Class 1 patients, 8.2 vs. 7.0 months for Class 2, and 5.3 vs. 5.5 months for Class 3, respectively. With adjustment by RPA class, there was no survival difference comparing RS alone initially to RS + up-front WBRT (p = 0.33, hazard ratio = 1.09). CONCLUSIONS: Omission of up-front WBRT does not seem to compromise length of survival in patients treated with RS for newly diagnosed brain metastases.

Risk analysis of Leksell Gamma Knife Model C with automatic positioning system.

PURPOSE: This study was conducted to evaluate the decrease in risk from misadministration of the new Leksell Gamma Knife Model C with Automatic Positioning System compared with previous models. METHODS AND MATERIALS: Elekta Instruments, A.B. of Stockholm has introduced a new computer-controlled Leksell Gamma Knife Model C which uses motor-driven trunnions to reposition the patient between isocenters (shots) without human intervention. Previous models required the operators to manually set coordinates from a printed list, permitting opportunities for coordinate transposition, incorrect helmet size, incorrect treatment times, missing shots, or repeated shots. RESULTS: A risk analysis was conducted between craniotomy involving hospital admission and outpatient Gamma Knife radiosurgery. A report of the Institute of Medicine of the National Academies dated November 29, 1999 estimated that medical errors kill between 44,000 and 98,000 people each year in the United States. Another report from the National Nosocomial Infections Surveillance System estimates that 2.1 million nosocomial infections occur annually in the United States in acute care hospitals alone, with 31 million total admissions. CONCLUSIONS: All medical procedures have attendant risks of morbidity and possibly mortality. Each patient should be counseled as to the risk of adverse effects as well as the likelihood of good results for alternative treatment strategies. This paper seeks to fill a gap in the existing medical literature, which has a paucity of data involving risk estimates for stereotactic radiosurgery.