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OBJECTIVE: Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers. METHODS: A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method. RESULTS: A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/ß = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%). CONCLUSIONS: Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.

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OBJECTIVE: Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years). METHODS: The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated. RESULTS: The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years. CONCLUSIONS: AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.

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OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

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Irradiación Craneana , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía , Meningioma/radioterapia , Meningioma/cirugía , Radiocirugia , Manejo de la Enfermedad , Humanos , Persona de Mediana Edad , Aceleradores de Partículas , Supervivencia sin Progresión , Estudios Retrospectivos , Resultado del Tratamiento

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OBJECTIVE: In meningiomas involving the orbit and optic canal, surgery is the mainstay of therapy. However, radical resection is often limited to avoid functional damage, so multidisciplinary treatment concepts are implemented. Data on the timing and value of early postoperative radiotherapy (PORT) are scarce. This retrospective study analyzes outcomes in patients who underwent targeted resection alone or in combination with early PORT. METHODS: Patients undergoing resection of orbit-associated WHO grade I meningiomas from January 1999 to December 2013 who presented to the authors' department at least twice for follow-up were included. Clinical and radiological findings were analyzed retrospectively. Patients were stratified into two cohorts: follow-up with MRI scans at regular intervals, i.e., the watch and wait (W&W) group, and a PORT group receiving PORT within 6 months after surgery in addition to MRI follow-up. Patients in the W&W group were scheduled for treatment when tumor progression was detected by imaging. RESULTS: One hundred twenty-two patients were included. The mean follow-up was 70 months. The most common symptoms at presentation were visual disturbances; 87.7% of patients received Simpson grade II-III targeted partial resection. Twenty-three patients received PORT, and 99 patients were regularly observed with MRI scans (W&W group). Tumor recurrence/progression occurred significantly later (76.3 vs 40.7 months) and less frequently in the PORT group (13%) than in the W&W group (46.5%). Cases of recurrence were diagnosed an average of 39 months after initial surgery in both groups. PORT patients demonstrated significantly less visual impairment at last follow-up. CONCLUSIONS: These results indicate that receiving PORT early after targeted partial resection might help to postpone tumor recurrence and the need for additional treatment, while preserving or even improving visual outcome.

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In BriefThere has been a significant shift in treatment paradigms for both primary and metastatic spine tumors over the last several decades. This article highlights some of the more important treatment advances that practitioners should be made aware of. It is important to not only incorporate these changes into individual practice but also appreciate the treatment trends that herald a significantly different future for spine tumor treatment.

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Neoplasias de la Columna Vertebral/cirugía , Humanos , Radiocirugia , Neoplasias de la Columna Vertebral/radioterapia

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OBJECTIVEAs patients with metastatic cancer live longer, an increased emphasis is placed on long-term therapeutic outcomes. The current study evaluates outcomes of long-term cancer survivors following surgery for spinal metastases.METHODSThe study population included patients surgically treated at a tertiary cancer center between January 2010 and December 2015 who survived at least 24 months postoperatively. A retrospective chart and imaging review was performed to collect data regarding patient demographics; tumor histology; type and extent of spinal intervention; radiation data, including treatment dose and field; long-term sequelae, including local tumor control; and reoperations, repeat irradiation, or postoperative kyphoplasty at a previously treated level.RESULTSEighty-eight patients were identified, of whom 44 were male, with a mean age of 61 years. The mean clinical follow-up for the cohort was 44.6 months (range 24.2-88.3 months). Open posterolateral decompression and stabilization was performed in 67 patients and percutaneous minimally invasive surgery in 21. In the total cohort, 84% received postoperative adjuvant radiation and 27% were operated on for progression following radiation. Posttreatment local tumor progression was identified in 10 patients (11%) at the index treatment level and 5 additional patients had a marginal failure; all of these patients were treated with repeat irradiation with 5 patients requiring a reoperation. In total, at least 1 additional surgical intervention was performed at the index level in 20 (23%) of the 88 patients: 11 for hardware failure, 5 for progression of disease, 3 for wound complications, and 1 for postoperative hematoma. Most reoperations (85%) were delayed at more than 3 months from the index surgery. Wound infections or dehiscence requiring additional surgical intervention occurred in 3 patients, all of which occurred more than a year postoperatively. Kyphoplasty at a previously operated level was performed in 3 cases due to progressive fractures.CONCLUSIONSDurable tumor control can be achieved in long-term cancer survivors surgically treated for symptomatic spinal metastases with limited complications. Complications observed after long-term follow-up include local tumor recurrence/progression, marginal tumor control failures, early or late hardware complications, late wound complications, and progressive spinal instability or deformity.

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OBJECTIVE: Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects. METHODS: The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome. RESULTS: The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044). CONCLUSIONS: SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

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Ganglios Basales/cirugía , Malformaciones Arteriovenosas Intracraneales/cirugía , Radiocirugia/métodos , Tálamo/cirugía , Adolescente , Adulto , Ganglios Basales/irrigación sanguínea , Ganglios Basales/diagnóstico por imagen , Embolización Terapéutica , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/terapia , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Hemorragia Posoperatoria/etiología , Dosis de Radiación , Traumatismos por Radiación/etiología , Radiocirugia/efectos adversos , Estudios Retrospectivos , Tálamo/irrigación sanguínea , Tálamo/diagnóstico por imagen , Resultado del Tratamiento , Adulto Joven

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OBJECTIVE: Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas. METHODS: Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression. RESULTS: Nineteen patients (median age 64.5 years, range 50-78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1-3) and 2 (range 1-4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9-92.0 cm3). The median radiation dose from BT was 63 Gy (range 54-80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03-47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9-321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically. CONCLUSIONS: R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

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Materiales Biocompatibles/administración & dosificación , Braquiterapia/métodos , Radioisótopos de Cesio/administración & dosificación , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Anciano , Colágeno/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/cirugía , Meningioma/mortalidad , Meningioma/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento

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OBJECTIVEThe morbidity of gross-total resection of jugular paraganglioma (JP) is often unacceptable due to the potential for irreversible lower cranial neuropathy. Stereotactic radiosurgery (SRS) has been used at the authors' institution since 1990 for the treatment of JP and other benign intracranial tumors. Conventional means of assessing tumor progression using linear measurements or elliptical approximations are imprecise due to the irregular shape and insinuating growth pattern of JP. The objective of this study was to assess long-term tumor control in these patients by using slice-by-slice 3D volumetric segmentation of serial MRI data.METHODSRadiographic data and clinical records were reviewed retrospectively at a single, tertiary-care academic referral center for patients treated from 1990 to 2017. Volumetric analyses by integration of consecutive tumor cross-sectional areas (tumor segmentation) of serial MRI data were performed. Tumor progression was defined as volumetric growth of 15% or greater over the imaging interval. Primary outcomes analyzed included survival free of radiographic and clinical progression. Secondary outcomes included new or worsened cranial neuropathy.RESULTSA total of 85 patients were treated with Gamma Knife radiosurgery (GKRS) for JP at the authors' institution over the last 27 years. Sixty patients had pretreatment and serial posttreatment contrast-enhanced MRI follow-up suitable for volumetric analysis. A total of 214 MR images were analyzed to segment tumor images in a slice-by-slice fashion to calculate integral tumor volume. The median follow-up duration was 66 months (range 7-202 months). At 5 years the tumor progression-free survival rate was 98%. Three tumors exhibited progression more than 10 years after GKRS. Estimated survival free of radiographic progression rates (95% confidence interval [CI]; n = number still at risk) at 5, 10, and 15 years following radiosurgery were 98% (95% CI 94%-100%; n = 34), 94% (95% CI 85%-100%; n = 16), and 74% (95% CI 56%-98%; n = 6), respectively. One patient with tumor progression required treatment intervention using external beam radiation therapy, constituting the only case of clinical progression. Two patients (3%) without preexisting lower cranial nerve dysfunction developed new ipsilateral vocal fold paralysis following radiosurgery.CONCLUSIONSSRS achieves excellent long-term tumor control for JP without a high risk for new or worsened cranial neuropathy when used in primary, combined modality, or recurrent settings. Long-term follow-up is critical due to the potential for late radiographic progression (i.e., more than 10 years after SRS). As none of the patients with late progression have required salvage therapy, the clinical implications of this degree of tumor growth have yet to be determined.

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OBJECTIVEThe role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.METHODSThe authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988-2000) or modern (2001-2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).RESULTSThe study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.CONCLUSIONSDespite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.

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OBJECTIVEThe authors conducted this retrospective study to investigate the clinical outcomes of intracranial solitary fibrous tumor (SFT) and hemangiopericytoma (HPC), defined according to the 2016 WHO classification of central nervous system (CNS) tumors.METHODSHistopathologically proven intracranial SFT and HPC cases treated in the period from June 1996 to September 2014 were retrospectively reviewed and analyzed. Two neuropathologists reviewed pathological slides and regraded the specimens according to the 2016 WHO classification. Factors associated with progression-free survival (PFS) and overall survival (OS) were statistically evaluated with uni- and multivariate analyses.RESULTSThe records of 47 patients-10 with SFT, 33 with HPC, and 4 with anaplastic HPC-were reviewed. A malignant transition from conventional SFT to WHO grade III SFT/HPC was observed in 2 cases, and 13 HPC cases were assigned grade III SFT/HPC. Mean and median follow-ups were 114.6 and 94.7 months, respectively (range 7.1-366.7 months). Gross-total resection (GTR) was significantly associated with longer PFS and OS (p = 0.012 for both), and adjuvant radiation therapy versus no such therapy led to significantly longer PFS (p = 0.018). Extracranial metastases to the liver, bone, lung, spine, and kidney occurred in 10 patients (21.3%). Grade III SFT/HPC was strongly correlated with the development of extracranial metastases (p = 0.031).CONCLUSIONSThe 2016 WHO classification of CNS tumors reflected the different types of pathological malignant progression and clinical outcomes better than prior classifications. Gross-total resection should be the primary treatment goal in patients with SFT/HPC, regardless of the pathological grade, and radiation can be administered as adjuvant therapy for patients with SFT/HPC that shows an aggressive phenotype or that is not treated with GTR.

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Neoplasias Encefálicas/patología , Hemangiopericitoma/patología , Tumores Fibrosos Solitarios/patología , Adulto , Anciano , Neoplasias Encefálicas/cirugía , Progresión de la Enfermedad , Femenino , Hemangiopericitoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Tumores Fibrosos Solitarios/cirugía , Organización Mundial de la Salud , Adulto Joven

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OBJECTIVE The aim of this systematic review was to provide an objective summary of the published literature pertaining to the use of stereotactic body radiation therapy (SBRT) specific to previously untreated spinal metastases. METHODS The authors performed a systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of the literature found in a search of Medline, PubMed, Embase, and the Cochrane Library up to March 2015. The search strategy was limited to publications in the English language. RESULTS A total of 14 full-text articles were included in the analysis. All studies were retrospective except for 2 studies, which were prospective. A total of 1024 treated spinal lesions were analyzed. The median follow-up time ranged from 9 to 49 months. A range of dose-fractionation schemes was used, the most common of which were 16-24 Gy/1 fraction (fx), 24 Gy/2 fx, 24-27 Gy/3 fx, and 30-35 Gy/5 fx. In studies that reported crude results regarding in-field local tumor control, 346 (85%) of 407 lesions remained controlled. For studies that reported actuarial values, the weighted average revealed a 90% 1-year local control rate. Only 3 studies reported data on complete pain response, and the weighted average of these results yielded a complete pain response rate of 54%. The most common toxicity was new or progressing vertebral compression fracture, which was observed in 9.4% of cases; 2 cases (0.2%) of neurologic injury were reported. CONCLUSION There is a paucity of prospective data specific to SBRT in patients with spinal metastases not otherwise irradiated. This systematic review found that SBRT is associated with favorable rates of local control (approximately 90% at 1 year) and complete pain response (approximately 50%), and low rates of serious adverse events were found. Practice guidelines are summarized based on these data and International Stereotactic Radiosurgery Society consensus.

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Radiocirugia , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/secundario , Humanos , Radiocirugia/efectos adversos

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OBJECTIVE Stereotactic radiosurgery (SRS) of the spine is a conformal method of delivering a high radiation dose to a target in a single or few (usually ≤ 5) fractions with a sharp fall-off outside the target volume. Although efforts have been focused on evaluating spinal cord tolerance when treating spinal column metastases, no study has formally evaluated toxicity to the surrounding organs at risk (OAR), such as the brachial plexus or the oropharynx, when performing SRS in the cervicothoracic region. The aim of this study was to evaluate the radiation dosimetry and the acute and delayed toxicities of SRS on OAR in such patients. METHODS Fifty-six consecutive patients (60 procedures) with a cervicothoracic spine tumor involving segments within C5-T1 who were treated using single-fraction SRS between February 2006 and July 2014 were included in the study. Each patient underwent CT simulation and high-definition MRI before treatment. The clinical target volume and OAR were contoured on BrainScan and iPlan software after image fusion. Radiation toxicity was evaluated using the common toxicity criteria for adverse events and correlated to the radiation doses delivered to these regions. The incidence of vertebral body compression fracture (VCF) before and after SRS was evaluated also. RESULTS Metastatic lesions constituted the majority (n = 52 [93%]) of tumors treated with SRS. Each patient was treated with a median single prescription dose of 16 Gy to the target. The median percentage of tumor covered by SRS was 93% (maximum target dose 18.21 Gy). The brachial plexus received the highest mean maximum dose of 17 Gy, followed by the esophagus (13.8 Gy) and spinal cord (13 Gy). A total of 14 toxicities were encountered in 56 patients (25%) during the study period. Overall, 14% (n = 8) of the patients had Grade 1 toxicity, 9% (n = 5) had Grade 2 toxicity, 2% (n = 1) had Grade 3 toxicity, and none of the patients had Grade 4 or 5 toxicity. The most common (12%) toxicity was dysphagia/odynophagia, followed by axial spine pain flare or painful radiculopathy (9%). The maximum radiation dose to the brachial plexus showed a trend toward significance (p = 0.066) in patients with worsening post-SRS pain. De novo and progressive VCFs after SRS were noted in 3% (3 of 98) and 4% (4 of 98) of vertebral segments, respectively. CONCLUSIONS From the analysis, the current SRS doses used at the Cleveland Clinic seem safe and well tolerated at the cervicothoracic junction. These preliminary data provide tolerance benchmarks for OAR in this region. Because the effect of dose-escalation SRS strategies aimed at improving local tumor control needs to be balanced carefully with associated treatment-related toxicity on adjacent OAR, larger prospective studies using such approaches are needed.

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Vértebras Cervicales/cirugía , Órganos en Riesgo/patología , Radiocirugia/efectos adversos , Fracturas de la Columna Vertebral/etiología , Neoplasias de la Columna Vertebral/cirugía , Anciano , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Órganos en Riesgo/diagnóstico por imagen , Tolerancia a Radiación , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Factores de Tiempo , Tomógrafos Computarizados por Rayos X

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OBJECTIVE Nelson-Salassa syndrome (NSS) is a rare consequence of bilateral adrenalectomy (ADX) for refractory hypercortisolism due to Cushing disease (CD). Although classically defined by rapid growth of a large, invasive, adrenocorticotropin hormone (ACTH)-secreting pituitary tumor after bilateral ADX that causes cutaneous hyperpigmentation, visual disturbance, and high levels of ACTH, clinical experience suggests more variability. METHODS The authors conducted a retrospective chart review of all patients 18 years and older with a history of bilateral ADX for CD, adequate pituitary MRI, and at least 2 years of clinical follow-up. Statistical tests included Student's t-test, chi-square test, Fisher's exact test, multivariate analysis, and derived receiver operating characteristic curves. RESULTS Between 1956 and 2015, 302 patients underwent bilateral ADX for the treatment of hypercortisolism caused by CD; 88 had requisite imaging and follow-up (mean 16 years). Forty-seven patients (53%) had radiographic progression of pituitary disease and were diagnosed with NSS. Compared with patients who did not experience progression, those who developed NSS were significantly younger at the time of CD diagnosis (33 vs 44 years, p = 0.007) and at the time of bilateral ADX (35 vs 49 years, p = 0.007), had larger tumors at the time of CD diagnosis (6 mm vs 1 mm, p = 0.03), and were more likely to have undergone external-beam radiation therapy (EBRT, 43% vs 12%, p = 0.005). Among NSS patients, the mean tumor growth was 7 mm/yr (SE 6 mm/yr); the median tumor growth was 3 mm/yr. Prevalence of pathognomonic symptoms was low; the classic triad occurred in 9%, while hyperpigmentation without visual field deficit was observed in 23%, and 68% remained asymptomatic despite radiographic disease progression. NSS required treatment in 14 patients (30%). CONCLUSIONS NSS is a prevalent sequela of CD after bilateral ADX and affects more than 50% of patients. However, although radiological evidence of NSS is common, it is most often clinically indolent, with only a small minority of patients developing the more aggressive disease phenotype characterized by clinically meaningful symptoms and indications for treatment. Young age at the time of CD diagnosis or treatment with bilateral ADX, large tumor size at CD diagnosis, and EBRT are associated with progression to NSS and may be markers of aggressiveness.

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Adrenalectomía/efectos adversos , Síndrome de Nelson/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Síndrome de Nelson/diagnóstico por imagen , Síndrome de Nelson/etiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Estudios Retrospectivos , Adulto Joven

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OBJECTIVE Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes. METHODS The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses. RESULTS The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm3, 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis. CONCLUSIONS Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.

Asunto(s)

Malformaciones Arteriovenosas Intracraneales/radioterapia , Radiocirugia , Adulto , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico , Masculino , Estudios Retrospectivos , Rotura Espontánea/diagnóstico , Rotura Espontánea/radioterapia , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

OBJECTIVE The objective of this study was to define symptomatic and radiographic outcomes following spine stereotactic radiosurgery (SRS) for the treatment of multiple myeloma. METHODS All patients with pathological diagnoses of myeloma undergoing spine SRS at a single institution were included. Patients with less than 1 month of follow-up were excluded. The primary outcome measure was the cumulative incidence of pain relief after spine SRS, while secondary outcomes included the cumulative incidences of radiographic failure and vertebral fracture. Pain scores before and after treatment were prospectively collected using the Brief Pain Inventory (BPI), a validated questionnaire used to assess severity and impact of pain upon daily functions. RESULTS Fifty-six treatments (in 38 patients) were eligible for inclusion. Epidural disease was present in nearly all treatment sites (77%). Moreover, preexisting vertebral fracture (63%), thecal sac compression (55%), and neural foraminal involvement (48%) were common. Many treatment sites had undergone prior local therapy, including external beam radiation therapy (EBRT; 30%), surgery (23%), and kyphoplasty (21%). At the time of consultation for SRS, the worst, current, and average BPI pain scores at these treatment sites were 6, 4, and 4, respectively. The median prescription dose was 16 Gy in a single fraction. The median clinical follow-up duration after SRS was 26 months. The 6- and 12-month cumulative incidences of radiographic failure were 6% and 9%, respectively. Among painful treatment sites, 41% achieved pain relief adjusted for narcotic usage, with a median time to relief of 1.6 months. The 6- and 12-month cumulative incidences of adjusted pain progression were 13% and 15%, respectively. After SRS, 1-month and 3-month worst, current, and average BPI scores all significantly decreased (p < 0.01). Vertebral fracture occurred following 12 treatments (21%), with an 18% cumulative incidence of fracture at 6 and 12 months. Two patients (4%) developed pain flare following spine SRS. CONCLUSIONS This study reports the largest series of myeloma lesions treated with spine SRS. A rapid and durable symptomatic response was observed, with a median time to pain relief of 1.6 months. This response was durable among 85% of patients at 12 months following treatment, with 91% local control. The efficacy and minimal toxicity of spine SRS is likely related to the delivery of ablative and conformal radiation doses to the target. SRS should be considered with doses of 14-16 Gy in a single fraction for patients with multiple myeloma and limited spinal disease, myelosuppression requiring "marrow-sparing" radiation therapy, or recurrent disease after EBRT.

Asunto(s)

Mieloma Múltiple/cirugía , Radiocirugia , Fracturas de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Dolor/epidemiología , Radiocirugia/métodos , Estudios Retrospectivos , Fracturas de la Columna Vertebral/etiología , Neoplasias de la Columna Vertebral/complicaciones , Resultado del Tratamiento

RESUMEN

OBJECTIVE This study is a multi-institutional pooled analysis specific to imaging-based local control of spinal metastases in patients previously treated with conventional external beam radiation therapy (cEBRT) and then treated with re-irradiation stereotactic body radiotherapy (SBRT) to the spine as salvage therapy, the largest such study to date. METHODS The authors reviewed cases involving 215 patients with 247 spinal target volumes treated at 7 institutions. Overall survival was calculated on a patient basis, while local control was calculated based on the spinal target volume treated, both using the Kaplan-Meier method. Local control was defined as imaging-based progression within the SBRT target volume. Equivalent dose in 2-Gy fractions (EQD2) was calculated for the cEBRT and SBRT course using an α/ß of 10 for tumor and 2 for both spinal cord and cauda equina. RESULTS The median total dose/number of fractions of the initial cEBRT was 30 Gy/10. The median SBRT total dose and number of fractions were 18 Gy and 1, respectively. Sixty percent of spinal target volumes were treated with single-fraction SBRT (median, 16.6 Gy and EQD2/10 = 36.8 Gy), and 40% with multiple-fraction SBRT (median 24 Gy in 3 fractions, EQD2/10 = 36 Gy). The median time interval from cEBRT to re-irradiation SBRT was 13.5 months, and the median duration of patient follow-up was 8.1 months. Kaplan-Meier estimates of 6- and 12-month overall survival rates were 64% and 48%, respectively; 13% of patients suffered a local failure, and the 6- and 12-month local control rates were 93% and 83%, respectively. Multivariate analysis identified Karnofsky Performance Status (KPS) < 70 as a significant prognostic factor for worse overall survival, and single-fraction SBRT as a significant predictive factor for better local control. There were no cases of radiation myelopathy, and the vertebral compression fracture rate was 4.5%. CONCLUSIONS Re-irradiation spine SBRT is effective in yielding imaging-based local control with a clinically acceptable safety profile. A randomized trial would be required to determine the optimal fractionation.

Asunto(s)

Radiocirugia/métodos , Reirradiación/métodos , Terapia Recuperativa/métodos , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Radiocirugia/efectos adversos , Dosificación Radioterapéutica , Reirradiación/efectos adversos , Terapia Recuperativa/efectos adversos , Neoplasias de la Columna Vertebral/mortalidad , Columna Vertebral/cirugía , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven

RESUMEN

OBJECTIVE The authors investigated the outcomes following spine stereotactic radiosurgery (SSRS) for patients with oligometastatic disease of the spine. METHODS The study was a secondary analysis of 38 of 209 patients enrolled in 2 separate institutional Phase I/II prospective protocols and treated with SSRS between 2002 and 2011. Of these 38 patients, 33 (87%) were treated for a solitary spine metastasis, with no other history of metastatic disease. SSRS was prescribed to 24 Gy in 1 fraction (8%), 18 Gy in 1 fraction (18%), 16 Gy in 1 fraction (11%), 27 Gy in 3 fractions (53%), 30 Gy in 5 fractions (8%), or 20 Gy in 5 fractions (3%). Seventeen patients (45%) received prior conventional external beam radiation therapy. RESULTS The median overall survival (OS) was 75.7 months, and the 2- and 5-year OS rates were 84% and 60%, respectively. In multivariate analysis, patients who had prior spine surgery and a better Karnofsky Performance Scale score had an improved OS (HR 0.16, 95% CI 0.05-0.52, p < 0.01, and HR 0.33, 95% CI 0.13%-0.84%, p = 0.02, respectively), and those who had undergone prior radiation therapy had a worse OS (HR 3.6, 95% CI 1.2%-10%, p = 0.02). The 1-, 2-, and 5-year local progression-free survival rates were 85%, 82%, and 78%, respectively. The median time to systemic therapy modification was 41 months. Two patients (5%) experienced late Grade 3-4 toxicity. CONCLUSIONS Patients with oligometastatic disease of the spine treated with SSRS can experience long-term survival and a long time before needing a modification in systemic therapy. In addition, SSRS leads to excellent local control and minimal late toxicity.

Asunto(s)

Radiocirugia/métodos , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Estado de Ejecución de Karnofsky , Persona de Mediana Edad , Análisis Multivariante , Radiocirugia/efectos adversos , Adulto Joven

RESUMEN

OBJECTIVE The purpose of this study was to evaluate long-term treatment results, radiation-related toxicity, and prognostic factors for the progression-free survival (PFS) of patients with pilocytic astrocytomas treated by means of stereotactic radiosurgery with a Leksell Gamma Knife. METHODS A total of 25 patients with pilocytic astrocytomas underwent Gamma Knife surgery during the period 1992-2002. The median target volume was 2700 mm(3) (range 205-25,000 mm(3)). The 18 patients treated with 5 daily fractions received a median minimum target dose of 25 Gy. Doses for the 2 patients treated with 10 fractions over 5 days (2 fractions delivered on the same day at least 6 hours apart) were 23 and 28 Gy. For the 5 patients treated with a single fraction, the minimum target dose ranged from 13 to 20 Gy (median 16 Gy). RESULTS Complete regression occurred in 10 patients (40%) and partial regression in 10 patients (40%). The 10-year overall survival rate was 96% and the 10-year PFS rate was 80%. Target volume appeared to be a significant prognostic factor for PFS (p = 0.037). Temporary Grade 3 toxicity appeared in 2 patients (8%), and these patients were treated with corticosteroids for 2 months. Permanent Grade 4 toxicity appeared in 2 patients (8%) and was associated with neurocognitive dysfunction. In these 2 individuals, the neurocognitive dysfunction was also felt to be in part the result of the additional therapeutic interventions (4 in one case and 6 in the other) required to achieve durable control of their tumors. CONCLUSIONS Radiosurgery represents an alternative treatment modality for small residual or recurrent volumes of pilocytic astrocytomas and provides long-term local control. Target volume appears to be the most important factor affecting PFS.

Asunto(s)

Astrocitoma/diagnóstico por imagen , Astrocitoma/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Radiocirugia/tendencias , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Radiocirugia/métodos , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

OBJECTIVE Reconstruction of large solitary cranial defects after multiple craniotomies is challenging because scalp contraction generally requires more than simple subcutaneous undermining to ensure effective and cosmetically appealing closure. In plastic and reconstructive surgery, soft tissue expansion is considered the gold standard for reconstructing scalp defects; however, these techniques are not well known nor are they routinely practiced among neurosurgeons. The authors here describe a simple external tissue expansion technique that is associated with low morbidity and results in high cosmetic satisfaction among patients. METHODS The authors reviewed the medical records of patients with large cranial defects (> 5 cm) following multiple complicated craniotomies who had undergone reconstructive cranioplasty with preoperative tissue expansion using the DermaClose RC device. In addition to gathering data on patient age, sex, primary pathology, number of craniotomies and/or craniectomies, history of radiation therapy, and duration of external scalp tissue expansion, the authors screened patient charts for cerebrospinal fluid (CSF) leak, meningitis, intracranial abscess formation, dermatitis, and patient satisfaction rates. RESULTS The 6 identified patients (5 female, 1 male) had an age range from 36 to 70 years. All patients had complicating factors such as recalcitrant scalp infections after multiple craniotomies or cranial radiation, which led to secondary scalp tissue scarring and retraction. All patients were deemed to be potential candidates for rotational flaps with or without skin grafts. All patients underwent the same preoperative tissue expansion followed by standard cranial bone reconstruction. None of the patients developed CSF leak, meningitis, intracranial abscess, dermatitis, or permanent cosmetic defects. None of the patients required a reoperation. Mean follow-up was 117 days. CONCLUSIONS Preoperative scalp tissue expansion with the DermaClose RC device allows for simple and reliable completion of complicated cranial reconstruction with low morbidity rates and high cosmetic satisfaction among patients.

Asunto(s)

Craneotomía , Cuero Cabelludo/cirugía , Cráneo/cirugía , Expansión de Tejido/métodos , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos