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Stereotactic spine radiosurgery: Review of safety and efficacy with respect to dose and fractionation.

ABSTRACT: BACKGROUND:Stereotactic body radiotherapy (SBRT) is an emerging treatment option for spinal metastases with demonstrated efficacy in the upfront, postoperative, and re-treatment settings, as well as for tumor histologies considered radioresistant. Uncertainty exists regarding the optimal dose and fractionation schedule, with single and multifraction regimens commonly utilized. METHODS:A literature search of the PubMed and Medline databases was conducted to identify papers specific to spine SBRT and the effect of varying dose/fractionation regimens on outcomes. Bibliographies of relevant papers were searched for further references, and international spine SBRT experts were consulted. RESULTS:Local control rates generally exceed 80% at 1 year, while high rates of pain control have been attained. There is insufficient evidence to suggest superiority of either single or multiple fraction regimens with respect to local control and pain control. Low rates of toxicity have been reported, assuming strict dose constraints are respected. Radiation myelopathy may be the most morbid toxicity, although the rates are low. The risk of vertebral compression fracture appears to be associated with higher doses per fraction such as those used in single-fraction regimens. The Spinal Instability Neoplastic Score should be considered when evaluating patients for spine SBRT, and prophylactic stabilisation may be warranted. Pain flare is a relatively common toxicity which may be mediated with prophylactic dexamethasone. Because of the treatment complexity and potentially serious toxicities, strict quality assurance should occur at the organizational, planning, dosimetric, and treatment delivery levels. CONCLUSION:Both single and multifraction regimens are safe and efficacious in spine SBRT for spinal metastases. There may be advantages to hypofractionated treatment over single-fraction regimens with respect to toxicity. Ongoing investigation is underway to define optimal dose and fractionation schedules.

SUBMITTER: Huo M

PROVIDER: S-EPMC5339918 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Stereotactic spine radiosurgery: Review of safety and efficacy with respect to dose and fractionation.

Huo Michael M Sahgal Arjun A Pryor David D Redmond Kristin K Lo Simon S Foote Matthew M

Surgical neurology international 20170220

<h4>Background</h4>Stereotactic body radiotherapy (SBRT) is an emerging treatment option for spinal metastases with demonstrated efficacy in the upfront, postoperative, and re-treatment settings, as well as for tumor histologies considered radioresistant. Uncertainty exists regarding the optimal dose and fractionation schedule, with single and multifraction regimens commonly utilized.<h4>Methods</h4>A literature search of the PubMed and Medline databases was conducted to identify papers specific ...[more]

PMID: 28303210

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Project description:OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6-50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7-86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2-70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

Project description:PurposeTo document the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases.Methods and materialsA retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16 Gy (range, 12-24 Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications.ResultsNine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range, 4.2-59.0 months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED3) > 200 Gy (or EQD22Gy [2-Gy equivalent dose calculated using an α/β ratio of 2] > 130 Gy) was associated with grade ≥2 late toxicity (P = .036). Maximum point BED3 > 110 Gy (or EQD22Gy > 70 Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P = .017). Nine VCFs (18%) occurred at a median time of 10.2 months (range, 3.2-57.2 months), with 5- and 10-year VCF rates of 17% and 17%, respectively.ConclusionStereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 > 200 Gy and spinal cord or cauda equina point BED3 > 110 Gy. Patients remain at moderate risk of VCF up to 5 years after treatment, with a plateau in incidence thereafter up to 10 years.

Project description:PurposeStereotactic radiosurgery (SRS) has been increasingly used to treat intracranial pathologies in elderly patients. The treatment efficiency of SRS has been demonstrated in meningiomas, with excellent local control. We aimed to analyze the safety of robotic SRS in elderly patients with meningiomas.MethodsWe searched for patients with suspected WHO °I meningioma ≥ 60 years old, who underwent CyberKnife (CK) SRS from January 2011 to December 2021. Tumor localization was categorized using the "CLASS" algorithmic scale. Tumor response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria for meningiomas. Adverse effects were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and a cox regression was performed to investigate possible predictors.ResultsWe identified 82 patients with 102 CK-treated lesions that matched the criteria for the first SRS. The median age was 70 [IQR 64-75] years, and 24.3% of the patients were aged > 75 years. Multiple lesions (up to six) were treated in 14.1% of the SRS-sessions. A previous surgery was performed in 57.3% of lesions, with a median time interval of 41 [IQR 10 - 58] months between the initial surgical procedure and the SRS treatment. In 47.9% of cases, CLASS 3 meningiomas at high-risk locations were irradiated. Single fraction radiosurgery was applied to 62.5% of the lesions, while in the remaining cases multi-session SRS with three to five fractions was used. During the median follow-up period of 15.9 months, lesion size progression was observed in 3 cases. Karnofsky Performance Status (KPS) declined by ≥ 20 points in four patients. Adverse effects occurred in 13 patients, while only four patients had CTCAE ≥2 toxicities. Hereby only one of these toxicities was persistent. The occurrence of complications was independent of age, planned target volume (PTV), high-risk localization, and surgery before SRS.ConclusionThe data indicates that SRS is a safe, efficient, and convenient treatment modality for elderly patients with meningioma, even at high-risk locations.

Project description:PurposeAs radiation therapy treatment precision increases with advancements in imaging and radiation delivery, dose painting treatment becomes increasingly feasible, where targets receive a nonuniform radiation dose. The high precision of stereotactic radiosurgery (SRS) makes it a good candidate for dose painting treatments, but no suitable metrics to assess dose painting SRS plans exist. Existing dose painting assessment metrics weigh target overdose and underdose equally but are unsuited for SRS plans, which typically avoid target underdose more. Current SRS metrics also prioritize reducing healthy tissue dose through selectivity and dose fall-off, and these metrics assume single prescriptions. We propose a set of metrics for dose painting SRS that would meet clinical needs and are calculated with nonuniform dose painting prescriptions.Methods and materialsSample dose painting SRS prescriptions are first created from Gamma Knife SRS cases, apparent diffusion coefficient magnetic resonance images, and various image-to-prescription functions. Treatment plans are found through semi-infinite linear programming optimization and using clinically determined isocenters, then assessed with existing and proposed metrics. Modified versions of SRS metrics are proposed, including coverage, selectivity, conformity, efficiency, and gradient indices. Quality factor, a current dose painting metric, is applied both without changes and with modifications. A new metric, integral dose ratio, is proposed as a measure of target overdose.ResultsThe merits of existing and modified metrics are demonstrated and discussed. A modified conformity index using mean or minimum prescription dose would be suitable for dose painting SRS with integral or maximum boost methods, respectively. Either modified efficiency index is a suitable replacement for the existing gradient index.ConclusionsThe proposed modified SRS metrics are appropriate measures of plan quality for dose painting SRS plans and have the advantage of giving equal values as the original SRS metrics when applied to single-prescription plans.

Project description:PurposeDespite excellent tumor control after stereotactic radiosurgery (SRS) for vestibular schwannoma (VS), the hearing preservation rate remains unsatisfactorily low. Although many factors have been associated with hearing loss, the dose to cochlea has gained more interest in recent years. However, studies investigating the relation between cochlear dose and hearing outcomes have produced inconsistent results. The purpose of this work is to systematically review the literature and critically analyze the studies that investigated the correlation between cochlear dose and hearing loss.Methods and materialsA literature search of Ovid MEDLINE, Embase, and Scopus was performed. Studies were included if the SRS dose used was 11 to 14 Gy and included adult patients with sporadic VS, initially serviceable hearing, and at least 24 months of mean or median follow-up.ResultsTwenty-one cohort studies and 1 case-control study were eligible for inclusion, and none were considered to be truly prospective. There was substantial heterogeneity between studies in terms of baseline hearing status, cochlear dosimetry, definition and reporting of hearing outcome, and duration of follow-up, limiting comparison between studies and precluding formal meta-analysis. Eleven studies showed a statistically significant correlation between cochlear dose and hearing outcome, but there was considerable variation in the reported cochlear dose parameter that predicted hearing outcome and whether it was an independent predictor. The definition of hearing outcome and whether the outcome variable is continuous or dichotomous have a bearing on the reported correlation between cochlear dose and hearing outcome.ConclusionsWhether cochlear dose is a predictor of hearing preservation after SRS for VS could not be unequivocally determined. Future studies should use consistent cochlear dosimetry and hearing outcomes for reliable assessment. In the meantime, based on currently available data, a practical approach will be to aim for a mean cochlear dose <4 to 6 Gy without compromising tumor dose.

Project description:PurposeAs part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).Methods and materialsEligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases.ResultsData from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V12) of 5 cm3, 10 cm3, or >15 cm3 were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For brain metastases, brain plus target volume V20 (3-fractions) or V24 (5-fractions) <20 cm3 was associated with <10% risk of any necrosis or edema, and <4% risk of radionecrosis requiring resection.ConclusionsThe risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks.

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Stereotactic spine radiosurgery: Review of safety and efficacy with respect to dose and fractionation.

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Stereotactic spine radiosurgery: Review of safety and efficacy with respect to dose and fractionation.

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