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JAMA Oncology Jun 2023Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. (Randomized Controlled Trial)
Randomized Controlled Trial
Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.
IMPORTANCE
Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control.
OBJECTIVE
To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases.
DESIGN, SETTING, AND PARTICIPANTS
In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020.
INTERVENTIONS
Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below.
MAIN OUTCOMES AND MEASURES
The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord.
RESULTS
A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00922974.
Topics: Humans; Male; Adolescent; Female; Radiosurgery; Spinal Fractures; Quality of Life; Fractures, Compression; Spine; Pain
PubMed: 37079324
DOI: 10.1001/jamaoncol.2023.0356 -
Lung Cancer (Amsterdam, Netherlands) Aug 2023Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location... (Meta-Analysis)
Meta-Analysis
Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines.
BACKGROUND
Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS).
METHODS
We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes.
RESULTS
602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events.
CONCLUSION
SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design.
Topics: Humans; Lung Neoplasms; Radiosurgery; Retrospective Studies; Lung; Dose Fractionation, Radiation; Observational Studies as Topic
PubMed: 37393758
DOI: 10.1016/j.lungcan.2023.107281 -
Epilepsia Nov 2022Surgery can cure or significantly improve both the frequency and the intensity of seizures in patients with medication-refractory epilepsy. The set of diagnostic and... (Review)
Review
Surgery can cure or significantly improve both the frequency and the intensity of seizures in patients with medication-refractory epilepsy. The set of diagnostic and therapeutic interventions involved in the path from initial consultation to definitive surgery is complex and includes a multidisciplinary team of neurologists, neurosurgeons, neuroradiologists, and neuropsychologists, supported by a very large epilepsy-dedicated clinical architecture. In recent years, new practices and technologies have emerged that dramatically expand the scope of interventions performed. Stereoelectroencephalography has become widely adopted for seizure localization; stereotactic laser ablation has enabled more focal, less invasive, and less destructive interventions; and new brain stimulation devices have unlocked treatment of eloquent foci and multifocal onset etiologies. This article articulates and illustrates the full framework for how epilepsy patients are considered for surgical intervention, with particular attention given to stereotactic approaches.
Topics: Humans; Electroencephalography; Treatment Outcome; Epilepsy; Stereotaxic Techniques; Drug Resistant Epilepsy; Seizures
PubMed: 35908245
DOI: 10.1111/epi.17381 -
JAMA Oncology Oct 2021Evidence is lacking from randomized clinical trials to guide the optimal approach for stereotactic ablative body radiotherapy (SABR) in patients with pulmonary... (Randomized Controlled Trial)
Randomized Controlled Trial
Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II): The Trans Tasman Radiation Oncology Group 13.01 Phase 2 Randomized Clinical Trial.
IMPORTANCE
Evidence is lacking from randomized clinical trials to guide the optimal approach for stereotactic ablative body radiotherapy (SABR) in patients with pulmonary oligometastases.
OBJECTIVE
To assess whether single-fraction or multifraction SABR is more effective for the treatment of patients with pulmonary oligometastases.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, unblinded, phase 2 randomized clinical trial of 90 patients across 13 centers in Australia and New Zealand enrolled patients with 1 to 3 lung oligometastases less than or equal to 5 cm from any nonhematologic malignant tumors located away from the central airways, Eastern Cooperative Oncology Group performance status 0 or 1, and all primary and extrathoracic disease controlled with local therapy. Enrollment was from January 1, 2015, to December 31, 2018, with a minimum patient follow-up of 2 years.
INTERVENTIONS
Single fraction of 28 Gy (single-fraction arm) or 4 fractions of 12 Gy (multifraction arm) to each oligometastasis.
MAIN OUTCOMES AND MEASURES
The main outcome was grade 3 or higher treatment-related adverse events (AEs) occurring within 1 year of SABR. Secondary outcomes were freedom from local failure, overall survival, disease-free survival, and patient-reported outcomes (MD Anderson Symptom Inventory-Lung Cancer and EuroQol 5-dimension visual analog scale).
RESULTS
Ninety participants were randomized, of whom 87 were treated for 133 pulmonary oligometastases. The mean (SD) age was 66.6 [11.6] years; 58 (64%) were male. Median follow-up was 36.5 months (interquartile range, 24.8-43.9 months). The numbers of grade 3 or higher AEs related to treatment at 1 year were 2 (5%; 80% CI, 1%-13%) in the single-fraction arm and 1 (3%; 80% CI, 0%-10%) in the multifraction arm, with no significant difference observed between arms. One grade 5 AE occurred in the multifraction arm. No significant differences were found between the multifraction arm and single-fraction arm for freedom from local failure (hazard ratio [HR], 0.5; 95% CI, 0.2-1.3; P = .13), overall survival (HR, 1.5; 95% CI, 0.6-3.7; P = .44), or disease-free survival (HR, 1.0; 95% CI, 0.6-1.6; P > .99). There were no significant differences observed in patient-reported outcomes.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, neither arm demonstrated evidence of superior safety, efficacy, or symptom burden; however, single-fraction SABR is more efficient to deliver. Therefore, single-fraction SABR, as assessed by the most acceptable outcome profile from all end points, could be chosen to escalate to future studies.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01965223.
Topics: Child; Humans; Lung; Male; Neoplasms; Progression-Free Survival; Proportional Hazards Models; Radiosurgery; Treatment Outcome
PubMed: 34455431
DOI: 10.1001/jamaoncol.2021.2939 -
Deutsches Arzteblatt International Jun 2021
Topics: Brain Neoplasms; Humans; Radiosurgery
PubMed: 34369372
DOI: 10.3238/arztebl.m2021.0206 -
JAMA Oncology Dec 2022Long-term outcomes of radiotherapy are important in understanding the risks and benefits of therapies for patients with brain metastases. (Randomized Controlled Trial)
Randomized Controlled Trial
Association of Long-term Outcomes With Stereotactic Radiosurgery vs Whole-Brain Radiotherapy for Resected Brain Metastasis: A Secondary Analysis of The N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group) Randomized Clinical Trial.
IMPORTANCE
Long-term outcomes of radiotherapy are important in understanding the risks and benefits of therapies for patients with brain metastases.
OBJECTIVE
To determine how the use of postoperative whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) is associated with quality of life (QOL), cognitive function, and intracranial tumor control in long-term survivors with 1 to 4 brain metastases.
DESIGN, SETTING, AND PARTICIPANTS
This secondary analysis of a randomized phase 3 clinical trial included 48 institutions in the US and Canada. Adult patients with 1 resected brain metastases but limited to those with 1 to 4 brain metastasis were eligible. Unresected metastases were treated with SRS. Long-term survivors were defined as evaluable patients who lived longer than 1 year from randomization. Patients were recruited between July 2011 and December 2015, and data were first analyzed in February 2017. For the present study, intracranial tumor control, cognitive deterioration, QOL, and cognitive outcomes were measured in evaluable patients who were alive at 12 months from randomization and reanalyzed in June 2017.
INTERVENTIONS
Stereotactic radiosurgery or WBRT.
MAIN OUTCOMES AND MEASURES
Intracranial tumor control, toxic effects, cognitive deterioration, and QOL.
RESULTS
Fifty-four patients (27 SRS arm, 27 WBRT arm; female to male ratio, 65% vs 35%) were included for analysis with a median follow-up of 23.8 months. Cognitive deterioration was less frequent with SRS (37%-60%) compared with WBRT (75%-91%) at all time points. More patients declined by 2 or more standard deviations (SDs) in 1 or more cognitive tests for WBRT compared with SRS at 3, 6, and 9 months (70% vs 22%, 46% vs 19%, and 50% vs 20%, respectively). A 2 SD decline in at least 2 cognitive tests was associated with worse 12-month QOL in emotional well-being, functional well-being, general, additional concerns, and total scores. Overall QOL and functional independence favored SRS alone for categorical change at all time points. Total intracranial control for SRS alone vs WBRT at 12 months was 40.7% vs 81.5% (difference, -40.7; 95% CI, -68.1% to -13.4%), respectively. Data were first analyzed in February 2017.
CONCLUSIONS AND RELEVANCE
The use of SRS alone compared with WBRT resulted in less cognitive deterioration among long-term survivors. The association of late cognitive deterioration with WBRT was clinically meaningful. A significant decline in cognition (2 SD) was associated with overall QOL. However, intracranial tumor control was improved with WBRT. This study provides detailed insight into cognitive function over time in this patient population.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01372774; ALLIANCE/CCTG: N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group).
Topics: Adult; Humans; Male; Female; Radiosurgery; Cranial Irradiation; Quality of Life; Canada; Brain Neoplasms; Brain
PubMed: 36264568
DOI: 10.1001/jamaoncol.2022.5049 -
Clinical Neurophysiology : Official... Mar 2021As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective... (Review)
Review
As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines.
Topics: Brain; Clinical Competence; Humans; Practice Guidelines as Topic; Stereotaxic Techniques; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 33549501
DOI: 10.1016/j.clinph.2020.11.018 -
International Journal of Radiation... May 2021
Topics: Age Factors; Dose-Response Relationship, Radiation; Humans; Neoplasms; Organ Specificity; Organs at Risk; Practice Guidelines as Topic; Radiation Dose Hypofractionation; Radiosurgery; Radiotherapy Planning, Computer-Assisted; Systematic Reviews as Topic
PubMed: 33864823
DOI: 10.1016/j.ijrobp.2020.10.039 -
Neurosurgical Review Jun 2020Beginning with basic stereotactic operative methods in neurosurgery, intraoperative navigation and image guidance systems have since become the norm in that field.... (Review)
Review
Beginning with basic stereotactic operative methods in neurosurgery, intraoperative navigation and image guidance systems have since become the norm in that field. Following the introduction of image guidance into spinal surgery, there has been a dramatic increase in its utilization across disciplines and pathologies. Spine tumor surgery encompasses a wide range of complex surgical techniques and treatment strategies. Similarly to deformity correction and trauma surgery, spine navigation holds potential to improve outcomes and optimize surgical technique for spinal tumors. Recent data demonstrate the applicability of neuro-navigation in the field of spinal oncology, particularly for spinal stabilization, maximizing extent of resection and integration of minimally invasive therapies. The rapid introduction of new, less invasive, and ablative surgical techniques in spine oncology coupled with the rising incidence of spinal metastatic disease make it imperative for spine surgeons to be familiar with the indications for and limitations of imaging guidance. Herein, we provide a practical, current concepts narrative review on the use of spinal navigation in three areas of spinal oncology: (a) extent of tumor resection, (b) spinal column stabilization, and (c) focal ablation techniques.
Topics: Humans; Imaging, Three-Dimensional; Minimally Invasive Surgical Procedures; Neurosurgical Procedures; Spinal Neoplasms; Spine; Stereotaxic Techniques; Surgery, Computer-Assisted
PubMed: 31154546
DOI: 10.1007/s10143-019-01123-2 -
Seizure Apr 2020Stereoelectroencephalography-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) consists of coupling SEEG investigation with RF-TC stereotactic lesioning... (Review)
Review
Stereoelectroencephalography-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) consists of coupling SEEG investigation with RF-TC stereotactic lesioning directly through the recording electrodes. In this systematic review the surgical technique, indications, and outcomes are described. Maximum accuracy is reached when a frame-based procedure with a robotic assistance and a per-operative vascular X-ray imaging are performed. Monitoring of the lesioning procedure based on the impedance, a sharp modification of which indicates that the thermocoagulation has reached its maximum volume, allows the optimization of the lesion size. The first indication concerns patients in whom a SEEG is required to determine whether surgery is feasible and in whom resection is indeed possible. Even if surgery is performed owing to insufficient efficacy of SEEG-guided RF-TC, the procedure remains interesting owing to its high positive predictive value for good outcome after surgery. The second indication concerns patients in whom phase I non-invasive investigations have concluded to surgical contraindication and who may still undergo SEEG in a purely therapeutic perspective (small deep zones inaccessible to surgery and network nodes of large epileptic networks). Lastly, SEEG-guided RF-TC can be considered as a first-line treatment for periventricular nodular heterotopia (PNH). Independently of indication, the overall seizure-free rate is 23% and the responder rate is 58%. The best results are obtained for PNH (38% seizure-free and 81% responders), while the worst results have been reported for temporal lobe-epilepsy in a dedicated study. The overall complication rate is 2.5%. More evidence is needed to help determine the exact place of SEEG-guided RF-TC in the surgical management algorithm.
Topics: Drug Resistant Epilepsy; Electrocoagulation; Electrocorticography; Epilepsies, Partial; Humans; Periventricular Nodular Heterotopia; Stereotaxic Techniques
PubMed: 30711397
DOI: 10.1016/j.seizure.2019.01.021