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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 -
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 -
Lancet (London, England) May 2019The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised... (Comparative Study)
Comparative Study Randomized Controlled Trial
Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial.
BACKGROUND
The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions.
METHODS
This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744.
FINDINGS
99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.
INTERPRETATION
SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit.
FUNDING
Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.
Topics: Aged; Disease-Free Survival; Dose Fractionation, Radiation; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Palliative Care; Radiosurgery; Survival Analysis; Treatment Outcome
PubMed: 30982687
DOI: 10.1016/S0140-6736(18)32487-5 -
Seminars in Radiation Oncology Jul 2017
Topics: Dose Fractionation, Radiation; Humans; Neoplasms; Radiosurgery
PubMed: 28577825
DOI: 10.1016/j.semradonc.2017.03.005 -
Progress in Neurological Surgery 2018Tremor is a common movement disorder that can be disabling, and its initial treatment is in the form of medical therapies. Often patients are refractory and seek... (Review)
Review
Tremor is a common movement disorder that can be disabling, and its initial treatment is in the form of medical therapies. Often patients are refractory and seek surgical intervention. Treatment options for these patients include surgical radiofrequency thalamotomy and deep brain stimulation. There are a subset of patients who, for various reasons, are not candidates for open surgical procedures, or who opt to avoid them. For these patients, radiosurgical thalamotomy is a safe and useful alternative. Herein, we provide a review of the use of radiosurgical thalamotomy for the treatment of medically refractory tremor by discussing its history, defining the technique and its indications, evaluating its efficacy, and exploring its complications and shortcomings.
Topics: Humans; Radiosurgery; Thalamus; Tremor
PubMed: 29332079
DOI: 10.1159/000481081 -
Progress in Neurological Surgery 2018Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the reference technique in Parkinson's disease (PD) at different stages of complications. Some patients... (Review)
Review
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the reference technique in Parkinson's disease (PD) at different stages of complications. Some patients cannot afford DBS due to anticoagulation or comorbidities or due to pecuniary reasons. Radiosurgery is a minimally invasive stereotactic technique, with no craniotomy and subsequently no risk of bleeding or infection. Its good safety efficacy profile has been established in the treatment of tremor, and the postoperative care issues are simple with a much shorter hospital stay (mean 48 h). The application of radiosurgery to STN target in PD as an alternative to DBS is being debated. The lesion of the STN is presumed to induce hemiballism. Experimental works suggest a potential lower risk of hemiballism in animal models of PD. However, radiofrequency ablation of the STN is associated with a significant rate of severe dyskinesia, sometimes permanent and severe enough to request salvage pallidotomies. The positive experience of VIM radiosurgery in tremor and its capacity to create precise, accurate and well-controlled lesions provides reasonable rationale for the evaluation of this technique when applied to STN in PD. Preliminary results till date have shown the absence of severe permanent dyskinesia. Prospective controlled trials are mandatory to evaluate the safety efficacy of this technique in PD.
Topics: Humans; Parkinson Disease; Radiosurgery; Subthalamic Nucleus
PubMed: 29332081
DOI: 10.1159/000481084 -
JPMA. the Journal of the Pakistan... May 2020The approach to treating vestibular schwannomas ranges from wait-and-scan policies to micro-and radiosurgery. However, in the past few decades, Stereotac tic... (Review)
Review
The approach to treating vestibular schwannomas ranges from wait-and-scan policies to micro-and radiosurgery. However, in the past few decades, Stereotac tic Radiosurgery (SRS) has emerged as an approved primary treatment option as well. In this review, we have assessed some of the existing literature on the role of SRS in the management of vestibular schwannomas, and to estimate its efficacy in tumour control and conservation of cranial nerve function.
Topics: Humans; Neuroma, Acoustic; Radiosurgery; Treatment Outcome
PubMed: 32400760
DOI: No ID Found -
Journal of Neurosurgical Sciences Feb 2019Stereotactic radiosurgery (SRS) is the use of a single high dose of radiation, stereotactically directed to an intracranial region of interest, in order to create a... (Review)
Review
Stereotactic radiosurgery (SRS) is the use of a single high dose of radiation, stereotactically directed to an intracranial region of interest, in order to create a lesion or obliterate a preexisting one. This technology has evolved over the years into the use of multiple radiation sources oriented at a variety of angles, thus permitting the creation of various treatment target shapes. This allows for non-open surgical treatment of intracranial pathologies, which significantly decreases the risk of morbidity. The destruction of pathological tissue following radiosurgery is a stepwise process that involves a number of different stages, beginning with the necrotic stage, followed by the resorption stage, and concluding with the glial scar formation stage. There are currently a number of different delivery methods of SRS, including linear accelerators, Gamma Knife units, and charged particle methods (Bragg-peak and plateau-beam). Various intracranial lesions exhibit different responses to radiosurgery; however, most lesions of appropriate size tend to respond favorably. Radiosurgery is used today in the treatment of brain metastases, meningiomas, vestibular schwannomas, sellar and suprasellar lesions, and arteriovenous malformations. SRS is widely used to treat functional conditions, such as trigeminal neuralgia and intractable tremor. The treatment of intracranial lesions with radiosurgery can result in undesirable effects on the adjacent normal brain, resulting in adverse radiation effects. The distinction between tumor progression and adverse radiation effects can be challenging but is aided by various imaging modalities. Treatment options for this condition include observation, corticosteroids, pentoxifylline and vitamin E, bevacizumab, laser-interstitial thermal therapy, and surgical resection.
Topics: Arteriovenous Fistula; Brain Neoplasms; Humans; Intracranial Arteriovenous Malformations; Radiosurgery; Tremor; Trigeminal Neuralgia
PubMed: 28945054
DOI: 10.23736/S0390-5616.17.04210-2 -
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 -
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