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Journal of Clinical Oncology : Official... May 2019Patients with centrally located early-stage non-small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG...
PURPOSE
Patients with centrally located early-stage non-small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC.
MATERIALS AND METHODS
Medically inoperable patients with biopsy-proven, positron emission tomography-staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it.
RESULTS
One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively.
CONCLUSION
The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.
Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Radiosurgery; Treatment Outcome
PubMed: 30943123
DOI: 10.1200/JCO.18.00622 -
Clinical Oncology (Royal College of... Jan 2018Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different...
Six UK studies investigating stereotactic ablative radiotherapy (SABR) are currently open. Many of these involve the treatment of oligometastatic disease at different locations in the body. Members of all the trial management groups collaborated to generate a consensus document on appropriate organ at risk dose constraints. Values from existing but older reviews were updated using data from current studies. It is hoped that this unified approach will facilitate standardised implementation of SABR across the UK and will allow meaningful toxicity comparisons between SABR studies and internationally.
Topics: Consensus; Guidelines as Topic; Humans; Radiosurgery; United Kingdom
PubMed: 29033164
DOI: 10.1016/j.clon.2017.09.007 -
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 -
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 -
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 -
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 -
Missouri Medicine 2024The landscape of the cranial neurosurgery has changed tremendously in past couple of decades. The main frontiers including introduction of neuro-endoscopy, minimally... (Review)
Review
The landscape of the cranial neurosurgery has changed tremendously in past couple of decades. The main frontiers including introduction of neuro-endoscopy, minimally invasive skull base approaches, SRS, laser interstitial thermal therapy and use of tubular retractors have revolutionized the management of intracerebral hemorrhages, deep seated tumors other intracranial pathologies. Introduction of these novel techniques is based on smaller incisions with maximal operative corridors, decreased blood loss, shorter hospital stays, decreased post-operative pain and cosmetically appealing scars that improves patient satisfaction and clinical outcomes. The sophisticated tools like neuroendoscopy have improved light source, and better visualization around the corners. Advanced navigated tools and channel-based retractors help us to target deeply seated lesions with increased precision and minimal disruption of the surrounding neurovascular tissues. Advent of stereotactic radiosurgery has provided us alternative feasible, safe and effective options for treatment of patients who are otherwise not medically stable to undergo complex cranial surgical interventions. This paper review advances in treatment of intracranial pathologies, and how the neurosurgeons and other medical providers at the University of Missouri-Columbia (UMC) are optimizing these treatments for their patients.
Topics: Humans; Neurosurgical Procedures; Radiosurgery; Cerebral Hemorrhage; Brain Neoplasms; Neuroendoscopy
PubMed: 38694609
DOI: No ID Found -
Technology in Cancer Research &... 2020Spinal metastases are a common manifestation of malignant tumors that can cause severe pain, spinal cord compression, pathological fractures, and hypercalcemia, and... (Review)
Review
Spinal metastases are a common manifestation of malignant tumors that can cause severe pain, spinal cord compression, pathological fractures, and hypercalcemia, and these clinical manifestations will ultimately reduce the health-related quality of life and even shorten life expectancy in patient with cancer. Effective management of spinal bone metastases requires multidisciplinary collaboration, including radiologists, surgeons, radiation oncologists, medical oncologists, and pain specialists. In the past few decades, conventional radiotherapy has been the most common form of radiotherapy, which can achieve favorable local control and pain relief; however, it lacks precise methods of delivering radiation and thus cannot provide sufficient tumoricidal dose. The advent of stereotactic radiosurgery has changed this situation by using highly focused radiation beams guided by 3-dimensional imaging to deliver a high biologic equivalent dose to the target region, and the spinal cord can be identified and excluded from the target volume to reduce the risk of radiation-induced myelopathy. Separation surgery can provide a 2- to 3-mm safe separation of tumor and spinal cord to avoid radiation-induced damage to the spinal cord. Targets for separation surgery include decompression of metastatic epidural spinal cord compression and spinal stabilization without partial or en bloc tumor resection. Combined with conventional radiotherapy, stereotactic radiosurgery can provide better local tumor control and pain relief. Several scoring systems have been developed to estimate the life expectancy of patients with spinal metastases treated with radiotherapy. Thorough understanding of radiotherapy-related knowledge including the dose-fractionation schedule, separation surgery, efficacy and safety, scoring systems, and feasibility of combination with other treatment methods is critical to providing optimal patient care.
Topics: Combined Modality Therapy; Disease Management; Dose Fractionation, Radiation; Humans; Radiosurgery; Radiotherapy; Radiotherapy Dosage; Spinal Neoplasms; Treatment Outcome
PubMed: 32757820
DOI: 10.1177/1533033820945798 -
The Journal of Thoracic and... Jun 2016
Topics: Radiosurgery
PubMed: 27207128
DOI: 10.1016/j.jtcvs.2015.12.069