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Radiotherapy and Oncology : Journal of... Dec 2023This study aimed to compare SBRT and cEBRT for treating spinal metastases through a systematic review and meta-analysis of randomized controlled trials (RCTs). (Meta-Analysis)
Meta-Analysis Review
Stereotactic body radiation therapy versus conventional external beam radiotherapy for spinal metastases: A systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
This study aimed to compare SBRT and cEBRT for treating spinal metastases through a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
PubMed, EMBASE and Cochrane Library were searched up to 6 May 2023 for RCTs comparing SBRT and cEBRT for spinal metastases. Overall and complete pain response, local progression, overall survival, quality of life and adverse events were extracted. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) for dichotomous outcomes, and hazard ratios (HRs) for time-to-event outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I statistic.
RESULTS
Three RCTs were identified involving 642 patients. No differences were seen in overall pain response comparing SBRT and cEBRT (RR at 3 months: 1.12, 95% CI, 0.74-1.70, p = 0.59; RR at 6 months: 1.29, 95% CI, 0.97-1.72, p = 0.08). Only two of three studies presented complete pain response data. SBRT demonstrated a statistically significant improvement in complete pain response compared to cEBRT (RR at 3 months: 2.52; 95% CI, 1.58-4.01; P < 0.0001; RR at 6 months: 2.48; 95% CI, 1.23-4.99; P = 0.01). There were no significant differences in local progression and overall survival. Adverse events were similar, except for any grade radiation dermatitis, which was significantly lower in SBRT arm (RR 0.17, 95% CI 0.03-0.96, P = 0.04).
CONCLUSION
SBRT is a safe treatment option for spine metastases. It may provide better complete pain response compared to cEBRT. Additional trials are needed to determine the potential benefits of SBRT in specific patient subsets.
Topics: Humans; Radiosurgery; Spinal Neoplasms; Randomized Controlled Trials as Topic; Pain
PubMed: 37739318
DOI: 10.1016/j.radonc.2023.109914 -
International Journal of Radiation... Aug 2023Because patients with untreated brain arteriovenous malformations (BAVMs) are at variable risks of cerebral hemorrhage and associated mortality and morbidity, it is... (Observational Study)
Observational Study
PURPOSE
Because patients with untreated brain arteriovenous malformations (BAVMs) are at variable risks of cerebral hemorrhage and associated mortality and morbidity, it is essential to identify patient populations who benefit most from prophylactic interventions. This study aimed to examine age-dependent differences in the therapeutic effect of stereotactic radiosurgery (SRS) on BAVMs.
METHODS AND MATERIALS
This retrospective observational study enrolled patients with BAVMs who underwent SRS at our institution between 1990 and 2017. The primary outcome was post-SRS hemorrhage, and the secondary outcomes included nidus obliteration, post-SRS early signal changes, and mortality. To investigate age-related differences in outcomes after SRS, we performed age-stratified analyses using the Kaplan-Meier analysis and weighted logistic regression with the inverse probability of censoring weighting (IPCW). To address significant differences in patient baseline characteristics, we also performed inverse probability of treatment weighting (IPTW) adjusted for possible confounders to investigate age-related differences in outcomes after SRS.
RESULTS
A total of 735 patients with 738 BAVMs were stratified by age. Age-stratified analysis using a weighted logistic regression model with IPCW showed a direct correlation between patient age and post-SRS hemorrhage (odds ratio [OR], 95% confidence interval [CI], and P value: 2.20, 1.34-3.63, and .002 at 18 months; 1.86, 1.17-2.93, and .008 at 36 months; and 1.61, 1.05-2.48, and .030 at 54 months, respectively). The age-stratified analysis also showed an inverse relationship between age and obliteration over the first 42 months after SRS (OR, 95% CI, and P value: 0.05, 0.02-0.12, and <.001 at 6 months; 0.55, 0.44-0.70, and <.001 at 24 months; and 0.76, 0.63-0.91, and .002 at 42 months, respectively). These results were also confirmed with the IPTW analyses.
CONCLUSIONS
Our analysis demonstrated that patients' age at SRS is significantly associated with hemorrhage and the nidus obliteration rate after treatment. In particular, younger patients are more likely to exhibit reduced cerebral hemorrhages and achieve earlier nidus obliteration compared with older patients.
Topics: Humans; Child, Preschool; Treatment Outcome; Follow-Up Studies; Radiosurgery; Intracranial Arteriovenous Malformations; Brain; Retrospective Studies; Cerebral Hemorrhage
PubMed: 36907366
DOI: 10.1016/j.ijrobp.2023.02.059 -
Practical Radiation Oncology 2023Stereotactic radiosurgery treatment delivery can be performed with a range of devices, each of which have evolved over recent years. We sought to evaluate the...
PURPOSE
Stereotactic radiosurgery treatment delivery can be performed with a range of devices, each of which have evolved over recent years. We sought to evaluate the differences in performance of contemporary stereotactic radiosurgery platforms and also to compare them with earlier platform iterations from a previous benchmarking study.
METHODS AND MATERIALS
The following platforms were selected as "state of the art" in 2022: Gamma Knife Icon (GK), CyberKnife S7 (CK), Brainlab Elements (Elekta VersaHD and Varian TrueBeam), Varian Edge with HyperArc (HA), and Zap-X. Six benchmarking cases were used from a 2016 study. To reflect the evolution of increasing numbers of metastases treated per patient, a 14-target case was added. The 28 targets among the 7 patients ranged from 0.02 to 7.2 cc in volume. Participating centers were sent images and contours for each patient and asked to plan them to the best of their ability. Although some variation in local practice was allowed (eg, margins), groups were asked to prescribe a specified dose to each target and tolerance doses to organs at risk were agreed upon. Parameters compared included coverage, selectivity, Paddick conformity index, gradient index (GI), R50%, efficiency index, doses to organs at risk, and planning and treatment times.
RESULTS
Mean coverage for all targets ranged from 98.2% (Brainlab/Elekta) to 99.7% (HA-6X). Paddick conformity index values ranged from 0.722 (Zap-X) to 0.894 (CK). GI ranged from a mean of 3.52 (GK), representing the steepest dose gradient, to 5.08 (HA-10X). The GI appeared to follow a trend with beam energy, with the lowest values from the lower energy platforms (GK, 1.25 MeV; Zap-X, 3 MV) and the highest value from the highest energy (HA-10X). Mean R50% values ranged from 4.48 (GK) to 5.98 (HA-10X). Treatment times were lowest for C-arm linear accelerators.
CONCLUSIONS
Compared with earlier studies, newer equipment appears to deliver higher quality treatments. CyberKnife and linear accelerator platforms appear to give higher conformity whereas lower energy platforms yield a steeper dose gradient.
Topics: Humans; Brain Neoplasms; Benchmarking; Radiosurgery; Particle Accelerators; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Radiotherapy Planning, Computer-Assisted
PubMed: 37290672
DOI: 10.1016/j.prro.2023.05.005 -
International Journal of Radiation... Jul 2023Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases, particularly when these therapies are...
Concurrent Administration of Immune Checkpoint Inhibitors and Single Fraction Stereotactic Radiosurgery in Patients With Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma Brain Metastases.
PURPOSE
Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases, particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting.
METHODS AND MATERIALS
Patients with brain metastases from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Time-to-event analyses were conducted for any grade RN and symptomatic RN (SRN) with death incorporated as a competing risk. As a secondary analysis, recursive partitioning analysis (RPA) was used for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. Brain V12 Gy thresholds identified on RPA were then incorporated into the competing risks analysis. Concurrent SRS and ICI administration.
RESULTS
Six hundred fifty-seven patients with 4182 brain metastases across 11 international institutions were analyzed. The median follow-up for all patients was 13.4 months. The median follow-up was 12.8 months and 14.1 months for the concurrent and nonconcurrent groups, respectively (P = .03). The median patient age was 66 years, and the median Karnofsky Performance Status was 90. In patients with any grade RN, 1- and 2-year rates were 6.4% and 9.9%, respectively. In patients with SRN, 1- and 2-year rates were 4.8% and 7.2%, respectively. On RPA, the highest-fidelity models consistently identified V12 Gy as the dominant variable predictive of RN. Three risk groups were identified by V12 Gy: (1) < 12 cm; (2) 20 cm ≥ V12 Gy ≥ 12 cm; (3) V12 Gy > 20 cm. In patients with any grade RN, 1-year rates were 3.7% (V12 Gy < 12 cm), 10.3% (20 cm ≥ V12 Gy ≥ 12 cm), and 12.6% (V12 Gy > 20 cm); the 2-year rates were 7.5% (V12 Gy < 12 cm), 13.8% (20 cm ≥ V12 Gy ≥ 12 cm), and 15.4% (V12 Gy > 20 cm) (P < 0.001). In patients with any SRN, 1-year rates were 2.4% (V12 Gy < 12 cm), 8.9% (20 cm ≥ V12 Gy ≥ 12 cm), and 10.3% (V12 Gy > 20 cm); the 2-year rates were 4.4% (V12 Gy < 12 cm), 12.4% (20 cm ≥ V12 Gy ≥ 12 cm), and 13.1% (V12 Gy > 20 cm; P < 0.001). There were no statistically significant differences in rates of any grade RN or SRN when accounting for therapy timing for all patients and by V12 risk group identified on RPA.
CONCLUSIONS
The use of SRS and ICI results in a low risk of any grade RN and SRN. This risk is not increased with concurrent administration. Therefore, ICI can safely be administered within 4-weeks of SRS. Three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN.
Topics: Humans; Aged; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Carcinoma, Renal Cell; Radiosurgery; Lung Neoplasms; Retrospective Studies; Brain Neoplasms; Melanoma; Kidney Neoplasms
PubMed: 36690161
DOI: 10.1016/j.ijrobp.2023.01.017 -
International Journal of Radiation... Sep 2023The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction...
PURPOSE
The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC.
METHODS AND MATERIALS
Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire.
RESULTS
Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment.
CONCLUSIONS
For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted.
Topics: Humans; Aged; Quality of Life; Radiosurgery; Pancreas; Neoplasms, Second Primary; Pancreatic Neoplasms
PubMed: 36918130
DOI: 10.1016/j.ijrobp.2023.03.036 -
Journal For Immunotherapy of Cancer Dec 2023Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in... (Randomized Controlled Trial)
Randomized Controlled Trial
First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial.
BACKGROUND
Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in.
METHODS
The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2-6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery.
RESULTS
Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37-69. All patients received SBRT and underwent surgery 2-4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4-5 AE were documented. Overall cosmetical breast evaluation after surgery was 'excellent' in four patients and 'good' in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3.
CONCLUSIONS
This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial.
TRIAL REGISTRATION NUMBER
NCT03875573.
Topics: Humans; Adult; Middle Aged; Aged; Female; Breast Neoplasms; B7-H1 Antigen; Radiosurgery; Prognosis; Combined Modality Therapy
PubMed: 38056900
DOI: 10.1136/jitc-2023-007279 -
European Urology Sep 2023Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may...
BACKGROUND
Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.
OBJECTIVE
To investigate whether SAbR is effective in the management of primary RCCs.
DESIGN, SETTING, AND PARTICIPANTS
Patients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 mm/yr on active surveillance) and pathologic evidence of tumor response at 1 yr. Secondary endpoints included LC by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), safety, and preservation of kidney function. Exploratory tumor cell-enriched spatial protein and gene expression analysis were conducted on pre- and post-treatment biopsy samples.
RESULTS AND LIMITATIONS
Target accrual was reached with the enrollment of 16 ethnically diverse patients. Radiographic LC at 1 yr was observed in 94% of patients (15/16; 95% confidence interval: 70, 100), and this was accompanied by pathologic evidence of tumor response (hyalinization, necrosis, and reduced tumor cellularity) in all patients. By RECIST, 100% of the sites remained without progression at 1 yr. The median pretreatment growth rate was 0.8 cm/yr (interquartile range [IQR]: 0.3, 1.4), and the median post-treatment growth rate was 0.0 cm/yr (IQR: -0.4, 0.1, p < 0.002). Tumor cell viability decreased from 4.6% to 0.7% at 1 yr (p = 0.004). With a median follow-up of 36 mo for censored patients, the disease control rate was 94%. SAbR was well tolerated with no grade ≥2 (acute or late) toxicities. The average glomerular filtration rate declined from a baseline of 65.6 to 55.4 ml/min at 1 yr (p = 0.003). Spatial protein and gene expression analyses were consistent with the induction of cellular senescence by radiation.
CONCLUSIONS
This clinical trial adds to the growing body of evidence suggesting that SAbR is effective for primary RCC supporting its evaluation in comparative phase 3 clinical trials.
PATIENT SUMMARY
In this clinical trial, we investigated a noninvasive treatment option of stereotactic radiation therapy for the treatment of primary kidney cancer and found that it was safe and effective.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Radiosurgery; Prospective Studies; Response Evaluation Criteria in Solid Tumors; Treatment Outcome
PubMed: 36898872
DOI: 10.1016/j.eururo.2023.02.016 -
International Journal of Radiation... Nov 2023
Topics: Humans; Emotions; Radiosurgery; Lung Neoplasms
PubMed: 37838448
DOI: 10.1016/j.ijrobp.2023.08.050 -
JAMA Oncology Aug 2023Preoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential...
IMPORTANCE
Preoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential benefits in adverse radiation effects (AREs) and meningeal disease (MD). However, mature large-cohort multicenter data are lacking.
OBJECTIVE
To evaluate preoperative SRS outcomes and prognostic factors from a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases-PROPS-BM).
DESIGN, SETTING, AND PARTICIPANTS
This multicenter cohort study included patients with BMs from solid cancers, of which at least 1 lesion received preoperative SRS and a planned resection, from 8 institutions. Radiosurgery to synchronous intact BMs was allowed. Exclusion criteria included prior or planned whole-brain radiotherapy and no cranial imaging follow-up. Patients were treated between 2005 and 2021, with most treated between 2017 and 2021.
EXPOSURES
Preoperative SRS to a median dose to 15 Gy in 1 fraction or 24 Gy in 3 fractions delivered at a median (IQR) of 2 (1-4) days before resection.
MAIN OUTCOMES AND MEASURES
The primary end points were cavity local recurrence (LR), MD, ARE, overall survival (OS), and multivariable analysis of prognostic factors associated with these outcomes.
RESULTS
The study cohort included 404 patients (214 women [53%]; median [IQR] age, 60.6 [54.0-69.6] years) with 416 resected index lesions. The 2-year cavity LR rate was 13.7%. Systemic disease status, extent of resection, SRS fractionation, type of surgery (piecemeal vs en bloc), and primary tumor type were associated with cavity LR risk. The 2-year MD rate was 5.8%, with extent of resection, primary tumor type, and posterior fossa location being associated with MD risk. The 2-year any-grade ARE rate was 7.4%, with target margin expansion greater than 1 mm and melanoma primary being associated with ARE risk. Median OS was 17.2 months (95% CI, 14.1-21.3 months), with systemic disease status, extent of resection, and primary tumor type being the strongest prognostic factors associated with OS.
CONCLUSIONS AND RELEVANCE
In this cohort study, the rates of cavity LR, ARE, and MD after preoperative SRS were found to be notably low. Several tumor and treatment factors were identified that are associated with risk of cavity LR, ARE, MD, and OS after treatment with preoperative SRS. A phase 3 randomized clinical trial of preoperative vs postoperative SRS (NRG BN012) has began enrolling (NCT05438212).
Topics: Humans; Female; Middle Aged; Radiosurgery; Cohort Studies; Retrospective Studies; Risk Factors; Brain Neoplasms
PubMed: 37289451
DOI: 10.1001/jamaoncol.2023.1629 -
Neurosurgical Review Jan 2024Central neurocytomas (CN) are rare tumors within the central nervous system. Originating from the septum pellucidum and subependymal cells, they are typically found in... (Meta-Analysis)
Meta-Analysis Review
Central neurocytomas (CN) are rare tumors within the central nervous system. Originating from the septum pellucidum and subependymal cells, they are typically found in the third and lateral ventricles. For this reason, they may lead to hydrocephalus and increased intracranial pressure. CNs are generally benign lesions that exhibit locally aggressive behavior and a high recurrence rate. Complete surgical resection is the preferred treatment; however, due to their anatomical location, this is often not feasible. Based on these findings, Gamma Knife radiosurgery (GKRS) has been introduced for managing both residual and recurrent tumors and as an initial therapy in selected cases. This study aimed to systematically review the available knowledge regarding GKRS for CN. A systematic investigation of the scientific literature was undertaken through an exhaustive search across prominent databases, including PubMed, Web of Science, and Google Scholar, by employing precise MeSH terms such as "Central neurocytoma," "Radiosurgery," "Gamma Knife," and "Stereotactic Radiosurgery." A comprehensive quantitative systematic review and meta-analysis were meticulously conducted, focusing on cases of CN treated with GKRS for a thorough evaluation of outcomes and efficacy. Seventeen articles, including 289 patients, met the inclusion criteria. Random effects meta-analysis estimates for disease control and local tumor control were 90% (95% CI 87-93%; I2 = 0%, p < 0.74) and 94% (95% CI 92-97%; I2 = 0%, p < 0.98), respectively. When considering only studies with at least 5 years of follow-up, progression-free survival was 89% (95% CI 85-94%; I2 = 0.03%, p < 0.74). The mean clinical control rate was 96%. This systematic review and meta-analysis confirmed the safety and efficacy of GKRS in managing CN.
Topics: Humans; Radiosurgery; Neurocytoma; Central Nervous System; Databases, Factual; Hydrocephalus
PubMed: 38265530
DOI: 10.1007/s10143-024-02301-7