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International Journal of Molecular... Jun 2023Research regarding the mechanisms of brain damage following radiation treatments for brain tumors has increased over the years, thus providing a deeper insight into the... (Review)
Review
Research regarding the mechanisms of brain damage following radiation treatments for brain tumors has increased over the years, thus providing a deeper insight into the pathobiological mechanisms and suggesting new approaches to minimize this damage. This review has discussed the different factors that are known to influence the risk of damage to the brain (mainly cognitive disturbances) from radiation. These include patient and tumor characteristics, the use of whole-brain radiotherapy versus particle therapy (protons, carbon ions), and stereotactic radiotherapy in various modalities. Additionally, biological mechanisms behind neuroprotection have been elucidated.
Topics: Humans; Cranial Irradiation; Brain Neoplasms; Brain; Radiosurgery; Combined Modality Therapy
PubMed: 37445846
DOI: 10.3390/ijms241310669 -
Chinese Clinical Oncology Apr 2022This review will focus on the late neurological complications from cranial irradiation and relevant mitigation strategies. (Review)
Review
OBJECTIVE
This review will focus on the late neurological complications from cranial irradiation and relevant mitigation strategies.
BACKGROUND
Radiotherapy (RT) remains an important pillar in the management of brain metastases. Patients being treated in the modern era do experience longer survival, because of superior intra- and extra-cranial disease control. As a result, they can be more prone to developing and manifesting late complications post-brain radiotherapy.
METHODS
A search and narrative review of prospective clinical trials relating to neurological toxicity outcomes was conducted.
CONCLUSIONS
Neurological toxicities can be challenging to diagnose and manage and should be considered during consideration of radiotherapy in brain metastasis, hence more emphasis should be placed on prevention and upfront mitigation of these complications, with novel strategies showing promising results in prospective trials being adopted into clinical practice.
Topics: Brain Neoplasms; Cranial Irradiation; Humans; Prospective Studies; Radiosurgery; Risk Reduction Behavior
PubMed: 35400164
DOI: 10.21037/cco-21-121 -
Journal of Radiation Research Jan 2023In this study, the dose schedule efficacy, safety and late adverse effects of stereotactic radiosurgery (SRS) were evaluated for patients with symptomatic cavernomas who...
In this study, the dose schedule efficacy, safety and late adverse effects of stereotactic radiosurgery (SRS) were evaluated for patients with symptomatic cavernomas who were not eligible for surgery and treated with SRS. Between January 2013 and December 2018, 53 patients with cavernomas were treated using SRS with the CyberKnife® system. Patients' diseases were deeply located or were in subcortical functional brain regions. In addition to bleeding, 23 (43.4%) patients had epilepsy, 12 (22.6%) had neurologic symptoms and 16 patients (30.2%) had severe headaches. The median volume was 741 (range, 421-1351) mm3, and the median dose was 15 (range, 14-16) Gy in one fraction. After treatment, six (50%) of 12 patients with neurologic deficits still had deficits. Rebleeding after treatment developed in only two (3.8%) patients. The drug was completely stopped in 14 (60.9%) out of 23 patients who received epilepsy treatment, and the dose of levetiracetam decreased from 2000 mg to 1000 mg in four (17.3%) of nine patients. Radiologically, complete response (CR) was observed in 13 (24.5%) patients, and partial responses (PR) were observed in 32 (60.2%) patients. Clinical response of CR was observed in 30 (56.6%) patients, PR was observed in 16 (30.2%), stable disease (SD) was observed in three (5.7%) and four (7.5%) patients progressed. In conclusion, SRS applied in the appropriate dose schedule may be an effective and reliable method in terms of symptom control and prevention of rebleeding, especially in patients with inoperable cavernomas.
Topics: Humans; Radiosurgery; Hemangioma, Cavernous, Central Nervous System; Epilepsy; Levetiracetam; Brain; Treatment Outcome; Retrospective Studies; Follow-Up Studies
PubMed: 36208871
DOI: 10.1093/jrr/rrac056 -
Neurosurgery Jun 2023Stereotactic radiosurgery (SRS) is one of the main treatment options in the management of small to medium size vestibular schwannomas (VSs), because of high tumor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stereotactic radiosurgery (SRS) is one of the main treatment options in the management of small to medium size vestibular schwannomas (VSs), because of high tumor control rate and low cranial nerves morbidity. Series reporting long-term hearing outcome (>3 years) are scarce.
OBJECTIVE
To perform a systematic review of the literature and meta-analysis, with the aim of focusing on long-term hearing preservation after SRS.
METHODS
Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed articles published between January 1990 and October 2020 and referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical study or case series of VSs treated with SRS (single dose), reporting hearing outcome after SRS with a median or mean audiometric follow-up of at least 5 years. Hearing preservation, cranial nerves outcomes, and tumor control were evaluated.
RESULTS
Twenty-three studies were included. Hearing preservation was found in 59.4% of cases (median follow-up 6.7 years, 1409 patients). Main favorable prognostic factors were young age, good hearing status, early treatment after diagnosis, small tumor volume, low marginal irradiation dose, and maximal dose to the cochlea. Tumor control was achieved in 96.1%. Facial nerve deficit and trigeminal neuropathy were found in 1.3% and 3.2% of patients, respectively, both significantly higher in Linear Accelerator series than Gamma Knife series ( P < .05).
CONCLUSION
Long-term hearing preservation remains one of the main issues after SRS, with a major impact on health-related quality of life. Our meta-analysis suggests that hearing preservation can be achieved in almost 60% of patients after a median follow-up of 6.7 years, irrespective of the technique.
Topics: Humans; Neuroma, Acoustic; Radiosurgery; Treatment Outcome; Quality of Life; Hearing; Follow-Up Studies; Retrospective Studies
PubMed: 36735500
DOI: 10.1227/neu.0000000000002354 -
Asian Journal of Surgery May 2023Many studies have reported the combination of radiosurgery and immune checkpoint inhibitors (ICI) in the treatment of brain metastasis, but these studies have not... (Meta-Analysis)
Meta-Analysis Review
Many studies have reported the combination of radiosurgery and immune checkpoint inhibitors (ICI) in the treatment of brain metastasis, but these studies have not reached a consistent conclusion. Therefore, we conducted this systematic review and meta-analysis to evaluate the effect of combination therapy compared with radiosurgery alone on the prognosis of patients with brain metastasis. The Pubmed-MEDLINE and Ovid-EMBASE databases were comprehensively searched to identify relevant articles until May 5, 2022. The search results were filtered by the inclusion and exclusion criteria described in this paper. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were presented as estimates effect to reflect the effect of combined therapy on each outcome. A total of 17 eligible studies covering 2079 patients were included in this meta-analysis. The pooled results showed that the use of targeted drugs could significantly improve the overall survival (HR = 0.62, 95%CI: 0.51-0.76; P<0.01), reduce the risk of local recurrence (HR = 0.48, 95%CI: 0.38-0.62; P<0.01) and distant brain recurrence (HR = 0.70, 95%CI: 0.50-0.97; P<0.05). Overall, SRS combined with ICIs could significantly improve overall survival, local control, and distant brain control of patients with brain metastasis compared to SRS alone, but the effect varies for different pathological types. Our results verified the rationality of the current treatment strategy for brain metastasis which emphasizes the combination of local and systematic therapy.
Topics: Humans; Radiosurgery; Immune Checkpoint Inhibitors; Brain Neoplasms; Combined Modality Therapy; Prognosis
PubMed: 36207214
DOI: 10.1016/j.asjsur.2022.09.080 -
International Journal of Radiation... Nov 2022To develop and compare tumor-control probability (TCP) models for single-fraction stereotactic radiosurgery (SRS) for brain metastasis (BMs) with and without retreatment.
PURPOSE
To develop and compare tumor-control probability (TCP) models for single-fraction stereotactic radiosurgery (SRS) for brain metastasis (BMs) with and without retreatment.
METHODS AND MATERIALS
We developed three different schemas to model TCP of BMs treated with linear accelerator-based SRS. Dose to 99% of each planning target volume (PTV D) and 6-month local control were fit using linear-quadratic-linear (LQ-L) models based on equivalent-dose conversions in 2 Gy (EQD2). The M1 schema had separate LQ-L TCP models for initial dose (M1-initial) and retreatment dose (M1-retreat), and the M2 schema had an LQ-L model using the sum of 50% of the initial SRS dose plus the retreatment SRS dose. The M1-initial and M1-retreat schema modeled local control after first SRS to 48 lesions (patients = 22) and second SRS to 46 lesions (patients = 21). The M0 schema included a whole data set of 349 lesions (patients = 136) receiving first SRS (no retreatment and M1-initial).
RESULTS
LQ-L models fitted the data well (χ = 0.059-0.525 and P = 0.999-1.000). For M0 and M1-retreat, the fitted models EQD2 and γ parameters were similar. The LQ-L fitted EQD2 was ∼8.0 Gy for M0 and M1-retreat, ∼24 Gy for M1-initial, and ∼19 Gy for M2. The model fitted γ was 0.1 Gy for M0, M1-retreat, and M2 and 0.5 for M1-initial. For the PTV D of 10 and 20 Gy, the steepest to shallowest dose-response or largest change in TCP, that is, TCP - TCP, was observed in M1-initial (0.49) and M2 (0.17). M0 and M1-retreat showed a similar change in TCP of 0.21.
CONCLUSIONS
The model-fitted parameters predicted the recurrent BMs required a higher threshold dose and had a steeper dose-response for first SRS versus second SRS and M0. Alternatively, the recurrent BMs required ∼2 Gy higher predicted PTV D dose for first SRS to achieve the same TCP of 0.75 compared with second SRS and M0. Further investigations on larger patient cohorts are needed for validating our findings in predictive modeling of recurrent BMs.
Topics: Brain Neoplasms; Humans; Probability; Radiosurgery; Retreatment
PubMed: 35863671
DOI: 10.1016/j.ijrobp.2022.06.102 -
Neurology India 2023
Topics: Humans; Radiosurgery; Treatment Outcome; Follow-Up Studies
PubMed: 37026327
DOI: 10.4103/0028-3886.373630 -
JAMA Oncology Nov 2022After the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy...
Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial.
IMPORTANCE
After the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy (SABR) for oligometastases.
OBJECTIVE
To document toxic effects of treatment with SABR in a large cohort from a population-based, provincial cancer program.
DESIGN, SETTING, AND PARTICIPANTS
From November 2016 to July 2020, 381 patients across all 6 cancer centers in British Columbia were treated in this single-arm, phase 2 trial of treatment with SABR for patients with oligometastatic or oligoprogressive disease. During this period, patients were only eligible to receive treatment with SABR in these settings in trials within British Columbia; therefore, this analysis is population based, with resultant minimal selection bias compared with previously published SABR series.
INTERVENTIONS
Stereotactic ablative body radiotherapy to up to 5 metastases.
MAIN OUTCOMES AND MEASURES
Rate of grade 2, 3, 4, and 5 toxic effects associated with SABR.
FINDINGS
Among 381 participants (122 women [32%]), the mean (SD; range) age was 68 (11.1; 30-97) years, and the median (range) follow-up was 25 (1-54) months. The most common histological findings were prostate cancer (123 [32%]), colorectal cancer (63 [17%]), breast cancer (42 [11%]), and lung cancer (33 [9%]). The number of SABR-treated sites were 1 (263 [69%]), 2 (82 [22%]), and 3 or more (36 [10%]). The most common sites of SABR were lung (188 [34%]), nonspine bone (136 [25%]), spine (85 [16%]), lymph nodes (78 [14%]), liver (29 [5%]), and adrenal (15 [3%]). Rates of grade 2, 3, 4, and 5 toxic effects associated with SABR (based on the highest-grade toxic effect per patient) were 14.2%; (95% CI, 10.7%-17.7%), 4.2% (95% CI, 2.2%-6.2%), 0%, and 0.3% (95% CI, 0%-0.8%), respectively. The cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 by Kaplan-Meier analysis was 8%, and for grade 3 or higher, 4%.
CONCLUSIONS AND RELEVANCE
This single-arm, phase 2 clinical trial found that the incidence of grade 3 or higher SABR toxic effects in this population-based study was less than 5%. Furthermore, the rates of grade 2 or higher toxic effects (18.6%) were lower than previously published for SABR-COMET (29%). These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and potentially support further enrollment in randomized phase 3 clinical trials.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02933242.
Topics: Male; Humans; Radiosurgery; Lung Neoplasms; Dose Fractionation, Radiation; Prostatic Neoplasms; Kaplan-Meier Estimate
PubMed: 36173619
DOI: 10.1001/jamaoncol.2022.4394 -
Radiotherapy and Oncology : Journal of... Jun 2023Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report...
PURPOSE
Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report the 5-year overall survival (OS) rates for patients with metastatic disease treated with this combined-modality therapy in a phase II trial (NCT02239900).
METHODS AND MATERIALS
SABR was delivered to patients with metastatic lesions in the liver and lung either during the first dose (concurrent) or 1 week after the second dose (sequential) of ipilimumab (every 3 weeks for 4 cycles). SABR was administered to liver or lung metastases as 50 Gy in 4 fractions or 60 Gy in 10 fractions, considering the tumor location. The OS rates at 12, 36, and 60 months were estimated by the Kaplan-Meier method; subgroup analyses of progression-free survival (PFS) and OS by SABR-targeted lesions (liver/lung) were performed by log-rank tests.
RESULTS
A total of 106 patients were enrolled in this long-term follow-up analysis. At the median follow-up time of 15.32 months (range, 0.97-82.13 months), the median PFS was 6.52 months (95% CI, 5.86-7.14) and the median OS was 15.32 months (95% CI,13.03-17.23). The 12-, 36-, and 60-month OS rates were 61%, 23%, and 15%, respectively. There was a significant difference in OS between cohorts (P = 0.039), with a stronger response observed in lung-treated subgroups. Patients who had received sequential fractions (50 Gy/4f) to the lung had improved OS compared to those who had received sequential fractions (18.29 vs 8.9 months, P = 0.043) to the liver. Subgroup analysis of SABR-targeted lesions showed that lung-targeted groups had significantly longer PFS (6.87 months vs. 5.63 months, P = 0.034) and OS (18.67 months vs. 13.63 months, P = 0.013) compared to liver-targeted groups. The sequence did not affect the outcomes of PFS and OS. Exploratory analyses showed that SABR-targeted lesions and smoking history comprised an independent risk factor for OS.
CONCLUSIONS
Updated 5-year OS data from the phase II trial demonstrate the long-term clinical benefit of ipilimumab and SABR, which warrants further research and cumulative data.
Topics: Humans; Ipilimumab; Liver Neoplasms; Lung; Lung Neoplasms; Neoplasms, Second Primary; Radiosurgery; Treatment Outcome
PubMed: 36921766
DOI: 10.1016/j.radonc.2023.109618 -
Journal of Applied Clinical Medical... Mar 2020
Topics: Humans; Neoplasms; Practice Patterns, Physicians'; Radiosurgery
PubMed: 32176454
DOI: 10.1002/acm2.12853