Stereotactic Radiosurgery: Adjacent Tissue Injury and Response after High-Dose Single Fraction Radiation—Part II: Strategies for Therapeutic Enhancement, Brain Injury Mitigation, and Brain Injury Repair

Neurosurgery ◽  
2007 ◽  
Vol 60 (5) ◽  
pp. 799-814 ◽  
Author(s):  
Bryan C. Oh ◽  
Charles Y. Liu ◽  
Michael Y. Wang ◽  
Paul G. Pagnini ◽  
Cheng Yu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Tissue Injury ◽  
Whole Brain Radiotherapy ◽  
Molecular Data ◽  
Phase Iii ◽  
High Dose ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Axonal Regrowth

Abstract IN THE FIRST part of this series, we reviewed the histological, radiographic, and molecular data gathered regarding the brain parenchymal response to radiosurgery and suggested future studies that could enhance our understanding of the topic. With this article, we begin by addressing methods of potentiating the effect of radiosurgery on target lesions of the central nervous system. Much of the work on potentiating the effects of cranial radiation has been performed in the field of whole-brain radiotherapy. Data from Phase III trials evaluating the efficacy of various agents as radiosensitizers or radioenhancers in whole-brain radiotherapy are reviewed, and trials for investigating certain agents as enhancers of radiosurgery are suggested. The roles of gene therapy and nanotechnology in enhancing the therapeutic efficacy of radiosurgery are then addressed. Focus is then shifted to a discussion of strategies of protecting healthy tissue from the potentially deleterious aspects of the brain's response to radiosurgery that were presented in the first article of this series. Finally, comments are made regarding the role of neural progenitor or stem cells in the repair of radiation-induced brain injury after radiosurgery. The importance of both the role of the extracellular matrix and properly directed axonal regrowth leading to appropriate target reinnervation is highlighted.

scholarly journals A Dutch phase III randomized multicenter trial: whole brain radiotherapy vs. stereotactic radiotherapy for 4-10 brain metastases

2021 ◽  
Author(s):  
Dianne Hartgerink ◽  
Anna Bruynzeel ◽  
Danielle Eekers ◽  
Ans Swinnen ◽  
Coen Hurkmans ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Brain Metastases ◽  
Survival Rates ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
One Year

Abstract Background The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods Patients with 4 to 10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at three months post-treatment. Results The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range, 4-9) and the median total treatment volume was 13.0 cc 3 (range, 1.8-25.9 cc 3). QOL at three months decreased in the SRS group by 0.1 (SD=0.2), compared to 0.2 (SD=0.2) in the WBRT group (p=0.23). The actuarial one-year survival rates were 57% (SRS) and 31% (WBRT) (p=0.52). The actuarial one-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (p=0.22). Conclusion In patients with 4 to 10 BM, SRS alone resulted in one-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

scholarly journals High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial

2010 ◽  
Vol 11 (11) ◽  
pp. 1036-1047 ◽  
Author(s):  
Eckhard Thiel ◽  
Agnieszka Korfel ◽  
Peter Martus ◽  
Lothar Kanz ◽  
Frank Griesinger ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Phase 3 ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

The Changing Role of Whole-Brain Radiotherapy

JAMA Oncology ◽  
2017 ◽  
Vol 3 (8) ◽  
pp. 1021 ◽  
Author(s):  
Minesh P. Mehta ◽  
Hidefumi Aoyama ◽  
Vinai Gondi
Keyword(s):  
Whole Brain Radiotherapy ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Changing Role

scholarly journals Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001

2020 ◽  
Vol 38 (10) ◽  
pp. 1019-1029 ◽  
Author(s):  
Paul D. Brown ◽  
Vinai Gondi ◽  
Stephanie Pugh ◽  
Wolfgang A. Tome ◽  
Jeffrey S. Wefel ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Reliable Change Index ◽  
Whole Brain ◽  
Phase Iii Trial ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance ◽  
Patient Reported

PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [ P = .049] and 16.4% v 33.3% [ P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( P = .04), less difficulty with remembering things ( P = .01), and less difficulty with speaking ( P = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( P = .008) and fewer cognitive symptoms ( P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

Randomized phase III study of high-dose methotrexate and whole brain radiotherapy with or without concomitant and adjuvant temozolomide in patients with newly diagnosed primary central nervous system lymphoma: JCOG1114C.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2500-2500
Author(s):  
Kazuhiko Mishima ◽  
Ryo Nishikawa ◽  
Yoshitaka Narita ◽  
Junki Mizusawa ◽  
Minako Sumi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Hazard Ratio ◽  
Phase Iii ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

2500 Background: Temozolomide (TMZ) is an oral alkylating agent that penetrates the blood-brain barrier with moderate toxicity, and has shown anti-tumor activity in primary central nervous system lymphoma (PCNSL) in single arm studies. Our goal was to determine whether the addition of concomitant and adjuvant TMZ chemotherapy to standard treatment of high-dose methotrexate (HD-MTX) and whole brain radiotherapy (WBRT) for PCNSL improves survival in a randomized controlled trial. Methods: We did an open-label, randomized phase III trial at 30 hospitals in Japan enrolling immunocompetent patients (pts) aged 20-70 years with histologically confirmed newly diagnosed PCNSL. Pts enrolled at step 1 registration received HD-MTX (MTX; 3.5 g/m2 at day 1, 15, 29). Pts who received at least 1 cycle of HD-MTX were randomly assigned (1:1) at step 2 registration to receive WBRT (30 Gy) ± 10 Gy boost (control arm: A) or WBRT ± boost with concomitant TMZ (75 mg/m2 daily) and adjuvant TMZ (150-200 mg/m2 daily for 5 days every 28 days) for two years after initiation of HD-MTX or until tumor progression (experimental arm: B). Randomization was adjusted by institution, PS (0-1 / 2-3), age (≤60/≥61 years), presence or absence of intraparenchymal tumor after HD-MTX. The primary endpoint was overall survival (OS). The planned sample size was 130 pts in total, to provide an 80% power to detect a 0.52 hazard ratio (65% vs 80% in 2y-OS) for arm B to A and a one-sided alpha of 5%. Results: Between September 29, 2014 and October 15, 2018, 134 pts were enrolled, of whom 122 were randomly assigned and analyzed; 62 to arm A and 60 to arm B. At the planned interim analysis, the 2-y OS was 86.8% (95% CI: 72.5-94.0) in arm A and 71.4% (56.0-82.2) in arm B. The hazard ratio was 2.18 (95% CI: 0.95 to 4.98) with predictive probability for showing the superiority of arm B at the final analysis was calculated to be 1.3%. The study was terminated due to futility. The 2-y progression-free survival was 60.6% (43.6-73.8) in arm A and 49.9% (34.4-63.5) in arm B with a hazard ratio of 1.54 (0.88 to 2.70). The most common grade 3 and 4 toxicities were lymphopenia, observed in 7 (11.5%) pts during WBRT in arm A, 18 (30%) pts during WBRT + concomitant TMZ and 18 (37.5%) pts during adjuvant TMZ in arm B. Conclusions: This study failed to demonstrate the benefit of the addition of TMZ to WBRT and adjuvant TMZ in newly diagnosed PCNSL. Possible biomarkers including methylation status of the MGMT promoter in the tumors will be analyzed. Clinical trial information: jRCTs031180207 .

scholarly journals NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi22-vi22
Author(s):  
Keiichi Kobayashi ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Yuki Yamagishi ◽  
Naomi Hanayama ◽  
...  
Keyword(s):  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Study Results

Abstract Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.

Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery ◽  
2018 ◽  
Vol 85 (2) ◽  
pp. 257-263 ◽  
Author(s):  
Ryan T Hughes ◽  
Emory R McTyre ◽  
Michael LeCompte ◽  
Christina K Cramer ◽  
Michael T Munley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Outcomes ◽  
Whole Brain Radiotherapy ◽  
Cox Proportional Hazards ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Increased Risk

Abstract BACKGROUND The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial. OBJECTIVE To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group. METHODS A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox proportional hazards. RESULTS Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respectively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume parameters predicted for death, neurologic death or toxicity. CONCLUSION SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

Possible role of aprepitant for intractable nausea and vomiting following whole brain radiotherapy—a case report

2016 ◽  
Vol 5 (4) ◽  
pp. 315-318 ◽  
Author(s):  
Deepti Ahuja ◽  
Sachidanand J. Bharati ◽  
Nishkarsh Gupta ◽  
Ritesh Kumar ◽  
Sushma Bhatnagar
Keyword(s):  
Case Report ◽  
Whole Brain Radiotherapy ◽  
Nausea And Vomiting ◽  
Whole Brain ◽  
Brain Radiotherapy
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