Analysis of Risk Factors for Development of Radiation Necrosis Following Gamma Knife Radiosurgery for Brain Metastases

Abstract Recent advances in the systemic treatment of various cancers have resulted in longer survival and higher incidence of brain metastases. Phase 3 trials in north America and in Japan have demonstrated that stereotactic radiosurgery will be a standard adjuvant modality following surgery for resectable brain metastases. However, we don’t know the optimal sequence of this combination therapy. We hypothesized that pre-operative stereotactic radiosurgery for resectable brain metastases provides favorable rates of local control, overall survival, leptomeningeal dissemination and symptomatic radiation necrosis. We have experienced 4 cases of resected brain metastases within 1–7 days after Gamma-knife surgery (median margin dose:22Gy) and have been following their clinical course. We will show the repressive cases.

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Systemic Treatment and Radiation Necrosis Following Gamma Knife Radiosurgery in the Treatment of Brain Metastases

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2014.05.1035 ◽

2014 ◽

Vol 90 (1) ◽

pp. S310

Author(s):

R.J. Colaco ◽

P. Martin ◽

J.S. Bond ◽

R.S. Bindra ◽

J.N. Contessa ◽

...

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Systemic Treatment ◽

Radiation Necrosis ◽

Gamma Knife Radiosurgery

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Novel biomarker identification using metabolomic profiling to differentiate radiation necrosis and recurrent tumor following Gamma Knife radiosurgery

Journal of Neurosurgery ◽

10.3171/2016.8.jns161395 ◽

2017 ◽

Vol 127 (2) ◽

pp. 388-396 ◽

Cited By ~ 8

Author(s):

Alex Y. Lu ◽

Jack L. Turban ◽

Eyiyemisi C. Damisah ◽

Jie Li ◽

Ahmed K. Alomari ◽

...

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Radiation Necrosis ◽

Imaging Techniques ◽

Statistical Significance ◽

Gamma Knife Radiosurgery ◽

Metabolic Imaging ◽

Management Decision ◽

Recurrent Tumor ◽

Metabolite Profiles

OBJECTIVEFollowing an initial response of brain metastases to Gamma Knife radiosurgery, regrowth of the enhancing lesion as detected on MRI may represent either radiation necrosis (a treatment-related inflammatory change) or recurrent tumor. Differentiation of radiation necrosis from tumor is vital for management decision making but remains difficult by imaging alone. In this study, gas chromatography with time-of-flight mass spectrometry (GC-TOF) was used to identify differential metabolite profiles of the 2 tissue types obtained by surgical biopsy to find potential targets for noninvasive imaging.METHODSSpecimens of pure radiation necrosis and pure tumor obtained from patient brain biopsies were flash-frozen and validated histologically. These formalin-free tissue samples were then analyzed using GC-TOF. The metabolite profiles of radiation necrosis and tumor samples were compared using multivariate and univariate statistical analysis. Statistical significance was defined as p ≤ 0.05.RESULTSFor the metabolic profiling, GC-TOF was performed on 7 samples of radiation necrosis and 7 samples of tumor. Of the 141 metabolites identified, 17 (12.1%) were found to be statistically significantly different between comparison groups. Of these metabolites, 6 were increased in tumor, and 11 were increased in radiation necrosis. An unsupervised hierarchical clustering analysis found that tumor had elevated levels of metabolites associated with energy metabolism, whereas radiation necrosis had elevated levels of metabolites that were fatty acids and antioxidants/cofactors.CONCLUSIONSTo the authors' knowledge, this is the first tissue-based metabolomics study of radiation necrosis and tumor. Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for brain metastases have unique metabolite profiles that may be targeted in the future to develop noninvasive metabolic imaging techniques.

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Low-Dosage Bevacizumab Treatment: Effect on Radiation Necrosis After Gamma Knife Radiosurgery for Brain Metastases

Frontiers in Surgery ◽

10.3389/fsurg.2021.720506 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuxiang Weng ◽

Jie Shen ◽

Luyuan Zhang ◽

Zebin Fang ◽

Feng Xiao ◽

...

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Low Dose ◽

Radiation Necrosis ◽

Karnofsky Performance Status ◽

Performance Status ◽

Gamma Knife Radiosurgery ◽

High Price ◽

Bevacizumab Treatment ◽

Low Dosage

Cerebral radiation necrosis (RN), a complication of Gamma Knife radiosurgery, is difficult to treat, although bevacizumab seems to be effective. However, clinical data pertaining to bevacizumab treatment for RN are scarce, and its high price is problematic. This study explored the effectiveness of low-dose bevacizumab for RN caused by Gamma Knife. We retrospectively analyzed 22 patients who suffered cerebral RN post-Gamma Knife, and received bevacizumab treatment because of the poor efficacy of glucocorticoids. Low-dose bevacizumab (3 mg/kg) was administered for two cycles at 2-week intervals. T1- and T2-enhanced magnetic resonance imaging (MRI) images were examined for changes in RN status. We also monitored the dose of glucocorticoid, Karnofsky Performance Status (KPS) score, and adverse drug reactions. The mean volume of RN lesions decreased by 45% on T1-weighted images with contrast enhancement, and by 74% on T2-weighted images. All patients discontinued the use of glucocorticoids. According to the KPS scores, all patients showed an improvement in their symptoms and neurological function. No side effects were observed. Low-dosage bevacizumab at a dose of 3 mg/kg every 2 weeks is effective for treating cerebral RN after Gamma knife for brain metastases.

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Outcome evaluation of patients treated with fractionated Gamma Knife radiosurgery for large (> 3 cm) brain metastases: a dose-escalation study

Journal of Neurosurgery ◽

10.3171/2019.5.jns19222 ◽

2020 ◽

Vol 133 (3) ◽

pp. 675-684 ◽

Cited By ~ 4

Author(s):

Kyung Hwan Kim ◽

Doo-Sik Kong ◽

Kyung Rae Cho ◽

Min Ho Lee ◽

Jung-Won Choi ◽

...

Keyword(s):

Overall Survival ◽

Risk Factor ◽

Brain Metastases ◽

Treatment Failure ◽

Gamma Knife ◽

Dose Escalation ◽

Radiation Necrosis ◽

Local Treatment ◽

Gamma Knife Radiosurgery ◽

Dose Escalation Study

OBJECTIVEFractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM.METHODSThe exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival.RESULTSBetween September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5–25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%–29%) in the 9-Gy group, and 37% (95% CI 1%–58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1–51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1–29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups.CONCLUSIONSIn this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

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Gamma knife radiosurgery for renal cell carcinoma brain metastases

Journal of Neurosurgery ◽

10.3171/jns.2002.97.supplement_5.0489 ◽

2002 ◽

Vol 97 ◽

pp. 489-493 ◽

Cited By ~ 42

Author(s):

Laura Hernandez ◽

Lucia Zamorano ◽

Andrew Sloan ◽

James Fontanesi ◽

Simon Lo ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Brain Metastases ◽

Cell Carcinoma ◽

Gamma Knife ◽

Median Survival ◽

Renal Cell ◽

Univariate Analysis ◽

Gamma Knife Radiosurgery ◽

Content Type ◽

Fine Print

Object. The purpose of this study was to clarify the effectiveness of gamma knife radiosurgery (GKS) in achieving a partial or complete remission of so-called radioresistant metastases from renal cell carcinoma (RCC) and to propose guidelines for optimal treatment Methods. During a 5-year period, 29 patients (19 male and 10 female) with 92 brain metastases from RCC underwent GKS. The median tumor volume was 4.7 cm3 (range 0.5–14.5 cm3). Fourteen patients (48%) also underwent whole-brain radiotherapy (WBRT) before GKS, and two patients (6.8%) after GKS. The mean GKS dose delivered to the 50% isodose at the tumor margin was 16.8 Gy (range 13–30 Gy). All cases were categorized according to the Recursive Partitioning Analysis (RPA) classification for brain metastases. Univariate analysis was performed to determine significant prognostic factors and survival. The overall median survival was 7 months after GKS treatment. Age, sex, Karnofsky Performance Scale score, and controlled primary disease were not predictors of survival. Combined WBRT/GKS resulted in median survival of 18, 8.5, and 5.3 months for RPA Classes I, II, and III, respectively, compared with the median survival 7.1, 4.2, and 2.3 months for patients treated with WBRT alone. Conclusions. These results suggest that WBRT combined with GKS may improve survival in patients with brain metastases from RCC. Furthermore, this improvement in survival was seen in all RPA classes.

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Validation of the updated renal graded prognostic assessment (GPA) for patients with renal cancer brain metastases treated with gamma knife radiosurgery

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03793-9 ◽

2021 ◽

Author(s):

Niels J. van Ruitenbeek ◽

Vincent K. Y. Ho ◽

Hans M. Westgeest ◽

Laurens V. Beerepoot ◽

Patrick E. J. Hanssens

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Renal Cancer ◽

Gamma Knife Radiosurgery ◽

Prognostic Assessment ◽

Graded Prognostic Assessment

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Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

Case Reports in Gastroenterology ◽

10.1159/000445976 ◽

2016 ◽

Vol 10 (1) ◽

pp. 204-211 ◽

Cited By ~ 2

Author(s):

Nobuhiro Morinaga ◽

Naritaka Tanaka ◽

Yoshinori Shitara ◽

Masatoshi Ishizaki ◽

Takatomo Yoshida ◽

...

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Brain Metastasis ◽

Brain Metastases ◽

Sigmoid Colon ◽

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Sigmoid Colon Cancer ◽

Ovarian Lesion ◽

Node Metastases

Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy.

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