Linac-based fractionated stereotactic radiotherapy with a micro-multileaf collimator for large brain metastasis unsuitable for surgical resection

Abstract The aim of this study was to assess clinical outcomes using linac-based, fractionated, stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for large brain metastasis (LBM) unsuitable for surgical resection. Between January 2009 and October 2018 we treated 21 patients with LBM using linac-based fSRT. LBM was defined as a tumor with ≥30 mm maximal diameter in gadolinium-enhanced magnetic resonance images. LBMs originated from the lung (n = 17, 81%), ovary (n = 2, 9.5%), rectum (n = 1, 4.8%) and esophagus (n = 1, 4.8%). The median pretreatment Karnofsky performance status was 50 (range: 50–80). Recursive partition analysis (RPA) was as follows: Classes 2 and 3 were 7 and 14 patients, respectively. The median follow-up was 5 months (range: 1–86 months). The range of tumor volume was 8.7–26.5 cm3 (median: 17.1 cm3). All patients were basically treated with 35Gy in 5 fractions, except in three cases. The progression-free survival was 3.0 months. The median survival time was 7.0 months. There was no permanent radiation injury in any of the patients. Radiation-caused central nervous system necrosis, according to the Common Terminology Criteria for Adverse Events version 4.0, occurred in one patient (grade 3). One patients received bevacizumab for radiation necrosis. Two patients underwent additional surgical resection due to local progression and cyst formation. For patients with LBM unsuitable for surgical resection, linac-based fSRT is a promising therapeutic alternative.

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MET-01 Linac-based fractionated stereotactic radiotherapy with micro-multileaf collimeter for large brain metastasis unsuitable for surgical resection

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.080 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii18-ii18

Author(s):

Ryosuke Matsuda ◽

Tetsuro Tamamoto ◽

Takayuki Morimoto ◽

Yasuhiro Takeshima ◽

Kentaro Tamura ◽

...

Keyword(s):

Brain Metastasis ◽

Surgical Resection ◽

Stereotactic Radiotherapy ◽

Karnofsky Performance Status ◽

Performance Status ◽

Magnetic Resonance Images ◽

Fractionated Stereotactic Radiotherapy ◽

Maximal Diameter ◽

Local Progression ◽

Large Brain

Abstract To assess clinical outcomes using linac-based, fractionated, stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for large brain metastasis (LBM) unsuitable for surgical resection. Between January 2009 and October 2018, we treated 21 patients with LBM using linac-based fSRT. LBM was defined as a tumor >30mm maximal diameter in gadolinium-enhanced magnetic resonance images. LBMs originated from the lung (n=17, 81%), ovary (n=2, 9.5%), rectum (n =1, 4.8%), and esophagus (n=1, 4.8%). The median pretreatment Karnofsky Performance Status was 50 (range: 50~80). Recursive partition analysis (RPA) was as follows: Classes 2 and 3 were 7 and 14 patients, respectively. The median follow-up was 5 months (range: 1~86 months). The range of tumor volume was 8.7~26.5 cm3 (median: 17.1 cm3). All patients were basically treated with fSRT ranged from 35 Gy with 7 Gy daily fractions, except in three cases. The progression-free survival was 3.0 months. The median survival time was 7.0 months. There was no permanent radiation injury in any of the patients. Radiation-caused central nervous system necrosis, according to the Common Terminology Criteria for Adverse Events version 4.0, occurred in one patient (grade 3). One patients received bevacizumab for radiation necrosis. Two patients underwent additional surgical resection due to local progression and cyst formation. For patients with LBM unsuitable for surgical resection, linac-based fSRT is a promising therapeutic alternative.

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Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases

Strahlentherapie und Onkologie ◽

10.1007/s00066-012-0122-3 ◽

2012 ◽

Vol 188 (8) ◽

pp. 696-701 ◽

Cited By ~ 22

Author(s):

R. Wiggenraad ◽

A. Verbeek-de Kanter ◽

M. Mast ◽

R. Molenaar ◽

H.B. Kal ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiotherapy ◽

Fractionated Stereotactic Radiotherapy ◽

Single Fraction ◽

Local Progression ◽

Large Brain

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Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection

Radiation Oncology ◽

10.1186/s13014-016-0653-3 ◽

2016 ◽

Vol 11 (1) ◽

Cited By ~ 24

Author(s):

Pierina Navarria ◽

Federico Pessina ◽

Luca Cozzi ◽

Anna Maria Ascolese ◽

Fiorenza De Rose ◽

...

Keyword(s):

Brain Metastases ◽

Surgical Resection ◽

Stereotactic Radiotherapy ◽

Volumetric Modulated Arc Therapy ◽

Fractionated Stereotactic Radiotherapy ◽

Large Brain ◽

Arc Therapy ◽

Radiotherapy Alone

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MET-6 Neoadjuvant fractionated stereotactic radiotherapy followed by piecemeal resection for metastatic brain tumor

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab159.099 ◽

2021 ◽

Vol 3 (Supplement_6) ◽

pp. vi26-vi26

Author(s):

Koichi Mitsuya ◽

Shoichi Deguchi ◽

Manabu Muto ◽

Kazuaki Yasui ◽

Tsuyoshi Onoe ◽

...

Keyword(s):

Brain Metastasis ◽

Stereotactic Radiosurgery ◽

Stereotactic Radiotherapy ◽

Progression Free Survival ◽

Lesion Size ◽

Fractionated Stereotactic Radiotherapy ◽

Tumor Diameter ◽

Whole Brain Radiation ◽

Large Brain ◽

Piecemeal Resection

Abstract BACKGROUND: Large brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative stereotactic radiosurgery (SRS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (Na-SRS) followed by surgery was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation necrosis (RN). We treated with neoadjuvant fractionated stereotactic radiotherapy (Na-fSRT) followed by surgery for large brain metastasis with piecemeal resection. METHODS: Twelve patients received Na-fSRT followed by surgery between July 2019 and April 2021. Na-fSRT dose was based on lesion size and was standard dosing. Surgery generally followed within 7 days after radiotherapy. RESULTS: The mean age was 68 years (51–79). Sixteen men and five women. Mean follow-up period was 8.5 months (1–24.9). Primary were lung; 10 (NSCLC; 9, SCLC (recurrence); 1), esophagus; 3, colon; 2, melanoma; 2, kidney; 2 (recurrence1), uterus body; 1, and liver; 1. The median maximum tumor diameter was 3.6 cm (2.6–4.9). Median PTV, GTV volume were 21.7ml, 15.5ml, respectively. The median fSRT dose was 30Gy/5fr, and the median time from fSRT to surgery was 4 days (1–7). As preoperative adverse event, intracranial hypertension and partial seizure grade 2 (CTCAE ver.5) were occurred, but controlled with steroid and osmotic diuretics and anticonvulsant. Grade 3 and more adverse events were not occurred. Gross total removal was performed in 95.2%. Event cumulative incidence as follows: cavity local recurrence 4.8% (subtotal removal case); distant brain failure 33%; LMD 4.8%; and symptomatic RN 0%. The median intracranial progression free survival was 7 months, and median overall survival was 8.4 months. CONCLUSIONS: Na-fSRT followed by piecemeal resection is safety and feasible, and may have therapeutic value for deep large brain metastasis and eloquent lesion. Further prospective investigations in multi-institutional settings are warranted.

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MET-02 Neoadjuvant fractionated stereotactic radiotherapy followed by surgery for large brain metastasis with difficulty in en-block resection

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.081 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii19-ii19

Author(s):

Koichi Mitsuya ◽

Shoichi Deguchi ◽

Tsuyoshi Onoe ◽

Kazuaki Yasui ◽

Hirofumi Ogawa ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastasis ◽

Small Cell Lung Cancer ◽

Stereotactic Radiosurgery ◽

Cell Lung Cancer ◽

Stereotactic Radiotherapy ◽

Small Cell ◽

Fractionated Stereotactic Radiotherapy ◽

Small Cell Lung ◽

Large Brain

Abstract BACKGROUND: Large brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative stereotactic radiosurgery (SRS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (Na-SRS) followed by surgery was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation necrosis (sRN). However, local control rate was not significantly improved. We treated with neoadjuvant fractionated stereotactic radiotherapy (Na-frSRT) followed by surgery for large brain metastasis with difficulty in en-block resection. METHODS: Nine patients received Na-frSRT followed by surgery between July 2019 and June 2020. Na-frSRT dose was based on lesion size and was standard dosing. Surgery generally followed within 7 days after radiotherapy. RESULTS: The mean age was 64 years (55–78). Eight men and one woman. Median follow-up period was 5.3 months (1.7–12.5). Primary cancers were non-small cell lung cancer 2, esophageal cancer 2, colon cancer 1, melanoma 1, hepato-cellular carcinoma 1 and recurrence of BM from small cell lung cancer and renal cell cancer. The median maximum tumor diameter was 4.3cm (2.6–4.9). The median SRT dose was 30Gy/5fr, and the median time from SRT to surgery was 4 days (1–7). Median PTV was 15.4ml (5.6–49.7), and median GTV was 21.7ml (8.6–61.4). As preoperative adverse event, intracranial hypertension grade2 (CTCAE ver.4.0) was occurred one patient, but controlled with steroid and osmotic diuretics. Grade 3 and more adverse events were not occurred. Gross total resection with intra-tumoral decompression and piece-meal technique was performed in all cases as planning. Event cumulative incidence as follows: surgical site recurrence 0%; local recurrence 11.1%; distant brain failure 11.1%; LMD 0%; and sRN 0%. The median overall survival was not reached. CONCLUSIONS: Na-frSRT followed by surgery is safety and feasible, and may have therapeutic value for large brain metastasis. Further prospective investigations in multi-institutional settings are warranted.

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RADI-05. FRACTIONATED TREATMENT OF BRAIN METASTASES WITH GAMMA KNIFE ICON

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.098 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i22-i22

Author(s):

Jameson Mendel ◽

Ankur Patel ◽

Toral Patel ◽

Robert Timmerman ◽

Tu Dan ◽

...

Keyword(s):

Brain Metastasis ◽

Brain Metastases ◽

Gamma Knife ◽

Local Control ◽

Stereotactic Radiotherapy ◽

Tumor Volume ◽

Univariate Analysis ◽

Local Failure ◽

Fractionated Stereotactic Radiotherapy

Abstract PURPOSE/OBJECTIVE(S): Stereotactic radiosurgery with Gamma Knife is a common treatment modality for patients with brain metastasis. The Gamma Knife ICON allows for immobilization with an aquaplast mask, permitting fractionated treatments. We describe one of the first experiences utilizing this technique with brain metastasis and evaluate outcomes. MATERIALS/METHODS: From June 2017 to November 2018, 29 patients with 43 separate intracranial lesions were treated with fractionated stereotactic radiotherapy using the gamma knife ICON at a single institution. Patients received between 20–30 Gy in 3–5 fractions with no margin over the course of 5 to 23 days. Local control was physician assessed. Local failure over time was modeled using cumulative incidence; lesions were censored at last radiographic follow up. RESULTS: Median tumor volume and prescription isodose was 7.7 cm3 (range 0.3–43.9) and 50% (range 40–65), respectively. Median radiographic follow-up was 7 months and median survival was 9 months. Radiation necrosis occurred in 3/3 patients treated with 27 Gy in 3 fractions, one requiring therapeutic resection. Incidence of local failure for all treated lesions was 9% at 1 year. Tumor volume >7 cm3 was associated with local failure on univariate analysis (p=0.025). 100% (2/2) lesions treated with 20 Gy in 5 fractions developed local recurrence. CONCLUSION: Fractionated stereotactic radiotherapy with the Gamma Knife ICON provides excellent local control for small and large brain metastases with minimal toxicity. Tumors >7 cm3 should receive at least 30 Gy in 5 fractions for optimal control. Treatment with 27 Gy in 3 fractions appears to have high rates of treatment related toxicity and should be avoided.

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Adjuvant hypofractionated stereotactic radiotherapy after resection of single large brain metastasis in patients with oligo-metastatic disease: a strategy finally validated?

Translational Cancer Research ◽

10.21037/tcr.2020.04.15 ◽

2020 ◽

Vol 9 (5) ◽

pp. 3177-3179

Author(s):

Paul Lesueur ◽

William Kao ◽

Julien Geffrelot ◽

Dinu Stefan

Keyword(s):

Brain Metastasis ◽

Metastatic Disease ◽

Stereotactic Radiotherapy ◽

Hypofractionated Stereotactic Radiotherapy ◽

Large Brain

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Stereotactic Radiosurgery for Renal Cancer Brain Metastasis: Prognostic Factors and the Role of Whole-Brain Radiation and Surgical Resection

Journal of Oncology ◽

10.1155/2015/636918 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 12

Author(s):

Franziska M. Ippen ◽

Anand Mahadevan ◽

Eric T. Wong ◽

Erik J. Uhlmann ◽

Soma Sengupta ◽

...

Keyword(s):

Prognostic Factors ◽

Brain Metastasis ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Surgical Resection ◽

Karnofsky Performance Status ◽

Performance Status ◽

Patient Treatment ◽

Consecutive Series ◽

Additional Surgery

Background. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection.Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed.Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31–85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60–100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively.Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate.

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SURG-01. Management of solitary brain metastasis less than 4 cm in diameter. Surgical resection versus stereotactic radiotherapy: a meta-analysis

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab071.094 ◽

2021 ◽

Vol 3 (Supplement_3) ◽

pp. iii23-iii23

Author(s):

David T Krist ◽

Anant Naik ◽

Susanna S Kwok ◽

Mika Janbahan ◽

William C Olivero ◽

...

Keyword(s):

Surgical Treatment ◽

Brain Metastasis ◽

Surgical Resection ◽

Stereotactic Radiotherapy ◽

Observational Studies ◽

Meta Analysis ◽

Cochrane Library ◽

Tumor Diameter ◽

Solitary Brain Metastasis ◽

Solitary Tumor

Abstract Introduction To treat a solitary metastasis in the brain, surgical resection and/or radiotherapy are the standard treatments of care. However, the clinical scenarios in which to use these techniques alone or in combination are controversial. While a course of stereotactic radiotherapy is often administered to a patient who presents with multiple metastases, surgical resection is often directed against a larger solitary brain metastasis before irradiating the resection bed. The management of a smaller solitary tumor (diameter less than 4 cm) is less clear. Accordingly, our meta-analysis assembled studies that focused on patients with a solitary tumor less than 4 cm in diameter. Methods Following PRISMA guidelines (PROSPERO ID: CRD42021242434), we searched PubMed, Web of Knowledge, and Cochrane Library databases for randomized controlled trials (RCT) and observational studies comparing surgery to radiotherapy for solitary metastatic brain tumors less than 4 cm in diameter. From 498 total records, we included 9 studies for meta-analysis. Analysis was performed on R. Results 2 RCTs and 7 observational studies were identified. 431 patients underwent surgical intervention, and 349 patients exclusively underwent radiotherapy. The surgical treatment cohort did not exhibit a difference in 1-year (OR [95% CI] = 0.866 [0.609–1.289]), 2-year (1.7 [0.843–3.428]), or overall survival (1.18 [0.598–2.327]). However, the surgical treatment group demonstrated greater local tumor recurrence after 1-year (3.975 [1.979–7.987]) and overall local recurrence (3.045 [1.276 - 7.268]). There was no difference between the overall rates of distant recurrence (0.565 [0.218 - 1.466]). Conclusions Our analysis opens more discussion about the management of solitary brain metastasis. Patient selection is paramount in achieving better local control. Stereotactic radiotherapy should be considered for treatment of solitary brain metastasis less than 4 cm in diameter in selected patients. Future randomized control trials for small solitary masses are recommended.

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