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

Navarria, Pierina; Pessina, Federico; Cozzi, Luca; Ascolese, A.M.; Rose, F. De; Fogliata, Antonella; Franzese, Ciro; Franceschini, Davide; Tozzi, A.; D’Agostino, Giuseppe; Comito, Tiziana; Iftode, C.; Maggi, G; Reggiori, G.; Bello, Lorenzo; Scorsetti, Marta

doi:10.1186/s13014-016-0653-3

Cited by 66 publications

(58 citation statements)

References 31 publications

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“…The dose selection and fractionation protocols for brain metastases with a size of 2.5-3.0 cm or larger varied from 18-53 Gy with 2-15 fractionations. 10,15,17,19,21,23 Cumulative incidences of local tumor control were reportedly 61%-96% at the 12th post-irradiation month and crude incidences of fSRSrelated complications were 6%-14%. Our herein-reported 15 Our neurological death results, 14.3% in the C-series and 13.8% in the M-series, were slightly better than those of the 2 above-described series.…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned above, fSRS has been widely applied for managing relatively large brain metastases. 10,15,17,19,21,23 Formerly, however, GK was rarely employed for oligo-fractionation because the standard GK radiosurgery technique required a pin-based head frame. For the past few years, the Elekta Extend bite-block palatal vacuum immobilization system has been available.…”

Section: Discussionmentioning

confidence: 99%

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Three-stage Gamma Knife treatment for metastatic brain tumors larger than 10 cm3: a 2-institute study including re-analyses of earlier results using competing risk analysis

Yamamoto

Higuchi

Serizawa

et al. 2018

Journal of Neurosurgery

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OBJECTIVEThe results of 3-stage Gamma Knife treatment (3-st-GK-Tx) for relatively large brain metastases have previously been reported for a series of patients in Chiba, Japan (referred to in this study as the C-series). In the current study, the authors reappraised, using a competing risk analysis, the efficacy and safety of 3-st-GK-Tx by comparing their experience with that of the C-series.METHODSThis was a retrospective cohort study. Among 1767 patients undergoing GK radiosurgery for brain metastases at Mito Gamma House during the 2005–2015 period, 78 (34 female, 44 male; mean age 65 years, range 35–86 years) whose largest tumor was > 10 cm3, treated with 3-st-GK-Tx, were studied (referred to in this study as the M-series). The target volumes were covered with a 50% isodose gradient and irradiated with a peripheral dose of 10 Gy at each procedure. The interval between procedures was 2 weeks. Because competing risk analysis had not been employed in the published C-series, the authors reanalyzed the previously published data using this method.RESULTSThe overall median survival time after 3-st-GK-Tx was 8.3 months (95% CI 5.6–12.0 months) in the M-series and 8.6 months (95% CI 5.5–10.6 months) in the C-series (p = 0.41). Actuarial survival rates at the 6th and 12th post–3-st-GK-Tx months were, respectively, 55.1% and 35.2% in the M-series and 62.5% and 26.4% in the C-series (HR 1.175, 95% CI 0.790–1.728, p = 0.42). Cumulative incidences at the 12th post–3-st-GK-Tx, determined by competing risk analyses, of neurological deterioration (14.2% in C-series vs 12.8% in M-series), neurological death (7.2% vs 7.7%), local recurrence (4.8% vs 6.2%), repeat SRS (25.9% vs 18.0%), and SRS-related complications (2.3% vs 5.1%) did not differ significantly between the 2 series.CONCLUSIONSThere were no significant differences in post–3-st-GK-Tx results between the 2 series in terms of overall survival times, neurological death, maintained neurological status, local control, repeat SRS, and SRS-related complications. The previously published results (C-series) are considered to be validated by the M-series results.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Three-stage Gamma Knife treatment for metastatic brain tumors larger than 10 cm3: a 2-institute study including re-analyses of earlier results using competing risk analysis

Yamamoto

Higuchi

Serizawa

et al. 2018

Journal of Neurosurgery

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“…In 2016, Navarria published the results of a similar study, administering a dose of 27 Gy in three fractions to lesions of 21 to 30 mm and a dose of 32 Gy in four fractions to lesions of 31 to 50 mm. The technique resulted in local control and an overall survival at 2 years of 96% and 33%, respectively [66] .…”

Section: Srs Treatment Dosementioning

confidence: 98%

Diagnosis and management of brain metastases: an updated review from a radiation oncology perspective

Gutierrez-Valencia¹,

Irving²,

Ricardo³

et al. 2019

JCMT

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Brain metastasis are the most common intracranial malignancy in the adult population. Their incidence has increased dramatically over the last 20 years, as a result of the increasing number of cases stemming from lung and breast cancer together with the higher cancer survival rates due to diagnostic and therapeutic advances. More than 40% of cancer patients develop brain metastases during the course of their disease: specifically, they appear in 50% of patients with lung cancer, more than 25% of patients with breast cancer, and 20% of patients with melanoma. Diagnosis is made using different imaging approaches, such as computed tomography and magnetic resonance imaging, accompanied by clinical manifestations and a history of malignancy supporting the diagnosis of a brain metastasis. Current treatment options should be oriented to the patient's current performance, the number of intracranial and extracranial lesions, and related factors. Although surgical resection and whole-brain radiotherapy have been standard treatments for many years, numerous treatment modalities have become more easily available and accepted worldwide, producing more favorable and reliable results. Among these is stereotactic radiosurgery, and the latest clinical trials support this treatment.

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“…Large brain metastases (LBM) are typically described as measuring either ≥ 2-4 cm in maximum diameter or ≥ 4-15 cm 3 in volume and, traditionally, these tumors have been treated with surgery and WBRT. 4,22,32,42,44,52 Recently, SRS, fractionated stereotactic radiotherapy, or a combination of these modalities with more conventional treatment options has been studied in the management of LBM. 15,18,27,34,42,76 However, optimal treatment paradigms with radiosurgery remain unclear and controversial and are associated with a relatively inferior control rate compared with smaller lesions.…”

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confidence: 99%

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

Angelov

Mohammadi

Bennett

et al. 2018

Journal of Neurosurgery

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OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm (range 2.4-31.3 cm) and 7.0 cm (range 1.0-29.7 cm). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm (range 0.1-23.1 cm). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) ...

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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

Cited by 66 publications

References 31 publications

Three-stage Gamma Knife treatment for metastatic brain tumors larger than 10 cm3: a 2-institute study including re-analyses of earlier results using competing risk analysis

Three-stage Gamma Knife treatment for metastatic brain tumors larger than 10 cm3: a 2-institute study including re-analyses of earlier results using competing risk analysis

Diagnosis and management of brain metastases: an updated review from a radiation oncology perspective

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

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