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Yomo S.,Aizawa Comprehensive Cancer Center | Hayashi M.,Saitama Gamma Knife Center
Journal of Neuro-Oncology | Year: 2013

The aim of the present study was to evaluate the efficacy and limitations of repeat stereotactic radiosurgery (SRS) salvage for patients with recurrence of brain metastases (BM) after whole brain radiotherapy (WBRT). This is a retrospective, observational, single-center trial analyzing 77 consecutive patients with recurrent BM who were treated primarily with WBRT. All patients underwent SRS as salvage treatment. Median age was 62 years, and median Karnofsky performance status (KPS) was 80. The median interval between the starting date of WBRT and radiosurgery was 10.6 months. One, two and more than two SRS sessions were required in 42, 13 and 22 patients, respectively. The median total planning target volume (PTV) was 8.1 mL and the median dose prescribed was 20 Gy. The median follow-up was 7.7 months. 1- and 2-year neurological death-free survival (NS) rates were 87 and 78 %, respectively. Competing risk analysis demonstrated active extra-central nervous system (CNS) disease [Hazard ratio (HR) 0.236, P = 0.041] and total PTV on initial SRS (≥5 mL) (HR 4.22, P = 0.033) to be associated with the NS rate. 1- and 2-year overall survival (OS) rates were 41 and 11 %, respectively. The median OS time was 8.2 months. Active extra-CNS disease (HR 1.94, P = 0.034) and high KPS (≥90) (HR 0.409, P = 0.006) were associated with the OS rate. In total, 798 tumors (75 %) in 66 patients (86 %) with sufficient radiological follow-up data were evaluated. 1- and 2-year metastasis local control rates were 76.6 and 57.9 %, respectively. Prescribed dose (≥20 Gy) (HR 0.326, P < 0.001), tumor volume (≥2 mL) (HR 1.98, P = 0.007) and metastases from breast cancer (HR 0.435, P < 0.001) were independent predictive factors for local tumor control. Repeat salvage SRS for recurrent BM after WBRT appeared to be a safe and effective treatment. In the majority of patients, even those with numerous BM, neurological death could be delayed or even prevented. © 2013 Springer Science+Business Media New York.

Yamamoto M.,Katsuta Hospital Mito Gamma House | Serizawa T.,Tokyo Gamma Unit Center | Shuto T.,Yokohama Rosai Hospital | Akabane A.,Nippon Telegraph and Telephone | And 29 more authors.
The Lancet Oncology | Year: 2014

Background: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. Methods: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. Findings: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). Interpretation: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. Funding: Japan Brain Foundation. © 2014 Elsevier Ltd.

Yomo S.,Aizawa Comprehensive Cancer Center | Hayashi M.,Saitama Gamma Knife Center
Radiation Oncology | Year: 2014

Background: Although the efficacy of prophylactic or therapeutic whole brain radiotherapy (WBRT) for brain metastases (BM) from small cell lung cancer (SCLC) is well established, the role of stereotactic radiosurgery (SRS) has yet to be determined. In the present retrospective analysis, we investigated whether upfront SRS might be an effective treatment option for patients with BM from SCLC.Methods: We analyzed 41 consecutive patients with a limited number of BM (≤ 10) from SCLC who received SRS as the initial treatment. No prophylactic and therapeutic WBRT was given prior to SRS. The median patient age was 69 years and the median Karnofsky performance status (KPS) score was 90. Repeat SRS was given for new distant lesions detected on follow-up neuroradiological imaging, as necessary. Overall survival, neurological death, and local and distant BM recurrence rates were analyzed. The survival results were tested with three prognostic scoring systems validated for SCLC: Diagnosis-specific graded prognostic assessment (DS-GPA), Radiation therapy oncology group -recursive partitioning analysis and Rades's survival score.Results: One- and 2-year overall survival rates were 44% and 17%, respectively. The median survival time was 8.1 months. Survival results replicated the DS-GPA (P = 0.022) and Rades's survival score (P = 0.034). On multivariate analysis, patients with high KPS (hazard ratio (HR): 0.308, P = 0.009) and post-SRS chemotherapy (HR: 0.324, P = 0.016) had better overall survival. In total, 95/121 tumors (79%) in 34 patients (83%) with sufficient radiological follow-up data were evaluated. Six- and 12-month rates of local control failure were 0% and 14%, respectively. Six- and 12-month distant BM rates were 22% and 44%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 18, 7 and one patient, respectively. Symptomatic radiation injury developed in two patients and both were treated conservatively.Conclusions: Our survival analyses with the validated prognostic grading systems suggested upfront SRS for limited BM from SCLC to be a potential treatment option, with patient survival being slightly more than eight months after SRS. Although SRS provided durable local tumor control, repeat treatment was needed in nearly half of patients to achieve control of distant BM. © 2014 Yomo and Hayashi; licensee BioMed Central Ltd.

Yomo S.,Aizawa Comprehensive Cancer Center | Hayashi M.,Saitama Gamma Knife Center
Radiation Oncology | Year: 2014

Background: Large brain metastases (BM) remain a significant cause of morbidity and death for cancer patients despite current advances in multimodality therapies. The goal of the present study was to evaluate the efficacy and limitations of 2-session Gamma Knife stereotactic radiosurgery (SRS) for patients with large BM.Methods: This is a prospective, open-label and single arm study analyzing 58 consecutive patients who received 2-session SRS for large BM (≥ 10 mL). The median age was 66 years, and the median Karnofsky performance status (KPS) score was 70. SRS was the initial treatment in 51 large tumors (84%) and was used as salvage after failed prior treatments for 10 tumors (16%). The fraction protocol was 20-30 Gy given in 2 fractions with 3-4 weeks between fractions. Overall survival (OS) and neurological death (ND), local tumor control and KPS were analyzed.Results: The median follow-up time was 9.0 months. One- and 2-year OS rates were 47% and 20%, respectively. The median OS time was 11.8 months (95% CI: 5.5-15.6). The causes of death were intracranial local progression in 5 cases, meningeal carcinomatosis in 3 and progression of the primary lesion in 39. One- and 2-year ND-free survival rates were 91% and 84%, respectively. In 52 of 61 large BM (85%) with sufficient radiological follow-up data, 6- and 12-month local tumor control rates were 85% and 64%, respectively. The mean KPS improved from 70 at the 1st SRS to 82 at the 2nd; the first follow-up mean KPS was 87 (P < 0.001). Symptomatic radiation injury developed and required conservative treatment in 3 patients (5%).Conclusions: Long-term follow-up showed that two-session Gamma Knife SRS achieved durable tumor control rates as well as acceptable treatment-related morbidity. This treatment method may potentially merit being offered to patients with large BM who are in poor condition or are otherwise ineligible for standard care. © 2014 Yomo and Hayashi; licensee BioMed Central Ltd.

Yomo S.,Saitama Gamma Knife Center | Hayashi M.,Tokyo Womens Medical University
Brain and Nerve | Year: 2011

Cavernous malformations (CMs) consist of dilated vascular channels that have a characteristic appearance on MRI. They can present with seizures, neurological deficits due to lesion hemorrhage, or as incidental findings on neuroradiological studies. Treatment options include conservative therapy; medical management of seizures; surgical intervention; and in selected cases, stereotactic radiosurgery. The role of radiosurgery in the treatment of CMs remains controversial, in part, because of the absence of neuroimaging criteria to gauge their successful obliteration as well as its higher complication rates. Radiosurgery is recommended only for symptomatic lesions that are surgically inaccessible or located in eloquent brain. We reviewed previously published papers on CMs with respect to hemorrhage rates, seizure control, and radiation-induced morbidity in order to better understand the balance of benefits and risks associated with the radiosurgical treatment for CMs. The data in this review provides convincing evidence that stereotactic radiosurgery is a relatively safe procedure with acceptable risks of morbidity and that its use could reduce the rebleeding rate and the frequency of seizures caused by for CMs located in the high-surgical-risk regions of the brain. We also present our experience of treating for 16 patients with CMs and show that our results were comparable to those previously reported.

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