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Yomo S.,Aizawa Comprehensive Cancer Center | Yomo S.,Saitama Gamma Knife Center | Hayashi M.,Saitama Gamma Knife Center
Journal of Neuro-Oncology | Year: 2015

It is not uncommon for brain metastasis (BM) treated with stereotactic radiosurgery (SRS) to demonstrate radiographic enlargement, with the patient developing neurological deficits attributable to a lesion at the site of SRS. The management of both local recurrence and radiation-induced necrosis (RN) poses a significant therapeutic dilemma, if surgical resection is not feasible, and effective therapies have yet to be established. This preliminary study introduces our initial experience with salvage SRS using adjuvant bevacizumab for this refractory entity. We retrospectively reviewed five patients who had received salvage SRS using adjuvant bevacizumab for recurrent BM complicated by RN. The diagnosis was based on clinical features, serial imaging studies and/or histopathological findings. Patients underwent salvage SRS followed by the first cycle of bevacizumab (7.5–10 mg/kg intravenous). Bevacizumab was repeated every 3–4 weeks until tumor progression or significant toxic events. The number of bevacizumab doses ranged from 2 to 16 (median 4). Follow-up MR imaging demonstrated a clear radiographic response in all lesions. Neurological symptoms improved in three patients and stabilized in two. In two patients, bevacizumab treatment was discontinued due to anemia and gastrointestinal bleeding, respectively. At the time of data analysis, four patients had died and the other was still alive. The causes of death were neurological decline and systemic disease progression in two patients each. Salvage SRS with adjuvant bevacizumab use appeared to provide an adequate radiographic response as well as neurological palliation for selected patients with heavily treated recurrent BM complicated by RN. © 2015 Springer Science+Business Media New York Source


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. Source


Yomo S.,Aizawa Comprehensive Cancer Center | Yomo S.,Saitama Gamma Knife Center | Hayashi M.,Saitama Gamma Knife Center
BMC Cancer | Year: 2015

Background: Because of the high likelihood of multiple brain metastases (BM) from small cell lung cancer (SCLC), the role of focal treatment using stereotactic radiosurgery (SRS) has yet to be determined. We aimed to evaluate the efficacy and limitations of upfront and salvage SRS for patients with BM from SCLC. Methods: This was a retrospective and observational study analyzing 70 consecutive patients with BM from SCLC who received SRS. The median age was 68 years, and the median Karnofsky performance status (KPS) was 90. Forty-six (66%) and 24 (34%) patients underwent SRS as the upfront and salvage treatment after prophylactic or therapeutic whole brain radiotherapy (WBRT), respectively. Overall survival (OS), neurological death-free survival, remote and local tumor recurrence rates were analyzed. Results: None of our patients were lost to follow-up and the median follow-up was 7.8 months. One-and 2-year OS rates were 43% and 15%, respectively. The median OS time was 7.8 months. One-and 2-year neurological death-free survival rates were 94% and 84%, respectively. In total, 219/292 tumors (75%) in 60 patients (86 %) with sufficient radiological follow-up data were evaluated. Six-and 12-month rates of remote BM relapse were 25% and 47%, respectively. Six-and 12-month rates of local control failure were 4% and 23%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 30, 8 and one patient, respectively. Symptomatic radiation injury, treated conservatively, developed in 3 patients. Conclusions: The present study suggested SRS to be a potentially effective and minimally invasive treatment option for BM from SCLC either alone or after failed WBRT. Although repeat salvage treatment was needed in nearly half of patients to achieve control of distant BM, such continuation of radiotherapeutic management might contribute to reducing the rate of neurological death. © 2015 Yomo and Hayashi; licensee BioMed Central. Source


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. Source


Sugie C.,Nagoya City University | Shibamoto Y.,Nagoya City University | Ayakawa S.,Red Cross | Mimura M.,Red Cross | And 4 more authors.
Technology in Cancer Research and Treatment | Year: 2011

The purpose of this study was to evaluate acute toxicity of craniospinal irradiation (CSI) using helical tomotherapy (HT) and compare its dose distribution with that of conventional linac-based plans. Twelve patients with various brain tumors were treated with HT-CSI. Median patient age was 14 years (range: 4-37 years). Median CSI dose was 30.6 Gy in 18 fractions (range: 23.4-40 Gy in 13-25 fractions). Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4.0. Before CSI, 11 patients (92%) received neoadjuvant chemotherapy, so acute toxicity was evaluated by comparing patient status before and after CSI. HT-CSI plans were compared with linac-based CSI plans made using Pinnacle3 planning system in 9 patients. All patients completed planned CSI without interruption. Grade 3 or higher toxicities were leukopenia seen in 11 patients (92%), anorexia in 6 (50%), anemia in 5 (42%), and thrombopenia in 5 (42%). Administration of granulocyte colony-stimulating factor, platelet transfusion and total parenteral nutrition were required in 8 (67%), 5 (42%) and 5 (42%) patients, respectively. HT plans were superior to linac-based plans in terms of homogeneity and conformality in planning target volume (PTV). For most organs at risk (OARs), volumes receiving more than 10 Gy (V10 Gy) or 20 Gy (V20 Gy) were lower in HT plans. However, HT plans significantly increased mean doses to the lung, kidneys and liver, and V5 Gy of 6 OARs including the lung. Despite intensive neoadjuvant chemotherapy, acute toxicity of HT-CSI was acceptable. HT provided better dose distribution in PTV than conventional linac. In most OARs, smaller volumes received >10-20 Gy in HT plans, although larger volumes received 5-10 Gy. ©Adenine Press (2011). Source

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