Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases

PURPOSE: Renal cell carcinoma (RCC) and melanoma have been considered ‘radioresistant’ due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases.MATERIALS AND METHODS: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors.RESULTS: We identified 53 radioresistant brain metastases (28% RCC and 72% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 ± 9.5 mL and 95.5% ± 2.9%, respectively. The mean prescription dose was 20 ± 4.9 Gy. Forty lesions (75%) demonstrated a complete/partial response and 13 lesions (24%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS.CONCLUSION: SRS is an effective management option with up to 75% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.

Metastatic papillary serous carcinoma of testis: A rare case

Papillary serous carcinomas of testis are very rare, and only case reports have been reported in the literature. These neoplasms are characterised histologically by papillary fronds and numerous psammoma bodies and exhibit immunoreactivity for markers of ovarian serous carcinomas. These are very aggressive and are both chemo and radioresistant with surgery remained the main stay of management.

Relationship between DNA damage repair and radioresistance in nasopharyngeal carcinoma CNE-2R cells / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the differential gene expression of nasopharyngeal carcinoma cell line CNE-2 and CNE-2R exposed to X-rays.Methods We used neutral comet assay to detect the intrinsic radiosensitiv-ity of tumor cells,immunofluorescence to detect the phosphorylated histone γH2AX and Rad5 1 foci formation and to assay the time-dose effects on cell radiation injury and radiation radiosensitivity change after irradiation.The dif-ferential gene expression was screened with cDNA microarray by DNA damage repair related gene chip.Differenti-ally expressed proteins screened were confirmed by Western blot.Results After 2 h of 4 Gy 9MeV-β-ray irradia-tion,CNE-2R cells had aggravated DNA damage compared to CNE-2 cells and the damage was more obvious with the prolongation of time.It suggested that cell DNA damage severity was more obvious.The immunofluorescence showed the positive rates ofγH2AX cells in CNE-2 cell line were higher than those in CNE-2R cell line.There were 37 different genes related to DNA damage repair in CNE-2 cell line compared with CNE-2R cell line,while 24 up-regulated and 13 down-regulated genes were found in SiHaR cells.In them,there were 6 genes whose ratios were 6 times higher and 3 genes whose ratios were lower than 0.1.Western blot verified the results of four differentially expressed proteins compared with CNE-2 cells,in which GADD45a and RRAD1 expression levels were significantly lowered in CNE-2R while the RAD9a and RCF2 protein significantly increased.Conclusion The radioresistance of CNE-2R cells is significantly related to DNA damage repair capacity in certain mutations at the gene level.It is possible to regulate cell radiosensitivity by regulating the related gene.

The Usefulness of Stereotactic Radiosurgery for Radioresistant Brain Metastases

OBJECTIVE: We investigated the effectiveness of stereotactic gamma knife Radiosurgery (GKR) for radioresistant brain metastases with the impact upon histology. METHODS: Between April 2004 and May 2011, a total of 23 patients underwent GKR for 67 metastatic brain tumors from 12 renal cell cancers, 5 sarcomas and 6 melanomas. The mean age was 56 years (range, 18 to 79 years). Most of the patients were classified as the Radiation Therapy Oncology Group recursive partitioning analysis class II (91.3%). The synchronous metastasis was found in 6 patients (26.1%) and metachronous metastasis in 17 patients (73.9%). We analyzed the local control rate, intracranial progression-free survival (PFS) and overall survival (OS). RESULTS: The mean tumor volume for GKR was 2.24 cc and the mean prescription dose was 19.4 Gy (range, 10 to 24) to the tumor margin. Out of metachronous metastases, the median duration to intracranial metastasis was 3.3 years in renal cell cancer (RCC), 2.4 years in melanoma and 1.1 years in sarcoma (p=0.012). The total local control rate was 89.6% during the mean 12.4 months follow-up. The six-month and one-year local control rate was 90.2% and 83% respectively. Depending on the pathology, the control rate of RCC was 95.7%, sarcoma 91.3% and melanoma 80.5% during the follow-up. The common cause of local failure was the tumor bleeding in melanoma. The median PFS and OS were 5.2 and 8.4 months in RCC patients, 6.5 and 9.8 months in sarcoma, and 3.8 and 5.1 months in melanoma. CONCLUSION: The GKR can be one of the effective management options for the intracranial metastatic tumors from the radioresistant tumors. The melanoma showed a poor local control rate compared to other pathologies because of the hemorrhage.

A New Ionizing-radiation Resistant Strain WGR702 Isolated,Identified, and Radioresistant Character / 微生物学通报

A new ionizing-radiation resistant strain WGR702 was isolated from arid soils which had been ra-diated. The strain WGR702 was Gram-positive and coccus, the diameter of the cell was 1.5 ?m～2.5?m.The strain WGR702 was pink-pigmented, motile, facultative anaerobe and non-spore forming. The range tem-perature and pH for strain WGR702 growth were 10℃～35℃ and pH 5.0～10.0 respectively. The strain WGR702 had a G+C content of 60.5 mol%. UV and gamma radiation survival curves showed the strain WGR702 had highly ionizing-radiation resistant. Phylogenetic analysis of the 16S rDNA gene sequences (EU315117) showed 94.79%～98.53% similarities with other recognized Serratia species. Primary charac-teristics that distinguish isolate WGR702 from the species of genus Serratia include the cells are spherical and Gram-positive. Based on the phenotypic, biochemical and physiological characteristics differences it is proposed that the new isolated strain WGR702 might be classified as a novel species of Serratia.