[First treatment for brain metastases by stereotactic radiosurgery]. / Traitement premier des métastases cérébrales par irradiation en conditions stéréotaxiques.

Local control of brain metastases is better with first treatment by stereotactic radiosurgery than with radiosurgery for recurrence. We reported a retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery realised in first intention. From January 1994 to December 1997, 26 patients presenting with 43 metastases underwent radiosurgery. The median age was 61 years and the median Karnofsky index 70. Primary sites included: lung (12 patients), kidney (7 patients), breast (2 patients), colon (1 patient), melanoma (2 patients), osteosarcoma (1 patient), it was unknown for one patient. Seven patients had extracranial metastases. Twenty-one sessions of radiosurgery have been realized for one metastase, and 9 for two, three or four lesions. The median diameter was 21 mm and the median volume 1.8 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. Forty-two metastases were evaluable for response analysis. The overall local control rate was 90.5% and the 1-year, 2- and 3-year actuarial rates were 85% and 75%. In univariate analysis, theorical radioresistance was significantly associated with better local control (100% versus 77%, p < 0.05). All patients were evaluable for survival. The median survival rate was 15 months. Four patients had a symptomatic oedema (RTOG grade II). Two lesions have required a surgical excision. In conclusion, low dose radiosurgery (14 Gy delivered at the periphery of metastasis) can be proposed in first intention for brain metastases, in particularly for theorical radioresistant lesions.

[Importance of radiotherapy in stereotactic conditions (radiosurgery) in brain metastasis: experience and results of the Hôpital Pitié-Salpêtrière Group]. / Intérêt de la radiothérapie en conditions stéréotaxiques (radiochirurgie) des métastases cérébrales: expérience et résultats du groupe hospitalier Pitié-Salpêtrière.

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.

CD4 cell eligibility thresholds: an analysis of the time to antiretroviral treatment in HIV-1 seroconverters.

BACKGROUND: WHO recommends initiating combination antiretroviral treatment at the minimal CD4 cell threshold of 350 cells/µl. In sub-Saharan Africa, the time for a recently infected patient to reach this threshold is unclear. METHOD: We estimated the probability of reaching different CD4 cell thresholds over time in the ANRS 1220 cohort of HIV-1 seroconverters in Côte d'Ivoire. CD4 cell slopes were estimated using a mixed linear model. Probabilities of crossing the 350 and 500 cells/µl CD4 cell thresholds were estimated by the Kaplan-Meier method. RESULTS: Between 1997 and 2009, 304 recent seroconverters have been enrolled in the Primo-CI cohort (62% men, median baseline age 29 years and median time since the estimated date of seroconversion 9 months). The probability of having a first CD4 cell count below 500 cells/µl was 0.57, 0.72, 0.79 and 0.84 at study entry, 2, 4 and 6 years, respectively. For a first CD4 cell count below 350 cells/µl, these figures were 0.29, 0.40, 0.55 and 0.67. The time for 75% of patients to reach the threshold was 3.0 years for 500 cells/µl and 7.0 years for 350 cells/µl.

Markers of chemoresistance in ovarian carcinomas: an immunohistochemical study of 86 cases.

Markers of chemoresistance have been rarely investigated in human ovarian cancer. This study evaluates the clinical value in ovarian cancer of metallothionein (MT), heat-shock protein-27 (HSP-27) and glutathione-S-transferase pi and alpha (GST pi, GST alpha), recognized for their relation with drug resistance in vitro. The expression of these markers was evaluated by immunohistochemistry on paraffin-embedded tumor specimens from 86 patients with ovarian carcinomas diagnosed between 1977 and 1990 who received chemotherapy. Response to chemotherapy was evaluated using well-defined criteria. Marker expression was evaluated on a section of the primary tumor (81 cases) and, when available, on a section of tumor following chemotherapy (48 cases). MT was expressed in 38.3% of primary tumors unexposed to chemotherapy, HSP-27 in 50.6%, GST pi in 37%, and GST alpha in 50.6%. The expression of all four markers did not help to predict chemoresistance. The concordance between marker expression by the tumor before and after chemotherapy was weak (concordance, 51.2%-70.7%). Immunostaining was not associated (p > 0.1) with any prognostic factor such as stage, residual tumor after surgery and grade. Ovarian cancer is a highly heterogeneous neoplasm and the expression of markers of chemoresistance reflects this heterogeneity. Our data suggest that chemoresistance is more likely multifactorial and confirms the complexity of the in vivo model.