Tokuhashi score and other prognostic factors in 260 patients with surgery for vertebral metastases.

BACKGROUND: Metastatic disease of the spine is an increasingly common public health problem. Surgery should be an integral component of the overall cancer treatment plan and, importantly, must neither delay not jeopardize any of the other components. The prognosis governs the choice of the surgical strategy. Tokuhashi et al. developed a prognostic score in 1990, then revised it in 2000 and 2005. Here, our objective was to evaluate the performance of the Tokuhashi score in a cohort of 260 patients and to look for other variables that might improve preoperative outcome prediction. MATERIAL AND METHOD: We retrospectively established a single-centre cohort of 260 patients who underwent spinal metastasis surgery between 1998 and 2008. For each patient, the following data were collected prospectively: socio-demographic features, history of the malignancy, variables needed to determine the Tokuhashi score, and treatments used. SAS 9.0 software was chosen for the statistical analysis. Variables were described as mean ± SD, overall survival was estimated using the Kaplan-Meier method, and survivals in subgroups were compared by the log-rank test. To assess agreement between survival predicted by the Tokuhashi score and observed survival, we computed Cohen's kappa and interpreted the results according to Landis and Koch. RESULTS: There were 143 females and 117 males with a mean age of 59 years and overall median survival of 10 months. Median observed survivals in the three Tokuhashi score categories (< 6, 6-12, and > 12 months predicted survival) were 5, 10, and 36 months, respectively. These survival times differed significantly (P < 0.0001). Cohen's kappa indicated moderate agreement between predicted and observed survivals. Other factors associated with significant survival differences were time from cancer diagnosis to metastasis diagnosis (synchronous, < 2 years, 2-5 years, or > 5 years; P < 0.0001) and age (< 70 years or ≥ 70 years, P = 0.0053). CONCLUSION: Our cohort study supports the validity and reproducibility of the Tokuhashi score. Our finding that shorter time to metastasis diagnosis and age ≥ 70 years were also significantly associated with survival in our population invites further efforts to improve and update the Tokuhashi score.

CD95 engagement mediates actin-independent and -dependent apoptotic signals.

CD95 is a death receptor whose stimulation by either the physiologic ligand CD95L or the agonistic antibodies leads to the formation of a multi-molecular complex termed DISC (death-inducing signaling complex) and the subsequent induction of a caspase-driven apoptotic signal. According to the magnitude of the DISC formation, two types of cells have been identified. Although type I cells generate an important DISC, the complex is barely found in type II cells. Analyzing the early stages preceding the DISC formation, we found that unlike CD95L, the commonly used agonistic antibody APO1-3 internalized the death receptor. Using inhibitors of actin polymerization, we showed that the remodeling of the actin cytoskeleton did not alter the capping of the CD95 receptor or its partitioning into the lipid rafts. In addition, whereas the disruption of F-actin prevented the internalization of CD95, the DISC formation and the apoptotic signal induced by the agonistic antibody APO1-3 in type I cells, it did not affect the signal triggered by the soluble and membrane-bound CD95L, regardless of the type of cells. In conclusion, the addition of APO1-3 on type I cells triggers an actin-dependent apoptotic signal, which is absent or marginal in cells (both types I and II) treated with CD95L.

[Ductal carcinoma in situ: role of the boost]. / Radiothérapie des carcinomes canalaires in situ: impact du complément d'irradiation du lit tumoral.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Nonadherent cells switch to a Rac-mediated, SHIP regulated, Akt activation mode for survival.

Constitutively active Rac stimulates Akt activity in T lymphocytes cultured in suspension. This regulation contrasts with findings obtained in fibroblasts, endothelial or neuronal cells grown on substrate, where Akt stimulation occurs independently of Rac. We now show that V12Rac-mediated stimulation of Akt is not restricted to the hematopoietic lineage but is dependent on the adherence status of the cell. V12Rac-mediated stimulation of Akt as well as molecular association between Rac and Akt occurred exclusively in cells kept in suspension. Stimulation and complex formation are dependent on SHIP but in a manner that differs from its role in dephosphorylation of phosphoinositide lipids. Adherent cells lacking SHIP, but not those lacking PTEN, are able to activate Akt through the Rac pathway. Our data reveal the existence of a bona fide Rac to Akt signaling pathway, tightly regulated by SHIP and operational in suspended cells only. This pathway may point to an alternative survival signal that is called into action when cells lose contact with the substrate and/or with other cells.

[Accelerated partial breast irradiation: a concept to individualize treatment in breast cancer]. / Irradiation partielle et accélérée du sein: un concept pour une individualisation thérapeutique dans le cancer du sein.

Whole breast irradiation delivering an equivalent dose of 50 Gy in 5 weeks, followed by a 10 to 16 Gy-boost to the tumor bed is the standard of care after breast-conserving surgery for early-breast cancer. Accelerated partial breast irradiation (APBI) is currently under investigations in large multi-institutional, prospective, randomized trials to objectively address the critical endpoints of treatment efficacy, toxicity and cosmesis. Patient's selection for this new approach is crucial to individualise treatments and define the subgroups of patients who will really benefit from APBI in terms of quality of life without decreasing long-term results of the disease control and cosmesis. In this review, we will discuss the patients' profiles selection for APBI regarding their general and tumor criteria. The differences between APBI techniques either performed intra or post operatively will be also discussed.