Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.

The personalization of neuropathic pain treatment could be improved by identifying specific sensory phenotypes (ie, specific combinations of symptoms and signs) predictive of the response to different classes of drugs. A simple and reliable phenotyping method is required for such a strategy. We investigated the utility of an algorithm for stratifying patients into clusters corresponding to specific combinations of neuropathic symptoms assessed with the Neuropathic Pain Symptom Inventory (NPSI). Consistent with previous results, we first confirmed, in a cohort of 628 patients, the existence of a structure consisting of 3 clusters of patients characterized by higher NPSI scores for: pinpointed pain (cluster 1), evoked pain (cluster 2), or deep pain (cluster 3). From these analyses, we derived a specific algorithm for assigning each patient to one of these 3 clusters. We then assessed the clinical relevance of this algorithm for predicting treatment response, through post hoc analyses of 2 previous controlled trials of the effects of subcutaneous injections of botulinum toxin A. Each of the 97 patients with neuropathic pain included in these studies was individually allocated to one cluster, by applying the algorithm to their baseline NPSI responses. We found significant effects of botulinum toxin A relative to placebo in clusters 2 and 3, but not in cluster 1, suggesting that this approach was, indeed, relevant. Finally, we developed and performed a preliminary validation of a web-based version of the NPSI and algorithm for the stratification of patients in both research and daily practice.

BackgroundTemporal and local fluctuations in O2 in tumors require adaptive mechanisms to support cancer cell survival and proliferation. The transcriptome associated with cycling hypoxia (CycHyp) could thus represent a prognostic biomarker of cancer progression.MethodsWe exposed 20 tumor cell lines to repeated periods of hypoxia/reoxygenation to determine a transcriptomic CycHyp signature and used clinical data sets from 2,150 breast cancer patients to estimate a prognostic Cox proportional hazard model to assess its prognostic performance.ResultsThe CycHyp prognostic potential was validated in patients independently of the receptor status of the tumors. The discriminating capacity of the CycHyp signature was further increased in the ER+ HER2- patient populations including those with a node negative status under treatment (HR=3.16) or not (HR=5.54). The CycHyp prognostic signature outperformed a signature derived from continuous hypoxia and major prognostic metagenes (P<0.001). The CycHyp signature could also identify ER+HER2 node-negative breast cancer patients at high risk based on clinicopathologic criteria but who could have been spared from chemotherapy and inversely those patients classified at low risk based but who presented a negative outcome.ConclusionsThe CycHyp signature is prognostic of breast cancer and offers a unique decision making tool to complement anatomopathologic evaluation.

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