BackgroundMinimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed that MSC could induce OCC chemoresistance without contact using transwell setting. Further experiments showed that this induced chemoresistance was dependent on IL-6 OCC stimulation.MethodsWe combined meticulous in vitro profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC intereactions.ResultsWe demonstrated that Tocilizumab® (anti-IL-6R therapy) in association with chemotherapy significantly reduced the peritoneal carcinosis index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6 induced chemoresistance was dependent on PYK2 phosphorylation.ConclusionsThese findings highlight the potential key role of the stroma in protecting minimal residual disease from chemotherapy, thus favoring recurrences. Future clinical trials targeting stroma could use anti-IL-6 therapy in association with chemotherapy.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0787-z) contains supplementary material, which is available to authorized users.

Background/Aim: We evaluated patients undergoing salvage hysterectomy after brachytherapy (BT) following concomitant chemoradiation (CRT) for locally advanced cervical cancers (LACC), when residual disease was suspected. Patients and Methods: From 2004 to 2013, 29 patients had a radical hysterectomy at the Gustave Roussy for suspicion of clinical and/or radiological residual disease. Outcomes, morbidities and the accuracy of the evaluation of response to CRT and BT were evaluated. Results: The rate of complications grade>IIIa was 24%, with no difference between the 14 patients with histological residual disease and the 15 with a complete response. Magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) revealed a sensitivity of 92% and 100%, but a poor specificity of less than 40%. Three recurrences occurred in patients with residual disease (brain, rectosigmoid colon, peritoneum and lung). Conclusion: The clinical examination, MRI and PET-CT are suboptimal for diagnosing residual disease after CRT and BT.

Background Most recent trials evaluating extensive screening strategies for occult cancer in patients with unprovoked venous thromboembolism have failed, because, among other reasons, of an overall low rate of occult cancer. The RIETE investigators recently proposed a score aimed at identifying a subgroup at higher risk. Methods We retrospectively computed the RIETE score for all patients included in the MVTEP study, which evaluated the accuracy of [¹⁸F]fluorodeoxyglucose-positron emission tomography in the screening of occult cancer in patients with unprovoked venous thromboembolism. Performance of the RIETE score was assessed according to the proportion of patients classified in each risk group, and the corresponding rates of cancer diagnosis. Results Among the 386 patients included in the analysis, 136 patients (35.3%) were classified as high risk by the RIETE score. Cancer was diagnosed in 16 (11.8%) of them, whereas it was diagnosed in nine (3.6%) of the 250 patients with a low RIETE cancer score: odds ratio of 3.6 (95% confidence interval [CI] 1.53-8.32). The area under the receiver operating characteristic curve was 0.63 (95% CI 0.51-0.74). Conclusion The RIETE score seems to be able to identify a subgroup at high risk for cancer (10%) in our specific dataset of patients with unprovoked venous thromboembolism.

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