Search

Simple Summary Within a multicentric clinical trial context for the treatment of recurrent high-grade brain tumors, the aim of our study was to assess the potential added value of multiparametric MRI harmonization to improve a classification problem based on radiomics analysis. We confirmed that harmonization reduced the so-called “scanner effect” related to the variability of multiparametric MRI protocol settings between the participating centers and improved the predictive performance of radiomics-based classification model. Radiomics features extracted from MRI perfusion gave the best accuracy for the classification between radionecrosis and tumor progression. Interestingly, our study revealed that radiomics features extracted from T1-weigthed MRI alone, before any injection of contrast product reached accuracies close to the perfusion model. Abstract In this study, a radiomics analysis was conducted to provide insights into the differentiation of radionecrosis and tumor progression in multiparametric MRI in the context of a multicentric clinical trial. First, the sensitivity of radiomic features to the unwanted variability caused by different protocol settings was assessed for each modality. Then, the ability of image normalization and ComBat-based harmonization to reduce the scanner-related variability was evaluated. Finally, the performances of several radiomic models dedicated to the classification of MRI examinations were measured. Our results showed that using radiomic models trained on harmonized data achieved better predictive performance for the investigated clinical outcome (balanced accuracy of 0.61 with the model based on raw data and 0.72 with ComBat harmonization). A comparison of several models based on information extracted from different MR modalities showed that the best classification accuracy was achieved with a model based on MR perfusion features in conjunction with clinical observation (balanced accuracy of 0.76 using LASSO feature selection and a Random Forest classifier). Although multimodality did not provide additional benefit in predictive power, the model based on T1-weighted MRI before injection provided an accuracy close to the performance achieved with perfusion.

Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSLCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor’s features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.

Objective To evaluate the effect of chemotherapy added to a surgical locoregional treatment (LRT) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Materials and Methods We studied the sub-group of trials with surgical LRT included in the meta-analysis on chemotherapy in head and neck cancer (MACH-NC). Data from published and unpublished randomized trials comparing the addition of chemotherapy to LRT in HNSCC patients were sought using electronic database searching for the period 1965–2000, hand searching and by contacting experts in the field. Trials with less than 60 patients, or preoperative radiotherapy or where the type of LRT could not be individually determined were excluded. All individual patient data were checked for internal consistency, compared with published reports, and validated with trialists. Data were pooled using a fixed-effect model. Heterogeneity was assessed using Cochrane test and I 2 statistic. Results Twenty-four trials were eligible (5000 patients). Chemotherapy improved overall survival (HR = 0.92 [95%CI: 0.85–0.99] p = 0.02). There was a significant interaction between treatment effect and timing of chemotherapy (p = 0.08 at pre-specified threshold of 0.10) with a greater effect for concomitant chemotherapy (HR = 0.79, 95%CI: 0.69–0.92). The benefit of chemotherapy was greater in women (HR women = 0.63, 95%CI: 0.50–0.80) compared to men (HR men = 0.96, 95%CI: 0.89–1.04; p for interaction = 0.001). Conclusions This analysis confirmed the benefit of concomitant chemotherapy added to surgical LRT. The role of induction therapy as yet to be determined as it did not improve OS. Women may benefit more than men from chemotherapy.