A deep learning model to generate synthetic CT for prostate MR-only radiotherapy dose planning: a multicenter study

IntroductionFor radiotherapy based solely on magnetic resonance imaging (MRI), generating synthetic computed tomography scans (sCT) from MRI is essential for dose calculation. The use of deep learning (DL) methods to generate sCT from MRI has shown encouraging results if the MRI images used for training the deep learning network and the MRI images for sCT generation come from the same MRI device. The objective of this study was to create and evaluate a generic DL model capable of generating sCTs from various MRI devices for prostate radiotherapyMaterials and methodsIn total, 90 patients from three centers (30 CT-MR prostate pairs/center) underwent treatment using volumetric modulated arc therapy for prostate cancer (PCa) (60 Gy in 20 fractions). T2 MRI images were acquired in addition to computed tomography (CT) images for treatment planning. The DL model was a 2D supervised conditional generative adversarial network (Pix2Pix). Patient images underwent preprocessing steps, including nonrigid registration. Seven different supervised models were trained, incorporating patients from one, two, or three centers. Each model was trained on 24 CT-MR prostate pairs. A generic model was trained using patients from all three centers. To compare sCT and CT, the mean absolute error in Hounsfield units was calculated for the entire pelvis, prostate, bladder, rectum, and bones. For dose analysis, mean dose differences of D99% for CTV, V95% for PTV, Dmax for rectum and bladder, and 3D gamma analysis (local, 1%/1 mm) were calculated from CT and sCT. Furthermore, Wilcoxon tests were performed to compare the image and dose results obtained with the generic model to those with the other trained models.ResultsConsidering the image results for the entire pelvis, when the data used for the test comes from the same center as the data used for training, the results were not significantly different from the generic model. Absolute dose differences were less than 1 Gy for the CTV D99% for every trained model and center. The gamma analysis results showed nonsignificant differences between the generic and monocentric models.ConclusionThe accuracy of sCT, in terms of image and dose, is equivalent to whether MRI images are generated using the generic model or the monocentric model. The generic model, using only eight MRI-CT pairs per center, offers robust sCT generation, facilitating PCa MRI-only radiotherapy for routine clinical use

'Off-the-shelf’ allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies

Background Epstein-Barr virus (EBV), an oncogenic human gammaherpesvirus, is associated with a wide range of human malignancies of epithelial and B-cell origin. Recent studies have demonstrated promising safety and clinical efficacy of allogeneic ‘off-the-shelf’ virus-specific T-cell therapies for post-transplant viral complications.Methods Taking a clue from these studies, we developed a highly efficient EBV-specific T-cell expansion process using a replication-deficient AdE1-LMPpoly vector that specifically targets EBV-encoded nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2), expressed in latency II malignancies.Results These allogeneic EBV-specific T cells efficiently recognized human leukocyte antigen (HLA)-matched EBNA1-expressing and/or LMP1 and LMP2-expressing malignant cells and demonstrated therapeutic potential in a number of in vivo models, including EBV lymphomas that emerged spontaneously in humanized mice following EBV infection. Interestingly, we were able to override resistance to T-cell therapy in vivo using a ‘restriction-switching’ approach, through sequential infusion of two different allogeneic T-cell therapies restricted through different HLA alleles. Furthermore, we have shown that inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis in combination with EBV-specific T-cell therapy significantly improved overall survival of tumor-bearing mice when compared with monotherapy.Conclusion These findings suggest that restriction switching by sequential infusion of allogeneic T-cell therapies that target EBV through distinct HLA alleles may improve clinical response

Computed tomography synthesis from magnetic resonance imaging using cycle Generative Adversarial Networks with multicenter learning

International audienceBackground and Purpose: Addressing the need for accurate dose calculation in MRI-only radiotherapy, the generation of synthetic Computed Tomography (sCT) from MRI has emerged. Deep learning (DL) techniques, have shown promising results in achieving high sCT accuracies. However, existing sCT synthesis methods are often center-specific, posing a challenge to their generalizability. To overcome this limitation, recent studies have proposed approaches, such as multicenter training . Material and methods: The purpose of this work was to propose a multicenter sCT synthesis by DL, using a 2D cycle-GAN on 128 prostate cancer patients, from four different centers. Four cases were compared: monocenter cases, monocenter training and test on another center, multicenter trainings and a test on a center not included in the training and multicenter trainings with an included center in the test. Trainings were performed using 20 patients. sCT accuracy evaluation was performed using Mean Absolute Error, Mean Error and Peak-Signal-to-Noise-Ratio. Dose accuracy was assessed with gamma index and Dose Volume Histogram comparison. Results: Qualitative, quantitative and dose results show that the accuracy of sCTs for monocenter trainings and multicenter trainings using a seen center in the test did not differ significantly. However, when the test involved an unseen center, the sCT quality was inferior. Conclusions: The aim of this work was to propose generalizable multicenter training for MR-to-CT synthesis. It was shown that only a few data from one center included in the training cohort allows sCT accuracy equivalent to a monocenter study