2460 Poster Board II-437 Replicating viruses that selectively lyse transformed cells are promising agents for cancer therapy. Attenuated measles virus (MV) has particular tropism for B cells and is oncolytic in murine models of myeloma and lymphoma. These results have led to phase 1 studies in myeloma. Here we investigated the anti-tumour potential of MV in adult B lineage acute lymphoblastic leukaemia (ALL) and Chronic lymphocytic leukaemia (CLL). GFP expressing attenuated MV derived from the Edmonston vaccine lineage (MV-Edm) was used to infect ALL (n = 6) or chronic lymphocytic leukaemia (CLL, n = 7) primary specimens. All CLL and ALL cells expressed the MV receptor CD46. The second MV receptor SLAM was consistently expressed in all the CLL cells but only in 5/6 of the ALL cells. Both ALL and CLL cells were efficiently infected by MV-Edm as indicated by quantitation of viral nucleocapsid mRNA by RQ-PCR and immunoblotting of viral proteins N,H and F. Large multinucleated syncytia, characteristic of MV- induced cytopathology, were found in all infected ALL cultures (Figure 1), by contrast syncitium formation was less prominent in the infected CLL specimens. Despite this, both CLL and ALL cells were efficiently killed by MV-Edm, as characterised by FACS and trypan blue based assays as well as immunoblotting for PARP cleavage. Specificity of lysis for tumor cells was confrmed by infection of normal mononuclear cell controls, which showed minimal syncitium formation and death even after prolonged infection. To investigate the contribution of cell-to-cell fusion in the pathogenesis of MV-induced oncolysis we investigated a relatively non-fusogenic MV:MV-Moraten in our models. Surprisingly, both CLL and ALL cultures infected with MV-Moraten demonstrated a reduction in cell viability compared to uninfected controls despite the absence of typical features of MV cytopathology. Our data suggest that both ALL and CLL are targets for MV-mediated lysis and that cell-cell- fusion might not be an important determinant of this effect in-vitro. Ongoing in vivo studies of MV oncolysis in B-cell malignancy should further inform the therapeutic potential of vaccine MV for these neoplasms. Figure 1 MV-Edm infection results in prominent syncytia formation in primary ALL cells (A and B). Figure 1. MV-Edm infection results in prominent syncytia formation in primary ALL cells (A and B). Disclosures: No relevant conflicts of interest to declare.
To assess a model to predict anatomical changes in head and neck cancer patients and explore the applicability of the model as a tool for adaptive replanning in intensity-modulated proton therapy (IMPT). Materials/Methods: 20 radiotherapy patients with nasopharyngeal cancer were included in this retrospective study. Each patient had a planning CT and weekly CTs during radiotherapy. To build the anatomical model, we deform the weekly CTs to planning CTs of our training population (n = 19) and obtain the average anatomical change per week. To predict a deformation for the remaining patient, the average deformation of the training population is applied to the patient's planning CT. The model is updated based on the patient's progression during treatment. K-fold cross validation (n = 5) was used to obtain a sample of 5 patients. For those 5 patients, we compare the accumulated dose of two adaptive IMPT strategies. 1) Predictive replan (PR): Replans were optimized on predicted images of weeks 3 and 5 and applied to week 3/4 and week 5/6 respectively. 2) Best-case replan (BcR): Adaptive replan on weekly CT is triggered when target coverage D95% criteria are not met and parotid gland mean dose deviation > 3 Gy (RBE). All plans (original plan, PR, BcR) were robustly optimized (+/-3 mm setup and +/-3.5% range uncertainty). Dosimetric goals: CTV D95(%) > 95% prescription dose in robust evaluation; maximum dose to spinal cord and brainstem < 45 Gy (RBE) and < 55 Gy (RBE), respectively. To ensure fairness of comparison, we kept dosimetric parameters between BcR and PR consistent. Results: Accumulated dose differences from two adaptive strategies (PR-BcR) of our 5 testing patients are shown (tab 1). We observe a maximum dose difference of 2.2% in the CTV D 95 , -1.35 Gy (RBE) in the brainstem D max , and -1.24 Gy (RBE) in the parotid D mean . The parentheses indicate the dose difference of the replans only (no accumulation). Conclusion: A predictive model was applied to the replanning process for adaptive proton therapy and compared to a best-case replan strategy. Our suggested PR produces clinically acceptable plans, comparable to the bestcase replan strategy, suggesting that the predictive models can be used for adaptive replanning. Application of predictive replanning provides the possibility to prepare adaptive plans in advance, streamlining the clinical workflow.Abstract 3173 − Table 1: Dose differences between predictive strategy and standard replan Accumulated dose difference PS-SR (replan dose difference) Id High-risk CTV Low-risk CTV Spinal cord Brainstem Parotid
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