Fuller, C. D. | bioRxiv Science

bioRxiv2017

Imaging-Genomics Study Of Head-Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes And Genomic Mechanisms Via Integration Of TCGA And TCIA

PurposeRecent data suggest that imaging radiomics features for a tumor could predict important genomic biomarkers. Understanding the relationship between radiomic and genomic features is important for basic cancer research and future patient care. For Head and Neck Squamous Cell Carcinoma (HNSCC), we perform a comprehensive study to discover the imaging-genomics associations and explore the potential of predicting tumor genomic alternations using radiomic features.\n\nMethodsOur retrospective study integrates whole-genome multi-omics data from The Cancer Genome Atlas (TCGA) with matched computed tomography imaging data from The Cancer Imaging Archive (TCIA) for the same set of 126 HNSCC patients. Linear regression analysis and gene set enrichment analysis are used to identify statistically significant associations between radiomic imaging features and genomic features. Random forest classifier is used to predict two key HNSCC molecular biomarkers, the status of human papilloma virus (HPV) and disruptive TP53 mutation, based on radiomic features.\n\nResultsWide-spread and statistically significant associations are discovered between genomic features (including miRNA expressions, protein expressions, somatic mutations, and transcriptional activities, copy number variations, and promoter region DNA methylation changes of pathways) and radiomic features characterizing the size, shape, and texture of tumor. Prediction of HPV and TP53 mutation status using radiomic features achieves an area under the receiver operating characteristics curve (AUC) of 0.71 and 0.641, respectively.\n\nConclusionOur analysis suggests that radiomic features are associated with genomic characteristics in HNSCC and provides justification for continued development of radiomics as biomarkers for relevant genomic alterations in HNSCC.

cancer biology↗

bioRxiv2017

Temporally-Feathered Intensity Modulated Radiation Therapy: A technique to reduce normal tissue toxicity

PurposeIntensity modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients quality of life and often a dose-limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery. We term this novel treatment planning strategy \"temporally feathered radiotherapy\" (TFRT).\n\nMethodsTFRT plans were generated as a composite of five simulated treatment plans each with altered constraints on particular hypothetical organs at risk (OARs) to be delivered sequentially. For each of these TFRT plans, OARs chosen for feathering receive higher doses while the remaining OARs receive lower doses than the standard fractional dose delivered in a conventional fractionated IMRT plan. Each TFRT plan is delivered a specific weekday, which in effect leads to a higher dose once weekly followed by four lower fractional doses to each temporally feathered OAR. We compared normal tissue toxicity between TFRT and conventional fractionated IMRT plans by using a dynamical mathematical model to describe radiation-induced tissue damage and repair over time.\n\nResultsModel-based simulations of TFRT demonstrated potential for reduced normal tissue toxicity compared to conventionally planned IMRT. The sequencing of high and low fractional doses delivered to OARs by TFRT plans suggested increased normal tissue recovery, and hence less overall radiation-induced toxicity, despite higher total doses delivered to OARs compared to conventional fractionated IMRT plans. The magnitude of toxicity reduction by TFRT planning was found to depend on the corresponding standard fractional dose of IMRT and organ-specific recovery rate of sublethal radiation-induced damage.\n\nConclusionsTFRT is a novel technique for treatment planning and optimization of therapeutic radiotherapy that considers the non-linear aspects of tissue repair to optimize toxicity profiles. Model-based simulations of TFRT to carefully conceptualized clinical cases have demonstrated potential for normal tissue toxicity reduction in a previously described dynamical model of normal tissue complication probability (NTCP).

biophysics↗