Personalization of therapy pertains to every type of therapy. For example, in radiation therapy, technological advances in recent years culminated in development of image-guided radiotherapy techniques that can deliver dose to the tumor reproducibly and with extremely high precision. In order to account for high biological heterogeneity of tumors (due to regional radiosensitivity differences), a new paradigm of biologically conformal radiotherapy has been proposed. Similarly, treatment response heterogeneity affects management of advanced metastatic cancers, where multiple lesions often show dramatically different responses – some responding and some not. Biological complexity does not only project in tumors, but also elsewhere, for example in brain, where different diseases (e.g., Parkinson’s disease) result in characteristic brain activity patterns that can be assessed with advanced molecular imaging methods and then explored for more efficient patient management.
The main Therapy efforts will be focused on addressing these key problems through investigations of:
- Personalized radiation therapy: Personalization of radiotherapy requires not only adjustment of the total dose prescribed, but also a shift from the current standard of uniform dose prescription to a non-uniform dose prescription, which will be tailored to the spatial distribution of biological properties in the tumor – the process most often termed “dose-painting”. The main goal of our research is to test feasibility of dose painting approach in head and neck, and lung tumors through both, biologically conformal targeting of tumors, as well as biologically conformal avoidance of normal tissues.
- Personalized therapy for advanced cancers: AR-directed therapies (e.g., Abiraterone, Enzalutamide) are a new treatment option for men with metastatic castrate resistant prostate cancer (mCRPC). While the majority of patients achieve a PSA decline during treatment (biomarker of treatment response), some patients do not respond due to intrinsic resistance to treatment. Eventually all patients progress due to developed acquired resistance. Using molecular imaging we observed non-responding lesions in patients with durable PSA decline, as well as some responding lesions in patients that did not have good PSA decline, indicating tremendous treatment response heterogeneity. The main goal of our work is to compare novel molecular imaging using 18F fluorocholine (FCH) PET/CT to conventional 18F-fluorodeoxyglucose (FDG) PET/CT to assess heterogeneity of response and guide clinical management of mCRPC.
- Biomarkers of neurodegenerative brain disorders: Neurodegenerative brain diseases express characteristics metabolic brain patterns, typically assessed with 1 8Ffluorodeoxygluocose (FDG) PET and dopamine transporter imaging. Analysis of these patterns, for example by Scaled Subprofile Model/Principal Component Analysis (SSM/PCA) in Parkinson’s and Alzheimer’s disease patients, can provide us a reliable biomarker of the disease progression. It could be detected already in the preclinical disease stages, which may last for decades. Detecting and understanding these earliest disease stages is crucial for the development of etiological treatments.