PROGRAMME Day 1. Friday 26 th October Session (presentation summaries attached) Speakers

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1 PROGRAMME Day 1 Friday 26 th October Session (presentation summaries attached) Speakers 09:00 09:15 Summer School 2018 Welcome Julia Green 09:15 10:15 Session 1 Introduction (1.0hrs) 1.1 What a Quantitative Biomarker is (and isn t) 1.2 Properties of Quantitative Biomarkers (Some of the basic mathematics and statistics) 1.3 Evaluation of the Clinical Utility of Quantitative Biomarkers 1.0 John Cormack 10:15 10:45 Break - Morning Tea 10:45 12:15 Session 2 Nuclear Medicine Biomarkers (1.5hrs) 2.1 Oncology Biomarkers 2.2 Neurological Biomarkers 2.3 Dynamic Imaging Biomarkers 12:15 13:15 Break - Lunch 13:15 14:45 Session 3 Biomarkers in MRI (1.5hrs) 3.1 Overview of Functional MRI and chemical shift imaging 3.2 MRI Biomarkers 14:45 15:15 Break - Afternoon Tea 15:15 16:15 Session 4 CT Biomarkers (1hr) 4.1 Overview 4.2 CT ventilation imaging: Is it ready for clinical implementation? 16:15 17:15 Session 5 Biomarkers in Radiation Oncology (1hr) 5.0 Radiation Dose, Therapeutic Ratio and Survival Parameters 2.1 Kevin Hickson 2.2 Leighton Barnden 2.3 Peter Collins 3.1 Donald McRobbie 3.2 Greg Brown 4.0 John Kipritidis 5.0 Wendy Phillips * Attendance at this Summer School will qualify for CPD points and, for registrars, should provide useful information addressing components of several TEAP modules.

2 PROGRAMME Day 2 Saturday 27 th October Session (presentation summaries attached) Speakers 9:00 10:30 Session 6 Quantitative biomarkers in Practice: Part 1 Radiology (1.5hrs) 6.1 Fluoroscopy/US/CT 6.2 MRI 10:30 11:00 Break - Morning Tea 11:00 12:30 Session 7 Quantitative Biomarkers in Practice: Part 2 Nuclear Medicine & Radiation Oncology (1.5hrs) 7.1 MIM in Nuclear Medicine 7.2 MIM in Radiation Oncology 12:30 13:30 Break - Lunch 13:30 15:00 Session 8 Modelling External Dose (1.5hrs) 8.1 Collapsed Cone 8.2 Monte Carlo Algorithms 8.3 CT dosimetry 6.1 Mark Schinnick (Cannon) 6.2 Vicky Sherwood (Siemens) 7.1 Jason Beirne(MIM/NL-Tec) 7.2 Kristie Harrison (GCC/NL- Tec) 8.1 Justin Shepherd 8.2 Jessica Lye 8.3 Zoe Brady 15:00-15:30 Break Afternoon Tea 15:30 16:30 Session 9: Discussion and Assignment (30 min) Facilitator: Julia Green Discussion : Available speakers 16:30 17:30 Session 10 - Modelling Internal Dose (1.5hrs) 10.0 George Sgouros 17:30 17:45 Summer School 2018 Close Julia Green * Attendance at this Summer School will qualify for CPD points and, for registrars, should provide useful information addressing components of several TEAP modules.

3 Summary of Presentations Session 1: Quantitative Biomarkers - Introduction 1.1 Definitions and overview of the general concepts with some examples. 1.2 Overview of the relevant mathematics and parameters: - Accuracy, precision, reproducibility and error propagation. - Sensitivity, specificity, prevalence, positive and negative predictive values. - Normal ranges and decision thresholds. 1.3 Evaluation of the utility of quantitative biomarkers in patient management and treatment: - Survival. - Progression free survival. - Quality Adjusted Life Years( QALYs). - Risk/benefit ratios. - Cost/benefit ratios. Session 2: Nuclear Medicine Biomarkers 2.1 Oncology Biomarkers in Nuclear Medicine This presentation will briefly explain the mechanisms of uptake for FDG into normal tissues and tumours. Will briefly describe the proportionality between the metabolic rate of glucose and SUV and will conclude by introducing different radiopharmaceuticals used for oncology imaging and therapy. 2.2 Neurological Biomarkers - Voxel-based analysis in brain imaging: Principles and Practice. - Introduction to the methodology - spatial normalization, global signal normalization and statistics. - SPM in Nuclear Medicine. - Alternative packages. 2.3 Dynamic Imaging Biomarkers Nuclear Medicine is a medical imaging discipline that provides quantitative information (biomarkers) that can be used to diagnose disease and monitor progression. Dynamic studies, that produce a temporal sequence of images of the distribution of the radiopharmaceutical within the body are particularly suited to quantification. This presentation will outline studies that assess the function of several critical organ/systems including cardiac, renal, gastro-intestinal and lung. It will also discuss the importance of auditing clinical software. Session 3: Biomarkers in MRI 3.1 Numbers on the brain quantitative MR neuro-imaging. Recently neo-quantitative biomarkers have revolutionised neuro-imaging in the clinical and research arenas. BOLD fmri uses T2* mediated signal intensity changes resulting from micro-oxygenation levels to infer information about brain activation and networks. Diffusion tractography computes the eigenvectors of white matter tracts, whilst voxel-based morphometry

4 estimated regional grey and white matter volumes and atrophy. Perfusion imaging measures cerebral blood flow, volume and transit time. The methodologies and applications of each technique will be presented. 3.2 Liver Iron quantification, and Liver fat quantification methods. MR based liver iron concentration assessments have evolved from observational to quantitative methods to serve niche patient groups. The presentation will describe R2 and R2* based relaxometry methods used in different clinical and funding settings. Non-alcoholic fatty liver disease(nafld) is currently becoming prevalent, and considered a precursor to primary liver cancer. The implementation of MR methods that measure liver fat fraction (Dixon, spectroscopy, and relaxometry) will be described. Session 4: CT Biomarkers 4.1 Overview - CT number to density in CT - Volume measurements. - Calcification measurements in CT. - Dynamic CT (4D CT) parameters. 4.2 CT as a biomarker for ventilation imaging CT ventilation imaging (CTVI) is an experimental functional lung imaging technique that combines four-dimensional computed tomography with deformable image registration, and may hold the key to establishing functionally-adaptive lung cancer RT as standard of care. This talk will explain the rationale for using CTVI in radiotherapy departments, explain its successes and pitfalls following 10+ years of clinical validation, and above all emphasise the continued need for Physics expertise and patient specific QA. Session 5: Biomarkers in Radiation Oncology This session will focus on biological indicators from tumour and normal tissues of interest in Radiation Oncology. These involve biomarkers producing data to aid in the individualisation of RT planning, i.e. biomarkers reported to hold correlations to treatment outcome end-points such as tumour differentiation status and levels of gene mutation, or else those involving samples which are exposed and analysed for more direct RT response or tolerability related end-points. Potential benefits for combined-modality RT planning will also be mentioned. Imaging biomarkers play a role in this field, such as those utilised for tumour oxygenation assessment and therefore hypoxia-induced radioresistance, as well as those used to increase the accuracy of RT target and boost volume definitions. Biomarkers will be broken down into categories including the types of biomarkers (genetic, protein, cellular, metabolic or microenvironmental) and corresponding analysis processes, the direct data and corresponding predictive data inferred, the aims/uses for the data, the cancer type for which they are most commonly applied, the method and invasiveness of sampling processes, and the current status of research or clinical trial application. Biomarker data suitable for input into computational models will also be discussed, such as high-level clinical Decision Support Systems (DSS) or first principals-based Monte Carlo individual cell models of RT response. Finally, some of the challenges and future outlook of this field will be summarised. Session 6: Quantitative biomarkers in practice Part Practical demonstrations of quantitative biomarker applications in diagnostic radiology by Cannon 6.2 Practical demonstrations of quantitative biomarker applications in MRI by Siemens Session 7: Quantitative biomarkers in practice Part Practical demonstrations of quantitative biomarker applications in Nuclear Medicine using MIM software covering the following: An an overview of MIM Encore with a live demonstration of the software. MIM Encore provides vendor-neutral, single platform solutions for PET and Nuclear Medicine applications. This software includes tools for image review, fusion, and treatment monitoring for use in multiple modalities (PET, SPECT, CT and MRI). MIM Software Inc. continues to develop solutions in cardiac imaging, neuroimaging, radiology and nuclear medicine.

5 7.2 Practical demonstrations of quantitative biomarker applications in Radiation Oncology using MIM covering the following: An overview of MIM with a live demonstration of the software, including: - Image Registration and QA - Image Segmentation In addition, the use of biomarkers in Radiation Oncology processes following image segmentation will be covered: - Plan optimisation and evaluation - Delivery and Verification Session 8: Modelling External Dose 8.1 Collapsed Cone Convolution/superposition is the most commonly employed algorithm for dose calculation in radiation oncology and has been in use for around two decades. This lecture will outline the physics behind the algorithm and focus on specific implementations in currently available treatment planning systems. We will cover the different methods employed to increase accuracy and decrease calculation time and compare and contrast with other algorithms.e.g. pencil beam convolution, Monte Carlo, LBE solvers. 8.2 Monte Carlo Algorithms In Australia a few years ago the majority of Treatment Planning Systems photon dose calculations were performed using expanded pencil beam or superposition convolution type algorithms. More recently there has been an increase in using Monte Carlo based algorithms and Grid based Boltzmann solvers. These algorithms offer increased accuracy of dose calculation in heterogeneous medium but can take longer to calculate and they inherently calculate dose to medium rather than dose to water. 8.3 CT dosimetry The Ins and Outs of CT Dosimetry If you ask 5 physicists for a CT dose estimate, you will most likely get 5 different answers. There are many ways to estimate dose for CT and this talk will go through some of the options from physical measurements (the art of thermoluminescent dosimetry for low doses) through to some of the different software packages (eg ImPACT, CTExpo and NCICT). Size specific dose estimates and some fetal dosimetry will also be covered. Session 9: Discussion - Open discussion and questions from the floor - Summary of sessions - final assessment of assignments undertaken during Summer School Session 10: Modelling Internal Dose The Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine and Molecular Imaging was formed in 1965 to provide medical and scientific communities with the most accurate estimate of the dose that a patient receives from radiopharmaceuticals administered for diagnostic studies. The S-value based formalism and efforts to extend the committee s mission to dosimetry for radiopharmaceutical therapy, including alpha-emitter therapy will be highlighted in the presentation.

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