Clinical and Experimental Radiobiology Course 2025 - Learner Website

L1: Importance of Radiobiology in the Clinic – Dr. Scott Bratman

1. Recognize the role of single dose and fractionated radiotherapy in cancer treatment.
2. Identify the 5 R’s of radiotherapy: radiosensitivity, repopulation, re-oxygenation, repair, redistribution.
3. Understand the basic concepts relating to acute and late radiotherapy toxicity.

L2: Hallmarks of Cancer – Dr. Marianne Koritzinsky

1. Define “driver” and “passenger” mutations in cancer.
2. Estimate the number of “driver” and “passenger” mutations in a tumor.
3. Identify processes commonly altered in cancer by genetic alterations.
4. Understand how genetic alterations in cancer may influence tumor radiation response.

L3: Molecular Basis of Cell Death – Dr. Marianne Koritzinsky

1. Identify the main cell pathways of cell death that lead to loss of clonogenic survival in tumor cells.
2. Describe the relative importance of different forms of cell death caused by ionizing radiation.
3. Distinguish between early cell death and mitotically linked cell death.

L4: Radiation Induced Damage & DNA Damage Response – Dr. Shane Harding

1. Understand how DNA damage is sensed.
2. Describe how a DNA damage signal is transduced to DNA repair, cell cycle checkpoint and apoptosis machinery.
3. Identify the major pathways involved in the repair in DNA DSBs and their importance for radiosensitivity.

L5: Cell Survival and Tumor Growth – Dr. Deepak Dinakaran

1. Describe the concept of clonogenic survival to assess radiation response.
2. Identify in-vivo models to assess clonogenic survival
3. Understand cell and tumor microenvironment factors that contribute to radioresistance

L6: Quantifying Cell Kill and Cell Survival – Dr. Marianne Koritzinsky

1. Describe the clonogenic survival assay.
2. Describe the stochastic nature of cell kill by radiation.
3. Provide the formula for the linear-quadratic equation for cell survival and explain the parameters.
4. Describe parameters used to compare radiation responses in vitro.
5. Describe a few limitations of the LQ model.

L7: RBE and LET – Dr. Patricia Lindsay

1. Clinical application of high LET radiation treatment.
2. Describe how energy deposition varies with charge and velocity.
3. Illustrate the concept of a Bragg peak.
4. Define LET and RBE.
5. Explain how LET affects the shape of the cell survival curve and effect of fractionation.

L8: Particles in Radiotherapy – Dr. Patricia Lindsay

1. Understand the physical benefits of dose deposition with particle therapy.
2. Understand the biological basis for high LET particle therapy.
3. Understand the benefits and challenges of particle therapy.
4. Illustrate examples of the clinical use of particle therapy.

L9: The Linear-Quadratic Approach to Fractionation – Dr. Tim Craig

1. To understand the importance of fractionation in radiation therapy.
2. To understand the use of a/b to describe the sensitivity of tissue to changes in fractionation.
3. To understand how to use the linear-quadratic model to estimate the biological effect of a fractionation change.

L10: Dose-Response Relationships - Therapeutic Ratio – Dr. Andrew Hope

1. Identify the clinical significance of radiation dose response curves.
2. Explain how steepness and position of the dose response curve may be quantified.
3. Identify the most commonly used normal tissue complication probability models.

W1-1: Workshop 1: The LQ Model (Part 1) – Dr. Tim Craig

1. To be able to compute EQD2 to compare radiation fractionation schemes.

L11: Pathogenesis of Normal Tissue Side Effects – Dr. Jennifer Kwan

1. Understand the pathophysiology of normal tissue response to ionizing radiation.
2. Apply general radiobiologic principles to the clinical practice of radiation oncology.

L12: The Volume Effect for Normal Tissues – Dr. Jennifer Kwan

1. Distinguish the difference between structural and functional tissue tolerance.
2. Describe the concept of serial and parallel tissue organization.
3. Understand the importance of cell migration from the edge of irradiated fields and their contribution to the tolerance of specific tissues.

L13: Modified Fractionation Schedule (and Limits) – Dr. Scott Bratman

1. Define hyperfractionation, accelerated fractionation, hypofractionation and oligofractionation.
2. Identify the balance between tumor control and early and late toxicity when changing dose-time-fractionation.
3. Explain the current interest in hypofractionation schedules in several tumor types.

L14: Dose Rate Effect – Dr. Hedi Mohseni

1. Understand the concept of dose-rate effect.
2. Understand the mechanism of dose-rate effect and its key components.
3. Identify clinical significance of dose-rate in conventional radiotherapy.
4. Understand the potential for ultrahigh dose-rate

L15: Clinical Radiobiology of Brachytherapy – Dr. Amandeep Taggar

1. Understand how classic radiobiologic principles apply to
   brachytherapy.
2. Understand radiobiological differences of brachytherapy and fractionated external beam.
3. Compare the effects of different brachytherapy treatments from clinical examples.

W1-2: Workshop 1: The LQ Model (Part 2) – Marianne Koritzinsky

1. Recap some key concepts re: α/β, fractionation and EQD2.
2. Practice calculations.

L16: Retreatment Tolerance of Normal Tissues – Dr. Hanbo Chen

1. Understand the response of normal tissues to re-irradiation.
2. Use concepts of radiobiology to identify low risk vs. high risk scenarios for re-irradiation.
3. Be able to suggest strategies to mitigate risks if re-irradiation is to occur.

L17: Tumor Microenvironment and the Oxygen Effect – Dr. Bradly Wouters

1. Understand how oxygen levels influence radiation response.
2. Describe why oxygen availability influences clonogenic radiation survival.
3. Identify the main causes of hypoxia in tumors.
4. Describe the spatial and temporal heterogeneities of oxygenation.
5. Explain why fractionating radiotherapy is beneficial from the perspective of tumor oxygenation.
6. Understand how oxygen levels are important in other key aspects of tumor biology and patient outcome.

L18: Stereotactic and High Dose Radiotherapy – Dr. David Shultz

1. To understand practical applications of radiobiology in the clinic pertaining to SBRT for spine tumors.
2. To obtain a general udnerstanding of the indications for spine SBRT and how it is administered.

L19: Clinical Approaches to Target Hypoxia – Dr. Kathy Han

1. Identify ways of measuring hypoxia in human tumors.
2. Describe the relationship between hypoxia in human tumors and clinical outcome following conventional cancer treatments, including surgery, radiotherapy and chemotherapy.
3. Understand ways of targeting hypoxia in human tumors and opportunities for future research and clinical development.

L20: Biological Response Modifiers – Dr. Marianne Koritzinsky

1. Identify different classes of biological response modifiers and how they work.
2. Describe rationales to obtain a therapeutic index using biological response modifiers in cancer and radiotherapy.
3. Discuss challenges and opportunities for implementation of radiotherapy with targeted drugs.

L21: Radiation-Induced Malignancies – Dr. David Hodgson

1. Explain the relationship between radiation dose to normal tissue and second cancer risk.
2. Understand the patient factors that affect second cancer risk after radiation therapy.
3. Describe factors that contribute to the uncertainty of estimating second cancer risk associated with modern radiation therapy techniques.

L22: Predictive Biomarkers – Dr. Scott Bratman

1. Describe the concept of personalized radiation medicine based on biomarkers.
2. Distinguish between prediction versus prognostic biomarkers.
3. Understand examples of molecular and imaging biomarkers used in radiation oncology.

L23: Combined Radiotherapy and Immunotherapy – Dr. Shane Harding

1. Recognize the connections between RT-induced cellular responses and inflammatory signaling.
2. Appreciate how this signalling alters TME.
3. Gain insight to how these signals might manifest and be harnessed in the clinic.

L24: Combined Radiotherapy and Chemotherapy – Dr. Andrew Hope

1. Explain the rationale and application of combined radio- and chemotherapy in clinical practice.
2. Learn the mechanisms of action for various chemotherapeutics with radiotherapy.
3. Assess the impact of scheduling and dose of chemotherapeutics on efficacy and toxicity.

W3: Workshop 3: Practical Application of Radiobiology (Clinical) – Drs. Marianne Koritzinsky, Hanbo Chen and Irene Karam

1. Apply the LQ model in evaluating reirradiation schedules.
2. Review tolerances doses to organs-at-risk in cases of reirradiation.
3. Highlight clinical example(s) of reirradiation and the quantitative and qualitative application of radiobiological principles.

W3: Workshop 3: Practical Application of Radiobiology (Physics) – Drs. Edward Taylor and Monica Serban

Part I: Use of TCP and NTCP models in the clinic

1. Briefly review TCP and NTCP models.
2. Discuss AAPM Task Group report No. 166: The Use and QA of Biologically Related Models for Treatment Planning.
3. Discuss some benefits and challenges with using TCP and NTCP models as a part of treatment planning (i.e., optimization) and evaluation.
4. Highlight the use of NTCP models for liver SBRT treatment planning (RTOG trial)

Part II: Reirradiation

1. Discuss the application and limitations of the LQ model in evaluating reirradiation.
2. Review calculations of tolerances doses to organs-at-risk in cases of reirradiation.
3. Highlight clinical example(s) of reirradiation and the quantitative and qualitative application of radiobiological principles.