Advanced Radiobiology related to Radiotherapy

Details

Title

Advanced Radiobiology related to Radiotherapy

Type

Stage Two

Module code

HPE124

Requirement

Compulsory

Module objective

By the end of this module the Clinical Scientist in HSST will apply their advanced expert knowledge of radiobiology to external beam radiotherapy and brachytherapy practice and provide advice on the therapeutic effects and toxicity of ionising radiation at the level of cells, organs and organisms, including possible genomic effects; the efficacy of different fractionation regimens in both external beam radiotherapy and brachytherapy; appropriate corrective action relating to scheduled and unscheduled gaps in fractionation of both external beam radiotherapy and brachytherapy and bio-effect planning and modelling. They will be expected to perform a range of technical, clinical and communication skills while critically evaluating their own response to both normal and complex situations using the professional attributes and insights required of a Consultant Clinical Scientist.

Knowledge and understanding

By the end of this module the Clinical Scientist in HSST will demonstrate critical application of their knowledge and understanding of advanced radiobiology to include:

Principles of tumour biology

• How to define and distinguish between different types of growth disorder, e.g. dysplasia and carcinoma in situ
• The cell cycle, basic cell kinetics and control mechanisms.
• The mechanisms of spread, local invasion/migration, metastasis.
• The effects of tumours: local (e.g. pressure), distant (metastatic and non- metastatic).
• The importance of tumour vasculature and and angiogenesis.
• The mechanisms of DNA damage and repair:
  • single-strand DNA breaks:
    • base excision repair (BER)
    • nucleotide excision repair (NER)
    • mismatch repair (MMR)
  • double-strand DNA breaks:
    • non-homologous end joining (NHEJ)
    • homologous recombination.
• The potential role of cancer stem cells.
• The mechanisms of cell death, e.g. apoptosis, autophagy.
• The molecular targets for anti-cancer therapy.

General principles of radiobiology

• The cellular systems (hierarchical, flexible) and their response to radiation.
• The difference between parallel and serial systems.
• The principles of cell survival curves, regrowth curves, clonogenic assay.
• The relevance of linear energy transfer (LET) to cellular damage.
• Radiation damage at the cellular level (including outcome phenotypes, chromosome damage and cell radiosensitivity).
• The molecular biology of radiation damage and repair.
• The differences between bystander and direct effects of radiation.
• Interactions between systemic anti-cancer therapies and radiotherapy.
• Secondary carcinogenic effects.
• Hypoxia.

Normal tissue radiobiology

• Normal tissue damage (early and late).
• Normal tissue tolerance.
• Equivalent uniform dose (EUD).
• Genetic factors and co-morbidities, including auto-immune factors, which influence tolerance.
• Effects of radiation on different tissues and organs, including unplanned whole body exposure.
• Organ tolerance to retreatment with radiation.

Radiotherapy fractionation

• Lethal, sub-lethal, potentially lethal damage.
• Early and late repair.
• Effect of cell cycle on radiation sensitivity.
• Repopulation.
• Role of the cell survival curve as a basis for fractionation.
• Linear quadratic model and alternative models.
• Cellular sensitivity (SF2, α, β, mean inactivation dose).
• α/β ratio and its relevance to tumours, acute and late-responding tissues.
• Calculation of biological effective dose (BED).
• Definition and use of equivalence dose 2Gy (EQD2).
• Fractionation and its influence on tumour control with different α/β ratio.
• Hyperfractionation, accelerated fractionation and hypofractionation.
• Influence of gaps in radiotherapy and their management.
• Influence of dose rate effects, including low, pulsed, medium and high dose rate.
• Relative biological effect (RBE) and discuss its relationship to LET.
• Influence of oxygen on radiosensitivity, including oxygen enhancement ratio (OER).
• Role of re-oxygenation.
• The relationship between OER and LET.
• Role of radiosensitisers and chemotherapy.

Technical and clinical skills

By the end of this module the Clinical Scientist in HSST will demonstrate critical understanding of current research and its application to the performance and mastery of a range of technical, communication and clinical skills and will:

• Provide expert advice on comparison of different fractionation regimens.
• Provide expert advice on the effect of treatment gaps and how to compensate.
• Provide expert advice on retreatment options.
• Communicate with the multidisciplinary team and participate as an active member of multidisciplinary teams.
• Reflect on the challenges of applying research to practice in relation to these areas of practice and suggest improvements, building on a critique of available evidence.

Attitudes and behaviours

By the end of this module the Clinical Scientist in HSST will consistently demonstrate the attitudes and behaviours necessary for the role of a Consultant Clinical Scientist and will:

• Promote the importance of improving patient outcomes through innovation in a safe and verifiable manner.
• Promote evidence-based medicine.
• Collaborate with multidisciplinary groups on local, national and international levels with the aim of improving clinical and scientific outcomes related to external beam radiotherapy and brachytherapy.