C Orton¹*, C Borras²*, C Orton³*, K Parodi⁴*, J Jin⁵*, J Deasy⁶*, (1) Wayne State University, The Villages, FL, (2) Washington, DC, (3) Wayne State University, The Villages, FL, (4) Ludwig-Maximilians-Universitat Munchen, Garching B. Munich, (5) University Hospitals, Case Medical Center, Cleveland, OH, (6) Memorial Sloan Kettering Cancer Center, New York, NY

• 
  C Orton
• 
  C Borras
• 
  K Parodi
• 
  J Jin
• 
  J Deasy

SU-EF-TRACK 7-0 (Sunday, 7/25/2021) 3:30 PM - 5:30 PM [Eastern Time (GMT-4)]

The course will start with an introduction to radiation biology. The mechanisms involved in biological effects from ionizing radiation at the cellular and tissue levels and the radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Concepts such as Linear Energy Transfer (LET) and Relative Biological Effectiveness (RBE) will be defined. Epidemiological data on cancer induction and tissue injuries, including radiation effects on children and the developing embryo, will be described. Increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20-40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose for stochastic effects and the threshold doses for tissue injuries will be presented and their potential impact on radiotherapy treatments assessed.

Fractionation of radiotherapy treatments will be discussed. Topics presented will include: Why has radiotherapy been fractionated (repair of late-reacting normal tissue cells, the L-Q model and the narrow “Window of Opportunity”), and what is the effect of overall treatment time (repopulation of cancer cells and representation in the L-Q model)? Also presented will be the radiobiological basis of clinical trials of various fractionation schemes such as hyperfractionation, accelerated fractionation, accelerated hyperfractionation, and hypofractionation, and the reason for all the recent interest in hypofractionation (highly conformal radiotherapy widens the Window of Opportunity).

Proton and light ion beams are rapidly emerging external-beam radiotherapy modalities. These combine the advantages of ballistic selectivity with distinguished biological properties emerging from their elevated ionization density which, especially for heavier ions, can result in a selectively enhanced biological effectiveness in the tumor region. However, this introduces a new level of complexity to be properly accounted for in treatment planning. This presentation will review the basic radiobiological principles, quantities, and models for clinical application of protons and light ions, along with highlighting the still open questions, emerging new trends, and instrumentation requirements for addressing them.

The physics and biology of ultra-fast FLASH radiation will be discussed at two levels: the cell and body levels. At the cell level, a recombination theory during radiolysis will be discussed. FLASH radiation increases the recombination of intermediate products that leads to reduction of free radicals and hence reduces DNA damage. A simulation and an experimental study will be presented to support this theory. At the body level, FLASH radiation can “freeze” motion and blood flow. A simulation study demonstrated that FLASH radiation dramatically reduces the radiation killing of immune cells in blood, and thus potentially reduces radiation-induced lymphopenia, which may lead to improve tumor control and normal tissue sparing.

Outcome-related mathematical models seek to capture the known trends in dose-volume-tolerance for normal tissues (normal tissue complication probability, or NTCP), or dose-volume-eradication for tumors (tumor control probability, or TCP). We will briefly review the underlying radiobiological and mathematical characteristics of a few predictive models for normal tissues and tumors and point to their uses to understand radiobiological mechanisms, design protocols, and, eventually, guide personalized plan optimization.

Outcome-related mathematical models seek to capture the known trends in dose-volume-tolerance for normal tissues (normal tissue complication probability, or NTCP), or dose-volume-eradication for tumors (tumor control probability, or TCP). We will briefly review the underlying radiobiological and mathematical characteristics of a few predictive models for normal tissues and tumors and point to their uses to understand radiobiological mechanisms, design protocols, and, eventually, guide personalized plan optimization.


The course will end with a general discussion.

Learning Objectives:
1.To distinguish between stochastic effects and tissue reactions and their impact on radiotherapy treatments
2.To realize how the linear-quadratic equations model the effects of radiobiological parameters in radiotherapy
3.To understand the radiobiological rationale of proton and heavier ion therapy, along with remaining challenges and opportunities
4.To learn outcome-related mathematical models for normal tissues and tumors that eventually will guide personalized plan optimization
5.To understand the FLASH mechanism and its potential reduction of normal tissue toxicity

Handouts

• 166-57907-15651646-171534-1506409181.pdf (Colin Orton)
• 166-57909-15651646-171275-1771023564.pdf (Jian-Yue Jin)
• 166-57908-15651646-171558-1312028558.pdf (Katia Parodi)

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