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Lecture 19

Lecture 19. Therapeutic Ratio. Tumor control probability (TCP) curves: Calculation of TCP and factors affecting shape and slope of TCP curves Influence of tumor repopulation/regeneration on TCP: Normal tissue complication probability (NTCP) curves

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Lecture 19

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  1. Lecture 19 Therapeutic Ratio

  2. Tumor control probability (TCP) curves: Calculation of TCP and factors affecting shape and slope of TCP curves Influence of tumor repopulation/regeneration on TCP: Normal tissue complication probability (NTCP) curves Influence of normal tissue regeneration on responses: Response of subclinical disease; Causes of treatment failure; Factors determining tissue tolerance; Normal tissue volume effects (Dose-volume histogram analysis) Effect of adjuvant or combined treatments on therapeutic ratio

  3. Tumor Control Probability (TCP) curves The relationship between total dose and response (e.g. tumor control or normal tissue injury) is threshold-sigmoid. Above a certain threshold tumor control and complication rates increase steeply

  4. Tumor Control Probability (TCP) curves Calculations of TCP The threshold reflects the necessity for reducing survival of tumor clonogens or target cells per functional subunit to less than 1. For tumor control, this may require a reduction in clonogenic cell survival by factors of 109 to 1012. The steepness of the curves in Fig. is greatest between about 10% and 85% being maximal at 37% which corresponds to an average survival of one clonogen per tumor.

  5. Tumor Control Probability (TCP) curves Calculations of TCP When tumor control rates lie between about 10% and 85%, a useful practical description of the slope of the TCP curves is the percentage point change in TCP for a 1% change in tumor dose, the γ-value. The γ-value is determined by clonogen radiosensitivity, the curve being steeper the more sensitive the tumor cells.

  6. Tumor Control Probability (TCP) curves Factors affecting shape and slope of TCP curves • The fundamental goal in radiation oncology is to deliver a • sufficiently high dose of radiation to sterilize the tumor • cells with minimal damage to the surrounding normal tissues, • with the ultimate result being complete eradication of the • tumor with sufficient normal tissue remaining • to ensure viability and function. • Problems: • interaction of radiation in matter, including cells, tissues • and organs, is a nonspecific, random process, with no • specificity to tumor cells; • radiation delivered from the sources outside the body is • absorbed by normal tissues in its path to the tumor, • and the damage to the normal cells occurs.

  7. Tumor Control Probability (TCP) curves Factors affecting shape and slope of TCP curves The γ-values derived from the literature average less than 2%, compared with an expected average value of at least 5% based on reasonable estimates of tumor cell radiosensitivity • This reflects the enormous heterogeneity of tumor-related and treatment-related factors which may affect the dose required for tumor control. • Tumor-related factors include: • variations in clonogen content within a given stage of a specific • site and histology of the tumor, • variations in intrinsic tumor clonogen sensitivity, • variability in radiosensitivity related to heterogeneity of oxygenation, • variation in the rates of growth of tumors during radiation therapy, • which causes variability in the “effective” number of clonogens • during sterilization

  8. Tumor Control Probability (TCP) curves Factors affecting shape and slope of TCP curves Treatment-related factors which influence the results of retrospective analyses include: • heterogeneity of dose calibration, specification, • and distribution (including geographic miss), • variations in overall treatment duration, • inconsistency of criteria for tumor control, • - other factors in the methods of analysis

  9. Tumor control probability (TCP) curves: Calculation of TCP and factors affecting shape and slope of TCP curves Influence of tumor repopulation/regeneration on TCP: Normal tissue complication probability (NTCP) curves Influence of normal tissue regeneration on responses: Response of subclinical disease; Causes of treatment failure; Factors determining tissue tolerance; Normal tissue volume effects (Dose-volume histogram analysis) Effect of adjuvant or combined treatments on therapeutic ratio

  10. Normal tissue complication probability (NTCP) curves Curves for normal tissue complications are less well-defined than tumor control curves because treatment philosophy is to avoid a high incidence of injury. However, it is likely they are steeper than for tumor control, reflecting less heterogeneity in the biology of normal tissues than that of tumors. Thus, in practice, the curve for tumor control is always likely to be shallower than, and may actually cross that of complications.

  11. Normal tissue complication probability (NTCP) curves

  12. Influence of normal tissue regeneration on responses. Normal tissue tolerance. As in the tumor, more cells are killed in the normal tissue as the dose is increased and the probability of damage occuring increases. However, all normal tissues have a limit as to the amount of radiation they can receive and still remain functional; this is defined as Radiation tolerance The amount of radiation used to treat a specific malignant tumor is limited by the tolerance of the surrounding normal tissue, not by the tumor.

  13. Influence of normal tissue regeneration on responses. Tissue tolerance. Many different fractionation and protraction schedules and total doses were used in early years of radiation therapy. In an attempt to correlate these various time-dose relationships with clinical results, Strandqvist reviewed 280 cases of carcinoma for 5 years.

  14. Influence of normal tissue regeneration on responses. Tissue tolerance.

  15. Influence of normal tissue regeneration on responses. Tissue tolerance.

  16. Influence of normal tissue regeneration on responses. Tissue tolerance.

  17. IMRT is a technique of radiation delivery developed to improve target dose conformity and normal tissue sparing. The impact of IMRT delivery time on local tumor control will be discussed on the following slides.

  18. Biological indices for IMRT evaluation and optimization

  19. Tumor control probability (TCP) curves: Calculation of TCP and factors affecting shape and slope of TCP curves Influence of tumor repopulation/regeneration on TCP: Normal tissue complication probability (NTCP) curves Influence of normal tissue regeneration on responses: Response of subclinical disease; Causes of treatment failure; Factors determining tissue tolerance; Normal tissue volume effects (Dose-volume histogram analysis) Effect of adjuvant or combined treatments on therapeutic ratio

  20. Response of subclinical disease

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