Establish the NTCP Evaluation System for Radiotherapy

1. Establish the NTCP Evaluation System for Radiotherapy 學生: 蕭安成指導老師: 陳為立教授

2. The goal of radiotherapy • To deliver a sufficient dose to the tumor to provide a high probability of cure while inducing minimal damage in the surrounding normal tissues, leaving them architecturally intact and functionally competent.

3. Radiotherapy treatment planning 1980’sConformal Therapy 1990’sIntensity Modulated Radiation Therapy (IMRT) • New treatment techniques drove the developers of models to evaluate the resultant complex dose distribution plans

4. CTV2 CTV2 CTV2 CTV2 CTV1 GTV GTV P P GTV P P GTV GTV SC CTV1 BSP CTV1 CTV1 CTV1 Fig 1 (a) Radiotherapy treatment planning • Target and critical organ SC Fig 1 (c)

5. Radiotherapy treatment planning Tumor Control Probability (TCP) Normal Tissue Complication Probability (NTCP) DOSE

6. Plan evaluation • Geometric dose distribution Sequential-IMRT SIB-IMRT

7. Plan evaluation • Dose-volume histogram (DVH) • DVHs obtained with different IMRT planning techniques for (left) CTV, (right) right parotid. 1:SIB-IMRT;2:sequential-IMRT

8. Plan evaluation • Dose-volume histogram • the location of high-dose or other regions cannot be determined from the DVHs • the geometric distribution of dose was irrelevant to its biological impact

9. Plan evaluation • Biological indices • Normal tissue complication probability (NTCP) • Tumor control probability(TCP)

10. Plan evaluation • The probability of uncomplicated tumor control (PUTC): PUTC=TCP(1-NTCP)

11. Normal tissue complication probability • These models aim to predict the probability of a complication as a function of the dose or biologically equivalent dose and volume

12. Normal tissue complication probability • Functionally, the whole organ does not fail if some part of it is destroyed • Withers suggested that the tolerance of tissues depends on the ability of the remaining clonogenic cells to maintain a sufficient number of mature cells suitably structured to maintain organ function

13. Normal tissue complication probability • Organ function depend upon the aggregation of cells into functional sub-units ( FSUs ) • FSUs in an organ can be organized in series or parallel • Series: gastrointestinal tract and spinal cord, damage in one portion of the organ may produce total organ fail • Parallel: lung or kidney, function is often maintained since the undamaged part operates independently from the damage part

14. Normal tissue complication probability • Volume dependence • A lot to a little or a little to a lot ? • Whether it is better to give a lot to a little as unconventional treatment, or a little to a lot as in 3D and IMRT

15. Models for NTCP • Homogeneous dose distribution • Empirical model • Probit model : Lyman (1985) • Logistic model • Tissue architecture model • Inhomogeneous dose distribution • Effective dose method : Lyman and Wolbarst (1987) • Effective volume method : Kutcher and Burman (1989) • Integral probability model : Schultheiss et al. (1983)

16. Probit model (Lyman) TD50(1) : the tolerance dose for reference volume irradiation m : the steepness slope of the dose response curve Vref : the reference volume n : tissue-specific parameter

17. Tolerance Data: Emami et al., 1991Lung Vol 1/3 2/3 3/3 TD5/5 4500 3000 1750 TD50/56500 4000 2450 TD5/5 is the dose to the partial organ that would have a 5 % probability of complication in 5 years. TD50/5 is the dose to the partial organ that would have a 50 % probability of complication in 5 years.

18. Fitting of Tolerance Data: Burman et al., 1991Lung, brainstem, optic nerve organ n m TD50 end point Lung 0.87 0.18 24.5 Pneumonitis Brainstem 0.16 0.14 65 necrosis/infarction Optic nerve 0.25 0.14 65 blindness TD5/5 TD50/5 organ 1/3 2/3 1 1/3 2/3 1 Lung 45 30 17.5 65 40 24.5 (fitted data) 45 24 17 64 35 25 Brainstem 60 53 50 - - 65 (fitted data)60 53 50 65 Optic nerve - - 50 - - 65 (fitted data)- - 50 - - 65

19. NTCP vs. dose, fixed partial irradiated volume 2/3 3/3 3/3 2/3 NTCP NTCP 1/3 1/3 dose dose Large volume effect, n  1.0 small volume effect, n  0.0

20. Logistic model γ50 D50 : the dose resulting in a 50% complication probability for some specified complication or end point k : 4γ50D50 (γ50 : slope of D50) D50

21. Lyman model or logistic model Effective dose method DN’ From Lyman et al. 1987

22. Lyman model or logistic model Effective volume method From Kutcher et al.1989

23. Clinical application • Application software program for NTCP evaluation • Biological evaluation for four different radiation techniques for left side breast cancer: (1) 3-dimensional tangential plan (3D) (2) 2-field tangential IMRT plan (2T) (3) 2-field optimized IMRT plan (2O) (4) 4-field IMRT plan (4I)

24. Clinical application 3-dimensional tangential plan

25. Clinical application 2-field tangential IMRT plan

26. Clinical application 2-field optimized IMRT plan

27. Clinical application 4-field IMRT plan

28. Clinical application

29. Clinical application

30. Future work • Evaluate the clinical treatment plans by the NTCP program • Modify the NTCP calculation parameters by comparing the calculated NTCP values and the clinical follow up results • To establish the NTCP evaluation model for the specific radiation treatment department

31. THANK YOU !!