Physics 2: IMRT in Cervix Cancer

1. Physics 2: IMRT in Cervix Cancer Tomas Kron, PhD Peter MacCallum Cancer Centre AUSTRALIA

2. Preface • Despite the “availability of IMRT” in approximately 30% of radiotherapy centres in the western world, IMRT is rarely used for treatment of cervix cancer.

3. Objectives of the lecture • Discuss the need for imaging in the assessment of target volumes in external beam RT of cervix cancer • Introduce the concept of inverse treatment planning in IMRT • Discuss pro- and cons of IMRT • Compare IMRT and brachytherapy dose distributions for cervix radiotherapy

4. Some anatomy

5. …is it constant? From Huh, SJ et al Radiother. Oncol. 71 (2004) 73 2 MRI T2 weighted images of the same patient 4 weeks and 35Gy apart

6. Conventional treatment Region 2: 45Gy (para-aortic LN) Region 1: 45Gy + 5.4Gy EBT + brachytherapy boost Mutic S et al IJROBP 55 (2003) 28

7. Role of imaging for target definition • Patterns of Care Study 1988/89 in US – Ling et al IJROBP 1996: • “Fairly uniform approach” • CT scans 11% • MRI none • Target volume outline 14% • Small bowel outline <1% From ICRU report 38 based on G Fletcher’s work

8. The impact of patient positioning on the adequate coverage of the uterus in the primary irradiation of cervical carcinoma: a prospective analysis using magnetic resonance imaging. Weiss E et al Radiother. Oncol. 63 (2002) 83 Results: Standard portals [ie 4 field box] did not completely cover the uterus in supine position in 7/21 (33%), in prone position with belly board in 7/21 (33%) and without belly board in 5/21 (24%). Insufficient uterine coverage was found only in the anteroposterior direction. The mean distance (± standard deviation) between the field borders of the lateral portals and the uterus was in supine position anteriorly 3.4 cm (±2.2 cm) and posteriorly 1.8 cm (±1.3 cm), in prone position with belly board anteriorly 2.2 cm (±2.7 cm) and posteriorly 2.6 cm (±1.6 cm), prone without belly board anteriorly 3.3 cm (±2.4 cm) and posteriorly 1.9 cm (±1.1 cm). The difference was statistically significant between supine and prone position with belly board and between prone position with and without belly board. Repeated MRI controls during therapy showed no significant changes compared to the MRIs at the beginning of therapy. Conclusions: The use of standard radiation fields results in a high percentage of geographical misfits. Three-dimensional treatment planning is a prerequisite for adequate uterus coverage.

9. … what has changed in 10 years? • Patterns of Care Study 1996-99 in US – Eifel et al IJROBP 2004: • 1/3 stage IIIA - IVA • CT most common • 92.4% radical patients had brachytherapy • 1999: 63% had concurrent chemotherapy • Small centres (less than about 4 cervix patients per year) tend to provide worse treatment (<80Gy pt A, >70d total treatment time)

10. Role of imaging for target definition • CT: • Treatment planning • Nodal assessment • MRI: • Extra cervical spread • Design of lateral portals • PET: • Lymph node involvement • US/TRUS Mutic S et al IJROBP 55 (2003) 28

11. What can IMRT do ? • Reduction of dose to normal structures - ‘conformal avoidance’ • Deliver multiple dose levels at one time • simultaneous in-field boost • mimicking brachytherapy distributions

12. Forward planning: • select parameters • calculate dose • check if it is ok Radiotherapy treatment planning Patient information Treatment unit data Planning • Inverse planning: • define what is ok • tell the computer • iterative optimization Treatment plan Treatment

13. Inverse planning process • CT scan - 3D, large volume, small slices • Outlining of ALL (!) relevant structures (targets and critical organs) • DICOM transfer of CT data sets and structures to planning system • Definition of dose constraints • Computer optimization • Verification

14. Eg Tomotherapy planning station interface Everything of interest MUST be outlined… The system does not care about anything else.

15. Need for customisation? Courtesy A Fyles

16. …scope for customisation IMRT beneficial Collage courtesy S Van Dyk, K Narayan

17. What are the target outlines? IMRT difficult, if not impossible Prior to Txt After chemoradiation (40Gy) K Narayan and Quinn 2003

18. Prescription panel Three ways to guide the optimisation: 1. Precedence, 2. Importance, 3. Dose penalty

19. Inverse treatment planning • Many automatic optimisation algorithms are in use • gradient based • iterative least square minimisation • simulated annealing • Do not necessarily find the best solution (local minima!) • Can only be as good as the specified constraints • Very computer and time consuming Tomotherapy 30processor

20. Planning as part of a network Issues: reliability, compatibility, security

21. What can IMRT do ? • Reduction of dose to normal structures - ‘conformal avoidance’ • Deliver multiple dose levels at one time • simultaneous in-field boost • mimicking brachytherapy distributions Lujan et al IJROBP 57 (2003) 516

22. What can IMRT do ? • Reduction of dose to normal structures - ‘conformal avoidance’ • Deliver multiple dose levels at one time • simultaneous in-field boost • mimicking brachytherapy distributions Mutic et al IJROBP 55 (2003) 28

23. IMRT to mimic Brachytherapy HDR brachy HDR brachy 7 field IMRT 7 field IMRT Schefter et al. Med Dosim 27 (2002) 177

24. Point/Counterpoint: Can IMRT replace brachytherapy in the management of cervical cancer? K Alektiar (New York): Brachy-therapy A Mundt, J Roeske (Chicago): IMRT The first issue of a new journal (Elsevier):Brachytherapy 1 (2002) 191

25. K Alektiar: • Brachytherapy is more suitable: • Can give 80-90Gy to point A safely (even higher to cervix point) • Target volume difficult to define for EBRT (parametrium particularly) • Organ motion likely to be larger than in prostate

26. Inter-fraction Organ Motion 7 July 03 21 July 03 Courtesy A Fyles 5 Aug 03 14 July 03

27. Some comments • Optimisation of HDR applicators and stepping source pattern will further improve • Experience is very important in brachytherapy • Must consider overall treatment time when using external beam and brachytherapy combination Dose distributions from four different HDR source movements as determined using film Nucletron

28. A Mundt and J Roeske: “IMRT is a revolution in the treatment of cancer”

29. For pelvic treatment sparing of normal structures (bone marrow, intestines) Potentially replace brachytherapy (80Gy possible with 0.5cm margin) - alternatively applicator based IMRT (Low et al 2002) Simultaneous integrated boost Role of IMRT in cervix cancer Lujan 2003 “...IMRT may one day rival and perhaps replace brachytherapy...” Mundt and Roeske 2002

30. What can IMRT do ? • Reduction of dose to normal structures - ‘conformal avoidance’ • Deliver multiple dose levels at one time • simultaneous in-field boost • mimicking brachytherapy distributions Unlikely Ahmed et al IJROBP 60 (2004) 550

31. Considering IMRT • And also: • Leakage • Integral dose, dose dumping • Treatment time • Dose rate • Resources required for set-up, maintenance and QA

32. Green Journal 1992: > 50 occasions of data transfer from one point to another for each patient!

33. Role of Ultrasound likely to increase Two final comments... Small bowel dose with ‘limited arc’ technique • Positioning of the patient is important • Imaging is not all ‘high cost’ Adli et al IJROBP 57 (2003) 230

34. Summary (personal opinion) • Cervix cancer radiotherapy is likely to include brachytherapy in years to come • Promising imaging techniques because of soft tissue contrast are MRI and US • IMRT is likely to play a role in • optimising ‘conventional part’ of external beam delivery • allow for simultaneous boost of involved lymph nodes

35. Any questions?

36. Thank you • Acknowledgements: • A Fyles • K Narayan • S Van Dyk