1. Clinical Site specific IMRT Bulent Aydogan, PhD Department of Radiation and Cellular Oncology University of Chicago Nov 2007 Antalya, Turkiye

2. ➫ You can download the full-blown version of this talk which has site specific clinical IMRT info for H&N, Prostate and GYN from ASTRO website under the refresher courses. ➫ You can email me @ baydogan@radonc.uchicago.edu

3. Target Audience Everybody New to treating with IMRT Planning to treat a new site Learn from others mistakes!

4. IMRT ➫ IMRT is a method of treatment planning and delivery that conforms the high dose region to the shape of the target volume while sparing surrounding critical organs

5. IMRT in numbers ➫ In US ☣ 80% are using ☣ 80% started in the last 3-4 yrs ☣ 90% non-user are planning to use. ➫ Outside of USA ☣ Turkiye!

6. IMRT ALARMING RPC STATISTICS ➫ Dose accuracy ☣ Recommended 3% dose and 3mm ➫ RPC IMRT validation experience (ASTRO 2006 Abstract, A. Molineau et. al.) ☣ 155 inst. 196 irradiations ☣ 7% dose and 4mm DTA ☣ 54 failure ~>1/3 failed (33 on dose)

7. IMRT

8. Purpose ➫ To illustrate how various aspects of the IMRT planning process can influence the resultant treatment plan and delivery ➫ To provide an update of IMRT planning techniques for gynecologic malignancies AND H&N, prostate ➫ How IGRT influence IMRT process

9. Summary ➫ IMRT treatment planning is a multi-step process ➫ Careful consideration throughout the entire process is necessary to ensure that an optimal plan is achieved ➫ Decisions made at the time of simulation, target and tissue delineation, planning and the delivery/verification process itself impact the overall plan

10. Simulation – Prone vs. Supine; Type of immobilization  Target and Tissue Delineation – Multiple imaging modalities  Treatment Planning/Optimization – Number of beams/orientation  Plan Evaluation – High conformity vs. dose homogeneity  Quality Assurance – Verification of calculated dose  Treatment Delivery/Verification – Verification scheme Treatment Planning Process

11. SUMMARY ➫ IGRT ☣ Changing the way we do IMRT ʚ Margins ʚ Biological targeting ʚ Intrafraction vs. interfraction ʚ Organ motion management ٩ Gating, IID ʚ Adaptation ☣ Requires more resources and careful planning

12. PTV Margin and IGRT Litzenberg DW, IJROB, 65(2), 2006

13. General issues In Treatment Planning ➫ Dose distribution depends ☣ Treatment planning system / optimization ☣ Dose calculation method ʚ PBC, Superposition Convolution, MC ☣ User experience ☣ Realistic expectations (e.g., dose constraints) ☣ Beam configuration, Energy?

14. 3 – Field 7 – Field Number of Beams ➫ More beams = Better plan? ➫ Generally Yes ☣ But improvement can be marginal over 7 beams ☣ Degree of improvement depends on tumor shape and proximity to critical structures

15. Beam Angles and Energies ➫ Nearly all studies report using 6 MV ➫ Generally use 6-9 co- planar beams ➫ Avoid parallel opposed beams ➫ Beams are equidistant but may not be uniformly distributed ➫ Non-uniform beam distribution may be used for special sites

16. Beam configuration 9 Field 8 Field

17. User Dependency Can you guess which plan is done by a experienced user?

18. Realistic expectation

19. Managing Hot Spots “Tuning” Structures ➫ Occasionally “hot” spots or unwanted dose in surrounding unspecified tissue ➫ Adding an additional (“tuning”) structure can reduce these “hot” spots and improve dose conformity around the PTV ➫ However, improved conformity may reduce dose homogeneity within the target

20. Use of “Tuning” Structure to Improve Dose Conformity Pawlicki T et al. Plan Evaluation. IMRT: A Clinical Perspective 2005

21. Optimizing with Base Plan Aydogan et al, TCRT, 2006

22. Fluence editing ➫ It is very handy ➫ Needs experience ➫ Exercise caution when using ➫ Works better for smaller hot spots

23. IMRT for Gynecologic Malignancies

24. GYN IMRT ➫ Rationale ☣ Reduce volume of small bowel, bladder and rectum irradiated ☣ Decrease volume of pelvic bone marrow irradiated in patients receiving CRT ☣ Potentially useful in delivering higher than conventional doses ☣ Alternative boost technique for patient who are not amenable to BC

25. Immobilization ➫ Patient in supine position ➫ Immobilized using alpha cradles indexed to the treatment table Univ of Chicago

26. Immobilization (Prone) ➫ Others favor the prone position ➫ Data from the U Iowa suggest ↑dosimetric benefits to the prone position ( Adli et al. Int J Radiat Oncol Biol Phys 2003;57:230-238) Univ of Colorado Schefter T, Kavanagh B. Cervical Cancer: Case Study IMRT: A Clinical Perspective 2005

27. Planning CT Scan ➫ Scan extent: L3 vertebral body to 3 cm below ischial tuberosities ➫ Typically use 3 mm slice thickness ➫ Larger volumes used only if treating extended field whole abdomen or pelvic- inguinal IMRT

28. Contrast Administration ➫ Oral, IV and rectal contrast are commonly used ➫ IV contrast is important to delineate vessels which serve as surrogates for lymph nodes ➫ Generally bladder contrast is not needed

29. Normal Tissues ➫ Normal tissues delineated depends on the clinical case: In most cases, include: Small bowel, rectum, bladder may be femoral heads ➫ In patients receiving concomitant or sequential chemotherapy, include the bone marrow (experimental) ➫ Kidneys and liver included only if treating more comprehensive fields

30. PTV Considerations ➫ Organ motion in the inferior portion of the CTV due to differential filling of the bladder and rectum ➫ Set-up uncertainty ➫ Appropriate expansion remains unclear; various reports ranging from 1 – 1.5 cm ➫ At Univ of Chicago, we use a 1 cm expansion ➫ Less is known about normal tissues ➫ Other centers (e.g., MD Anderson) routinely expand normal tissues

31. Set-up Uncertainties ➫ Dependent on type of immobilization ➫ Therapist ➫ University of Chicago immobilization: Alpha cradle under legs and upper body with arms above head*   LR = 3.2 mm  SI = 3.7 mm  AP = 4.1 mm * Haslam JJ et al. Med Dosim. 2005 Spring;30(1):36-42

32. Treatment Planning ➫ 7-9 co-axial beam angles (equally spaced) ➫ Most centers use 6 MV ➫ Comparative plans of 6 vs. 18 MV show little or no difference ➫ However, 18 MV associated with higher total body doses

33. ➫ Prescription dose: 45-50.4 Gy ☣ 45 Gy in pts receiving vaginal brachytherapy ☣ 45-50.4 Gy if external beam alone ➫ 1.8 Gy daily fractions ☣ Avoids hot spots > 2 Gy ➫ “Dose painting” (concomitant boost) remains experimental ☣ Potentially useful in pts with high risk factors (positive nodes and/or margins) Treatment Planning

34. Small bowel input DVH based on NTCP data INPUT DVH

35. NTCP Analysis GYN IMRT Patients Volume receiving 45 Gy Probability of Moderate to Severe Acute GI Toxicity Conventional Pelvic RT IMRT Roeske et al : IJROB

36. IMRT Isodose Distribution PTV 100%70%

37. AcceptableUnacceptable ConformityGoodPoor PTV Coverage> 98%< 96% Hot Spots LocationWithin CTVEdge of PTV Preferably within GTVRectal or bladder walls in ICB region Magnitude 20% (110% dose) 2% (115% dose) Cold Spots LocationEdge of PTV Within CTV or GTV Magnitude<1% of the total dosenone Plan Evaluation

38. ➫ A concern in the region of the vaginal cuff ➫ Two approaches are being studied at our institution to address this: ☣ IGRT (CBCT) ☣ Vaginal immobilization ➫ Now we simply avoid tight CTV volumes and use a 1 cm CTV →PTV expansion ☣ Produces very generous volumes around the vaginal cuff Organ Motion

39. “Integrated Target Volume” ➫ A creative solution to the organ motion problem developed at MDAH ➫ Two planning scans: one with a full and one with an empty bladder ➫ Scans are then fused ➫ An integrated target volume (ITV) is drawn on the full bladder scan (encompassing the cuff and parametria on both scans) ➫ ITV is expanded by 0.5 cm → PTV ITV

40. Small Bowel Bladder Integrated Target Volume (ITV) PTV Nodes MD Anderson Illustration of ITV Rectum

41. Vaginal Immobilization Device ➫ Cervical and Endometrial cancer pts treated with IM-PRT and vaginal (cylinder) HDR ➫ Goal: Use vaginal cylinder-type immobilization device and IGRT B Aydogan, PhD – Univ of Chicago, Patent pending Treatment table mount and indexing IID adjustment and indexing

42. Adaptive approach in Gynecologic IMRT ➫ Many cervical tumors rapidly shrink during RT (especially with concomitant chemotherapy) ➫ Tight margins (CTV-to-PTV expansions) early on may be too large by the end of treatment

43. ➫ 14 cervical cancer pts ➫ MRI before RT and after 30 Gy ➫ 46% ↓GTV Impact of Tumor Regression in Cervical Cancer Patients Van de Bunt et al. Int J Radiat Oncol Biol Phys 64(1):189-96, 2006.

44. Bladder Rectum Tumor Bladder Tumor Rectum Prescription Isodose Week 1Week 3 Tumors Shrink Plan Adapts

45. IMRT <> ICB ? ➫ IMRT has been used to reduce volume of normal tissues irradiated ➫ In selective sites (e.g., head and neck, prostate), IMRT has been used to deliver higher than conventional doses ➫ Can the same paradigm be applied to cervical cancer?

46. Approaches ➫ SRS Boost ☣ Molla et al. Int J Radiat Oncol Biol Phys 62: 118-24, 2005. ➫ Vaginal Immobilization Device ☣ Aydogan B. Int J Radiat Oncol Biol Phys 65:266-73, 2006. ➫ SIB ☣ Guerrero M, et al. Int J Radiat Oncol Biol Phys 62(3):933-39, 2005.

47. HDR vs. IMRT in early and recurrent endometrial cancer Aydogan B. Int J Radiat Oncol Biol Phys 65:266-73, 2006. HDR IMRT

48. 45 Gy 25 x 1.8 Gy 60 Gy 25 x 2.4 Gy 20 Gy X. Allen Li, PhD – Med Col of Wisconsin IMRT-SIB Planning Approach

49. BMS-IMRT ➫ Rationale ☣ CRT Improved tumor control and survival ☣ Increased toxicity in particular HT ʚ Acute grade >2 HT is up to 50% more ʚ Acute grade >3 HT is up to 35% more ☣ BMS-IMRT may reduce HT Aydogan et al: IJROB, under review ASTRO 2007 ARRO Poster # 2353

50. Dose comparison

51. BMS-IMRT DVH

52. Advancement in IMRT ➫ NEW IMRT DELIVERY METHODS ☣ Helical therapy ☣ IMAT ʚ More Conformal target dose distribution ʚ Further reduction in OAR dose ʚ Faster treatment ➫ NEW GENERATION TREATMENT MACHINES ☣ Online tumor tracking ☣ Tumor Chasing Courtesy : Paul Keal, Stanford Unv.

53. Summary ➫ IMRT treatment planning is a multi-step process ➫ Careful consideration throughout the entire process is necessary to ensure that an optimal plan is achieved ➫ Decisions made at the time of simulation, target and tissue delineation, planning and the delivery/verification process itself impact the overall plan

54. SUMMARY ➫ IGRT ☣ Changing the way we do IMRT ʚ Margins ʚ Biological targeting ʚ Intrafraction vs. interfraction ʚ Organ management ٩ Gating, IID ʚ Adaptation ☣ Requires more resources and careful planning

55. THANKS ➫ John Roeske, PhD, Loyola University ➫ Arno J Mundt, MD, UCSD ➫ Loren K Mell, MD, Unv. of Chicago ➫ Brett Smith,MS, Unv. ofChicago ➫ Hanifi Tiryaki, PhD, Unv. of Illinois at Chicago ➫ Joel Wilkie, PhD, Unv. of Chicago