1. Aperture-based IMRT for GYN malignancies Myriam Bouchard S. Nadeau, I. Germain, P.-É. Raymond, F. Harel, F. Beaulieu, L. Beaulieu, R. Roy, L. Gingras Department of radiation oncology of L’Hotel-Dieu de Quebec, QC, Canada Results from the dosimetric study – 2005/2006

2. Objectives Contours definition Contours definition –Target –Organs at risk Aperture-based vs Beamlet-based IMRT Aperture-based vs Beamlet-based IMRT Gains vs Uncertainties in IMRT for GYN Gains vs Uncertainties in IMRT for GYN

3. Selected cases Endometrial / Uterus cervix cancer Post-operative EBRT = Local Control benefit PORTEC, Creutzberg et al. Lancet (2000) (endometrium) GOG-99 (endometrium) Sedlis Gyn Oncology (1999) (cervix) Purpose of tx No survival benefit, attempt to reduce side effects from adjuvant treatments

4. What do we treat? GYN postop EBRT

5. CTV External iliac nodes External iliac nodes Internal iliac nodes Internal iliac nodes Obturator nodes Obturator nodes Presacral region Presacral region 1/2 superior of vagina 1/2 superior of vagina Parameters Parameters

6. Controversies CTV

7. Controversies -- CTV Endometrium CTV Þ Cervix CTV Endometrium CTV Þ Cervix CTV –Presacral region

8. Presacral CTV / 4-field CTV 95% Isodose

9. Controversies -- CTV Endometrium CTV Þ Cervix CTV Endometrium CTV Þ Cervix CTV –Presacral region Upper limit ? Upper limit ? –L5-S1, L4-L5… (common iliac LN) External iliac limit External iliac limit

10. Ant limit / Ext. Iliac LN

11. Controversies -- CTV Endometrium CTV Þ Cervix CTV Endometrium CTV Þ Cervix CTV –Presacral region Upper limit ? Upper limit ? –L5-S1, L4-L5… (common iliac LN) External iliac limit External iliac limit Margin around vessels Margin around vessels –How big?

12. Pelvic LN mapping literature

13. Taylor et al 20 patients, GYN malignancies 20 patients, GYN malignancies MRI + iron oxyde particles MRI + iron oxyde particles CTV = CTV = –margins 3-5-7-10-15 mm – PTV = CTV + 1 cm

14. Taylor et al CTV Margins N coverage Bowel inside PTV 5 mm 76%--- 7 mm 88% 146,9 cc 10 mm 94% 190 cc 15 mm 99% 266 cc

15. Taylor et al 99% coverage modified-7 mm

16. 18 patients with prostate cancer N+ 18 patients with prostate cancer N+ Margin 2 cm around vessels (includes PTV) Margin 2 cm around vessels (includes PTV) 94,5 % N coverage 94,5 % N coverage

17. Controversies -- CTV Endometrium CTV Þ Cervix CTV Endometrium CTV Þ Cervix CTV –Presacral region Upper limit ? Upper limit ? –L5-S1, L4-L5… (common iliac LN) External iliac limit External iliac limit Margin around vessels Margin around vessels –How big? ITV… bladder filling ITV… bladder filling –MDACC = fusion pre-postmictional CTsim

18. ITV 1 cm

19. CTV – our initial choices* External iliac nodes External iliac nodes Internal iliac nodes Internal iliac nodes Obturator nodes Obturator nodes Presacral region Presacral region 1/2 superior of vagina 1/2 superior of vagina Parameters Parameters + 5 mm around vessels ITV 1 cm *Before RTOG 0418, Shih et al. and Taylor et al. publications

20. 3D CTV

21. PTV = CTV + 1 cm

22. OARs Bowel (colon + small bowel) Bowel (colon + small bowel) –Region at risk to find bowel = RAR-B Rectum Rectum Bladder Bladder Bone marrow Bone marrow

23. Bowel / RAR-B

24. Why IMRT for GYN ?

25. Inadequate coverage PTV Conventional 4-fields 95% Isodose

26. Inadequate coverage Greer et al. (1990) Greer et al. (1990) S2-3 post limit : 49% inadequate coverage S2-3 post limit : 49% inadequate coverage 87% com. il. bifurcation above L5-S1 87% com. il. bifurcation above L5-S1 Bonin et al. / Pendelbury et al. (1993) Bonin et al. / Pendelbury et al. (1993) 45% / 62% inadequate coverage ext. il LN 45% / 62% inadequate coverage ext. il LN Finlay et al. (2006) Finlay et al. (2006) 95,4% at least 1 inadequate margin with bony landmarks 95,4% at least 1 inadequate margin with bony landmarks

27. IMRT for GYN malignancies Mundt et al.(Chicago, 2000) Portelance et al.(St. Louis, 2001) Heron et al.(Pittsburgh, 2003) Lujan et al.(Chicago, 2003) Mundt et al.(Chicago, 2000) Portelance et al.(St. Louis, 2001) Heron et al.(Pittsburgh, 2003) Lujan et al.(Chicago, 2003) D’Souza et al. (Houston, 2005) Adequate target coverage OARs sparing Small bowel Small bowel Rectum Rectum Bladder Bladder Bone marrow Bone marrow

28. IMRT for GYN malignancies Good clinical results with IMRT 1 Good clinical results with IMRT 1 –36 patients, whole-pelvis IMRT Median FU = 19,6 month Median FU = 19,6 month –13.9% less GI-GII toxicity –3 year Pelvic LC 87,5% * (62 patients) Cervix cancer Cervix cancer 71% intact uterus 71% intact uterus 1 Mundt et al. IJROBP, vol.56 #5 (2003) pp.1354-1360 * Kochanski et al. ASTRO 2005 Abst #1114

29. Disadvantages of IMRT Target volume definition controversies Target volume definition controversies Impact of Impact of –Machine errors (MLC) –Patient positioning errors

30. Disadvantages of IMRT Large # of segments and MU Large # of segments and MU –Scattered dose –Calculation uncertainties Time consuming Time consuming –Planning –Treatment –Quality assurance

31. Can we improve treatment delivery issues? Ballista = Aperture-based IMRT A feasability study - dosimetric - clinic

32. Let’s talk about IMRT Beamlet-based vs vsAperture-based

33. Types of planning Forward planning (conventional) Forward planning (conventional) –Manual (human) field definition –Followed by calculation Inverse planning (IMRT) Inverse planning (IMRT) –Dose objectives in specific areas (contours) –Solution found by computer-assisted calculation

34. IMRT Intensity Modulated Radiation Therapy Dose intensity varies inside the beam Dose intensity varies inside the beam –Several sub-fields (segments) –Inverse planning

35. No Yes Final plan Does the plan meet the clinical objectives? Segmentation Optimization of beam intensity profiles Field geometry Basic objectives Beamlet-based IMRT 2 nd 1 st *** Calculation steps

36. Aperture-based IMRT

37. Ballista 1 Inverse planning system Inverse planning system –Recently developed at L’Hotel-Dieu de Qc Intensity modulation Intensity modulation –Anatomy-based MLC field Simultaneous optimization Simultaneous optimization –Gantry, table and collimator angles –Wedge angle and beam weights 1 BEAULIEU et al. Med.Phys.31, 1546-1557 (2004)

38. Aperture-based Segmentation Basic objectives Field geometry Ballista

39. Anatomy-based fields

40. Field weights optimization Aperture-based Segmentation Basic objectives Field geometry Ballista Yes Final plan Does the plan meet the clinical objectives? No Minor leaf corrections Only 1 *** Calculation steps X

41. Dosimetric study Ballista for GYN Pilot study -- Part I CHUQ -- Hotel-Dieu de Quebec Quebec city

42. Dosimetric objectives Evaluate Ballista as an alternative Evaluate Ballista as an alternative –Between 4-field and IMRT –For post-operative whole-pelvis radiotherapy in gynecologic malignancies

43. Hypothesis Same target coverage Same target coverage Organs at risk (OARs) sparing Organs at risk (OARs) sparing –Better than 4-field –As good as IMRT ? Treatment delivery advantages Treatment delivery advantages

44. Materials and methods 10 patients 10 patients Endometrial or cervix malignancies Endometrial or cervix malignancies Post-operative external radiotherapy Post-operative external radiotherapy 45 Gy / 25 fractions, whole-pelvis 45 Gy / 25 fractions, whole-pelvis + brachy HDR boost

45. Materials and methods For comparison purposes 4 plans created for each patient Conventional 4-field Conventional 4-field Enlarged 4-field Enlarged 4-field –Results for OARs at same PTV coverage IMRT IMRT Ballista Ballista Inverse planning

46. Materials and methods Forward planning 4-field enlarged 4-field

47. Materials and methods Planning CTscan as usual Planning CTscan as usual Conventional planning : Conventional planning : –4-field plans based on bony landmarks –Created before other plan conception Enlarged 4-field Enlarged 4-field –Aperture shaped to PTV

48. Materials and methods Inverse planning IMRTBallista

49. IMRT Plans created with Pinnacle 3 system Plans created with Pinnacle 3 system Step-and-shoot Step-and-shoot 7 coplanar and equidistant 6 MV beams 7 coplanar and equidistant 6 MV beams –1 extraction –10-12 intensity levels –Minimum field area = 4 cm 2

50. Beam orientation for Ballista plans 9 beams 23 MV

51. Analysis For each plan (4) created for each patient (10) DVH DVH –PTV and OARs Number of segments Number of segments Number of MU Number of MU Statistics : Student’s paired t-test Statistics : Student’s paired t-test

52. Results Target coverage

53. 4-fieldEnlarged 4-field IMRTBallista

54. PTV coverage / homogeneity 4-field Enlarged 4-field IMRTBallista 77% p =0.03 (Mean±SEM, n=10)

55. Results OARs sparing

56. RAR-B 40 and 45 Gy + 34.7 % 4-field Enlarged 4-field IMRTBallista (Mean±SEM, n=10) For the same PTV coverage

57. RAR-B 4-field Enlarged 4-field IMRTBallista + 20.8 % Ballista vs 4-field : V45 Gy, p < 0,001 (Mean±SEM, n=10)

58. RAR-B 45 Gy : p = 0.15 40 Gy : p < 0.001 (diff. = 61.4 cm 3 or 9.9% ) 4-field Enlarged 4-field IMRTBallista (Mean±SEM, n=10)

59. Results Treatment delivery

60. Number of segments 4-fieldEnlarged4-fieldIMRTBallista  4 4 4 4  4 4 4 4 128.6 ± 0.8 33.3 ± 0.7 (Mean±SEM, n=10)

61. Number of MU Monitor Units 4-field (Mean±SEM, n=10)

62. Calculated / delivered doses Impact of leaf position errors Impact of leaf position errors ± 1.4 Gy

63. Discussion

64. Advantages Ballista vs IMRT Number of segments reduced by 75% Number of segments reduced by 75% Number of MU reduced by 55% Number of MU reduced by 55% Result in  scattered radiation – –  risk of second malignancies – –Concerns with 23 MV sec. neutrons…

65. Advantages Ballista vs IMRT Dose calculation + precise and + robust Dose calculation + precise and + robust  treatment time (door-to-door)  treatment time (door-to-door) – –40-45 min IMRT – –20-25 min Ballista  quality assurance time  quality assurance time –Dosimetric QA measurements can be avoided Larger segments Larger segments

66. IMRT for GYN malignancies Post-operative Post-operative –More bowel to spare –Less organ motion Main objective = bowel sparing Main objective = bowel sparing –Less bladder filling = more bowel to spare High sparing objectives on bladder too High sparing objectives on bladder too

67. Movements vs shape of CTV Effect of AP-PA rotation of the pelvis

68. Modified Immobilization

69. Movements vs shape of CTV Effect of lateral rotation Less impact if spheric…

70. OARs results To enhance sparing… Organ motion study necessary 2 Organ motion study necessary 2 –To limit as possible expansion for PTV In our study, ITV/PTV limited sparing of rectum In our study, ITV/PTV limited sparing of rectum Optimal patient immobilization Optimal patient immobilization –essential 2 AHAMAD et al. (MDACC). IJROBP 62 (4) p.1117-1124 (2005)

71. Conclusions Ballista A new inverse planning approach

72. Conclusions – Ballista PTV coverage improved PTV coverage improved OARs sparing OARs sparing –Similar to IMRT planning

73. Conclusions – Ballista Advantages Ballista vs IMRT Advantages Ballista vs IMRT –Better dose calculation –Less treatment time –Less scattered dose –Less quality assurance time  Therapeutic ratio probably improved

74. Perspectives Clinical results to come Clinical results to come 15 patients treated 15 patients treated –Acute toxicity analyzed –Feasibility in a busy clinic

75. Anatomy-based MLC Field Optimization for the Treatment of Gynecologic Malignancies Coauthors : Myriam Bouchard* Sylvain Nadeau* Isabelle Germain* Paul-Émile Raymond* François Harel Frédéric Beaulieu** Luc Beaulieu* René Roy ** Luc Gingras** ASTRO 2005 AAPM 2005 CARO 2005 COMP 2005 SFRO 2005 AROQ 2005 Questions : myriam.bouchard.1@ulaval.ca * Dep. of radiation oncology of L’Hotel-Dieu de Quebec, QC, Canada ** Dep. of Physics, Physics Engineering and Optics, Laval University, Quebec, Canada

76. References Beaulieu Med.Phys. 31, 1546-1557 (2004) Mundt 52 1330-1337 (2002) Mundt IJROBP 52 1330-1337 (2002) Mundt 56 1354-1360, (2003) Mundt IJROBP 56 1354-1360, (2003) Portelance 51, 261-266 (2001) Portelance IJROBP 51, 261-266 (2001) Ahamad (MDACC). IJROBP 62 (4) 1117-24 (2005) Taylor IJROBP 63 (5) 1604- 12 (2005) Shih IJROBP 63 (4) 1262-69 (2005) Kochanski et al. ASTRO 2005 Abst #1114 Finlay 64 (1) 205-09 (2006) Finlay IJROBP 64 (1) 205-09 (2006)

77. Addendum

78. Bone marrow 4-field Enlarged 4-field IMRTBallista (Mean±SEM, n=10) Enlarged 4-field vs Ballista : V40 Gy, p < 0,001 (for the same PTV coverage )

79. V 50% and V 95% Volume traitéVolume irradié Irradiated volumeTreated volume 4-field Enlarged 4-f (Mean±SEM, n=10)

80. Rectum – mean V 45 Gy 4-champsIMRTBallista p value (difference) 61.7 % 50.0%59.9% NS (1.8%)

81. Rectum – mean V 45 Gy 4-champsIMRTBallista p value (difference) 61.7 % 50.0%59.9% SS (9.9%)

82. Bladder – mean V 45 Gy 4-champsIMRTBallista p value (difference) 91.3%46.0%47.8% SS (43.5%)

83. Bladder – mean V 45 Gy 4-champsIMRTBallista p value (difference) 91.3%46.0%47.8% NS (1.8%) NS (1.8%)

84. Number of fields Gantry and table angle optimization Feasibility Selection of a fixed geometry (class solution) StepsResult / conclusion Addition of sub- anatomic structures New treatment that is comparable to IMRT Ballista

85. Number of fields Gantry and table angle optimization Feasibility Selection of a fixed geometry (class solution) StepsResult / conclusion Addition of sub- anatomic structures New treatment that is comparable to IMRT Ballista

86. Sub-anatomic structures