Richard Ptter Department of Radiotherapy - Medical University of - PowerPoint PPT Presentation

ICARO MEETING: CURRENT TRENDS IN BRACHYTHERAPY VIENNA, 28 April 2009 Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer Richard Pötter Department of Radiotherapy - Medical University of Vienna

Background X-Ray Based Brachytherapy DOSE TO POINTS OR REFERENCE VOLUME Dose to points Point A ‐ ICRU rectum point ‐ ICRU bladder point ‐ Dose to reference volume (60 Gy) ICRU Report 38, 1985, Bethesda

Background X-Ray Based Brachytherapy DOSE EFFECT RELATIONSHIP POINT A N=1499 Dose pt A pelvic failure Stage IB and IIA (<2 cm) 70-80 Gy <10% (>2 cm) 85-90 Gy 25-37% Stage IIB 70 Gy 50% nonbulky >80 Gy 20% bulky >80 Gy 30% Stage III unilateral ≤ 70 Gy 50% >70 Gy 35% Stage III bilateral/bulky < 70 Gy 60% >70 Gy 50% >85 Gy 35% Increasing dose, increasing local control Modified from Perez et al 1998

Background X-Ray Based Brachytherapy MORBIDITY RATES AFTER RADIOTHERAPY (EBRT+BT) (b) Rectosigmoidal (a) Genitourinary Increasing dose, increasing morbidity Perez CA in Perez/Brady 1998

2cm Point A 2cm 2cm 2cm

2cm Point A 2cm 2cm 2cm

60 Gy 84 Gy D90 = 65 Gy 2cm Point A 2cm 2cm 2cm 84 Gy

~ 500 Gy 84 Gy D90 = 90 Gy 2cm Point A 2cm 2cm 2cm 84 Gy

GYN GEC ESTRO RECOMMENDATIONS From 2D to 3D/4D Necessity of Introduction of 3D-images Prescription of dose to a Target Volume and dose volume constraints to organs at risk B 45 Gy EBRT + 4 x 7 45 Gy EBRT + 4 x 7 GTV Gy BT = 84 Gy Gy BT = 84 Gy HR- -CTV CTV HR (EQD2) (EQD2) 60 Gy 60 Gy R To apply to gynaecological brachytherapy necessity of a common language

GYN GEC ESTRO RECOMMENDATIONS From 2D to 3D/4D Necessity of Introduction of 3D-images Prescription of dose to a Target Volume B 45 Gy EBRT + 4 x 7 45 Gy EBRT + 4 x 7 GTV Gy BT = 84 Gy Gy BT = 84 Gy HR- -CTV CTV HR (EQD2) (EQD2) 60 Gy 60 Gy R To apply to gynaecological brachytherapy necessity of a common language

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer DVH parameters for Target and OAR TARGET OAR D0.1, 1, 2cm 3 (Bladder, Rectum, Sigmoid) GTV, HR CTV, IR CTV: D90, D100 GTV Sigmoid Tumor at time D90 (IR CTV) of diagnosis. D90 (HR CTV) GTV GTV Rectum Bladder IR CTV HR CTV 0.1cc 1cc 2cc ICRU 38 Ref. Points GYN GEC ESTRO Recommendations(II) Radiother Oncol 2006

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer „simple“ integration of EBRT and Brachytherapy 45 Gy EBRT + 4 x 7 Gy BT 45 Gy EBRT + 4 x 7 Gy BT - HR CTV of BT receives the = 84 Gy (EQD2) = 84 Gy (EQD2) prescribed dose of EBRT B - High and medium dose regions of BT in OAR receive the prescribed dose of EBRT 84 Gy 84 Gy GTV D90, D100 (HR CTV) D0.1cm3, D1cm3, D2cm3 HR- -CTV CTV HR 60 Gy 60 Gy (Bladder, Rectum, Sigmoid) R

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer „simple“ integration of EBRT and Brachytherapy - D90, D100 (HR CTV) - D0.1cm 3 , D1 cm 3 , D2cm 3 (Bladder, Rectum, Sigmoid) Volume D90 (HR CTV) = 7 Gy 100% D 2cc (Bladder) = 6.0 Gy D 2cc (Rectum, Sigmoid) = 2.3 Gy D90 Overall dose (EQD2) 80% 45 Gy EBRT + 4x7Gy HDR-Brachytherapy D90 (HR CTV) =45+4x7= 84 Gy αβ 10 60% D 2cc (Bladder) =45+4x6= 86 Gy αβ 3 HR-CTV D 2cc (Rectum) =45+4x2.3= 53 Gy αβ 3 40% D 2cc (Sigmoid) =45+4x2.3= 53 Gy αβ 3 Bladder 20% Rectum Sigmoid D 2cc Dose [Gy] 2 4 6 8 10 12 14

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer 3D Image Guided BT – LOCAL CONTROL Local control TREATMENT PERIOD and SIZE 145 consecutive patients (1998-2003) Two treatment periods: -learning: 1998-2000 -systematic application: 2001-2003 D90 for HR CTV (mean) -1998-2000: 81 Gy -2001-2003: 90 Gy (p<< 0.01) Pötter R. et al Radioth Oncol 2007

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer 3D Image Guided BT : DVH PARAMETERS Summary volume and dose values values HR CTV (EQD2) Summary volume and dose HR CTV (EQD2) Mean Gy Intracavitary 1 interstitial 2 145 patients 3 Prescribed 85 85 83 HR CTV Vol. 35cm³ 44cm³ 36cm³ HR CTV D90 87 96 86 Point A 82 - - 1 Kirisits et al Int J Radiat Oncol Biol Phys 2005, 22 pts 2 Kirisits et al Int J Radiat Oncol Biol Phys 2006, 22 pts 3 Pötter et al Radiother Oncol 2007, 145 pts

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer HR TARGET: DVH PARAMETERS – LOCAL CONTROL n=141, 523 treatment plans / 608 fractions GTV HR CTV Subgroup n D100 [Gy] D90 [Gy] D100 [Gy] D90 [Gy] V [cm 3 ] V [cm 3 ] 1998 – 2000 71 11 ± 9 83 ± 20 113 ± 28 35 ± 20 62 ± 10 81 ± 16 2001 –2003 70 12 ± 15 97 ± 25 133 ± 38 37 ± 27 68 ± 9 90 ± 15 p value p > 0.05 p > 0.05 p < 0.05 p < 0.05 p < 0.05 p < 0.05 1998-2003 141 12 ± 13 90 ± 23 123 ± 35 36 ± 23 65 ± 10 86 ± 16 GTV HR CTV Subgroup n V [cm 3 ] V [cm 3 ] D100 [Gy] D90 [Gy] D100 [Gy] D90 [Gy] LR 18 13 ± 10 82 ± 13 113 ± 23 50 ± 24 60 ± 7 75 ± 12 No LR 123 11 ± 13 91 ± 24 124 ± 36 34 ± 23 66 ± 10 87 ± 16 p value p > 0.05 p > 0.05 p > 0.05 p < 0.05 p < 0.05 p < 0.05 Dimopoulos et al. IJROBP 2009

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer HR TARGET: DVH PARAMETERS – LOCAL CONTROL n=141, 523 treatment plans / 608 fractions GTV HR CTV IR CTV Subgroup n D100 [Gy] D90 [Gy] D100 [Gy] D90 [Gy] D100 [Gy] D90 [Gy] 65 95 ± 27 131 ± 39 65 ± 11 89 ± 17 51 ± 8 65 ± 10 ( 1 ) 2-5cmDIAG LR 2 92 ± 13 124 ± 19 69 ± 1 92 ± 3 53 ± 1 69 ± 1 2-5cm No LR 63 95 ± 27 131 ± 39 65 ± 12 89 ± 17 51 ± 8 65 ± 10 p value p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 76 86 ± 19 116 ± 29 65 ± 8 83 ± 15 55 ± 5 66 ± 8 ( 2 ) >5cmDIAG LR 16 80 ± 12 111 ± 24 59 ± 6 73 ± 11 53 ± 5 61 ± 6 >5cm No LR 60 87 ± 20 117 ± 31 66 ± 8 86 ± 15 56 ± 4 67 ± 8 p value p > 0.05 p > 0.05 p < 0.05 p < 0.05 p < 0.05 p < 0.05 45 90 ± 21 122 ± 32 67 ± 8 88 ± 15 56 ± 4 68 ± 7 ( 2a ) >5cmDIAG • 2-5cmBT LR 5 90 ± 15 134 ± 29 62 ± 4 83 ± 7 52 ± 7 64 ± 4 No LR 40 90 ± 22 121 ± 33 68 ± 8 88 ± 15 56 ± 4 68 ± 7 p value p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05 ( 2b ) >5 cmDIAG • >5 cmBT 31 79 ± 14 106 ± 22 61 ± 8 77 ± 13 55 ± 5 63 ± 8 LR 11 76 ± 9 101 ± 12 57 ± 7 69 ± 9 53 ± 4 60 ± 6 No LR 20 81 ± 17 109 ± 25 64 ± 7 81 ± 13 56 ± 5 65 ± 8 p value p > 0.05 p > 0.05 p > 0.05 p > 0.05 p < 0.05 p < 0.05 Dimopoulos et al. IJROBP 2009

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer HR TARGET: DVH PARAMETERS – LOCAL CONTROL n=141, 523 treatment plans / 608 fractions Number (and %) of LRs above or below a cut-off Subgroup n D90 HR CTV D100 HR CTV < 87 Gy ≥ 87 Gy < 66 Gy ≥ 66 Gy Entire population 141 15/73 (20%) 3/68 (4%) 14/81 (17%) 4/60 (7%) ( 2 ) >5cmDIAG 76 15/45 (33%) 1/31 (3%) 14/44 (32%) 2/32 (6%) 45 4/21 (19%) 1/24 (4%) 4/21 (19%) 1/24 (4%) ( 2a ) >5cmDIAG · 2-5cmBT 11/24 (46%) 0/7 10/23 (43%) 1/8 (13%) ( 2b ) >5cmDIAG · >5cmBT 31 D90 for the HR CTV: cut-off 87 Gy EQD2 Local control 4% versus 20% D100 for the HR CTV: cut-off 66 Gy EQD2 Local control 7% versus 17% Dimopoulos et al. IJROBP 2009

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer HR TARGET: DVH PARAMETERS – LOCAL CONTROL n=141, 523 treatment plans / 608 fractions 100 80 Extensive disease Local control [%] D90 HR CTV 86 Gy EQD2 60 90% probability for local control 40 20 total tumour tumour population group 2 group 2b 0 80 - <100 100 - <120 <60 60 - <80 >120 <60 60 - <80 80 - <100 100 - <120 >120 80 - <100 100 - <120 <60 60 - <80 >120 D90 HR CTV [Gy] Dimopoulos et al. In press R&O 2009

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer TARGET: DVH PARAMETERS – LOCAL CONTROL n=141, 523 treatment plans / 608 fractions Diagnosis GTV GTV Diagnosis Brachytherapy HR CTV HR CTV B B B B B B GTV DG GTV DG GTV DG GTV DG 84 Gy EQD2 84 Gy EQD2 R R R R a a b b c c 6 mths after treatment 6 mths after treatment 9 mths after treatment C C C C d d e e f f Dimopoulos et al. IJROBP 2009

Potential and Limitations of Image Guided Brachytherapy of Cervix Cancer OAR: DVH PARAMETERS – MORBIDITY Maximum dose: no relevant clinical endpoint in 3D brachytherapy Fixed volumes ~ tolerance dose (overall dose) „minimal dose to the most exposed tissue“* 0.1 cc: 3D „dose maximum“: ulceration (fistula) 1 cm 3 /2 cm 3 : teleangiectasia (20 mm x 20 mm x 5 mm) (20 mm x 20 mm x 5 mm) 2 cm 3 0.1 cm 3 >5 cc: end point fibrosis * * GYN GEC ESTRO Recommendations(II) S i g Radiother Oncol 2006 m o i d GTV Georg P et al. R&O 2009 Rectum Bladder 0.1cc 1cc 2cc ICRU 38 Ref. Points