Linking DVH-parameters to clinical outcome. Richard Pötter, Medical University of Vienna, General Hospital of Vienna, Austria

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1 Linking DVH-parameters to clinical outcome Richard Pötter, Medical University of Vienna, General Hospital of Vienna, Austria

2 Outline DVH parameters for HR CTV (D90) and OAR (2 ccm) simple integration of 3D EBRT and Brachytherapy Clinical endpoints: local failure, morbidity Material: mono-institutional series of consecutive patients Method: Prospective evaluation of clinical outcome 3D assessment of failures and morbidity + link Results: links between DVH parameters and outcome CTV D90 and local control OAR 2 ccm and morbidity Conclusions and limitations

3 D90 (IR CTV) D90 (HR CTV) HR CTV IR CTV D90 (IR CTV) D90 (HR CTV) GTV GTV HR CTV IR CTV GTV, HR CTV, IR CTV and D 90 D90 (IR CTV) D90 (HR CTV) GTV GTV HR CTV IR CTV Tumor at time of diagnosis. D90 (IR CTV) Tumor at time of diagnosis. D90 (HR CTV) GTV GTV IR CTV HR CTV GYN GEC ESTRO Recommendations(II) Radiother Oncol 2006

3D-based Dose Volume Parameters for OAR Sigmoid

endpoint Bladder GTV Rectum FIXED VOLUME: tolerance

tissue * 1cm3/2cm3:teleangiectasia (20 mm x 20 mm x

1 cm3: 3D maximum dose : ulceration(fistula) 2 cm 3

4 3D-based Dose Volume Parameters for OAR Sigmoid CLASSICAL MAX DOSE : in 3D no clinical relevant endpoint Bladder GTV Rectum FIXED VOLUME: tolerance dose (total dose)- minimum dose to the most exposed tissue * 1cm3/2cm3:teleangiectasia (20 mm x 20 mm x 5 mm) 0.1cc 1cc 2cc ICRU 38 Ref. Points 0.1 cm3: 3D maximum dose : ulceration(fistula) 2 cm cm 3 *GYN GEC ESTRO Recommendations(II) Radiother Oncol 2006

5 Linking DVH-parameters to clinical outcome HR CTV and GTV and Recurrence Analysis (n=141, FIGO: IB-IVA, median follow-up=51 months) 145 consecutive patients 523 treatment plans / 608 fractions 141 with MRI assisted cervix cancer brachytherapy 18 local recurrences (18/145: crude 12%) Analysis of recurrence topography and morbidity in 3D relation to HR-CTV and D90 3D Dose-volume-effect relationships Dimopoulos et al. IJROBP 2009

6 Summary dose values HR CTV (EQD2) Mean Gy Intracavitary 1 interstitial patients 3 Prescribed Depending on treatment period HR CTV Vol. 35cm³ 44cm³ 36cm³ (experience, modification of application) HR CTV D D90: 81 Gy (98-00) 90 Gy (01-03) Point A 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

7 Linking DVH-parameters to clinical outcome HR CTV and GTV and Recurrence 3D Analysis of recurrence topography FIGO stage IIB Diagnosis Diagnosis Brachytherapy GTV HR CTV B B B GTV DG GTV DG 84 Gy EQD2 R a b 6 mths after treatment 6 mths after treatment 9 mths after treatment R c C C d e Dimopoulos et al. IJROBP 2009 f

8 Vienna experience 18% 22% 81 Gy vs. 90 Gy in HR CTV Pötter R. et al Radiother Oncol 2007

9 Probability of local control Linking DVH-parameters to clinical outcome HR CTV/Tumour Analysis (n=141, FIGO: IB-IVA, median follow-up=51 months) D90 for the HR-CTV and probability of local control Entire population (n=141) Tumours > 5cm (n=76) D90 HR CTV 90 Gy EQD2 90% probability for local control D90 HR CTV 70 Gy EQD2 65% probability for local control D90 (HR CTV) Dimopoulos et Radioth & Oncol 2010

TREATMENT OUTCOME Continuous Complete Remission True Pelvis 1998-2000

70 83 8 150 95 < 5 cm 1 33 96 1 53 97 >= 5 cm 9 37 71 7 97 94 1998-2000

10 TREATMENT OUTCOME Continuous Complete Remission True Pelvis n events n total 3 year, % n events n total 3 year, % CCR TP < 5 cm >= 5 cm patients All 2-5 cm > 5 cm Evaluation

11 TREATMENT OUTCOME Cancer Specific Survival at 3 years % % 228 patients 0 All 2-5 cm > 5 cm Evaluation

12 Radioth & Oncology 100, 2011 Figure 1 a) b) Vienna : 156 patients Mean D90: 93 Gy, 91 Gy for tumours >5 cm, 96 Gy 2-5 cm c) d)

13 Linking DVH-parameters to clinical outcome morbidity 145 consecutive patients with MRI assisted cervix cancer brachytherapy prospective assessment of morbidity Analysis of morbidity topography in 3D for organs and (n=141, FIGO: IB-IVA, median follow-up=51 months) 523 treatment plans / 608 fractions subgroups 2 ccm organ volume (1 ccm, 0.1 ccm) LENT/ SOMA G1 G2 CR* G1/2 *CR: actuarial complication rate G3 G4 CR* G3/4 Bladder % 1 2 4% 3D Dose-volume- effect relationships Rectum 2 6 9% 2 0 2% P. Georg et al. IJROBP 2011; Sigmoid 0 1 1% 0 2 2%

14 Summary dose values OAR (EQD2) Mean Gy Intracavitary 1 interstitial patients 3 Bladder D 3 2cm ICRU Rectum D 3 2cm ICRU Sigmoid D 2cm Kirisits et al Int J Radiat Oncol Biol Phys Kirisits et al Int J Radiat Oncol Biol Phys Pötter et al Radiother Oncol 2007 treatment period

15 Endoscopic mapping ventral 1,1 1,0 4/4 1/1 p 0,9 0,8 0,7 0,6 0,5 high dose area 0,4 corresponding to 0.1cc 0,3 0,2 Rectum N=141 2/7 5/9 3/6 dorsal D 2cc = 81 Gy EQD 2 D 1cc = 90 Gy EQD 2 D 0.1cc = 108 Gy EQD 2 0,1-0/4 0/ D2cc Georg et al. IJROBP 2011

16 Incidence VRS > Koom et al. IJROBP D2 ccm D1 ccm D0.1 ccm DICRU Dose volume effects for rectal morbidity applying GEC ESTRO recommendations N = 35 patients with rectosigmoidoscopy 100 Incidence LENT/SOMA > VRS: Vienna Rectoscopy Score Clinical late Effects LENT SOMA score Dose [Gy] P. Georg et al. Radioth&Oncol 2009

17 Dose Volume Effect for sigmoid for 2 ccm (?) 1 0,9 0,8 Sigma N=141 0,7 P 0,6 0,5 0,4 0,3 0,2 2/10 Topographical interfractional changes 0,1 1/28 0/11 4 0/2 0/1 0/9 0/7 0/15 0/22 0/24 0/10 0/ D2cc (Sigmoid) In addition: No clear correlation in endoscopy study VS score Patients (2007) Sturdza et al. Boston 2008 mean VS common observation

$Uncertainties in assessing sigmoid DVH parameters Assessment of sigmoid topography changes between HDR-brachytherapy fractions Is the worst case assumption valid for the sigmoid colon?$

18 Uncertainties in assessing sigmoid DVH parameters Assessment of sigmoid topography changes between HDR-brachytherapy fractions Is the worst case assumption valid for the sigmoid colon? Results 23/44 common observations between observers Easy to find or obvious change (score=3-4) in sigmoid topography between fractions in 15/22 (68%) significant movement Difficult to find or no change (score=1-2) in remaining little or no movement Sturdza et al. Boston 2008

Linking DVH-parameters to outcome Bladder - evaluation for 34 patients with D 2 ccm > 90 Gy Bladder wall(bw) Position P = 0.

19 Linking DVH-parameters to outcome Bladder - evaluation for 34 patients with D 2 ccm > 90 Gy Bladder wall(bw) Position P = Low bw Medium bw With Side effect 10 3 No Side effect 6 15 Arie et al./berger et al., Vienna 2008/10 Weak overall dose volume effect for all patients, e.g. 2 ccm (Georg et al. 2010, in press) Bladder D2cm3 100 Gy >100 Gy G1-G4 13% (12/94) 17% (8/47)

20 Vaginal dose assessment and reporting DVH parameters have HIGH uncertainty for representative vaginal dose estimation They are influenced by the resolution of sectional imaging, contouring accuracy and applicator reconstruction Berger et al, IJROBP 2007

ACTUARIAL LATE SIDE EFFECTS (LENT/SOMA) G1 / G2 n=145 G1/G2= 114 G3/G4= 5 G3 / G4 0,0 20,0 40,0 60,0

21 LENT SOMA 1 or 2 Vaginal morbidity was not (significantly) correlated to any DVH-parameters which were applied in 3D MRI-based cervical cancer brachytherapy percent 1,0 0,8 0,6 0,4 fibrosis bleeding 0,2 0,0 ACTUARIAL LATE SIDE EFFECTS (LENT/SOMA) G1 / G2 n=145 G1/G2= 114 G3/G4= 5 G3 / G4 0,0 20,0 40,0 60,0 80,0 100,0 months after RT shortening Upper vagina teleangiectasia Fidarova et al. Radioth&Oncol in press 2010

22 CONCLUSIONS AND LIMITATIONS Linking DVH parameters to clinical outcome D90 HR CTV and local control: 2 ccm for rectal morbidity: strong link strong link 2 ccm for bladder morbidity: weak link improvement by location assessment? 2 ccm for sigmoid morbidity: weak link improvement by movement assessment? Any parameter for vaginal morbidiy: no link within a given institutional system improvement by point doses and length (volume) Limitations: limited numbers, no prospective studies

Image guided brachytherapy in cervical cancer Clinical Aspects

Image guided brachytherapy in cervical cancer Clinical Aspects Richard Pötter MD Department of Radiation Oncology, Medical University of Vienna, Austria ICARO-2, IAEA, Vienna, June, 22, 2017 Outline Tumor