1. Outcome of patients treated with Image Guided Brachytherapy for Locally Advanced Carcinoma of the Cervix at Royal Devon & Exeter Hospital 2010- 2015 Dr Jenny Forrest Clinical Oncologist RD&E Jennifer.Forrest1@nhs.net

2. Overview Image Guided Brachytherapy for Cervical Cancer Introduction Combined intra-cavity and interstitial Brachytherapy International & RD&E Experience and outcome

3. Image Guided Brachytherapy Ca Cervix Background Standard RX: EBRT + Cisplatin + Brachytherapy (BT) Brachytherapy crucial for cure of cervix cancer Place an intra-uterine tube and 2 ovoids / ring in vagina under GA Standard technique Standard doses Prescribed to fixed point Standard plans Plain x-ray imaging 2005 European Brachytherapy Society (GEC-ESTRO) published recommendations for image guided brachytherapy (IGBT) Endorsed by American Brachytherapy Society (ABS) 2009 RCR Guidelines re implementation IGBT over next 5 years

4. RCR Guidelines 2009: Benefits IGBT Accurate verification of applicator position 3-D imaging (CT/MRI/USS) should be routinely used to verify applicator position within the uterine canal Accurate definition of normal tissue dosimetry Reporting of OAR point doses minimum requirement, DVH recommended Opportunity for conformal dose distributions to tumour volume and OAR IGBT improved local control and reduced toxicity Opportunity for dose escalation Dose escalation with MRI based IGBT improved local control without increased toxicity should be implemented as soon as reasonable achievable

5. Utrecht / Vienna Applicators MRI / CT Compatible Needles

6. Bladder full Bladder empty UT USS to guide insertion and reduce risk of perforation

7. / / dd/mm/yy Signature w = __ _ cm h = __ _ cm t = __ _ cm Vagina Involveme nt = _ _ cm h t w Infiltrativ e Exophyti c Cervix Vagina Parametria Rectum or Bladder Clinical Drawing Patient: EBRT Gy At Brachytherapy At Diagnosis

8. MRI at Brachytherapy

9. MRI plan

10. CT plan

11. RCR AUDIT 2011 Brachytherapy N=20658% IGBT Dose RateNumber Patients HDR15575% Brachytherapy Planning X-Ray7536% MRI (at least one fraction)4421% CT (all fractions)7637% Unknown115%

12. RCR Audit Cervix Cancer: Results – Total Dose MDR Standard:EQD2 should be at least 75Gy = 83% Median 76.7 (Inter-quartile Range 70.9-79.6)

13. RCR Audit Cervix Cancer: Results – Total Dose HDR Standard:EQD2 should be at least 75Gy = 27% Median 72.1 (Inter-quartile Range 69.4 -75.8)

14. IGBT

15. The use of interstitial needles

16. International Clinical Evidence: Single Institution Series Vienna Experience (Potter2011): N=156 45-50.4Gy plus 4 x7Gy HDR Brachytherapy High Risk CTV D90>85Gy 44%interstitial needles, 66% >5cm tumours, 48% N+ D2cc max rectum/sigmoid 70-75Gy. Bladder 90Gy Local control at 3 years 95% (98% 2-5cm, 92% >5cm) Overall survival @ 3yrs 68% Cancer Specific Survival @ 3yrs74% 74% IB 78% IIB 45% IIIB G3/4 Toxicity 10-15%reduced to <5% Also Aarhus/ Leiden/ Addenbrookes

17. Multicentre Retrospective Study: RetroEmbrace 652 patient 610 full data EBRT mainly 45Gy in 25# 75% Concurrent cisplatin HDR 58% PDR 40% LDR 1% 25% needles Pelvic Failure 1B 8%2B 15%3B 32% Overall Survivial @5yrs67% (Vale 55% US SEER 58%)

18. Current Guidelines: Embrace 2 EBRT 45Gyin 25# Risk adapted IGBT Aim D90>90Gy D2cc rectum /sigmoid < 70Gy (<65Gy) D2cc bladder <90Gy (<80Gy) Vaginal dose

19. Exeter Results: Dose & Outcome 201020112012201320142015 Total number of Patients 1618212016 15 Recurrence Number (%) 8 (50%)5 (28%)6 (28%)4 (20%)4 (25%) Overall Survival (%) 7 (44%)13 (72%)17 (81%)19 (95%)12 (75%) Local recurrence 11001 Mean HRV size cc (range) 37.6cc (13-60) 24.7cc (10-91) 20.3cc (10-63) 22.5cc (10-59) 33.9cc (7-100) 28.2cc (12-63) Mean Dose: EQD2 D90 (range) 70.5 Gy (61-89) 84.2 Gy (74-110) 88.7 Gy (63-110) 91.9 Gy (72-144) 86.7Gy (63-131) 87.3Gy (66-99) Current Aim 85-95Gy

21. RD&E 2-d 2005-10 RD&E 3-d 2011-14 Vienna 3-d Toronto 2-d 2003-7 Dose EQD2 74Gy85-90Gy 85Gy N3975145122 OS DSS 44% 55% 81% 75% 64% 74% 70% 75% Pelvic Recurrence 30%5%10%14% Toxicity11%<10%5%11% Comparison of Outcomes

22. Conclusions Advances in radiotherapy and brachytherapy techniques have led to a significant improvement in survival and reduction in recurrence for patients with locally advanced cancer cervix with a reduction in toxcity An update to the RCR brachytherapy guidelines 2009 is underway.

23. Acknowledgements Peter Bliss Dorothy Ingham Jo Bostock Jackie Clarke and RCR audit committee John Mc Grane Liz Lim