LCA Breast Pathway Clinical Forum 10 th March 2015
Survivorship issues following breast radiotherapy Dr Anna Kirby Consultant Clinical Oncologist Royal Marsden Hospital
3 Post-RT survivorship issues Radiotherapy tattoos Skin changes (acute and late) Breast oedema Post-treatment dip Effects on the reconstructed breast Arm lymphoedema Shoulder stiffness Late cardiac effects Second malignancies
4 Post-RT survivorship issues Radiotherapy tattoos Skin changes (acute and late) Breast oedema Post-treatment dip Effects on the reconstructed breast Arm lymphoedema Shoulder stiffness Late cardiac effects Second malignancies
5 Post-RT survivorship issues Radiotherapy tattoos Skin changes (acute and late) Breast oedema Post-treatment dip Effects on the reconstructed breast Arm lymphoedema Shoulder stiffness Late cardiac effects Second malignancies
6 Post-RT survivorship issues Radiotherapy tattoos Skin changes (acute and late) Breast oedema Post-treatment dip Effects on the reconstructed breast Arm lymphoedema Shoulder stiffness Late cardiac effects Second malignancies
7 Post-RT survivorship issues Radiotherapy tattoos Skin changes (acute and late) Breast oedema Post-treatment dip Effects on the reconstructed breast Arm lymphoedema Shoulder stiffness Late cardiac effects Second malignancies
8 Post-RT survivorship issues Radiotherapy tattoos Skin changes (acute and late) Breast oedema Post-treatment dip Effects on the reconstructed breast Arm lymphoedema Shoulder stiffness Late cardiac effects Second malignancies
9 Post-RT survivorship issues Radiotherapy tattoos Skin changes (acute and late) Breast oedema Post-treatment dip Effects on the reconstructed breast Arm lymphoedema Shoulder stiffness Late cardiac effects Second malignancies
Radiotherapy tattoos: what s the issue?
11 BRITER 14/3/2014.. they are too visible and I mind them more now than I did at the time, cracking jokes about joining them up etc. Tired of the jokes; tired of them looking like wee bits of dirt - or blackheads I would rather have had the choice about telling people rather than have it advertised on my chest when I do see them [RT tattoos] they remind me of my treatment which I could do without Courtesy: Steve Landeg
12 How can we improve patient experience? Change the colour of the ink Pen marks and tegaderm Semi-permanent tattoo materials Use ink that is only visible in ultraviolet light
13 Invisible tattoos Ultraviolet (UV) responsive fluorescent tattoo ink Invisible under normal lighting Stable Hypoallergenic Courtesy: Steve Landeg
14 Pilot work Courtesy: Steve Landeg
15 The BRITER Study: Breast Radiotherapy: Invisible Tattoos for External References Single centre 46 patients Fluorescent tattoos Dark ink tattoos Primary endpoint: Inter-fraction Reproducibility Hypothesis: Random errors in patients positioned using fluorescent tattoos will not be inferior to those using dark ink tattoos
16 BRITER 14/3/2014 Secondary endpoints: Patient body image (using Body Image Scale questionnaire) Visibility in dark skin tone (Radiographer Satisfaction Scores by group as defined by Chromatic Scale) White European [1] East Asian [2] Sub-Saharan [3] Courtesy: Steve Landeg
17 BRITER 14/3/2014 Timeline T: 0 T:6 months Pre Tx Treatment BIS RSQ EPI BIS: Body Image Scale Questionnaire RSQ:Radiographer Satisfaction Questionnaire EPI:Electronic Portal imaging Courtesy: Steve Landeg
18 Change Presentation title and date in Footer dd.mm.yyyy Results: Patient characteristics Average age 57 (age 30-69) Skin tone category Fluorescent tattoos Dark ink tattoos White European [1] 16 13 East-Asian [2] 5 5 Subsaharan [3] 2 4 Total 23 22
19 Results: Primary endpoint No significant difference in systematic or random set-up errors in either AP or CC directions (random errors <2.8mm across whole population) (sig. 0.001; sig. 0.009 respectively) Courtesy: Steve Landeg
20 Body Image Scale Scores Courtesy: Steve Landeg
21 Change in BIS scores from pre-rt to post-rt. Courtesy: Steve Landeg
22 BRITER 14/3/2014 Patient comments I am glad my tattoos will only be visible under special lights & I will be able to complete my radiotherapy with no lasting signs I feel much better without tattoos being visible. Much more confident Courtesy: Steve Landeg
23 BRITER 14/3/2014 Visibility in dark skin tone Courtesy: Steve Landeg
24 Summary BRITER 14/3/2014 Clinically acceptable inter-fraction reproducibility Suitability for sub-saharan skin-tone remains inconclusive Patients feel better without dark ink tattoos Fluorescent tattoos offer patient choice and the potential to ameliorate cosmetic and psychological concerns associated with conventional radiotherapy tattoos
25 Cardiac-Sparing Breast Radiotherapy Why? Risks of standard adjuvant breast radiotherapy Potential benefits of heart-sparing breast radiotherapy How? Cardiac-sparing techniques, research findings to date (HeartSpare Trial) From research to implementation Translation into day-to-day practice Ongoing work Combining heart-sparing RT and new technologies in locoregional RT
RT after BCS reduces recurrence rates and improves survival Early Breast Cancer Trialists Collaborative Group, Lancet, 2011
but increases non-breast-ca mortality Early Breast Cancer Trialists Collaborative Group, Lancet, 2005
Cardiac doses from breast RT are falling 25 20 15 10 Mean heart dose (Gy) Mean LAD dose (Gy) 5 0 1970s 1990s 2006 Taylor et al, 2007 & 2008
29 Quantifying the dose-effect relationship No lower threshold Darby et al, NEJM, 2013
What dose reductions are achievable using cardiac-sparing breast RT? 25 20 15 10 5 0 2.4Gy 0.8Gy 1970s 1990s 2006 2010 (Breathhold) Mean heart dose (Gy) Mean LAD dose (Gy) Vikstrom 2011, RMH service evaluation 2012
Potential benefit of heart-sparing breast RT for an individual patient 50-year old woman Irradiated for left breast cancer No cardiac risk factors Mean heart dose reduced from 2.4Gy to 0.8Gy Heart-sparing breast radiotherapy reduces risk of a radiation-related cardiac event from 1% to 0.3%.
More women are surviving breast cancer By year 2040: 1.7 million UK breast cancer survivors Age-standardised incidence of and mortality from female breast cancer, England, 1971-2004
Potential population benefits of heartsparing breast RT Small risk reduction large number of patients = large population benefit Assuming: 1.7 million breast cancer survivors in 2040 Mean heart doses reduced from 3Gy to 1Gy Number of radiation-related acute coronary events reduced from around 20,000 to 6000 Number of IHD deaths from 9000 to 2000 Bartlett, Yarnold & Kirby, Clin Onc, 2013
34 Heart-Sparing Breast RT techniques MLC MLC IMRT Prone
35 Prone position benefits larger-breasted women N=65 260 plans Median cup size C (range A-G) Kirby et al, Rad & Onc, 2010
36 But is difficult to reproduce N=25 Crossover design Median cup-size D (range C-G) Kirby et al, Rad & Onc, 2011
Treatment in breath-hold Normal breathing Breath hold
Breath-hold techniques Active breathing controlled breath-hold Real-time positioning monitored breath-hold
39 The voluntary breath-hold technique
Number of cases Use of heart-sparing breast RT in UK in 2012 200 180 160 140 49% *Respondents could give more than one answer Total cases answering yes to Heart in Field n=377 RCR Breast Audit 120 100 80 60 40 20 0 No Cardiac Sparing Cardiac Shielding with MLC Compromise of WB_CTV Gating of Treatment 4% Treatment in Breath Hold Local Policy Not Known EORTC Survey 2008: 20% of European institutions Courtesy: using breath-holding Dr Imogen Locke techniques
The UK HeartSpare Study: Objectives IA: IB: II: To optimise breath-hold technique To individualise heart-sparing breast RT in larger-breasted women To make heart-sparing radiotherapy available to all left-breast affected women in UK Funded by NIHR Research for Patient Benefit Programme
42 HeartSpare Study IA ABC_DIBH N=23 Randomised crossover design ABC V vs V ABC v_dibh Endpoints Primary Secondary Interfraction reproducibility (electronic portal imaging) Normal tissue doses (heart, LAD, lungs) Interfraction reproducibility (cone-beam CT) Intrafraction reproducibility (cine-loop) Patient comfort Radiographer satisfaction Time & cost
43 HeartSpare IA: Results Mean errors (mm) n = 23 ABC Voluntary p FB Systematic 1.9 2.0 1.5 1.8 0.52 2.2-4.7 Random 2.0 2.4 1.7 2.5 0.74 1.7-5.8 ABC Voluntary p Heart NTD mean (Gy) 0.6 (0.2) 0.6 (0.1) 0.45 LAD NTD mean (Gy) 3.8 (2.9) 3.5 (2.3) 0.09 LAD max (Gy) 32.6 (11.5) 30.6 (12.4) 0.09 Ipsilateral lung NTD mean (Gy) 4.2 (0.7) 4.2 (0.7) 0.50 Whole lungs NTD mean (Gy) 2.0 (0.3) 2.0 (0.3) 0.27 Chest wall V 20Gy (cm 3 ) 222.8 (63.5) 223.2 (64.3) 0.66 Standard deviations in brackets
44 HeartSpare IA: Results Free breathing ABC_DIBH v_dibh Bartlett et al, Rad & Onc, 2013
45 HeartSpare IA: Time & satisfaction Timings 14 Questionnaires 12 10 8 Time (mins) 6 4 n ABC preferred VBH preferred 2 No preference 0 Pts Rads
46 HeartSpare IA: Costs ABC costs Device: 49,500 (+vat) Mouthpieces: 100/patient Linac time (mins)
Voluntary deep-inspiratory breath-hold (V-DIBH) is as reproducible as ABC-DIBH spares heart to the same extent as ABC-DIBH is better tolerated by patients takes less time at scanning and less time to set up is less expensive to implement
HeartSpare 1B: v_dibh versus prone N=34 ( D cup) Randomised crossover design VBH Prone Prone VBH
49 HeartSpare IB: Endpoints Primary: Difference in mean LAD NTD mean (Gy) Secondary: Heart, lung & contralateral breast doses Interfraction reproducibility (EPI & CBCT) Patient comfort Radiographer satisfaction Time
50 HeartSpare IB: Normal tissue data analysis n = 28 Prone (Gy) VBH (Gy) p Heart NTD mean 0.66 [0.61-0.71] 0.44 [0.38-0.51] <0.001 LAD NTD mean 7.8 [6.4-9.2] 2.9 [1.8-3.9] <0.001 LAD max 36.8 [35.2-38.4] 21.0 [15.8-26.2] <0.001 Left lung NTD mean 0.34 [0.27-0.42] 3.73 [3.42-4.04] <0.001 Whole lungs NTD mean 0.20 [0.16-0.24] 1.81 [1.65-1.97] <0.001 Mean doses with 95% confidence intervals in brackets Baseline RM doses (for comparison): Heart NTD mean 0.8 (0.3) Gy LAD NTD mean 6.7 (4.3) Gy LAD max 40.3 (10.1) Gy Courtesy: Dr F Bartlett
51 HeartSpare IB: Heart falls forward in prone position Prone VBH Courtesy: Dr F Bartlett
52 HeartSpare IB: CBCT analysis Clip-based match (mm) Prone VBH Systematic 5.2 6.5 1.9 2.0 Random 4.5 5.4 2.0 2.4 Total 174 CBCTs (86 prone, 88 VBH) 3/28 patients could not complete prone RT Courtesy: Dr F Bartlett
53 HeartSpare IB: Conclusions Conclusions: 1. Better heart-sparing with VBH 2. VBH more reproducible 3. Shorter treatment session times with VBH 4. Patients find VBH more comfortable 5. Prone feasible with CBCT-based correction protocol Bartlett et al, Rad Onc 2014
HeartSpare II: Multicentre Trial Is VBH in other people s hands still heartsparing & reproducible? 2.4Gy 2.7Gy 3.2Gy Aim: To increase UK use of heart-sparing RT through trial participation 15 Fractions (3 weeks) Non-randomised VBH 10 FF centres N=101 (closed Oct 2014)
From research to implementation Local service implementation RM Sutton- Lower left breast cancers Transfer of VBH technique to different platforms RM Chelsea- Selection based on free-breathing CT
From research to implementation National: Direct effect of HeartSpare II on participating 2.4Gy centres 2.7Gy 3.2Gy 6/10 HeartSpare II centres have implemented VBH into routine practice 15 Fractions (3 weeks)
From research to implementation 2.4Gy 2.7Gy 3.2Gy 34 UK centres trained in breath-holding techniques 15 Fractions (3 weeks)
From research to implementation 2.4Gy International 2.7Gy 3.2Gy 15 Fractions (3 weeks)
From research to implementation Video publication: Journal of Visual Experimentation http://www.jove.com/video/51578/voluntary-breath-hold-technique-for-reducing-heart-dose-left-breast
Future work: HeartSpare-Plus 25 20 15 10 5 Mean heart dose (Gy) Mean LAD dose (Gy) 0 1970s 1990s 2006 2010 (VBH) 2010 (incl LNs) Taylor et al, 2007 & 2008, Hjelstuen 2012
The challenge of treating the internal mammary chain
Volumetric-modulated arc therapy
63 HeartSpare-Plus (HS-Plus) Anticipates use of IMC RT HS-Plus IA combines use of breath-hold with complex RT techniques (incl arc therapies) with a view to identifying optimal techniques to treat IMC HS-Plus IB is a nonrandomised phase II testing resource requirements & acute toxicities of new techniques
Conclusions We can improve cosmetic outcomes in breast cancer survivors by adopting innovative solutions for radiotherapy mark-up We can improve late outcomes in breast cancer survivors by adopting heart-sparing RT techniques National use of heart-sparing breast RT techniques is increasing and is a pre-requisite to treating internal mammary chain
Acknowledgements National Institute for Health Research Research for Patient Benefit Grant (HS) NIHR funding to RM/ICR Biomedical Research Centre (BRITER & HS) The HeartSpare Working Group The BRITER Working Group RM Radiographers Independent Cancer Patients Voice