1. This house believes that routine 3D planning and treatment of breasts should be mandatory Proposing the Motion

2. Overview Dosimetric benefits Normal / critical tissues Comparison with prostates Costs

3. Dosimetric Benefits Central axis image of 2D planned breast All is well!

4. Dosimetric Benefits Inferior image of 2D planned breast Hotspots galore Coronary Artery! High lung dose

5. Dosimetric Benefits Superior image of 2D planned breast Very hot indeed! Brachial Plexus

6. Critical Structures Left Anterior Descending Coronary Artery – Potential cause of increased mortality post-RT – Radiotherapy reduces breast cancer mortality by 13% but increases annual mortality rate from other causes by 21% (EBCTCG 2000) Lung – Fibrosis Brachial Plexus – Largely ignored

7. Cardiac Time Bomb Increasing use of adjuvant cardio-toxic drugs Taxanes Anthracyclines Trastuzumab 3D planning can reduce heart doses – 90% of patients had improved heart V 30 and V 47.5 – (Fong 2009) Mortality rate can be reduced – Probability of death reduced from 6% to 0.25% by IMRT – (Lohr 2009)

8. Other Structures Breast Tissue Reduced hotspots – 2D: 15% received >105% to over 20% of breast – IMRT: 1% received >105% to over 10% of breast – (Donovan 2007) Improved acute side effects with IMRT – Radiation dermatitis – (Pignol 2010) Lung Tissue Reduced ipsilateral lung dose – 4.9–5 Gy (IMRT) – 5.6 Gy (standard) – (Pignol 2010)

9. Vote for Bridge

10. Its not all about the Prostate

11. In the Blue Corner… Prostate 25% of male tumours Improvements: – 3DCRT plans standard for many years in UK – Some IMRT, ART, protons – Some IGRT / seeds Risks associated: – Rectal morbidity – Impotence

12. In the Pink Corner… Breast 31% of female tumours Improvements: – Some CT planning – Some routine IMRT ongoing – Some studies on respiration Risks associated: – Fibrosis of lung – Increased mortality (LAD dose)

13. Potential Costs and Myths Increased time demands is a common myth – Similar planning and delivery times (Fong 2009, Pignol 2010) Side effects cost – Acute effects reduced – Long term cardiac sparing (15 years later) – Reduced incidence of recurrence

14. Summary Potential for large improvement in: – Mortality rate – Acute side effects – Chronic side effects 3D breast planning is routine in some centres Why should 3DCRT be standard practice for prostates and not for breasts?

15. Vote for Bridge

16. References Donovan E, Bleakley N, Denholm E, Evans P, Gothard L, Hanson J, Peckitt C, Reisea, Ross S, Sharp G, Symonds-Tayler R, Tait D, Yarnold J. 2007. Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy. Radiother Oncol; 82: 254–264 Early Breast Cancer Trialists' Collaborative Group. 2000. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet; 355: 1757-1770 Fong A, Bromley R, Beat M, Vien D, Dineley J, Morgan G. 2009. Dosimetric comparison of intensity modulated radiotherapy techniques and standard wedged tangents for whole breast radiotherapy. J Med Im Rad Onc; 53(1): 92–99 Lohr F, El-Haddad M, Dobler B, Grau R, Wertz HJ, Kraus-Tiefenbacher U, Steil V, Madyan YA, Wenz F. 2009. Potential effect of robust and simple IMRT approach for left-sided breast cancer on cardiac mortality. Int J Radiat Oncol Biol Phys; 74(1):73-80 Pignol JP, Olivotto I. 2010. Breast Intensity-Modulated Radiation Therapy to Reduce Radiation Dermatitis. Eur J Clin Med Onc; 2 (2): 93-100

17. 'This house believes that routine 3D planning and treatment of breast cancer should be mandatory' Dr Heidi Probst Sheffield Hallam University

18. 2D – usually single slice planned (may have 3 slices produced with dosimetry information),generally standard tangential opposing (or slightly tilted) beams with wedge modification. 3D conformal RT- Full 3D planning data set with optimisation through manual iterative process to select beam angles, and beam shapes but with uniform beam intensities or if wedges are used monotonically variable in one dimension. Let’s be clear about what is meant by 3D conformal RT

19. Does 3D conformal RT improve survival? X Does 3D conformal RT improve local control? X Does 3D conformal RT reduce normal tissue toxicity? Maybe? Does 3D conformal RT increase resource use? √ Are all centres in the UK capable of undertaking a 3D conformal approach for all adjuvant breast X irradiation? Why do I think 3D conformal shouldn’t be madatory?

20. 5-year Survival (across all ages in England) has increased by 12% for the 10 year period ‘91-’93 and 2001-2003- 5 year relative survival now in the region of 80% (National Cancer statistics). EBCTCG report 1995 reported an increased risk of death from non-cancer related causes for breast cancer patients treated with post operative radiotherapy. survival disadvantages from postoperative radiotherapy are less obvious in studies after the 1970’s Survival

21. Wide Local excision + RT- relapse rate ≈ 03.- 10% at 5 years Mastectomy + RT- relapse rate 9-11.5% at 5 years EBCTCG Report 2005 local recurrence rates following WLE +RT = 7% (includes trials published from 1976- 1991) Local Control

22. The associated lateral scatter of orthovoltage energies, used up to the late 1970’s, has been implicated in increasing the risk of cardiac related injury. It is considered that the left anterior descending coronary artery receives a substantial radiation dose because it lies close to or within the target volume. Reducing Normal Tissue Toxicity

23. How often are critical volumes of heart included in the chest-wall tangents? In an electronic portal imaging study of 169 women with left- sided breast tumours receiving tangential field irradiation, only 9% of women were identified as including the cardiac apex Simple techniques can reduce the dose to the heart- arm position (Canney et al) –reducing mean heart dose by 60% p<0.001). Reducing Normal Tissue Toxicity

24. Inverse relationship between beam tangent angle and heart dose- changing the gantry angle of the tangents can reduce volume of heart- in 80% of women studied % of irradiated heart volume was <3% (Das et al). Better technology doesn’t automatically translate into better outcomes despite planning studies demonstrating dosimetry improvements Very few RCTs in Radiotherapy comparing 2D vs 3D CRT Reducing Normal Tissue Toxicity

25. Lessons from early stage cervix- 3D planning not associated with better relapse free survival or grade 3-5 toxicity (Galloway et al 2010) RCT (Elmesidy et al 2009, n=60) 3D conformal did not improve locoregional recurrence, survival or toxicity (although FU ≈ 2.5 years) pts that received 3D conformal had less reduction in cardiac ejection fraction than those that received 2D planning, however volume included IMN. Evidence that 3D results in better outcomes than 2D

26. If using 3D conformal approach is about optimising dosimetry what do the comparative studies comparing 2D vs IMRT tell us? IMRT can reduce incidence of moist desquamation (Pignol et al 2008, Harsolia et al 2007). Reducing Normal Tissue Toxicity

27. IMRT2D Pignol et al 200827.1%36.7% Fernando et al31.5% Moist Desquamation 2D vs IMRT Pignol et al 2008 -Skin toxicity- grade 3-4 NCI Common Toxicity criteria (v2) Fernando et al 1996- Moderate to severe skin toxicity- Marked erythema with between 5% and 10% desquamation (dry or moist), Dry or moist desquamation in >10% of field; treatment gap required due to skin reaction; incomplete healing 1 month post-treatment P>0.05

28. Moody et al (1994)

29. Japanese for ‘unusual tool’, often described as unuseless as they are developed to solve a particular problem but often create many more new problems. Chindogu

30. As you increase treatment complexity with 3D conformal there is a need for improved patient positioning and reproducibility. Treatment machine costs are considered to account for only 40% of a patient’s radiotherapy experience, with clinical assessment, preparation and follow-up consuming most of the resources. Costs analysis for prostate comparing conventional with conformal RT has shown a 2.5 increase in costs. Complexities of using 3D conformal

31. The UK is in the worst recession since 1945

33. Conformal RT for prostate has been about the opportunity to dose escalate in an effort to increase survival benefit. For breast cancer this isn’t the case, treatment refinements are about improving the therapeutic ratio and enhancing QoL for survivors. Comparing Breast with Prostate

34. Should 3D conformal RT be mandatory for all adjuvant breast cancer cases? 1.Can’t be mandatory as some centres would no longer be able to treat breast cases or no longer be able to treat the volume of cases currently treated. 2.Insufficient research evidence to support outcome improvements for 3D over 2D approaches – although evidence exists to suggest IMRT is beneficial specifically in patients with larger breasts. 3.Movement to 3D CRT or IMRT should only be considered in conjunction with set up procedures that allow greater immobilisation of breast tissue to ensure adequate reproducibility. Finally….

35. 3D conformal or IMRT should be used where resources allow, or in those cases where a significant improvement in outcome can be predicted with the more complex approaches. At the moment the only possible vote must be against mandatory 3D conformal How to vote…

36. References Early Breast Cancer Trialists Collaborative Group. Effects of radiotherapy and surgery in early breast cancer: an overview of the randomised trials. N Engl J Med 1995;33:1444e1455. Hojris I, Overgaard M, Christensen JJ, Overgaard J. Morbidity and mortality of ischaemic heart disease in high-risk breast cancer patients after adjuvant post mastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Lancet 1999;354:1425e1430. Magee B, Coyle C, Kirby M, Kane B, Williams P. Use of electronic portal imaging to assess cardiac irradiation in breast radiotherapy. Clin Oncol 1997;9:259e261. Das IJ, Cheng EC, Freedman G, Fowble B. Lung and heart dose volume analysis with CT simulator in radiation treatment ofbreast cancer. Int J Radiat Oncol Biol Phys 1998;42:11-19. Fisher B, Anderson M, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow up in a randomised clinical trial comparing total mastctomy with lumpectomy with or without irradiation in the treatment of breast cancer. The New England Journal of Medicine 36, 1456. 1995. Rutqvist LE, Ingmar L, Fonander T, Johansen H. Cardiovascular mortality in a randomised trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. Int J Rad Oncol Biol Physics 1992; 22:887-896 Delaney G, Blakey D, Drummond R, Kenny L, Centre RO. Breast radiotherapy: an Australasian survey of current treatment techniques. Australas Radiol 2001; 45(2):170-178. Dunscombe P, Roberts G, Walker J. The cost of radiotherapy as a function of facility size and hours of operation. British Journal of Radiology 1999; 72(598):603. Poon I, Pintilie M, Potvin M, McGowan T. The changing costs of radiation treatment for early prostate cancer in Ontario: a comparison between conventional and conformal external beam radiotherapy. Can J Urol 2004; 11(1):2125-2132.

37. Fernando IN, Ford HT, Powles TJ, Ashley S, Glees JP, Torr M et al. Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: A prospective study of treatment practice at the Royal Marsden Hospital. Clinical Oncology 1996; 8:226-233. Harsolia A, Kestin L, Grills I, Wallace M, Jolly S, Jones C et al. Intensity-modulated radiotherapy results in significant decrease in clinical toxicities compared with conventional wedge-based breast radiotherapy. Int J Radiat Oncol Biol Phys 2007; 68(5):1375-1380. Pignol JP, Olivotto I, Rakovitch E, Gardner S, Sixel K, Beckham W et al. A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol 2008; 26(13):2085-2092. Moody AM, Mayles WP, Bliss JM, A'Hern RP, Owen JR, Regan J et al. The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity. Radiother Oncol 1994; 33(2):106-112. Cho BCJ, Schwarz M, Mijnheer BJ, Bartelink H. Simplified intensity-modulated radiotherapy using pre-defined segments to reduce cardiac complications in left-sided breast cancer. Radiotherapy and Oncology 2004; 70(3):231-241. References continued