Philip Poortmans, MD, PhD
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2 Past President President Elect Philip Poortmans, MD, PhD 2
3 To treat or not IMN: Balancing Risks and Benefits 3
4 Conflict of interest: I am a radiation oncologist 4
5 To treat or not to treat the IMN 1. Introduction 2. The recent trials 3. Technical improvements 4. Discussion 5. Conclusions 5
6 To treat or not to treat the IMN: Introduction EBCTCG. Lancet. 2014;383:
7 To treat or not to treat the IMN: Introduction Interpretation: RT reduced both recurrence and breast cancer mortality in women with positive lymph nodes. Similar effects: Irrespective of the number of involved lymph nodes Whether systemic therapy was given or not More benefit after partial or no AD Less benefit if only regional RT EBCTCG Lancet 2011; 378: & 2014;383:
8 To treat or not to treat the IMN: Introduction Darby S et al. NEJM 2013:368:
9 To treat or not to treat the IMN: Introduction Non-anthracycline (CMF) ChT RT + ChT RT No RT Risk of congestive heart failure Poortmans P, et al. N Engl J Med 2015;373:
10 To treat or not to treat the IMN: Introduction Reduction of the dose to the cardiac structures with tangential field irradiation (left breast) Year Heart Left anterior descending artery Mean dose (Gy) Right coronary artery Circumflex coronary artery Sweden s* Sweden s* UK Taylor et al. IJROBP 2007, IJROBP 2008, R&O
11 To treat or not to treat the IMN 1. Introduction 2. The recent trials 3. Technical improvements 4. Discussion 5. Conclusions 11
12 To treat or not to treat the IMN: Recent trials Poortmans P, et al. N Engl J Med 2015;373:
13 To treat or not to treat the IMN: Recent trials Whelan T, et al. N Engl J Med 2015;373:
14 To treat or not to treat the IMN: Recent trials Thorsen LB, et al. J Clin Oncol. 2016;34:
15 To treat or not to treat the IMN: Recent trials Disease free survival at 10 years: Improved with regional irradiation Distant metastases free survival at 10 years: Improved with regional irradiation Overall survival at 10 years: Overall trend towards improvement with regional irradiation Breast cancer specific survival at 10 years: Improved with regional irradiation Late side effects at 10 years following regional RT: Pulmonary and skin Limited; most often grade 2; some transient No increased lethal toxicity 15
16 To treat or not to treat the IMN: Recent trials Disease free survival at 10 years: Improved with regional irradiation Distant metastases free survival at 10 years: Improved with regional irradiation Overall survival at 10 years: Overall trend towards improvement with regional irradiation Breast cancer specific survival at 10 years: Improved with regional irradiation Late side effects at 10 years following regional RT: Pulmonary and skin Limited; most often grade 2; some transient No increased lethal toxicity 16
17 To treat or not to treat the IMN: Recent trials Disease free survival at 10 years: Improved with regional irradiation Distant metastases free survival at 10 years: Improved with regional irradiation Overall survival at 10 years: Overall trend towards improvement with regional irradiation Breast cancer specific survival at 10 years: Improved with regional irradiation Late side effects at 10 y following regional RT: Pulmonary and skin Limited; most often grade 2; some transient No increased lethal toxicity 17
18 To treat or not to treat the IMN: Recent trials 18
19 To treat or not to treat the IMN: Recent trials Overall survival + 1,6% Poortmans P, et al. N Engl J Med 2015;373:
20 To treat or not to treat the IMN: Recent trials Overall survival + 13 months DFS + 16,5 months Poortmans P, et al. N Engl J Med 2015;373:
21 To treat or not to treat the IMN: Recent trials But whom to select for regional RT? 21
22 To treat or not to treat the IMN 1. Introduction 2. The recent trials 3. Technical improvements 4. Discussion 5. Conclusions 22
23 To treat or not to treat the IMN: Techniques Breast Boost PBI Thoracic wall LN supraclavicular LN axilla level III LN axilla level II LN axilla Rotter LN axilla level I LN internal mammary Heart Offersen BV, et al. Radiother Oncol 2015;114:3 10 & 2016;118:
24 ) Brachiocephalic vein 2+7) Subclavian vessels 3+8) Axillary vessels 4) Internal jugular vein 5) External jugular vein 6) Brachiocephalic trunk 9) Common carotid artery 10) Vertebral artery 8 3
25 To treat or not to treat the IMN: Techniques Level 1 level 2 Rotter level 3 level 4 Offersen BV, et al. Radiother Oncol 2015;114:3 10 & 2016;118:
26 To treat or not to treat the IMN: Techniques 26
27 To treat or not to treat the IMN: Techniques Thorsen LB, et al. J Clin Oncol. 2016;34:
28 PHP, 14 junio 2012
29 To treat or not to treat the IMN: Techniques RT of the thoracic wall with IM MS: the next steps. 29
30 To treat or not to treat the IMN: Techniques Free breathing Breath Hold vimrt 3D CRT 30
31 To treat or not to treat the IMN: Techniques Free breathing Breath hold 3D-CRT vimrt 3D-CRT vimrt Heart V 30Gy (%) Heart V 20Gy (%) IL Lung V 20Gy (%) IL Lung V 10Gy (%) CL breast D mean (Gy) Osman SO, et al. Radiother Oncol. 2014;112:
32 To treat or not to treat the IMN: Techniques Free breathing Breath hold 3D-CRT vimrt 3D-CRT vimrt Heart V 30Gy (%) Heart V 20Gy (%) IL Lung V 20Gy (%) IL Lung V 10Gy (%) CL breast D mean (Gy) Osman SO, et al. Radiother Oncol. 2014;112:
33 To treat or not to treat the IMN: Techniques Free breathing Breath hold 3D-CRT vimrt 3D-CRT vimrt Heart V 30Gy (%) Heart V 20Gy (%) IL Lung V 20Gy (%) IL Lung V 10Gy (%) CL breast D mean (Gy) Osman SO, et al. Radiother Oncol. 2014;112:
34 To treat or not to treat the IMN: Techniques 34
35 To treat or not to treat the IMN: Techniques 35
36 To treat or not to treat the IMN: Techniques Patients with unfavourable anatomy: e.g. pectus excavatus IMPT IMRT But wouldn t breath hold +/ vimrt be a better solution? Mast M, et al. Breast Cancer Res Treat. 2014;148:
37 To treat or not to treat the IMN: Techniques What are the benefits of proton therapy for breast cancer patients? Proton therapy is a relatively newer cancer treatment for early stage breast cancer, but it has already shown remarkable promise and advantages over conventional therapy in the treatment of breast cancer. The accuracy and low impact of proton radiation therapy is a non invasive and low risk option for breast cancer treatment used to destroy cancerous cells or tissue. Proton radiation treatment is extremely precise and therefore more effective at targeting cancerous cells without causing damage to surrounding breast tissue. Proton therapy is not a substitute for a lumpectomy. Rather, it is an alternative to traditional radiation therapy. After the lumpectomy has been complete, a breast cancer patient would receive 10 days of proton treatment instead of five to six weeks of traditional radiation therapy. Breast cancer patients benefit from non invasive proton therapy treatment. Proton treatment is noninvasive and painless Proton therapy is effective for treating early stage breast cancer Treatment offers quicker recovery times with minimal side effects Causes less cosmetic damage compared with the burn marks caused by regular radiation It is more accurate and precise than other kinds of radiation Treatment is provided in an outpatient setting Proton radiation has little to no impact on patient energy level Loma Linda University, website 14 June 2015: treatments/breast cancer/benefits of proton treatment.page? 37
38 To treat or not to treat the IMN: Techniques 38
39 To treat or not to treat the IMN: Techniques Margins IGRT M = 2.5 Σ tot (σ tot σ p ) In room MRI 39
40 To treat or not to treat the IMN 1. Introduction 2. The recent trials 3. Technical improvements 4. Discussion 5. Conclusions 40
41 To treat or not to treat the IMN: Discussion Proof of principle: Elective regional treatment less DM improved S It is likely that not the full effect of regional RT has been obtained: see also EORTC IJROBP 2001 paper. Nowadays CT based target volume delineation and better RT techniques (IMRT): better target volume coverage higher efficacy lower doses to organs at risk less toxicity 41
42 To treat or not to treat the IMN: Discussion Lymphoedema rates Rate (%) SLNB ALND SLNB+RT ALND+RT Z0011 (1y): 6 19 AMAROS (5y): EORTC (10.9y): MA.20 (9.5y):
43 To treat or not to treat the IMN: Discussion Better local treatment adds to the effects of systemic therapy on local recurrence and on breast cancer mortality. EBCTCG Lancet 2005; 365: ; EBCTCG Lancet 2005; 366:
44 To treat or not to treat the IMN: Discussion EORTC NCIC MA.20 DBCG IMN
45 To treat or not to treat the IMN: Discussion Systemic therapy CMF ACx4 Anthr +/ T CEF CMF Tam AI Tam Tam AI/Tam EORTC NCIC MA.20 DBCG IMN
46 To treat or not to treat the IMN: Discussion Harris JR, Hellman S. Put the "hockey stick" on ice. IJROBP 1988;15:
47 To treat or not to treat the IMN: Discussion 47
48 To treat or not to treat the IMN: Discussion consensus agreements 48
49 To treat or not to treat the IMN: Discussion 1. Mastectomy for ct1 4; cn0 (US); no PST Protocol Radboud umc, March
50 Haute couture tailoring of RT: Surgery or RT? 2. BCT for ct1 3; cn0 (US); no PST Protocol Radboud umc, March
51 To treat or not to treat the IMN: Discussion 3.1. PST; cn0 (US +/ FNA) Protocol Radboud umc, March
52 To treat or not to treat the IMN: Discussion 3.2. PST; cn+(1 3) (US +/ FNA); MARI advised Protocol Radboud umc, March
53 To treat or not to treat the IMN: Discussion Precision radiation medicine Personalised/individualised/stratified approaches: Biological optimisation Technological optimisation Shared decision making 53
54 To treat or not to treat the IMN 1. Introduction 2. The recent trials 3. Technical improvements 4. Discussion 5. Conclusions 54
55 To treat or not to treat the IMN: Conclusions Poortmans P, et al. Breast. 2017;31:
56 To treat or not to treat the IMN: Conclusions Regional RT improves outcome. Interaction with risk factors & other treatments. (Very) limited toxicity. No treatment related mortality (yet?) Selection of pts to be worked out. If you do it, do it safe! 56
57 To treat or not to treat the IMN: Conclusions Regional RT improves outcome. Interaction with risk factors & other treatments. (Very) limited toxicity. No treatment related mortality (yet?) Selection of pts to be worked out. If you do it, do it safe! 57
58 Selecting for RT: Acknowledgements All the patients participating to the trials. All the investigators participating to the trials. The research teams of the trials. The research fellows involved in the trials. Special words of thanks to (alphabetically): Marianne Aznar; Harry Bartelink; Liesbeth Boersma; Laurence & Sandra Collette; Marion Essers; Sandra Hol; Birgitte Offersen; Emiel Rutgers; John Yarnold; Walter Van den Bogaert; Timothy Whelan In fact: to many to list here!!!! 58
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