Philip Poortmans, MD, PhD 2 - GBCCgbcc2016.gbcc.kr/GBCC2017_upload/PFile_03_14_SP5 … · · 2017-05-18Conflict of interest: ... radiation treatment is extremely precise and therefore

2Philip Poortmans, MD, PhD

Past‐President

President‐Elect

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To treat or not

IMN: Balancing Risks and Benefits

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Conflict of interest:

I am a radiation oncologist

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To treat or not to treat the IMN

1. Introduction

2. The recent trials

3. Technical improvements

4. Discussion

5. Conclusions

6EBCTCG. Lancet. 2014;383:2127‐35.

To treat or not to treat the IMN: Introduction

7EBCTCG Lancet 2011; 378: 1707–1716 & 2014;383:2127–35.

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


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Darby S et al. NEJM 2013:368:987‐998.

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Poortmans P, et al. N Engl J Med 2015;373:317‐27.

Risk of congestive heart failure

Non-anthracycline (CMF) ChT

No RT

RT

RT + ChT

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Taylor et al. IJROBP 2007, IJROBP 2008, R&O 2009.

Reduction of the dose to the cardiac structures with tangential field irradiation (left breast)

Mean dose (Gy)

Year Heart Left anterior descending

artery

Right coronary artery

Circumflex coronary artery

Sweden 1970s*

13.3 31.8 9.1 6.9

Sweden 1990s*

4.7 21.9 2.0 2.8

UK 2006 2.3 7.6 2.0 1.2

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1. Introduction



4. Discussion

5. Conclusions

12Poortmans P, et al. N Engl J Med 2015;373:317‐27.

To treat or not to treat the IMN: Recent trials

13Whelan T, et al. N Engl J Med 2015;373:307‐16.


14Thorsen LB, et al. J Clin Oncol. 2016;34:314‐320.


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Disease‐free survival at 10 years:Improved with regional irradiation

Distant metastases‐free survival at 10 years:Improved with regional irradiationOverall 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


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Disease‐free survival at 10 years:


Distant metastases‐free survival at 10 years:


Overall survival at 10 years:Overall trend towards improvement with regional irradiation

Breast cancer specific survival at 10 years:Improved with regional irradiationLate side effects at 10 years following regional RT:

‐ Pulmonary and skin




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Disease‐free survival at 10 years:


Distant metastases‐free survival at 10 years:


Overall survival at 10 years:

Overall trend towards improvement with regional irradiation

Breast cancer specific survival at 10 years:


Late side effects at 10 y following regional RT:‐ Pulmonary and skin




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Overall survival + 1,6%


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Overall survival + 13 monthsDFS + 16,5 months


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But whom to select for

regional RT?

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1. Introduction



4. Discussion

5. Conclusions

23Offersen BV, et al. Radiother Oncol 2015;114:3‐10 & 2016;118:205‐8.

• Breast

• Boost

• PBI

• Thoracic wall

• LN supraclavicular

• LN axilla level III

• LN axilla level II

• LN axilla Rotter

• LN axilla level I

• LN internal mammaryHeart

To treat or not to treat the IMN: Techniques

1) Brachiocephalic vein2+7) Subclavian vessels3+8) Axillary vessels4) Internal jugular vein5) External jugular vein6) Brachiocephalic trunk9) Common carotid artery10) Vertebral artery

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5 54

32

4

277

8

9

3

109

86

www.ikonet.com

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Offersen BV, et al. Radiother Oncol 2015;114:3‐10 & 2016;118:205‐8.

Level 1 ‐ level 2 ‐ Rotter ‐ level 3 ‐ level 4

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Thorsen LB, et al. J Clin Oncol. 2016;34:314‐320.

PHP, 14 junio 2012

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RT of the thoracic wall ‐ with IM‐MS:the next steps.

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To treat or not to treat the IMN: Techniques3D

‐CRT

vIMRTFree breathing Breath Hold

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Osman SO, et al. Radiother Oncol. 2014;112:17‐22.

3D-CRT vIMRT 3D-CRT vIMRT

Heart V30Gy (%) 2.7 0 0.5 0

Heart V20Gy (%) 7.7 0.6 2.4 0.5

IL Lung V20Gy(%) 16.4 5.8 16.5 5.3

IL Lung V10Gy(%) 26.5 16.4 23.25 15.3

CL breast Dmean(Gy) 0.29 3.7 0.62 2.3

Free breathing Breath hold

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Heart V30Gy (%) 2.7 0 0.5 0

Heart V20Gy (%) 7.7 0.6 2.4 0.5

IL Lung V20Gy(%) 16.4 5.8 16.5 5.3

IL Lung V10Gy(%) 26.5 16.4 23.25 15.3



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Heart V30Gy (%) 2.7 0 0.5 0

Heart V20Gy (%) 7.7 0.6 2.4 0.5

IL Lung V20Gy(%) 16.4 5.8 16.5 5.3

IL Lung V10Gy(%) 26.5 16.4 23.25 15.3



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35


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Mast M, et al. Breast Cancer Res Treat. 2014;148:33‐9.

Patients with unfavourable anatomy: e.g. pectus excavatusIMPT IMRT

But wouldn’t breath hold +/‐ vIMRT be a better solution?

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Loma Linda University, website 14 June 2015: http://www.protons.com/proton‐therapy/proton‐treatments/breast‐cancer/benefits‐of‐proton‐treatment.page?

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

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• Margins

• IGRT

• In‐room MRI

M = 2.5 Σtot + 1.64 (σtot‐σp)

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1. Introduction



4. Discussion

5. Conclusions

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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

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Rate (%) SLNB ALND SLNB+RT ALND+RT

Z0011 (1y): 6 19

AMAROS (5y): 28.0 13.6

EORTC 22922 (10.9y): 9.8 11.1

MA.20 (9.5y): 4.5 8.4

Lymphoedema rates

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EBCTCG Lancet 2005; 365: 1687‐1717; EBCTCG Lancet 2005; 366: 2087–2106

Better local treatment adds to the effects of systemic therapy on local recurrence and on breast cancer mortality.

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1996 – 2004 2000 – 2007 2003 ‐ 2007

EORTC 22922 NCIC MA.20 DBCG IMN

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1996 – 2004 2000 – 2007 2003 ‐ 2007

EORTC 22922 NCIC MA.20 DBCG IMN

Systemic therapy

CMF – ACx4 Anthr +/‐ T CEF ‐ CMFTam AI – Tam Tam – AI/Tam

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Harris JR, Hellman S.

Put the "hockey stick" on

ice.

IJROBP 1988;15:497‐9.

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consensus agreements


49Protocol Radboud umc, March 2016.

1. Mastectomy for cT1‐4; cN0 (US); no PSTTo treat or not to treat the IMN: Discussion

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Haute couture tailoring of RT: Surgery or RT?

Protocol Radboud umc, March 2016.

2. BCT for cT1‐3; cN0 (US); no PST


3.1. PST; cN0 (US +/‐ FNA) To treat or not to treat the IMN: Discussion


3.2. PST; cN+(1‐3) (US +/‐ FNA); MARI advised


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Personalised/individualised/stratified approaches:

• Biological optimisation

• Technological optimisation

• Shared decision making

Precision radiation medicine

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1. Introduction



4. Discussion

5. Conclusions

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To treat or not to treat the IMN: Conclusions

Poortmans P, et al. Breast. 2017;31:295‐302.

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• 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!

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• 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!

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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; BirgitteOffersen; Emiel Rutgers; John Yarnold; Walter Van den Bogaert; Timothy Whelan

‐ In fact: to many to list here!!!!

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Documents

Philip Poortmans, MD, PhD 2 - GBCCgbcc2016.gbcc.kr/GBCC2017_upload/PFile_03_14_SP5 … · · 2017-05-18Conflict of interest: ... radiation treatment is extremely precise and therefore