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Future options: The potential role of proton irradiation 16th - - PowerPoint PPT Presentation

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Future options: The potential role of proton irradiation 16th St.Gallen International Breast Cancer Conference; March 22, 2019 John Maduro, Radiation Oncologist Introduction Should proton irradiation be the treatment of choice for

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Future options: The potential role of proton irradiation

16th St.Gallen International Breast Cancer Conference; March 22, 2019 John Maduro, Radiation Oncologist

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Introduction

  • Should proton irradiation be the treatment of choice

for locoregional irradiation in breast cancer patients?

  • Yes, but………

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It is not a matter of caution but selection!

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Physical properties

  • Photons (x-rays)
  • Protons

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120 140 160 180 200 30 20 40 60 80 100 5 10 15 20 25

Photon Proton Proton Proton Proton

Bragg Peak Spread out Bragg Peak Skin Depth (cm) 

Physical properties

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Why in breast cancer?

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Cardiac toxicity

Boekel et al, Br J Cancer 2018

Heart failure Ischaemic heart disease Valvular heart disease

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Tumor induction

Tumor RR

All cancers* 1.12 (95% CI: 1.06 to 1.19) Lung cancer* 1.39 (95% CI: 1.28 to 1.51) Esophageal cancer* 1.53 (95% CI: 1.01 to 2.31) Contralateral BC#(age <40yrs) 2.5 (95% CI: 1.4 to 4.5)

*Grantzau et al, Radiother Oncol 2015, #Stovall et al, IJROBP 2008

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Organs at risk

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Dose distribution

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Dose to organs at risk

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Organ Mean dose (Gy) Photon Proton

Heart 6.53 0.02 LAD 24.98 0.27 Left lung 8.12 0.87 Right lung 1.07 Right breast 1.56 0.17

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Dose to organs at risk

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1.7 Gy 2.0 Gy

Dasu et al, Physica Medica 2018 Pierce et al, IJROBP 2017

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Plan comparative studies

  • Lower dose in:

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Heart

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Lung(s)

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Contralateral breast

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Shoulder muscles

Ares et al, IJROBP 2010; MacDonald et al, Radiother Oncol 2013; Mast et al, Breast Canc Res Treat 2014; Farace et al, Br J Radiol 2015

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Why not in breast cancer?

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Availability and cost

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2019: +33 2017: +199,845

Website PTCOG, March 2019; Jermann et al, Int J Particle Therapy 2015; Zubizarreta et al, Clinical Oncology 2017

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No randomized controlled trials

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Most patients will not have a clinical benefit

  • Low dose to heart and lung in most breast cancer

patients

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Breast only

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Partial breast

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Breath hold

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Prone position

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Right sided breast cancer

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What’s the literature?

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Clinical experience

  • Older proton technique (passive scattering)

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Higher skin toxicity

  • Partial breast

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Excellent local control

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Good cosmetic result(except patients 8 fractions twice daily)

  • Whole breast/chest wall

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Feasible and well tolerated

  • Ongoing RCT’s

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Teichman et al, Cancer Med 2018; Luo et al, Radiother Oncol 2019;, Verma et al, Radiother Oncol 2017; Gallant-Girodet et al, IJROBP 2014; MacDonald et al, IJROBP 2013

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Clinical data

  • National Cancer database (United States)

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2004 – 2014

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871 (0.1%) proton RT, 723,621 non proton RT

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58.3 % stage 0-1

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Median follow up: 62.2 months

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Equal overall survival

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Chowdhary et al, Frontiers in Oncology 2019

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How to select?

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Dutch model for patient selection

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Langendijk et al, Radiother and Oncology 2013

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Model based selection

  • Dose effect relation (normal tissue complication

probability (NTCP))

  • Individual risk calculation
  • Cardiac risk photons – Cardiac risk protons > 2%

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Cardiac risk model

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Life time: 7.4% per Gy

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Individual cardiac risk

  • Individual risk based on national cardiac events

statistics

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Age

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Presence or absence of cardiac risk factor

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Mean heart dose

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Example

  • 40 year female patient with cardiac risk factor
  • Photon plan

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Mean heart dose (Gy) Cardiac event risk (%)

Photons 5.0 4.3 Protons ∆ NTCP

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Example

  • 40 year female patient with cardiac risk factor
  • Proton plan

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Mean heart dose (Gy) Cardiac event risk (%)

Photons 5.0 4.3 Protons 1.0 0.6 ∆ NTCP 3.7

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Patients that could benefit

  • Internal mammary chain irradiation
  • Young patients
  • Bilateral breast cancer
  • Special anatomy (pectus excavatum)
  • Cardiac risk factor

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Conclusions

  • Dosimetric all breast cancer patients benefit from

proton irradiation (ALARA)

  • Not all breast cancer patient should get protons

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Cost effectivness

  • Some breast cancer patients will have a clinical

benefit

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Adequate patient selection

  • Life expectancy
  • Relative higher dose to organs at risk

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Acknowledgment

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Anne Crijns, UMCG Hans Langendijk, UMCG Liesbeth Boersma, MAASTRO Karolien Verhoeven, MAASTRO Dutch National breast proton indication committee