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

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 locoregional irradiation in breast cancer patients? • Yes, but……… It is not a matter of caution but selection! 2

Physical properties • Photons (x-rays) • Protons 3

Physical properties 200 180 160 Photon Spread out 140 Bragg Peak 120 Proton 100 80 Proton 60 Bragg Peak Proton 40 Proton 20 Depth (cm )  5 10 15 20 25 30 Skin 4

Why in breast cancer? 5

Cardiac toxicity Heart failure Ischaemic heart disease Valvular heart disease Boekel et al, Br J Cancer 2018 6

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 7

Organs at risk 8

Dose distribution 9

Dose to organs at risk Mean dose (Gy) Organ Photon Proton Heart 6.53 0.02 LAD 24.98 0.27 Left lung 8.12 0.87 Right lung 1.07 0 Right breast 1.56 0.17 10

Dose to organs at risk 2.0 Gy 1.7 Gy Dasu et al, Physica Medica 2018 Pierce et al, IJROBP 2017 11

Plan comparative studies • Lower dose in: Heart ─ Lung(s) ─ Contralateral breast ─ 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 12

Why not in breast cancer? 13

Availability and cost 2019: +33 2017: +199,845 Website PTCOG, March 2019; Jermann et al, Int J Particle Therapy 2015; Zubizarreta et al, Clinical Oncology 2017 14

No randomized controlled trials 15

Most patients will not have a clinical benefit • Low dose to heart and lung in most breast cancer patients Breast only ─ Partial breast ─ Breath hold ─ Prone position ─ Right sided breast cancer ─ 16

What’s the literature? 17

Clinical experience • Older proton technique (passive scattering) Higher skin toxicity ─ • Partial breast Excellent local control ─ Good cosmetic result(except patients 8 fractions twice daily) ─ • Whole breast/chest wall Feasible and well tolerated ─ • Ongoing RCT’s 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 18

Clinical data • National Cancer database (United States) 2004 – 2014 ─ 871 (0.1%) proton RT, 723,621 non proton RT ─ 58.3 % stage 0-1 ─ Median follow up: 62.2 months ─ Equal overall survival ─ Chowdhary et al, Frontiers in Oncology 2019 19

How to select? 20

Dutch model for patient selection Langendijk et al, Radiother and Oncology 2013 21

Model based selection • Dose effect relation (normal tissue complication probability (NTCP)) • Individual risk calculation • Cardiac risk photons – Cardiac risk protons > 2% 22

Cardiac risk model Life time: 7.4% per Gy 23

Individual cardiac risk • Individual risk based on national cardiac events statistics Age ─ Presence or absence of cardiac risk factor ─ Mean heart dose ─ 24

Example • 40 year female patient with cardiac risk factor • Photon plan Mean heart Cardiac event dose (Gy) risk (%) Photons 5.0 4.3 Protons ∆ NTCP 25

Example • 40 year female patient with cardiac risk factor • Proton plan Mean heart Cardiac event dose (Gy) risk (%) Photons 5.0 4.3 Protons 1.0 0.6 ∆ NTCP 3.7 26

Patients that could benefit • Internal mammary chain irradiation • Young patients • Bilateral breast cancer • Special anatomy (pectus excavatum) • Cardiac risk factor 27

Conclusions • Dosimetric all breast cancer patients benefit from proton irradiation (ALARA) • Not all breast cancer patient should get protons Cost effectivness ─ • Some breast cancer patients will have a clinical benefit Adequate patient selection ─ • Life expectancy • Relative higher dose to organs at risk 28

Acknowledgment Anne Crijns, UMCG Hans Langendijk, UMCG Liesbeth Boersma, MAASTRO Karolien Verhoeven, MAASTRO Dutch National breast proton indication committee 29