Stereotactic MR-guided adaptive radiotherapy for central lung tumors. Professor Suresh Senan, VU University Medical Center

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1 Stereotactic MR-guided adaptive radiotherapy for central lung tumors Professor Suresh Senan, VU University Medical Center

2 Disclosures Research grants: Varian Medical Systems, ViewRay Inc. Advisory boards: Eli Lilly, AstraZeneca, Merck

3 Outline Patient selection for SMART Clinical workflow Illustrative cases What will not be discussed? Geometric accuracy of breath-hold SABR [van Sörnsen de Koste J, submitted] Adaptive treatment planning for lung tumors [Senan S, Proc ASTRO 2017] Daily on-table plan adaption [Bohoudi O, Radioth Oncology 2017]

4 SMART for thoracic tumors at VUMC Indications for SMART Moderately central tumors [fatal toxicity possible/likely in 7.5% of patients, Tekatli H, Radioth Oncol 2015] Interstitial lung disease [fatal toxicity in 15%, Chen H, IJROBP 2017] Re-irradiation for peripheral lung cancer [5-30% incidence of G3 or higher toxicity, De Bari B, Cancer Trt Rev 2015] Tumors adjacent to left hemi-diaphragm Paracardial tumors

5 SMART using breath-hold delivery (3mm margins) Moderately central tumors Ultracentral tumors SABR is feasible ASTRO guidelines [Videtic GMM, Prac Rad Onc 2017] SABR has higher toxicity [Haseltine JM, PRO 2016, Tekatli H, JTO 2016; Lindberg K, WCLC 2016]

6 SMART workflow at VUMC: Initial simulation Comfortable patient positioning (SMART takes up to 1 h) Image in MR-only mode in 3 planes Select respiratory phase for SMART 17 sec MR-sim in selected breathhold phase GTV tracking test 3D-CT scan in seclected breath-hold phase

7 SMART simulation: MR-only mode

8 SMART workflow at VUMC: Daily treatment Patient positioning 17 sec MR-sim in selected respiratory phase Recontour OAR s within 3 cm of GTV Create a plan of the day On-table plan QA SMART delivery

9 Central tumor Benchmark case (EORTC , LungTech) Adebahr S, VUMC SMART case

10 VUMC SMART case

11 SMART delivery (3 mm PTV margin)

12 SMART: patient-assisted gated delivery

13 Cardiac mortality in lung cancer Of all patients with lung cancer, 40 70% have COPD1 COPD patients have 2-5 fold higher risk of ischaemic heart disease, cardiac dysrhythmia, heart failure 2 A 5-8 fold higher risks of cardiovascular mortality is seen in some sub-groups of COPD 3 COPD patients have a 34% higher risk for sudden cardiac death 4 1Congleton J, Resp Med 2005; 2 Chen W, Lancet Resp Med 2015; 3 Lange P, AJRCCM 2012; 4 Lahousse L, Eur H J 2015

14 SMART: 2 nd case showing 4DCT simulation

15 Radiographic and clinical toxicity [data driven] 195 central tumors (585 bronchial structures); 12 fractions at 2 Dutch centers, between Doses recalculated to an equivalent dose of 2Gy with an α/β ratio of 3 Radiographic toxicity defined as: Airway stenosis Occlusion without atelectasis Occlusion with atelectasis Tekatli H, IJROBP 2017 Main stem bronchi (n=9), intermediate bronchus (n=8), upper lobe bronchi (n=25), middle lobe bronchi (n=6), and lower lobe bronchi (n=33)

16 Pooled analysis of central tumors: NTCP modelling Univariate logistic regression analyses of dosimetric parameters for clinical high grade pulmonary toxicity (n = 193) G3 toxicity (number of patients with toxicity = 24) Total D max,eqd Total V 65Gy,EQD Total V 80Gy,EQD Total V 90Gy,EQD Total V 100Gy,EQD Total V 130Gy,EQD OR % CI P-value <0.001 <0.001 <0.001 <0.001 <0.001 Tekatli, H, IJROBP 2017 ~ 5 fractions: 50.0 Gy ~ 8 fractions: 61.1 Gy

17 SMART: 2 nd case showing MR-simulation

18 SMART: 2 nd case showing 4DCT simulation

19 On-table quality assurance for SMART

20 SMART: 2 nd case showing treatment delivery

21 SMART: A new approach for central tumors Haasbeek CJA, J Thoracic Oncol 2011 Tekatli, H, Radioth Oncol 2015 Tekatli, H, J Thoracic Oncol 2016

22 SMART for thoracic tumors at VUMC Indications for SMART Moderately central tumors [fatal toxicity possible/likely in 7.5% of patients, Tekatli H, Radioth Oncol 2015] Interstitial lung disease [fatal toxicity in 15%, Chen H, IJROBP 2017] Re-irradiation for peripheral lung cancer [5-30% incidence of G3 or higher toxicity, De Bari B, Cancer Trt Rev 2015] Tumors adjacent to left hemi-diaphragm Paracardial tumors

23 Thank you for your attention

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