Regional Variation of Interfraction Tumor Breathing Motion in Lung Stereotactic Body Radiation Therapy (SBRT)

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1 Regional Variation of Interfraction Tumor Breathing Motion in Lung Stereotactic Body Radiation Therapy (SBRT) Katelyn M. Atkins, Ph.D. Department of Radiation Medicine KNIGHT CANCER INSTITUTE Oregon Health & Science University

2 Nothing to disclose Disclosures

3 Introduction-SBRT SBRT delivers radioablative doses in a hypofractionated regimen Effective for non-operable, early stage NSCLC and the local control of pulmonary metastasis 1,2 Utilizes sharp dose gradients, delivering BEDs up to 180 Gy, while minimizing dose to surrounding structures 1. Timmerman et al., JAMA Baschnagel et al., Clin. Oncol. 2013

4 Respiratory Motion Influences tumor volume, position, and motion Tumor motion is largest in the superior-inferior direction Greatest in unfixed tumors in the lower and posterior lung fields max exp. Inspiration Chest wall max insp. Diaphragm Expiration The 3D projection of tumor breathing motion is elliptical and susceptible hysteresis Shirato et al. Sem. Rad. Onc Purdie et al., Acta Oncolog Seppenwoolde et al., IJROBP 2002

5 Inter-fraction Tumor Motion Intra-fraction: Inter-fraction:... supradiaphragmatic tumors Despite significant regional differences in intrafraction motion 1,3, overall changes in interfraction motion for all tumors are small 1,2 Known variability in patient respiratory patterns during RT 4 There remains a need to identify regional differences in inter-fraction tumor motion Day-to-day changes may lead to geometric errors local control or toxicity, thereby decreasing the therapeutic ratio Local control Therapeutic ratio Diaphragm position as a function of time Toxicity 1. Shirato et al., IJROBP Bissonnette et al., IJROBP Maxim et al., IJROBP Hugo et al., Rad. And Onc Dose (Gy) Brizel et al. JCO 2007

6 Current Study Working hypothesis: Tumors in distinct anatomic regions will be differentially susceptible to day-to-day respiratory-associated motion amplitude changes beyond that which is observed at simulation Specific aim: To determine the impact of anatomic tumor location on interfraction tumor motion

7 Methods Retrospectively analyzed 4DCT datasets from 41 consecutive patients (43 tumors) treated with lung SBRT No abdominal compression or breath-holding techniques were used Patients underwent standard free-breathing 4DCT at simulation daily pre-treatment 4DCTs Centroid values from each respiratory phase were used to determine absolute intra- and inter-fraction tumor motion amplitude in the ML, AP, and SI directions Intra-fraction motion Simulation Fraction 1 Fraction 2... Inter-fraction motion

8 Regional Variation of Intra-fraction Breathing-Associated Tumor Motion Mean intra-fraction motion (SD) (mm), [95%CI] Grouping, n (%) ML AP SI All locations, 43 (100) 1.6(1.4), [ ] 2.4(1.9), [ ] 5.0(5.0), [ ] Upper, 26 (60.5) 1.5(1.3), [ ] 2.3(1.7), [ ] 2.0(1.9), [ ] Lower, 14 (32.6) 1.7(1.6), [ ] 2.2(1.6), [ ] 10.4(4.8), [ ] p value <0.001

9 Regional Variation of Intra-fraction Breathing-Associated Tumor Motion Mean intra-fraction motion (SD) (mm), [95%CI] Grouping, n (%) ML AP SI All locations, 43 (100) 1.6(1.4), [ ] 2.4(1.9), [ ] 5.0(5.0), [ ] Upper, 26 (60.5) 1.5(1.3), [ ] 2.3(1.7), [ ] 2.0(1.9), [ ] Lower, 14 (32.6) 1.7(1.6), [ ] 2.2(1.6), [ ] 10.4(4.8), [ ] p value <0.001 supradiaphragmatic tumors Shirato et al. Sem. Rad. Onc Maxim et al., Int J Radiat Oncol Biol Phys 2007

10 Variation of Inter-fraction Breathing- Associated Tumor Motion by Anatomic Lobe Mean inter-fraction motion (SD) (mm), [95%CI] Grouping, n (%) ML AP SI All locations, 43 (100) 1.1(1.5), [ ] 1.9(2.4), [ ] 2.2(3.0), [ ] Upper, 26 (60.5) 0.8(0.9), [ ] 1.4(1.7), [ ] 1.3(1.6), [ ] Lower, 14 (32.6) 1.6(2.1), [ ] 2.4(3.1), [ ] 4.0(4.3), [ ] p value <0.001

11 Variation of Inter-fraction Breathing- Associated Tumor Motion by Anatomic Lobe Mean inter-fraction motion (SD) (mm), [95%CI] Grouping, n (%) ML AP SI All locations, 43 (100) 1.1(1.5), [ ] 1.9(2.4), [ ] 2.2(3.0), [ ] Upper, 26 (60.5) 0.8(0.9), [ ] 1.4(1.7), [ ] 1.3(1.6), [ ] Lower, 14 (32.6) 1.6(2.1), [ ] 2.4(3.1), [ ] 4.0(4.3), [ ] p value <0.001 Extent of SI inter-fraction motion in upper and lower lobe tumors upper lobe 24, 92% 2, 8% < 5 mm > 5 mm 10, 72% 4, 28% 2, 14% 2, 14% < 5 mm mm > mm lower lobe

12 Variation of Inter-fraction Breathing-Associated Tumor Motion by Bronchial Segment Superior lobe apical posterior anterior Middle lobe lateral medial Lower lobe superior anterior-basal lateral-basal R Lateral views Inspiration Chest wall Diaphragm L Superior lobe apicoposterior anterior superior-lingular inferior-lingular Lower lobe superior anteromedial-basal lateral-basal Superior lobe apical posterior anterior Middle lobe medial R Medial views Expiration L Superior lobe apicoposterior anterior superior-lingular inferior-lingular Lower lobe superior medial-basal anterior-basal lateral-basal posterior-basal Lower lobe superior anteromedial-basal lateral-basal posterior-basal Shirato et al. Sem. Rad. Onc. 2004

13 Variation of Inter-fraction Breathing-Associated Tumor Motion by Bronchial Segment Mean inter-fraction motion (SD) (mm), [95%CI] Bronchial Segment, n (%) ML AP SI RUL apical, 6 (14) 0.6(0.6), [ ] 0.7(0.8), [ ] 0.9(0.9), [ ] RUL posterior, 5 (11.6) 0.8(0.7), [ ] 1.5(1.8), [ ] 2.6(2.8), [ ] RUL anterior, 2 (4.7) 1.6(1.8), [ ] 1.1(1.3), [0-2.1] 1.2(0.7), [ ] RML lateral, 2 (4.7) 1.2(0.8), [ ] 4.0(2.4), [ ] 2.3(2.3), [ ] RML medial, 1 (2.3) 5.7(NA), [NA] 1.4(NA), [NA] 1.5(NA), [NA] RLL superior, 2 (4.7) 0.5(0.5), [ ] 5.5(6.3), [ ] 1.2(0.5), [ ] RLL lateral-basal, 2 (4.7) 1.9(1.4), [ ] 1.9(0.3), [ ] 6.6(6.7), [ ] RLL posterior-basal, 3 (7) 1.3(1.0), [ ] 2.2(1.1), [ ] 3.1(4.0), [ ] LUL apicoposterior, 11 (25.6) 0.7(0.6), [ ] 1.8(2.1), [ ] 1.2(0.9), [ ] LUL anterior, 1 (2.3) 1.5(1.1), [ ] 0.5(0.3), [ ] 0.5(0.7), [ ] LUL inferior-lingular, 1 (2.3) 0.8(NA), [NA] 0.3(NA), [NA] 0.9(NA), [NA] LLL superior, 2 (4.7) 0.3(0.3), [ ] 1.0(1.0), [ ] 2.3(1.8), [ ] LLL anteromedial-basal, 2 (4.7) 1.6(1.5), [ ] 2.4(1.3), [ ] 9.5(5.7), [ ] LLL posterior-basal, 1 (2.3) 6.3(3.0), [ ] 1.8(0.8), [ ] 6.1(2.7), [ ] LLL lateral-basal, 2 (4.7) 0.8(0.6), [ ] 0.9(0.7), [ ] 2.4(1.3), [ ]

14 Basal Segment Lower Lobe Tumors have increased SI inter-fraction motion 3D motion projection R Lateral views L Superior of lobe LL basal segment tumors with >5 mm SI inter-fraction apical motion posterior anterior Reference Middle lobe (simulation) lateral medial Lower lobe superior anterior-basal lateral-basal Mean inter-fraction motion (SD) (mm), [95%CI] Superior lobe apicoposterior anterior superior-lingular inferior-lingular Segments, n (%) SI LL superior, 4 (9.3) 1.7(1.3), [ ] Lower lobe superior anteromedial-basal LL basal, 10 (23.3) 5.2(4.9), [ ] p value lateral-basal Superior lobe apical posterior anterior Middle lobe medial Lower lobe superior medial-basal anterior-basal lateral-basal posterior-basal R Medial views L Mean Superior intra-fraction lobe motion apicoposterior (SD) (mm), [95%CI] anterior superior-lingular inferior-lingular Segments, n (%) SI LL superior, 4 (9.3) 10.5(3.7), [8.7- Lower lobe LL basal, 10 (23.3) 12.3] 10.8(5.1), [9.1- superior p anteromedial-basal value 12.5] 0.8 lateral-basal posterior-basal Adapted from Netter Anatomy, 4 th ed.

15 Location-Dependent Inter-fraction Motion in a Single Patient Patient 7: metastatic osteosarcoma Underwent SBRT to a LLL metastasis Tumor #1 Tumor #2 3 months later, underwent SBRT to an apical RUL metastasis Simulation 4DCT Mean inter-fraction motion (SD) (mm), [95%CI] Single treatment 4DCT Grouping, Patient n C (%) ML AP SI Central/peripheral LLL, antmed-basal Central, RUL, apical 12 (27.9) 1.6(2.1) 1.1(1.2), 0.2(0.3) [ ] 3.0(1.1) 1.6(1.7), 0.8(0.6) [ ] 12.1(5.0) 2.6(3.4), 0.7(0.1) [ ] Peripheral, 31 (72.1) 1.2(1.6), [ ] 2.0(2.6), [ ] 2.1(2.9), [ ] p value Size (cm 3 ) <5, 22 (51.2) 1.3(1.8), [ ] 1.9(1.9), [ ] 1.8(2.1), [ ] 5-20, 14 (32.6) 0.9(0.9), [ ] 2.6(3.5), [ ] 2.7(3.6), [ ] >20, 7 (16.2) 1.1(1.0), [ ] 0.9(0.7), [ ] 2.8(4.1), [ ] p value

16 Study Limitations Retrospective Exclusion of 4DCT datasets with extensive motion-induced artifact precluding reasonable assessment of motion amplitude When analyzed by bronchial segment, small n in certain groupings Dosimetric implications are unknown

17 Conclusions This is the first study to localize tumors based on bronchial segments to analyze the impact of anatomic tumor location on inter-fraction tumor motion 40% of tumors in the basal segments of the lower lobe exhibited >5 mm SI inter-fraction motion, suggesting typical ITV-to-PTV margins may be insufficient for a subset of lower lobe tumors Increased PTV margins in the SI direction, daily breathing motion reassessment and/or adaptive re-planning may benefit these patients

18 Dr. Mark Deffebach, Dept. of Medicine, OHSU, VA Medical Ctr Dr. Steven Primack, Dept. of Radiology, OHSU Dr. Martin Fuss Tulsee Doshi, Stanford University Sanja Ognjenovic, Oregon State University Yan Zhang, Portland State University Dr. Yiyi Chen, Public Health & Preventative Medicine, OHSU Acknowledgements OHSU Department of Radiation Medicine Dr. James Tanyi Dr. David Elliott Dr. Charlotte Kubicky Arjun Varchani Monica Kishore Dr. Charles Thomas Dick and Deanne Rubinstein Dorothy Hargrove Andrea Dale James Price Scott Madsen Linette Chapman Erica Ryu JoAnne Reasoner Andrea Tewson

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27 Variation of Inter-fraction Breathing-Associated Tumor Motion by Bronchial Segment Superior lobe apical posterior anterior Middle lobe lateral medial Lower lobe superior anterior-basal lateral-basal R Lateral views L Mean inter-fraction motion (SD) (mm), [95%CI] Superior lobe apicoposterior anterior superior-lingular inferior-lingular Segments, n (%) SI LL superior, 4 (9.3) 1.7(1.3), [ ] Lower lobe superior anteromedial-basal LL basal, 10 (23.3) 5.2(4.9), [ ] p value lateral-basal Superior lobe apical posterior anterior Middle lobe medial Lower lobe superior medial-basal anterior-basal lateral-basal posterior-basal R Medial views L Mean Superior intra-fraction lobe motion apicoposterior (SD) (mm), [95%CI] anterior superior-lingular inferior-lingular Segments, n (%) SI LL superior, 4 (9.3) 10.5(3.7), [8.7- Lower lobe LL basal, 10 (23.3) 12.3] 10.8(5.1), [9.1- superior p anteromedial-basal value 12.5] 0.8 lateral-basal posterior-basal Adapted from Netter Anatomy, 4 th ed.