Beam specific PTV incorporating 4DCT for PBS proton therapy of thoracic tumors Minglei Kang, PhD Authors: Liyong Lin1*, Minglei Kang1*, Sheng Huang1, Rulon Mayer2, Andy Thomas2, James E McDonough1, Timothy D Solberg1, Charles Simone II1 1Department of Radiation Oncology, University of Pennsylvania 2Henry Jackson Foundation (* Equally contributing authors) Supported by the US Army Medical Research and Materiel Command under Contract Agreement No. DAMD17-W81XWH-07-2-0121 and W81XWH-09-2- 0174.

Challenges for PBS to treat thoracic tumors Proton PBS treatment planning can achieve better organs sparing than IMRT and DS techniques for thoracic tumors. PBS is not a good choice. Due to commercial TPSs are unable to calculate: (1). Accurate treatment margins to compensate for range uncertainties (2). PBS spots delivery interplay with organs motion Chang, JY, Zhang X, Wang X et al. Int J Radiat Oncol Biol Phys., 65: 1087-1096, 2006 Kang Y, Zhang X, Chang JY et al. Int J Radiat Oncol Biol.,67:906-914, 2007 Lomax AJ. Phys Med Biol., 53: 1043, 2008 Lomax AJ , Phys Med Biol; 53: 1027, 2008 Zhang X, Li Y, Pan X et ,Int J Radiat Oncol Biol Phys., 77:357-366, 2010

BSPTV: Beam specific planning target volume SPR: HU to stopping power ratio(SPR) conversion uncertainty Setup errors: cause cold or hot area. Motion: move the heterogeneity tissue into beam path to cause overshoot or miss shoot BSPTV iCTV Park P C, Zhu X R, Lee AK et al. Int J Radiat Oncol Biol Phys; 82:329–36, 2012 Flampouri S, Hoppe BS, Slopsema RL et al. Phys Med Biol; 59:4549-58. 2014

BSPTV: SPR, Setup errors and Motion Stopping power ratio: ± 3%, Setup errors: ±3 mm Motion quantification: 4DCT MIP-AVG iCTV Distal M Mim IP-AVG Proximal M

BSPTV: Sum 3 uncertainties Sum: linear or quadratic summation 3 uncertainties margins are displayed as Stopping power ratio, Setup and Motion, respectively. Stopping power ratio(SPR) Motion Setup Magenta: Linear Sum Yellow: Quadratic Sum

BSPTV: Contribution of 3 uncertainties BSPTV volume: Linear and quadratic summation The volume of BSPTV by linear summation can be ~7% larger than that by quadratic.

BSPTV: Gantry angle optimization Minimizing the overlapped volumes along with the BSPTV will help spare lung, heart and cord before the start of plan optimization. G270 BSPTV overlap lung beam overlap lung beam overlap cord

BSPTV applied in PBS for lung tumor 10 patients were re-planed using PBS based on BSPTV method Evaluation: 12 Perturbations were applied on 8 CT phase for both PBS and DS plans ±3% uncertainty in stopping power ratio (2×) ± 3 mm for setup errors in x, y and z direction (2×3) 8 CT phases(8×) Total 96=12*8 evaluation plans for each patient

BSPTV PBS plans vs. DS The robustness of PBS and DS plans were evaluated. The bands are displayed to show all perturbations of iCTV.

BSPTV PBS plans vs. DS Average (solid lines) and 25th and 75th percentile (dashed lines) OAR DVHs for PBS (red) and DS (blue) of 10 patient plans. Average uncertainties of DVH per patient are represented separately with red and blue error bars over the average DVH.

Interplay effect Energy (MeV) Spots 8 CT Phases 0% 12.5% 25% 37.5% 50% Having a breathing cycle of ~3.5 seconds with delivery durations of ~60 seconds and ~46 seconds for the involved two beams. The spots’ time sequence was read out from the beam delivery log files. For different treatment fractions or beam paintings in the same fraction, the beams randomly start from a position of the 3.5-second breathing period. PBS spots were therefore grouped into the eight different breathing phases. One treatment plan was split into eight plans outside of Eclipse using our in-house Matlab program. All doses were deformed to CT-50. Energy (MeV) Spots 8 CT Phases 0% 12.5% 25% 37.5% 50% 62.5% 75% 87% 110 38 122 78 145 104 26 160 151 138 13 176 197 14 170 180 232 60 169 3 190 265 66 175 24 199 260 25 172 63 202 279 93 186 210 298 178 72 48 218 304 96 192 16 MUs 567.0 42.53 75.83 124.1 55.70 50.68 45.63 98.35 74.12

Interplay effect 110% 100% 95% 50%

Conclusion 1. BSPTV can give more accurate treatment target volumes. 2. BSPTV can give best gantry angle before the plan optimization. 3. PBS+ BSPTV could achieve better organ sparing and improve target coverage using a repainting or multi-fraction method for treating thoracic tumors.

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