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Dose-Linear Energy Transfer (LET) Volume Histogram (DLVH) for Adverse Events in Prostate Cancer Patients Treated by Intensity-Modulated Proton Therapy (IMPT)

Y Yang*, C Vargas, R Bhangoo, W Wong, S Schild, T Daniels, S Keole, J Rwigema, J Shen, M Fatyga, W Liu, Mayo Clinic Arizona, Phoenix, AZ


(Wednesday, 7/15/2020) 11:30 AM - 12:30 PM [Eastern Time (GMT-4)]

Room: Track 3

We propose dose-linear-energy-transfer (LET) volume histogram (DLVH) to present dose and LET in one plot and retrospectively analyzed rectal bleeding in prostate cancer treated by IMPT.

Physical dose and LET distributions of IMPT plans were calculated using Monte Carlo simulations. DLVH was constructed with physical dose and LET as two horizontal axes. The normalized volume of the structure was contoured as iso-volume lines. We defined DLVH index, DLv%(d,l), v% of the structure have a dose of =d Gy[RBE] and an LET of =l keV/µm. Six patients with rectal bleeding (CTCAE grade=2) were considered the adverse event group, while 17 patients without rectal bleeding from a similar time period were considered the control group. We applied Welch’s t-tests to measure the correlation of DLVH indices with rectal bleeding and derived a p-value map in the dose-LET plane. Dose-LET volume constraints (DLVCs) were derived as local minimums in the p-value map. The obtained DLVCs were cross-validated using three normal tissue complication probability (NTCP) models based on logistic regression, naïve Bayes, and support vector machines.

One DLVC was observed: V_(72.6 Gy[RBE],1.46 keV/µm)<4.9% (p=0.0021) (DLVC1), revealing high dose volumes effect within rectum for adverse event group. The other DLVC was observed: V_(4.27 Gy[RBE],3.93 keV/µm)>0.25‰ (p=5.6×10-5) (DVLC 2), revealing favorable high-LET in low-dose regions within rectum for control group. Area-under-the-curve of 0.892, 0.922, and 0.941 were obtained for three NTCP models respectively.

Our results demonstrate the importance of rectum “hot spots” in relation to rectal bleeding (DLVC1) and suggest redistributing high LET from high-dose to low-dose regions within rectum may prevent rectal bleeding (DLVC2). All three NTCP models confirmed the DLVCs as good predictors for rectal bleeding in IMPT to treat prostate cancer. DLVH can be a powerful tool in adverse event prediction and lead to better treatment planning in IMPT.

Funding Support, Disclosures, and Conflict of Interest: Supported by the National Cancer Institute Career Developmental Award K25CA168984, by Arizona Biomedical Research Commission Investigator Award, by The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, and by The Kemper Marley Foundation.


Protons, LET, Biological Dosimetry


TH- External Beam- Particle/high LET therapy: Proton therapy – Development (new technology and techniques)

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