Exploratory Investigation of Dose-Linear Energy Transfer (LET) Volume Histogram (DLVH) for Adverse Events Study in Intensity Modulated Proton Therapy (IMPT).

Abstract

PURPOSE:

We proposed a novel tool-a dose linear energy transfer (LET)-volume histogram (DLVH)-and performed an exploratory study to investigate rectal bleeding in prostate cancer treated with intensity modulated proton therapy.

METHODS AND MATERIALS:

The DLVH was constructed with dose and LET as 2 axes, and the normalized volume of the structure was contoured in the dose-LET plane as isovolume lines. We defined the DLVH index, DLv%(d,l) (ie, v% of the structure) to have a dose of ≥d Gy and an LET of ≥l keV/μm, similar to the dose-volume histogram index Dv%. Nine patients with prostate cancer with rectal bleeding (Common Terminology Criteria for Adverse Events grade ≥2) were included as the adverse event group, and 48 patients with no complications were considered the control group. A P value map was constructed by comparison of the DLVH indices of all patients between the 2 groups using the Mann-Whitney U test. Dose-LET volume constraints (DLVCs) were derived based on the P value map with a manual selection procedure facilitated by Spearman's correlation tests. The obtained DLVCs were further cross-validated using a multivariate support vector machine (SVM)-based normal tissue complication probability (NTCP) model with an independent testing data set composed of 8 adverse event and 13 control patients.

RESULTS:

We extracted 2 DLVC constraints. One DLVC was obtained, Vdose/LETboundary:2.5keVμmat 75 Gy to 3.2keVμmat8.65Gy <1.27% (DLVC1), revealing a high LET volume effect. The second DLVC, V(72.2Gy,0keVμm) < 2.23% (DVLC2), revealed a high dose volume effect. The SVM-based NTCP model with 2 DLVCs provided slightly superior performance than using dose only, with an area under the curve of 0.798 versus 0.779 for the testing data set.

CONCLUSIONS:

Our results demonstrated the importance of rectal "hot spots" in both high LET (DLVC1) and high dose (DLVC2) in inducing rectal bleeding. The SVM-based NTCP model confirmed the derived DLVCs as good predictors for rectal bleeding when intensity modulated proton therapy is used to treat prostate cancer.

• Authors: Yunze Yang, Carlos E Vargas, Ronik S Bhangoo, William W Wong, Steven E Schild, Thomas B Daniels, Sameer R Keole, Jean-Claude M Rwigema, Jennifer L Glass, Jiajian Shen, Todd A DeWees, Tianming Liu, Martin Bues, Mirek Fatyga, Wei Liu
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 110 Issue 4 Pg. 1189-1199 (07 15 2021) ISSN: 1879-355X [Electronic] United States
• PMID: 33621660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Topics

• Humans
• Linear Energy Transfer
• Male
• Prostatic Neoplasms (radiotherapy)
• Proton Therapy (adverse effects)
• Radiation Dosage
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted
• Radiotherapy, Intensity-Modulated (adverse effects)