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

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

Research output: Contribution to journalArticlepeer-review


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, [Formula presented] <1.27% (DLVC1), revealing a high LET volume effect. The second DLVC, [Formula presented] < 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.

Original languageEnglish (US)
Pages (from-to)1189-1199
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
StatePublished - Jul 15 2021

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


Dive into the research topics of 'Exploratory Investigation of Dose-Linear Energy Transfer (LET) Volume Histogram (DLVH) for Adverse Events Study in Intensity Modulated Proton Therapy (IMPT)'. Together they form a unique fingerprint.

Cite this