Gastrointestinal Cancer

PV QA 1 - Poster Viewing Q&A 1

SU_13_2131 - Proton Therapy and the Role of Dosimetric Parameters as Predictors for Normal Tissue Complications after Liver-Directed Stereotactic Body Radiation Therapy

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Proton Therapy and the Role of Dosimetric Parameters as Predictors for Normal Tissue Complications after Liver-Directed Stereotactic Body Radiation Therapy
K. V. Hoebel1,2, B. Y. Yeap3, J. Y. Wo2, C. Eyler2, J. A. Wolfgang2, H. Paganetti2, T. S. Hong2, and C. Grassberger2; 1Harvard-MIT Division of Health Sciences and Technology, Cambrigde, MA, 2Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 3Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Purpose/Objective(s): To determine the effect of proton vs. photon therapy and dose-volume factors on the increase in Child-Pugh (CP) scores for hepatobiliary malignancies, using a DVH estimation model.

Materials/Methods: We searched PubMed for eligible studies containing ≥20 patients treated either with SBRT or proton beam therapy (PBT) for hepatobiliary malignancies. Clinical outcome of interest was liver toxicity assessed by an increase in Child-Pugh (CP) score by 2+ points or decrease in CP class. Additionally, we developed a model based on in-house patients treated with SBRT and PBT, to derive an average DVH based on a given dosimetric parameter. This enables us to estimate dose-volume parameters that were not provided by the studies evaluated. Dose distributions for uninvolved liver were converted into EQD2 by the linear quadratic model (α/β=3 Gy). Linear regression analysis was performed on the probit-transformed outcome variable to correlate the percentage of CP score increase in each study to the predictor variables.

Results: We found 20 eligible studies, of these five pro- and 15 retrospective, 14 using SBRT (n=1114) and six using PBT (n=486). Fraction sizes ranged from 3-15Gy, and four studies reported CP score increase separately depending on patients’ initial CP class A and B. Results of univariate analyses reveal a significantly higher risk for an increase in CP score of 2+ points for patients with an initial CP class B compared to initial CP class A, and receiving SBRT compared to PBT (p= 0.012 and p=0.048, respectively). We evaluated the DVH-estimation model by testing it on data from external studies that provided MLD and at least one more dose-volume parameter. The model’s error estimation was determined for SBRT and PBT separately. Given the MLD as input, the estimated error of parameters derived from the model was 9% for SBRT and 7% for PBT, based on 4 studies each. Using the DVH-estimation model, regression testing for correlation of dosimetric parameters with increase in CP score reveals no significant result, but shows increasingly trending associations for the lower dose-volume parameters. Restricting the analysis to studies with fraction sizes of ≤8Gy per fraction (13 studies) further indicates that low dose volumetric factors correlate better with CP score increase.

Conclusion: Initial CP score is a powerful confounding factor that needs to be controlled for to allow valid analysis of the predictive value of dose-volume factors for models of liver toxicity. Our results indicate that PBT results in less CP score increase for similar MLD and that low dose parameters (V10-V20) might show better correlation with toxicity.
All studies (N=20) Fx <=8 Gy (N=13)
Dosimetric parameter Coefficient p-value Coefficient p-value
MLD 0.02 0.29 0.03 0.27
V30 0.87 0.45 1.8 0.33
V20 1.05 0.23 1.96 0.14
V15 1.11 0.15 2 0.08
V10 1.09 0.09 1.71 0.05

Author Disclosure: K.V. Hoebel: None. B.Y. Yeap: None. J.Y. Wo: None. C. Eyler: None. J.A. Wolfgang: None. H. Paganetti: Research Grant; National Cancer Institute, General Electric Global Research, INCOM Inc. Honoraria; National Cancer Institute. Travel Expenses; National Cancer Institute. Editorial Board Member; Institute of Physics (IOP). T.S. Hong: Research Grant; Novartis, Taiho. C. Grassberger: Research Grant; NIH.

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