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MO_9_2696 - A Contour-Based Approach for Predicting Corneal Toxicity in Patients with Uveal Melanoma Treated with Proton Therapy

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

A Contour-Based Approach for Predicting Corneal Toxicity in Patients with Uveal Melanoma Treated with Proton Therapy
H. J. Lee Jr1, A. Stacey2, T. Klesert3, C. Wells3, A. Skalet4, C. Bloch5, A. Fung6, S. R. Bowen5,7, T. P. Wong6, D. Shibata7, L. M. Halasz5, and R. Rengan5; 1Duke University School of Medicine, Durham, NC, 2University of Washington, Department of Ophthalmology, Seattle, WA, 3Vitreoretinal Associates of Washington, Seattle, WA, 4Oregon Health and Science University, Portland, OR, 5University of Washington, Department of Radiation Oncology, Seattle, WA, 6SCCA Proton Therapy Center, Seattle, WA, 7University of Washington, Department of Radiology, Seattle, WA

Purpose/Objective(s): Corneal toxicity is a complication of proton beam radiation therapy (PBT) for uveal melanoma, especially in anteriorly-positioned tumors. However, in the previous era of model-based treatment planning, the corneal dose was difficult to accurately quantify. Treatment planning today has shifted to contour-based planning from a model-based approach, allowing for dose-volume histogram (DVH) analysis of the cornea and development of optimization approaches to minimize the risk of this toxicity. The primary objective of this study was to examine comparative corneal substructure doses in patients who experienced corneal toxicity with those who did not in order to develop dose constraints.

Materials/Methods: The medical records of 71 patients with uveal melanoma who received PBT at a single institution (either 50 Gy(RBE) in 5 fractions or 56 Gy(RBE) in 4 fractions) were retrospectively reviewed with IRB approval and analyzed for toxicity. Minimum follow-up was 6 months. 36 patients, including all patients with anterior tumors for whom MR images were available for contouring, were included in the DVH analysis. All patients were treated using uniform scanning technique. Corneal contours for DVH analysis were generated in a commercially available deformable registration algorithm using 3D T2-weighted MRI of the orbit co-registered to a treatment planning CT scan. The cornea was defined as a 12 mm diameter contour along the anterior surface of the eye, extending to the limbus, defined as the inflection point between the corneal and scleral curvatures. ROC analysis and Mann-Whitney testing with Benjamini-Hochberg false discovery rate correction were used to predict incidence of corneal toxicity. We also report cutoff values that maximize the Youden Index = sensitivity + (specificity minus one) for predicting toxicity incidence and are most applicable as planning constraints.

Results: All eight patients experiencing toxicity had anteriorly positioned tumors, with tumor extension anterior to the equator of the globe. PTV volume dichotomized by the median did not correlate with corneal toxicity (Fisher p=0.16). Median PTV D95% was 50.9 Gy(RBE) for both groups (p=0.89). Mean dose, max dose, V5, V20, V45, and V50 for the limbus were all significantly higher in patients experiencing corneal toxicity (p≤0.007). Candidate DVH cutoff parameters for the corneal V5, V20, V45, V50, as well as mean and max corneal doses are given in the table. All cases of toxicity occurred within 1-6 months of follow up, at a median follow up of 3 months.

Conclusion: Corneal toxicity is a notable side effect of PBT for anteriorly positioned uveal melanoma, and dosimetry can aid prediction of patients at risk for toxicity who may benefit from early intervention.
Limbus Parameter Toxicity median (n=8) No Toxicity median (n=63) Cutoff ROC AUC P-value
V5 % 100 58.29 79.27 0.80 0.007
V20 % 100 4.17 36.96 0.91 <0.001
V45 % 48.16 0 3.95 0.96 <0.001
V50 % 26.74 0 0.41 0.91 <0.001
Mean Dose Gy(RBE) 41.90 10.40 17.16 0.95 <0.001
Max Dose Gy(RBE) 52.47 30.00 48.29 0.97 <0.001

Author Disclosure: H.J. Lee: None. A. Stacey: None. T. Klesert: None. C. Bloch: Chair, Online Learning Services Subcommittee; American Association of Medical Physicist. A. Fung: None. S.R. Bowen: Research Grant; National Cancer Institute. L.M. Halasz: Research Grant; Fred Hutch/Univ of Washington Cancer Consortium. R. Rengan: Honoraria; Apollo Oncology Group. Consultant; Astra-Zeneca, Apollo Oncology Group. Advisory Board; Apollo Oncology Group. Travel Expenses; Apollo Oncology Group.

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