Deformable Registration and Dose Accumulation to Investigate Marginal Liver Cancer Recurrences

Abstract

Image guided radiotherapy (IGRT) combined with deformable registration enables calculation of the accumulated treatment dose to normal tissues and targets. Correlating the delivered dose with follow-up images of patients who developed local recurrences can help to establish if the recurrences were marginal (within dose fall off region). The purpose of this research is to quantify the accumulated dose to the liver and gross tumor volume (GTV) and correlate this with location of recurrences in liver cancer patients treated with SBRT. Six liver cancer patients who developed local recurrences following six-fraction, image guided SBRT were investigated. The median time between IGRT and the most recent follow-up image was 17 months (range, 5 - 31 months). The liver was delineated on the planning CT image, CBCT images, and follow-up CT images and the GTV on the planning and follow-up CT images. Deformable registration and dose accumulation was performed using MORFEUS, a biomechanical model-based deformable registration algorithm. The accumulated dose was calculated based of deformable registration of the planning images and the CBCT images obtained immediately before each fraction. Deformable registration was then performed between the planning image, with the accumulated dose over treatment delivery, and the follow-up images in which local recurrences were delineated. The mean and minimum accumulated dose to the treated GTV was compared to the planned doses. The mean and minimum dose delivered to the region of progressive and/or new local recurrences were quantified. The accumulated dose to the liver and GTVs were compared to the planned doses (37 to 57 Gy in 6 fractions). The minimum dose to the GTV was more than 5% less than the planned minimum dose for 1 patient (1 Gy). This patient developed local progression and 4 additional lesions, 2 correlated to a minimum dose of less than 4 Gy, indicating ‘out of field’ recurrences. Complete response of the GTV was seen in 1 patient, who developed apparent new disease correlated with a minimum dose of 14% of the minimum accumulated dose in the GTV, indicating a possible marginal recurrence. Two patients had no change in accumulated minimum dose correlated with the recurrence on the follow-up image, but additional hepatic recurrences occurred in regions of the liver that received doses less than 12 Gy, indicating out of field or ‘de novo’ recurrences. Deformable dose accumulation and correlation with follow-up images can aid in deciphering if local recurrences are marginal (due to residual dosimetric or geometric uncertainties, inadequate CTV margin or insufficient dose) or occur ‘de novo’ (unrelated to physical factors).