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Albert Liao, Pardeep Mittal, Yi Jiang, Hans E Grossniklaus; Metastatic Uveal Melanoma in the Liver Exhibit Two Distinct Patterns with Different Growth Kinetics. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4409. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The optimal time interval for detecting the presence of metastatic uveal melanoma in the liver after primary treatment in the eye is unknown. Previous mathematical models and growth rate extrapolations addressing this question relied on the assumption that there is a homogenous population of cancer cells demonstrating exponential growth. We have shown that there are two distinct forms of metastatic uveal melanoma growth: nodular and infiltrative. We hypothesize that the growth kinetics of these two patterns, as measured using doubling time, are different from each other.
A total of 57 liver lesions (nodular = 40; infiltrative = 17) among 15 patients, with a diagnosis of metastatic uveal melanoma in the liver from January 1st 2008 to October 31st 2016, were tracked using MRI scans. Tumor diameter was measured over time. Both infiltrative and nodular tumor doubling times were calculated from these measurements using modified Schwartz’s formula. Two-tailed Student’s t-test and linear regression modeling was used for statistical analysis.
Mean average doubling time for infiltrative form of metastatic uveal melanoma was 51.94 days (95% CI: 33.36 – 70.52 days), significantly less than the nodular form, which was 106.98 days (95% CI: 82.77 – 131.2 days) (p=.0005). Doubling times for both nodular and infiltrative forms do not appear to be correlated with primary tumor volume (R2 = .2391 and .1665, respectively) or metastatic tumor volume (R2 = .0554 and .1176, respectively).
Our results are consistent with the hypothesis that in metastatic uveal melanoma to the liver, the infiltrative pattern exhibits different growth kinetics compared to the nodular pattern, independent of primary tumor size or metastatic tumor size. Our previous studies of human tissue and animal models have shown differences in the liver microenvironment in the infiltrative versus nodular pattern of uveal melanoma hepatic metastasis. We propose to develop two different mathematical models for infiltrative versus nodular metastatic uveal melanoma to the liver and to determine rational follow-up periods for imaging for hepatic metastases after primary tumor treatment.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
MRI with contrast of the nodular pattern of metastatic uveal melanoma in the liver
MRI with contrast of the infiltrative pattern of metastatic uveal melanoma in the liver
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