Abstract
Recently we showed that delta radiomics features (DRF) from daily CT-guided chemoradiation therapy (CRT) is associated with early prediction of treatment response for pancreatic cancer. CA19-9 is a widely used clinical biomarker for pancreatic cancer. The purpose of this work is to investigate if the predictive power of such biomarkers (DRF or CA19-9) can improve by combining both biomarkers. Daily non-contrast CTs acquired during routine CT-guided neoadjuvant CRT for 24 patients (672 datasets, in 28 daily fractions), along with their CA19-9, pathology reports and follow-up data were analyzed. The pancreatic head was segmented on each daily CT and radiomic features were extracted from the segmented regions. The time between the end of treatment and last follow-up was used to build a survival model. Patients were divided into two groups based on their pathological response. Spearman correlations were used to find the DRFs correlated to CA19-9. A regression model was built to examine the effect of combining CA19-9 and DRFs on response prediction. C-index was used to measure model effectiveness. The effect of a decrease in CA19-9 levels during treatment vs. failure of CA19-9 levels to normalize on survival was examined. Univariate- and multivariate Cox-regression analysis were performed to determine the effect of combining CA19-9 and DRFs on survival correlations. Spearman correlation showed that CA19-9 is correlated to DRFs (Entropy, cluster tendency and coarseness). An Increase in CA19-9 levels during treatment were correlated to a bad response, while a decline was correlated to a good response. Incorporating CA19-9 with DRFs increased the c-index from 0.57 to 0.87 indicating a stronger model. The univariate analysis showed that patients with decreasing CA19-9 had an improved median survival (68 months) compared to those with increasing levels (33 months). The 5-years survival was improved for the decreasing CA19-9 group (55%) compared to the increasing group (30%). The Cox-multivariate analysis showed that treatment related decrease in CA19-9 levels (p = 0.031) and DRFs (p = 0.001) were predictors of survival. The hazard-ratio was reduced from 0.73, p = 0.032 using CA19-9 only to 0.58, p = 0.028 combining DRFs with CA19-9. DRFs-CA19-9 combination has the potential to increasing the possibility for response-based treatment adaptation.
Highlights
Pancreatic cancer (PC) is a devastating malignancy and one of the leading causes of cancer death in the United States
Medical college of Wisconsin IRB approved HIPPA compliant study, daily non-contrast CTs acquired during routine CT-guided chemoradiation therapy (CRT) for 24 patients, along with their CA19-9 tests, post-CRT pathology reports and follow up data were analyzed
A modified Ryan Scheme for tumor regression score recommended by the College of American Pathologists was used to evaluate treatment effect as follows: Grade 0 (G0): no viable cancer cells, Grade 1 (G1): single cells or small groups of residual cancer, Grade 2 (G2): residual cancer with evident tumor regression, but more than single cells or rare small groups of cancer cells, and Grade 3 (G3): extensive residual cancer with no evident of tumor regression [20]
Summary
Pancreatic cancer (PC) is a devastating malignancy and one of the leading causes of cancer death in the United States. Advances in cancer care have substantially improved outcomes for particular tumor sites over the past years, little change has been seen in the pancreatic cancer patient outcomes. Surgical resection is considered a prerequisite for curing pancreatic cancer and achieving long term survival. Based on our institutional recommendations, tumor with 50% narrowing in the tumor-vein anatomy are considered borderline resectable. Neoadjuvant therapy with chemo-radiation usually precedes surgery to downstage the tumor from being borderline resectable to resectable [3]
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