Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize that heterogeneity reflects underlying differences at the histologic or genetic level and will therefore correlate with patient outcome. We quantify heterogeneity of PDAC with texture analysis to predict 2-year survival. Using fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes classifier, the proposed features achieve an area under receiver operating characteristic curve (AUC) of 0.90 and accuracy (Ac) of 82.86% with the leave-one-image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross-validation. We conclude that texture analysis can be used to quantify heterogeneity in CT images to accurately predict 2-year survival in patients with pancreatic cancer. From these data, we infer differences in the biological evolution of pancreatic cancer subtypes measurable in imaging and identify opportunities for optimized patient selection for therapy.

Fig 1. Schematic of the methods.

Fig 2

(a) Extracted CT slice after acquisition, (b) magnified view of tumor region with (top) and without (bottom) the manually drawn boundary, (c) 3-D view of manually segmented pancreas with tumor, (d) 2-D slices of tumor.

Fig 3. Exemplar tumors with rendered texture features displayed by converting data into gray levels with range [0, 255].

Resultant matrices rendered from GLCM, RLM, ACM1, and ACM2. Histogram used in the derivation of IH features. LBP and FD values at each pixel. Gradient angle computed with Sobel operator on each pixel used in ACM1 and ACM2 features. Gradient magnitude computed with Sobel operator on each pixel used in ACM2 features.

Fig 4. ROC curves obtained with different feature sets extracted from the tumor region using (a) leave-one-image-out and (b) three-fold cross-validation techniques.