Stromal Content Is Correlated With Tissue Site, Contrast Retention, and Survival in Pancreatic Adenocarcinoma

TY - JOUR

T1 - Stromal Content Is Correlated With Tissue Site, Contrast Retention, and Survival in Pancreatic Adenocarcinoma

AU - Torphy, Robert J

AU - Wang, Zhen

AU - True-Yasaki, Aisha

AU - Volmar, Keith E

AU - Rashid, Naim

AU - Yeh, Benjamin

AU - Anderson, Judy M

AU - Johansen, Julia S.

AU - Hollingsworth, Michael A

AU - Yeh, Jen Jen

AU - Collisson, Eric A

PY - 2017

Y1 - 2017

N2 - Purpose Desmoplastic stroma is a cardinal feature of primary pancreatic ductal adenocarcinoma (PDA), but its effects on the biology, prognosis, and therapeutic outcomes in the disease are not known. We developed an automated method to assess tumor stroma density (TSD) and investigated computed tomography (CT) correlates of stroma in PDA. Patients and Methods We collected PDA samples from rapid autopsy and resection series and digitally annotated samples to quantify TSD. A series of patients who had undergone resection also underwent preoperative multiphasic CT imaging. Results Automated and manual assessments of TSD were highly correlated (ρ = 0.65; P <.001). Solid organ metastases had a lower median TSD than primary tumors (P <.001). Patients whose tumors had high TSD had prolonged recurrence-free survival (hazard ratio [HR] = 0.51; P =.003) and overall survival (HR = 0.57; P =.008). In another independent dataset, patients whose tumors had high TSD had decreased risk for recurrence (HR = 0.03; P =.003) and death (HR = 0.03; P =.003) at time of resection; however, the protective effect of high TSD diminished over time. Patients with a normalized portovenous phase CT tumor enhancement ratio ≥ 0.40 had a longer time to recurrence after resection (P =.020). Normalized portovenous phase CT tumor enhancement ratio was significantly correlated with TSD (P =.003). Conclusion Objective quantitative assessment of stroma in PDA revealed several clinically relevant observations. Stroma was less abundant in metastatic PDA, the primary cause of mortality associated with PDA. High stromal content correlated with favorable outcome in patients with resected tumors, implying a protective effect of stroma and suggesting careful consideration of active stromal depletion therapies. Standard, multiphase CT imaging correlated with stroma content and clinical outcome, indicating that noninvasive assessment of stroma is a feasible sensitivity enrichment approach in PDA.

AB - Purpose Desmoplastic stroma is a cardinal feature of primary pancreatic ductal adenocarcinoma (PDA), but its effects on the biology, prognosis, and therapeutic outcomes in the disease are not known. We developed an automated method to assess tumor stroma density (TSD) and investigated computed tomography (CT) correlates of stroma in PDA. Patients and Methods We collected PDA samples from rapid autopsy and resection series and digitally annotated samples to quantify TSD. A series of patients who had undergone resection also underwent preoperative multiphasic CT imaging. Results Automated and manual assessments of TSD were highly correlated (ρ = 0.65; P <.001). Solid organ metastases had a lower median TSD than primary tumors (P <.001). Patients whose tumors had high TSD had prolonged recurrence-free survival (hazard ratio [HR] = 0.51; P =.003) and overall survival (HR = 0.57; P =.008). In another independent dataset, patients whose tumors had high TSD had decreased risk for recurrence (HR = 0.03; P =.003) and death (HR = 0.03; P =.003) at time of resection; however, the protective effect of high TSD diminished over time. Patients with a normalized portovenous phase CT tumor enhancement ratio ≥ 0.40 had a longer time to recurrence after resection (P =.020). Normalized portovenous phase CT tumor enhancement ratio was significantly correlated with TSD (P =.003). Conclusion Objective quantitative assessment of stroma in PDA revealed several clinically relevant observations. Stroma was less abundant in metastatic PDA, the primary cause of mortality associated with PDA. High stromal content correlated with favorable outcome in patients with resected tumors, implying a protective effect of stroma and suggesting careful consideration of active stromal depletion therapies. Standard, multiphase CT imaging correlated with stroma content and clinical outcome, indicating that noninvasive assessment of stroma is a feasible sensitivity enrichment approach in PDA.

U2 - 10.1200/po.17.00121

DO - 10.1200/po.17.00121

M3 - Journal article

C2 - 30506016

SN - 2473-4284

VL - 2

SP - 1

EP - 12

JO - JCO Precision Oncology

JF - JCO Precision Oncology

ER -