Pros and Cons: High Proportion of Stromal Component Indicates Better Prognosis in Patients With Pancreatic Ductal Adenocarcinoma—A Research Based on the Evaluation of Whole-Mount Histological Slides

Abstract

The study aimed to investigate the potential of tumor–stroma ratio (TSR) on digitalized whole-mount histopathology to predict prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). The effectiveness were evaluated through internal validation. Data were retrospectively collected from consecutive patients who underwent primary pancreatic resection from December 2016 to August 2017 (developing cohort) and from September 2017 to April 2018 (validation cohort). Digitalized whole-mount slide images were used to evaluate TSR by both pathologists and a computerized model based on Conditional Generative Adversarial Model (cGAN), respectively. TSR>1 and ≤ 1 denoted low and high stromal component. Logistic regression analysis revealed intratumoral necrosis and R1 independently associated with low stromal component in the developing cohort. Cox regression analysis revealed tumor–node–metastasis (TNM) stage [II vs. I: hazard ratio (HR), 2.584; 95% CI, 1.386–4.819; P = 0.003; III vs. I: HR, 4.384; 95% CI, 2.285–8.411; P < 0.001], stromal component (low vs. high: HR, 1.876; 95% CI, 1.227–2.870; P = 0.004), tumor grade (G3 vs. G1/2: HR, 2.124; 95% CI, 1.419–3.179; P < 0.001), and perineural invasion (with vs. without: HR, 2.147; 95% CI, 1.187–3.883; P = 0.011) were independent prognostic factors in the developing cohort. Stromal component categories could classify patients into subgroups within TNM stages I, II, and III based on over survival. All results were validated in the validation cohort. The weighted kappa value for categorical assessments between pathologists' evaluation and computer-aided evaluation was 0.804 (95% CI, 0.573–0.951). TSR represents a simple and reliable metric for combining the prognostic value of TNM stage in patients with PDAC.

Cellular and molecular mechanisms of perineural invasion of pancreatic ductal adenocarcinoma

“…One recent multicenter retrospective study enrolling 778 PDAC patients who received surgical treatment between 2009 and 2014 showed that the rate of PNI was 87% among these patients (T0/1, 61.6%; T2, 86.7%; T3/4, 90.1%; N0, 72.5%; and N1, 93.0%) [ 102 ]. PNI was an independent risk factor for disease‐free survival (DFS) and/or OS ( P < 0.0001) [ 103 ], and could serve as a prognostic indicator [ 99 , 104 , 105 ]. Being PNI‐free was independently protective for long‐term survival (longer than 10 years) in PDAC patients [ 106 ].…”

Computerized Assessment of the Tumor-stromal Ratio and Proposal of a Novel Nomogram for Predicting Survival in Invasive Breast Cancer

“…TSR was automatically calculated as the area of stroma divided by the area of the whole core (tumor and stroma). Compared with similar studies of computer aided-recognition methods [27][28][29], several technical improvements have been made in our study. Firstly, as mentioned above, the key for computerized TSR assessment is to identify the boundary of tumor nests more accurately.…”

Comparison of 4- and 4 plus-courses S-1 administration as adjuvant chemotherapy for pancreatic ductal adenocarcinoma

“…The statistics analysis was also refered to our previous research [13]. Categorical data are presented as percentages and were examined using the chi-squared test or Wilcoxon rank-sum test Univariate and multivariable Cox regression analyses were performed to identify independent prognostic factors, and hazard ratios (HRs) were calculated.…”

“…We referred our previous research [13] 7) patients who did not complete 4 courses of S-1 administration. The therapy schedule was approved by the Institutional Review Board of Changhai Hospital and Hospital and all informed consent was obtained from participants or from the legally authorized representatives for participating in this study for chemotherapy for the start of oncological treatment, and the study was conducted in accordance with the Declaration of Helsinki and national guidelines.…”

“…We refereed the follow-up protocol and analyzed variables reported in our previous research [13]. The main outcome was over survival (OS).…”