Development of Clinical Radiomics-Based Models to Predict Survival Outcome in Pancreatic Ductal Adenocarcinoma: A Multicenter Retrospective Study.

PURPOSE: This multicenter retrospective study aims to identify reliable clinical and radiomic features to build machine learning models that predict progression-free survival (PFS) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: Between 2010 and 2020 pre-treatment contrast-enhanced CT scans of 287 pathology-confirmed PDAC patients from two sites of the Hopital Universitaire de Bruxelles (HUB) and from 47 hospitals within the HUB network were retrospectively analysed. Demographic, clinical, and survival data were also collected. Gross tumour volume (GTV) and non-tumoral pancreas (RPV) were semi-manually segmented and radiomics features were extracted. Patients from two HUB sites comprised the training dataset, while those from the remaining 47 hospitals of the HUB network constituted the testing dataset. A three-step method was used for feature selection. Based on the GradientBoostingSurvivalAnalysis classifier, different machine learning models were trained and tested to predict OS and PFS. Model performances were assessed using the C-index and Kaplan-Meier curves. SHAP analysis was applied to allow for post hoc interpretability. RESULTS: A total of 107 radiomics features were extracted from each of the GTV and RPV. Fourteen subgroups of features were selected: clinical, GTV, RPV, clinical & GTV, clinical & GTV & RPV, GTV-volume and RPV-volume both for OS and PFS. Subsequently, 14 Gradient Boosting Survival Analysis models were trained and tested. In the testing dataset, the clinical & GTV model demonstrated the highest performance for OS (C-index: 0.72) among all other models, while for PFS, the clinical model exhibited a superior performance (C-index: 0.70). CONCLUSIONS: An integrated approach, combining clinical and radiomics features, excels in predicting OS, whereas clinical features demonstrate strong performance in PFS prediction.

The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review.

Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.

Determining age and sex-specific distribution of pancreatic whole-gland CT attenuation using artificial intelligence aided image segmentation: Associations with body composition and pancreatic cancer risk.

BACKGROUND & AIMS: Increased intrapancreatic fat is associated with pancreatic diseases; however, there are no established objective diagnostic criteria for fatty pancreas. On non-contrast computed tomography (CT), adipose tissue shows negative Hounsfield Unit (HU) attenuations (-150 to -30 HU). Using whole organ segmentation on non-contrast CT, we aimed to describe whole gland pancreatic attenuation and establish 5th and 10th percentile thresholds across a spectrum of age and sex. Subsequently, we aimed to evaluate the association between low pancreatic HU and risk of pancreatic ductal adenocarcinoma (PDAC). METHODS: The whole pancreas was segmented in 19,456 images from 469 non-contrast CT scans. A convolutional neural network was trained to assist pancreas segmentation. Mean pancreatic HU, volume, and body composition metrics were calculated. The lower 5th and 10th percentile for mean pancreatic HU were identified, examining the association with age and sex. Pre-diagnostic CT scans from patients who later developed PDAC were compared to cancer-free controls. RESULTS: Less than 5th percentile mean pancreatic HU was significantly associated with increase in BMI (OR 1.07; 1.03-1.11), visceral fat (OR 1.37; 1.15-1.64), total abdominal fat (OR 1.12; 1.03-1.22), and diabetes mellitus type 1 (OR 6.76; 1.68-27.28). Compared to controls, pre-diagnostic scans in PDAC cases had lower mean whole gland pancreatic HU (-0.2 vs 7.8, p = 0.026). CONCLUSION: In this study, we report age and sex-specific distribution of pancreatic whole-gland CT attenuation. Compared to controls, mean whole gland pancreatic HU is significantly lower in the pre-diagnostic phase of PDAC.

Changes in total lymphocyte count and neutrophil-to-lymphocyte ratio after curative pancreatectomy in patients with pancreas adenocarcinoma and their prognostic role.

BACKGROUND AND OBJECTIVES: To assess the prognostic significance of postoperative changes in immune status represented by total lymphocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) in resectable pancreatic cancer. METHODS: Patients who underwent curative pancreatectomy for pancreatic adenocarcinoma were divided into high and low groups according to cut-off values of TLC, and NLR measured preoperatively, immediately after surgery, and 1 or 6 months after surgery. Oncologic outcomes were compared between the two groups at different times, and prognostic roles of TLC and NLR were evaluated. RESULTS: Of 193 patients, the median follow-up time was 22 months, and median survival was 18 months. Their immunologic status deteriorated within 3 to 4 days after the operation and recovered after that. At 1 and 6 months postoperatively, overall survival rates were significantly lower in the group with high NLR (>2.535 and >3.21, respectively) and low TLC (<1.66 × 109 and <1.62 × 109 /L, respectively). In multiple regression analyses, elevated NLR at postoperative 1 and 6 months and decreased TLC at postoperative 1 month were significant prognosis predictors. CONCLUSIONS: Changes in immune status such as decreased TLC and elevated NLR at postoperative 1 and 6 months are effective prognostic predictors after curative pancreatectomy in patients with pancreatic adenocarcinoma.

Prognostic evaluation of pancreatic ductal adenocarcinoma: Associations between molecular biomarkers and CT imaging findings.

OBJECTIVES: To investigate association between molecular biomarkers and computed tomography (CT) imaging findings in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Fifty-three consecutive patients with PDAC (34 men and 19 women; mean age, 70.6 ±â€¯8.1 years; range, 56-86 years) who underwent dynamic contrast-enhanced CT prior to pancreatectomy were included. The Ki-67 index and expressions of E-cadherin, Vimentin, and TWIST were immunohistochemically evaluated. Qualitative image analysis and histogram analysis of CT numbers were conducted. Clinical and molecular biomarkers were tested as possible prognostic factors for overall survival (OS) using Kaplan-Meier method and Cox proportional hazards regression. In addition, associations between CT imaging findings and significant molecular biomarkers were investigated. RESULTS: The TNM stage (P = 0.018) and E-cadherin expression status (P = 0.018) were independently associated with OS. E-cadherin-negative PDACs had a worse prognosis than E-cadherin-positive PDACs (hazard ratio: 2.21). Irregular tumor margin was observed more frequently in E-cadherin-negative PDACs (54.7%) than in E-cadherin-positive PDACs (45.3%) (P = 0.00054). The kurtosis of CT number during the pancreatic parenchymal phase was significantly higher in E-cadherin-negative PDACs than in E-cadherin-positive PDACs (P = 0.035). CONCLUSIONS: E-cadherin suppression was found to be a prognostic factor for OS in patients with PDAC, and irregular tumor margin and kurtosis of CT numbers during the pancreatic parenchymal phase could be indicators for E-cadherin suppression.

Neurotensin receptors in pancreatic ductal carcinomas.

BACKGROUND: The frequent expression of neurotensin receptors (NT-R) in primaries of pancreatic ductal carcinomas has triggered the development of radioactive neurotensin analogs for possible in vivo targeting of these tumors. However, the complete lack of information regarding NT-R in liver metastases of pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) makes an in vitro study of NT-R in these tissues indispensable. METHODS: Using in vitro receptor autoradiography with (125)I-[Tyr(3)]-neurotensin, NT-R were investigated in 18 primaries and 23 liver metastases of pancreatic ductal carcinomas as well as in 19 PanIN lesions. RESULTS: We report here that 13 of 18 ductal carcinoma primaries and 14 of 23 liver metastases expressed NT-R. Moreover, none of the six PanIN 1B cases expressed NT-R, while two of six PanIN 2 and five of seven PanIN 3 expressed NT-R. Binding was fully displaced by the type 1 NT-R-selective antagonist SR48692, indicating that the NT-R in the tumors are of the type 1 NT-R subtype. CONCLUSIONS: These in vitro data extend the currently available information on NT-R in invasive and non-invasive pancreatic ductal tumors. They suggest that type 1 NT-R may be a novel, specific marker of PanIN of higher degree. The high expression of NT-R in primaries and metastases of invasive cancer strongly support the need to develop radioactive neurotensin analogs for the diagnosis and therapy of this tumor type.