The Role of MRI Pancreatic Protocol in Assessing Response to Neoadjuvant Therapy for Patients With Borderline Resectable Pancreatic Cancer

BackgroundBorderline Resectable Pancreatic Cancer (BRPC) remains a unique entity that is difficult to categorize due to variance in definitions and the small number of patients. The ultimate goal is to achieve a free resection (R0) after a favorable response to neoadjuvant therapy that is somewhat difficult to assess by current radiological parameters.AimTo evaluate the role of Magnetic Resonance Imaging (MRI) pancreatic protocol, including Diffusion-Weighted Imaging (DWI), in patients with BRPC receiving neoadjuvant therapy, and further compare it to RECIST criteria and outcome.MethodsHistologically confirmed BRPC patients were prospectively included. DWI-MRI was performed pre- and post-therapy. Clinical characteristics with ensuing operability were recorded and correlated to radiological RECIST/apparent diffusion coefficient (ADC) change, preoperative therapy administrated, surgical resection status, and survival.ResultsOut of 30 BRPC cases, only 11 (36.7%) ultimately underwent pancreaticoduodenectomy. Attaining a stationary or stable disease via ADC/RECIST was achieved in the majority of cases (60%/53.3% respectively). Of the 12 patients (40%) who achieved a regression by ADC, 11 underwent surgery with an R0 status. These surgical cases showed variable RECIST responses (PR=5, SD=4, PD=3). Responders by ADC to neoadjuvant therapy were significantly associated to presenting with abdominal pain (p =0.07), a decline in post-therapy CA19-9 (p<0.001), going through surgery (p<0.001), and even achieving better survival (p<0.001 vs. 0.66).ConclusionDWI-MRI ADC picked up patients most likely to undergo a successful operative procedure better than traditional RECIST criteria. An algorithm incorporating novel radiological advances with CA19-9 deserves further assessment in future studies.

Predictive factors of operability after neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer: a single-center retrospective study

Background/Aims Recently neoadjuvant chemotherapy (NAC) for pancreatic cancer has been shown to be superior to upfront surgery, but it remains a matter of debate for resectable cases. In clinical practice, some resectable cases may become unresectable after NAC. This study aimed to reveal the outcomes after NAC and to clarify the characteristics of unresected cases. Methods The medical records of 142 patients who underwent NAC between 2016 and 2020 were retrospectively reviewed. Patient characteristics, effectiveness of NAC, and outcomes were compared between the surgical group and non-surgical group (NSG). Furthermore, the risk of recurrence limited to in the patients who received NAC with gemcitabine plus nab-paclitaxel, which were mostly administered in this cohort, following R0/R1 resection was assessed. Results The overall and R0 resection rates after NAC were 89.1% and 79.7%, respectively. The neutrophil to lymphocyte ratio (NLR) > 2.78 (p = 0.0120) and anatomical borderline resectable pancreatic cancer (p = 0.0044) revealed a statistically significantly correlation with the NSG. On the other hand, NAC week < 8 (p = 0.0285), radiological response, stable disease or progression disease (p = 0.0212), and pathological stage > IIA (P = 0.0003) were significantly associated with recurrence. The tumor response rate was approximately 26.1%, and three patients with ≥ 30% reduction of primary tumor lost excision opportunities because of metastasis, interstitial pneumonia, and vascular invasion. Conclusions This study shows incomplete tumor shrinkage benefits, but pre-NAC NLR is a predictive factor for predicting operability after NAC. The NLR can be easily calculated by normal blood test, and can be considered as a suitable marker of operability.

TGFβ Drives Metabolic Perturbations during Epithelial Mesenchymal Transition in Pancreatic Cancer: TGFβ Induced EMT in PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy wherein a majority of patients present metastatic disease at diagnosis. Although the role of epithelial to mesenchymal transition (EMT), mediated by transforming growth factor beta (TGFβ), in imparting an aggressive phenotype to PDAC is well documented, the underlying biochemical pathway perturbations driving this behaviour have not been elucidated. We used high-resolution mass spectrometry (HRMS) based molecular phenotyping approach in order to delineate metabolic changes concomitant to TGFβ-induced EMT in pancreatic cancer cells. Strikingly, we observed robust changes in amino acid and energy metabolism that may contribute to tumor invasion and metastasis. Somewhat unexpectedly, TGFβ treatment resulted in an increase in intracellular levels of retinoic acid (RA) that in turn resulted in increased levels of extracellular matrix (ECM) proteins including fibronectin (FN) and collagen (COL1). These findings were further validated in plasma samples obtained from patients with resectable pancreatic cancer. Taken together, these observations provide novel insights into small molecule dysregulation that triggers a molecular cascade resulting in increased EMT-like changes in pancreatic cancer cells, a paradigm that can be potentially targeted for better clinical outcomes.

P-P55 CT-PET use in potentially resectable pancreatic cancer

Background CT-PET has become increasingly used in the diagnostic pathway for pancreatic cancer (PC)and was introduced into National Guidelines (NICE) in 2018 in the United Kingdom. It can improve the diagnosis of metastatic disease, though some believe it is not significantly better than a staging CT and MRI, and there are concerns that it can significantly delay the treatment pathway for patients, without adding benefit. Methods A retrospective national study undertaken by 26/27 specialist pancreatic resectional centres in the United Kingdom. All adult patients listed for pancreatoduodenectomy for suspected PC were included. Baseline demographics, length of pathway (days from MDT to surgery), number and type of investigations, interventions (ERCP or PTC) and associated complications were recorded, in addition to the operation performed and 12-month survival. Patients undergoing neoadjuvant chemotherapy were excluded. Results 1709 cases were entered from 2017-2020. 155 patients were excluded due to neoadjuvant chemotherapy, with 8 further patients excluded due to incomplete data entry. The median age was comparable for patients undergoing CT-PET (68 years IQR 60.0-73.0) and those who did not undergo CT PET (68 years IQR 60.0-74.0). 363/1546 patients (23.5%) underwent a pre-operative CT-PET. There was a significantly longer pathway with CT-PET (56 vs 42 days, p &lt; 0.001) and a non-significant tendency towards an increased bypass rate with CT-PET (9.9% vs. 7.8%, p = 0.065), and no improvement in survival (1-year survival 76.9% vs 75.7%, p = 0.712). Conclusions There is a statistically significant increase in the length of pathway with CT-PET, without any improvement in bypass rate or one year survival compared the no-CT-PET group. CT-PET undoubtedly has benefits but should be used selectively rather as standard investigation for all patients as failed to demonstrate survival improvement.