Perfusion CT to Assess Response to Neoadjuvant Chemotherapy and Radiation Therapy in Pancreatic Ductal Adenocarcinoma: Initial Experience

Abstract

ancreatic cancer is the fourth leading cause of cancerrelated mortality in the United States. In 2018, an estimated 55 440 people were diagnosed with pancreatic cancer, and 44 330 people died of it (1). Neoadjuvant chemotherapy and radiation therapy (CRT) is increasingly used to treat potentially resectable pancreatic ductal adenocarcinoma (PDA), especially for borderline resectable disease, as an alternative to surgery. CRT improves the rates of negativemargin resections and possibly treats early micrometastatic disease. However, neoadjuvant CRT is not entirely safe and is sometimes associated with toxicity and disease progression. Consequently, it is important to identify patients likely to respond to CRT to avoid unnecessary drug toxicity while maximizing the chances of tumor regression.In PDA, conventional multiphasic CT is the most widely used imaging modality to evaluate response to therapy by using the Response Evaluation Criteria in Solid Tumors (RECIST). However, it is becoming evident that conventional CT imaging-through assessment of serial tumor size changes-is insufficient for reliable response evaluation after neoadjuvant CRT because of poor correlation with histologic grading of response (2-4). This poor performance can be explained by the abundant fibrous stroma of PDA, which cannot be differentiated from posttherapy fibrous scarring.Obtaining negative pathologic margins (R0) after surgery is an important marker of therapy in PDA. Patients with PDA with R0 have significantly longer survival than patients with positive margins (5,6). Recently, the rate of R0 resection is increasing with the use of neoadjuvant CRT. In a study by Chatterjee et al ( 7), R0 resection was achieved in approximately 90% of patients with PDA

Multiparametric MRI for prediction of treatment response to neoadjuvant FOLFIRINOX therapy in borderline resectable or locally advanced pancreatic cancer

“…Our findings argued against the results of previous studies that demonstrated the value of the DCE-CT (i.e., blood volume or K trans ) and DCE-MRI (i.e., K trans ) parameters in predicting the response of PDACs to gemcitabine-based chemoradiation therapy [9,12] or antiangiogenic therapy [36]. One possible reason for this difference may be the use of different therapeutic regimens in our and previous studies [9,12]. In addition, unlike our study, all previous studies evaluated only DCE-CT or MRI parameters, which may have not accounted for the confounding effects of other clinical and imaging factors on tumor response.…”

“…None of the DCE-MRI parameters evaluated in our study showed significant association with tumor response in multivariable analysis, though model-free iAUC and peak enhancement showed significance in the univariable analysis. Our findings argued against the results of previous studies that demonstrated the value of the DCE-CT (i.e., blood volume or K trans ) and DCE-MRI (i.e., K trans ) parameters in predicting the response of PDACs to gemcitabine-based chemoradiation therapy [9,12] or antiangiogenic therapy [36]. One possible reason for this difference may be the use of different therapeutic regimens in our and previous studies [9,12].…”

“…Previous studies have suggested the potential role of imaging in predicting biologic tumor behavior, post-surgical prognosis, and response to chemo-or chemoradiation therapy in patients with PDAC by using visually assessed or quantitatively measured tumor enhancement metrics on CT or MRI, diffusion-weighted imaging (DWI) parameters, and perfusion parameters obtained from dynamic contrast-enhanced (DCE) CT or MRI [8][9][10][11][12]. Multiparametric MRI is a functional and quantitative technique yielding multiple quantitative parameters that potentially reflect various tissue characteristics beyond anatomic imaging.…”

Quantitative CT perfusion imaging in patients with pancreatic cancer: a systematic review

“…In 15 out of 21 studies, BF was measured in both PDAC and non-tumorous pancreatic parenchyma, including a total of 519 patients. In all these studies, mean blood flow was significantly lower in tumor tissue compared to pancreatic parenchyma outside the tumor or in healthy pancreatic tissue in a control group [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Mean BF ranged from 17 to 60 mL/100 g/min for PDAC and 71-164 mL/100 g/min for pancreatic parenchyma.…”

Role of imaging in evaluating the response after neoadjuvant treatment for pancreatic ductal adenocarcinoma

“…The accumulation of extracellular matrix, including collagen, fibronectin, proteoglycan, and hyaluronic acid, can induce the formation of rigid extracellular matrix to compress blood vessels, leading to perfusion damage and ultimately hindering the transmission of anti-cancer drugs to the tumor cells[ 58 ] (Figure 3 ). Based on the above theoretical assumptions, Hamdy et al [ 59 ] investigated the value of perfusion CT in predicting the response of PDAC to neoadjuvant chemotherapy and radiation therapy. The results showed that participants who responded to NAT had higher baseline blood flow than those who did not respond (median, 44 mL/100 g/min vs 28 mL/100 g/min, respectively).…”