Analyzing the Effect of Neoadjuvant Stereotactic Ablative Body Radiotherapy on Pancreatic Tumour Perfusion Using Computed Tomography Perfusion
Surgical resection is currently the primary curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, surgery is only feasible for patients who have resectable pancreatic cancer (RPC), which is nonmetastatic, well-localized, and has minimal involvement of the critical vessel structures around the primary tumour. Patients with limited but non-negligible involvement of the surrounding vasculature, known as borderline-resectable pancreatic cancer (BRPC) patients, often have poor surgical prognosis. Thus, to potentially reduce the tumour-vessel contact and downstage the overall tumour conditions for better surgical outcome, neoadjuvant chemotherapy is typically administered for BRPC patients. Unfortunately, due to the presence of a desmoplastic stroma, PDAC characteristically has a high tumour density, which can significantly limit tumour perfusion and restrict the systemic delivery of chemotherapy drugs to the tumour site. To overcome this barrier, several studies have demonstrated that irradiating the tumour volume with a high dose of radiation in hypofractionated radiotherapy can induce an acute increase in tumour perfusion. While chemoradiation is already the current standard of care for the non-resectable, locally advanced pancreatic cancer patients, conventional fractionation schemes typically deliver around 2-3 Gy per fraction. In contrast, treatment using higher doses in the range of 9-10 Gy per fraction or greater can be achieved with an emerging technique known as stereotactic ablative body radiotherapy (SABR), which can deliver intense doses of radiation for tumour ablation in just 3-5 fractions, with high precision leveraged by the guidance of an integrated imaging system, such as computed tomography (CT). As of now, however, there is a lack of clinical studies that have investigated the effect of high-dose radiotherapy on pancreatic tumour perfusion, especially in terms of monitoring its effect on reducing the PDAC tissue density, which may ultimately increase the volume that the anticancer drug molecules can distribute across within the tumour interstitial space—thus potentially enhancing the delivery and biodistribution of systemic therapeutic agents. Therefore, the primary objective of this study was to analyze the effect of neoadjuvant SABR on pancreatic tumour perfusion, specifically in patients with RPC and BRPC, using a functional imaging modality known as computed tomography perfusion (CTP).
Pancreatic Ductal Adenocarcinoma, Neoadjuvant Therapy, Stereotactic Ablative Body Radiotherapy, Tumour Perfusion, 4-Dimensional Volumetric Computed Tomography, Computed Tomography Perfusion
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