Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard?

Abstract

<jats:p> Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid tumours with an estimated 5-year overall survival rate of 7% for all stages combined. In this highly resistant disease that is located in the vicinity of many radiosensitive organs, the role of radiotherapy (RT) and indications for its use in this setting have been debated for a long time and are still under investigation. Although a survival benefit has yet to be clearly demonstrated for RT, it is the only technique, other than surgery, that has been demonstrated to lead to local control improvement. The adjuvant approach is now strongly challenged by neoadjuvant treatments that could spare patients with rapidly progressive systemic disease from unnecessary surgery and may increase free margin (R0) resection rates for those eligible for surgery. Recently developed dose-escalated RT treatments, designed either to maintain full-dose chemotherapy or to deliver a high biologically effective dose, particularly to areas of contact between the tumour and blood vessels, such as hypofractionated ablative RT (HFA-RT) or stereotactic body RT (SBRT), are progressively changing the treatment landscape. These modern strategies are currently being tested in prospective clinical trials with encouraging preliminary results, paving the way for more effective treatment combinations using novel targeted therapies. This review summarizes the current literature regarding the use of RT for the treatment of primary PDAC, describes the limitations of conventional RT, and discusses the emerging role of dose-escalated RT and heavy-particle RT. </jats:p>

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial

“…R0 resection was achieved in 13.9% of all included patients and 19.8% (25/126) of all those who completed the study treatment. These percentages are lower than those published in the literature [ 15 , 16 ]. After FOLFIRINOX ± chemoradiotherapy, Hosein et al., Nanda et al., Nitsche et al., Sadot et al., and Marthey et al.…”

“…R0 resection was achieved in 13.9% of all included patients and 19.8% (25/126) of all those who completed the study treatment. These percentages are lower than those published in the literature [15,16] This variance in the proportions of patients with surgery and R0 resection can be attributed to differences in selection criteria between studies. In our trial, all patients were treated and observed prospectively.…”

EUS-guided placement of fiducial markers for stereotactic body radiation therapy in pancreatic cancer: feasibility, security and a new quality score

“…The pancreatic SBRT technique allows delivery of ablative doses in a highly conformational way, particularly at the tumor/vessel interface in few sessions (3 to 5), while reducing collateral damage to adjacent organs [4,5]. It can be easily integrated into a neoadjuvant approach, notably as an attempt to sterilize these tumor/vessels interface regions, contributing to a higher curative (R0) resection rate, as suggested by previous retrospective and phase I/II studies [6]. Insertion of inert radiopaque gold or polymerbased markers in or close to the tumor is a prerequisite for pancreatic SBRT treatments, allowing for precise targeting and real-time tracking of the tumor.…”

The Cellular and Biological Impact of Extracellular Vesicles in Pancreatic Cancer

“…In addition to chemotherapeutic protocols, radiotherapy is under investigation to “downstage” pancreatic tumors, delay recurrence and prolong patients’ survival [ 56 ]. However, chemoradiation often results in tumor repopulation, where residual tumor cells proliferate following radiation, causing relapse.…”