Discussion

Locally advanced pancreatic cancer (LAPC) accounts for 30% of newly diagnosed pancreatic cancer, with approximately one-third of the cases becoming resectable after systemic chemotherapy and/or radiation therapy.² Since most of these tumors remain unresectable, survival rates following systemic chemotherapy and traditional radiation therapy have been low.³ Recent studies of systemic therapy, followed by higher biologically effective dose regimens, either alone⁴ or with a tumor modifier,⁵ have reported improved outcomes with low toxicity rates.

In this case, the patient was treated with MRI-guided stereotactic body radiation therapy to a dose of 50 Gy in 5 fractions following 6 months of systemic FOLFIRINOX using daily adaptation. The precision provided by SMART allows for both higher control rates and lower toxicity rates. A recent prospective phase 2 study of both borderline patients and patients with LAPC reported 2-year rates of local control of 78.2% and overall survival of 40.5% following treatment with no acute-grade ≥3 acute toxicity and minimal late-grade ≥ 3 toxicity.⁴ While acute-, late-, and high-grade toxicities are minimized using SMART, they can still occur.

The patient had a complicated course following her treatment with chemotherapy and radiation, including stent migration and fistula formation. The location of the fistula was in the precise region where the needle-knife fistulotomy was performed. The antecedent injury to the biliary mucosa was associated with bleeding during and following the procedure, so much so that an endoscopic clip had to be placed to stop the bleeding. Although we cannot be certain as to the exact etiology of the post-treatment-related fistula, the iatrogenic mucosal defect may have been a predisposing factor in this case. The importance of multidisciplinary evaluation with gastroenterology to individualize risk assessments for each case is important. Specifically, pretreatment endoscopy prior to radiation therapy can provide critical information to the radiation oncologist when tailoring the treatment plan. In this case, the patient is now 18 months post treatment and remains asymptomatic. No endoscopic intervention has been required to date since the identification of the duodenal fistula.

Grade 2 and above rates of GI toxicity postablative radiation therapy have been seen at rates of 2% to 47%, including biliary tract injuries of ulcers, fistulas, and gastric or duodenal mucositis.^{2, 3, 6, 7} Grade 3-4 events such as ulcers, fistulas, and gastric or duodenal mucositis have been seen at rates of 13% to 22.7%.³ For duodenal and other GI fistulas, depending on the severity and containment of the fistula, treatments can vary from conservative management, advanced surgical procedures, and varying endoscopic techniques.^{8, 9} In patients with endobiliary stents, there are reported complications associated with radiation therapy. Minimal stent position changes have been described following RT, with stent migration rates of 4.9% proximally and 5.9% distally.¹⁰ However, adverse events such as stent migration and fistula formation occur more frequently in patients who have undergone previous chemoradiotherapy treatment vs those who have undergone stent placement alone.¹¹ The significant interfraction deformation of GI structures, such as the pancreatic head, duodenum, and stomach that may occur during radiation treatment, may affect stent migration.¹⁰ Additionally, a dilated common bile duct, complete sphincterotomy, prolonged stent insertion, benign strictures, and covered metal stents were the factors associated with stent migration.^{12, 13}