Remarkable regression of inoperable pancreatic grade 3 neuroendocrine neoplasm after radioligand therapy with [¹⁷⁷Lu]Lu-DOTATATE and [⁹⁰Y]Y-DOTATATE

A 65-year-old woman with pancreatic neuroendocrine neoplasm (NEN), type 2 diabetes, and hypertension was admitted in November 2021 to the Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine – National Research Institute for radioligand therapy (RLT). She complained of abdominal pain that had appeared 5 months prior to the admission. Ultrasonography of the abdomen showed a large hypoechogenic mass in the epigastrium. The lesion measured 30 mm × 35 mm × 40 mm. Endoscopic ultrasonography-guided biopsy and laboratory workup confirmed it was a nonfunctioning grade 3 (G3) NEN with a Ki-67 index of 23%. The tumor was tightly surrounding the abdominal part of the aorta and the abdominal arteries, thereby disqualifying the patient from any surgical intervention. Then, expression of somatostatin receptors was confirmed by high uptake of the radiotracer on a [⁶⁸Ga]Ga-DOTA-0-Tyr3-Octreotate (DOTATATE) positron emission tomography / computed tomography (PET/CT) scan in the pancreatic tumor (standardized uptake value [SUV] = 14.6), second segment of the liver (SUV = 22.13), left femur, and sacral bone, suggesting metastatic lesions (Figure 1A and 1B). The patient was prescribed monthly lanreotide injections (120 mg) and was qualified for RLT. After approval of the Ethics Committee of the Military Medical Chamber (154/17) a “tandem therapy” consisting of 4 courses of 1.85 GBq of [¹⁷⁷Lu]Lu-DOTATATE combined with 1.85 GBq of [⁹⁰Y]Y-DOTATATE was administered. The initial chromogranin A (CgA) concentration was 102.8 ng/ml (LDN, Nordhorn, Germany) (reference range, 19–100 ng/ml). The first post-therapeutic scintigraphy with single photon emission computed tomography/CT confirmed the presence of 2 loci collecting the radiotracer, which corresponded to the results of the previous PET/CT (Figure 1C–1E). Prior to the final course of RLT, the CgA concentration was 45.6 ng/ml, and the final post-therapeutic scintigraphy showed complete regression of the tumor and the liver metastasis (Figure 1F). A follow-up CT scan after 3 months confirmed complete regression of the pancreatic tumor, with no marked change in the liver. Six months after the treatment, the patient underwent a [⁶⁸Ga]Ga-DOTATATE PET/CT scan, which showed only a single residual lesion in the pancreatic location (7 mm × 7 mm × 10 mm; SUV = 7.3), without any other pathologic radiotracer uptake (Figure 1G and 1H). The patient was referred for surgery requalification and awaits surgical intervention.

Currently, the only commercially registered radiopharmaceutical for the treatment of inoperable or metastatic, progressive, well-differentiated (G1 and G2) NENs of the pancreas and gastrointestinal tract is ¹⁷⁷Lu-DOTATATE administered in 4 courses of 7.4 GBq activity each.¹ The presented case confirms that even in patients with G3 NEN, RLT can yield outstanding results that make the surgical intervention possible (even in initially inoperable cases), and prolong the patient’s life. Despite the fact that a tandem therapy with the use of ⁹⁰Y is considered to have a higher complication rate, it should not be disregarded as a treatment option, as it could provide better treatment outcomes.² In recent literature, the possibility of a complete or partial response is estimated at about 2% and 28%, respectively.³ However, these results concerned G1 and G2 tumors and the use of [¹⁷⁷Lu]Lu-DOTATATE only. Therefore, the presented case opens new possibilities for the treatment of patients with NENs.