Background: Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma. Materials and methods: Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC). Results: A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 versus 18.2 months, p = 0.02; PFS: 24.1 versus 7.1 months, p < 0.001). There was no survival difference between the BR and LAPC patients. The 1-year LC from SBRT was 74.1% and the median locoregional PFS was not reached for both BR and LAPC patients. Conclusions: iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials.

We investigated on the added prognostic value of a three-scale combined molecular imaging with 68 Ga-DOTATATE and 18 F-FDG PET/CT, (compared to Ki-67 based histological grading), in gastroenteropancreatic neuroendocrine neoplasia patients. 85 patients with histologically proven metastatic gastroenteropancreatic neuroendocrine neoplasias, who underwent combined PET/CT imaging were retrospectively evaluated. Highest Ki-67 value available at time of 18 F-FDG PET/CT was recorded. Patients were classified according to World Health Organization/European Neuroendocrine Tumor Society histological grades (G1, G2, G3) and into three distinct imaging categories (C1: all lesions are 18 F-FDG negative/ 68 Ga-DOTATATE positive, C2: patients with one or more 18 F-FDG positive lesions, all of them 68 Ga-DOTATATE positive, C3: patients with one or more 18 F-FDG positive lesions, at least one of them 68 Ga-DOTATATE negative). The primary endpoint of the study was Progression-Free Survival, assessed from the date of 18 F-FDG PET/CT to the date of radiological progression according to Response Evaluation Criteria In Solid Tumors version 1.1. Classification according to histological grade did not show significant statistical difference in median Progression-Free Survival between G1 and G2 but was significant between G2 and G3 patients. In contrast, median Progression-Free Survival was significantly higher in C1 compared to C2 and in C2 compared to C3 patients, revealing three distinctive imaging categories, each with highly distinctive prognosis. Our three-scale combined 68 Ga-DOTATATE/ 18 F-FDG PET imaging classification holds high prognostic value in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias. www.oncotarget.com

Small-bowel disorders remain a diagnostic and therapeutic challenge due to intestinal length. Their management was revolutionized by the emergence of deep enteroscopy. In comparison with video capsule endoscopy, deep enteroscopy allows diagnostic and therapeutic interventions. Spiral enteroscopy (Spirus Medical Endo-Ease Overtube) achieves progression by gentle push and manual clockwise rotation inducing pleating of the small bowel on the endoscope. It has the advantage of shorter examination time and more stability during withdrawal but requires two operators. The Novel Motorized Spiral Enteroscope (Olympus Corp.) incorporates a user-controlled motor contained in the handle of the endoscope. This would offer the possibility to accelerate the procedure, facilitate insertion, and simplify the technique with a single operator.