Intratumoral injection therapies for locally advanced pancreatic cancer: systematic review.

INTRODUCTION: Pancreatic cancer has one of the worst prognoses of all cancers. Patients with locally advanced pancreatic cancer have a 12.7-20.2 per cent chance of receiving curative surgery after induction systemic chemotherapy. Intratumoral injection therapies have been studied as complementary treatment options for improved local tumour control. The aim of this systematic review was to provide an overview of intratumoral injection therapies, their safety, and oncological outcome in patients with locally advanced pancreatic cancer. METHODS: A literature search was conducted in PubMed, Embase and the Cochrane Library for articles written in English up to 28 November 2022. All study designs involving at least five patients with locally advanced pancreatic cancer who were treated with an intratumoral injection therapy were included. Critical appraisal of the included studies was performed using the Newcastle-Ottawa scale. RESULTS: After evaluation of the 1680 articles yielded by the systematic search, 52 studies treating 1843 patients were included. Included intratumoral injection treatment modalities comprised iodine-125 (125I) seed brachytherapy (32 studies, 1283 patients), phosphorus-32 (32P) microbrachytherapy (5 studies, 133 patients), palladium-103 (103Pd) seed brachytherapy (2 studies, 26 patients), immunotherapy (9 studies, 330 patients), and chemotherapy (4 studies, 71 patients). Overall survival ranged between 7.0 and 16.0 months for 125I, 5.2 and 15.5 months for 32P, 6.9 and 10.0 months for 103Pd, 5.8 and 13.8 months for immunotherapy, and 9.0 and 16.2 months for chemotherapy. Severe complication (greater than or equal to grade III complications using Clavien-Dindo classification) rates were 6.2 per cent for 125I, 49.2 per cent for 32P, 15 per cent for 103Pd, 57.9 per cent for immunotherapy, and 0 per cent for chemotherapy. CONCLUSION: Five intratumoral injection therapies are described and an overview is reported. Some intratumoral injection therapies for patients with locally advanced pancreatic cancer seem safe, although 32P microbrachytherapy and immunotherapy require additional evidence. Currently available data are insufficient to provide firm conclusions regarding the added value to survival. The potential advantage of intratumoral injection therapies complementary to conventional care should be studied in well designed RCTs.

Case Report: Radioactive Holmium-166 Microspheres for the Intratumoral Treatment of a Canine Pituitary Tumor.

Introduction: In this case study, a client-owned dog with a large pituitary tumor was experimentally treated by intratumoral injection of radioactive holmium-166 microspheres (166HoMS), named 166Ho microbrachytherapy. To our knowledge, this is the first intracranial intratumoral treatment through needle injection of radioactive microspheres. Materials and Methods: A 10-year-old Jack Russell Terrier was referred to the Clinic for Companion Animal Health (Faculty of Veterinary Medicine, Utrecht University, The Netherlands) with behavioral changes, restlessness, stiff gait, and compulsive circling. MRI and CT showed a pituitary tumor with basisphenoid bone invasion and marked mass effect. The tumor measured 8.8 cm3 with a pituitary height-to-brain area (P/B) ratio of 1.86 cm-1 [pituitary height (cm) ×10/brain area (cm2)]. To reduce tumor volume and neurological signs, 166HoMS were administered in the tumor center by transsphenoidal CT-guided needle injections. Results: Two manual CT-guided injections were performed containing 0.6 ml of 166HoMS suspension in total. A total of 1097 MBq was delivered, resulting in a calculated average tumor dose of 1866 Gy. At 138 days after treatment, the tumor volume measured 5.3 cm3 with a P/B ratio of 1.41 cm-1, revealing a total tumor volume reduction of 40%. Debulking surgery was performed five months after 166HoMS treatment due to recurrent neurological signs. The patient was euthanized two weeks later at request of the owners. Histopathological analysis indicated a pituitary adenoma at time of treatment, with more malignant characteristics during debulking surgery. Conclusion: The 40% tumor volume reduction without evident severe periprocedural side effects demonstrated the feasibility of intracranial intratumoral 166HoMS treatment in this single dog.