Published online Jun 7, 2022. doi: 10.3748/wjg.v28.i21.2383
Peer-review started: December 10, 2021
First decision: January 8, 2022
Revised: January 18, 2022
Accepted: April 22, 2022
Article in press: April 22, 2022
Published online: June 7, 2022
Processing time: 173 Days and 14.6 Hours
Many new treatment options for pancreatic cancer are being explored owing to its poor prognosis. Advent of therapeutic Endoscopic ultrasound (EUS) guided therapies in recent years paved the way to explore the local delivery of injectable agents. In the last 22 years, very few studies have explored the use of EUS-guided fine-needle injection (EUS-FNI) to treat pancreatic ductal adenocarcinoma (PDAC). These are mostly phase I/II clinical studies using different agents and varied methodologies with mixed results.
EUS-FNI has the theoretical advantage of targeted delivery of anti-tumor agents under real-time visualization and minimal invasiveness. It can also overcome the limitations of systemic therapy mainly the low penetration of these agents into the desmoplastic tumor mass of PDAC. Limited literature and heterogeneity in methodologies and outcomes necessitated a systematic review of the present literature to understand and guide future research in this promising field.
To evaluate the current status of research in the novel area of EUS-guided injectable treatment for PDAC. This has helped to understand the progress made so far and draw meaningful conclusions based on the limitations and gaps found in the literature. This has also enabled the development of focused future directives for research on this topic which can potentially advance the treatment of PDAC.
A systematic and comprehensive review of clinical studies which used EUS-guided injectable therapy for the treatment of PDAC was done. Expert librarian assisted in the electronic search of various databases. Screening of papers for eligibility was done by two study members independently. Data were collected in a standardized manner with regard to the methodologies and outcomes of these studies. A critical appraisal of the present literature on this topic was performed.
Our study demonstrates that immunotherapy, chemotherapy, oncolytic viral, and other biological therapies have been used via EUS-guided injection technique in different ways to study the safety and efficacy of such treatment in PDAC patients. The review of the present literature indicates that these therapies are well tolerated and feasible overall. Mixed results are demonstrated in terms of clinical efficacy.
This study concludes that EUS-FNI based treatment may be administered to patients with advanced PDAC without significant toxicity. Clinical efficacy with respect to the standard of care (SOC) is not yet established. Further research should be undertaken to find out the most effective therapeutic agent, dose, and techniques that may be employed to the appropriate population of PDAC patients who would benefit the most from these.
The direction of future research should be to design controlled studies and phase III trials using the data from present literature to establish efficacy in terms of tumor response and survival with respect to the SOC. Anti-tumor agents may be administered at higher doses and multiple EUS-FNI sessions to maintain the appropriate concentration in the tumor bed. Studies using appropriate combination therapies (using chemotherapy and/or radiotherapy) and different EUS-FNI techniques, for example, multiple needle passes should be encouraged as they may help in overcoming hostile tumor microenvironment of pancreatic cancer.