PMID- 37305036
OWN - NLM
STAT- MEDLINE
DCOM- 20230811
LR  - 20230811
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - Precision radiotherapy using MR-linac for pancreatic neuroendocrine tumors in 
      MEN1 patients (PRIME): a protocol for a phase I-II trial, and systematic review 
      on available evidence for radiotherapy of pNETs.
PG  - 994370
LID - 10.3389/fendo.2023.994370 [doi]
LID - 994370
AB  - BACKGROUND: Surgical resection is the standard of care for the treatment of 
      pancreatic neuro-endocrine tumors (pNETs) in patients with Multiple Endocrine 
      Neoplasia Type 1 (MEN1). However, surgery can cause significant short- and 
      long-term morbidity. Magnetic resonance-guided radiotherapy (MRgRT) is a 
      potential effective treatment with little side effects. With traditional 
      radiotherapy techniques, irradiation of pancreatic tumors to high dose levels was 
      hampered by poor visibility of the tumor during treatment. MRgRT uses onboard MRI 
      to guide the treatment, thereby enabling delivery of ablative irradiation doses 
      to the tumor, while sparing surrounding tissues. In this study, we describe 
      results from a systematic review assessing efficacy of radiotherapy in pNET and 
      present the protocol of the PRIME study. METHODS: PubMed, Embase and Cochrane 
      Library were searched for articles assessing efficacy and side effects of 
      radiotherapy for the treatment of pNETs. Risk of bias was assessed using the 
      ROBINS-I Risk of Bias Tool for observational studies. Descriptive statistics were 
      used to describe results of included trials. RESULTS: Four studies comprising of 
      33 patients treated by conventional radiotherapy were included. Despite the 
      heterogeneity of studies, radiotherapy appeared to be effective for the treatment 
      of pNETs with most patients responding (45.5%) or stabilizing (42.4%) in tumor 
      size. CONCLUSION AND TRIAL DESIGN: Due to the limited literature available and 
      concerns about damage to surrounding tissue, conventional radiotherapy is 
      currently little used for pNETs. The PRIME study is a phase I-II trial with a 
      single arm prospective cohort study design, investigating the efficacy of MRgRT 
      in MEN1 patients with pNET. MEN1 patients with growing pNETs with a size between 
      1.0 and 3.0 cm without malignant features are eligible for inclusion. Patients 
      are treated with 40 Gy in 5 fractions on the pNET, using online adaptive MRgRT on 
      a 1.5T MR-linac. The primary endpoint is the change in tumor size at MRI 12 
      months follow-up. Secondary endpoints include radiotoxicity, quality of life, 
      endocrine and exocrine pancreas function, resection rate, metastatic free and 
      overall survival. When MRgRT is found effective with low radiotoxicity, it could 
      reduce the need for surgery for pNET and preserve quality of life. SYSTEMATIC 
      REVIEW REGISTRATION: PROSPERO https://clinicaltrials.gov/, (CRD42022325542).
CI  - Copyright (c) 2023 van Vliembergen, Eijkelenkamp, Valk, Vriens, Meijer, Intven and 
      de Laat.
FAU - van Vliembergen, Eline N M
AU  - van Vliembergen ENM
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, 
      Netherlands.
AD  - Department of Internal Medicine, Division of Endocrinology, Radboud University 
      Medical Center, Nijmegen, Netherlands.
FAU - Eijkelenkamp, Hidde
AU  - Eijkelenkamp H
AD  - Department of Radiotherapy, University Medical Center Utrecht, Utrecht, 
      Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, 
      Netherlands.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht, 
      Utrecht, Netherlands.
FAU - Meijer, Gert J
AU  - Meijer GJ
AD  - Department of Radiotherapy, University Medical Center Utrecht, Utrecht, 
      Netherlands.
FAU - Intven, Martijn P W
AU  - Intven MPW
AD  - Department of Radiotherapy, University Medical Center Utrecht, Utrecht, 
      Netherlands.
FAU - de Laat, Joanne M
AU  - de Laat JM
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, 
      Netherlands.
AD  - Department of Internal Medicine, Division of Endocrinology, Radboud University 
      Medical Center, Nijmegen, Netherlands.
LA  - eng
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20230526
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
SB  - IM
MH  - Humans
MH  - Clinical Trial Protocols as Topic
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Magnetic Resonance Imaging
MH  - *Multiple Endocrine Neoplasia Type 1
MH  - *Neuroectodermal Tumors, Primitive
MH  - *Neuroendocrine Tumors/radiotherapy
MH  - Prospective Studies
MH  - Quality of Life
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
PMC - PMC10250693
OTO - NOTNLM
OT  - MR-guided radiotherapy (MRgRT)
OT  - MR-linac
OT  - multiple endocrine neoplasia type 1 (MEN1)
OT  - pancreatic neuroendocrine tumor (pNET)
OT  - radiosensitivity
OT  - radiotherapy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/06/12 06:42
MHDA- 2023/06/13 06:42
PMCR- 2023/01/01
CRDT- 2023/06/12 04:18
PHST- 2022/07/14 00:00 [received]
PHST- 2023/05/09 00:00 [accepted]
PHST- 2023/06/13 06:42 [medline]
PHST- 2023/06/12 06:42 [pubmed]
PHST- 2023/06/12 04:18 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.994370 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2023 May 26;14:994370. doi: 
      10.3389/fendo.2023.994370. eCollection 2023.