A systematic methodology review of fluorescence-guided cancer surgery to inform the development of a core master protocol and outcome set
Authors: Vallance Abigail E. ,   The CLEARER study collaborative*, Elson Daniel , Giuliani Stefano , Rankin Kenneth , Stasiuk Graeme , Smith Myles , Leff Daniel , Paleri Vinidh , McNair Angus , Ahmad Erum , Ahmed Hashim , Antypas Antony , Anuar Amir , Appleton Alice , Beattie Cara , Bhadbury Disha , Brignall Rhiannon , Burton Claudia , Burton Ollie , Chow Janice , Chu Howard , Chu Kelly , Cunningham Brian , Daly Elizabeth , Dhakal Noor , Douek Michael , Doughty Ben , Feeney Kaylem , Fleet Alex , Fowler Hayley , Fu Michael , Galea Mark , Glatzel Hannah , Goh Esther , Grimes Hannah , Gruber Mei-Yin , Hackett Natalia , Hanson Mark , Helm Jessica , Higginbottham George , Islam Rayyan , Jaffer Alisha , Jama Marwa , Jha Rama , Kabbani Jade , Kabbani Jamil , Kahn Ayesha , Kennett Jessica , Levene Ariella , Losty Ethan , Lun Andie , Macierzanka Krzysztof , Mahmood Fahad , Maliyil Jed , Mitchell Emily-Jane , Mohamed Intisar , Mohammed Ali , Mund Marco , Odedra James , Olatigbe Olufemi , O’Neill Maeve , Osei-Bordom Daniel-Clement , Papadopoulou Ariadni , Patel Manal , Purushotham Arnie , Quek Fang Fang , Ramsay Euan , Roberts Luke James , Rottenberg Augustus , Harper Elizabeth Ryan , Scales Lucy , Shah Preeyan , Short Chloe , Lee Keng Siang , Smyth Eleanor , Squires Ollie , Sukumar Aiswarya , Thangavijayan Harsha , Thirunavukarasu Arun , Thomas Dalia , Thorpe Carrie , Uren Alexandra , Vaidya Jayant , Wallace Florence , Murage Nora Wangari , Lee Mary Xie , Ahmed Clayton Yang Hashim , Avery Kelly , Blazeby Jane , Blencowe Natalie , Bryant Richard , Chang David , Cousins Sian , Douek Michael , Hoffman Christin , Jayne David , Jones Connor , Macefield Rhiannon , Main Barry , Pathak Samir , Potter Shelley , Purushotham Arnie , Stewart Grant , Stoyanov Danail , Vaidya Jayant , Vercauteren Tom , Vimalachandran Dale , Brewster Oliver , Wijeyaratne Manuk 
Published: June 2024

Abstract
Background
Fluorescence-guided precision cancer surgery may improve survival and minimize patient morbidity. Efficient development of promising interventions is however hindered by a lack of common methodology. This methodology review aimed to synthesize descriptions of technique, governance processes, surgical learning and outcome reporting in studies of fluorescence-guided cancer surgery to provide guidance for the harmonized design of future studies.

Methods
A systematic search of MEDLINE, EMBASE and CENTRAL databases from 2016–2020 identified studies of all designs describing the use of fluorescence in cancer surgery. Dual screening and data extraction was conducted by two independent teams.

Results
Of 13,108 screened articles, 426 full text articles were included. The number of publications per year increased from 66 in 2016 to 115 in 2020. Indocyanine green was the most commonly used fluorescence agent (391, 91.8%). The most common reported purpose of fluorescence guided surgery was for lymph node mapping (195, 5%) and non-specific tumour visualization (94, 2%). Reporting about surgical learning and governance processes incomplete. A total of 2,577 verbatim outcomes were identified, with the commonly reported outcome lymph node detection (796, 30%). Measures of recurrence (32, 1.2%), change in operative plan (23, 0.9%), health economics (2, 0.1%), learning curve (2, 0.1%) and quality of life (2, 0.1%) were rarely reported.

Conclusion
There was evidence of methodological heterogeneity that may hinder efficient evaluation of fluorescence surgery. Harmonization of the design of future studies may streamline innovation.