[18F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer: a multicenter prospective study (PLASTIC-3 study)

Lianne Triemstra; Sarah W J M Spruijt; PLASTIC-3 Study Group; Dennis Vriens; Erik Vegt; Wilma E Mesker; Lukas J A C Hawinkels; Sopany Saing; Marije Slingerland; Vera Kemp; Stijn A L P Crobach; Jelle J Goeman; Martin Pool; Petra Dibbets-Schneider; Roel J Bennink; Mark I van Berge Henegouwen; Marc J van Det; Boudewijn J van Etten; Henk H Hartgrink; Richard van Hillegersberg; Marnix G E H Lam; Nanda M Smulders; Misha D P Luyer; Walter Noordzij; Emilia C Owers; Wim J G Oyen; Johanna W van Sandick; Wendy Schreurs; Wobbe O de Steur; Jan H M B Stoot; Leo E Weijs; Bas P L Wijnhoven; Bart P L Witteman; Jelle P Ruurda; Lioe-Fee de Geus-Oei

doi:10.1186/s12885-025-15347-7

[18F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer: a multicenter prospective study (PLASTIC-3 study)

Lianne Triemstra
, Sarah W J M Spruijt
, PLASTIC-3 Study Group
, Dennis Vriens
, Erik Vegt
, Wilma E Mesker
, Lukas J A C Hawinkels
, Sopany Saing
, Marije Slingerland
, Vera Kemp
, Stijn A L P Crobach
, Jelle J Goeman
, Martin Pool
, Petra Dibbets-Schneider
, Roel J Bennink
, Mark I van Berge Henegouwen
, Marc J van Det
, Boudewijn J van Etten
, Henk H Hartgrink
, Richard van Hillegersberg

Marnix G E H Lam, Nanda M Smulders, Misha D P Luyer, Walter Noordzij, Emilia C Owers, Wim J G Oyen, Johanna W van Sandick, Wendy Schreurs, Wobbe O de Steur, Jan H M B Stoot, Leo E Weijs, Bas P L Wijnhoven, Bart P L Witteman, Jelle P Ruurda, Lioe-Fee de Geus-Oei^*

^*Corresponding author for this work

University Medical Centre Utrecht
Leiden University Medical Centre
Radboud University Medical Center
University of Twente
Amsterdam UMC, Locatie UvA/AMC
Department of Surgery
University Medical Centre Groningen
Department of Radiology and Nuclear Medicine
Catharina Hospital
The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Rijnstate Hospital
Zuyderland MC, Quality and Safety
Department of Nuclear Medicine

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND:

Treatment decisions for locally advanced gastric adenocarcinoma rely on staging with gastroscopy, computed tomography (CT), and staging laparoscopy (SL). However, CT often fails to detect peritoneal and other distant metastases, and SL is an invasive procedure with complication risks and costs. Therefore, an accurate non-invasive imaging biomarker to detect such metastases could improve the care for gastric cancer patients. Radiolabeled fibroblast-activating protein inhibitors (FAPI), targeting stromal cancer-associated fibroblasts, are promising radiotracers. Preliminary Asian studies indicate that FAPI PET/CT outperforms [18F]FDG PET/CT in tracer uptake, tumor-to-background ratio and diagnostic sensitivity in gastric cancer. However, larger studies using FAPI PET/CT in homogeneous, representative cohorts are needed to validate and translate these findings to Western populations. This study evaluates the clinical impact and diagnostic accuracy of [18F]AlF-FAPI-74 PET/CT for optimizing patient staging, aiming to reduce futile toxic neoadjuvant and surgical treatments. This may help optimize treatment pathways, enhance quality of life (QoL), and reduce patient burden and healthcare costs.

METHODS:

This Dutch multicenter prospective clinical trial will recruit 250 patients with resectable, locally advanced gastric adenocarcinoma (cT3-4N0-3M0) as determined by gastroscopy and CT, planned for curative treatment. The modality under investigation is [18F]AlF-FAPI-74 PET/CT. The primary outcome is the proportion of patients in whom [18F]AlF-FAPI-74 PET/CT leads to a change in treatment intent. Secondary outcomes include diagnostic performance, patient burden from incidental or false-positive PET/CT findings, diagnostic delay, and clinicopathological correlation between [18F]AlF-FAPI-74 PET/CT and intra-operative findings during SL. The composite reference standard for 'true' (intraperitoneal) tumor burden includes SL-based peritoneal cancer index scores, biopsy, imaging and intra-operative findings. If [18F]AlF-FAPI-74 PET/CT proves reliable, its cost-effectiveness will be compared to the PLASTIC-study. Recruitment started July 3rd 2025 and will continue for 36 months.

DISCUSSION:

This study hypothesizes that [18F]AlF-FAPI-74 PET/CT can detect two-thirds of all gastric cancer patients with M1-disease according to the reference standard. Additionally, an [18F]AlF-FAPI-74 PET/CT scan may reduce healthcare costs, optimize treatment pathways and patients' QoL. The study findings will be relevant for countries with similar treatment algorithms and healthcare systems.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT07018661. This trial was registered prospectively on June 12th, 2025.

Original language	English
Article number	135
Pages (from-to)	135
Number of pages	1
Journal	BMC Cancer
Volume	26
Issue number	1
Early online date	27 Nov 2025
DOIs	https://doi.org/10.1186/s12885-025-15347-7
Publication status	Published - 27 Jan 2026

Bibliographical note

Publisher Copyright:
© 2025. The Author(s).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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[18F]F-FAPI PET CT and LAparoscopy in STagIng advanced gastric CancerFinal published version, 1.26 MBLicence: CC BY-NC-ND

Cite this

Triemstra, L., Spruijt, S. W. J. M., PLASTIC-3 Study Group, Vriens, D., Vegt, E., Mesker, W. E., Hawinkels, L. J. A. C., Saing, S., Slingerland, M., Kemp, V., Crobach, S. A. L. P., Goeman, J. J., Pool, M., Dibbets-Schneider, P., Bennink, R. J., van Berge Henegouwen, M. I., van Det, M. J., van Etten, B. J., Hartgrink, H. H., ... de Geus-Oei, L.-F. (2026). [18F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer: a multicenter prospective study (PLASTIC-3 study). BMC Cancer, 26(1), 135. Article 135. https://doi.org/10.1186/s12885-025-15347-7

@article{e0056f1dcbc9498988beb439525b237e,

title = "[18F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer: a multicenter prospective study (PLASTIC-3 study)",

abstract = "BACKGROUND: Treatment decisions for locally advanced gastric adenocarcinoma rely on staging with gastroscopy, computed tomography (CT), and staging laparoscopy (SL). However, CT often fails to detect peritoneal and other distant metastases, and SL is an invasive procedure with complication risks and costs. Therefore, an accurate non-invasive imaging biomarker to detect such metastases could improve the care for gastric cancer patients. Radiolabeled fibroblast-activating protein inhibitors (FAPI), targeting stromal cancer-associated fibroblasts, are promising radiotracers. Preliminary Asian studies indicate that FAPI PET/CT outperforms [18F]FDG PET/CT in tracer uptake, tumor-to-background ratio and diagnostic sensitivity in gastric cancer. However, larger studies using FAPI PET/CT in homogeneous, representative cohorts are needed to validate and translate these findings to Western populations. This study evaluates the clinical impact and diagnostic accuracy of [18F]AlF-FAPI-74 PET/CT for optimizing patient staging, aiming to reduce futile toxic neoadjuvant and surgical treatments. This may help optimize treatment pathways, enhance quality of life (QoL), and reduce patient burden and healthcare costs.METHODS: This Dutch multicenter prospective clinical trial will recruit 250 patients with resectable, locally advanced gastric adenocarcinoma (cT3-4N0-3M0) as determined by gastroscopy and CT, planned for curative treatment. The modality under investigation is [18F]AlF-FAPI-74 PET/CT. The primary outcome is the proportion of patients in whom [18F]AlF-FAPI-74 PET/CT leads to a change in treatment intent. Secondary outcomes include diagnostic performance, patient burden from incidental or false-positive PET/CT findings, diagnostic delay, and clinicopathological correlation between [18F]AlF-FAPI-74 PET/CT and intra-operative findings during SL. The composite reference standard for 'true' (intraperitoneal) tumor burden includes SL-based peritoneal cancer index scores, biopsy, imaging and intra-operative findings. If [18F]AlF-FAPI-74 PET/CT proves reliable, its cost-effectiveness will be compared to the PLASTIC-study. Recruitment started July 3rd 2025 and will continue for 36 months.DISCUSSION: This study hypothesizes that [18F]AlF-FAPI-74 PET/CT can detect two-thirds of all gastric cancer patients with M1-disease according to the reference standard. Additionally, an [18F]AlF-FAPI-74 PET/CT scan may reduce healthcare costs, optimize treatment pathways and patients' QoL. The study findings will be relevant for countries with similar treatment algorithms and healthcare systems.TRIAL REGISTRATION: ClinicalTrials.gov, NCT07018661. This trial was registered prospectively on June 12th, 2025.",

author = "Lianne Triemstra and Spruijt, \{Sarah W J M\} and \{PLASTIC-3 Study Group\} and Dennis Vriens and Erik Vegt and Mesker, \{Wilma E\} and Hawinkels, \{Lukas J A C\} and Sopany Saing and Marije Slingerland and Vera Kemp and Crobach, \{Stijn A L P\} and Goeman, \{Jelle J\} and Martin Pool and Petra Dibbets-Schneider and Bennink, \{Roel J\} and \{van Berge Henegouwen\}, \{Mark I\} and \{van Det\}, \{Marc J\} and \{van Etten\}, \{Boudewijn J\} and Hartgrink, \{Henk H\} and \{van Hillegersberg\}, Richard and Lam, \{Marnix G E H\} and Smulders, \{Nanda M\} and Luyer, \{Misha D P\} and Walter Noordzij and Owers, \{Emilia C\} and Oyen, \{Wim J G\} and \{van Sandick\}, \{Johanna W\} and Wendy Schreurs and \{de Steur\}, \{Wobbe O\} and Stoot, \{Jan H M B\} and Weijs, \{Leo E\} and Wijnhoven, \{Bas P L\} and Witteman, \{Bart P L\} and Ruurda, \{Jelle P\} and \{de Geus-Oei\}, Lioe-Fee",

note = "Publisher Copyright: {\textcopyright} 2025. The Author(s).",

year = "2026",

month = jan,

day = "27",

doi = "10.1186/s12885-025-15347-7",

language = "English",

volume = "26",

pages = "135",

journal = "BMC Cancer",

issn = "1471-2407",

publisher = "BioMed Central Ltd.",

number = "1",

}

Triemstra, L, Spruijt, SWJM, PLASTIC-3 Study Group, Vriens, D, Vegt, E, Mesker, WE, Hawinkels, LJAC, Saing, S, Slingerland, M, Kemp, V, Crobach, SALP, Goeman, JJ, Pool, M, Dibbets-Schneider, P, Bennink, RJ, van Berge Henegouwen, MI, van Det, MJ, van Etten, BJ, Hartgrink, HH, van Hillegersberg, R, Lam, MGEH, Smulders, NM, Luyer, MDP, Noordzij, W, Owers, EC, Oyen, WJG, van Sandick, JW, Schreurs, W, de Steur, WO, Stoot, JHMB, Weijs, LE, Wijnhoven, BPL, Witteman, BPL, Ruurda, JP & de Geus-Oei, L-F 2026, '[18F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer: a multicenter prospective study (PLASTIC-3 study)', BMC Cancer, vol. 26, no. 1, 135, pp. 135. https://doi.org/10.1186/s12885-025-15347-7

TY - JOUR

T1 - [18F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer

T2 - a multicenter prospective study (PLASTIC-3 study)

AU - Triemstra, Lianne

AU - Spruijt, Sarah W J M

AU - PLASTIC-3 Study Group

AU - Vriens, Dennis

AU - Vegt, Erik

AU - Mesker, Wilma E

AU - Hawinkels, Lukas J A C

AU - Saing, Sopany

AU - Slingerland, Marije

AU - Kemp, Vera

AU - Crobach, Stijn A L P

AU - Goeman, Jelle J

AU - Pool, Martin

AU - Dibbets-Schneider, Petra

AU - Bennink, Roel J

AU - van Berge Henegouwen, Mark I

AU - van Det, Marc J

AU - van Etten, Boudewijn J

AU - Hartgrink, Henk H

AU - van Hillegersberg, Richard

AU - Lam, Marnix G E H

AU - Smulders, Nanda M

AU - Luyer, Misha D P

AU - Noordzij, Walter

AU - Owers, Emilia C

AU - Oyen, Wim J G

AU - van Sandick, Johanna W

AU - Schreurs, Wendy

AU - de Steur, Wobbe O

AU - Stoot, Jan H M B

AU - Weijs, Leo E

AU - Wijnhoven, Bas P L

AU - Witteman, Bart P L

AU - Ruurda, Jelle P

AU - de Geus-Oei, Lioe-Fee

PY - 2026/1/27

Y1 - 2026/1/27

N2 - BACKGROUND: Treatment decisions for locally advanced gastric adenocarcinoma rely on staging with gastroscopy, computed tomography (CT), and staging laparoscopy (SL). However, CT often fails to detect peritoneal and other distant metastases, and SL is an invasive procedure with complication risks and costs. Therefore, an accurate non-invasive imaging biomarker to detect such metastases could improve the care for gastric cancer patients. Radiolabeled fibroblast-activating protein inhibitors (FAPI), targeting stromal cancer-associated fibroblasts, are promising radiotracers. Preliminary Asian studies indicate that FAPI PET/CT outperforms [18F]FDG PET/CT in tracer uptake, tumor-to-background ratio and diagnostic sensitivity in gastric cancer. However, larger studies using FAPI PET/CT in homogeneous, representative cohorts are needed to validate and translate these findings to Western populations. This study evaluates the clinical impact and diagnostic accuracy of [18F]AlF-FAPI-74 PET/CT for optimizing patient staging, aiming to reduce futile toxic neoadjuvant and surgical treatments. This may help optimize treatment pathways, enhance quality of life (QoL), and reduce patient burden and healthcare costs.METHODS: This Dutch multicenter prospective clinical trial will recruit 250 patients with resectable, locally advanced gastric adenocarcinoma (cT3-4N0-3M0) as determined by gastroscopy and CT, planned for curative treatment. The modality under investigation is [18F]AlF-FAPI-74 PET/CT. The primary outcome is the proportion of patients in whom [18F]AlF-FAPI-74 PET/CT leads to a change in treatment intent. Secondary outcomes include diagnostic performance, patient burden from incidental or false-positive PET/CT findings, diagnostic delay, and clinicopathological correlation between [18F]AlF-FAPI-74 PET/CT and intra-operative findings during SL. The composite reference standard for 'true' (intraperitoneal) tumor burden includes SL-based peritoneal cancer index scores, biopsy, imaging and intra-operative findings. If [18F]AlF-FAPI-74 PET/CT proves reliable, its cost-effectiveness will be compared to the PLASTIC-study. Recruitment started July 3rd 2025 and will continue for 36 months.DISCUSSION: This study hypothesizes that [18F]AlF-FAPI-74 PET/CT can detect two-thirds of all gastric cancer patients with M1-disease according to the reference standard. Additionally, an [18F]AlF-FAPI-74 PET/CT scan may reduce healthcare costs, optimize treatment pathways and patients' QoL. The study findings will be relevant for countries with similar treatment algorithms and healthcare systems.TRIAL REGISTRATION: ClinicalTrials.gov, NCT07018661. This trial was registered prospectively on June 12th, 2025.

AB - BACKGROUND: Treatment decisions for locally advanced gastric adenocarcinoma rely on staging with gastroscopy, computed tomography (CT), and staging laparoscopy (SL). However, CT often fails to detect peritoneal and other distant metastases, and SL is an invasive procedure with complication risks and costs. Therefore, an accurate non-invasive imaging biomarker to detect such metastases could improve the care for gastric cancer patients. Radiolabeled fibroblast-activating protein inhibitors (FAPI), targeting stromal cancer-associated fibroblasts, are promising radiotracers. Preliminary Asian studies indicate that FAPI PET/CT outperforms [18F]FDG PET/CT in tracer uptake, tumor-to-background ratio and diagnostic sensitivity in gastric cancer. However, larger studies using FAPI PET/CT in homogeneous, representative cohorts are needed to validate and translate these findings to Western populations. This study evaluates the clinical impact and diagnostic accuracy of [18F]AlF-FAPI-74 PET/CT for optimizing patient staging, aiming to reduce futile toxic neoadjuvant and surgical treatments. This may help optimize treatment pathways, enhance quality of life (QoL), and reduce patient burden and healthcare costs.METHODS: This Dutch multicenter prospective clinical trial will recruit 250 patients with resectable, locally advanced gastric adenocarcinoma (cT3-4N0-3M0) as determined by gastroscopy and CT, planned for curative treatment. The modality under investigation is [18F]AlF-FAPI-74 PET/CT. The primary outcome is the proportion of patients in whom [18F]AlF-FAPI-74 PET/CT leads to a change in treatment intent. Secondary outcomes include diagnostic performance, patient burden from incidental or false-positive PET/CT findings, diagnostic delay, and clinicopathological correlation between [18F]AlF-FAPI-74 PET/CT and intra-operative findings during SL. The composite reference standard for 'true' (intraperitoneal) tumor burden includes SL-based peritoneal cancer index scores, biopsy, imaging and intra-operative findings. If [18F]AlF-FAPI-74 PET/CT proves reliable, its cost-effectiveness will be compared to the PLASTIC-study. Recruitment started July 3rd 2025 and will continue for 36 months.DISCUSSION: This study hypothesizes that [18F]AlF-FAPI-74 PET/CT can detect two-thirds of all gastric cancer patients with M1-disease according to the reference standard. Additionally, an [18F]AlF-FAPI-74 PET/CT scan may reduce healthcare costs, optimize treatment pathways and patients' QoL. The study findings will be relevant for countries with similar treatment algorithms and healthcare systems.TRIAL REGISTRATION: ClinicalTrials.gov, NCT07018661. This trial was registered prospectively on June 12th, 2025.

UR - https://www.scopus.com/pages/publications/105028868784

U2 - 10.1186/s12885-025-15347-7

DO - 10.1186/s12885-025-15347-7

M3 - Article

C2 - 41299326

SN - 1471-2407

VL - 26

SP - 135

JO - BMC Cancer

JF - BMC Cancer

IS - 1

M1 - 135

ER -

[18F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer: a multicenter prospective study (PLASTIC-3 study)

Abstract

Bibliographical note

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