[68Ga]Ga-FAPI PET/CT in Gastric and Gastroesophageal Junctional Cancer

Study Overview
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Brief Summary
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Twenty (n=20) patients with gastric cancer or gastro-esophageal junctional cancer will undergo FAPI PET/CTs in addition to routing diagnostic workup (including FDG PET/CT) at primary staging and restaging. The FAPI PET/CT results will be compared to conventional imaging (including FDG PET/CT) using histopathology as reference standard, and the diagnostic accuracy will be determined. FAP-immunohistochemistry will be conducted in surgical specimens. FAPI PET/CT's impact on patient management and the prognostic value of FAPI PET/CT will be evaluated.

Detailed Description
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A new and promising PET-tracer in oncology has been developed; Gallium-68 labelled fibroblast activation protein inhibitor (FAPI). In general, FAPI PET/CT delivers increased sensitivity compared to 18F-Fluorodeoxyglucose (FDG) PET/CT in cancer types of mesenchymal origin (i.e., sarcomas), and in cancers characterized by a large proportion of stromal cells such as gastric and pancreatic cancers. It is currently debated whether FAPI PET/CT will take over FDG PET/CTs well-established role in oncological PET/CT, but more studies are needed to evaluate the diagnostic accuracy. The clinical interest in FAPI extends beyond the use as a diagnostic tool, as the 68Ga-isotope can be replaced by a β-emitting isotope, e.g., 177-Lu or 90-Y, enabling radionuclide therapy of FAPI-avid cancers. In recent comparative studies of FDG- and FAPI PET/CT, all primary tumors of the stomach were detected on FAPI PET, whereas the reported detection rate on FDG PET ranged from 40% to 86%. Regarding metastases, FAPI PET/CT showed comparable or better detection rate for regional lymph nodes, but outperformed FDG PET/CT in the detection of peritoneal and other distant metastases. Re-staging with FAPI PET after chemotherapy has been attempted in only a handful of patients and seems feasible. Even though the results of FAPI PET/CT compared to conventional imaging seem convincing, there are several limitations and therefore FAPI PET/CT is not yet implemented in cancer diagnostics. The investigators are conducting a prospective explorative study complying with the Standard for Reporting Diagnostic Accuracy (STARD) criteria where 20 patients with gastric cancer or gastro-eophageal junctional cancer are recruited. Study subject will undergo FAPI PET/CT at primary staging (before treatment, i.e., neoadjuvant chemotherapy or surgery) and at restaging (after neoadjuvant chemotherapy - before surgery) in addition to routing diagnostic workup (including FDG PET/CT). The FAPI PET/CT will be blinded and the choice of treatment will not be influence by the FAPI PET/CT results'. The additional scans will not interfere with or delay routine diagnostic workup or treatment. The FAPI PET/CTs (at primary staging and restaging) will be compared to the corresponding FDG PET/CTs, and histopathology of biopsied material and surgical specimens will serve as reference standard. FAPI PET/CTs before and after neoadjuvant chemotherapy will be assessed and compared to the FDG PET/CTs. FAP-immunohistochemistry will be conducted in surgical specimens. A tentative retrospective Multi-Disciplinary Team conference (MDT) will be arranged where treating clinicans are presented the FAPI PET/CT, and potential changes in patient management will be evaluated. This tentative MDT will not influence patient management. Follow up will be conducted for 10 years to evaluate the prognostic value of FAPI PET/CT.

Official Title
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[68Ga]Ga-FAPI PET/CT: The Dagnostic Accuracy for Primary Staging and Re-staging After Chemotherapy in Patients With Gastric and Gastro-esophageal Junctional Cancer

Conditions
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Gastric Cancer, Gastro Esophageal Junctional Cancer, Cancer

Intervention / Treatment
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* Drug: 68Ga-FAPi-46


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed with biopsy verified gastric or GEJ cancer and referred to primary staging FDG PET/CT Deemed resectable and operable at the MDT, with or without neoadjuvant chemotherapy Considered physically and mentally able to participate in the research project Can read and understand Danish 18-years or older and able to consent to project participation Exclusion Criteria: Patients with non-resectable, inoperable, or recurrent gastric or GEJ cancer Patients with an imminent need for surgery or in an emergency Known concurrent other malignancy within the previous 5 years other than non-melanoma skin cancer Patients not suited for surgery or neoadjuvant chemotherapy followed by surgery Subject weighing more than 180 kg (weight limit scanner) or unable to fit within the imaging gantry History of allergic reactions / hypersensitivity attributed to 18F-FDG or 68Ga-FAPI-46. Severe claustrophobia unresponsive to oral anxiolytics Subjects with any medical condition or other circumstances that, in the opinion of the Investigator, would significantly decrease the reliability of data, achievement of study objectives or completing the study. Pregnant, lactating, or breastfeeding women. Potential pregnant women of childbearing potential[1] not using effective contraceptives[2]. Potential pregnancy will be ascertained by a pregnancy test (urine humane choriogonadotropin (HCG) or serum HCG) < 48 hours before injection with 68Ga-FAPI-46. Inability to remain still for the duration of the examination Women of childbearing potential are defined as all women physiologically capable of becoming pregnant, i.e., not sterilized (bilateral tubectomy/occlusion, hysterectomy, bilateral oophorectomy) and not post-menopausal. In cases of uncertain menopausal status, serum follicle stimulating hormone (FSH) levels and menstruation history can be assessed. Effective contraceptives include sexual abstinence, vasectomized partner, combined hormonal contraception (oral, intravaginal, transdermal), progesterone-only contraceptive (oral, injectable, implantable), or working intrauterine device (hormonal, non-hormonal).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Twenty consecutive patients newly diagnosed with gastric or gastro-esophageal junction cancer are recruited.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gastric or gastro-esophageal junctioncancer<br>Patients with biopsy verified gastric or gastro-esophageal junction cancer undergo FAPI PET/CT in addition to conventional imaging | Drug: 68Ga-FAPi-46<br>* Gastric or gatro-esophageal junction cancer patients undergo 68Ga-FAPi-46 PET/CT at primary staging and at restaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy | Compare the FAPI PET/CT and FDG PET/CT findings in primary tumor, regional lymph nodes and distant metastases to a histopathological reference standard where the sensitivity, specificity, positive predicative value, and negative predicative values of the PET/CTs are determined, both at primary staging and at restaging | 1.5 years | 
| Staging | Compare the cancer stage (according to AJCC 8th edition TNM-classification) as determined by FAPI PET/CT compared to conventional imaging (including FDG PET/CT) at primary staging and at restaging (after neoadjuvant chemotherapy). The proportion of patients downstaged, unchanged stage, and upstaged, due to the added FAPI PET/CT are determined. | 1.5 years | 
| Patient management | Investigate what proportion of patients will be (hypothetically) treated differently due to an added FAPI PET/CT at primary staging and at restaging (after neoadjuvant chemotherapy) by the treating clinicians | 1.5 - 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake values | Standardized uptake value (SUV) and tumor to background ratio (TBR) values for primary, regional lymph nodes, and distant metastases for FAPI PET/CT and compare these values to FDG PET/CT, both at primary staging and at restaging (after neoadjuvant chemotherapy) | 1.5 years | 
| Chemotherapy effect on uptake values | Changes in SUV and TBR in primary, regional lymph nodes, and distant metastases for FAPI PET/CT - from before to after neoadjuvant chemotherapy and compare these values to the FDG PET/CT parameters. | 1.5 - 2 years | 
| Unexpected FAPI PET/CT findings | Seek supplementary information in medical records, biochemistry, pathology, or other imaging modalities for a final diagnosis/condition in cases of unexpected FAPI PET/CT findings not related to the known cancer | 1 -2 years | 
| Interobserver readability | Conduct an interobserver study of FAPI PET/CTs performed in the present and other future FAPI PET/CT in cancers studies. | 4 years | 
| Prognostic value | Investigate the prognostic value of FAPI PET/CT versus FDG PET/CT by conducting a 10 years follow up on included cancer patients. Overall survival (OS) and Recurrence free survival (RFS) will be estimated | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET/CT, Cancer, Fibroblast activation protein inhibitor, FAPI, FAPI PET/CT