Rationale and Trial Design of PFB-03 Study: Diagnostic Performance and Clinical Application of 18F-FAPI-PET/CT for Detecting Axillary Lymph Node Metastasis in Breast Cancer Patients After Neoadjuvant Therapy

Axillary lymph node (ALN) status is a crucial prognostic factor in breast cancer. Accurate, non-invasive methods for evaluating axillary lymph node metastasis after neoadjuvant therapy (NAT) are needed to optimize surgical decisions and minimize patient morbidity. Fibroblast Activation Protein Inhibitor (FAPI) PET/CT targets cancer-associated fibroblasts and may improve diagnostic accuracy. This study aims to assess the diagnostic performance and clinical utility of 18F-FAPI PET/CT in detecting ALN metastasis after NAT in breast cancer patients. This prospective, single-center study will enroll breast cancer patients with cT1-4N0-1M0 stage before NAT, who will undergo pre-surgical 18F-FAPI PET/CT followed by sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) guided by protocol stratification based on FAPI PET/CT and clinical findings. The primary endpoint is the diagnostic accuracy of 18F-FAPI PET/CT for ALN metastasis versus pathology. Secondary endpoints include false-negative rates (FNR) of SLNB, lymphedema rates, and long-term outcomes such as local recurrence and survival rates.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer

• Study Type: Observational
• Enrollment (Estimated): 172

Contacts and Locations

• Study Contact: Name: Ru Yao; Phone Number: +861069158724; Email: albertyaopumc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study is designed as a single-center, prospective observational diagnostic accuracy trial. It will be conducted at the Department of Breast Sugery and Nuclear Medicine of PUMCH, Beijing, China, between June 2025 and May 2027. The study population consists of stage cT1-4N0-1M0 breast cancer patients with who received NAT (Fig. 1). After completion of NAT, surgical approach (ALND/SLNB) is guided by protocol stratification based on 18F-FAPI PET/CT and clinical findings. There is no randomization in this study, and all enrolled patients will undergo the index test and the reference standard surgical evaluation.

Description

Inclusion Criteria:

• Must provide written informed consent
• Female at 18-80 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• With anticipated survival of at least 36 months
• Pathologically confirmed invasive breast cancer with clinical stage of T1-4N0-1M0
• Received standard NAT for BC (including either neoadjuvant chemotherapy or neoadjuvant targeted therapy, or a combination)
• Have willingness to take the 18F-FAPI PET/CT imaging
• With adequate organ function (neutrophil count ≥ 1.5 × 10⁹/L; platelet count ≥ 90 × 10⁹/L; hemoglobin ≥ 90 g/L; total bilirubin ≤ 1.5 × upper limit of normal [ULN]; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; blood urea nitrogen (BUN) and serum creatinine (Cr) ≤ 1.5 × ULN; international normalized ratio (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN).

Exclusion Criteria:

• Evidence of distant metastatic disease (M1)
• Pregnant or lactating women
• Failure to complete the planned NAT
• Prior surgical intervention in the ipsilateral axilla
• Diagnosis of any other malignancy within the past 5 years (exceptions: adequately treated non-melanoma skin cancer, cervical carcinoma in situ, papillary thyroid cancer)
• Known hypersensitivity to the FAPI tracer or any excipients
• With any serious uncontrolled medical condition that would make the patient unsuitable for surgery or PET/CT (e.g. unstable cardiac disease, severe claustrophobia unresponsive to anxiolytics, renal failure preventing CT contrast if needed)
• Failure to lie still for imaging (about 20-30 minutes) or adhere to follow-up due to psychiatric, cognitive, or social reasons.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Double positive; If clinical exam and 18F-FAPI PET/CT are positive for ALN involvement both before and after NAT, the patient proceeds directly to ALND as per standard guidelines.
Single Positive; If clinically/pathologically node-positive (c/pN1) pre-NAT but becomes clinically and 18F-FAPI PET/CT negative post-NAT, the patient undergoes ALND as per standard guidelines. However, within this ALND procedure, sentinel lymph nodes (SLNs) will be identified and sent separately for pathological analysis to assess the FNR of FAPI-PET guided SLNB evaluation in this specific scenario, without additional trauma or cost to the patient.
Double Negative; Includes two subgroups: (a) Patients who were clinically/pathologically node-negative pre-NAT and remain clinically and 18F-FAPI PET/CT negative post-NAT. (b) Patients who were clinically node-negative pre- and post-NAT, but 18F-FAPI-PET/CT becomes positive post-NAT. Within Cohort 3, management depends on patient preference: either proceed directly to ALND or undergo SLNB first (using dual tracer). If SLNB is positive, completion ALND follows; if negative, ALND is omitted. Dual tracer methods include methylene blue, contrast-enhanced ultrasound, or radionuclide imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diagnostic accuracy of 18F-FAPI PET/CT for detecting residual axillary lymph node metastases after NAT	The primary endpoint of the study is the diagnostic accuracy of 18F-FAPI PET/CT for detecting residual axillary lymph node metastases after NAT, on a patient-level analysis. This will be assessed by calculating: i)Sensitivity: proportion of patients with pathologically proven residual nodal metastasis who had a positive 18F-FAPI PET/CT (true positive rate). ii)Specificity: proportion of patients with no residual nodal metastasis (pathologic nodal pCR) who had a negative PET/CT (true negative rate). iii)Positive predictive value (PPV): probability that a PET-positive patient truly has nodal disease on pathology. iv)Negative predictive value (NPV): probability that a PET-negative patient is truly node-negative on pathology. v)Overall accuracy: proportion of all patients correctly classified by PET (true positives + true negatives divided by total).	Through study completion, an average of 3 years.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: May 26, 2025
• First Submitted That Met QC Criteria: June 7, 2025
• First Posted (Actual): June 10, 2025

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Breast Diseases; Neoplasm Metastasis; Breast Neoplasms; Lymphatic Metastasis
• Other Study ID Numbers: PUMCH-PFB03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No