68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT for locally advanced or recurrent pancreatic cancer staging and restaging after chemoradiotherapy

Abstract

Purpose: ⁶⁸Ga-labeled fibroblast activation protein inhibitor (FAPI) is a novel PET tracer with great potential for staging pancreatic cancer. Data on locally advanced or recurrent disease is sparse, especially on tracer uptake before and after high dose chemoradiotherapy (CRT). The aim of this study was to evaluate [⁶⁸Ga]Ga-FAPI-46 PET/CT staging in this setting. Methods: Twenty-seven patients with locally recurrent or locally advanced pancreatic adenocarcinoma (LRPAC n = 15, LAPAC n = 12) in stable disease or partial remission after chemotherapy underwent FAPI PET/CT and received consolidation CRT in stage M0 with follow-up FAPI PET/CT every three months until systemic progression. Quantitative PET parameters SUV_max, SUV_mean, FAPI-derived tumor volume and total lesion FAPI-uptake were measured in baseline and follow-up PET/CT scans. Contrast-enhanced CT (ceCT) and PET/CT data were evaluated blinded and staged according to TNM classification. Results: FAPI PET/CT modified staging compared to ceCT alone in 23 of 27 patients in baseline, resulting in major treatment alterations in 52% of all patients (30%: target volume adjustment due to N downstaging, 15%: switch to palliative systemic chemotherapy only due to diffuse metastases, 7%: abortion of radiotherapy due to other reasons). Regarding follow-up scans, major treatment alterations after performing FAPI PET/CT were noted in eleven of 24 follow-up scans (46%) with switch to systemic chemotherapy or best supportive care due to M upstaging and ablative radiotherapy of distant lymph node and oligometastasis. Unexpectedly, in more than 90 % of the follow-up scans, radiotherapy did not induce local fibrosis related FAPI uptake. During the first follow-up, all quantitative PET metrics decreased, and irradiated lesions showed significantly lower FAPI uptake in locally controlled disease (SUV_max p = 0.047, SUV_mean p = 0.0092) compared to local failure. Conclusion: Compared to ceCT, FAPI PET/CT led to major therapeutic alterations in patients with LRPAC and LAPAC prior to and after radiotherapy, which might help identify patients benefiting from adjustments in every treatment stage. FAPI PET/CT should be considered a useful diagnostic tool in LRPAC or LAPAC before and after CRT.

Keywords: fibroblast activation protein inhibitor; locally advanced pancreatic adenocarcinoma; locally recurrent pancreatic adenocarcinoma; positron emission tomography; radiochemotherapy.

Figure 1

Changes in TNM staging based on differences between blinded reading of FAPI-PET/CT and CT scans before treatment and during first, second and third follow-up.

Figure 2

Baseline [⁶⁸Ga]Ga-FAPI-46 PET/CT of a patient with locally recurrent pancreatic adenocarcinoma at the mesentery root. A maximum intensity projection with a red line representing axial slices B-E, B and D transaxial fusion of PET/CT data of the upper abdomen, C and E transaxial, corresponding contrast-enhanced CT scan in arterial phase. Suspicious peripancreatic lymph nodes with a short axis diameter over 10 mm (red arrows) without FAPI signal were rated benign and consequently downstaged.

Figure 3

A major treatment changes after baseline [⁶⁸Ga]Ga-FAPI-46 PET/CT, B major treatment changes after follow-up [⁶⁸Ga]Ga-FAPI-46 PET/CT (1^st, 2^nd and 3^rd follow-up combined).

Figure 4

[⁶⁸Ga]Ga-FAPI-46 PET/CT of a patient with locally recurrent pancreatic adenocarcinoma before (Baseline, A-C) and 3 months after (first follow-up D-F) treatment with chemoradiotherapy (Patient #7). A and D maximum intensity projections, B and E transaxial fusion of PET/CT of the upper abdomen, C and F transaxial contrast-enhanced CT scan of the upper abdomen. Red arrows (A-C) mark intense FAPI uptake of small-volume tumor tissue at the minor gastric margin. The red arrow in F marks stable tumor tissue without measurable FAPI signaling post-treatment. SUV_max at 1^st follow-up was 8,2 / SUV_mean was 5,0 and at 2^nd follow-up 1,7 / 1,4, respectively. In the absence of the detection of vital tumor remnants in the [⁶⁸Ga]Ga-FAPI-46 PET/CT, complete remission of the disease was assumed. In this case, the significant decrease of the FAPI uptake in the 1^st follow-up scan was associated with local tumor control within the next 6 months after therapy. Patient #7 showed local progression in the 3^rd follow-up scan 9 months post CRT.

Figure 5

3^rd follow-up [⁶⁸Ga]Ga-FAPI-46 PET/CT of a patient with locally recurrent pancreatic adenocarcinoma 9 months after chemoradiotherapy (Patient #2) A maximum intensity projection, B and D transaxial and sagittal PET/CT fusion, C and E contrast-enhanced CT scan (bone window). Red arrows (A, B, D) mark intense FAPI signal of first lumbar vertebra without a detectable lesion in the bone. In the absence of any morphological finding in the CT scan, this scan was classified as M upstaging and, in the consensus of an interdisciplinary tumor board, considered as singular metastatic spread to the bone. Biopsy and histopathological confirmation were not performed. The patient received curative intended local radiotherapy of the first lumbar vertebra.

Figure 6

Quantitative FAPI-PET parameters FAPI-derived tumor volume (FDTV), SUV_max, SUV_mean, and total lesion FAPI-uptake (TLF) of all irradiated patients (n = 27) before treatment and during 1^st, 2^nd and 3^rd follow-up.

Figure 7

A quantitative FAPI-PET parameters FAPI-derived tumor volume (FDTV), SUV_max, SUV_mean, and total lesion FAPI-uptake (TLF) three months after chemoradiation. B delta values before treatment and three months after treatment of quantitative PET parameters. Patients without local progression up to six months after treatment (PD no, 4/7) were compared with patients who experienced early local progression (PD yes, 3/7).