Characteristics of tumour stroma in regional lymph node metastases in colorectal cancer patients: a theoretical framework for future diagnostic imaging with FAPI PET/CT

Abstract

Purpose The recently developed fibroblast activation protein inhibitor (FAPI) tracer for PET/CT, binding tumour-stromal cancer-associated fibroblasts, is a promising tool for detection of positive lymph nodes. This study provides an overview of features, including sizes and tumour-stromal content, of lymph nodes and their respective lymph node metastases (LNM) in colorectal cancer (CRC), since literature lacks on whether LNMs contain sufficient stroma to potentially allow FAPI-based tumour detection. Methods Haematoxylin and eosin-stained tissue slides from 73 stage III colon cancer patients were included. Diameters and areas of all lymph nodes and their LNMs were assessed, the amount of stroma by measuring the stromal compartment area, the conventional and total tumour-stroma ratios (TSR-c and TSR-t, respectively), as well as correlations between these parameters. Also, subgroup analysis using a minimal diameter cut off of 5.0 mm was performed. Results In total, 126 lymph nodes were analysed. Although positive correlations were observed between node and LNM for diameter and area (r = 0.852, p < 0.001 and r = 0.960, p < 0.001, respectively), and also between the LNM stromal compartment area and nodal diameter (r = 0.612, p < 0.001), nodal area (r = 0.747, p < 0.001) and LNM area (r = 0.746, p < 0.001), novel insight was that nearly all (98%) LNMs contained stroma, with median TSR-c scores of 35% (IQR 20–60%) and TSR-t of 20% (IQR 10–30%). Moreover, a total of 32 (25%) positive lymph nodes had a diameter of < 5.0 mm. Conclusion In LNMs, stroma is abundantly present, independent of size, suggesting a role for FAPI PET/CT in improved lymph node detection in CRC.

Visualization of metabolic parameters after colorectal carcinoma patients using [68Ga]Ga-FAPI PET

“…and peritoneal implants (100.0% vs. 55.0%). Regarding the detection of lymph nodes and distant metastasis, N and M stages are crucial for the treatment and prognosis of patients with CRC [29,30]. In our study, there were no signi cant differences in the FAPI PET parameters among patients with different N and M stages.…”

“…The SUVmax thresholds(30, 40, 50, and 60%) and SUVmean thresholds(30, 40, and 50%) in patients with stage T4 tumors were higher than those in patients with stage T3 tumors. Furthermore, the tumor SUVmean 30% in our analysis can be reliably applied in future studies.…”

Results from the UNITED study: a multicenter study validating the prognostic effect of the tumor–stroma ratio in colon cancer

“…The intricate and dynamic tumor–stroma crosstalk has been observed to include the cancer-associated fibroblasts as important players, potentially also enabling the seed-and-soil principle of Paget and causing stromal metastases in lymph nodes. 14 , 33 The TSR can be scored on these metastases as well, and patients with stroma-high primary tumors and stroma-high lymph node metastases have been observed to have the worst survival. 34 , 35 Even small lymph nodes ≤5 mm in diameter, during routine radiologic imaging not suspected of malignancy, can contain metastases.…”

“…Scoring the TSR in lymph nodes in the future, as well as more research on improving positive lymph node detection, is pertinent for an even more tailored treatment. 33 …”

FAPI PET/CT in Diagnostic and Treatment Management of Colorectal Cancer: Review of Current Research Status

“…A study of 28 cases of malignant tumors in the lower digestive tract showed for the first time that FAPI showed high uptake and good TBR in primary and metastatic colorectal cancer lesions, which further changed the clinical stage of TNM in related patients and improved target volume delineation [ 46 ]. For the lymph node metastasis of colorectal cancer, the present research shows that there are many stroma in the lymph nodes and corresponding lymph node metastases (LNM) of CRC, which indicates that FAPI PET/CT may improve the identification of lymph node metastases of CRC [ 47 ].…”