Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial
The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). <sup>68</sup>Ga-NOTA-AE105 is a novel positron emission tomography (PET) radioligand with high affinity to urokinase-type plasminogen activator receptor (uPAR),...
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MDPI AG
2023-10-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/21/3303 |
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| author | Mads Lawaetz Anders Christensen Karina Juhl Giedrius Lelkaitis Kirstine Karnov Esben Andreas Carlsen Birgitte W. Charabi Annika Loft Dorota Czyzewska Christian von Buchwald Andreas Kjaer |
| author_facet | Mads Lawaetz Anders Christensen Karina Juhl Giedrius Lelkaitis Kirstine Karnov Esben Andreas Carlsen Birgitte W. Charabi Annika Loft Dorota Czyzewska Christian von Buchwald Andreas Kjaer |
| author_sort | Mads Lawaetz |
| collection | DOAJ |
| description | The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). <sup>68</sup>Ga-NOTA-AE105 is a novel positron emission tomography (PET) radioligand with high affinity to urokinase-type plasminogen activator receptor (uPAR), a receptor expressed on the surfaces of tumor cells. The aim of this study was to investigate the diagnostic value of uPAR-PET/CT (computerized tomography) in detecting regional metastatic disease in patients with OSCC and OPSCC compared to the current imaging work-up. In this phase II trial, patients with OSCC and OPSCC referred for surgical treatment were prospectively enrolled. Before surgery, <sup>68</sup>Ga-NOTA-AE105 uPAR-PET/CT was conducted, and SUVmax values were obtained from the primary tumor and the suspected lymph nodes. Histology results from lymph nodes were used as the standard of truth of metastatic disease. The diagnostic values of <sup>68</sup>Ga-uPAR-PET/CT were compared to conventional routine preoperative imaging results (CT and/or MRI). The uPAR expression in resected primary tumors and metastases was determined by immunohistochemistry and quantified digitally (H-score). A total of 61 patients underwent uPAR-PET/CT. Of the 25 patients with histologically verified lymph node metastases, uPAR-PET/CT correctly identified regional metastatic disease in 14 patients, with a median lymph node metastasis size of 14 mm (range 3–27 mm). A significant correlation was found between SUVmax and the product of the H-score and tumor depth (r = 0.67; <i>p</i> = 0.003). The sensitivity and specificity of uPAR-PET/CT in detecting regional metastatic disease were 56% and 100%, respectively. When added to CT/MRI, uPAR-PET was able to upstage 2/11 (18%) of patients with occult metastases and increase the sensitivity to 64%. The sensitivity and specificity of <sup>68</sup>Ga-NOTA-AE105 uPAR-PET/CT were equivalent to those of CT/MRI. The significant correlation between SUVmax and uPAR expression verified the target specificity of <sup>68</sup>Ga-NOTA-AE105. Despite the target specificity, the sensitivity of imaging is too low for nodal staging and it cannot replace neck dissection. |
| first_indexed | 2024-03-11T11:31:48Z |
| format | Article |
| id | doaj.art-8ae4584e4d7948c28d639b68eece44b4 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T11:31:48Z |
| publishDate | 2023-10-01 |
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| series | Diagnostics |
| spelling | doaj.art-8ae4584e4d7948c28d639b68eece44b42023-11-10T15:00:55ZengMDPI AGDiagnostics2075-44182023-10-011321330310.3390/diagnostics13213303Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II TrialMads Lawaetz0Anders Christensen1Karina Juhl2Giedrius Lelkaitis3Kirstine Karnov4Esben Andreas Carlsen5Birgitte W. Charabi6Annika Loft7Dorota Czyzewska8Christian von Buchwald9Andreas Kjaer10Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, DenmarkDepartment of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, DenmarkDepartment of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital—Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, DenmarkDepartment of Pathology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, DenmarkDepartment of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, DenmarkDepartment of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital—Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, DenmarkDepartment of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, DenmarkDepartment of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital—Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, DenmarkDepartment of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital—Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, DenmarkDepartment of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, DenmarkDepartment of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital—Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, DenmarkThe detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). <sup>68</sup>Ga-NOTA-AE105 is a novel positron emission tomography (PET) radioligand with high affinity to urokinase-type plasminogen activator receptor (uPAR), a receptor expressed on the surfaces of tumor cells. The aim of this study was to investigate the diagnostic value of uPAR-PET/CT (computerized tomography) in detecting regional metastatic disease in patients with OSCC and OPSCC compared to the current imaging work-up. In this phase II trial, patients with OSCC and OPSCC referred for surgical treatment were prospectively enrolled. Before surgery, <sup>68</sup>Ga-NOTA-AE105 uPAR-PET/CT was conducted, and SUVmax values were obtained from the primary tumor and the suspected lymph nodes. Histology results from lymph nodes were used as the standard of truth of metastatic disease. The diagnostic values of <sup>68</sup>Ga-uPAR-PET/CT were compared to conventional routine preoperative imaging results (CT and/or MRI). The uPAR expression in resected primary tumors and metastases was determined by immunohistochemistry and quantified digitally (H-score). A total of 61 patients underwent uPAR-PET/CT. Of the 25 patients with histologically verified lymph node metastases, uPAR-PET/CT correctly identified regional metastatic disease in 14 patients, with a median lymph node metastasis size of 14 mm (range 3–27 mm). A significant correlation was found between SUVmax and the product of the H-score and tumor depth (r = 0.67; <i>p</i> = 0.003). The sensitivity and specificity of uPAR-PET/CT in detecting regional metastatic disease were 56% and 100%, respectively. When added to CT/MRI, uPAR-PET was able to upstage 2/11 (18%) of patients with occult metastases and increase the sensitivity to 64%. The sensitivity and specificity of <sup>68</sup>Ga-NOTA-AE105 uPAR-PET/CT were equivalent to those of CT/MRI. The significant correlation between SUVmax and uPAR expression verified the target specificity of <sup>68</sup>Ga-NOTA-AE105. Despite the target specificity, the sensitivity of imaging is too low for nodal staging and it cannot replace neck dissection.https://www.mdpi.com/2075-4418/13/21/3303urokinase-type plasminogen activator receptor (uPAR)PET/CT<sup>68</sup>Ga-NOTA-AE105lymph node metastaseshead and neck cancer |
| spellingShingle | Mads Lawaetz Anders Christensen Karina Juhl Giedrius Lelkaitis Kirstine Karnov Esben Andreas Carlsen Birgitte W. Charabi Annika Loft Dorota Czyzewska Christian von Buchwald Andreas Kjaer Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial Diagnostics urokinase-type plasminogen activator receptor (uPAR) PET/CT <sup>68</sup>Ga-NOTA-AE105 lymph node metastases head and neck cancer |
| title | Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial |
| title_full | Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial |
| title_fullStr | Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial |
| title_full_unstemmed | Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial |
| title_short | Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial |
| title_sort | diagnostic value of preoperative upar pet ct in regional lymph node staging of oral and oropharyngeal squamous cell carcinoma a prospective phase ii trial |
| topic | urokinase-type plasminogen activator receptor (uPAR) PET/CT <sup>68</sup>Ga-NOTA-AE105 lymph node metastases head and neck cancer |
| url | https://www.mdpi.com/2075-4418/13/21/3303 |
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