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Title Diagnostic accuracy of FDG-PET-CT to identify unknown primary tumor and/or distant metastasis in patients with cervical node involvement.
Clinical Question Is FDG-PET-CT a valid diagnostic modality than the reference standard to identify unknown primary tumors and/or distant metastasis when patient presents with cervical lymph node involvement?
Clinical Bottom Line In patients presenting with neck lymph node involvement by unknown primary tumor, FDG-PET-CT is valid to identify unknown primary tumor or distant metastasis. This is supported by a systematic review performed on 20 articles including a large group of 1942 patient and by two clinical studies (retrospective). The FDG-PET showed 74% and 78% sensitivity and specificity respectively to diagnose unknown primary tumors. The FDG-PET-CT is a functional imaging modality which depends on uptake of radioactive labelled [18F] fluorodeoxyglucose by highly metabolizing malignant tissues. Because of its high sensitivity, it helps the oncologist/surgeon to plan or modify the treatment by detecting the location of primary or metastatic tumor.
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 19952921Zeynep Yapa / 201090 patients (66 male, 34 female) Gold standard-controlled diagnostic study
Key resultsThe histology and/or follow-up data were used as gold standards. In 5 patients out of 90, no tumor was found on FDG-PET-CT. In remaining 85 patients, 27 (32%) showed single organ involvement and 58 (32%) showed multiple organ involvement. 53 out of 90 (59%) malignancies were proved histologically. In 27 solitary sites, FDG-PET-CT identified 12 cases. 39/58 multiple sites were identified by FDG-PET-CT. A second primary tumor was also found in one patient. To identify primary site, the findings of FDG/PET was in accordance with the gold standard in 70 patients. Out of these 70 patients, 31 were true negative and 39 were true positive. The primary tumor site was not found to be in accordance with gold standard in three patients. The sensitivity and specificity of FDG-PET-CT was found to be 74% and 78% respectively. The positive (PPV) and negative predictive value (NPV) were 81 and 69%, respectively.
#2) 17414886Myriam Wartski/200738 patients with cervical lymph node metastases, of unknown primary tumor Gold standard-controlled diagnostic study
Key resultsThe results of this study showed uptake of FDG in 68% of patients which in turn helped to biopsy during a second rigid panendoscopy in 17 of these 26 patients. 13 out of these 17 tumors were histologically proven. The distant metastasis was confirmed in three patients. The FDG-PET-CT helped to modify the treatment in 23/38 (60%) patients.
#3) 28422888Synne Alexandra Burglin/201720 studies and 1942 adult patientsMeta-Analysis
Key resultsThe meticulous literature search in this study established the current evidence for the use of FDG-PET-CT in adult patients with unknown primary tumor with special emphasis to detection rate and false-positive findings in patients with extra cervical metastases. The study defined the term ‘Data Extraction’ as the number of patients with positive FDG-PET-CT findings which were confirmed by biopsy or composite reference standard including follow-up and other imaging modalities, divided by the total number of patients included. The author identified 20 studies with an overall detection rate of 40.93% (95% CI: 38.99%–42.87%); median detection rate and median false-positive proportion were 36.3% and 7.5%, respectively.
Evidence Search (("Positron-Emission Tomography"[Mesh]) AND "Neoplasms, Unknown Primary"[Mesh]) AND "Neoplasm Metastasis"[Mesh]
Comments on
The Evidence
Validity: According to systematic review by Synne Alexandra Burglin, the validity of FDG-PET-CT is limited when used in early diagnostic work up of tumor. As the tumor involves multiple sites, it becomes more difficult for the examiner to identify the primary site. This contradicting situation can lead to “false negative primary tumor” when it is present. The only solution to this problem is to start the diagnostic work up during initial stages. It is not always possible in clinical setting because patient is not always aware about the presence of tumor during initial stages. The other problem found in the same systematic review is heterogeneity of standard diagnostic workup. The comparison of any study should be made against the gold standard i.e. histopathological confirmation in case of tumor. Many studies included other imaging modalities, endoscopies and clinical follow up in case of unavailability or inconclusive histopathological test. Further prospective studies are needed to validate FDG-PET-CT, compare it against conventional imaging modalities and including patients with unknown primary tumors. Perspective: The highly sensitive FDG-PET-CT modality has the key role in diagnosing unknown primary tumor. It can be used as the screening tool to identify unknown primary tumors as well as distant metastasis. The results of FDG-PET-CT are also beneficial to decide the further biopsy sites and plan treatment for a patient.
Applicability FDG-PET-CT is a highly sensitive modality to detect primary or metastatic tumor. Hence it significantly reduces the cost of unnecessary diagnostic work up and directly helps to plan the treatment. Despite of all these benefits, the regulation of radiopharmaceutical agent used along with PET-CT varies across the world. The demanding regulation limits the business of pharmaceutical companies. As a result, only, few companies are present in the market to meet the increasing demand. The other problem with PET-CT is the coverage policies of different insurance companies and private payers are very restrictive. Although its horizon is expanding in US, but the large randomized controlled trials requested by many national agencies are difficult to conduct. On an individual patient basis, the benefits of PET-CT outweigh the problems by accurately diagnosing the tumor sites and can drastically improve the outcome.
Specialty/Discipline (Oral Medicine/Pathology/Radiology) (Oral Surgery)
Keywords FDG-PET-CT, unknown primary tumor, distant metastasis
ID# 3344
Date of submission: 11/20/2018spacer
E-mail sonamkhurana@uthscsa.edu
Author Sonam Khurana
Co-author(s) e-mail
Faculty mentor/Co-author Dr. Rujuta Katkar
Faculty mentor/Co-author e-mail KatkarR@uthscsa.edu
Basic Science Rationale
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