Nonspecific FDG uptake in the tongue mimicking the primary tumor in a patient with cancer of unknown primary

Abstract Purpose [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in location of primary tumor for patients with head and neck cancer of unknown primary (HNCUP). But sometimes, [18F]FDG PET/CT still cannot find the primary malignancy. As 68Ga-radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT has promising results in detecting different tumor entities, our study aimed to evaluate the performance of [68Ga]Ga-DOTA-FAPI-04 PET/CT for detecting the primary tumor in HNCUP patients with negative [18F]FDG findings.Methods A total of eighteen patients (16 males and 2 females; median age, 55 years; range, 24-72 years) with negative [18F]FDG findings were eligible in this study. All patients underwent [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within one week. Biopsy and histopathological examinations were done in the sites with positive [68Ga]Ga-DOTA-FAPI-04 PET/CT findings. Results [68Ga]Ga-DOTA-FAPI-04 PET/CT detected the primary tumor in 7 of 18 patients (38.89%). The primary tumors sites were in nasopharynx (1/7), palatine tonsil (2/7), submandibular gland (2/7), and hypopharynx (2/7). The primary tumors showed mild to intensive uptake of FAPI (mean SUVmax, 8.79; range, 2.60-16.50) and excellent tumor-to-contralateral normal tissue ratio (mean SUVmax ratio, 4.50; range, 2.17-8.21). In lesion-based analysis, a total of 65 lymph nodes and 17 bone metastatic lesions were identified. The mean SUVmax of lymph node metastases were 9.05 ± 5.29 for FDG and 9.08 ± 4.69 for FAPI (p = 0.975); as for bone metastases, the mean SUVmax were 8.11 ± 3.00 for FDG and 6.96 ± 5.87 for FAPI, respectively (p = 0.478). The mean tumor-to-background ratio (TBR) values of lymph node and bone metastases were 10.65 ± 6.59 vs. 12.80 ± 8.11 (p = 0.100) and 9.08 ± 3.35 vs. 9.14 ± 8.40 (p = 0.976), respectively.Conclusion We present first evidence of diagnostic role of [68Ga]Ga-DOTA-FAPI-04 PET/CT in HNCUP, and our study demonstrated that [68Ga]Ga-DOTA-FAPI-04 PET/CT had the potential to improve the detection rate of primary tumor in HNCUP patients with negative FDG findings. Moreover, [68Ga]Ga-DOTA-FAPI-04 had similar performance in assessing metastases with [18F]FDG.

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Can Computed Tomography Characteristics of the Oropharynx in Cancer of Unknown Primary Predict Primary Tumor Site?

Otolaryngology ◽

10.1177/0194599814541629a66 ◽

2014 ◽

Vol 151 (1_suppl) ◽

pp. P157-P158

Author(s):

Ryan P. McSpadden ◽

Thomas P. Sullivan ◽

Jordan Rosenblum ◽

Carol M. Bier-laning

Keyword(s):

Computed Tomography ◽

Primary Tumor ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

Tumor Site ◽

Primary Tumor Site

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Cancer of unknown primary origin: utility and futility in clinical practice

Italian Journal of Medicine ◽

10.4081/itjm.2012.315 ◽

2012 ◽

Author(s):

Gianluca Airoldi

Keyword(s):

Quality Of Life ◽

Primary Tumor ◽

Metastatic Cancer ◽

Performance Status ◽

Cancer Of Unknown Primary ◽

Current Evidence ◽

Unknown Primary ◽

Dismal Prognosis ◽

Poorly Differentiated

Introduction Metastatic cancer of unknown primary (CUP) origin is one of the 10 most frequent cancers in humans; it accounts for approximately 3% to 5% of all solid malignancies. Patients with CUP present with metastatic disease whose site of origin cannot be identified at the time of diagnosis despite a thorough history, physical examination and appropriate laboratory testing, histopathology investigations and modern imaging technology (including computed tomography, magnetic resonance imaging, and positron emission tomography).Materials and methods A “state of the art” review was written reflecting all articles retrieved through a PubMed Medline search with the keywords “cancer of unknown primary”, “occult primary tumor”, and “metastases of unknown origin”, with no limits regarding date of publication, type of article, or field.Results CUP represents a heterogeneous group of malignancies that can be classified into distinct clinicopathological entities. Certain entities are included in favorable sub-sets that are responsive to systemic chemotherapy and/or locoregional treatment: these include poorly differentiated carcinomas involving the mediastinal–retroperitoneal nodes, peritoneal papillary serous adenocarcinomatosis in females, poorly differentiated neuroendocrine carcinomas, isolated axillary node adenocarcinomas in females, cervical and inguinal node involvement by squamous cell carcinoma, and any other single metastatic site of limited extension. In these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Therefore, invasive endoscopic and laparoscopic procedures are rarely warranted in the absence of symptoms. Patients who belong to the non-favorable sub-sets (mainly metastatic CUP involving the liver, lung/pleura, brain, bones, or multiple sites) or have a poor performance status have a dismal prognosis (average median survival of 4-8 months).Discussion The current evidence does not support the hypothesis that palliative chemotherapy improves survival and/or quality of life in CUP patients who do not fit into any of the favorable sub-sets. Therefore, only low-toxicity empirical chemotherapy regimens should be offered to patients with a good performance status, and quality of life issues should be given priority for any choice of treatment.

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Prediction of Primary Tumors in Cancers of Unknown Primary

Journal of Integrative Bioinformatics ◽

10.1515/jib-2017-0013 ◽

2017 ◽

Vol 14 (2) ◽

Cited By ~ 3

Author(s):

Dan Søndergaard ◽

Svend Nielsen ◽

Christian N.S. Pedersen ◽

Søren Besenbacher

Keyword(s):

Primary Tumor ◽

Metastatic Cancer ◽

Large Fraction ◽

Molecular Data ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

Expression Data ◽

Tumor Biopsy ◽

Primary Tumors ◽

The Right

AbstractA cancer of unknown primary (CUP) is a metastatic cancer for which standard diagnostic tests fail to identify the location of the primary tumor. CUPs account for 3–5% of cancer cases. Using molecular data to determine the location of the primary tumor in such cases can help doctors make the right treatment choice and thus improve the clinical outcome. In this paper, we present a new method for predicting the location of the primary tumor using gene expression data: locating cancers of unknown primary (LoCUP). The method models the data as a mixture of normal and tumor cells and thus allows correct classification even in impure samples, where the tumor biopsy is contaminated by a large fraction of normal cells. We find that our method provides a significant increase in classification accuracy (95.8% over 90.8%) on simulated low-purity metastatic samples and shows potential on a small dataset of real metastasis samples with known origin.

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The Diminishing Importance of Primary Site Identification in Cancer of Unknown Primary: A Canadian Single-Center Experience

Frontiers in Oncology ◽

10.3389/fonc.2021.634563 ◽

2021 ◽

Vol 11 ◽

Author(s):

Boaz Wong ◽

Michael M. Vickers ◽

Paul Wheatley-Price

Keyword(s):

Primary Tumor ◽

Treatment Guidelines ◽

Descriptive Analysis ◽

Cancer Of Unknown Primary ◽

Primary Site ◽

Unknown Primary ◽

Primary Tumor Site ◽

Logistic Regression Models ◽

Factors Associated ◽

Site Identification

BackgroundCancer of unknown primary (CUP) describes patients with metastatic disease without an identified primary tumor site. Successful diagnosis and treatment of these patients remains difficult. Published guidelines on CUP have highlighted “favorable” subtype groups. We investigated a series of CUP patients to review adherence to guidelines, and identification of primary cancers or “favorable” subtypes.MethodsPatients with histologically confirmed CUP at an academic institution from 2012 to 2018 were identified. Patient demographics, tumor presentation, diagnostic work-up and treatment information were retrospectively collected from electronic data records for descriptive analysis and compared to published clinical guidelines. The primary endpoint was the proportion of patients where the primary site was identified. Multivariable logistic regression models were used to identify factors associated with primary site identification. Kaplan-Meier survival curves were used to determine factors associated with poorer OS.ResultsThree hundred and five patients were included with a median follow-up time of 4.3 months. Primary tumor sites were identified in 109 patients (37.5%), which was most commonly lung cancer (33%). Statistical analyses did not identify any demographic or initial presentation factors associated with identifying the primary or not. More diagnostic tests did not increase the likelihood of primary site identification (P=0.44). Patients with an identified primary did not have longer OS than other patients (median 5.2 months vs. 4.7 months, P=0.47). 57 patients (18.7%) who had a defined “favorable” subtype experienced superior OS (36.6 months vs. 3.8 months; P<0.0001). Further, patients with good prognostic status who followed published treatment guidelines had longer OS (17.6 months vs. 13.2 months; P=0.04).ConclusionsCUP remains a difficult cancer to diagnose and treat. These results suggest identifying the primary has less impact than anticipated, but particular efforts to identify patients with “favorable” subtypes of CUP is important prognostically.

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Detection of primary tumor by 18F-FDG PET/CT in cancer of unknown primary (+ Running poster)

Médecine Nucléaire ◽

10.1016/j.mednuc.2021.06.104 ◽

2021 ◽

Vol 45 (4) ◽

pp. 223

Author(s):

Y. Benameur ◽

S. Nabih Oueriagli ◽

O. Ait Sahel ◽

J. El Bekkali ◽

A. Doudouh

Keyword(s):

Primary Tumor ◽

Fdg Pet ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

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Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Cancers ◽

10.3390/cancers13030451 ◽

2021 ◽

Vol 13 (3) ◽

pp. 451

Author(s):

Noemi Laprovitera ◽

Mattia Riefolo ◽

Elisa Ambrosini ◽

Christiane Klec ◽

Martin Pichler ◽

...

Keyword(s):

Current Knowledge ◽

Distant Metastases ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

Diagnostic Strategies ◽

Molecular Features ◽

Tissue Of Origin ◽

Novel Therapeutic Strategies ◽

Aggressive Clinical Behavior

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3–5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.

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Cancer of unknown primary

Medicine ◽

10.1097/md.0000000000006693 ◽

2017 ◽

Vol 96 (16) ◽

pp. e6693 ◽

Cited By ~ 1

Author(s):

Anne-Kirstine Dyrvig ◽

Knud Bonnet Yderstræde ◽

Oke Gerke ◽

Peter Bjødstrup Jensen ◽

Søren Hess ◽

...

Keyword(s):

Cancer Of Unknown Primary ◽

Unknown Primary

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Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival

International Archives of Otorhinolaryngology ◽

10.1055/s-0040-1712106 ◽

2020 ◽

Author(s):

Lars Axelsson ◽

Erik Holmberg ◽

Jan Nyman ◽

Anders Högmo ◽

Helena Sjödin ◽

...

Keyword(s):

Head And Neck Cancer ◽

Prognostic Factors ◽

Head And Neck ◽

Neck Dissection ◽

Neck Cancer ◽

Multicenter Study ◽

Performance Status ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

N Stage

Abstract Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPV-positive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p < 0.001), performance status (p= 0.036), and N stage (p= 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and (chemo) radiation and primary (chemo) radiation gave similar survival outcomes. A randomized treatment study that includes quality of life is needed to establish the optimal treatment.

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