The Clinical Significance of Occult Gastrointestinal Primary Tumours in Metastatic Cancer: A Population Retrospective Cohort Study

Malek B. Hannouf,Eric Winquist,Salaheddin M. Mahmud,Muriel Brackstone,Sisira Sarma,George Rodrigues,Peter K. Rogan,Jeffrey S. Hoch,Gregory S. Zaric 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1

Purpose The purpose of this study was to estimate the incidence of occult gastrointestinal (GI) primary tumours in patients with metastatic cancer of uncertain primary origin and evaluate their influence on treatments and overall survival (OS). Materials and Methods We used population heath data from Manitoba, Canada to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients to have “occult” primary tumour if the primary was found at least 6 months after initial diagnosis. Otherwise, we considered primary tumours as “obvious.” We used propensity-score methods to match each patient with occult GI tumour to four patients with obvious GI tumour on all known clinicopathologic features. We compared treatments and 2-year survival data between the two patient groups and assessed treatment effect on OS using Cox regression adjustment. Results Eighty-three patients had occult GI primary tumours, accounting for 17.6% of men and 14% of women with metastatic cancer of uncertain primary. A 1:4 matching created a matched group of 332 patients with obvious GI primary tumour. Occult cases compared to the matched group were less likely to receive surgical interventions and targeted biological therapy, and more likely to receive cytotoxic empiric chemotherapeutic agents. Having an occult GI tumour was associated with reduced OS and appeared to be a nonsignificant independent predictor of OS when adjusting for treatment differences. Conclusion GI tumours are the most common occult primary tumours in men and the second most common in women. Patients with occult GI primary tumours are potentially being undertreated with available GI site-specific and targeted therapies.

The use of an immunohistochemical diagnostic panel to determine the primary site of cervical lymph node metastases of occult squamous cell carcinoma

Park, Jung Mee,Jung, Chan Kwon,Choi, Yeong Jin,Lee, Kyo Young,Kang, Jin Hyoung,Kim, Min Sik,Hu, Hae Jin Elsevier 2010 Human pathology Vol.41 No.3

<P><B>Summary</B></P><P>Cervical lymph node metastases from unknown primary sites account for approximately 3% to 9% of all head and neck malignant lesions. Squamous cell carcinoma is the most common type of cervical metastatic carcinoma. Our aim was to investigate the possibility of determining the site of primary tumors using an immunohistochemical diagnostic panel in metastatic cervical lymph nodes. Expression profiles of cytokeratins, 5/6; 8/18; 10; 13; 14; and 19, p16, and pRb were evaluated in 101 consecutive patients with cervical nodal metastasis who had undergone neck dissection to treat known head and neck squamous cell carcinoma (primary sites: 16, oral cavity; 38, oropharynx; 26, hypopharynx; 21, larynx). Cytokeratin 10 was more frequently expressed in oral cavity primary tumors, whereas cytokeratin 19 staining was more frequently observed in tumors originated from the pharynx and larynx. The expression of p16 and altered pRb status (0% or >50%) were more frequently observed in oropharynx primary tumors. To select the best subset among the 8 antibodies tested, classification and regression tree analysis was performed. The analysis correctly classified the four primary sites (25.0% of oral cavity, 89.5% of oropharynx, 30.8% of hypopharynx, and 57.1% of larynx) using 5 variables (histologic subtype, p16, cytokeratins 10 and 19, and pRb). The p16 was the single best predictor. The classification tree method using immunostaining profiles of p16, cytokeratins 10 and 19, or pRb may be helpful in the identification of the primary site of metastatic squamous cell carcinoma with occult primary.</P>

Diagnostic Value of 68Ga-DOTATATE PET/CT in Liver Metastases of Neuroendocrine Tumours of Unknown Origin

Teik Hin Tan,이분낭,Siti Zarina Amir Hassan 대한핵의학회 2014 핵의학 분자영상 Vol.48 No.3

Purpose In neuroendocrine liver metastases of unknown primary,a multimodality approach is usually adopted and consistsof transabdominal ultrasound, endoscopic ultrasound(EUS), computed tomography (CT), magnetic resonance imaging(MRI), nuclear medicine techniques, endoscopy andexploratory surgery. The purpose of the study is to evaluatethe diagnostic value of 68Ga-DOTATATE positron emissiontomography (PET)/CT as part of a multimodality approach inneuroendocrine liver metastases of unknown primary. Materials and Methods Six patients (M:F=5:1, age range 28–56 years) with immunohistochemically proven neuroendocrineliver metastases but inconclusive initial CT work-upwere retrospectively analysed. Clinical finding, histopathology,comparative imaging and follow-up were used to validatethe results when ethically justified. Results 68Ga-DOTATATE PET/CT identified the primarytumour in five out of six (83.3 %) patients: pancreas (n =4)and stomach (n =1). Out of three patients with indeterminateprimary on initial CT, two patients were confirmed by 68Ga-DOTATATE PET/CT. Absence of uptake in indeterminateprimary of one patient was later confirmed negative by histopathology. In another three patients with undetected primaryon initial CT, primary site was demonstrated in all patientswith unsuspected metastases in two patients on 68Ga-DOTATATE PET/ CT. No further work-up was done to confirmthe primary in patients with distantmetastases. Change ofmanagement was observed in three out of six (50 %) patients. Conclusion Our small study indicates that 68Ga-DOTATATEPET/CT is a promising diagnostic option in the multimodalityapproach to neuroendocrine liver metastases of unknownprimary origin.

FDG PET/CT and Conventional Imaging Methods in Cancer of Unknown Primary: an Approach to Overscanning

Neslihan Cetin Avci,Filiz Hatipoglu,Ahmet Alacacıoglu,Emine Ebru Bayar,Gonca Gul Bural 대한핵의학회 2018 핵의학 분자영상 Vol.52 No.6

Purpose To compare the performance of fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography(FDG PET/CT) with conventional imaging methods (CIM), including computed tomography (CT), magnetic resonanceimaging (MRI), and mammography (MMG) in cancer of unknown primary (CUP). Methods A total of 36 patients with CUP, who referred to our clinic for a FDG PET/CTscan, were enrolled in this study. Thirty ofthe patients were also examined through either diagnostic CT/MRI and/or MMG. The diagnostic performance of both methodsfor the primary cancer location was analyzed. The results of FDG PET/CT and CIM were compared based on the standardreference of the histopathology and/or clinical and laboratory follow-up. Results The primary cancer locations were detected in 24 patients (66.6%, 24/36) by FDG PET/CT, whereas CIM identified thelocations in 16 patients (53.3%, 16/30). Sensitivity, specificity, PPV, NPV, and accuracy rates of the detection of the primarytumor localizations were as follows: 83, 70, 89, 58, and 79% for FDG PET/CT; 70, 62, 84, 42, and 68% for CIM, respectively. There was no statistical significance between modalities regarding any of the categories in 30 patients. Conclusion FDG PET/CT detected the primary tumors of the patients with CUP more than CIM did. However, the differencebetween them was not found to be statistically significant. It may be considered that FDG PET/CT scan can be performed as afirst-line tool in the initial diagnosis of the patients with CUP and to add radiodiagnostic imaging in selective cases.We concludethat if the first-line examination of a CUP patient has been already performed by a CIM and the result was negative orinconclusive, FDG PET/CT can be considered to avoid unnecessary imaging procedures.

원발부위불명암의 진단과 치료

김영생 ( Young Saing Kim ),이순일 ( Soon Il Lee ) 대한내과학회 2021 대한내과학회지 Vol.96 No.5

Cancer of unknown primary (CUP) is a heterogenous group of cancers for which the anatomical site of origin is unidentifiable on the basis of standard evaluation and imaging. CUPs account for 2-5% of all malignancies and are characterized by early metastatic dissemination, aggressive clinical course, and poor response to palliative chemotherapy. It is important to identify favorable-risk CUP patients (10-20%), as they harbor chemo-sensitive and potentially curable tumors, and may require long-term disease control. Empirical combination chemotherapy has traditionally been the standard first-line therapy for most patients (80-90%), who do not belong to favorable-risk subsets; however, this approach has only modest benefits, with a median overall survival of < 1 year. Evidence supporting the clinical use of molecular tissue of origin (TOO) tests is still lacking. Two recent randomized clinical trials failed to show the benefit of TOO-based site-specific therapy over empirical chemotherapy. In an era of precision medicine, the use of comprehensive molecular profiling will provide opportunities to identify patient subsets who are susceptible to targeted therapies and immunotherapies. (Korean J Med 2021;96:408-414)

CEA, AFP, CA125, CA153 and CA199 in Malignant Pleural Effusions Predict the Cause

Wang, Xin-Feng,Wu, Yan-Hua,Wang, Mao-Shui,Wang, Yun-Shan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.

Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

( Hyun Jin Han ),( Won Seok Chang ),( Hyun Ho Jung ),( Yong Gou Park ),( Hae Yu Kim ),( Jong Hee Chang ) 대한뇌종양학회 대한신경종양학회 2016 Brain Tumor Research and Treatment Vol.4 No.2

Background Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. Methods We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. Results Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. Conclusion Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor.

Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

한현진,장원석,정현호,박용구,김해유,장종희 대한뇌종양학회 2016 Brain Tumor Research and Treatment Vol. No.

Background Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. Methods We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. Results Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. Conclusion Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor.

두경부 원발부위 불명암에서 치료 후 발견된 비인두암

김은지(Eun Ji Kim),홍기환(Ki Hwan Hong),홍용태(Yong Tae Hong) 대한두경부종양학회 2018 대한두경부 종양학회지 Vol.34 No.2

Despite adequate diagnostic work-up, unknown primary carcinoma(UPC) of the head and neck cannot be detected in approximately 2- 3% of patients.(1,2) There are several explanations for a cervical metastasis in the absence of a primary tumor. Here in, we report 2 patients, who were diagnosed with nasopharyngeal cancer after treatment of unknown primary cancer of the neck. Both patients had radical neck dissections and chemoradiation therapy, but 1 patient showed nasopharyngeal cancers 4 years after treatment and the other patient at 9 months after treatment for the unknown primary cancer. Therefore, we report 2 cases of nasopharyngeal cancer, which were diagnosed after treatment of unknown head and neck primary site.

Clinical Impact of F-18 FDG PET-CT on Biopsy Site Selection in Patients with Suspected Bone Metastasis of Unknown Primary Site

유수웅,Sunny Anam Chowdhury,전수빈,강세령,이창호,Jabin Zeenat,김자혜,조상건,송호천,범희승,민정준,권성영 대한핵의학회 2020 핵의학 분자영상 Vol.54 No.4

Purpose We investigated the clinical role of F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in the identification of the primary site and the selection of the optimal biopsy site in patients with suspected bone metastasis of unknown primary site. Methods The patients with suspected bone metastasis who underwent PET-CT for evaluation of primary site were enrolled in this study. The primary sites were identified by the histopathologic or imaging studies and were classified according to the FDG uptake positivity of the primary site. To evaluate the guiding capability of PET-CT in biopsy site selection, we statistically analyzed whether the biopsy site could be affected according to the presence of extra-skeletal FDG uptake. Results Among 74 enrolled patients, 51 patients had a metastatic bone disease. The primary site was identified in 48 of 51 patients (94.1%). Forty-six patients were eligible to test the association of clinical choice of biopsy site with PET positivity of extra-skeletal lesion. The extra-skeletal biopsies were done in 42 out of 43 patients with positive extra-skeletal uptake lesions. Bone biopsies were inevitably performed in the other three patients without extra-skeletal uptake lesions. The association came out to be significant (Fisher’s exact test, P < 0.001). Conclusion F-18 FDG PET-CT significantly contributed not only to identify the primary site but also to suggest optimal biopsy sites in patients with suspected bone metastasis.