scholarly journals Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Cancers ◽  
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.

Prediction of Tissue of Origin and Molecular Subtypes for Cancer of Unknown Primary Using Machine Learning

2020 ◽  
Author(s):  
Yue Zhao ◽  
Sandeep Namburi ◽  
Ziwei Pan ◽  
Carolyn A. Paisie ◽  
Honey V. Reddi ◽  
...  
Keyword(s):  
Machine Learning ◽  
Molecular Subtypes ◽  
Cancer Of Unknown Primary ◽  
Unknown Primary ◽  
Tissue Of Origin

Diagnostic accuracy of molecular tumor profiling in determining the tissue of origin in adult patients with cancer of unknown primary: A meta-analysis.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 20-20
Author(s):  
Rowena Torres Inocencio ◽  
Kavitha Kesari ◽  
Susan Smith
Keyword(s):  
Diagnostic Accuracy ◽  
Diagnostic Test ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Cancer Of Unknown Primary ◽  
Adult Patients ◽  
Unknown Primary ◽  
Test Accuracy ◽  
Tissue Of Origin ◽  
Tumor Profiling

20 Background: Appropriate cancer treatment requires determination of the primary site of origin. The standard of care for diagnosing Cancer of unknown primary (CUP) based on the 2016 NCCN Guidelines is a comprehensive clinical work-up including biopsy and immunohistochemistry (IHC). However, IHC was able to identify a primary tumor in only 25% of CUP. Molecular tumor profiling (MTP) validation studies demonstrated sensitivities of 74-89% and specificities of 95-99%. Only a few studies with small sample sizes using MTP to diagnose the primary in CUP have been performed yielding variable results. This study aims to evaluate the diagnostic accuracy of MTP in determining the tissue of origin in adult patients with CUP. Methods: Literature search included articles published in any language indexed in MEDLINE and Cochrane. A Google Scholar search and a review of all published articles’ references were performed. Unpublished studies and abstracts from conference proceedings were also reviewed. Studies involving adult patients with CUP who underwent both MTP and clinical evaluation with IHC were identified. Articles were included if they had primary data sufficient to calculate both sensitivity and specificity. Methodological qualities of the included studies were evaluated using the QUADAS-2 tool. Data was analyzed using Review Manager 5.3 and MetaDiSc 1.4. Results: Seven studies with 549 patients were analyzed. MTP was found to have a pooled sensitivity of 89% (95% CI 0.85-0.92)and pooled specificity of 74% (95% CI 0.67-0.80)with pooled positive and negative likelihood ratios of 2.97 (95% CI 1.17-7.63) and 0.20 (95% CI 0.07-0.51), respectively. Area under the curve was measured to be 0.9107. Conclusions: This meta-analysis suggests that MTP could be useful in determining the tissue of origin in adult patients with CUP. With an area under the curve of 0.9107, it is an excellent diagnostic test. The results showed considerable heterogeneity as expected in meta-analyses of diagnostic test accuracy. In this case, it may be due to variability among the MTP assays used which may reflect different cutoffs.

Prospective gene signature study using microRNA to predict the tissue of origin (ToO) in pts with cancer of unknown primary site (CUP).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 4151-4151 ◽  
Author(s):  
G. R. Varadhachary ◽  
T. B. Edmonston ◽  
S. Karanth ◽  
H. R. Carlson ◽  
D. Lebanony ◽  
...  
Keyword(s):  
Gene Signature ◽  
Cancer Of Unknown Primary ◽  
Primary Site ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Tissue Of Origin

Economic analysis of epicup, an epigenetic test to predict the tissue of origin in cancer of unknown primary site.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e12532-e12532
Author(s):  
Carmen Balana ◽  
Alfredo Gracia ◽  
Lisette Kaskens ◽  
Sebastian Chiavenna ◽  
Xavier Matias-Guiu ◽  
...  
Keyword(s):  
Economic Analysis ◽  
Cancer Of Unknown Primary ◽  
Primary Site ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Tissue Of Origin

Diagnostic accuracy of molecular tumor profiling in determining the tissue of origin in adult patients with cancer of unknown primary: A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23092-e23092
Author(s):  
Rowena Torres Inocencio ◽  
Kavitha Kesari ◽  
Susan Smith
Keyword(s):  
Diagnostic Accuracy ◽  
Diagnostic Test ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Cancer Of Unknown Primary ◽  
Adult Patients ◽  
Unknown Primary ◽  
Test Accuracy ◽  
Tissue Of Origin ◽  
Tumor Profiling

e23092 Background: Appropriate cancer treatment requires determination of the primary site of origin. The standard of care for diagnosing Cancer of unknown primary (CUP) based on the 2016 NCCN Guidelines is a comprehensive clinical work-up including biopsy and immunohistochemistry (IHC). However, IHC was able to identify a primary tumor in only 25% of CUP. Molecular tumor profiling (MTP) validation studies demonstrated sensitivities of 74-89% and specificities of 95-99%. Only a few studies with small sample sizes using MTP to diagnose the primary in CUP have been performed yielding variable results. This study aims to evaluate the diagnostic accuracy of MTP in determining the tissue of origin in adult patients with CUP. Methods: Literature search included articles published in any language indexed in MEDLINE and Cochrane. A Google Scholar search and a review of all published articles’ references were performed. Unpublished studies and abstracts from conference proceedings were also reviewed. Studies involving adult patients with CUP who underwent both MTP and clinical evaluation with IHC were identified. Articles were included if they had primary data sufficient to calculate both sensitivity and specificity. Methodological qualities of the included studies were evaluated using the QUADAS-2 tool. Data was analyzed using Review Manager 5.3 and MetaDiSc 1.4. Results: Seven studies with 549 patients were analyzed. MTP was found to have a pooled sensitivity of 89% (95% CI 0.85-0.92)and pooled specificity of 74% (95% CI 0.67-0.80)with pooled positive and negative likelihood ratios of 2.97 (95% CI 1.17-7.63) and 0.20 (95% CI 0.07-0.51), respectively. Area under the curve was measured to be 0.9107. Conclusions: This meta-analysis suggests that MTP could be useful in determining the tissue of origin in adult patients with CUP. With an area under the curve of 0.9107, it is an excellent diagnostic test. The results showed considerable heterogeneity as expected in meta-analyses of diagnostic test accuracy. In this case, it may be due to variability among the MTP assays used which may reflect different cutoffs.

Cancer of Unknown Primary Site: Improved Patient Management with Molecular and Immunohistochemical Diagnosis

2013 ◽  
pp. 175-181 ◽  
Author(s):  
F. Anthony Greco
Keyword(s):  
Cancer Of Unknown Primary ◽  
Primary Site ◽  
Diagnostic Tools ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Large Prospective Study ◽  
Tissue Of Origin ◽  
Immunohistochemical Diagnosis ◽  
Molecular Aberrations ◽  
Tumor Types

Cancer of unknown primary site (CUP) is a common heterogeneous clinicopathologic syndrome, but investigations and publications regarding these patients are rare. For the last 20 years, empiric “broad-spectrum” chemotherapy has been the standard therapy for the majority of these patients. More recently, improved immunocytochemistry and advent of gene-expression profiling have provided the diagnostic tools necessary to accurately define the tissue of origin in most patients. Molecular profiling assays complement standard pathologic diagnosis, and a recently reported large prospective study demonstrated an improvement in outcome for patients treated with site-specific therapy directed by the molecular assay diagnoses compared with empiric chemotherapy. Survival in molecularly diagnosed patients was as expected for those particular tumor types. The evaluation of patients has become more standardized. The empiric-chemotherapy era is ending and customized therapies based on accurate tissue of origin diagnoses have arrived. Eventually the recognition of the molecular aberrations responsible for the growth and metastasis of solid tumors, regardless of the tissue of origin, will lead to more precise and effective therapy for patients with advanced cancers.

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