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Prognostic clinicopathologic factors in carcinoma of unknown primary origin: a study of 106 consecutive cases.

ABSTRACT: A heterogeneous group of cancers for which the site of origin remains occult after detailed investigations is defined as carcinomas of unknown primary origin (CUPs). Because patients with CUP have a dismal prognosis, we have analyzed CUPs to highlight the implication of clinicopathologic factors related with patient survival. A total of 106 consecutive cases of CUP were collected. A two-step strategy of immunohistochemistry to assess CUPs according NCCN Guidelines is used to separate carcinomatous tumors and subtype carcinomas. Median follow up of censored patients was 26 months. Median survival time of whole patients was 13 months (95% confidence interval [CI], 8.43 - 19.1 months), with one, two and five-year survival rate of 53.7%, 35.1%, and 30.5%, respectively. Factors related with shorter overall survival was adenocarcinoma histology (P=0.001), increased CA19-9 (P=0.003), increased CEA (P=0.047), increased LDH (P<0.001), CK20 positivity (P=0.002), presence of bone metastasis (P=0.017), metastasis not confined to the lymph nodes (P=0.015), unfavorable clinical group based predefined category (P=0.017), and patients with no treatment (P<0.001). Multivariable analysis with cox regression model revealed factors related with overall survival; cases belonged to Culine's poor risk group (HR, 3.88; 95% CI, 1.75-8.64; P=0.001) and CK20 positivity (HR, 3.31; 95% CI, 1.42-7.70; P=0.005). In conclusion, the CK20 expression profile is a prognostic factor in patients with CUP and initial stratification of patient with Culine's model may provide a prognostic information in these patients. Assessment of clinical implication of these factors in the context of site specific therapy needs to be evaluated.

SUBMITTER: Choi J

PROVIDER: S-EPMC5617535 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Prognostic clinicopathologic factors in carcinoma of unknown primary origin: a study of 106 consecutive cases.

Choi Junjeong J Nahm Ji Hae JH Kim Sang Kyum SK

Oncotarget 20170308 37

A heterogeneous group of cancers for which the site of origin remains occult after detailed investigations is defined as carcinomas of unknown primary origin (CUPs). Because patients with CUP have a dismal prognosis, we have analyzed CUPs to highlight the implication of clinicopathologic factors related with patient survival. A total of 106 consecutive cases of CUP were collected. A two-step strategy of immunohistochemistry to assess CUPs according NCCN Guidelines is used to separate carcinomato ...[more]

PMID: 28977975

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Project description:BackgroundMetastatic adenocarcinoma of unknown primary site (MACUP) is the most common cancer of unknown primary site, and shows worse prognosis. Prediction of its tumor site origin attracts a growing attention. However, the site determined by gene expression profiling does not have a significant impact on the survival. Some other special method might need to be found out.MethodsWe reviewed 1011 MACUP patients diagnosed by pathological examination and immunohistochemistry based on the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2016. Kaplan-Meier curves and Cox proportional hazard model were analyzed to compare the survival. Logistic regression models and relevant nomograms were performed to predicting the probability of the primary site which including digestive system, respiratory system, and female breast. The validation and clinical utility of models were measured with relevant statistical approaches.ResultsAbout 324 (32.1%), 299 (29.6%), and 203 (20.1%) of MACUP patients were identified as the primary sites of digestive system, respiratory system, and female breast, respectively. Patients derived from digestive system and respiratory system showed poorer survival than these with other sites. Digestive system was significantly associated with liver (Odds ratio =13.21 [95% confidence interval =8.48-21.02]) or lung (2.36 [1.40-3.97]) metastasis, while respiratory system was linked to brain (11.68 [6.68-21.26]) or lymph node (3.39 [2.26-5.13]) metastasis. Patients identified as female breast were prone to occur bone metastasis (5.85 [3.68-9.45]). Logistic regression nomograms were developed to help clinicians intuitively predict the probabilities of tumor site origin with 0.867, 0.824, and 0.753 of the C-index, respectively. Decision curve analysis and clinical impact curves both revealed the clinical effectiveness.ConclusionsWe profiled different tumor site origin of MACUP patients and established prediction models. These features might be significant for clinicians to improve the probabilities of predicting the primary sites, and to decide subsequent treatment strategy.

Project description:BackgroundCarcinoma of unknown primary origin (CUP) accounts for 2%-5% of newly diagnosed advanced malignancies, with chemotherapy as the standard of care. CUPISCO (NCT03498521) is an ongoing randomized trial using comprehensive genomic profiling (CGP) to assign patients with CUP to targeted or immunotherapy treatment arms based on genomic profiling. We performed a retrospective analysis of CUP cases referred for CGP to determine how many were potentially eligible for enrollment into an experimental CUPISCO arm.Materials and methodsCentrally reviewed adenocarcinoma and undifferentiated CUP specimens in the FoundationCore database were analyzed using the hybrid capture-based FoundationOne CDx assay (mean coverage, >600×). Presence of genomic alterations, microsatellite instability (MSI), tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), and programmed death-ligand 1 (PD-L1) positivity were determined.ResultsA total of 96 of 303 patients (31.7%) could be matched to an experimental CUPISCO arm. Key genomic alterations included ERBB2 (7.3%), PIK3CA (6.3%), NF1 (5.6%), NF2 (4.6%), BRAF (4.3%), IDH1 (3.3%), PTEN, FGFR2, EGFR (3.6% each), MET (4.3%), CDK6 (3.0%), FBXW7, CDK4 (2.3% each), IDH2, RET, ROS1, NTRK (1.0% each), and ALK (0.7%). Median TMB was 3.75 mutations per megabase of DNA; 34 patients (11.6%) had a TMB ?16 mutations per megabase. Three patients (1%) had high MSI, and 42 (14%) displayed high PD-L1 expression (tumor proportion score ?50%). gLOH could be assessed in 199 of 303 specimens; 19.6% had a score of >16%.ConclusionsThirty-two percent of patients would have been eligible for targeted therapy in CUPISCO. Future studies, including additional biomarkers such as PD-L1 positivity and gLOH, may identify a greater proportion potentially benefiting from CGP-informed treatment. Clinical trial identification number. NCT03498521 IMPLICATIONS FOR PRACTICE: The findings of this retrospective analysis of carcinoma of unknown primary origin (CUP) cases validate the experimental treatment arms being used in the CUPISCO study (NCT03498521), an ongoing randomized trial using comprehensive genomic profiling to assign patients with CUP to targeted or immunotherapy treatment arms based on the presence of pathogenic genomic alterations. The findings also suggest that future studies including additional biomarkers and treatment arms, such as programmed death-ligand 1 positivity and genomic loss of heterozygosity, may identify a greater proportion of patients with CUP potentially benefiting from comprehensive genomic profiling-informed treatment.

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Prognostic clinicopathologic factors in carcinoma of unknown primary origin: a study of 106 consecutive cases.

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Prognostic clinicopathologic factors in carcinoma of unknown primary origin: a study of 106 consecutive cases.

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