Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin.

Abbruzzese, James L.; Abbruzzese, Marie C.; Lenzi, Renato; Hess, Kenneth R.; Raber, Martin N.

doi:10.1200/jco.1995.13.8.2094

Cited by 298 publications

(219 citation statements)

References 12 publications

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“…Multiple empirical chemotherapy regimens have been used for CUP patients, but there are few randomised data to support a specific regimen (Briasoulis et al, 2005). The median survival in randomised studies is approximately 7 months (Abbruzzese et al, 1995), which is both poor and significantly less than the expected survival for patients with breast and bowel malignancy following standard therapy. These data suggest that little further benefit can be gained from the use of empirical regimen, perhaps because of the heterogeneity of tumour phenotype represented in the true CUP population.…”

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confidence: 99%

Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary

et al. 2008

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Carcinomas of unknown primary (CUP) represent between 3 and 10% of malignancies. Treatment with nonspecific chemotherapy is commonly unhelpful and the median survival is between 3 and 6 months. Gene expression microarray (GEM) analysis has demonstrated that molecular signatures can aid in tumour classification and propose foster primaries. In this study, we demonstrate the clinical utility of a diagnostic gene expression profiling tool and discuss its potential implications for patient management strategies. Paraffin tumour samples from 21 cases of 'true' CUP patients in whom standard investigation had failed to determine a primary site of malignancy were investigated using diagnostic gene profiling. The results were reviewed in the context of histology and clinical history. Classification of tumour origin using the GEM method confirmed the clinicians' suspicion in 16 out of 21 cases. There was a clinical/ GEM inconsistency in 4 out of 21 patients and a pathological/GEM inconsistency in 1 patient. The improved diagnoses by the GEM method would have influenced the management in 12 out of 21 cases. Genomic profiling and cancer classification tools represent a promising analytical approach to assist with the management of CUP patients. We propose that GEM diagnosis be considered when the primary clinical algorithm has failed to provide a diagnosis.

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confidence: 99%

Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary

et al. 2008

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“…Extensive diagnostic procedures cause discomfort for the patient, require time and cause delay of treatment. In addition, they are often fruitless (Hainsworth and Greco, 1993;Abbruzzese et al, 1995;Schapira and Jarrett, 1995).…”

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“…For the minority of tumours that have been identified in the last two decades as being potentially sensitive to chemotherapy (van der Gaast et al, 1990;Pavlidis et al, 1992;Abbruzzese et al, 1995;Lenzi et al, 1997;Greco and Hainsworth, 2001b), the diagnostic procedures will delay these patients from receiving effective treatment.…”

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confidence: 99%

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

et al. 2004

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The aim of this study was to assess the activity and toxicity of a platinum-based treatment on a group of patients with unknown primary tumours (UPTs). Patients with a diagnosis of UPT underwent a standard diagnostic procedure. Treatment was started within 2 weeks from diagnosis and consisted of carboplatin 400 mg m À2 day 1, doxorubicin 50 mg m À2 day 1, etoposide 100 mg m À2 days 1 -3, every 21 days. Response was evaluated after three courses and treatment continued in case of objective response (OR) or symptom control. A total of 102 patients were eligible. The median age was 59 years, sex male/female 54/48, histology was mainly adenocarcinoma or poorly differentiated carcinoma. Nodes, bone, liver and lung were the most frequently involved sites. In all, 79 patients received at least three courses of treatment; 26 patients received six courses or more. Six complete responses and 21 partial responses were observed, for a total of 27 of 102 ORs or 26.5% (95% confidence interval 18.2 -36.1%). The median survival was 9 months and median progression-free survival was 4 months. Toxicity was moderate to severe, with 57.8% of patients experiencing grade III -IV haematological toxicity, mainly leucopenia. The regimen employed has shown activity in tumours of unknown primary site, but was associated with significant toxicity. Such toxicity may be considered unjustified, given the large proportion of patients with tumours not likely to respond. Efforts should therefore be addressed to identify predictors of response to chemotherapy, thus limiting aggressive treatment to those patients who could benefit from it.

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“…However, in spite of clinical, radiographic, and routine histologic studies, the primary site remains uncertain in approximately 3 -15% of cases (Abbruzzese et al, 1995;Hammar, 1998). A significant proportion of these cases are adenocarcinomas, and they present a challenge for the pathologist and the oncologist alike.…”

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Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma

et al. 2002

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The origin of metastatic adenocarcinoma lesions can sometimes be difficult to diagnose. The objectives of our study were to establish the cytokeratin staining pattern of primary and metastatic lung and colorectal adenocarcinomas, and to determine if this helps to identify the site of origin of metastatic lesions. We reviewed a total of 102 tissue samples from patients in our tumour registry, with either primary or metastatic lung or colorectal adenocarcinoma. Tissue sections were stained for cytokeratin 7 and 20 and read as positive or negative for staining. Clinical and radiologic information was reviewed from computerised charts. The cytokeratin 7+/cytokeratin 207 pattern characterised 96% (29 out of 30) of primary and 95% (21 out of 22) of metastatic lung adenocarcinomas. All the primary (26), and 88% (21 out of 24) of metastatic colorectal adenocarcinomas stained cytokeratin 77/cytokeratin 20+. Samples from a variety of metastatic sites were evaluated for cytokeratin 7 and 20 staining. Out of the 102 samples, in 95% (97 out of 102) of the cases, the cytokeratin 7 and cytokeratin 20 staining pattern characterised and differentiated between lung and colorectal adenocarcinoma. Primary and metastatic lung adenocarcinomas show a cytokeratin 7+/cytokeratin 207 staining pattern, while colorectal adenocarcinomas stain cytokeratin 77/cytokeratin 20+. Cytokeratin staining is helpful in the diagnostic differentiation of metastatic lesions from these two common primaries, and assists in determining the site of origin of metastatic lesions.

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Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin.

Cited by 298 publications

References 12 publications

Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary

Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma

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