Molecular Gene Expression Profiling to Predict the Tissue of Origin and Direct Site-Specific Therapy in Patients With Carcinoma of Unknown Primary Site: A Prospective Trial of the Sarah Cannon Research Institute

2013 ◽  
Vol 31 (2) ◽  
pp. 217-223 ◽  
Author(s):  
John D. Hainsworth ◽  
Mark S. Rubin ◽  
David R. Spigel ◽  
Ralph V. Boccia ◽  
Samuel Raby ◽  
...  
Keyword(s):  
Median Survival ◽  
Prospective Trial ◽  
Primary Site ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Specific Therapy ◽  
Site Specific ◽  
Tissue Of Origin ◽  
Tumor Types ◽  
Tumor Profiling

Purpose Molecular tumor profiling is a promising diagnostic technique to determine the tissue of origin in patients with carcinoma of unknown primary site (CUP). However, the clinical value of these molecular predictions is unknown. We used tumor profiling results to direct site-specific therapy for patients with CUP. Patients and Methods Tumor biopsy specimens from previously untreated patients with CUP were tested with a 92-gene reverse transcriptase polymerase chain reaction cancer classification assay. When a tissue of origin was predicted, patients who were treatment candidates received standard site-specific first-line therapy. Results Of 289 patients enrolled, 252 had successful assays performed, and 247 (98%) had a tissue of origin predicted. Sites most commonly predicted were biliary tract (18%), urothelium (11%), colorectal (10%), and non–small-cell lung (7%). Two hundred twenty-three patients were treatment candidates, and 194 patients received assay-directed site-specific treatment. In these 194 patients, the median survival time was 12.5 months (95% CI, 9.1 to 15.4 months). When the assay predicted tumor types that were clinically more responsive, the median survival was significantly improved when compared with predictions of more resistant tumors (13.4 v 7.6 months, respectively; P = .04). Conclusion In this large prospective trial, molecular tumor profiling predicted a tissue of origin in most patients with CUP. The median survival time of 12.5 months for patients who received assay-directed site-specific therapy compares favorably with previous results using empiric CUP regimens. Patients with CUP predicted to have more responsive tumor types had longer survival compared with patients with less responsive tumor types. Molecular tumor profiling contributes to the management of patients with CUP and should be a part of their standard evaluation.

Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients (pts) with carcinoma of unknown primary site (CUP): Results of a prospective Sarah Cannon Research Institute (SCRI) trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10530-10530
Author(s):  
Frank A. Greco ◽  
Mark S. Rubin ◽  
Ralph V. Boccia ◽  
Michael A. Scola ◽  
David R. Spigel ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Specific Treatment ◽  
Molecular Profiling ◽  
Unknown Primary ◽  
Specific Therapy ◽  
Accurate Identification ◽  
Site Specific ◽  
Tissue Of Origin ◽  
Tumor Types ◽  
Tumor Profiling

10530 Background: Tumor profiling is an emergent technique to determine tissue of origin in CUP patients. However, the value of these predictions in improving treatment efficacy is unknown. In this prospective trial, we used tumor profiling results to direct site-specific therapy for CUP pts. Methods: A 92-gene RT-PCR assay (CancerTYPE ID; bioTheranostics, Inc.) was performed on tumor biopsies from previously untreated CUP pts who consented. When a tissue of origin was predicted, pts who were treatment candidates were assigned standard site-specific first-line therapy. Results: Between 10/08 and 12/11, 289 pts were enrolled, 252 had successful assays performed, and 247 (98%) had a tissue of origin predicted. 224 pts were eligible for treatment; 197 pts received assay-directed treatment. 120 of 224 treated pts (54%) had assay diagnoses of tumor types known to derive substantial benefit from standard site-specific treatment (bladder 27, colorectal 26, NSCLC 24, breast 10, ovary 10, kidney 9, prostate 4, germ cell 4, others 6 (3 sites), while 104 pts (46%) had assay diagnoses of relatively resistant tumors (biliary tract 45, pancreas 12, gastroesophageal 10, liver 7, sarcoma 5, cervix 5, others 20 (8 sites). Median OS for all treated pts was 10.8 months (mos); OS for 197 pts with assay-directed treatment was 12.2 mos (versus 6.0 mos for 27 pts receiving empiric therapy). Median OS was better in the 120 pts with assay diagnoses of more responsive tumor types (12.8 vs 7.4 mos; p = .027). Median OS (mos) in specific subgroups: pancreas 9, kidney 12, colon 12, NSCLC 16, ovary 30. Conclusions: This is the first prospective trial in which molecular profiling has directed site-specific therapy in CUP pts. Assay-directed therapy in 197 pts produced a median OS (12.2 mos) that compares favorably with previous empiric CUP therapy. CUP pts predicted to have more responsive tumor types had longer survival compared to less responsive types, suggesting accurate identification by the assay. These results strengthen the rationale for molecular profiling in CUP management.

Gene expression profiling for prediction of tissue of origin to direct site-specific therapy in patients with CUP: Treatment outcomes by assay predictive probability.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21023-e21023
Author(s):  
Mark S. Rubin ◽  
Frank A. Greco ◽  
Ralph V. Boccia ◽  
Michael A. Scola ◽  
David R. Spigel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prospective Trial ◽  
High Confidence ◽  
Specific Therapy ◽  
Site Specific ◽  
Predictive Probability ◽  
Gene Assay ◽  
Tissue Of Origin ◽  
Treatment Responses ◽  
Tumor Types

e21023 Background: Tumor profiling as a diagnostic technique in CUP depends on the detection of similarities in gene expression between the cancer and the tissue of origin. Assay-directed site-specific therapy may be most effective in tumors with high-confidence molecular predictions, since a) the prediction may be more often correct due to greater similarity between the gene expression profile of the unknown tumor to the assay reference tumor database, and b) the tumor would more likely share biologic characteristics/treatment sensitivity with cancers of known origin. Methods: In a prospective trial performed by the Sarah Cannon Research Institute (SCRI), a 92-gene RT-PCR assay (CancerTYPE ID; bioTheranostics, Inc.) was performed on tumor biopsies from previously untreated CUP pts. Pts were then assigned standard site-specific treatment directed by the assay prediction. Treatment responses were evaluated based on the strength of the assay predictions; probabilities ≥80% were arbitrarily regarded as high confidence results. Results: Between 10/08 and 12/11, 224 pts (26 predicted tumor types) received treatment. Median overall survival (OS) was longer in 113 pts (50%) with high confidence predictions: 11.7 months (mos) vs 9.8 mos; p=.03. 120 pts (59%) had assay predictions of responsive tumor types, known to derive substantial benefit from standard site-specific therapy. Treatment responses, irrespective of predictive probability, were better in these pts vs those with less responsive tumor types (median OS 12.8 vs 7.4 mos; p=.027). Further stratification of high vs lower confidence assay predictions resulted in 4 groups with different OS (p=.03) (Table). Conclusions: Site-specific therapy for CUP pts directed by results of the 92-gene assay was more effective when the probability of the assay prediction was higher, particularly in pts with assay diagnoses of more responsive tumor types. [Table: see text]

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.

Simple prognostic model to predict survival in patients with undifferentiated carcinoma of unknown primary site.

1995 ◽  
Vol 13 (7) ◽  
pp. 1720-1725 ◽  
Author(s):  
A van der Gaast ◽  
J Verweij ◽  
A S Planting ◽  
W C Hop ◽  
G Stoter
Keyword(s):  
Alkaline Phosphatase ◽  
Prognostic Factors ◽  
Median Survival ◽  
Performance Status ◽  
Primary Site ◽  
Survival Duration ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Carcinoma Of Unknown Primary ◽  
Median Survival Duration

PURPOSE We performed this study to identify prognostic factors in a subgroup of patients with carcinoma of unknown primary site treated with cisplatin combination chemotherapy. PATIENTS AND METHODS Seventy-nine patients with poorly differentiated adenocarcinoma or undifferentiated carcinoma of unknown primary site were treated on two consecutive phase II chemotherapy protocols. The first protocol consisted of treatment with 3-week courses of cisplatin, etoposide, and bleomycin (BEP). In the second protocol, cisplatin was administered weekly combined with oral administration of etoposide (DDP/VP). To identify prognostic factors, univariate and multivariate analyses were conducted. RESULTS In the univariate analysis, performance status, histology, liver or bone metastases, and serum levels of alkaline phosphatase and AST were significant variables to predict survival. In the multivariate analysis, performance status and alkaline phosphatase were the most important prognostic factors. CONCLUSION Good-prognosis patients had a performance score of 0 (World Health Organization [WHO]) and an alkaline phosphatase serum level less than 1.25 times the upper limit of normal (N). These patients had a median survival duration greater than 4 years. Intermediate-prognosis patients were characterized by either a WHO performance status < or = 1 or an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of 10 months and a 4-year survival rate of only 15%. The poor-prognosis group had both a WHO performance status > or = 1 and an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of only 4 months and none survived beyond 14 months. Treatment strategies for these three groups are discussed. It is suggested that this prognostic model be validated in other patients series.

DNA-based genomic profiling for classification of tissue of origin for patients with carcinoma of unknown primary site.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 11519-11519
Author(s):  
Lee A Albacker ◽  
Michael E Goldberg ◽  
Lukas C. Amler ◽  
Garrett Michael Frampton ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Primary Site ◽  
Unknown Primary ◽  
Genomic Profiling ◽  
Unknown Primary Site ◽  
Carcinoma Of Unknown Primary ◽  
Tissue Of Origin

Site-specific Chemotherapy Based on Predicted Primary Site by Pathological Profile for Carcinoma of Unknown Primary Site

2018 ◽  
Vol 30 (10) ◽  
pp. 667-673 ◽  
Author(s):  
H. Hasegawa ◽  
M. Ando ◽  
Y. Yatabe ◽  
S. Mitani ◽  
K. Honda ◽  
...  
Keyword(s):  
Primary Site ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Site Specific ◽  
Carcinoma Of Unknown Primary

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
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