title: 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.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA. jhainsworth@tnonc.com
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Mark S
authors.initials: MS
authors.lastname: Rubin
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Boccia
authors.forename: Samuel
authors.initials: S
authors.lastname: Raby
authors.forename: Raven
authors.initials: R
authors.lastname: Quinn
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome