title: Cancer of Unknown Primary in Adolescents and Young Adults: Clinicopathological Features, Prognostic Factors and Survival Outcomes.
abstract: Cancer in adolescents and young adults (AYAs) (15-39 years) is increasingly recognized as a distinct clinical and biological entity. Cancer of unknown primary (CUP), a disease traditionally presenting in older adults with a median age of 65 years, poses several challenges when diagnosed in AYA patients. This study describes clinicopathological features, outcomes and challenges in caring for AYA-CUP patients.
  
  
  
  A retrospective review of 47 AYAs diagnosed with CUP at MD Anderson Cancer Center (6/2006-6/2013) was performed. Patients with favorable CUP subsets treated as per site-specific recommendations were excluded. Demographics, imaging, pathology and treatment data was collected using a prospectively maintained CUP database. Kaplan-Meier product limit method and log-rank test were used to estimate and compare overall survival. The cox-proportional model was used for multivariate analyses.
  
  
  
  Median age was 35 years (range 19-39). All patients underwent comprehensive workup. Adenocarcinoma was the predominant histology (70%). A median of 9 immunostains (range 2-29) were performed. The most common putative primary was biliary tract based on clinicopathological parameters as well as gene profiling. Patients presented with a median of 2 metastatic sites [lymph node (60%), lung (47%), liver (38%) and bone (34%)]. Most commonly used systemic chemotherapies included gemcitabine, fluorouracil, taxanes and platinum agents. Median overall survival for the entire cohort was 10.0 (95% confidence interval (CI): 6.7-15.4) months. On multivariate analyses, elevated lactate dehydrogenase (Hazard ratio (HR) 3.66; 95%CI 1.52-8.82; P = 0.004), ≥3 metastatic sites (HR 5.34; 95%CI 1.19-23.9; P = 0.029), and tissue of origin not tested (HR 3.4; 95%CI 1.44-8.06; P = 0.005) were associated with poor overall survival. Culine's CUP prognostic model (lactate dehydrogenase, performance status, liver metastases) was validated in this cohort (median overall survival: good-risk 25.2 months vs. poor-risk 6.1 months).
  
  
  
  AYA-CUP is associated with a poor prognosis. In the current "-omics" era collaborative research efforts towards understanding tumor biology and therapeutic targets in AYA-CUP is an unmet need, necessary for improving outcomes in young CUP patients.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Kanwal
authors.initials: K
authors.lastname: Raghav
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Hemendra
authors.initials: H
authors.lastname: Mhadgut
authors.affiliation: Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McQuade
authors.affiliation: Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Xiudong
authors.initials: X
authors.lastname: Lei
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Alicia
authors.initials: A
authors.lastname: Ross
authors.affiliation: Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Matamoros
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015233:Models, Statistical; D015999:Multivariate Analysis; D009382:Neoplasms, Unknown Primary / Q000473:pathology*; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D055815:Young Adult