TY - JOUR
T1 - Cancer of unknown primary in adolescents and young adults
T2 - Clinicopathological features, prognostic factors and survival outcomes
AU - Raghav, Kanwal
AU - Mhadgut, Hemendra
AU - McQuade, Jennifer L.
AU - Lei, Xiudong
AU - Ross, Alicia
AU - Matamoros, Aurelio
AU - Wang, Huamin
AU - Overman, Michael J.
AU - Varadhachary, Gauri R.
N1 - Publisher Copyright:
© 2016 Raghav et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
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U2 - 10.1371/journal.pone.0154985
DO - 10.1371/journal.pone.0154985
M3 - Article
C2 - 27171493
AN - SCOPUS:84969776754
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 5
M1 - e0154985
ER -