Abstract
ABSTRACT Background Carcinomas of unknown primary (CUP) incorporate tumours with heterogeneous biology and invariably poor prognosis. There is a lack of validated prognostic indices in this context. The presence of a cancer related systemic inflammatory reaction is both pathogenic and prognostic in advanced cancer. We aimed to assess whether a panel of inflammatory indices including the modified-Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) could predict prognosis and response to therapy in CUP. Methods Consecutive patients diagnosed with histologically proven CUP at the Imperial College oncology unit (1996-2011) were considered. Demographic, treatment, disease status and bloods were collected. The effect of candidate prognostic factors on overall survival (OS) was determined using Kaplan-Meier curves followed by multivariate Cox regression analysis. Normalisation of the NLR following 1 cycle of epirubicin cisplatin and capecitabine (ECX) chemotherapy was tested for its impact on OS in a subgroup of patients receiving ECX chemotherapy (n = 14). Results 60 patients were included: median age 61 (range: 33-86); 51% men; median OS 5.9 months (0.7-42.9); 88% had metastasatic disease. On univariate analysis NLR > 5 (p = 0.009) and mGPS (p = 0.027) correlated with OS, unlike PLR > 300 (p = 0.5). Multivariate analysis confirmed mGPS (Hazard Ratio (HR); 1.52, 95%CI 1.0-2.3 p = 0.029) and NLR > 5 (HR 2.02 95%CI 1.0-4.1, p = 0.043) as independent predictors of OS. NLR normalisation post 1 cycle of ECX was associated with improved OS (8.6 months vs 4.6 months, p = 0.014). Results from an independent validation set will be presented. Conclusion Inflammatory indices are independent prognostic predictors in patients with CUP. Additionally, correction of NLR appears to reflect successful disease modulating effects of chemotherapy and may be used to predict survival benefit from treatment. External validation of these scores is ongoing. Disclosure All authors have declared no conflicts of interest.
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