BACKGROUND. Recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is generally an incurable disease, with patients experiencing median survival of under 10 months and... Show moreBACKGROUND. Recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is generally an incurable disease, with patients experiencing median survival of under 10 months and significant morbidity. While immune checkpoint blockade (ICB) drugs are effective in approximately 20% of patients, the remaining experience limited clinical benefit and are exposed to potential adverse effects and financial costs. Clinically approved biomarkers, such as tumor mutational burden (TMB), have a modest predictive value in HNSCC.METHODS. We analyzed clinical and genomic features, generated using whole-exome sequencing, in 133 ICB-treated patients with R/M HNSCC, of whom 69 had virus-associated and 64 had non-virus-associated tumors.RESULTS. Hierarchical clustering of genomic data revealed 6 molecular subtypes characterized by a wide range of objective response rates and survival after ICB therapy. The prognostic importance of these 6 subtypes was validated in an external cohort. A random forest-based predictive model, using several clinical and genomic features, predicted progression-free survival (PFS), overall survival (OS), and response with greater accuracy than did a model based on TMB alone. Recursive partitioning analysis identified 3 features (systemic inflammatory response index, TMB, and smoking signature) that classified patients into risk groups with accurate discrimination of PFS and OS.CONCLUSION. These findings shed light on the immunogenomic characteristics of HNSCC tumors that drive differential responses to ICB and identify a clinical-genomic classifier that outperformed the current clinically approved biomarker of TMB. This validated predictive tool may help with clinical risk stratification in patients with R/M HNSCC for whom ICB is being considered. Show less
Aims: To describe the characteristics and outcomes of cancer patients receiving Whole Brain Radiotherapy (WBRT) and delineate poor outcome groups after WBRT.Materials and methods: From 1991 to 2007... Show moreAims: To describe the characteristics and outcomes of cancer patients receiving Whole Brain Radiotherapy (WBRT) and delineate poor outcome groups after WBRT.Materials and methods: From 1991 to 2007, 3459 patients receiving WBRT for brain metastases at three centres (in Australia and the Netherlands) were retrospectively reviewed. The effect of clinicodemographic factors, including age, gender, primary cancer, time to WBRT from primary cancer diagnosis and WBRT timing relative to other radiotherapy courses on overall survival, survival from WBRT commencement (WBRT-SV) and death within 6 weeks were analysed.Results: WBRT was the first radiotherapy course in 2161/3459 (63%) and the last in 2932/3459 (85%). The most common primary cancer sites with brain metastases were lung (n = 1800; 52%), breast (n = 568; 16%), melanoma (n = 350; 10%) and colorectal (n = 209; 6%). The median time to WBRT from primary cancer diagnosis was 34 weeks, overall survival 1.42 years (0.04-28.70) and WBRT-SV 0.33 years (0-8.60). Older age, male gender and a shorter time from the primary cancer diagnosis to WBRT predicted worse overall survival and WBRT-SV. Seventeen per cent survived less than 6 weeks. Older patients with a shorter time from the primary cancer diagnosis to WBRT and a lower WBRT episode number were more likely to die less than 6 weeks after WBRT.Conclusions: Cancer patients with brain metastases have poor overall outcomes. High mortality within 6 weeks of starting WBRT suggests patient selection remains challenging. (C) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Show less
