Purpose: To identify the tumor portrait of the minority of head and neck squamous cell carcinoma (HNSCC) patients with recurrent-metastatic (RM) disease who upon treatment with platinum-based chemotherapy plus cetuximab present a long-lasting response.Experimental Design: The gene expression of pretreatment samples from 40 HNSCC-RM patients, divided in two groups [14 long-progression-free survival (PFS) and 26 short-PFS (median ¼ 19 and 3 months, respectively)], was associated with PFS and was challenged against a dataset from metastatic colon cancer patients treated with cetuximab. For biologic analysis, we performed functional and subtype association using gene set enrichment analysis, associated biology across all currently available HNSCC signatures, and inferred drug sensitivity using data from the Cancer Genomic Project.Results: The identified genomic profile exhibited a significant predictive value that was essentially confirmed in the single publicly available dataset of cetuximab-treated patients. The main divergence between long-and short-PFS groups was based on developmental/differentiation status. The long-PFS patients are characterized by basal subtype traits such as strong EGFR signaling phenotype and hypoxic differentiation, further validated by the significantly higher association with the hypoxia metagene. The short-PFS patients presented a strong activation of RAS signaling confirmed in an in vitro model of two isogenic HNSCC cell lines sensitive or resistant to cetuximab. The predicted drug sensitivity for all four EGFR inhibitors was higher in long-versus short-PFS patients (P range: <0.0022-1eÀ07).Conclusions: Our data uncover the biology behind response to platinum-based chemotherapy plus cetuximab in RM-HNSCC cancer and may have translational implications improving treatment selection.

EudraCT# 2011-002564-24.

Abstract. Ewing's sarcoma (ES) is an aggressive tumour that may present with skeletal and extraskeletal forms. The extraskeletal form is rarely encountered in the head and neck region and is extremely rare in the sinonasal tract. This is the case report of a ES of the ethmoid sinus with intracranial and orbital extension in a 33-year-old male patient who presented with anosmia, epistaxis, reduction of visual acuity in the left eye and headache. On otorhinolaryngological clinical examination and biopsy via flexible endoscope, the lesion was misdiagnosed as ethmoid sinus carcinoma. The subsequent magnetic resonance imaging (MRI) of the brain revealed a large mass (6x7 cm) eroding the ethmoid and sphenoid sinuses, extending beyond the orbits and occupying the anterior cranial fossa with a maximum extension of ~5 cm. The patient underwent surgical resection and the microscopic examination of the specimen established the diagnosis of ES (immunohistochemically positive for CD99, neuron-specific enolase, CD56, synaptophysin, pancytokeratin, low-molecular weight cytokeratins and vimentin. The periodic acid Schiff stain exhibited strong intracytoplasmic block positivity and fluorescence in situ hybridization revealed a t(22;11) translocation. First-line chemotherapy was administered for 3 cycles; however, on restaging MRI, local disease progression was diagnosed. The patient received radiotherapy and second-line chemotherapy for 6 cycles. At 15 months after the diagnosis, the patient remains recurrence-free and maintains a good functional status and quality of life.

Distant metastases (DM) in head and neck squamous cell carcinoma (HNSCC) remain a challenge as treatment options are limited. To identify biomarkers predictive of DM in primary tumors (PT), gene expression profiling was performed in PT from patients who did, or did not develop DM (T-with and T-without, n = 25 and 24, respectively), and in matched DM. A total of 185 and 42 differentially expressed genes were identified in the T-with vs. T-without and the T-with vs. DM comparisons, respectively. The intersection between these two comparisons identified COX7A1 and TBX5 as common genes. In three independent datasets, both genes were able to significantly distinguish patients according to their DM-free survival. By functional biological analyses, the T-without group showed enrichment in immune-response pathways, whereas the T-with group showed an enrichment in B-plasma cells and Tregs. Increased enrichment of proliferation-related pathways was observed in the T-with group compared with that in the DM group. Further comparisons with/without DM are needed to confirm these data in order to improve clinical management of HNSCC.

Background The aim of this study was to determine whether apparent diffusion coefficient (ADC) bi-component curve-fitting histogram analysis and volume percentage change (VPC) prior to bevacizumab treatment can stratify progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma multiforme (GBM) on first recurrence. Methods We retrospectively evaluated 17 patients with recurrent GBM who received bevacizumab and fotemustine ( n = 13) or only bevacizumab ( n = 4) on first recurrence at our institution between December 2009 and July 2015. Both T2/FLAIR abnormalities and enhancing tumor on T1 images were mapped to the ADC images. ADC-L and ADC-M values were obtained trough bi-Gaussian curve fitting histogram analysis. Furthermore, the study population was dichotomized into two subgroups: patients displaying a reduction in enhancing tumor volume of either >55% or <55% between the mean value calculated at baseline and first follow-up. Subsequently, a second dichotomization was performed according to a reduction in the T2 / FLAIR volume >41% or <41% at first check after treatment. OS and PFS were assessed using volume parameters in a Cox regression model adjusted for significant clinical parameters. Results In univariate analysis, contrast-enhanced (CE)-ADC-L was significantly predictive of PFS ( p = 0.01) and OS ( p = 0.03). When we dichotomized our sample using the 55% cut-off for enhancing tumor volume, CE-VPC was able to predict PFS ( p = 0.01) but not OS ( p = 0.08). In multivariate analysis, only the CE-ADC-L was predictive of PFS ( p = 0.01), albeit not predictive of OS ( p = 0.14). CE-ADC-M, T2/FLAIR-ADC-L, T2/FLAIR-ADC, and T2/FLAIR VPC were not significantly predictive of PFS and OS ( p > 0.05) in both univariate and multivariate analysis. Conclusions CE-ADC and CE-VPC can stratify PFS for patients with recurrent glioblastoma prior to bevacizumab treatment.