A B S T R A C T PurposeTo determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial. Patients and MethodsPatients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction. ResultsSlides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P ϭ .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P ϭ .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P ϭ .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P ϭ .13). ConclusionHPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.

We found no evidence that the addition of TPZ to chemoradiotherapy, in patients with advanced head and neck cancer not selected for the presence of hypoxia, improves OS.

BACKGROUNDCutaneous squamous cell carcinoma (SCC) of the head and neck is a common cancer that has the potential to metastasize to lymph nodes in the parotid gland and neck. Previous studies have highlighted limitations with the current TNM staging system for metastatic skin carcinoma. The aim of this study was to test a new staging system that may provide better discrimination between patient groups.METHODSA retrospective multicenter study was conducted on 322 patients from three Australian and three North American institutions. All had metastatic cutaneous SCC involving the parotid gland and/or neck and all were treated for cure with a minimum followup time of 2 years. These patients were restaged using a newly proposed system that separated parotid disease (P stage) from neck disease (N stage) and included subgroups of P and N stage. Metastases involved the parotid in 260 patients (149 P1; 78 P2; 33 P3) and 43 of these had clinical neck disease also (22 N1; 21 N2). Neck metastases alone occurred in 62 patients (26 N1; 36 N2). Ninety percent of patients were treated surgically and 267 of 322 received radiotherapy.RESULTSNeck nodes were pathologically involved in 32% of patients with parotid metastases. Disease recurred in 105 (33%) of the 322 patients, involving the parotid in 42, neck in 33, and distant sites in 30. Parotid recurrence did not vary significantly with P stage. Disease‐specific survival was 74% at 5 years. Survival was significantly worse for patients with advanced P stage: 69% survival at 5 years compared with 82% for those with early P stage (P = 0.02) and for those with both parotid and neck node involvement pathologically: 61% survival compared with 79% for those with parotid disease alone (P = 0.027). Both univariate and multivariate analysis confirmed these findings. Clinical neck involvement among patients with parotid metastases did not significantly worsen survival (P = 0.1).CONCLUSIONSThis study, which included a mixed cohort of patients from six different institutions, provides further information about the clinical behavior of metastatic cutaneous SCC of the head and neck. The hypothesis that separation of parotid and neck disease in a new staging system is supported by the results. The benefit of having subgroups of P and N stage is uncertain, but it is likely to identify patients with unfavorable characteristics that may benefit from further research. Cancer 2006. © 2006 American Cancer Society.

Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.

Lung cancer affects over 1. 8 million people worldwide and is the leading cause of cancer related mortality globally. Currently, diagnosis of lung cancer involves a combination of imaging and invasive biopsies to confirm histopathology. Non-invasive diagnostic techniques under investigation include “liquid biopsies” through a simple blood draw to develop predictive and prognostic biomarkers. A better understanding of circulating tumor cell (CTC) dissemination mechanisms offers promising potential for the development of techniques to assist in the diagnosis of lung cancer. Enumeration and characterization of CTCs has the potential to act as a prognostic biomarker and to identify novel drug targets for a precision medicine approach to lung cancer care. This review will focus on the current status of CTCs and their potential diagnostic and prognostic utility in this setting.

Tumor biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumors change dynamically in response to therapy, and there remains a need for a more representative biomarker that can be assayed over the course of treatment. Circulating tumor cells (CTCs) may provide clinically important and comprehensive tumoral information that is predictive of treatment response and outcome. Blood samples were processed for CTCs from 56 patients using the ClearCell FX system. Captured cells were phenotyped for CTC clusters and markers for immunotherapy (PD‐L1) CTC chromosomal architecture (ALK, EGFR). CTCs were isolated in 11/23 (47.8%) of head and neck cancer (HNC) patients and 17/33 (51.5%) of non‐small‐cell lung cancer (NSCLC) patients. CTCs were determined to be PD‐L1‐positive in 6/11 (54.4%) HNC and 11/17 (64.7%) NSCLC cases, respectively. 3D chromosomal DNA FISH for ALK and EGFR molecular targets showed better resolution than in 2D when imaging CTCs. HNC CTC‐positive patients had shorter progression‐free survival (PFS) (hazard ratio[HR]: 4.946; 95% confidence internal[CI]:1.571‐15.57; P = 0.0063), and PD‐L1‐positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011‐26.33; P = 0.0485). In the advanced stage NSCLC patient cohort, PFS was not found to be associated with CTCs prior to therapy ([HR]:2.246; 95% [CI]:0.9565‐5.273; P = 0.0632), nor the presence of PD‐L1 expression ([HR]:1.646; 95% [CI]:0.5128‐5.283; P = 0.4023). This study demonstrated that CTCs are predictive of poorer outcomes in HNC and provides distinct and separate utility for CTCs in HNC and NSCLC, which may be more representative of the disease burden and overall survival than the parameters used to measure them.

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The risk categories in the guidelines are valid to assist early identification of swallowing and nutritional risk and guide decision-making on proactive gastrostomy tube insertion.