Shamir P. Chandarana

High stromal carbonic anhydrase IX expression is associated with nodal metastasis and decreased survival in patients with surgically-treated oral cavity squamous cell carcinoma

Every year, approximately 25,000 patients are diagnosed with oral cavity squamous cell carcinoma (OCSCC) in the USA. The 5-year survival rate for OCSCC is approximately 40%. Intratumoral hypoxia confers poor prognosis and treatment failure but direct tumor oxygen measurement is challenging. Carbonic anhydrase IX (CAIX) is a marker of tissue hypoxia and we have recently shown that stromal CAIX is associated with reduced survival in patients with HPV-negative head and neck cancer. We examined the importance of this observation in OCSCC patients. We identified patients diagnosed and treated with OCSCC in Calgary (Alberta, Canada) between 1998 and 2005. Clinical and pathologic data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of archived tumor tissue. Stromal CAIX expression was assessed by quantitative immunohistochemistry (AQUA-HistoRx). The primary endpoint was disease-specific survival. We identified 102 patients with OCSCC; 87 patients had surgery as their primary treatment and adequate tumor tissue for TMA construction was available for all patients. CAIX expression was evaluable for 61 patients. High (top quartile) stromal CAIX expression was associated with significantly reduced 5-year disease-specific survival compared to low stromal CAIX expression (p<0.006). This study confirms our previously reported association between high stromal CAIX expression and significantly reduced overall survival in an independent, predominantly p16-negative, cohort of surgically treated OCSCC. Assessment of stromal CAIX expression could identify patients with the least favorable prognosis and inform therapeutic strategies in OCSCC.

Basal Ki67 expression measured by digital image analysis is optimal for prognostication in oral squamous cell carcinoma

AIM The prognostic significance of Ki67 expression in cancers, including oral squamous cell carcinoma (OSCC), is unclear. This may be partly attributed to the lack of consensus surrounding the optimal approach for measuring tumour Ki67 expression. The aim of this study was to evaluate the association between different measures of Ki67 expression and disease-specific survival (DSS) in OSCC. METHODS Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded (FFPE) pre-treatment tumour tissue obtained from 121 OSCC patients diagnosed between 1998 and 2006. Ki67 expression was quantified using fluorescence immunohistochemistry (IHC) and AQUAnalysis® in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Intensity and percentage-based approaches for Ki67 scoring were tested for their association with survival. RESULTS Ki67 scores obtained from intensity and percentage-based approaches had similar associations with prognosis. We also found that high basal (lowest observed in triplicate cores) Ki67 expression was more strongly associated with improved 5-year disease-specific survival than hot-spot and average Ki67 measurements. The association of high basal Ki67 expression with improved prognosis was most pronounced in patients who received postoperative radiation. Cox proportional hazards analysis showed that the basal Ki67 expression is an independent prognostic marker in our OSCC cohort when adjusted for pathological T-stage, nodal status and treatment. CONCLUSIONS Our study provides a framework for reaching a consensus on the optimal approach for measuring Ki67 expression in cancers. Our results suggest that rigorous comparisons of measurement approaches should be applied in a tumour-type and treatment-specific manner to enhance the clinical application of Ki67 assessment.

MRI Texture Analysis Predicts p53 Status in Head and Neck Squamous Cell Carcinoma

BACKGROUND AND PURPOSE: Head and neck cancer is common, and understanding the prognosis is an important part of patient management. In addition to the Tumor, Node, Metastasis staging system, tumor biomarkers are becoming more useful in understanding prognosis and directing treatment. We assessed whether MR imaging texture analysis would correctly classify oropharyngeal squamous cell carcinoma according to p53 status. MATERIALS AND METHODS: A cohort of 16 patients with oropharyngeal squamous cell carcinoma was prospectively evaluated by using standard clinical, histopathologic, and imaging techniques. Tumors were stained for p53 and scored by an anatomic pathologist. Regions of interest on MR imaging were selected by a neuroradiologist and then analyzed by using our 2D fast time-frequency transform tool. The quantified textures were assessed by using the subset-size forward-selection algorithm in the Waikato Environment for Knowledge Analysis. Features found to be significant were used to create a statistical model to predict p53 status. The model was tested by using a Bayesian network classifier with 10-fold stratified cross-validation. RESULTS: Feature selection identified 7 significant texture variables that were used in a predictive model. The resulting model predicted p53 status with 81.3% accuracy (P < .05). Cross-validation showed a moderate level of agreement (κ = 0.625). CONCLUSIONS: This study shows that MR imaging texture analysis correctly predicts p53 status in oropharyngeal squamous cell carcinoma with ∼80% accuracy. As our knowledge of and dependence on tumor biomarkers expand, MR imaging texture analysis warrants further study in oropharyngeal squamous cell carcinoma and other head and neck tumors.

Cost-effectiveness analysis of a postoperative clinical care pathway in head and neck surgery with microvascular reconstruction

BackgroundThe objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction.MethodsThis is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate of pulmonary complications. Costing perspective was from the government payer.Results118 patients were included in the study. All outcomes demonstrated that the postoperative pathway group was both more effective and less costly, and is therefore a dominant clinical intervention. The overall mean pre- and post-pathway costs are

Impact of neuroradiologist second opinion on staging and management of head and neck cancer

22,733 and

Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

16,564 per patient, respectively. The incremental cost reduction associated with the postoperative pathway was

Diagnostic utility of central node necrosis in predicting extracapsular spread among oral cavity squamous cell carcinoma

6,169 per patient.ConclusionImplementing the postoperative clinical care pathway in patients undergoing head and neck oncologic surgery with reconstruction resulted in improved clinical outcomes and reduced costs.

Understanding the impact of a clinical care pathway for major head and neck cancer resection on postdischarge healthcare utilization

ObjectivePatients with head and neck cancer frequently present to academic tertiary referral centers with imaging studies that have been performed and interpreted elsewhere. At our institution, these outside head and neck imaging studies undergo formal second opinion reporting by a fellowship-trained academic neuroradiologist with expertise in head and neck imaging. The purpose of this study was to determine the impact of this practice on cancer staging and patient management.MethodsOur institutional review board approved the retrospective review of randomized original and second opinion reports for 94 consecutive cases of biopsy proven or clinically suspected head and neck cancer in calendar year 2010. Discrepancy rates for staging and recommended patient management were calculated and, for the 32% (30/94) of cases that subsequently went to surgery, the accuracies of the reports were determined relative to the pathologic staging gold standard.ResultsFollowing neuroradiologist second opinion review, the cancer stage changed in 56% (53/94) of cases and the recommended management changed in 38% (36/94) of patients with head and neck cancer. When compared to the pathologic staging gold standard, the second opinion was correct 93% (28/30) of the time.ConclusionIn a majority of patients with head and neck cancer, neuroradiologist second opinion review of their outside imaging studies resulted in an accurate change in their cancer stage and this frequently led to a change in their management plan.

Extent of central neck dissection among thyroid cancer surgeons: Cross-sectional analysis.

BackgroundResistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique.MethodsSixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model.ResultsBax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent predictor of DSS in OSCC [HR 0.241 (0.078-0.745), p = 0.013].ConclusionsThe AQUA technique used in our study eliminates observer bias and provides reliable and reproducible estimates for biomarker expression. AQUA also provides essential measures of quality control that cannot be achieved with manual biomarker scoring techniques. Our results support the use of Bax protein expression as a prognostic marker in conjunction with other clinico-pathological variables when designing personalized treatment strategies for OSCC patients.

Polyethylene Implants in Nasal Septal Restoration

Oral cavity squamous cell carcinoma (SCC) represents the most common SCC affecting the head and neck region. Long‐term survival of patients with oral cavity SCC is adversely affected by lymph node metastasis and further decreased by the presence of lymph node extracapsular spread (ECS).