T. Wayne Matthews

Clinical utility of PET/CT in the evaluation of head and neck squamous cell carcinoma with an unknown primary: A prospective clinical trial

Metastatic head and neck squamous cell carcinoma with an unknown primary is an uncommon but important problem. PET/CT, as an adjunct to diagnosis, is potentially useful but has never been studied in a prospective, single‐blinded clinical trial.

Soft-tissue sarcomas of the head and neck: a retrospective analysis of the Alberta experience 1974 to 1999.

Background: Soft‐tissue sarcomas (STS) of the head and neck constitute a heterogeneous group of rare malignant tumors occurring in an uncommon site. The most common subtypes of STS in the head and neck are malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, and fibrosarcoma. Evidence based subtype‐specific treatment decisions are often not possible.

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.

Absence of Planned Neck Dissection for the N2-N3 Neck After Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

OBJECTIVE To review our institutional experience of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) and N2-N3 neck disease with respect to neck recurrence after chemoradiation without planned neck dissection (ND). DESIGN Retrospective study. SETTING Tom Baker Cancer Centre, Calgary, Alberta, Canada. PATIENTS Fifty-four adults with locally advanced SCCHN and N2-N3 neck disease. INTERVENTIONS Eighty consecutive patients were treated with chemoradiation, 70 Gy given as 2 Gy daily for 7 weeks, with cisplatin, 20 mg/m(2), given on the first 4 days of weeks 1 and 5. Of the 80 patients, 54 were evaluable. MAIN OUTCOME MEASURES Primary outcomes were overall survival and absence or presence of neck disease after chemoradiation. Secondary outcomes included disease-specific survival and locoregional recurrence-free survival. RESULTS Median follow-up of living patients was 35 months. Patients with a complete response (CR) did not have any planned ND. Factors associated with the absence of recurrent neck disease included CR (P < .001), younger age (P = .02), and better Karnofsky Performance Status (P = .049). In patients achieving CR, 2-year overall, disease-specific, and locoregional recurrence-free survival was 92%, 95%, and 95%, respectively. Three of the 43 patients (7%) with N2 lesions obtaining CR subsequently experienced a neck recurrence at a median of 15 months (range, 7-24 months). CONCLUSIONS In these patients with locally advanced SCCHN and N2-N3 neck disease treated with chemoradiation and achieving CR, only a few patients with N2 neck disease experienced recurrence despite the absence of planned ND. Prospective trials are needed to identify patients with N2 neck disease who may still benefit from planned ND after chemoradiation. There were not enough patients with N3 neck disease to make any recommendations.

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.

Fiber-optic endoscopic evaluation of swallowing (FEES): predictor of swallowing-related complications in the head and neck cancer population.

The treatment of head and neck cancer is associated with significant dysphagia and morbidity. Prescribing a safe oral diet in this population is challenging.

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

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.

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

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.

The Utility of the Harmonic Scalpel in Selective Neck Dissection A Prospective, Randomized Trial

Objectives. To determine the impact of the harmonic scalpel on intraoperative blood loss and operative time in selective neck dissection (SND) (levels I-IV) for head and neck squamous cell carcinoma (HNSCC). Study Design. Prospective randomized controlled trial. Setting. A single, tertiary care institution (Foothills Medical Centre) in Calgary, Alberta, Canada. Subjects. A total of 31 patients (36 neck dissections) were prospectively enrolled between January 2009 and March 2010. Methods. Patients were randomized to receive a neck dissection with either the harmonic scalpel or the traditional technique of using electrocautery and sharp dissection. The study included adult patients older than age 18 years diagnosed with HNSCC and who required an SND (levels I-IV). Study exclusion criteria included previous treatment for head and neck cancer and all patients unwilling or unable to provide informed consent. Primary clinical outcomes were intraoperative blood loss and operative time. Secondary outcomes included intraoperative complications and surgical drain output. Results. Intraoperative blood loss was significantly lower in the harmonic scalpel group compared to the traditional group (158 vs 61 mL, P = .02). There was no difference in operative time (81 minutes harmonic vs 85 minutes traditional) or total drain output (at both 48 hours and 1 week) between the groups. There were no intraoperative complications reported in either group. Conclusions. Results from this study suggest that the harmonic scalpel can reduce blood loss during SND for HNSCC. The harmonic scalpel had no impact on operative time, postoperative drain output, or complication rate.

Delayed mobilization after microsurgical reconstruction: An independent risk factor for pneumonia

Large defects secondary to oral cancer resection are reconstructed with microsurgical free flaps. Pulmonary complications in these patients are common. Postoperative mobilization is recommended to decrease respiratory complications; however, many microsurgeons are reluctant to adopt early mobilization protocols due to the perceived risk of flap compromise. The purpose of this study was to determine the incidence of pneumonia among patients undergoing oral cancer resection and immediate free flap reconstruction and to compare the incidence of this complication between patients mobilized early (<4 days postoperative) versus later. A secondary goal was to determine whether early postoperative mobilization affected microvascular flap outcome.