Harold Lau

Physical activity for men receiving androgen deprivation therapy for prostate cancer: benefits from a 16-week intervention

Goals of workProstate cancer patients receiving androgen deprivation therapy (ADT) are vulnerable to a number of potentially debilitating side effects, which can significantly impact quality of life. The role of alternate therapies, such as physical activity (PA), in attenuating these side effects is largely understudied for such a large population. Thus, the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior, quality of life, and fitness measures.Patients and methodsOne hundred participants were randomized into an intervention (n = 53) or a wait-list control group (n = 47), with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing. The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions. PA, quality of life, fitness, and physiological outcomes were assessed pre and post the 16-week intervention.ResultsSignificant increases in PA, supported by changes in girth measures and blood pressure, support the beneficial impact of the intervention. Positive trends were also evident for depression and fatigue. However, due to the high dropout rate, these results must be interpreted with caution.ConclusionsPA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy. Determining the maintenance of this behavior change will be important for understanding how the long-term benefits of increased activity levels may alleviate the late effects of ADT.

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

Localized prostate cancer can be treated several different ways, but head‐to‐head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients.

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.

A Randomized Trial of External Beam Radiotherapy Versus Cryoablation in Patients With Localized Prostate Cancer: Quality of Life Outcomes

A recent randomized trial to compare external beam radiation therapy (EBRT) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival. We report on the quality of life (QOL) outcomes for this trial.

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.

Prognostic significance of p16 in locally advanced squamous cell carcinoma of the head and neck treated with concurrent cisplatin and radiotherapy

Human papillomavirus (HPV)–related squamous cell cancer of the head and neck (SCCHN) has emerged as a distinct clinical entity. The expression of p16 protein can be used as a surrogate for HPV status.

High stromal carbonic anhydrase IX expression is associated with decreased survival in P16-negative head-and-neck tumors.

PURPOSE Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. METHODS AND MATERIALS Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). RESULTS High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. CONCLUSIONS This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.

Clinical impact of using the deterministic patient dose calculation algorithm Acuros XB for lung stereotactic body radiation therapy

Abstract Purpose. To evaluate the clinical impact of using the deterministic dose calculation algorithm, Acuros XB, for early stage lung cancer patients undergoing stereotactic body radiotherapy (SBRT). Material and methods. Seventy-seven stage I non-small cell lung cancer patients who underwent lung SBRT from 2008 to 2012 at our center were included in this study. All treatment plans originally calculated by the anisotropic analytical algorithm (AAA) were recalculated using the AAA and Acuros XB algorithms with identical monitor units and beam arrangements. The dose, dose distribution, conformality number (CN) and heterogeneity index (HI) of the target were determined for each plan. A paired matched t-test was used to evaluate the difference between the mean dose, the dose distribution, and the CN and HI for the target. The importance of tumor (volume, location), patient (pulmonary functional, body mass index) and treatment (number of SBRT beams) on the dose distributions obtained from the two algorithms was statistically determined using linear regression analyses. Results. The mean target dose was same for both algorithms. Compared to AAA, a small and significant difference in dose distribution in the target was found for the Acuros XB algorithm, resulting in lower conformity (−2.1%, p < 0.0001) and higher heterogeneity (p < 0.0001) of dose. Single logistic regression identified pulmonary function, number of beams and target location as being correlated with the difference of CN between the two calculations. Multivariate analysis indicated that the patients pulmonary function (p = 0.0296) was the only predictor for the difference in conformality between the two dose calculation algorithms. Conclusions. In lung SBRT, the patients pulmonary function is responsible for the difference in target dose distribution between the Acuros XB and AAA algorithms. The Acuros XB algorithm could be used to advantage in patients with compromised pulmonary function based on its accurate modeling of lung tissue in comparison to AAA.

Concomitant low-dose cisplatin and three- dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck : Analysis of survival and toxicity

Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules.