Apostolos Christopoulos

Clinical Usefulness of Positron Emission Tomography–Computed Tomography in Recurrent Thyroid Carcinoma

OBJECTIVES To determine the efficacy of combined positron emission tomography-computed tomography (PET-CT) in identifying recurrent thyroid cancer and to elucidate its role in the clinical management of thyroid carcinoma. DESIGN Retrospective study. SETTING Tertiary care referral academic center. PATIENTS One hundred twenty-four patients with previously treated thyroid carcinoma who underwent PET-CT. MAIN OUTCOME MEASURES PET-CT images were correlated with clinicopathologic information. The influence of PET-CT findings on disease status determination and the treatment plan was evaluated. RESULTS Among 121 patients undergoing iodine I 131 ((131)I) imaging (an (131)I image was unavailable for 3 patients), 80.6% had negative findings on (131)I imaging before undergoing PET-CT. Among 75 patients who had positive findings on PET-CT, 71 were true positive results. Among 49 patients who had negative findings on PET-CT, 32 were true negative results. Therefore, PET-CT demonstrated a sensitivity of 80.7%, specificity of 88.9%, positive predictive value of 94.7%, and negative predictive value of 65.3%. A significant difference was noted in the mean serum thyroglobulin levels between patients with positive vs negative PET-CT findings (192.1 vs 15.0 ng/mL, P = .01) (to convert thyroglobulin level to micrograms per liter, multiply by 1.0). Overall, distant metastases were detected in 20.2% of patients using PET-CT. There was an alteration of the treatment plan in 28.2% of patients as a result of added PET-CT information, and 21.0% of patients underwent additional surgery. CONCLUSIONS PET-CT is usually performed in patients with thyroid cancer having elevated thyroglobulin levels but non-(131)I-avid tumors and has high diagnostic accuracy for identifying local, regional, and distant metastases. Additional information from PET-CT in patients with (131)I-negative and thyroglobulin-positive tumors frequently guides the clinical management of recurrent thyroid carcinoma.

Biology of vascular endothelial growth factor and its receptors in head and neck cancer: Beyond angiogenesis

Angiogenesis is a necessary process for tumor progression and is driven through molecular interactions between cancer cells and neighboring vascular endothelial cells. The primary mediators of angiogenesis are the vascular endothelial growth factors and their respective receptors on endothelial cells. There are several U.S. Food and Drug Administration–approved anti‐angiogenic agents in clinical use. In head and neck cancer there are clinical trials assessing the efficacy of anti‐angiogenic agents in combination with chemoradiation therapy. Although the aforementioned growth factors and receptors have been traditionally viewed as anti‐angiogenic targets, there are concomitant efforts to understand the role these molecules play within the tumor cells. In this review, we first discuss the biology of angiogenic proteins and the targeting of angiogenic molecules for cancer treatment. We summarize the current clinical trials of anti‐angiogenic therapies in head and neck squamous cell carcinoma. Finally, the additional role these molecules play in tumor progression independent of angiogenesis is discussed.

Oncologic and Functional Outcomes of Partial Laryngeal Surgery for Intermediate-Stage Laryngeal Cancer

Objective To evaluate the oncologic and functional outcomes of partial laryngeal surgery (PLS) using transoral laser microsurgery (TLM) and supracricoid laryngectomy (SCL) in patients with intermediate-stage laryngeal squamous cell carcinoma (LSCC). Study Design Historical cohort study. Setting Single tertiary care center. Subjects and Methods Retrospective review of oncologic and functional outcomes in intermediate-stage (T2-3/N0-1, stage II and III) LSCC patients who underwent TLM or SCL from 1998 to 2010. Results Sixty patients were included, of whom 28 (47%) underwent TLM and 32 (53%) underwent SCL. For the entire cohort, 2- and 5-year probabilities were 86.2% (95% confidence interval [CI], 73.0%-93.2%) and 72.9% (95% CI, 52.4%-85.6%), respectively, for overall survival (OS) and 79.3% (95% CI, 65.6%-88.0%) and 62.4% (95% CI, 41.9%-77.4%), respectively, for recurrence-free survival (RFS). There was no difference between the TLM and SCL cohorts in OS (P = .542) or RFS (P = .483). More than 75% of patients avoided adjuvant therapy. Communication Scale and Functional Outcome Swallowing Scale scores at median follow-up of 33 months were 2 or better in 97% and 91% of patients, respectively, reflecting functional voice and swallowing postoperatively. Eighty-eight percent of patients retained a functional larynx. Conclusion PLS provides excellent oncologic and functional outcomes for intermediate-stage LSCC and should be considered an alternative to chemoradiation or total laryngectomy in selected patients.

Cervical Lymph Node Metastases From Unknown Primary Cancer: A Single-Institution Experience With Intensity-Modulated Radiotherapy

PURPOSE To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer. METHODS AND MATERIALS Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method. RESULTS With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up. CONCLUSION In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities.

Predictive factors of survival and treatment tolerance in older patients treated with chemotherapy and radiotherapy for locally advanced head and neck cancer

PURPOSE To report outcomes and predictive factors of overall survival, hospitalization and treatment completion rates in elderly patients with locally advanced head and neck cancer treated with concurrent chemoradiotherapy (CRT). MATERIAL AND METHODS A retrospective analysis of patients aged 70years or older treated with concurrent CRT for locally advanced head and neck cancer was conducted. Univariate and multivariate analysis as well as competing risk survival analysis were used to determine predictors of mortality. Logistic regression was used to predict for hospitalization and treatment completion rates. RESULTS In total, 129 patients were included. Median follow-up was 27months (range: 1.7-125months). Completion rate of combined CRT was 84%. Actuarial OS and DSS at 4years were 56% and 75%. Hospitalization rate was 36%. On multivariate analysis, a Karnofsky performance status (KPS) ⩽80 was predictive of mortality. Using competing risks, KPS ⩽80 and weight loss >5% were predictive of cancer mortality whereas Charlson score ⩾3 was predictive of mortality due to other causes. On logistic regression, patients with abnormal renal function and lower body mass index were more likely to be hospitalized during their treatment course. Charlson score and chemotherapy regimen were predictive of treatment completion. CONCLUSION Concurrent CRT may be a feasible treatment option for healthier older patients at the cost of high hospitalization rates. Pre-treatment factors linked to physiological age such as KPS ⩽80, Charlson score ⩾3, abnormal renal function should be considered at the time of treatment decision.

North-American survey on HPV-DNA and p16 testing for head and neck squamous cell carcinoma.

OBJECTIVES Human papillomavirus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) have been shown to have a significantly better prognosis and response to current treatment modalities. Current guidelines recommend systematic HPV-DNA and/or p16 testing on HNSCCs, although treatment approach should not be directed by test results. The objectives of this study were to (1) assess whether HPV-DNA and/or p16 status are systematically evaluated across North American otolaryngologists-head and neck surgeons and (2) whether the status is used to direct treatment approach. MATERIALS AND METHODS A 15-question online survey was sent to three associations: the Association of Oto-rhino-laryngology-Head and Neck Surgery of Quebec, the Canadian Society of Otolaryngology-Head and Neck Surgery, and the American Head and Neck Society. RESULTS Sixty-seven percent of respondents systematically test for HPV-DNA and/or p16 on HNSCC sites, while 58.3% report using test results to direct treatment for oropharyngeal cancers. A lack of official guidelines was the primary reason (81.8%) physicians did not use test results to direct treatment. Academic centre physicians (83.3%) and physicians with ⩾50% oncologic practice (87.6%) were more likely to test for HPV-DNA and/or p16 in HNSCC compared to non-academic centre physicians (39.7%) and physicians with <50% oncologic practices (51.4%) (p<0.001). Cost of the tests (69.2%), lack of relevance (46.1%) and time constraints (30.8%) were the primary reasons HPV-DNA and/or p16 were not tested. CONCLUSION The majority of North American respondents in this survey systematically test for HPV-DNA and/or p16 in HNSCC sites, and most indicate that test results influence their treatment approach for oropharyngeal cancers.

Predicting Depression and Quality of Life among Long-term Head and Neck Cancer Survivors

Objective The aim of this study is to identify clinical factors that are predictive of depression and quality of life (QOL) among long-term survivors of head and neck squamous cell carcinoma and to develop predictive scores using these factors. Study Design Cohort study Setting Tertiary referral center. Subjects and Methods A total of 209 posttreatment (median follow-up, 38.7 months) head and neck cancer patients were prospectively evaluated using the Hospital Anxiety Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, and the EORTC Quality of Life Questionnaire Head and Neck 35, and pretreatment patient-related, tumor-related, and treatment-related predictors were identified using chart review. Bivariate (χ2 and t test) and multivariate (linear regression) analyses were used to construct predictive models. Results Significant pretreatment predictors of depression were identified on multivariate analysis as smoking at diagnosis, >14 alcoholic drinks per week, T3 or T4 status, and >3 medications (P < .001). Two or more of these factors yielded an 82.3% sensitivity in detecting significant depressive symptoms (defined as a HADS cutoff score of 5). Significant predictors of fatigue, global health/QOL, social contact, speech, pain, swallowing, and xerostomia were also identified. Conclusion Pretreatment predictors of long-term depression and QOL have been defined using multivariate models, and an easily applicable predictive score of long-term depression is proposed. Potential eventual clinical applications include prophylactic intervention in at-risk patients.

Perioperative practices in thyroid surgery: An international survey

Perioperative practices in thyroid surgery vary from one specialty, institution, or country to the next. We evaluated the preoperative, intraoperative, and postoperative practices of thyroid surgeons focusing on preoperative ultrasound, vocal cord evaluation, wound drains, and hospitalization duration, among others.

Prognostic value of cartilage sclerosis in laryngeal cancer treated with primary radiation therapy.

Objective In patients with laryngeal cancer, pretreatment diagnosis of cartilage invasion often warrants a surgical or a bimodal treatment. Controversy exists on whether laryngeal cartilage sclerosis on computed tomography (CT) scan is a sign of tumor invasion. Our objective is to evaluate locoregional, laryngectomy-free, disease-specific, and overall survival in patients with laryngeal cancer with or without laryngeal cartilage sclerosis treated with primary radiation therapy. Study Design Historical cohort study. Setting Tertiary referral university center. Subjects and Methods All laryngeal cancer patients treated with primary radiation therapy between 2002 and 2007 were included. Patients with and without laryngeal cartilage sclerosis on CT scan were identified. Patient, tumor, and treatment data were collected. Univariate and multivariate analyses were conducted using Kaplan-Meier survival analyses and Cox proportional-hazards regression. Results One hundred eleven patients were included for analysis. Seventy-nine patients were classified as T1 or T2, and 32 patients were classified as T3 or T4. Twenty-three percent of patients had any laryngeal cartilage sclerosis, and 77% of patients had no sclerosis. On univariate and multivariate analyses, there was no statistically significant difference between patients with or without sclerosis. Results did not vary when studying each cartilage separately. Conclusion Laryngeal cancer patients with cartilage sclerosis on CT scan do not have significantly different survival than patients without sclerosis. Validation of these results prospectively is warranted.

The Cost of Prolonged Hospitalization due to Postthyroidectomy Hypocalcemia: A Case-Control Study

The aim of this study is to evaluate the additional costs associated with calcium monitoring and treatment as well as evaluate the incidence and predictors of postthyroidectomy hypocalcemia. Methods. This case-control study involved thyroidectomy and completion thyroidectomy patients operated on between January 2012 and August 2013. Cases were defined as requiring calcitriol supplementation, and controls did not require supplementation. Patient (age, sex), nodule (cytology, pathology), surgical data (neck dissection, parathyroid identification, and reimplantation), and hospital stay (days hospitalized in total and after drain removal) were compared. Comparisons were made using -tests and chi-square tests with an alpha of 0.05. The estimated cost associated with the extended stay was then compared with the cost of supplementation. Results. A total of 191 patients were evaluated (61 cases and 130 controls). Predictors of hypocalcemia include female age, neck dissection, and parathyroid reimplantation. Hypocalcemic patients were hospitalized for a longer period of time after drain removal (2.5 versus 0.8 days, ), and hospitalization costs after neck drain removal were higher in this group as well (8,367.32