K. Alok Pathak

An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

BACKGROUND Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. METHODS A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. RESULTS Using age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. CONCLUSIONS A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.

The changing face of thyroid cancer in a population-based cohort.

In North America, the incidence of thyroid cancer is increasing by over 6% per year. We studied the trends and factors influencing thyroid cancer incidence, its clinical presentation, and treatment outcome during 1970–2010 in a population‐based cohort of 2306 consecutive thyroid cancers in Canada, that was followed up for a median period of 10.5 years. Disease‐specific survival (DSS) and disease‐free survival were estimated by the Kaplan–Meier method and the independent influence of various prognostic factors was evaluated by Cox proportional hazard models. Cumulative incidence of deaths resulting from thyroid cancer was calculated by competing risk analysis. A P‐value <0.05 was considered to indicate statistical significance. The age standardized incidence of thyroid cancer by direct method increased from 2.52/100,000 (1970) to 9.37/100,000 (2010). Age at diagnosis, gender distribution, tumor size, and initial tumor stage did not change significantly during this period. The proportion of papillary thyroid cancers increased significantly (P < 0.001) from 58% (1970–1980) to 85.9% (2000–2010) while that of anaplastic cancer fell from 5.7% to 2.1% (P < 0.001). Ten‐year DSS improved from 85.4% to 95.6%, and was adversely influenced by anaplastic histology (hazard ratio [HR] = 8.7; P < 0.001), male gender (HR = 1.8; P = 0.001), TNM stage IV (HR = 8.4; P = 0.001), incomplete surgical resection (HR = 2.4; P = 0.002), and age at diagnosis (HR = 1.05 per year; P < 0.001). There was a 373% increase in the incidence of thyroid cancer in Manitoba with a marked improvement in the thyroid cancer‐specific survival that was independent of changes in patient demographics, tumor stage, or treatment practices, and is largely attributed to the declining proportion of anaplastic thyroid cancers.

Sternocleidomastoid muscle interposition to prevent carotid artery blowout

Carotid blow‐out syndrome is the most dreaded complication in head and neck surgical oncology practice This article describes a simple technique of interposition of sternocleidomastoid muscle between pharynx and carotid sheath to isolate the latter from salivary contamination in the event of salivary leak. Authors have used this technique in 83 laryngectomies with excellent results. J. Surg. Oncol. 2008;98:565–566.

Transient early increase in thyroglobulin levels post-radioiodine ablation in patients with differentiated thyroid cancer

OBJECTIVES Treatment of differentiated thyroid cancer (DTC) includes surgical thyroidectomy and, in most cases, radioactive iodine (RAI) ablation. Measurement of serum thyroglobulin (Tg) levels is used for assessing disease burden and identifying persistent-recurrent DTC. This prospective study determined the Tg profile before and after RAI-ablation in patients with DTC. DESIGN AND METHODS Fifty-five DTC patients with complete resection received RAI-ablation and were assessed for Tg at baseline (non-stimulated), pre-ablation (stimulated), 7 days post-ablation (stimulated) and at 6 months (stimulated). Stimulation of Tg was achieved by thyroid hormone withdrawal to achieve serum thyroid stimulating hormone (TSH) ≥30 mU/L. Thyroid remnant size was estimated from whole body scintigraphy. Similar protocols were implemented for nine patients with incomplete resection/metastatic disease for comparison. RESULTS Mean stimulated Tg levels for DTC patients with complete resection at 7 days post-RAI increased 13-fold from 13.7 to 175.5 μg/L (p<0.0001), and the Tg levels reduced to 2.3 μg/L (p<0.0001 versus post-RAI) by follow-up. None of the patients had recurrence of disease. For the nine patients with incomplete resection/metastases, Tg levels were higher throughout compared to the patients with complete resection. There was no increase in Tg between pre- and post-RAI. We did not observe a significant correlation between the remnant size and Tg increase. CONCLUSIONS This study confirms a prominent transient early increase in Tg post-RAI ablation in DTC patients with complete resection, with the Tg levels falling below baseline by 6 months. This is presumed to reflect RAI-induced thyroid tissue destruction/inflammation with subsequent release of Tg from the thyroid remnant. Recognizing this transient phenomenon is important for post-ablation Tg interpretation and patient management.

A prospective cohort study to assess the role of FDG-PET in differentiating benign and malignant follicular neoplasms

Background Follicular and Hürthle cell neoplasms are diagnostic challenges. This prospective study was designed to evaluate the efficacy of [18F]-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting the risk of malignancy in follicular/Hürthle cell neoplasms. Materials and methods Fifty thyroid nodules showing follicular/Hürthle cell neoplasm on prior ultrasonography guided fine needle aspiration cytology (FNAC) were recruited into this study. A FDG-PET/CT scan, performed for neck and superior mediastinum, was reported by a single observer, blinded to the surgical and pathology findings. Receiver operating characteristic (ROC) curve analysis of maximum standardized uptake value (SUVmax) and the area under the curve (AUROC) were used to assess discrimination between benign from malignant nodules. Youden index was used to identify the optimal cut-off SUVmax for diagnosing malignancy. Sensitivity, specificity, predictive values and overall accuracy were used as measures of performance. Results Our study group comprises of 31 benign and 19 malignant thyroid nodules. After excluding all Hürthle cell adenomas, the AUROC for discriminating benign and malignant non-Hürthle cell neoplasms was 0.79 (95% CI, 0.64–0.94; p = 0.001); with SUVmax of 3.25 as the best cut-off for the purpose. PET/CT had sensitivity of 79% (95% CI, 54–93%), specificity of 83% (95% CI, 60–94%), positive predictive value (PPV) of 79% (95% CI, 54–93%), and negative predictive value (NPV) of 83% (95% CI, 60–94%). The overall accuracy was 81%. Conclusions FDG-PET/CT can help in differentiating benign and malignant non-Hürthle cell neoplasms. SUVmax of 3.25 was found to be the best for identifying malignant non-Hürthle cell follicular neoplasms.

Lateral approach to central compartment of neck.

Revision surgery in central compartment of neck is often a challenge for the head and neck surgical oncologists/endocrine surgeons. This is often required for completion thyroidectomies, central compartment lymph node dissections, and re‐exploration for persistent hyperparathyroidism. Scarring in midline due to prior surgery makes midline access to central compartment difficult and increases the risk of injury to recurrent laryngeal nerve and parathyroid glands. This article describes a simple technique of approaching central compartment between sternocleidomastoid and strap muscles. J. Surg. Oncol. 2011;103:101–102.

The Significance of Cervical Lymph Nodes in Well-Differentiated Thyroid Cancer

Well-differentiated thyroid cancer (WDTC), papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are relatively rare. In 2012, a total of 5,600 new cases of thyroid cancer were diagnosed in Canada. Death from thyroid cancer is an even rarer event, with <400 recorded deaths in the same year [1]. To put this in perspective, breast cancer accounted for 22,900 new cases and 5,200 deaths. WDTC has a good prognosis with minimal morbidity if treated properly. Adequate initial surgery offers the most useful contribution to both overall and relapse survival for WDTC. The extent of this surgery has generated controversy for decades and this controversy includes the indications and extent of surgery for cervical lymph nodes. The challenge in the management of this malignancy is to tailor the treatment to be aggressive enough to eradicate the disease, but not so excessive as to cause unnecessary morbidity.

Management of the Central Compartment in Well-Differentiated Thyroid Carcinoma

The central compartment of the neck is bounded superiorly by the hyoid bone, laterally by the carotid arteries, anteriorly by the superficial layer of the deep cervical fascia, posteriorly by the deep layer of the deep cervical fascia, and inferiorly by the innominate artery on the right and the corresponding axial plane on the left. [1] As illustrated in Fig. 3.1, the first echelon of lymphatic drainage of the thyroid is to the pretracheal, paratracheal and recurrent laryngeal nodes in the central compartment (level VI). This puts them at the highest risk of lymphatic metastasis in thyroid cancer. Subsequent lymphatic spread takes place to the superior mediastinal lymph nodes (level VII) and/or the lateral compartment of the neck (levels II–V), as has been outlined in Chap. 2 on lymph node metastasis in well-differentiated thyroid carcinoma (WDTC). Microscopic involvement of regional node occurs in 30–90 % of cases of papillary thyroid carcinomas (PTCs), with an incidence of clinically evident lymph node metastases at presentation ranging from 30 to 40 % [2–5]. The most commonly involved central lymph nodes in thyroid carcinoma are the prelaryngeal (Delphian), pretracheal, and the right and left paratracheal nodes [1].

Management of the Lateral Neck in Well-Differentiated Thyroid Cancer

Lymph node metastases to the lateral neck in well-differentiated thyroid cancer (WDTC) do not appear to significantly impact overall survival. They probably do play a role in recurrence- and disease-free survival. As reviewed elsewhere in this monograph the extent of surgical resection should depend on the extent of cancer with the aim to control the cancer and avoid reoperation if possible with minimal morbidity. Management decisions for the lateral neck are based on desire for regional control balanced with complications of surgery. These considerations have driven controversy in both the timing of treatment (elective versus therapeutic neck dissection) and the extent of surgery necessary to control disease. At present, the balance of opinion favours observation or expectant management of the clinically negative lateral neck. The extent of neck dissection for clinically evident disease remains controversial.

Surgical Management of Oral Cancer

Oral cancer represents a heterogeneous and complex group of tumours, variable in their behaviour and potentially lethal. In a historical cohort of 700 patients from the population-based cancer registry of the province of Manitoba, the 5-year disease-specific survival was 63 %. Survival was 74 % for stage I, 59 % for stage II, 52 % for stage III and 29 % for stage IV disease (p = 0.0000). A number of factors interacted to determine the outcome in this patient population. Major prognostic factors, as determined by multivariate analysis, included (i) gender, (ii) age, (iii) site in the oral cavity, (iv) clinical stage, and (v) initial treatment modality. Results were consistently superior with surgery. Radiotherapy as a single treatment modality was associated with an adverse outcome (HR 2.0; 95 % CI 1.8–2.7; p = 0.000). In 311 patients treated with surgery alone and 148 patients treated with surgery and adjunctive radiotherapy, involved surgical margins had a significant impact on survival after controlling for age and stage of disease (HR 2.0; 95 % CI 1.3–3.0; p = 0.0022) [1, 2].