Ashok R. Shaha

Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System

BACKGROUND A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. METHODS This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. RESULTS Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediate-risk, and 68% of the high-risk patients (p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. CONCLUSIONS Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.

Primary mucosal malignant melanoma of the head and neck

The relative rarity of mucosal melanomas of the head and neck (MMHN) has made analysis of treatment approaches difficult. Advances in diagnostic techniques and treatment interventions have had obvious impact on outcomes in cutaneous melanoma, but the effects on outcome in MMHN remain undefined. This study aims to assess the outcome and identify clinical and histologic prognostic indicators in a recent cohort of patients with MMHN treated at a single institution.

Follicular Variant of Papillary Thyroid Carcinoma A Clinicopathologic Study of a Problematic Entity

There is continuous debate regarding the optimal classification, prognosis, and treatment of the follicular variant of papillary thyroid carcinoma (FVPTC). The objective of this study was to assess the behavior of FVPTC, especially its encapsulated form, and shed more light on its true position in the classification scheme of well differentiated thyroid carcinoma.

Factors associated with complications in microvascular reconstruction of head and neck defects.

The use of microvascular free tissue transfer has allowed the reconstruction of increasingly complex defects in higher risk patients after head and neck cancer resections. However, the combination of these factors also gives rise to a higher risk for the development of complications. This study was performed to establish the pretreatment factors associated with complication development after microvascular free tissue transfer for the reconstruction of defects resulting from head and neck cancer ablations, with particular attention to the role of comorbid conditions. A retrospective cohort study was conducted including 200 consecutive microvascular free tissue transfers performed for the reconstruction of surgical defects in the head and neck region at a single tertiary care institution. Comorbidity severity was assessed using the Charlson comorbidity index, a novel approach to comorbid staging in this setting. The flap survival rate was 98 percent. Complications developed in 56 cases (28 percent), with multiple complications occurring in 21 of these cases (10.5 percent). Univariate analysis revealed that prior radiation treatment (p = 0.03), anesthesia time over 10 hours (0.05), and advanced Charlson comorbidity grade (0.002) were associated with an increased risk for the development of complications. However, only the presence of advanced Charlson grade proved significant after multivariate analysis (odds ratio 3.9; 95 percent CI = 1.5 to 10.1). In addition, increasing Charlson grade (p = 0.003) and age over 70 years (p = 0.04) correlated with increasing complication severity. Systemic complications occurred in 28 patients (14 percent), with advanced Charlson grade being the only significant factor associated with the development of complications after controlling for confounding factors (odds ratio 3.8; 95 percent CI = 1.5 to 9.7). In patients over 70 years of age, increasing operative time also impacted on the development of systemic complications (p = 0.002), especially in patients with advanced Charlson grades (0.01). Recipient site complications occurred in 30 patients (15 percent), with history of prior radiation therapy being the only factor associated with increased risk by multivariate analysis (odds ratio 2.5; 95 percent CI = 1.1 to 5.7). No factors predicted the development of donor-site complications, which occurred in 11 cases (5.5 percent). The median hospital stay for the entire population was 16 days. The development of complications increased the median hospital stay by 7.5 days (p < 0.001). The effect of the development of complication on hospital stay remained significant even after controlling for the effects of confounding variables (relative risk = 9.87; 95 percent CI = 5.9 to 19.9). Microvascular surgery is a highly successful and relatively safe method for the reconstruction of large head and neck defects. The Charlson comorbidity index grading may be useful for identifying patients at increased risk for the development of complications after microvascular reconstruction, allowing for improved perioperative planning. In addition, patients with prior radiation exposure have a significantly higher risk for developing complications at the recipient site. Although advanced age is not associated with an increased risk for complications, older patients may be more sensitive to the effects of prolonged anesthesia and are likely to develop more severe complications.

Concurrent Cetuximab, Cisplatin, and Concomitant Boost Radiotherapy for Locoregionally Advanced, Squamous Cell Head and Neck Cancer: A Pilot Phase II Study of a New Combined-Modality Paradigm

PURPOSE Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy. PATIENTS AND METHODS Eligible patients had stage III or IV, M0, squamous cell head and neck cancer. Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10). RESULTS Twenty-two patients were enrolled (median age, 57 years; range, 41 to 72 years; median Karnofsky status, 90%; range, 70% to 90%; oropharynx primary tumor, 59% of patients; T4, 36%; N2/3, 77%; stage IV disease, 86%). One patient did not receive study treatment because of an ineligible diagnosis. The severity of expected, acute toxicities was typical of concurrent cisplatin and radiotherapy alone. Grade 3 or 4 cetuximab-related toxicities included acne-like rash (10%) and hypersensitivity (5%). However, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. With a median follow-up of 52 months, the 3-year overall survival rate is 76%, the 3-year progression-free survival rate is 56%, and the 3-year locoregional control rate is 71%. CONCLUSION This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. However, preliminary efficacy is encouraging, and further development of this targeted combined-modality paradigm is warranted.

Anaplastic Thyroid Carcinoma: Biology, Pathogenesis, Prognostic Factors, and Treatment Approaches

BackgroundAnaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors known to affect humans and carries a dismal prognosis. Our primary aim was to review its epidemiology, biology, risk factors, and prognostic indicators. We also reviewed the individual and combined roles of surgery, radiotherapy, chemotherapy, and newer therapeutic options in the management of ATC.MethodsAn extensive literature review was conducted to include all published reports on ATC. The changing trends in the management of anaplastic thyroid cancer were analyzed to summarize the current practice of management of ATC.ResultsAlthough ATC is rare, there has been a decline in its incidence worldwide. ATC accounts for more than half of the 1200 deaths per year attributed to thyroid cancer. Long-term survivors are rare, with >75% and 50% of patients harboring cervical nodal disease and metastatic disease, respectively, at presentation. ATC can arise de novo or from preexisting well-differentiated thyroid cancer. Surgical management has shifted from tracheostomy only for palliation to curative resection when possible. Tracheostomy is performed for impending obstruction rather than for prophylaxis. Radiotherapy has evolved from postoperative administration only to preoperative treatment, combining preoperative and postoperative treatment and using higher doses, along with hyperfractionating and accelerating dose schedules. Chemotherapy has changed from monotherapy to combination therapy, and newer drugs such as paclitaxel show promise. Similarly, novel angiogenesis-inhibiting agents are currently being used, with early reports of some benefit.ConclusionsDespite multimodality approaches, ATC still carries a dismal prognosis. This should provoke innovative strategies beyond conventional methods to tackle this uniformly lethal disease.

American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer

BACKGROUND Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Rapid evaluation and establishment of treatment goals are imperative for optimum patient management and require a multidisciplinary team approach. Here we present guidelines for the management of ATC. The development of these guidelines was supported by the American Thyroid Association (ATA), which requested the authors, members the ATA Taskforce for ATC, to independently develop guidelines for ATC. METHODS Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee of the American College of Physicians, which in turn was developed by the Grading of Recommendations Assessment, Development and Evaluation workshop. RESULTS The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues including end of life. The guidelines include 65 recommendations. CONCLUSIONS These are the first comprehensive guidelines for ATC and provide recommendations for management of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for a clinical trial or hospice/palliative care, depending upon their preference.

Consensus Statement on the Classification and Terminology of Neck Dissection

OBJECTIVE To update the guidelines for neck dissection terminology, as previously recommended by the American Head and Neck Society. PARTICIPANTS Committee for Neck Dissection Classification, American Head and Neck Society; representation from the Committee for Head and Neck Surgery and Oncology, American Academy of Otolaryngology-Head and Neck Surgery (T.A.D.). EVIDENCE Review of current literature on neck dissection classification. CONSENSUS PROCESS Semiannual face-to-face meetings of the Committee for Neck Dissection Terminology and e-mail correspondence. CONCLUSIONS Standardization of terminology for neck dissection is important for communication among clinicians and researchers. New recommendations have been made regarding the following: boundaries between levels I and II and between levels III/IV and VI; terminology of the superior mediastinal nodes; and the method of submitting surgical specimens for pathologic analysis.

Impact of lymph node metastasis in differentiated carcinoma of the thyroid: A matched-pair analysis

Cervical lymph node metastasis in differentiated thyroid carcinoma has mostly been found to have little relationship to prognosis. However, some studies report nodal involvement to be an adverse factor, while others have found it to be favorable. We have undertaken a matched‐pair analysis of previously untreated patients, with and without ipsilateral neck metastasis, to examine the significance of nodal spread in patients with otherwise equivalent prognostic factors for differentiated thyroid cancer.

Prognostic factors and risk group analysis in follicular carcinoma of the thyroid

BACKGROUND The understanding of prognostic factors has facilitated stratification of risk groups in differentiated carcinoma of the thyroid. The prognostic factors have clearly identified the risk groups as low, intermediate, and high risk. Risk group categorization has facilitated a selective surgical approach for thyroid carcinoma. METHODS A retrospective review of 228 patients with follicular carcinoma of the thyroid was undertaken. Various prognostic factors and risk groups were analyzed. Univariate and multivariate analyses were performed, and the survival curves were plotted by the Kaplan-Meier method. Fifty-nine (26%) patients presented with Hürthle cell histology. The risk groups revealed 62 patients in the low, 84 in the intermediate, and 82 in the high risk groups. RESULTS The 10-year survival for low, intermediate, and high risk groups was 98%, 88%, and 56%, respectively, and the 20-year survival for the same groups was 97%, 87%, and 49%, respectively. Adverse prognostic factors included age older than 45 years (p < 0.001), Hürthle cell variety (p = 0.05), extrathyroidal extension, tumor size exceeding 4 cm, and the presence or absence of distant metastasis (p < 0.001). Gender, focality, and presence of lymph node metastasis had no significant impact on prognosis. CONCLUSIONS Patients in the low risk group have excellent survival, whereas the high risk group behaves poorly. Appropriate selection of treatment for the primary disease and adjuvant therapy should be considered on the basis of the prognostic factors and risk group analysis.