American Thyroid Association Guidelines for …

1 Thyroid CANCER AND NODULESA merican Thyroid Association Guidelinesfor Management of Patients with Anaplastic Thyroid CancerRobert C. Smallridge,1,*Kenneth B. Ain,2,3 Sylvia L. Asa,4,5 Keith C. Bible,6 James D. Brierley,4,5 Kenneth D. Burman,7 Electron Kebebew,8 Nancy Y. Lee,9 Yuri E. Nikiforov,10M. Sara Rosenthal,11 Manisha H. Shah,12 Ashok R. Shaha,9and R. Michael Tuttle9for the American Thyroid Association Anaplastic Thyroid Cancer Guidelines TaskforceBackground:Anaplastic Thyroid cancer (ATC) is a rare but highly lethal form of Thyroid cancer. Rapid evaluationand establishment of treatment goals are imperative for optimum patient management and require a multi-disciplinary team approach. Here we present Guidelines for the management of ATC.

2 The development of theseguidelines was supported by the American Thyroid Association (ATA), which requested the authors, membersthe ATA Taskforce for ATC, to independently develop Guidelines for :Relevant literature was reviewed, including serial PubMed searches supplemented with additionalarticles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee ofthe American College of Physicians, which in turn was developed by the Grading of Recommendations As-sessment, Development and Evaluation :The Guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches tolocoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), ap-proaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, andethical issues including end of life.

3 The Guidelines include 65 :These are the first comprehensive Guidelines for ATC and provide recommendations for man-agement of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the bestprognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stageIVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be con-sidered for a clinical trial or hospice/palliative care, depending upon their organization of these guidelinesis depicted inTable 1 and directs the reader to both text and the recom-mendations developed from the literature reviewed. Figure 1provides an illustrative overview of the initial management ofpatients suspected to have anaplastic Thyroid carcinoma (ATC),including accurate diagnosis, evaluation, and staging, followedpromptly by establishing goals of care desired by the malignancies are increasing in frequency and ac-count for of all cancers in the United States.

4 ATC, by far*Robert C. Smallridge, , is Chair of the American Thyroid Association Anaplastic Thyroid Cancer Guidelines Taskforce. All authorsafter the first author are listed in alphabetical Clinic, Jacksonville, Affairs Medical Center, Lexington, of Kentucky, Lexington, Margaret Hospital, University Health Network, Toronto, of Toronto, Toronto, Clinic, Rochester, Hospital Center, Washington, District of Oncology Branch, National Cancer Institute, Bethesda, Sloan-Kettering Cancer Center, New York, New of Pittsburgh, Pittsburgh, for Bioethics, University of Kentucky, Lexington, State University, Columbus, 22, Number 11, 2012 Mary Ann Liebert, : and definitions1107 Adjuvant therapy and neoadjuvant therapy1107 Standard radiation prescription1107 Altered fractionation1107 Radiotherapy dose1108 Concurrent chemoradiation1108 Conformal radiation1108 Intensity-modulated radiotherapy1108 Radiosurgery and stereotactic bodyradiotherapy (stereotactic surgeries)1108 TNM staging1108 RECIST response1108 Presentation of recommendations1108 DIAGNOSIS: HISTOPATHOLOGYand DIFFERENTIAL DIAGNOSIS1108 The importance of histopathology1108 Histopathological subtypes1108 Differential diagnosis1109 Poorly differentiated Thyroid cancer1109 Squamous cell Thyroid cancer1109 Other tumors.

5 The role of immunohistochemistry 1109&Recommendation 11109 Cytology and pathology procedures1109 Interobserver variability1109 FNA and core biopsy1109&Recommendation 21109 Intraoperative frozen section andpathology consultation1109&Recommendation 31110 Thyroid histopathology1110&Recommendation 41111 Molecular techniques1111&Recommendation 51111 INITIAL EVALUATIONS1111 Laboratory, biopsy, and imaging procedures1111&Recommendation 61112 Biopsy of distant masses1112&Recommendation 71112 Timing and nature of evaluation studies1112&Recommendation 81112 Airway and vocal cord assessment1112&Recommendation 91112 Staging and order of therapies1112&Recommendation 101113 Indications for neoadjuvant therapy1113&Recommendation 111113 Postdiagnostic care of ATC1113&Recommendation 121113 Prognostic factors1113&Recommendation 131114 ESTABLISHING TREATMENT GOALS1114 Treatment and care goals1114 Advanced care planning and goals of care1114&Recommendation 141114 Decision-making capacity and informed consent 1114&Recommendation 151114 Surrogate decision making1114&Recommendation 161115 PageTruth-telling.

6 Patient autonomy,and beneficent care1115&Recommendation 171115 Advance directives, surrogate decision making,and code status1115&Recommendation 181115 APPROACHES TO LOCOREGIONAL DISEASE1115 Roles of surgery1115 Criteria for resectability1116&Recommendation 191116 Optimal extent of surgery and control/survival 1116&Recommendation 201117&Recommendation 211117 Need for surgery after up-front radiotherapyand/or chemotherapy in initiallyunresectable ATC1117 Incidental ATC: surgical management1117&Recommendation 221117&Recommendation 231117 Surgical risk to recurrent laryngeal nerve1117&Recommendation 241118 Airway management and indicationsfor tracheostomy1118&Recommendation 251118 Securing the airway after surgery1118&Recommendation 261118 Benefits of tracheostomy1118&Recommendation 271118 Surgical airway and unresectable disease1118&Recommendation 281118 Radiotherapy and systemic chemotherapyin locoregional ATC1118 Radiotherapy after complete or near-complete(R0 or R1)

7 Resection1118&Recommendation 291119 Timing and sequencing of perioperativeradiation and/or systemic chemotherapy1119&Recommendation 301119&Recommendation 311119 Locoregional radiotherapy and/or systemictherapy in patients with unresected disease1119&Recommendation 321120&Recommendation 331120&Recommendation 341120 Radiation dose, field, and techniques(conventional, altered fractionation, IMRT)1120&Recommendation 351120 Role of systemic therapy combinedwith radiation1120&Recommendation 361121 Supportive care during active therapy1122 Airway management1122&Recommendation 371122 Maintenance of nutrition (PEG/feeding tube)1122&Recommendation 381122&Recommendation 391122 Parenteral nutrition in perioperativemanagement1122&Recommendati on 401122 Growth factor support duringchemoradiation therapy1122&Recommendation 411122(continued) of Guidelines for the Management of Patients with Anaplastic Thyroid CarcinomaANAPLASTIC Thyroid CANCER GUIDELINES1105the most deadly of Thyroid -derived tumors, fortunately ac-counts for but a small percentage.

8 In the United States, ATC isresponsible for of all Thyroid cancers, while geographi-cally the prevalence ranges from to (median= )(1). In several countries the prevalence of ATC has decreaseddramatically, due in part to increased dietary iodine and bettermanagement of differentiated Thyroid cancer (DTC) (2,3).Unlike DTC, which is derived from follicular Thyroid cells,and medullary Thyroid cancer (MTC), which are frequentlycured or associated with prolonged survival, ATC patientshave a median survival of 5 months and a 20% 1-year survivalrate (1). All patients are classified by the American JointCommittee on Cancer (AJCC) TNM system as stage IV (A, B,or C) at presentation, and counseling and establishing amanagement plan must be accomplished quickly.

9 While allthyroid cancer patients require a multidisciplinary team ofspecialists for optimal care, the coordinating physician isfrequently an endocrinologist who has established a long-standing relationship with the patient who has DTC or contrast, the sudden onset and explosive course of ATCnecessitates immediate involvement by surgeons, radiationand medical oncologists, and palliative care American Thyroid Association (ATA) has a history ofsupporting the development of Guidelines for the care of pa-tients with Thyroid disease.* This includes several guidelinesfor management of DTC (4 6) and recent first MTC Guidelines (7). No such ATA Guidelines exist for management of patientswith ATC. The Latin American Thyroid Society has alsopublished recommendations for DTC management (8).

10 Otherorganizations have made recommendations for patients withATC. The National Comprehensive Cancer Network devotes37 pages to treating and following DTC patients but onlythree pages for ATC (9). The American Association of ClinicalEndocrinologists Guidelines for Thyroid cancer discuss ATCmanagement in less than one page (10).PageAPPROACHES TO ADVANCED METASTATICDISEASE (STAGE IVC)1123 Defining therapeutic goals, expected/possible adverseevents, appropriate expectations, and limits of care1123 Timing of systemic therapies1123&Recommendation 421123 Approaches to systemic disease (cytotoxic)1123 Taxanes1123 Anthracyclines and platins1123 First-line therapy1124 Second-line or salvage therapy1124 Approaches to systemic disease (novel orinvestigational)1124&Recommendation 431125&Recommendation 441125&Recommendation 451125&Recommendation 461125 Systemic therapy: what is next?