Introduction

INTRODUCTION THE ORGANIZATION OF THESE GUIDELINES is depicted in Table 1 and directs the reader to both text and the recommendations developed from the literature reviewed. Figure 1 provides an illustrative overview of the initial management of patients suspected to have anaplastic thyroid carcinoma (ATC), including accurate diagnosis, evaluation, and staging, followed promptly by establishing goals of care desired by the patient.

TABLE 1. ORGANIZATION OF GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH ANAPLASTIC THYROID CARCINOMA
  Page
INTRODUCTION 1104
 Background 1104
METHODS 1107
 Terms and definitions 1107
  Adjuvant therapy and neoadjuvant therapy 1107
  Standard radiation prescription 1107
  Altered fractionation 1107
  Radiotherapy dose 1108
  Concurrent chemoradiation 1108
  Conformal radiation 1108
  Intensity-modulated radiotherapy 1108
  Radiosurgery and stereotactic body radiotherapy (stereotactic surgeries) 1108
  TNM staging 1108
  RECIST response 1108
 Presentation and endorsement of recommendations 1108
DIAGNOSIS: HISTOPATHOLOGY and DIFFERENTIAL DIAGNOSIS 1108
 The importance of histopathology 1108
 Histopathological subtypes 1108
 Differential diagnosis 1109
  Poorly differentiated thyroid cancer 1109
  Squamous cell thyroid cancer 1109
  Other tumors: the role of immunohistochemistry 1109
  ■ Recommendation 1 1109
 Cytology and pathology procedures 1109
  Interobserver variability 1109
  FNA and core biopsy 1109
  ■ Recommendation 2 1109
  Intraoperative frozen section and pathology consultation 1109
  ■ Recommendation 3 1110
  Thyroid histopathology 1110
  ■ Recommendation 4 1111
  Molecular techniques 1111
  ■ Recommendation 5 1111
INITIAL EVALUATIONS 1111
 Laboratory, biopsy, and imaging procedures 1111
  ■ Recommendation 6 1112
  Biopsy of distant masses 1112
  ■ Recommendation 7 1112
 Timing and nature of evaluation studies 1112
  ■ Recommendation 8 1112
  Airway and vocal cord assessment 1112
  ■ Recommendation 9 1112
  Staging and order of therapies 1112
  ■ Recommendation 10 1113
  Indications for neoadjuvant therapy 1113
  ■ Recommendation 11 1113
 Postdiagnostic care of ATC 1113
  ■ Recommendation 12 1113
 Prognostic factors 1113
  ■ Recommendation 13 1114
ESTABLISHING TREATMENT GOALS 1114
 Treatment and care goals 1114
  Advanced care planning and goals of care 1114
  ■ Recommendation 14 1114
  Decision-making capacity and informed consent 1114
  ■ Recommendation 15 1114
  Surrogate decision making 1114
  ■ Recommendation 16 1115
  Truth-telling, patient autonomy, and beneficent care 1115
  ■ Recommendation 17 1115
  Advance directives, surrogate decision making, and code status 1115
  ■ Recommendation 18 1115
APPROACHES TO LOCOREGIONAL DISEASE 1115
 Roles of surgery 1115
  Criteria for resectability 1116
  ■ Recommendation 19 1116
  Optimal extent of surgery and control/survival 1116
  ■ Recommendation 20 1117
  ■ Recommendation 21 1117
  Need for surgery after up-front radiotherapy and/or chemotherapy in initially unresectable ATC 1117
  Incidental ATC: surgical management 1117
  ■ Recommendation 22 1117
  ■ Recommendation 23 1117
  Surgical risk to recurrent laryngeal nerve 1117
  ■ Recommendation 24 1118
  Airway management and indications for tracheostomy 1118
  ■ Recommendation 25 1118
  Securing the airway after surgery 1118
  ■ Recommendation 26 1118
  Benefits of tracheostomy 1118
  ■ Recommendation 27 1118
  Surgical airway and unresectable disease 1118
  ■ Recommendation 28 1118
 Radiotherapy and systemic chemotherapy in locoregional ATC 1118
  Radiotherapy after complete or near-complete (R0 or R1) resection 1118
  ■ Recommendation 29 1119
  Timing and sequencing of perioperative radiation and/or systemic chemotherapy 1119
  ■ Recommendation 30 1119
  ■ Recommendation 31 1119
  Locoregional radiotherapy and/or systemic therapy in patients with unresected disease 1119
  ■ Recommendation 32 1120
  ■ Recommendation 33 1120
  ■ Recommendation 34 1120
  Radiation dose, field, and techniques (conventional, altered fractionation, IMRT) 1120
  ■ Recommendation 35 1120
  Role of systemic therapy combined with radiation 1120
  ■ Recommendation 36 1121
 Supportive care during active therapy 1122
  Airway management 1122
  ■ Recommendation 37 1122
  Maintenance of nutrition (PEG/feeding tube) 1122
  ■ Recommendation 38 1122
  ■ Recommendation 39 1122
  Parenteral nutrition in perioperative management 1122
  ■ Recommendation 40 1122
  Growth factor support during chemoradiation therapy 1122
  ■ Recommendation 41 1122
APPROACHES TO ADVANCED METASTATIC DISEASE (STAGE IVC) 1123
 Defining therapeutic goals, expected/possible adverse events, appropriate expectations, and limits of care 1123
 Timing of systemic therapies 1123
  ■ Recommendation 42 1123
 Approaches to systemic disease (cytotoxic) 1123
  Taxanes 1123
  Anthracyclines and platins 1123
  First-line therapy 1124
  Second-line or salvage therapy 1124
 Approaches to systemic disease (novel or investigational) 1124
  ■ Recommendation 43 1125
  ■ Recommendation 44 1125
  ■ Recommendation 45 1125
  ■ Recommendation 46 1125
 Systemic therapy: what is next? 1125
 Approaches to brain metastases 1125
  ■ Recommendation 47 1125
  ■ Recommendation 48 1125
  ■ Recommendation 49 1126
  ■ Recommendation 50 1126
 Approaches to bone metastases 1126
  ■ Recommendation 51 1127
  ■ Recommendation 52 1127
  ■ Recommendation 53 1127
 Approaches to other sites of metastases 1127
 Utility of cryoablation and selective embolization 1128
  ■ Recommendation 54 1128
 Approach to thrombosis and/or tumor invasion into vasculature 1128
  ■ Recommendation 55 1128
  ■ Recommendation 56 1128
  ■ Recommendation 57 1128
PALLIATIVE CARE AND HOSPICE 1128
 Definition of a palliative care service 1129
  When to involve palliative care in ATC 1129
  When to involve hospice care in ATC 1129
  Working effectively with a palliative care or hospice care team 1129
  ■ Recommendation 58 1129
  ■ Recommendation 59 1129
SURVEILLANCE AND LONG-TERM MONITORING 1129
 Surveillance after clinical remission 1130
  ■ Recommendation 60 1130
  ■ Recommendation 61 1131
  ■ Recommendation 62 1131
  ■ Recommendation 63 1131
 Restaging of patients with persistent metastatic disease 1131
  ■ Recommendation 64 1131
  ■ Recommendation 65 1131
SUMMARY 1131

     ATC, anaplastic thyroid cancer; FNA, fine-needle aspiration; IMRT, intensity-modulated radiotherapy; PEG, percutaneous gastrostomy; RECIST, Response Evaluation Criteria in Solid Tumors.

 

Figure 1

FIG. 1. An overview of management options for patients with anaplastic thyroid carcinoma includes confirming the diagnosis, thoroughly evaluating the patient to permit accurate staging of the disease, and subsequently establishing treatment goals according to the patient's wishes. Recommendations and figures that pertain to each topic are noted in this and subsequent figures.

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Background

Thyroid malignancies are increasing in frequency and account for 2.5% of all cancers in the United States. ATC, by far the most deadly of thyroid-derived tumors, fortunately accounts for but a small percentage. In the United States, ATC is responsible for 1.7% of all thyroid cancers, while geographically the prevalence ranges from 1.3% to 9.8% (median = 3.6%) (1). In several countries the prevalence of ATC has decreased dramatically, due in part to increased dietary iodine and better management of differentiated thyroid cancer (DTC) (2,3).

Unlike DTC, which is derived from follicular thyroid cells, and medullary thyroid cancer (MTC), which are frequently cured or associated with prolonged survival, ATC patients have a median survival of 5 months and a 20% 1-year survival rate (1). All patients are classified by the American Joint Committee on Cancer (AJCC) TNM system as stage IV (A, B, or C) at presentation, and counseling and establishing a management plan must be accomplished quickly. While all thyroid cancer patients require a multidisciplinary team of specialists for optimal care, the coordinating physician is frequently an endocrinologist who has established a long-standing relationship with the patient who has DTC or MTC. In contrast, the sudden onset and explosive course of ATC necessitates immediate involvement by surgeons, radiation and medical oncologists, and palliative care teams.

The American Thyroid Association (ATA) has a history of supporting the development of guidelines for the care of patients with thyroid disease.* This includes several guidelines for management of DTC (4–6) and recent first MTC guidelines (7). No such ATA guidelines exist for management of patients with ATC. The Latin American Thyroid Society has also published recommendations for DTC management (8). Other organizations have made recommendations for patients with ATC. The National Comprehensive Cancer Network devotes 37 pages to treating and following DTC patients but only three pages for ATC (9). The American Association of Clinical Endocrinologists guidelines for thyroid cancer discuss ATC management in less than one page (10).

Accordingly, the ATA Board of Directors requested that an independent task force, which authored this publication, develop a more comprehensive set of guidelines to assist practitioners in the management of critically ill patients with ATC. The authors include physicians who specialize in endocrinology, endocrine surgery, head/neck surgery, nuclear medicine, radiation oncology, medical oncology, pathology, and bioethics. The medical opinions expressed in these guidelines are those of the authors.

The final document was approved by the ATA Board of Directors, and was officially endorsed by (in alphabetical order) the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS), American Association of Clinical Endocrinologists (AACE), American Head and Neck Society (AHNS), Italian Association of Clinical Endocrinologists (AME), Asia and Oceania Thyroid Association (AOTA), The Endocrine Society, European Thyroid Association (ETA), International Association of Endocrine Surgeons (IAES), Latin American Thyroid Society (LATS), and the Brazilian Society of Head and Neck Surgery (SBCCP).

*For information provided by the ATA on guideline publications they approve and endorse, see the Supplementary Data, available online at www.liebertpub.com/thy