Airway management, symptom relief, and best supportive care in anaplastic thyroid cancer

Abstract

Purpose of review

Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer that is associated with significant morbidity and mortality. Because ATC is locally invasive, airway management is a critical component of treating these patients. Timely decisions regarding airway interventions can contribute to symptom relief and supportive care for patients. Over the last decade, there has been a paradigm shift in our recommendations for airway management. The purpose of this review is to summarize airway management, symptom relief, and best supportive care for patients with ATC.

Recent findings

More recent literature discusses the morbidities associated with tracheostomy and instead focuses on the benefits of supportive care and surgical resection. The multidisciplinary treating team should initiate early discussions for airway management, end-of-life care, and palliative goals for patients with ATC. Tracheostomy should be offered to patients with careful thought and preoperative planning.

Summary

Our goal in symptom relief and airway management is to improve the quality of life of patients with ATC and avoid the unnecessary morbidity of tracheostomy until clinically indicated.

Introduction

Anaplastic thyroid cancer (ATC) is a rare but aggressive disease that is a significant contributor to the morbidity and mortality burden of all thyroid cancers. Palliative discussions should be initiated soon after diagnosis of ATC and should include possible airway interventions and the timing of these procedures. Additionally, an emphasis on symptom relief and supportive care is best practice for management in these patients.

We recommend that treating physicians facilitate multidisciplinary discussions for every patient as soon as ATC is diagnosed. We believe it is imperative that patients develop clear plans of care with their clinical teams throughout the course of treatment. As physicians, we must maintain a realistic outlook with patients and their families, as overly zealous messages can dramatically affect patients’ decision making.

Background

ATCs are aggressive, undifferentiated tumors arising from the follicular epithelium of the thyroid gland [1]. They are thought to develop from the dedifferentiation of existing well-differentiated thyroid cancers, but there is evidence that some may develop de novo [2]. ATC has a uniformly poor prognosis, with a high rate of metastasis and a rapidly fatal course [3]. Disease-specific mortality is exceedingly high, often cited near 100 percent [4]. The median survival after diagnosis is between three and seven months, and the reported 5 year survival is as low as 5 percent in the literature [3]. Because of the poor prognosis and rapid progression of this disease, airway management and end-of-life discussions are of paramount importance after ATC is diagnosed.

ATC is quite rare, with approximately 1–2 cases per one million persons [5]. It is more prevalent in older adults, and the mean age at diagnosis is 65 years. It is also more common in women than men [6,7]. Although it comprises only 1% of all thyroid cancers, ATC accounts for 14–39% of deaths from thyroid cancer [8,9].

Diagnosis

Classically, patients with ATC initially present with a rapidly expanding neck mass [11]. Physical exam of the neck typically reveals a diffuse, but often asymmetric, enlarged thyroid. The mass is usually hard, immobile, and may be tender. There can be multifocal nodules or one large nodule, and the mass is often ill-defined in nature. At the time of presentation, the diameter of the tumor can exceed 5 centimeters [12].

Because of the rapidly expanding mass and size of the tumor, local invasion is common at presentation of disease. Nearby structures, including muscles, lymph nodes, esophagus, larynx, and trachea, can be involved. Local compression and invasion of these structures manifests clinically as aerodigestive symptoms. The most frequent symptoms are hoarseness (40%), dysphagia (40%), and dyspnea or stridor (24%) [8]. Acute enlargement of the neck mass usually indicates tumor hemorrhage into the thyroid tissue. Patients can present with painful enlargement and possible hemoptysis if there is tracheal invasion [2]. Local invasion is the critical determinant of airway management because intervention can become urgent with significant compression or invasion of the airway [8].

Because regional spread, including lymphadenopathy, is present in over 50 percent of cases [8], the comprehensive work-up for patients with ATC should include imaging. Thyroid and neck ultrasounds should be performed to evaluate the primary tumor and assess cervical lymph node basins for metastatic disease. Ultrasound is limited in assessing the airway, but it can provide an overall impression [13].

We recommend that all patients with ATC undergo cross-sectional imaging to adequately evaluate the airway at the time of diagnosis. High-resolution cross-sectional imaging is critical for surgical planning. Computed tomography (CT) of the neck and mediastinum are useful in assessing locoregional involvement and invasion of critical aerodigestive structures with high resolution. By CT, anaplastic masses will usually appear isodense or slightly hyperdense relative to muscle [15,16]. These masses are frequently heterogenous with areas of necrosis and calcifications. Careful attention must be paid to the imaging in cases of surgical resection as local structures may be confused with the heterogenous, poorly-defined nature of the mass.

To further evaluate the airway, patients should undergo vocal cord evaluation with fiberoptic laryngoscopy. A bronchoscopy should be performed to evaluate the trachea if the laryngoscopy shows evidence of airway invasion. Bronchoscopy is useful for determining disease extent, evaluation of the tracheal lumen and luminal obstruction and resectability of the tumor. Similarly, an esophagoscopy should be performed if there is suspected esophageal invasion, particularly in patients with dysphagia or odynophagia [13].

Staging of ATC, which is based on the American Joint Committee on Cancer (AJCC) 8^th edition (October 2016), can be useful in stratifying management strategies. As stage IV tumors, ATCs are subclassified as stage IVA (intrathyroidal tumor), IVB (gross extrathyroidal extension [ETE] or cervical lymph node metastasis), or IVC (distant metastasis). The T stage of ATC is dependent on tumor size and ETE (T1 ≤ 2 cm, T2 2–4 cm, T3 > 4 cm – T3a with disease limited to the thyroid and T3b with gross ETE into strap muscles, and T4 gross ETE into major neck structures) [20,21]. The staging system can be used to ensure that patients receive the appropriate treatment that will maximize their survival.

Prognosis

The prognosis of patients with ATC is poor. Despite improvements in treatment, most patients with ATC have a median survival of 5–6 months and a median 1-year survival of 20% [6,31]. Stage of disease directly correlates with survival in ATC; overall survival is 9 months for stage IVA disease, 4.8 months for stage IVB disease, and 3 months for stage IVC disease [32]. Additionally, there is a high incidence of recurrence despite appropriate treatment [3].

Treatment

Because of the aggressive nature of the disease, a diagnosis of ATC should immediately warrant the collaboration of a multidisciplinary team including experienced surgeons, medical oncologists, radiation oncologists, and palliative care providers [2]. After imaging and endoscopic assessment, initial treatment should be directed toward life-sustaining interventions, such as securing the airway and, if the patient has aerodigestive involvement, ensuring access for nutritional support. Treatment of ATC is generally multimodal, with the most recent ATA guidelines recommending surgery, external beam radiation, and chemotherapy. Different combinations are recommended depending on the characteristics of the particular case [13]. This multidisciplinary approach maximizes survival and provides for a well-balanced treatment plan to optimize quality of life.

Surgery is a critical component of treatment for ATC. We generally recommend primary surgical resection for patients with stage IVA or IVB disease—more specifically, patients without aerodigestive tract involvement. Primary surgical treatment should be planned when gross tumor resection (R1) is anticipated [13,22]. There are several studies that have demonstrated a survival benefit in patients with ATC if complete resection is achieved [10–11,17,23–29]. The ATA guidelines recommended a lobectomy or near-total thyroidectomy with lymph node dissection for patients with stage IVA (intrathyroidal) disease. En-bloc resection is advocated if grossly negative margins (R1) can be achieved for patients with stage IVB disease (extrathyroidal invasion).

It is important to note, however, that although most studies do show a survival benefit with R0 or R1 resection, only a small group of patients present with fully resectable disease; ultimately, the operating surgeon decides whether a primary tumor resection can be attempted with acceptable risk and morbidity. Many patients with initially unresectable disease benefit from external beam radiation (either full or partial course) or neoadjuvant chemotherapy to shrink the tumor before undergoing surgical resection [13].

The 2020 ATA Guidelines due out next year are anticipated to include a significant focus on multidisciplinary treatment, including systemic treatment for anaplastic thyroid cancer. It had previously been shown that BRAF-mutated ATC patients represent a subset of cases who can benefit from a combination therapy with BRAF and MEK inhibitors [38]. New data shows great promise for targeted therapies including dabrafenib and trametinib (DT). This trial describes success in six patients using neoadjuvant DT followed by complete surgical resection [37]. By using the combination targeted therapy, they demonstrated that it is possible to achieve complete resection, decrease need for tracheostomy, symptom relief and locoregional control. This type of targeted treatment can potentially change the paradigm for treating anaplastic thyroid cancer.

In addition to systemic treatment, the new guidelines will place a strong emphasis on the palliative arm of the multidisciplinary team. There will be recommendations on the ethics involved in managing anaplastic thyroid cancer, how to initiate discussions on terminal care and how to involve the palliative team early in diagnosis. These recommendations will improve the patient’s quality of life and symptom relief in this morbid disease. We agree that including these goals in treatment is the best approach for the patient.

Symptom Relief

As mentioned, many patients with ATC may present with dyspnea and stridor. Relieving these symptoms can include a range of treatments, with small interventions even providing relief. If there is no impending airway compromise, humidity, rest, and occasional use of short-term corticosteroids can be beneficial in acute management. [13]

Locoregional resection is often indicated for palliation of airway or esophageal obstruction. Tracheostomy has been discussed in the literature for symptom relief; however, patients often suffer from upper airway obstruction despite tracheostomy. Mortality is most commonly related to airway compromise, which reported in up to 60% of patients. Additionally, for patients with large tumors that cannot be fully resected, surgical debulking has been shown to improve survival, especially when combined with other therapies, and can help to prevent death from airway obstruction [13,30].

Nutrition and oral feeding are an important factor in patients’ symptoms and quality of life. If there is not significant compromise of the esophagus secondary to local invasion, patients can often tolerate an oral diet. In the cases of aggressive ATC with esophageal obstruction or invasion, enteral feeding may be required. In order to provide symptom relief and ensure adequate nutrition, placement of a gastrostomy tube is recommended. This is also warranted in patients after chemoradiation with functional side effects limiting an oral diet. Because of structural abnormalities or restrictions, it is often necessary to pursue feeding tube placement with interventional radiology. Endoscopic placement of gastrostomy tube can be limited because of tumor invasion or stenosis in the esophagus, as well as difficulties with intubation because of airway compromise. [13]

Best Supportive care

It is important for the multidisciplinary team to facilitate supportive care for patients with ATC as they will have many fundamental, palliative needs. Whenever possible, this team should include clinical ethicists and social workers to advocate for the quality of life of patients. These palliative team members can focus on multiple domains including the emotional, social, intellectual, and spiritual needs of the patient and family that can often be overlooked. Palliative team members should be experts in the field, trained in managing and mediating issues related to serious illness and end-of-life situations. [35]

Early discussion of treatment goals with patients and family members should incorporate patients’ preferences regarding code status, nutrition, and airway management; these should be explicitly documented in addition to advance directives and surrogacy appointments. This preparation is essential given the aggressive disease course of ATC. These decisions are critical to providing comprehensive supportive care for patients with ATC [33]. It is documented that participating in supportive and palliative care services helps patients remain engaged in daily activities.

If patients with ATC choose to decline life-prolonging therapies, hospice care should be offered. In these cases, patients often prefer to receive resources at home with the support of family. Physicians should actively participate with the hospice care team and remain engaged with the patient and families to help coordinate care and decision making. The physician-patient relationship should be maintained and continued through this phase of supportive care. [35]

Airway management

There have been changes in the ATC management paradigm in the last decade. [36] In the past, tracheostomy was offered as palliation, but current treatment is directed more towards appropriate surgical resection, if possible. Tracheostomy is approached with more hesitation and reservation because of possible complications; although tracheostomy may prolong survival, it may decrease quality of life because of the associated morbidity. The tumor can erode the tracheostomy site, or the tumor may fungate around the tracheostomy [34].

Because of the changes in recommendations, there has been considerable debate around the use of tracheostomy in patients with ATC. Prophylactic tracheostomy is generally not recommended for patients with ATC, as the procedure significantly deteriorates quality of life. Optimizing overall survival is best achieved with local control (R0 or R1 resection), but this should only be undertaken if all locoregional disease can be resected without sacrificing major structures or causing significant morbidity [13].

Recommendations

Our recommendations regarding management of the airway are focused on initiating palliative plans and end-of-life discussions from the outset of diagnosis of ATC. It is imperative to discuss the course of the disease with the patient and family to establish a clear plan. With these discussions, it would be our recommendation to avoid tracheostomy for as long as possible because of the potential complications and deterioration in quality of life. If surgical resection is feasible without tracheostomy, this should be pursued first. Because the stoma site is a potential tract for tumor invasion, early tracheostomy can potentially lead to extension of disease and the possibility of tumor fungating at the site. This leads to significant wound care complications and increased morbidity for patients, compromising their quality of life.

Alternatively, once a patient develops acute symptoms, such as stridor or unmanageable secretions, a tracheostomy may be considered. However, it may prolong misery for the patient. Keeping in mind, emergent tracheostomy at the bedside should be avoided because of the potential difficulty securing the airway secondary to overlying disease. In as much as possible, the tracheostomy should be planned in advance and performed in the operating room with a skilled surgical team and necessary resources. In the operating room, a planned tracheostomy should involve a fiberoptic intubation. A due consideration should be given to cricothyrotomy versus tracheostomy as cricothyrotomy may be an easier surgical procedure, as well as less likely to dislodge secondary to bulk of disease.

We also recommend monitoring the airway closely after debulking or resection. After the procedure, patients should remain intubated for 24 to 48 hours under close observation. Extubation may be considered if the patient meets appropriate extubation goals and if their airway was secure preoperatively. Plans for reintubation or other intervention should be discussed prior to extubation in case of decompensation. An experienced surgical team and critical care staff should be available for extubation in the event further intervention is required.

Conclusions

ATC is a devastating disease with a dismal prognosis. Airway management is a critical determinant in the patient’s disease management and contributes to quality of life. Upon diagnosis of ATC, our recommendation is to address airway management and supportive care goals for patients and their families. It is our philosophy to manage patients surgically and avoid tracheostomy if clinically possible. We believe that limiting complications and morbidities associated with tracheostomy will be less detrimental to patients’ overall quality of life.

Key points.

• Multidisciplinary approach is strongly recommended in management of ATC, with timely and urgent consultations.

• Because ATC has a rapid and aggressive course, end-of-life and palliative care discussions should be initiated with patients at the time of diagnosis.

• Airway management is paramount after a diagnosis of ATC because of local involvement of the aerodigestive tract and tracheostomy should be avoided as long as possible, with surgical resection and debulking attempted when feasible.

• Best supportive care and symptom management includes safe gastrostomy tube placement, respiratory support and palliative measures when appropriate