ED Care of Head and Neck Cancer Patients

Authors: Laura Murphy, MD, MBA (Administration Fellow, Instructor of Emergency Medicine, Vanderbilt University Medical Center); Kathryn Ritter, MD (Chief Resident, Instructor of Emergency Medicine, Vanderbilt University Medical Center); Matthew Pirotte, MD (Program Director, Assistant Professor of Emergency Medicine, Vanderbilt University Medical Center) // Reviewed by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Background:

According to a 2018 study, head and neck cancer was the 7th most common cancer worldwide with 890,000 cases and 450,000 deaths. In the United States, it accounted for 3% of all cancers and 1.5% of cancer deaths.1 Head and neck cancer may affect the oral cavity, oropharynx, hypopharynx, larynx, nasal cavities, paranasal sinuses, thyroid gland, salivary glands, or the skin. Squamous cell carcinoma is the most common subtype.2 Risk factors for developing head and neck cancer include human papilloma virus (HPV) infection as well as the use of tobacco, alcohol, marijuana, and e-cigarettes.3

Globally, the incidence of head and neck cancer is declining due to decreased use of tobacco.4 However, there is an increase in HPV-associated oropharyngeal cancer in North America and Europe. HPV accounted for 16.3% of cases in the 1980s, and the rate increased to 71.7% in the 2000s.5 With HPV vaccination, there may eventually be a decline in these rates. Fortunately, HPV-positive oropharyngeal cancer tends to be more responsive to chemotherapy and radiation, which are two common therapies for head and neck cancer.6 Surgical excision may also be indicated.

Pearl: Risk factors for malignancy include HPV as well as the use of tobacco, alcohol, marijuana, and e-cigarettes.


Overview of Common ED Presentations:

Patients with head and neck cancer may present to the ED with common ENT complaints that lead to a new diagnosis; management of these patients is discussed in more detail below. However, patients with head and neck cancer may present to the emergency department for reasons related to complications of their disease. Some of the common complications leading to ED presentation are summarized below:

  • Airway Compromise: Airway compromise can occur due to direct extension of tumors or from obstructive lymphedema.2
  • Bleeding: Life-threatening bleeding may occur in this patient population. One of the most feared complications of head and neck cancer is rupture of the carotid artery or one of its major branches, which is defined as carotid blowout syndrome. This has a mortality rate of 40%.7
  • Thrombosis: Patients may develop venous thromboembolism as a complication of head and neck cancer.
  • Infection: Patients with head and neck cancer may experience dysphagia which increases their risk for developing aspiration pneumonia. In patients who are currently undergoing chemotherapy, opportunistic infections must also be considered due to the patient’s immunocompromised state.
  • Pain: 80% of patients suffer from pain due to spread of the primary site of malignancy or as a side effect from treatment including surgery, chemotherapy, or radiotherapy.8 These patients may present to the ED for management of pain that is refractory to their current outpatient medication regimen.
  • Nutritional Issues: Over 25% of patients with early-stage head and neck cancer have been shown to suffer from critical weight loss, which is defined as more than 5% of their original body weight.9 For patients undergoing radiotherapy treatment for their cancer, mucositis, dysgeusia, and xerostomia can all contribute to decreased oral intake. Thirty percent of radiotherapy patients also experience nausea and vomiting.9 Similar side effects can be caused by chemotherapy which may lead to decreased oral intake. Many patients will have feeding tubes and may present with complications associated with these.

Case 1:

A 61-year-old male with longstanding history of tobacco use presents to the ED with two weeks of sore throat and neck pain. Physical exam is notable for fullness of the right tonsil without exudates and right sided cervical adenopathy. CT demonstrates a right-sided tonsillar mass with several necrotic cervical lymph nodes. There are no findings of abscess or infection. What are the next steps in management?

Initial Presentation:

Head and neck cancer patients may initially present to the ED with pain in their throat, jaw, or neck. A new diagnosis of head and neck cancer should be considered in patients presenting with a neck mass, dysphagia, odynophagia, hemoptysis, or facial swelling especially if the patient has risk factors. Physical exam findings that increase suspicion for malignancy include fixation to adjacent tissues, firm consistency, size >1.5 cm, or ulceration of the overlying skin.10 Persistent lymphadenopathy for more than four weeks is another red flag that should prompt further investigation.11

Pearl: If an adult patient presents to the ED with a head and neck infection, the differential diagnosis should include an underlying malignancy. The suspicion for malignancy should especially increase in patients with persistence of symptoms, no responsiveness to appropriate antibiotics, or a social history of tobacco/alcohol use.12

Work-Up and Imaging:

If an adult patient presents with a new, undifferentiated soft tissue mass in the neck, there should be a high suspicion for malignancy in order to avoid a delayed diagnosis which would worsen prognosis.10 CT is the typical first-line imaging study for these new neck masses since it is quicker, cheaper, and more widely available in EDs compared to MRI imaging. Performing the CT with contrast improves characterization of the mass and allows for distinction between cystic versus solid lesions.10 Furthermore, IV contrast increases the sensitivity of identifying malignant lymph nodes.13 A recent meta-analysis evaluated the performance of CT in the diagnosis of metastatic cervical lymph nodes, and this study found that the pooled sensitivity was 55%. The pooled specificity was 87%.14 If more detailed imaging is needed, then an MRI with contrast can provide improved definition of tumor margins. Furthermore, it is superior to CT for evaluating intraspinal pathology. MRI may also be necessary before initiation of treatment in order to determine the specific plan for radiation therapy.13

For pediatric patients, ultrasound is the imaging modality of choice for new neck masses. This is performed using a high-frequency, linear transducer. Doppler can be utilized to assess the vascularity of masses and lymph nodes. In general, the more vascular a lesion is, the more aggressive it likely is.13 There are multiple benefits to using ultrasound in the pediatric population. First, using ultrasound instead of CT imaging will limit the pediatric patient’s exposure to potentially harmful ionizing radiation. Since ultrasound studies can often be performed quickly, there typically is no need for sedation which may be required for longer imaging studies such as MRI. Ultrasound is also non-invasive and inexpensive. Furthermore, ultrasound can be performed by pediatric emergency physicians, and point-of-care ultrasound of neck masses in children has been shown to have a high inter-rater reliability (κ = 0.87; 95% confidence interval, 0.72–1.00) when performed by physicians with POCUS fellowship training.15 Another study compared diagnoses from the point-of-care ultrasound of a soft tissue neck mass performed by the pediatric emergency physician to imaging performed by the radiology department, and they found that there was agreement in 78% of cases.16 In addition, ultrasound imaging is used in adult patients for evaluation of thyroid masses or nodules which may be malignant.17 Nevertheless, there are some limitations of ultrasound imaging. It can only evaluate superficial soft tissue structures including the thyroid gland, salivary glands, and lymph nodes in the jugular chain. It cannot show detailed images of deeper structures.13

When findings concerning for malignancy are identified on imaging in the ED, the next step in management may depend on the patient and ability to arrange follow-up. In some circumstances, admission will be indicated. However, if these patients are discharged, they will need prompt evaluation as an outpatient in order to perform a biopsy and establish a tissue diagnosis. They may also require additional imaging as an outpatient in order to perform staging.

Pearl: The use of contrast with CT or MRI imaging studies improves definition of tumor margins and identification of malignant lymph nodes.


Case 2:

The patient from the first case presents to the ED several months later after initiating systemic chemotherapy and radiation therapy with generalized weakness, malaise, vomiting, and poor oral intake. What complications of therapy should you consider in this patient?

Treatment:

Treatment of head and neck cancer differs according to anatomical location and stage of disease. It is often approached in a multidisciplinary fashion including specialists from medical oncology, surgical specialists (otolaryngology, oral and maxillofacial surgery) as well as ancillary services including nutrition, speech and language therapy, audiometry, and psychosocial services.18

Early-stage disease is often curable by surgery or definitive radiotherapy alone, and treatment depends on anatomical accessibility and efforts to minimize morbidity.18 Neck dissection (removal of cervical lymph nodes) or prophylactic radiotherapy decreases risk of recurrence and is often performed in patients undergoing surgical treatment. Treatment regimen depends on location and staging of the cancer. Timing of surgical treatment, chemotherapy (induction vs. adjuvant therapy), and concurrent radiation depends on tumor location, extent of local and distant metastases, and goal of therapy (curative vs. palliative).18 It is important for emergency physicians to understand the complications and side effects associated with these treatments.

Cytotoxic Chemotherapy:

Some common agents used in the treatment of head and neck cancer are included in the following table as well as their common toxicities.

Each of these agents have specific toxicities and side effects (summarized above), often dose-dependent, and can be synergistic in combination with other cytotoxic agents or radiation therapy.21 Chemotherapy-induced nausea and vomiting is very common and associated with most agents. Patients may require multiple agents to treat nausea and vomiting and may require IV hydration.22 Electrolyte abnormalities can be related to direct nephrotoxic effect of chemotherapeutic agents (e.g. proximal tubular necrosis from cisplatin leading to magnesium wasting) or from poor nutritional status.

Mucositis, which leads to inflammatory and ulcerative lesions in the oral cavity and GI tract, can lead to pain, dehydration, bleeding, and infection due to breakdown of the mucosal barrier. The risk is higher with combination regimens or when chemotherapy is combined with radiation therapy. Treatment includes topical and systemic analgesic therapy as well as ensuring adequate oral intake. Topical treatment frequently consists of topical viscous lidocaine23combined with mucosal protective agents (e.g. magnesium aluminum hydroxide) and anticholinergic agents such as diphenhydramine; there is no clear evidence to advise this, but these medications are often used for pain relief in the ED.23, 24 Patients are advised to “swish and spit,” but it is important to consider that patients may still experience effects of the medications contained in these mouthwashes. Other topical agents include morphine25 and doxepin.26 Consistent oral hygiene is recommended using a soft toothbrush with salt and soda mouth rinse, consisting of 1 liter of water with 1 teaspoon of salt and 1 teaspoon of baking soda.24

Neutropenia is common in patients undergoing cytotoxic chemotherapy, and the nadir in absolute neutrophil count (ANC) occurs at approximately 5-10 days after administration. Fever in neutropenic patients should undergo prompt assessment and treatment, including broad infectious workup and broad-spectrum antibiotics with consideration for atypical and opportunistic infections.27

Neurotoxicity can cause a variety of symptoms including headache, encephalopathy, cerebellar dysfunction, seizures, or focal deficits. Ototoxicity is particularly common with platinum-based agents. There can also be long-term effects including leukoencephalopathy and dementia.28 Peripheral neuropathy (very common with platinum-based agents and taxanes), which can lead to neuropathic pain, is often treated with topical agents, gabapentinoids, and duloxetine.21, 29

The use of immunotherapy to treat head and neck cancer has been increasing in recent years. This includes agents such as cetuximab (EGFR monoclonal antibody) and anti PD-1 agents such as pembrolizumab and nivolumab. Toxicities (termed immune-related adverse events or irAEs) associated with these therapies include dermatitis, colitis, hepatitis, pneumonitis, and endocrinopathies. Renal, cardiac, neurologic, and ocular toxicities have also been reported but are more rare.20, 30

Many head and neck cancer patients are treated with radiation therapy. Tissue toxicity can be divided into acute (<90 days), subacute (90 days to 2 years), and late (>2 years). Toxicity from radiation is exacerbated by concomitant chemotherapy or immunotherapy. Radiation effects mostly impact tissues with rapid self-renewal including the skin, head and neck, GI tract, and bone marrow. Mucositis is a common side effect of radiation treatment and is more severe in patients undergoing concurrent chemotherapy.31, 32 Xerostomia is a common acute and subacute side effect in patients undergoing head and neck radiation due to the location of salivary glands; this leads to dry mouth with thickened, sticky saliva and secretions.33 Other effects include dysgeusia, dermatitis (erythema, desquamation, or ulceration), osteonecrosis of the jaw, trismus, and dysphagia.33 Lymphedema and tissue fibrosis resulting from soft tissue injuries can lead to pain, trismus, and decreased mobility. Damage to other surrounding structures can lead to dysphagia, hypothyroidism, myelitis, optic neuropathy, retinopathy, ototoxicity, and secondary malignancies.34


Case 3:

A 71-year-old male patient with SCC of the base of the tongue with advanced locoregional disease status post chemoradiation and neck dissection presents to the ED with worsening pain, shortness of breath, and inspiratory stridor. The patient is afebrile, mildly tachycardic, and tachypneic with respiratory rate of 24 breaths/min with oxygen saturations of 93% on room air. He is quite anxious, and you note inspiratory stridor on exam. However, there is moderate air movement bilaterally when you auscultate his lungs. What are your next steps in management of this patient?

Complications: Airway Obstruction

One of the most life-threatening complications of head and neck cancer is airway obstruction. Approximately 80,000 patients annually in the US have airway obstruction caused by malignancy of the aerodigestive tract.35 This can be due to the tumor itself or from cervical adenopathy. Many patients will have prophylactic tracheostomy at some point in their treatment, but they can present to the ED with airway emergencies before this occurs. Signs of impending airway obstruction including drooling, stridor, respiratory distress, or hypoxia. These patients require emergent airway management. It is important to remember that these patients have distorted anatomy, making both endotracheal intubation and surgical airway management very difficult; the earlier you can involve experts (otolaryngology or available surgical team and/or anesthesia), the better. Ideally, these patients have airway management performed in a controlled setting in the operating room. Awake flexible fiberoptic laryngoscopy or tracheostomy are often performed in patients with an unsecured airway.36

In addition to direct tumor effects, treatment of head and neck cancer with radiation or with radical neck dissection can lead to anatomic changes which make airway management difficult.  Patients who have undergone radiation treatment can have tonic contraction and fibrosis of the muscles of mastication, leading to trismus which is not alleviated by paralytic medication. In addition, these patients will have significantly limited range of motion of their neck.37 A single-center retrospective study showed that for patients who had undergone head/neck radiotherapy, there was a higher percentage of patients with significantly limited range of motion of their neck compared to the control group.37 Surgical treatment can cause a postoperative hematoma, which can lead to distortion of airway anatomy or airway obstruction. Patients who have undergone radical neck dissection can develop pharyngeal edema due to venous obstruction of the jugular veins.38 Due to distorted anatomy, these patients are difficult endotracheal intubations and surgical airways, so early involvement of experts is best.

Pearl: Patients with head and neck cancer have significantly distorted anatomy, making endotracheal intubation and surgical airway management very difficult, and early involvement of experts (surgical and anesthesia teams) is ideal.

Head and neck cancer patients often undergo prophylactic tracheostomy or laryngectomy with construction of a stoma, which establishes a secured airway. However, patients with tracheostomy or laryngectomy stoma can present with airway obstruction or problems with their tracheostomy or stoma. As emergency physicians, it is important to understand the postsurgical anatomy following these procedures. Both types of patients have anterior neck stomas, but it is important to determine what type of procedure they have undergone.

A tracheostomy creates a surgical opening to the trachea. The larynx and upper airway remain intact. Head and neck cancer patients often have tracheostomy placed due to upper airway obstruction or distortion. On the other hand, in patients who have undergone total laryngectomy, the larynx has been removed and there is no access to the airway from the nose or mouth. Asking patients or reviewing operative reports can provide this information, but if unsure, end-tidal capnography can be placed on the patient’s nose; tracheostomy patients will have some CO2 exchange if the tracheostomy cuff is down, and laryngectomy patients will not.39 Post-laryngectomy patients often may have a tracheo-esophageal puncture (TEP) device which is a one-way connection for air flow from the trachea into the esophagus to allow for speech. When placing a cuffed device via a laryngectomy stoma, the cuff should be placed beyond the TEP device with care not to dislodge the device. If the device is dislodged, it is important to obtain a chest x-ray to rule out aspiration of the device. A red rubber catheter can be placed through the stoma to keep it patent until it can be replaced or repositioned by otolaryngology.

Airway obstruction in patients with tracheostomy or laryngectomy stoma is an emergency; expert management should be sought as soon as possible. Below is a brief summary of managing respiratory distress in patients with tracheostomy and laryngectomy patients. The key difference to remember between these two is that patients with a tracheostomy have a connection between the nose and mouth and the lower airway. They can be passively oxygenated or intubated from above; post-laryngectomy patients cannot.

See prior posts here and here about troubleshooting tracheostomies and review proposed algorithms for managing tracheostomy and laryngectomy airway emergencies here.

Pearl: Understanding the anatomy of patients who have undergone tracheostomy or laryngectomy is imperative to the ED management of these patients and alleviating airway obstruction.


Case 4:

A 67-year-old male patient with oropharyngeal SCC s/p surgical resection and chemoradiation presents after coughing up several blood clots at home. Exam is difficult due to trismus, but you note some dark blood in his sputum and several blood clots. He reports the bleeding has improved on the way to the hospital. He is afebrile and currently hemodynamically stable. He has a tracheostomy in place. What are the next steps in management?

Complications: Bleeding

Bleeding can occur as a result of tumor extension, but the most common cause is poor wound healing after surgery or radiation.2 Estimates of the incidence of oropharyngeal bleeding following treatment for head and neck cancer range from 0.5 to 10%, approximately 7.2% in one study.40 Approach to bleeding in these patients should follow a standard ABC approach, focusing on maintaining a secure airway and controlling bleeding. Radiation can lead to vasa vasorum, premature atherosclerosis, adventitial fibrosis, and weakening of the arterial wall. Surgery can strip the vascular supply of the arterial wall, which can lead to arterial bleeding.41 Exposure of tumor sites to salivary enzymes and infection can also contribute to increased bleeding. Major arterial bleeding is often preceded by sentinel bleeding, often from a pseudoaneurysm, so any bleeding in these patients should be taken very seriously. In stable patients, CT angiogram is the preferred imaging modality to determine the source of hemorrhage.42 This can guide endovascular or surgical management of bleeding, and prophylactic treatment of diseased vessels can prevent catastrophic bleeds. The most feared complication is carotid rupture or carotid blowout, which is uniformly fatal without rapid intervention. This is primarily managed with endovascular stenting, which has reduced mortality and neurologic morbidity compared to open surgical repair.42 In some cases, the carotid artery can be occluded, but this is associated with a high risk of neurologic complications.43 Definitive treatment includes surgical soft tissue reconstruction to prevent re-bleeding episodes. Surgical management often involves a head and neck surgery team in conjunction with interventional neuroradiology or neurosurgical teams, depending on the institution and location of the bleeding

In patients with significant bleeding, it is important to secure the airway, given the proximity of the tumor to the airway and the risk of aspiration. This can be done by endotracheal intubation or tracheostomy; in patients with tracheostomy, make sure the cuff is inflated to protect from aspiration. Arterial bleeding in the emergency department should be managed by direct pressure, which can be applied using a finger, Foley catheter balloon, or packing device. Another feared complication associated with tracheostomy is the tracheo-innominate fistula, which should be considered in any patient with bleeding from a tracheostomy site. In this instance, direct pressure can be applied digitally or with a cuffed tube as a temporizing measure pending definitive, emergent surgical treatment.

Venous bleeding is more rare than arterial bleeding and is usually much less severe. Bleeding from the internal jugular vein is often aggravated by coughing and usually associated with a pharyngo-cutaneous fistula. Treatment for this is surgical and requires ligation of the IJV.45


Case 5:

A 64-year-old female patient with recent diagnosis of squamous cell carcinoma of the soft palate presents with worsening pain, erythema, and swelling of left anterior neck. CT imaging demonstrates an occlusive thrombus in the left internal jugular vein. What are the next steps in management?

Complications: Thrombosis

Malignancy typically increases the risk of venous thromboembolism. To illustrate, the hazard ratio of venous thromboembolism has been shown to be 4.7 (95% confidence interval 4.5-4.9) for patients with cancer versus age-matched non-cancer controls.46 However, this risk has been reported to be lower for head and neck cancers compared to other cancers.47 In patients with head and neck cancer, the incidence of venous thromboembolism has been estimated to be 0.16%-3.125%.47 Deep vein thrombosis should be suspected in patients presenting to the ED with unilateral extremity swelling, pain, or tenderness. When evaluating patients with head and neck cancer, it is also crucial to consider the possibility of a thrombus in the internal jugular vein. IJ thrombus is rare and many are associated with malignancy of the head and neck.48

What should the EM physician do when managing a case of head/neck cancer with a thrombus in the IJ? Low molecular weight heparin is the preferred initial anticoagulant for patients with malignancy who have been diagnosed with venous thromboembolism. Treatment is typically continued for 3-6 months.47

Development of an IJ thrombus may be associated with Lemierre’s syndrome, which is septic thrombophlebitis of the IJ. Fusobacterium necrophorum is the most common etiology of Lemierre’s syndrome.48 Septic emboli may result from this condition. Patients with Lemierre’s syndrome need to be started on antibiotics covering anaerobic bacteria. Possible antibiotic regimens include meropenem 1 g IV every 8 hours, piperacillin-tazobactam 3.375 g IV every 6 hours, or ceftriaxone 2 g IV every 24 hours plus metronidazole 500 mg IV every 8 hours.

Pearl: A tumor with an associated thrombus in the IJ should be treated with low-molecular weight heparin. Disposition of patients with an IJ thrombus will depend on their clinical status and discussion with the appropriate specialty team. Patients with Lemierre’s syndrome should be admitted and started on IV antibiotics.


Summary:

  • Consider underlying malignancy in adult patients presenting with dysphagia, odynophagia, hoarseness, voice changes, or atypical or recurrent head and neck infections.
  • Patients undergoing treatment for head and neck cancer are at high risk for complications, including poor nutritional state, pain, dehydration, infection, and drug toxicities.
  • Airway obstruction in a patient with an unsecured airway warrants immediate expert consultation given distorted anatomy. It is important to understand the post-surgical anatomy and management of airway obstruction for patients after tracheostomy and laryngectomy.
  • Any bleeding in patients with head and neck cancer should be taken seriously, even if it seems minor, as it could represent a sentinel bleeding event which may precede catastrophic or life-threatening bleeding.
  • Tumor-associated thrombus should be treated with low-molecular-weight heparin along with consideration of septic thrombophlebitis.

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