• Cancer in the head and neck region can affect respiratory function, airway patency, and hemodynamic stability; therefore, it is important to obtain vital signs and assess patients for medical stability before proceeding with a full evaluation.

• In a stable patient, evaluation should begin with a general history and physical exam.

 Important points to cover in the general history:

– History of the present illness.

 Diagnosis, original site of disease.

    For head and neck tumors originating from the oropharynx, HPV status should be obtained if available.

 Prior treatments received (surgery, radiation, chemotherapy, and experimental agents).

    For surgeries in the head and neck region, review of prior operative notes can be of value.

    Time elapsed from the last dose of chemotherapy/restaging exams.

    Prior radiation therapy: Area treated, duration of treatment and dose, short- and long-term effects of therapy.

 Detailed records including radiation plans, dose-volume histograms, on treatment assessments, and completion summaries should be obtained for prior radiation treatment delivered to the head and neck region.

    Current systemic disease status (oligometastatic vs diffuse).

    Serious health problems, prior operations.

 Contraindications to radiation such as active connective tissue diseases.

 Recurrent pneumonias may be indicative of aspiration. A dedicated assessment for this may be indicated.

    Social history should note alcohol intake and all forms of tobacco usage.

• A focused history should then assess:

 Pain: Accurate assessment of pain in patients with cancers in the head and neck area helps guide effective analgesic treatment.

– OPQRST: Onset, provocation/palliation, quality, radiation, severity, and time course.

– Because pain may correspond with disease progression, note temporal aspects of pain.

– Distinguish between visceral, somatic, and neuropathic pain.

– Somatic and neuropathic pain are common in the head and neck.

– Although less common, visceral pain can be referred from the heart, lungs, and diaphragm to the jaw and neck.

– Other types of referred pain include head and neck pain from invasion of the clivus. Referred otalgia may result from nerve stimulation/damage secondary to the following causes:

 CN V: Trigeminal neuralgia, oral cavity carcinoma.

 CN VII: Dental pain, TMJ dysfunction, parotitis, parotid tumors.

 CN IX: Pharyngitis, tonsillitis, oropharyngeal carcinoma.

 CN X: GERD, laryngopharyngeal carcinoma.

 C2 and C3: Neuropathy, metastatic invasion.

 Bleeding: Patients with bleeding should be evaluated urgently to prevent hemodynamic compromise. Appropriate treatment depends on the underlying etiology.

– Local causes of bleeding include ulceration, exposure of intratumoral vessels, ischemic/inflammatory insult to surrounding vessels, and direct tumor extension into major vessels (e.g., carotids), which may be life-threatening.

– Medications that increase risk of bleeding (e.g., NSAIDs and anticoagulants) should be identified and discontinued, if indicated.

 Airway/Breathing: Airway obstruction is the most imminent threat to ventilation and oxygenation. Obstruction of the nasal cavity, oral cavity, and/or oropharynx may produce dyspnea.

– Initial presentation of airway obstruction may be inability of patient to lie supine.

– Acute respiratory distress from airway obstruction should be assessed by physical exam: tachypnea, use of accessory muscles, and inspiratory stridor.

– Oxygen saturation is a poor indicator of acute airway obstruction severity, as saturation may be maintained by compensatory mechanisms in spite of impending clinical demise.

– If airway compromise is imminent, urgent intubation or tracheostomy should be performed in collaboration with anesthesia or ENT surgery until a more permanent solution is achieved.

– Whether to proceed with tracheostomy, debulking, palliative radiation, or observation will depend on degree of airway obstruction and expected potential for shrinkage in response to ongoing or future therapies.

 In patients with bulky disease in the midline neck (e.g., anaplastic thyroid cancer), tracheostomy may be more challenging as tumor may impede surgical access.

 Advance planning (i.e., referral to head and neck surgery and multidisciplinary discussion with the patient regarding goals of care) is necessary as emergency tracheostomy may be exceedingly difficult.

 Speaking: Speech is produced by a complex series of active and static interactions among structures along the vocal tract.

– Optimal articulation requires proper movement and/or alignment of the lips, teeth, tongue, hard palate, soft palate, uvula, epiglottis, and larynx, as well as the nasal cavity, oral cavity, pharynx, and laryngeal cavity.

– Both primary and metastatic cancers may impair speech by disrupting the anatomic relationships between these structures and their functions.

– CNs V, VII, IX, X, XI, and XII all carry efferent fibers involved in speech. Damage to these may produce speech-impairing deficits.

– Speech impairments should prompt timely referral to a speech-language pathologist, who may complete a comprehensive assessment of speech and aid in rehabilitation.

 Swallowing: Swallowing depends on complex neuromuscular coordination that enables the passage of solid or liquid from the oral cavity to the esophagus.

– The process of swallowing can be divided into three phases, each of which with its own neurologic control.

 Oral phase (voluntary): Bolus entry -> oral containment -> salivary moistening -> mastication -> trough formation -> tongue elevation -> bolus propelled into pharynx.

 Pharyngeal phase (involuntary): Nasopharyngeal closure -> pharyngeal constriction -> oropharyngeal closure -> laryngeal closure -> hyoid elevation -> pharyngeal peristalsis -> bolus propelled into esophagus.

 Esophageal phase (involuntary): Upper esophageal sphincter relaxation -> esophageal peristalsis (striated then smooth muscle) -> lower esophageal sphincter relaxation -> bolus propelled into stomach.

– If the mechanisms of swallowing are impaired, pulmonary aspiration may occur, leading to complications ranging from chemical pneumonitis to pneumonia.

– Pulmonary aspiration may be assessed with a bedside swallow test. A patient is asked to swallow a glass of water while oxygen saturation is measured. A desaturation of ≥2% in the minutes after swallowing may indicate silent aspiration.

– Deficiencies of cough, gag reflex, and motor speech functions also suggest an increased risk of aspiration.

– Videofluroscopic swallowing study enables more accurate diagnosis of swallowing dysfunction and may be used to rule out aspiration.

– Multidisciplinary care with involvement of a speech-language pathologist is helpful for diagnosis and treatment of dysphagia and aspiration.

 Nausea: While nausea may arise from a multitude of causes, identification of the underlying etiology is essential to guiding therapy, and is usually gleaned from a careful history.

– Common iatrogenic causes include chemotherapy, radiotherapy, and initiation of opioids.

– Other causes include anxiety, severe pain, anticipatory nausea, CN VIII damage/vestibulopathy, constipation, bowel obstruction, brain metastases, uremia, encephalopathy, gastritis, gastric ulcer disease, and metabolic derangements (hyponatremia and hypercalcemia).

– Etiology may be confirmed based on responsiveness to selected treatment.

– Nonpharmacologic interventions, such as frequent small feedings of cold meals and avoidance of triggering stimuli, may be helpful for nausea from variety of causes.

– Pharmacologic/interventional treatments should address the underlying cause: for example, prochlorperazine or ondansetron for chemo-induced and opioid-induced nausea, meclizine for vestibulopathy, dexamethasone for brain metastases, PPI or H2 blockers for gastritis, metoclopramide for gastroparesis, lorazepam for anxiety, and surgery/stenting for bowel obstruction.

 Nutrition/Weight loss: Nutritional status may be compromised by dysphagia, nausea, dysgeusia, and loss of appetite, as well as the metabolic effects of cancer itself.

– History should focus on uncovering specific causes of malnutrition/weight loss. However, in the majority of advanced cancer patients, anorexia occurs secondary to effects of cancer itself.

– Assess ability of patient to increase oral intake, and consult a dietician for careful monitoring of nutritional intake, which should be followed closely throughout treatment and recovery.

– Gastrostomy tube should be considered for patients with poor performance status, dysphagia, odynophagia, inadequate hydration, high risk of pulmonary aspiration, 5% weight loss over 1 month, or 10% weight loss over 6 months, if aligned with goals of care.

– Nasogastric tubes are extremely unpleasant for patients and should only be considered for short-term use under extenuating circumstances. Also, they may be difficult to place in a patient with anatomic abnormalities in the head and neck (either due to tumor or due to prior surgeries/radiation).

– If nasogastric tube is indicated in a patient with prior head and neck surgery, consult with surgeon prior to placement.

 Neurologic impairment: Numbness, tingling, weakness, and neuropathic pain may result from direct invasion or vascular compromise of nerves in the head and neck secondary to progression of cancer.

– Focal neurologic deficits in the head and neck may manifest as facial paralysis, dysphagia, speech impairments, and diplopia.

– These deficits negatively impact quality of life and may serve as a great source of frustration to patients.

– Neuropathic pain can be especially challenging to treat.

 In many cases neuropathic pain is refractory to gabapentin and pregabalin.

 Methadone may provide superior relief of neuropathic pain but ought to be prescribed cautiously or in conjunction with a palliative care specialist, as it carries a high risk of unintended overdose.

• Physical exam: A focused head and neck exam may include:

 Head: Hair, skull, facial contours, salivary glands, skin.

 Eyes: Vision, alignment, movements, pupils, light reflexes, fundi. Exophthalmos, diplopia, and ptosis may indicate the presence of metastases in the orbit or cavernous sinus.

 Ears: Auricles, canals, tympanic membranes, hearing. Dedicated hearing evaluation may be indicated.

 Nose and Sinuses: Mucosa, septum, sinus tenderness.

 Oral Cavity and Pharynx: Lips, buccal mucosa, gingiva, teeth, retromolar trigone, hard and soft palate, tongue, tonsils, speech, swallow evaluation, assessment for trismus. Consideration should be given for a dental evaluation prior to any treatment in the head and neck region based on symptoms and life expectancy.

 Neck: Lymph nodes, trachea, thyroid, range-of-motion.

• Fiberoptic nasolaryngoscopy, if indicated, enables better visualization of mucosal structures in the nasopharynx, oropharynx, larynx, and hypopharynx and extent of disease in these areas. It also allows for assessment of airway patency, and vocal cord function.

• Goals of care should be determined by the patient and physician based on a realistic discussion of near- and long-term hopes and expectations.

• Although there is a lack of data regarding the prognostic implications of disease metastatic to the head and neck area, patients with recurrent and/or metastatic head and neck cancers generally have median survival less than 1 year, even with aggressive treatment [1].

• Poor performance status may complicate the logistics of simulation and treatment. Specifically, patients with tumors compressing the tracheal region may be unable to lie flat. Frequent monitoring or individualized radiation techniques and setup may be needed.

• If prognosis is limited and/or performance status is poor, weigh the quality of life benefits of forgoing radiotherapy against the therapeutic benefits of receiving it.

• Encourage patients for whom time is short to make time for personal and professional goals.

• Allow for delays in radiotherapy, if necessary, for patients to fulfill these goals.

• Diligent supportive care of advanced cancer patients with disease in the head and neck region requires early recognition and treatment of nausea, nutritional deficiency, anemia, and pain.

• Feeding tubes or parenteral nutrition, if necessary, should be anticipated based on swallowing function, nutritional status, and goals of care.

• If there is concern for airway compromise, ENT specialists or otolaryngologists should be involved and potentially available for airway management, which may include tracheostomy tube placement.

• It is technically challenging and morbid to perform a tracheostomy in proximity to areas of gross disease.

• Referral to experienced head and neck providers and advanced planning, including a thorough discussion of the patient’s goals of care, are indicated.

• Effective treatment of pain should be of high priority. A significant proportion of cancer patients requiring analgesics in the outpatient setting are undertreated [2];

• Cancer patients likely have opioid preferences based on past experience: use this as a starting point.

• Set functional goals to guide pain management (e.g., “I want to be able to eat soft foods”).

• Treatment of neuropathic pain can be particularly challenging.

• For refractory moderate to severe neuropathic pain, consider methadone; however, prescribe with caution or in collaboration with palliative care specialist given complex pharmacokinetic profile and risk of unintended overdose.

• For patients with advanced, metastatic head and neck cancer, palliative chemotherapy alone is not curative. However, it may provide prolonged survival but with significant risk of associated toxicity.

• EXTREME trial (Vermorken NEJM 2008): 442 patients with untreated recurrent or metastatic SCC of the head and neck were randomized to either [1] cisplatin/carboplatin + 5-FU or [2] cisplatin/carboplatin + 5-FU and cetuximab (EGFR inhibitor).

 Patients receiving cetuximab showed improved median survival (10.1 months vs 7.4 months), PFS (5.6 months vs 3.3 months), and increased response rate (36% vs 20%).

 However, toxicity was greater with cetuximab (26 vs 16 patients had adverse events): mostly anemia, neutropenia, and thrombocytopenia, but nine patients in the cetuximab arm had sepsis (vs 1 in the chemo-alone, p=0.02) [1].

• Investigations of novel targeted agents and immunotherapy for various metastatic cancers, including head and neck cancers, are ongoing, with promising early results.

• A variety of chemotherapy agents administered to patients with advanced cancers may contribute to symptoms in the head and neck, which may be exacerbated by radiotherapy and hence potentially dose-limiting.

• Mucositis is one of the most common side effects of chemotherapy, in general, and can be treated with frequent saline and analgesic rinses. Other potential treatments include antimicrobials, amifostine, benzydamine hydrochloride, l-glutamine, GM-CSF, and superoxide dismutase inhibitors.

• Other potential head and neck side effects of chemotherapy include dermatitis, xerostomia, tongue swelling/tenderness, dysgeusia, neuropathy, mucosal pain, odynophagia, increased propensity for infection/dental abscess.

• Patients are likely to benefit from regular dental care.

• EGFR-inhibitors are also used in a variety of cancers (head and neck, lung, breast, colorectal) and may cause alopecia, hypertrichosis, dry skin, dermatitis, and mucositis.

• While most tumors arising in the head and neck region stem from primary tumors within the head and neck, other potential sources of disease include metastases from distant primaries (e.g., prostate, renal cell, bladder, lung, and breast), as well as various cutaneous malignancies.

• If a patient with distant metastases to the head and neck region has a low enough systemic disease burden to justify pursuit of aggressive local treatment (oligometastatic disease), then aggressive local treatment may be indicated.

• For patients with advanced cancer in the head and neck region for whom aggressive treatment is either inappropriate or inconsistent with goals of care, RT with palliative intent may potentially alleviate symptoms and improve quality of life.

• Similar treatment principles apply for patients with advanced, metastatic cancer from a head and neck primary and those with metastatic spread from distant sites, such as GU, lung, and breast.

• For a symptomatic tumor in the head and neck region, RT is typically more likely to produce a local response than chemotherapy.

• Treatment volume for palliative RT

 Should target only gross disease with an individualized margin to account for uncertainty and setup error.

 Focus on areas of tumor responsible for symptoms.

• More conformal techniques, such as IMRT, may be considered if durable palliation is desired, if there is concern for intolerable or unwanted treatment-related side effects, or potentially for protection of critical structures in the case of re-irradiation. The benefits of using IMRT or other advanced techniques should be balanced against the increased cost and the need to start treatment within a shorter time frame.

• Skin metastases may bleed or be otherwise symptomatic and thus may also benefit from palliative radiotherapy.

 Electrons may be preferable to photons for superficial lesions, depending on depth of invasion and surrounding anatomy.

 The use of a bolus enables the 100% isodose line to be approximated to the surface of the targeted lesion.

 If surface anatomy is complex, dose heterogeneity inherent to electron beam therapy may result in hot and cold spots. This can be addressed with a custom bolus.

• Stereotactic body radiotherapy (SBRT) may allow for hypofractionation and dose escalation, potentially improving rates of durable local control in patients with a longer life expectancy. SBRT also offers the practical benefit of reduced treatment time compared with conventional RT.

 Several small studies have shown that advanced stage head and neck cancer patients treated with palliative SBRT have favorable symptom control rates with relatively low rates of toxicity [26–28].

– SBRT for head and neck cancer [29]: 44 patients with primary, recurrent, or metastatic head and neck cancer underwent either single-dose (n=18; 13–18 Gy) or fractionated RT (n=37; 36–48 Gy) to 55 malignant lesions.

 Overall complete and partial response rate=77%. Tumor control rates at 1 year: primary=83.3%, recurrent=60.6%. Median OS: primary=28.7 months, recurrent=6.7 months, metastatic=5.6 months.

 Grade 3+ toxicity in 7 patients (16%) [29].

– Phase II study of SBRT for re-irradiation with cetuximab [30]: 56 patients with recurrent head and neck cancer treated with SBRT to 36 Gy/6 fx with concomitant cetuximab (2 week treatment course).

 At 3 months, response rate=58.4%, disease control rate=91.7%; 1 year OS=47.5%.

 Patients with Grade ≥3 toxicity=18 (32%). Skin toxicity: all grades=41 (73%), Grade ≥3=5 (9%). Treatment-related death=1 (hemorrhage) [30].

 SBRT may be a reasonable alternative to curative intent fractionated RT for primary treatment of inoperable head and neck cancer in elderly patients and those with poor performance status. While data is limited, published control rates, survival, and toxicity are encouraging [31,32].

• Brachytherapy may also provide therapeutic advantages in both curative and palliative situations by enabling dose-escalation, normal tissue avoidance, and the practical benefit of shortened treatment times.

 Regimens vary widely across institutions, but high-dose-rate intraoperative techniques are most commonly utilized [33].

 Modern studies of high-dose-rate brachytherapy for head and neck cancer recurrences report local control rates at 1–2 years approaching 70%, with Grade ≥3 toxicity occurring in <20% of patients [34,35].

• Radiation dermatitis occurs in the majority of patients who receive radiotherapy for advanced cancer in the head and neck region. Risk varies based on total RT dose, fraction size, treatment time, beam type and energy, and skin volume exposed [36].

 Grade 1: Faint erythema or dry desquamation.

 Grade 2: Moderate to brisk erythema; patchy, most desquamation mostly confined to skinfolds; moderate edema.

 Grade 3: Moist desquamation other than skinfolds; bleeding with minor trauma/abrasion.

 Grade 4: Skin necrosis or ulceration of full thickness dermis; spontaneous bleeding.

• Skin changes are sharply demarcated, as they reflect the associated treatment field.

• Other risk factors include poor nutrition, preexisting dermatologic conditions, overlapping skinfolds, concurrent cetuximab, connective tissue diseases, HIV, diabetes, receipt of radiosensitive agents, and inherited disorders of DNA repair [36,37].

• Basic management strategies: Counseling about skin care, daily use of Aquaphor, and consideration of low to moderate dose topical steroids (e.g., mometasone 0.1%). Consider topical antibiotic (e.g., mupirocin) if evidence of infection.

• Radiation-induced mucositis is a common side effect of radiation to the head and neck that may potentially result in pain, dysphagia, dehydration, nutritional deficiencies, weight loss, feeding tube dependency, and pulmonary aspiration [38].

• Stomatitis (mucositis of the oral cavity) is of particular concern with chemoradiation, as various chemotherapy agents are independently associated with stomatitis, frequently in the anterior structures of the oral cavity.

• There is no reliable prophylaxis for radiation-induced mucositis; nonetheless, patients should be encouraged to maintain excellent oral hygiene and undergo dental evaluation prior to treatment.

• Aggressive use of analgesics may be required if pain is function limiting.

• In the event of dysphagia/odynophagia, speech and swallow evaluation and therapy may be indicated.

• Feeding tube placement should be considered only as a temporizing measure and must be aligned with patient’s goals of care.

• Basic management strategies: consider regular oral rinses with baking soda/salt solution. Mild to moderate pain: consider Maalox/Benadryl/Lidocaine (MBL/Magic Mouthwash), or application of oral lidocaine gel to specific areas of pain. Acetaminophen and NSAIDs can also be considered, although care should be taken in patients with liver or renal dysfunction or those receiving systemic chemotherapy. Moderate to severe pain: consider opioid use (both short- and long-acting), potentially in conjunction with a bowel regimen.

• Xerostomia is caused by hyposalivation that results from irradiation of the salivary glands.

• Xerostomia may impair speech, chewing, and swallowing, cause pain and ulceration, and predispose to infection as well as rapidly progressing caries [39].

• IMRT and proton beam therapy may enable improved sparing of salivary glands, which may be worth pursuing in selected patients considering that management of xerostomia is challenging.

• Potential therapies include the cholinergic agonists cevimeline and bethanechol, acupuncture, and oral lubricants [39].

• Avoidance of sugar and good oral hygiene practices, with prophylactic daily fluoride rinses, may help prevent rapidly progressing caries.

• Medications that may contribute to xerostomia include antihistamines, anticholinergics, beta-blockers, diuretics, some anticonvulsants, antipsychotics, hypnotics, and morphine.

• Radiotherapy may cause lymphedema of the larynx and pharynx, leading to difficulty speaking and dysphagia.

• Laryngeal edema is often more pronounced in the case of re-irradiation.

• RTOG Scale for laryngeal edema (to be determined by flexible fiberoptic exam) [40]:

 Grade 0: No edema.

 Grade 1: Slight edema.

 Grade 2: Moderate edema.

 Grade 3: Severe edema.

 Grade 4: Necrosis.

• To prevent laryngeal edema, mean laryngeal dose should be ≤43.5 Gy [41].

• If airway is threatened, make sure ENT surgery is aware and available for acute management.

• Temporary radiation-induced dysgeusia occurs as a result of damage to the taste buds and/or chorda tympani.

• Avoidance of the anterior tongue in the treatment field is an effective strategy for preserving taste, even if the base of the tongue is irradiated [42].

• Dysgeusia may have a large negative impact on quality of life, contributing to weight loss and nutritional deficiencies.

• Other causes of dysgeusia include chemotherapeutics, especially taxanes and vincristine.

• Consultation with a nutritionist may be required to ensure that patient is able to maintain adequate dietary intake.

• Patients with advanced cancer in the head and neck are at high risk of developing a multitude of complications, both disease-related and iatrogenic.

• Early involvement of ENT surgeons, dentists, palliative care specialists, nutritionists, and speech-language pathologists is critical.

• Corticosteroids may be used to reduce inflammation and edema in the head and neck (consider Decadron 2–4 mg PO QD to BID for severe inflammation/edema).

• May also relieve neuropathic pain and nausea.

• Moderate potency topical steroids, such has 0.1% mometasone, have been shown to be effective as prophylaxis against discomfort, burning, and itching associated with radiation dermatitis [43].

• Skin dryness can be alleviated by Aquaphor or other moisturizes.

• Pruritis can be treated with Gold Bond or 1% hydrocortisone ointment.

• Sun exposure to treatment site should be limited either by covering affected area or with SPF 50 or greater sunscreen.

• For moderate to severe radiation dermatitis, Domeboro compresses and Aquaphor/xylocaine, topical lidocaine, or Pramasone may be beneficial.

• Prior to receiving head and neck radiation, patients should undergo a dental evaluation to assess baseline oral health and determine the need for restorative work or extractions.

• Typical recommendations for maintaining good oral hygiene include: regular brushing, soft toothbrush, mild toothpaste, baking soda gargle, floss gently as tolerated, use a humidifier, reduce intake of spicy foods, and avoid intake of alcohol and use of tobacco products.

• Daily prophylactic fluoride use is also recommended, as patients are at increased risk for caries.

• Close dental follow-up is recommended, as patients are at high risk for dental complications (Table 17.3).