• Asymptomatic or mild symptoms; intervention not indicated

• Moderate pain; not interfering with oral intake; modified diet indicated

• Severe pain; interfering with oral intake

• Life-threatening consequences; urgent intervention indicated

• Symptomatic (e.g., dry or thick saliva) without significant dietary alteration; unstimulated saliva flow >0.2 mL/min

• Moderate symptoms; oral intake alterations (e.g., copious water, other lubricants, diet limited to purees and/or soft, moist foods); unstimulated saliva 0.1 to 0.2 mL/min)

• Inability to adequately aliment orally; tube feeding or total parenteral nutrition indicated; unstimulated saliva <0.1 mL/min

• Life-threatening consequences; urgent intervention indicated

• Advise basic oral hygiene:
  • Tooth brushing (soft toothbrush, avoid toothpaste with whitening agents)
  • Use of dental floss daily
  • >1 mouth rinses to maintain oral hygiene (avoid commercial mouthwashes or those with alcohol)
• If patient wears dentures, assess for proper fit, areas of irritation, etc.
• Dental referral if necessary
• Assess patient & family understanding of prevention strategies and rationale
  • Identify barriers to adherence

• Anticipate immunotherapy to continue
• Advise ongoing basic oral hygiene
• Advise avoidance of hot, spicy, acidic foods
• Anticipate possible alternative treatment(s)
  • Zinc supplements or 0.2% zinc sulfate mouthwash
  • Probiotics with Lactobacillus
  • Benzydamine HCI
• Assess patient & family understanding of recommendations and rationale
  • Identify barriers to adherence

• Ipilimumab to be withheld for any Grade 2 event (resume when Grade 0/1)
• Immunotherapy to be discontinued for Grade 2 events persisting ≥6 (ipilimumab) or ≥12 weeks (pembrolizumab, nivolumab)
• Assess for Sicca syndrome, Sjӧgren’s syndrome
• Encourage vigilant oral hygiene

Xerostomia:

• Advise moistening agents
  • Saliva substitute
  • Synthetic saliva
  • Oral lubricants
• Advise secretagogues
  • Nonpharmacologic
    • Sugarless gum
    • Sugarless hard candies
    • Natural lemon
  • Pharmacologic
    • Pilocarpine
    • Cevimeline HCI

Mucositis:

• Vigilant oral hygiene
  • Increase frequency of brushing to Q4 hours and at bedtime
  • If unable to tolerate brushing, advise chlorhexidine gluconate 0.12% or sodium bicarbonate rinses
    • 1 tsp baking soda in 8 ounces of water or
    • ½ tsp salt and 2 tbsp sodium bicarbonate dissolved in 4 cups of water
• Encourage sips of cool water or crushed ice
  • Encourage soft, bland non-acidic foods
  • Anticipatory guidance regarding use of pharmacologic agents (as applicable)
    • Analgesics
      • Gelclair®, Zilactin®
      • 2% viscous lidocaine applied to lesions 15 minutes prior to meals
      • 2% morphine mouthwash
      • 5% doxepin mouthwash
      • “Miracle Mouthwash”: diphenhydramine/lidocaine/simethicone
    • Corticosteroid rinses
      • Dexamethasone oral solution
  • Monitor weight
  • Monitor hydration status
• Nutrition referral if appropriate

• Nivolumab to be withheld for first occurrence Grade 3 event. Immunotherapy to be discontinued for any Grade 4 event or for a Grade 3 event persisting ≥12 weeks (ipilimumab, pembrolizumab, nivolumab) or any recurrent Grade 3 event (pembrolizumab, nivolumab)
• Anticipate hospitalization if unable to tolerate oral solids or liquids
• Unclear role of systemic corticosteroids
• Anticipate need for supplemental nutrition
  • Enteral
  • Parenteral
• Anticipatory guidance regarding use of pharmacologic agents
  • Analgesics
    • Systemic opioids may be indicated
• Oral care
• Assess patient & family understanding of toxicity and rationale for interventions as well as treatment discontinuation
  • Identify barriers to adherence