Background
Methods
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Approach to and management of dermatological conditions arising from RT, CCRT and cetuximab/RT).
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Approach to and management of mucositis resulting from radiation, with or without the addition of chemotherapy or cetuximab.
Radiation dermatitis and skin toxicity from cetuximab/RT
Literature review and clinical experience
RT/CRT alone | Cetuximab + RT |
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Pathophysiological (for more details, please refer to text) | |
Clinical | |
Onset of dermatitis is within 3–5+ weeks of treatment | Onset of dermatitis is within 1 or 2 weeks of treatment |
No crusting | Crusting is present, which can result in sustained microtrauma, bleeding, and discomfort and can lead to infection |
Grade of radiation dermatitis | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
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Definition of radiation dermatitis (NCI CTCAE, v3.0) | Faint erythema or dry desquamation | Moderate to brisk erythema; patchy, moist desquamation, mostly confined to skin folds and creases; moderate oedema | Moist desquamation other than skin folds and creases; bleeding induced by minor trauma or abrasion | Skin necrosis or ulceration of full thickness of dermis; spontaneous bleeding from involved site |
General management approaches | See General management | |||
Maintain hygiene and gently clean and dry skin in the radiation field shortly before radiotherapy | ||||
Topical moisturisers, gels, emulsions and dressings should not be applied shortly before radiation treatment as they can cause a bolus effect, thereby artificially increasing the radiation dose to the epidermis | ||||
Grade-specific management approaches | Use of a moisturiser is optional | Keep the irradiated area clean, even when ulcerated | Verify that radiation dose and distribution are correct | |
If anti-infective measures are desired, antibacterial moisturisers (e.g. triclosan or chlorhexidine-based cream) may be used occasionally | In the absence of clinical signs of infection, one or combinations of the following topical approaches may be used: | Requires specialised wound care with the assistance of the radiation oncologist, dermatologist and nurse, and should be treated on a case by case basis | ||
•- Drying gels, possibly with the addition of antiseptics (e.g. chlorhexidine-based creams) | ||||
•- An anti-inflammatory emulsion, such as trolamine | ||||
•- Hyaluronic acid cream | ||||
•- Hydrophilic dressings, applied after radiotherapy to the cleaned, irradiated area, which may provide symptomatic relief | ||||
•- Zinc oxide paste, if easy to remove prior to radiotherapy | ||||
•- When used, silver sulfadiazine or beta glucan cream should be applied after radiotherapy (possibly in the evening) after cleaning the irradiated area | ||||
•- Where infection is suspected: | ||||
•- The treating physician should use best clinical judgement for identifying infection, including the consideration of swabbing the area for identification of the infectious agent | ||||
•- Topical antibiotics (should not be used prophylactically) | ||||
•- Doxycycline is not recommended at this stage | ||||
•- Blood granulocyte counts should be checked, particularly if the patient is receiving concomitant chemotherapy | ||||
•- Blood cultures should be carried out if there are additional signs of sepsis and/or fever | ||||
Management team | Can be managed primarily by nursing staff | Can be managed by an integrated management team comprising the radiation oncologist, nurse, medical oncologist (where appropriate) and dermatologist, as required | Should be managed primarily by a wound specialist, with the assistance of the radiation oncologist, medical oncologist (where appropriate), dermatologist and nurse, as required | |
Skin reactions should be assessed at least once a week |
Results
Recommendations based on clinical practice
Recommendations for management of skin conditions
Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
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Local treatment | • No treatment is required | • Keep the site clean and dry | • Keep the site clean and dry | • Keep the site clean and dry |
• Avoid rubbing and maintain moisture and hygiene | • Topical treatment with antiseptics/antibiotics/steroids is recommended | • Topical treatment with antiseptics/antibiotics/steroids is recommended | • Topical treatment with antiseptics/antibiotics/steroids is recommended | |
• Topical treatment with antiseptics/antibiotics/steroids may help | ||||
Systemic treatment | • No treatment is required | • No treatment is required | • Oral antibiotics, pain-killers, corticosteroids or antihistamines for symptom relief | • Oral antibiotics, pain-killers, corticosteroids or antihistamines for symptom relief |
• Regular monitoring is recommended | • Oral antibiotics, pain-killers, corticosteroids or antihistamines for symptom relief | |||
• Temporary discontinuation or delay of cetuximab treatment | ||||
• Temporary discontinuation of cetuximab and radiation treatment |
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Physician and patient education for skin care.
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Maintaining clean and dry skin, and avoiding perspiration during and especially after exposure to radiation dosing; the skin lesion with dermatitis should be kept moist.
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No viscous creams or jellies to be applied within the field of radiation during the radiation phase.
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Close monitoring once a week during start of therapy; and with emergence of erythema, monitoring must be more frequent up to twice a week, with utmost attention to early management strategies of the condition.
TERM | G1 | G2 | G3 | G4 |
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Dermatitis Bio-radiation | Faint erythema or dry desquamation; and lesions due to bio-treatment (e.g. xerosis, papules, pustules, and other clinical signs) which may or may not be associated with symptoms of pruritus or tenderness. | Moderate to brisk erythema; patchy moist desquamation in folds and creases; lesions due to bio-treatment (e.g. crusts, papules, pustules, and other clinical signs) mostly confined to less than 50 % of radiated area; bleeding lesions with friction or trauma. | Moist desquamation in areas other than skin folds and creases; extensive (>50 % of involved field) confluent lesions due to bio-treatment (e.g. crusts, papules, pustules, and other clinical signs) associated to bleeding by minor trauma or abrasion. | Life-threatening consequences; skin necrosis or ulceration of full thickness dermis; extensive (>50 % of involved field) confluent lesions due to bio-treatment (e.g. crusts, papules, pustules, and other clinical signs) associated to signs of spontaneous bleeding. Systemic inflammation response syndrome (SIRS) |
Activity of Daily living (ADL) | No limiting age-appropriate ADL | Limiting age-appropriate instrumental ADL | Limiting self-care ADL | |
Action | Topical therapy indicated (moisturizers, corticosteroids, antibiotics) | Topical and oral therapy indicated | Topical and oral therapy indicated; dressing and wound indicated; inpatient therapy may be necessary | Hospitalize the patient |
Grade-specific management approaches | Weekly follow-up is adequate, unless rapid progression is noted | Consider twice-weekly assessments to monitor rapid change | Evaluate the need for daily assessment Closely monitor signs of local or systemic infection For grade 3 reactions occurring at <50 Gy, consider brief interruption in treatment | Consider interrupting treatment with both radiotherapy and cetuximab. Cetuximab should be interrupted until the skin reaction has resolved to at least grade 2 In the case of severe superinfection, consider the use of i.v. antibiotics if unresponsive to oral antibiotics |
Mucositis arising from cetuximab/RT
Literature review and clinical experience
Systemic | Topical |
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1. Pain management | Diluting agentsb: Saline, bicarbonate rinses, frequent water rinses, dilute hydrogen peroxide rinses |
• Analgesics: WHO ladder | Topical anaestheticsb: Dyclonine HCl, xylocaine HCl, benzocaine HCl, diphenhydramine HCl |
• Adjuncts: Relaxation, imagery, biofeedback, hypnosis and transcutaneous electrical nerve stimulation | |
Analgesic agentsb: Benzydamine HCl | |
• Beta-carotene | |
Coating agentsc: Kaolin-pectin, aluminium chloride, aluminium hydroxide, magnesium hydroxide, hydroxypropyl cellulose, sucralfate | |
2. Radioprotectorsa | |
Lip Lubricantsc: Water-based lubricants, lanolin | |
• Amifostine: Scavenge free radicals | |
3. Biologic Response Modifiersa | |
• G-CSF, GM-CSF, Keratinocyte Growth Factor |
Discussion and recommendations based on clinical practice
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Patient-related risks: smoking, poor hygiene, clinical co-morbidities (such as diabetes, superadded candidal thrush).
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Tumour-related risks: site-related such as the oropharynx; tumours close to the midline are more related to mucositis than unilateral tumours.
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Treatment-related risks: radiation dose intensity, technique-related.
Grading of mucositis
Management of mucositis
Prevention
Grade 1 | Grade 2 | Grade 3 | Grade 4 |
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• Maintain oral hygiene | • Maintain oral hygiene | • Maintain oral hygiene | • Maintain oral hygiene |
• Frequent mouthwash use with agents like betadine, sodium bicarbonate | • Frequent mouthwash use with agents like betadine, sodium bicarbonate | • Frequent mouthwash use with agents like betadine, sodium bicarbonate | • Frequent mouthwash use with agents like betadine, sodium bicarbonate |
• Thymol and aspirin gargles/NSAIDs/local anesthetics for pain relief | |||
• NSAIDs/opioids/local anesthetics for pain relief | |||
• Thymol and aspirin gargles/ NSAIDs/local anesthetics for pain relief | • NSAIDs/opioids/local anesthetics for pain relief | • Systemic continuous use of steroidal therapy for mucositis prevention/therapy not recommended | |
• Parenteral nutrition used only if the bowel is not working or there are serious contra-indications to the placement of a device for enteral nutrition | |||
• Parenteral nutrition used only if the bowel is not working or there are serious contra-indications to the placement of a device for enteral nutrition | |||
• Stop radiation and cetuximab till the condition is resolved | |||
• Cetuximab dosing may be interrupted for a week or two, till the reaction has resolved to grade 2 |
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Physician and patient education for mucosal care.
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For prevention of mucositis, all experts recommended to follow the MASCC [28] guidelines in clinical practice. Adding saline and sodium bicarbonate rinses to the prevention guidelines was suggested. It was also mentioned that honey, used in some parts of the world, may be an effective and feasible option for preventing mucositis.
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Maintaining oral hygiene is of utmost importance in preventing mucositis. Frequent mouthwash use is also an important factor.
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Tobacco, betel nut-chewing, smoking etc. adds to irritability and hence should be avoided as a precautionary measure.
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Use of midline radiation blocks and three-dimensional radiation treatment to reduce mucosal injury is recommended.
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Chlorhexidine is not recommended for prevention of oral mucositis in patients with solid tumours of the head and neck and who are undergoing radiotherapy.
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Antimicrobial lozenges are not recommended for prevention of radiation-induced oral mucositis.
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Buccolingual guards, using hydroplastic material, can be easily oriented and adapted to an existing radiation stent, adding positional stability and patient comfort; with adequate thickness of material used, the guard can attenuate forward and back scatter radiation, separate the adjacent tissues from metal restorations, and protect the oral mucosa from localized incidents of mucositis [39].
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Patients are encouraged to sit upright at a 90° angle and lean their head slightly forward.
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Eat slowly. Food should be cut into small pieces and chewed completely.
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Eat small meals at frequent intervals instead of heavy meals.
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Food taken should be warm, or at room temperature. Hot food and drinks should be avoided. Similarly, crunchy foods such as potato chips and nuts should also be avoided.
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Soft food is always encouraged. Finely chopped cooked meat, fruits, and vegetables should be taken. Patients can also try commercial baby foods, which are nutritious, convenient, and very easy to swallow. Milkshakes that are very high in proteins can also be tried.
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Usage of straws will not only make drinking easy but will also avoid direct contact with the affected portion of the mouth.
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Do not talk while food is in the mouth.
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Acidic foods such as tomatoes, grapes, apple fruits or juices, alcohol and tobacco, and spicy foods should be avoided.
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To relieve the discomfort of dry mouth, patients are asked to rinse mouth with water before and after every meal.