From routine patient care to sophisticated clinical research settings, the importance of being able to describe precisely, classify objectively, and measure reproducibly the severity of mucosal damage cannot be overestimated. Ideally, a mucositis scoring system should be objective, validated, and reproducible across all clinical situations and applications. The scale should be sufficiently sensitive to measure appropriate parameters of the mucositis experience consistently across different treatment modalities, including cancer chemotherapy, radiotherapy, and chemoradiotherapy. It also should precisely measure elements associated with mucositis consistently (i.e., content validity). Minimal training should be necessary to produce systematic, accurate results, and the scale should be characterized by intrarater and interrater reliability. No scale established to date meets all these criteria or is accepted universally.
Because the need for mucositis measurement instruments has become more acute, a number of different scoring systems have been developed (Table 1).40–54 A few scales measure GI mucositis, but the majority of the scales measure oral mucositis. Oral mucositis scales range considerably in their complexity and have undergone varying degrees of validation.
Scoring of Oral Mucositis
The mucositis scales used most commonly were designed to define in global terms stomatotoxicity resulting from different cancer treatments. These tools are comprised of four-point or five-point scales that rate the overall status of the mouth relative to the clinically observed mucosal appearance, severity of patient pain, and, in some instances, the patient's functional capabilities relative to his or her oral status (e.g., the ability to eat). Historically, many of these simple, combined, variable toxicity scales have been based on a scale developed by the World Health Organization (WHO) for the clinical assessment of patients receiving cancer therapy. A number of similar scales have been developed and promoted as part of the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) scales, which are used frequently by cooperative oncology groups and oncology researchers (Table 1).
A second group of scales has evolved out of these simpler scales, and developed as nursing management and clinical research tools. These can be characterized as utilizing a combination of objective, functional, and symptomatic variables. Like the simpler toxicity scales, the oral mucositis scales combining objective, functional, and symptomatic descriptors apply them to specific anatomic areas, adding greater specificity with various aspects of oral function and subjective patient responses. A third series of scales, the detailed objective scoring scales, were designed for clinical research trials and tend to focus on directed, separately scored, objective and subjective end points (for a description of these scales, see Table 2).
Table 2. Comparison of Toxicity Grading of Oral Mucositis According to World Health Organization Criteria, National Cancer Institute—Common Toxicity Criteria, and Radiation Therapy Oncology Group Scales and Subscales
|WHO||Oral mucositis (stomatitis)||None||Oral soreness, erythema||Oral erythema, ulcers, solid diet tolerated||Oral ulcers, liquid diet only||Oral alimentation impossible||—|
|NCI-CTC||Chemotherapy-induced stomatitis/pharyngitis (oral/pharyngeal mucositis)||None||Painless ulcers, erythema, or mild soreness in the absence of lesions||Painful erythema, edema, or ulcers but eating or or swallowing possible||Painful erythema, edema, or ulcers requiring IV hydration||Severe ulceration or requiring parenteral or enteral nutritional support or prophylactic intubation||Death related to toxicity|
|NCI-CTC||Associated with HSCT (stomatitis/pharyngitis, oral/pharyngeal mucositis)||None||Painless ulcers, erythema, or mild soreness in the absence of lesions||Painful erythema, edema, or ulcers but swallowing possible||Painful erythema, edema, or ulcers preventing swallowing or requiring hydration or parenteral (or enteral) nutritional support||Severe ulceration requiring prophylactic intubation or resulting in documented aspiration pneumonia||Death related to toxicity|
|NCI-CTC||Mucositis due to radiation||None||Erythema of the mucosa||Patchy, pseudomembranous reaction (patches generally < 1.5 cm in greatest dimension and noncontiguous)||Pseudo-membranous reaction (contiguous patches generally > 1.5 cm in greatest dimension)||Ulceration and occasional bleeding not induced by minor trauma or abrasion||Death related to toxicity|
|RTOG||Acute oral mucous membrane toxicity caused by radiation||No change over baseline||Injection, may experience mild pain not requiring analgesic||Patchy mucositis that may produce inflammatory serosanguinitis discharge; may experience moderate pain requiring analgesia||Confluent, fibrinous mucositis, may include severe pain requiring narcotic||Ulceration, hemorrhage, or necrosis||—|
The most relevant scales for clinical management appear to be those based on NCI or WHO design. As noted earlier, symptoms, signs, and functional disturbances are assessed, and a global score is achieved readily. Analysis of approximately 400 trials, as a component of the evidence-based review for the clinical practice guidelines, determined that most of the studies utilized the NCI (43%) or WHO (38%) scales. Ten percent of studies employed a study-specific scale, and 5% used a cooperative group scale, such as scales used by the Radiation Therapy Oncology Group or the Eastern Cooperative Oncology Group (ECOG). Remaining scales, including the Stanford and Herzig scales, were used by < 0.5% of studies each.
Regardless of the scale used, increasing evidence confirms the importance of training and standardization to improving the accuracy and consistency of mucositis assessment. It is interesting to note that the clinical qualifications of the evaluator (M.D., D.M.D., R.N. degrees) appear to be less important, ultimately, than training and experience with using the scale.55
The frequency with which mucosal health needs to be assessed is a function of the objective of the examination. Whereas daily evaluations are of value for a nursing care plan, an intense, twice-weekly examination may be effective for an interventional study. In contrast, the success of a study in which mucositis duration is a primary endpoint may require daily evaluations.
Similar to other aspects of physical examination, sensitivity and accuracy are often a function of the conditions under which the examination takes place. Examination conditions are an issue of practicality—if the examiner cannot conduct an adequate visual inspection of the area to be examined, then results will be compromised. Adequate illumination of oral tissues is critical for an accurate assessment.
Halogen light sources can provide consistent intensity and color. In contrast, flashlights can vary significantly in intensity and may cast patterns based on the quality and type of light bulb, reflector, and lens. In addition, depending on bulb type (e.g., element and gas parameters), the color of light emitted from the flashlight can distort the color of the oral tissues and produce variable light intensity.
The convenience and comfort of both the examiner and the patient during the examination can influence the quality of the overall examination results. For example, whether the patient is being evaluated in a hospital bed, on a medical examination table, or in a dental chair may influence access and inspection of oral tissues.
Visualization of the oral cavity becomes compromised and, along with it, accuracy and reproducibility as a patient's medical condition deteriorates and/or as mucositis worsens. Oral debris, pseudomembranous candidiasis, and topical oral care therapies can obscure tissue conditions. If a patient requires orotracheal intubation, it becomes all but impossible to examine the entire oral cavity unless arrangements are made to examine the patient when tube care and retaping occur. At times, oral hemorrhage can compromise observation of oral tissues significantly.
Many scoring systems have not compensated for instances in which a patient cannot be examined because of these and other compromising situations—bleeding, pain, nausea, or emesis. Although, in some instances, the clinical situation may be a direct extension of the severity of the oral mucositis, whereas at other times it may be unrelated. Consideration must be given to these clinical parameters, especially if the scale is administered for research purposes and the assessment accuracy is paramount.
There is clear utility in separately scoring objective measures of mucosal damage and other variables related to oral mucositis (e.g., subjective variables such as pain and dryness and functional variables such as talking, swallowing, or ability to eat). Investigators have demonstrated that detailed oral mucositis scores, such as the Oral Mucositis Index and the Oral Mucositis Assessment Scale, correlate closely with oral mucositis pain scores.44, 56 Conversely, scoring of functional variables may not be correlated directly with oral mucosal events. For example, oral mucositis assessed with a scale such as the NCI-CTC scale may be rated Grade 4, which describes the patient as requiring “parenteral or enteral nutrition or support.” However, in the HSCT setting, many patients are placed on total parenteral nutrition because of intestinal toxicity; otherwise, they very well could continue with oral nutritional intake. Similar problems exist for the NCI-CTC Grade 3 oral toxicity category, in which the patient requires intravenous hydration. Consideration of how best to integrate these issues with the specific outcomes of the study should be determined during protocol design.
Scoring of GI Mucositis
Most of the available information regarding the incidence of GI toxicity relates to symptoms and functional changes. Making accurate evaluation of damage impossible are the problems of obtaining sequential biopsy before, during, and after treatment; the specimens' typically superficial nature; and the inaccessibility of important segments of the GI tract. With chemotherapy, 40–100% of patients experience GI mucositis, depending on the dose and type of chemotherapy.57 It is difficult to identify when the problem is based solely on symptoms: pain and diarrhea are universal and cannot be traced easily to the section of the GI tract that is affected (for a comparison of scoring systems used to assess GI tract mucositis, see Table 3).
Table 3. Grading Systems in Gastrointestinal Mucositis
|RTOG: Acute radiation morbidity scoring criteria|| || || || || |
| Pharynx and esophagus||No change over baseline||Mild dysphagia or odynophagia; may require topical anesthetic or nonnarcotic analgesis; may require soft diet||Moderate dysphagia or odynophadga; may require narcotic analgesics; may require purée or liquid diet||Severe dysphagia or odynophagia with dehydration or weight loss (> 15% from pretreatment baseline) requiring NG tube feeing and IV fluids or hyperalimentation||Complete obstruction, ulceration, perforation, fistula|
| Larynx||No change over baseline||Mild or intermittent hoarseness/though not requiring antitussive/erythema of mucosis||Persistent hoarseness but able to vocalize; referred ear pain, sore throat, patchy fibrinous exudates or mild arytenoid edema not requiring narcotics/cough requiring antitussive||Whispered speech, throat pain or referred ear pain requiring narcotic, confluent fibrinous exudate, marked arytenoid edema||Marked dyspnea, stridor, or hemoptysis with tracheostomy or intubation necessary|
| Upper GI tract||No change||Anorexia with ≤ 5% weight loss from pretreatment baseline, nausea not requiring antiemetics, abdominal discomfort not requiring parasympatholytis drugs or analgesics||Anorexia with ≤ 15% weight loss from pretreatment baseline, nausea and/or emesis requiring antemetics, abdominal pain requiring analgesics||Anorexia with > 15% weight loss from pretreatment baseline or requiring NG tube or parenteral support; nausea and/or emesis requiring tube or parenteral support; abdominal pain severe despite medication; hematemesis or melena; abdominal distention (flat-plate radiograph demonstrates distended bowel loops)||Ileus, subacute or acute obstruction, perforation. GI bleeding requiring transfusion, abdominal pain requiring tube decompression or bowel diversion|
| Lower GI tract, including pelvis||No change||Increased frequency or change in quality of bowel habits not requiring medication, rectal discomfort not requiring analgesics||Diarrhea requiring parasympatholytic drugs (e.g., Lomotil [diphenoxylate atropine]); mucous discharge not necessitating sanitary pads; rectal or abdominal pain requiring analgesics||Diarrhea requiring parenteral support, severe mucous or blood discharge necessitating sanitary pads, abdominal distention (flat-plate radiograph demonstrates distended bowel loops)||Acute or subacute obstruction, fistula or perforation, GI bleeding requiring transfusion; abdominal pain or tenesmus requiring tube decompression or bowel diversion|
|RTOG chronic toxicity: GI tract|| || || || || |
| Nausea||None||Able to eat, reasonable intake||Intake significantly decreased, but patient can eat||No significant intake||—|
| Emesis||None||One episode in 24 hrs||Two to 5 episodes in 24 hrs||Six to 10 episodes in 24 hrs||Greater than 10 episodes in 24 hrs or requiring parenteral support|
| Diarrhea||None||Increase of 2 to 3 stools per day over pretreatment level||Increase of 4 to 6 stools per day, nocturnal stools, or moderate cramping||Increase of 7 to 9 stools per day or incontinence or severe cramping||Increase of ≥ 10 stools per day or macroscopically bloody diarrhea, or need for parenteral support|
|RTOG-EORTC: Late radiation morbidity scoring system|| || || || || |
| Esophagus||None||Mild fibrosis, slight difficulty in swallowing solids, no pain on swallowing||Unable to take solid food normally, swallowing semisolid food, dilatation may be indicated||Severe fibrosis, able to swallow only liquids, may have pain on swallowing, dilatation required||Necrosis, perforation, fistula|
| Small/large intestine||None||Mild diarrhea, mild cramping, bowel movement 5 times daily, slight rectal discharge or bleeding||Moderate diarrhea and colic, bowel movement > 5 times daily, excessive rectal mucus or intermittent bleeding||Obstruction or bleeding requiring surgery||Necrosis, perforation, fistula|
| Emesis episodes/24 hr||—||1||2–5||6–10||> 10 or parenteral support|
| Diarrhea (increased frequency over normal)||—||2–3||4–6 or nocturnal||7–9 or incontinence or severe cramping||> 9, macroscopic blood, enteral support|