Oral mucositis: History
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Subjects: Oncology | Dentistry, Oral Surgery & Medicine
Contributor:
Angel López-González

Oral mucositis (OM) is a common side effect of cancer therapies. It causes ulcerative, painful lesions in the oral cavity that can provoke malnutrition, increased risk of infection, longer hospital stays, and seriously affect the quality of life. Cooling the mucosa with oral cryotherapy (OC) during and/or after chemotherapy is the most accessible and tolerable intervention available. The aim of this study is to define the efficacy of OC for preventing OM induced by chemotherapy/radiotherapy in adult patients with cancer. Secondary endpoints include associated problems as pain

  • oral mucositis
  • patients’ cancer

1. Introduction

Oral mucositis (OM) is one of the most frequent complications suffered by patients affected by various types of cancer who are treated with chemotherapy, radiotherapy, or a combination of both. OM is defined as an alteration of the oral mucosa that causes inflammation and ulcerative lesions [1][2][3].

OM occurs in 20–40% of patients treated with conventional chemotherapy, in 80% of patients treated with high-dose chemotherapy prior to autologous bone marrow transplantation (HSCT), and even in almost all patients with head and neck cancer treated with radiotherapy combined with chemotherapy[1][2][3][4][5]. 

The physiopathogenesis of OM is a “cascade” process; the currently most accepted explanatory model describes it in five phases. In the first phase or “initiation phase”, cytotoxic agents or radiation cause DNA breakage of the epithelial basal cells, causing cell damage. This damage then leads to increased production of proinflammatory cytokines, which, in turn, induce cell death (transcription phase). At this point, the initial response to cell damage is magnified, and a positive feedback process is created in which more and more tissue is damaged (amplification phase). All this leads to the formation of ulcerative wounds and bacterial colonization, which overstimulates the inflammatory response, increasing the damage of the oral mucosa (ulceration phase). The process concludes in the healing phase after the treatment action is completed, the cells regenerate, and normal microbiota is restored[1][2][3][4][5][6].

The scale proposed by the WHO classifies it in five degrees: Grade 0, incipient and asymptomatic lesions; Grade I, oral soreness and erythema; Grade II, oral erythema, ulcers, solid diet tolerated; Grade III, oral ulcers, liquid diet only; Grade IV, oral alimentation impossible. On this scale, Grades III and IV correspond to severe OM[3].

The first manifestation of OM usually appears between the third and seventh day at the beginning of treatment; there is localized or generalized erythema, and this may be accompanied by stinging, the most affected tissues being the soft palate, the lateral edges of the tongue, the buccal mucosa, the tonsils, and the pharyngeal wall. In patients receiving chemotherapy for the treatment of solid tumors, OM may not progress to more severe stages due to the use of lower doses of chemotherapy/radiation. However, a large number of patients evolve and develop one or more ulcers, this being the period in which the patient experiences greater pain and discomfort. In the majority of those affected, it evolves into mucosal ulceration, this being the period in which the patient experiences the most pain and discomfort [7][8][9].

Severe OM is characterized by intense pain associated with ulcerative lesions as the main complication, originating a difficulty in feeding and a decrease in caloric contribution [2][6][7]. The inadequate nutrition will affect the immune system, and the ulcers are usually colonized by oral bacterial flora, very often by the herpes simplex and candida viruses. In patients who are immunosuppressed by chemotherapy, these lesions can be a route of entry for systemic infections, causing sepsis and potentially posing a danger to life [7]. It may become necessary to reduce and even suspend the doses of chemo/radiotherapy, with the worsening of the prognosis of the disease and the patient’s quality of life[6][7][10].

The main factors related to its appearance are related to the type and dose of cytostatic agents used. Regarding the type of agent, the most important are the antimetabolites (methotrexate, fluoronacil, cytarabine), which affect DNA synthesis and are associated with about 40–60% of OM incidences. In terms of dosage, it has been shown that the risk of suffering from OM increases with the intensity of the treatment, whatever the drugs chosen. Moreover, the planning of the cycles, their duration, the route of administration, localized radiotherapy in the head and neck, and the combination of chemo/radiotherapy are risk factors. Therefore, almost all patients who undergo an HSCT develop OM induced by the conditioning treatments[2][6][9].

Other possible factors such as age, type of tumor, poor oral health before and after treatment, malnutrition, alterations in the production and composition of saliva, and liver and kidney function could not be demonstrated in the appearance of OM [8][9].

The objectives of OM treatment are to prevent or reduce the severity of the lesions and to manage the associated symptoms, allowing the continuity of the cancer therapy[1][2].

The Multinational Association of Supportive Care and the International Society of Oral Oncology (MASC/ISOO) (Aurora, Ontario, Canada) have proposed, among the treatment methods for OM, basic oral care, application of growth factors and cytosines, anti-inflammatory agents, antimicrobials, protective agents, anesthetics and analgesics, laser and other phototherapies, natural agents and the application of oral cryotherapy (OC) [1][2][11].

OC consists of the local cooling of oral mucosal tissues using small pieces or sheets of ice, which, in the case of administration of chemotherapeutic agents, will produce vasoconstriction and decrease the distribution of the drug by the cells of the oral cavity. In the case of radiation therapy, the cold decreases the inflammation of the tissue reached by the radiation, which, in turn, reduces cell damage and prevents ulcerations[12][13][14].

OC is a normally well-tolerated intervention, with headache, tooth sensitivity, and numbness of the mouth being the most common side effects. In addition, it is the most accessible and efficient technique of all the proposals [15][16].

OM is one of the adverse effects of chemotherapy and radiotherapy that mostly worsens the quality of life of cancer patients in addition to increasing hospitalizations and financial expenses. There are many treatments that have tried to reduce both its incidence and its severity, including OC.

The present literature review confirms the benefits of OC in the control of OM produced as an adverse effect of chemotherapy treatment in cancer patients, as well as being cheaper, more accessible, and better tolerated by patients.

2. OC in OM Prevention

The effectiveness of OC was demonstrated in six of the articles, where the incidence and severity of OM were found to be significantly lower in the EG than in the CG, to which it was not applied [20][21][22][23][24][25][26][27]. Only one of them proposed the use of chlorhexidine rinses instead of OC to decrease the incidence of OM and to facilitate an oral diet[22]. In the remaining study, it was proposed to replace conventional ice with ice cubes made with chamomile infusion since the incidence of OM and the pain perceived by the patients in that EG were lower[21].

Additionally, the occurrence of severe OM was studied in five articles, and in all of them, a significant reduction was observed in the groups to which OM was applied, even to the point of never occurring [20][24][25][26][27].

2.1. Influence of OC on the Occurrence of Pain in Adult Cancer Patients Treated with Chemotherapy

Pain is a variable that was taken into account in six of the studies, measured based on the need for the use of opioids or through rating scales [20][21][22][23][24][25][27]. In the first case, Marchesi et al. and Chen et al. reported that the administration of opioid analgesics was significantly lower in the EG[20][27]; however, Batlle et al. found no difference between the EG and the CG[25]. In terms of direct pain assessment, in two of the articles, patients treated with OC expressed lower scores than those who were not[21][24]. Furthermore, in the study by Svanberg et al., it was observed that the association of OC + Caphosol® offered no additional effect on pain compared to using OC alone[23].
Finally, seven of the eight selected articles support the use of OC, including a camomile-infused variant, as an effective measure to decrease its incidence and severity[20][21][23][24][25][26][27]. Finally, in all of them, the treatment was well-tolerated in its great majority and was without adverse effects.

2.2. Strengths and Limitations

The present review presents some limitations, such as a sample that does not allow the generalization of the results found and the variability of the types of OC used.
Among the strengths is the recent research included (from the last 10 years), so the information is current. In addition, the results of the studies are similar, and the quality of all of them is high. Moreover, the great variability of the countries where the studies have been carried out provides a global vision.
Due to the scarcity of articles on the effect of OC in the prevention of OM and its main complications, such as pain, more research should be carried out with larger population samples to obtain conclusive data.

2.3. Implications for Clinical Practice

OC is an effective treatment to decrease the incidence of OM in patients receiving chemotherapy/radiotherapy. It is also effective in preventing the progression of more severe phases of ulceration.
OC decreases pain in patients with OM that has developed as a result of their cancer treatment with chemotherapy/radiotherapy.
It is a very safe therapeutic option due to the great tolerance of the patients and the scarcity of adverse effects, besides being a very cheap and affordable resource for any institution.

3. Conclusions

After analyzing the selected articles, we conclude that OC is an effective treatment to prevent the appearance of oral OM in patients who are being treated for cancer with chemotherapy/radiotherapy. OC application avoids the worsening of OM to a more serious phase of ulceration and alleviates its main symptom, pain.

OC is a therapeutic option that has been shown to be safe for patients, with a high tolerance level, given the scarcity of adverse effects. OC is a very economical resource that is affordable for any institution, showing itself as a highly efficient therapeutic option.

OM is a very widespread complication with a high impact on the quality of life of patients.

This entry is adapted from the peer-reviewed paper 10.3390/ijerph18030994

References

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  2. Lalla, R.V.; Saunders, D.P.; Peterson, D.E. Chemotherapy or radiation-induced oral mucositis. Dent. Clin. North Am. 2014, 58, 341–349.
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