*Katarzyna Olszewska, Maria Mielnik-Błaszczak
Assessment of the prevalence of oral mucositis in children undergoing antineoplastic therapy
Ocena częstości występowania mucositis w jamie ustnej u dzieci w trakcie leczenia przeciwnowotworowego
Department of Paediatric Dentistry, Medical University of Lublin
Head of Department: Professor Maria Mielnik-Błaszczak, DMD, PhD
Streszczenie
Wstęp. Mucositis jest najczęstszym powikłaniem cytotoksycznego leczenia przeciwnowotworowego obserwowanym w jamie ustnej.
Cel pracy. Ocena częstości występowania zmian o charakterze mucositis w jamie ustnej u dzieci w trakcie leczenia przeciwnowotworowego.
Materiał i metody. Do grupy badanej zakwalifikowano 52 dzieci w wieku 3-17,5 roku (średni wiek: 7,83 ± 3,86) z rozpoznaną chorobą nowotworową, będących w trakcie leczenia przeciwnowotworowego, w tym 37 pacjentów z nowotworami układu krwiotwórczego oraz 15 pacjentów z guzami litymi. Pacjenci badani byli trzykrotnie w trakcie terapii. Pierwsze badanie przeprowadzano w okresie 7 dni od rozpoczęcia cyklu chemioterapii (T1), drugie badanie – 7-21 dni od rozpoczęcia leczenia (T2), trzecie badanie w okresie 21-30 dni od rozpoczęcia cyklu chemioterapii (T3). Do oceny zmian o charakterze mucositis użyto pięciostopniowej skali zaproponowanej przez WHO. Wyniki badań poddano analizie statystycznej z wykorzystaniem programu STATISTICA 10.
Wyniki. Zmiany o charakterze mucositis stwierdzono u 17,31% dzieci w badaniu (T1), u 48,08% w badaniu 2 (T2) i u 40,39% w badaniu 3 (T3). Analiza statystyczna wykazała największą intensywność zmian mucositis w okresie T2. Ponadto stwierdzono istotnie częstsze występowanie zmian o charakterze mucositis u dzieci z nowotworami hematologicznymi niż u dzieci z guzami litymi (p < 0,05).
Wnioski. Na podstawie badań własnych popartych doniesieniami z piśmiennictwa stwierdzono, że zmiany o charakterze mucositis są bardzo częstym powikłaniem terapii przeciwnowotworowej stwierdzanym w jamie ustnej u dzieci. Mucositis zwiększa ryzyko bakteriemii, posocznicy, infekcji systemowych. Dzieci z chorobą nowotworową powinny być objęte specjalistyczną opieką stomatologiczną przez cały okres leczenia przeciwnowotworowego przy ścisłej współpracy lekarzy stomatologów z zespołem lekarzy hematologów i onkologów dziecięcych.
Summary
Introduction. Mucositis is the most common side-effect of cytotoxic antineoplastic treatment observed in the oral cavity.
Aim. To assess the prevalence of oral mucositis in children undergoing antineoplastic therapy.
Material and methods. The study group comprised 52 children aged 3-17.5 years (mean age: 7.83 ± 3.86) diagnosed with cancer receiving antineoplastic treatment, including 37 patients with haematologic malignancies and 15 patients with solid tumours. The patients were examined three times during chemotherapy. The first examination was performed within 7 days after the onset of therapy (T1), the second one was performed between day 7 and 21 of treatment (T2), and the third examination was performed between day 21 and 30 of therapy (T3). The evaluation of oral mucositis lesions was performed with the use of the WHO classification. The data were subjected to statistical analysis by STATISTICA 10.
Results. Oral mucositis was observed in 17.31% of the patients in T1, 48.08% of the children in T2, and in 40.39% of the patients in T3. Statistical analysis revealed the highest incidence of oral mucositis lesions in T2. Moreover, significantly higher prevalence of oral mucositis in children with haematologic malignancies than in children with solid tumours was registered (p < 0.05).
Conclusions. Based on the study results and the available literature, oral mucositis has been confirmed as a very frequent complication of antineoplastic therapy observed in children, increasing the risk of bacteraemia, sepsis or systemic infections. During the entire course of anticancer therapy, paediatric patients should be provided with specialist dental care in close cooperation with paediatric haematologists and oncologists.
Introduction
In developing countries the prevalence of cancer in children under 15 years old is approximately 0.5-1.5% of all cancer cases. According to current statistics, in Europe it ranges from 130:1 000 000 in the UK to 160:1 000 000 in Sweden. In Poland, 1100-1200 cases of cancer in children and adolescents under 17 years old are noted every year (1, 2). The primary goal of cancer therapy in children is obtaining permanent remission and recovery. At present, many paediatric cancers have become treatable. For most paediatric cancers curability exceeds 80%, amounting to 90% for some types (3). In nearly all paediatric cancers it was only the advent of chemotherapy that facilitated treatment success, i.e. complete and permanent elimination of all neoplastic cells from the patient’s system. Factors that limit this treatment modality are, however, toxicity and resistance. Owing to the antiproliferative mechanism of action of cytotoxic agents, the tissues and organs most affected by their toxicity are the ones where cells divide the most. Hence, leucopenia, neutropenia, thrombocytopenia, anemia, mucositis, diarrhea, nausea, vomiting, and hair loss are among the most common adverse effects of chemotherapy.
As for the oral cavity, the most frequent complication tends to be mucositis, which affects 30-70% of patients treated with cytostatic drugs and 60-100% of patients treated with hematopoietic stem cell transplantation (HSCT), and is a result of myeloablative chemotherapy. The term “mucositis” refers to lesions of the oral mucosa, involving damage of the epithelium as a result of chemo- or radiotherapy. Mucosal barrier injury (MBI) is a more precise term that is now in common use. Inflammatory lesions may be situated within the oral cavity, whereby they are known as oral MBI (OMBI) or in further portions of the alimentary tract. OMBI presents with pain, swelling, presence of pseudomembrane, increased mucus production, decreased saliva production, and bleeding. Patients are most symptomatic when their granulocyte count is at its lowest, with lesions gradually resolving as it rises again. Hence, the severity of oral lesions reflects the level of neutropenia. Cytostatic agents of highest toxicity for the mucosa include anthracyclines, etoposide, busulfan, cytarabine, methotrexate, fluorouracil, dactinomycin, chlormethine, vinblastine and melphalan (4-7).
The aetiology of mucositis is multifactorial and complex. During antineoplastic therapy, the injured oral epithelial cells do not regenerate in time, leading to erosions and ulceration of the oral mucosa which then become an open gateway for endo- and exogenic pathogens. A hypothetical 5-stage pathologic model of mucositis was developed by Sonis, who identified the following phases: initiation, over-sensitivity, amplification, ulceration and healing. Clinically visible ulceration in the mouth means that mucositis has transitioned to its phase 4 where microorganisms present in the oral cavity amplify the mutotoxic process, posing a serious risk for the patient whose immune response is down due to cytostatic therapy. Sonis came up also with a 4-stage morphological model of mucositis, dividing it into vascular-inflammatory, epithelial, bacterial-erosive, and healing phase (8, 9).
There risk factors for OMBI comprise multiple aspects. Its course is affected by the patient’s age and sex, weight, use of stimulants, oral health status, activity of salivary glands, but also genetic predisposition. The risk factors associated directly with therapy include the type of drugs received, dosage, other medication, type of transplant, or the radiation site (4-9).
Aim
The study was aimed at the evaluation of the prevalence of oral mucositis in paediatric patients treated for cancer.
Material and methods
A total of 52 children were enrolled for the study, aged 3-17.5 years, diagnosed with a neoplastic disease, and currently receiving antineoplastic therapy at the Hematology, Oncology and Paediatric Transplantology Clinic. The group comprised 22 girls and 30 boys. The mean age was 7.83 ± 3.86. 37 of the patients had haematologic malignancies and 15 had solid tumours. Treatment was according to the guidelines of the Polish Paediatric Group for Treatment of Leukaemia and Lymphomas and the Polish Paediatric Group for Treatment of Solid Tumours. The patients were evaluated 3 times during their hospitalization. The first examination took place within the initial 7 days since chemotherapy onset (T1), the second on day 7-21 (T2), and the third (T3) – on day 21-30. The oral mucosa was evaluated in clinical examination to screen for mucositis lesions. A 5-grade WHO scale was used to evaluate the mucosa:
0 – no pathological lesions of the oral mucosa,
1 – redness, erythema, soreness,
2 – erythema, erosions, soreness, solid diet tolerated,
3 – extensive erythema, ulcerations, acute pain, liquid diet only,
4 – symptoms of severe inflammation, oral alimentation not possible, parenteral feeding necessary.
The study was approved by the Bioethics Committee of the Medical University in Lublin.
The results have been subjected to statistical analysis using STATISTICA 10 software (StatSoft Inc., Tulsa, USA). Friedman ANOVA test was applied to compare the results of evaluation at different times (T1, T2, T3). Mann-Whitney U-test was used to compare the prevalence of mucositis in two independent groups, e.g. the group of patients with haematologic malignancies and the group of patients with solid tumours. P < 0.05 was assumed as significance threshold.
Results
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