Differences between the oral changes presented by patients with solid and hematologic tumors during the chemotherapeutic treatment

Objective: This study sought to identify the differences between the oral changes presented by patients with solid and hematologic tumors during chemotherapeutic treatment. Methodology: This is an observational, prospective and quantitative study using direct documentation by follow-up of 105 patients from 0 to 18 years using the modified Oral Assessment Guide (OAG). Of the 105 patients analyzed, 57 (54.3%) were boys with 7.3 years (±5.2) mean age. Hematologic neoplasms accounted for 51.4% of all cases. Results: Voice, lips, tongue, and saliva changes were not significantly different (p>0.05) between patients with solid or hematologic tumors and during the follow-up. From the 6 th until the 10 th week of chemotherapeutic treatment alterations in swallowing function, in the mucous membrane (buccal mucosa and palate), in the labial mucosa, and in the gingiva occurred and were distributed differently between the two tumors groups (p<0.05). The main alterations were observed in patients with hematologic tumors. Conclusion: It was concluded that the oral changes during the chemotherapeutic treatment occurred especially in swallowing function, in the mucous membrane, in the labial mucosa and in the gingiva, and these alterations were found mainly in patients with hematologic tumors.


Introduction
Cancer is one of the most significant public health problems, and its global incidence has increased by approximately 20.0% over the last decade, with a projected onset of 27 million new cases in 2030. 1 Pediatric cancers are rare when compared with those affecting adults, accounting for 1% to 3% of the malignant tumors worldwide. Although these tumors usually have brief latency periods and are aggressive and fast growing, they respond well to antineoplastic therapies, with positive prognoses and likelihoods of cure, provided they are diagnosed early. [2][3][4] Chemotherapy is involved in most treatments for pediatric cancers, 5 and acts on most types of tumors affecting children and adolescents via chemical agents that affect cell growth and division processes. 6 This effect causes changes throughout the gastrointestinal tract, given the cell renewal rate of cancer. Younger patients are more likely to be affected by chemotherapy in the oral cavity. 5 The main alterations include oral mucositis, xerostomia, dysgeusia, and difficulties in swallowing saliva and food. 5,7 Oral mucositis is one of the most common and important alterations in the lips and oral cavity, and when associated to xerostomia these are responsible for extremely debilitating conditions such as the painful inflammatory/ulcerative reaction of the oral mucosa, which stands out among these alterations.
From these changes, complications in oral functions also occur and patients may become unable to feed or communicate. Moreover, oral mucositis can spread throughout the gastrointestinal tract, 8,9 resulting in severe discomfort that can prevent these individuals from chewing, swallowing, and speaking. [10][11][12][13] Such ulcerations resulting from chemotherapy can cause intense pain and may require the use of is also significantly associated with oral candidosis lesions and HSV infection. 16 The tumor type is one of the factors that affect the occurrence, severity and duration of oral mucositis. 8

Data collection
Data collection was performed at the dental office of the Pediatrics Department and at the bedsides of inpatients. The evaluations were performed by a single and previously calibrated examiner (kappa=0.87), using artificial lighting to improve the visualization of the oral cavity.
The modified Oral Assessment Guide (OAG; Figure   1) was used for data collection. This guide evaluates the oral functions and structures according the degree of commitment, and is recognized by the scientific community for the evaluation of changes in the oral mucosa resulting from antineoplastic treatment using chemotherapeutic agents. This instrument evaluates 8 items according to the oral health impairment scale, scoring each item from 1 to 3, being: 1=normal conditions; 2=mild-to-moderate changes in epithelial integrity or function; and 3=severe impairment, with severe alterations to epithelial integrity or function. [17][18][19][20] The oral health conditions were monitored for 10 weeks from the start of chemotherapy because this period is critical for the onset of oral alterations resulting from chemotherapy. 19 The chemotherapeutic agent classes that were administered to patients in each week of treatment were also collected.

Data analysis
Descriptive and inferential statistics (association tests such as the Chi-square test with Yates's continuity correction) were applied to analyze the data using IBM SPSS 21.0 at 5% significance level.

Results
The mean age of the patients was 7.3 (±5.2) years, with a median of 7.3 years (range=0-18 years), with a higher concentration of malignant neoplasms at the Conversely, from the 6 th week of treatment onwards, the oral changes began to appear differently between the two groups of patients with different types of tumors. For the better presentation of these results, the differences verified will be described in the sequence these alterations were evaluated by the data collection instrument (OAG).
Regarding swallowing function, a significant difference (p=0.028) in impairment was assessed between the patients with solid and hematologic tumors on the 10 th week, with 3.9% of patients with solid tumors showing moderate impairments (e.g., swallowing difficulty) when compared with 9.3% of patients with hematologic tumors showing the more severe alteration (e.g., swallowing impossibility).
In mucous membrane (buccal mucosa and palate), On the 10 th week, a significant difference (p=0.040) was also found between the patient groups. Patients with solid tumors showed no changes, whereas 9.3% of the patients with hematologic tumors presented spontaneous gingiva bleeding. and miscellaneous products); 9 th week (82.0% when isolated and 100.0% in association to alkylating agents, natural and miscellaneous products); and in the 10 th week (81.1%).

Discussion
Oral changes caused by oral mucositis are the most significant comorbidities after the start of chemotherapy, [8][9][10][11] and based on the assumption that these manifestations may be different between groups of patients with solid and hematologic tumors, we conducted this study to evaluate this hypothesis, seeking to serve as a guide for decision making in oral health care for these patients.
According to previous studies, the incidence of oral complications resulting from chemotherapeutic treatments ranges from 30% to 100% in pediatric cancer patients, 7,20-22 thus, these children are a highrisk group for developing oral manifestations due to the high mitosis rates in the oral mucosa. 23 This study conducted a prospective evaluation of  especially in the labial mucosa. The concern with these patients becomes even greater because their hematologic malignancies compromise the immune system, disrupting its homeostasis. 25 In the 10 th week of evaluation, an additional concern arose because of the greater changes in swallowing among patients with solid disease. This oral ability is crucial for children and adolescents to reach the nutritional indices that support antineoplastic therapies. 27 Although worse swallowing impairments have been assessed among patients with solid tumors, moderate degrees of impairment might progress to greater functional impairments in patients with hematologic tumors, and according to our results, moderate alterations were more frequently found in patients with hematologic tumors; therefore, the oral care should be equally focused in both groups of neoplasms.
The differences found between the patient     Continued from previous page Differences between the oral changes presented by patients with solid and hematologic tumors during the chemotherapeutic treatment