Πολυχρονοπούλου Αργυρώ, Καθηγήτρια, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Καττάμης Αντώνης, Καθηγητής, Τμήμα Ιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Καββαδία Κατερίνα, Αναπληρώτρια Καθηγήτρια, Τμήμα Οδοντιατρικής, Πανεπιστήμιο Louisville, Kentucky, USA
Γκιζάνη Σωτηρία, Αναπληρώτρια Καθηγήτρια, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Παπαϊωάννου Βασίλης, Αναπληρωτής Καθηγητής, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Βάρδας Εμμανουήλ, Επίκουρος Καθηγητής, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Μητσέα Αναστασία, Επίκουρη Καθηγήτρια, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Early diagnosis and contemporary advanced cancer treatment modalities have increased the 5year survival rate of childhood cancer survivors. This increase is associated with a linear increase in the percentage of children (60-90%) that present with at least one late effect of the antineoplastic treatment (Oeffinger et al. 2006, Blaauwbroek et al. 2007). The effects on the teeth and the craniofacial complex are common, develop early and can interfere directly and indirectly with cranio-facial growth, and child's dental development (Effinger et al. 2014).
The most common dental effects that have been reported in the literature are increased caries experience, developmental defects of the size, shape and mineralization of the crown of the teeth (hypodontia, hypoplasia, microdontia), tooth agenesis, impaired or arrested root growth, bony defects (facial asymmetry, TMJ problems) and xerostomia (Dahllof 2008, Effinger et al. 2014, Gawade et al. 2014). The development and the extend of these defects depends on factors associated with both the disease and its treatment. Associated risk factors are age at diagnosis, type and duration of treatment, absorbed dose of therapeutic agents and the developmental stage of the tooth (Scully & Epstein 1996, Cheng et al. 2000).
Up to date, the available data on the literature are limited and report only the dental late effects without any association between specific characteristics of the treatment and the extend of the effects (Effinger et al. 2014, Gawade et al. 2014). Very few are also the reports that offer clear guidelines for screening of these patients with appropriate indices for the long term monitoring of the progression of the defects as well as the development of the craniofacial complex. Early diagnosis in association with appropriate knowledge of the defects and their evolution is necessary for effective treatment planning and counseling of the patient and their carer in order to improve their quality of life.
The study aimed to record the dental late effects of antineoplastic treatment in children treated for any type of malignancy early in life. The main objective was to record the crown and root defects in childhood cancer survivors over a 5-year post-treatment follow-up period.
Further objectives were:
a) to record and assess the oral health status of childhood cancer survivors
b) to record and assess their caries experience
c) to associate the above findings with disease and treatment specific characteristics in order to identify possible risk factors that can alter the development and the severity of the incidence of the defects.
d) to assess the late nature of the effect of antineoplastic treatment on major salivary glands through estimation of salivary flow rate and buffer capacity of childhood cancer survivors.
e) to associate salivary flow rate and buffer capacity with specific treatment and patient characteristics.
to associate subjective xerostomia, through a patient-reported xerostomia inventory, with clinically measured hyposalivation.
The present study is a retrospective cohort report of clinical and radiographic findings in children and adolescents diagnosed with any type of malignancy and treated with various protocols early in life. The sample derived from the Division of Pediatric Hematology-Oncology, First Department of Pediatrics (Medical School, National and Kapodistrian University of Athens). The research protocol was submitted and approved by the Ethics Committee of the School of Dentistry National and Kapodistrian University of Athens (N363, approved on 22/6/2018). All eligible patients who accepted to participate were thoroughly informed of the nature, potential risks and benefits of their participation and were asked (them or their legal guardians) to sign a written informed consent.
The sample consisted of 70 children and adolescents, with a history of malignancy, being in remission after antineoplastic treatment. Specific inclusion criteria were children and adolescent cancer survivors, aged 4-21 years old, with a history of malignancy presenting early in life, that have been treated with various protocols between ages 0-10 years and have completed antineoplastic treatment for at least 1year at the day of the examination.
Data were recorded in three different parts. In the first part, patients’ demographics and specific characteristics regarding disease and its treatment were collected by reviewing of medical records. In the second part, data regarding patients' dental history, oral hygiene and dietary habits were collected. A structured questionnaire in the form of an interview was completed by the patients or their legal guardians in cases of younger patients. The third part involved thorough clinical and radiographic examination. Clinical examination evaluated oral hygiene (OHI-s), periodontal status (CPI), caries experience at the cavitation level (DMFT using ICDAS rating), crown defects, dental occlusion and orthodontic treatment needed (IOTN). Radiographic examination included evaluation of changes in crown size (microdontia, macrodontia); tooth number (agenesis); root shape (tapered roots, blunted roots, thinning of the roots, taurodontia) and root development (impaired and arrested root growth). Finally, saliva sample was collected and stimulated salivary flow rate and salivary buffer capacity were measured.
The collected data were analyzed using the Statistical Package for Social Sciences (SPSS v. 17.0) and statistical signiﬁcance was set at p < 0.05. Initially, patients’ demographics and data regarding disease and treatment protocols were presented using frequency tables. Data regarding clinical findings were also presented using frequency tables followed by the incidence of each crown defects. Data analysis through chi-square and Kruskal-Wallis tests was used to associate the defects with disease and treatment-specific characteristics. Salivary variables were presented using charts and frequency tables. Univariate ordinal logistic regression analysis was performed to associate the dependent variables (salivary flow rate and buffer capacity) with the continuous independent variables (disease and treatment characteristics). Comparisons were also performed, to explore significant differences in gender, age at examination, caries status, radiation dose and site, and administration of different chemotherapeutic agents. Multivariate ordinal logistic regression analysis with backward elimination of nonsignificant predictors (deletion criterion p>0.05) was also performed to identify possible risk factors for the development of deviations in physiological salivary flow rate and buffer capacity of childhood cancer survivors. Regarding radiographic findings the cumulative incidence of each late dental defect was calculated. Data analysis through chi-square and Kruskal-Wallis tests was used to associate the defects with disease and treatment-specific characteristics. Univariate analysis was tested by chi-square test and Kruskal-Wallis to associate the defects with disease and treatment-specific characteristics. Statistically significant associations revealed the factors that increased the risk for the development of late dental defects. Multivariate regression analysis was used to record the association of severely abnormal disturbances and possible risk factors.
Of the 70 survivors who participated in the study, 32 were boys and 38 girls, with an average age at 11.2 years. Most participants were diagnosed with leukemia and the average age at diagnosis was 4.17 years. 71% had only undergone chemotherapy and the average time from completion of treatment to the day of examination was 5.48 years. Most participants were in mixed dentition, their oral hygiene was moderate, and they had calculus based on the corresponding periodontal index. The average value of the caries index was 1.65 for permanent teeth and 1.26 for primary teeth. The age distribution of the oral hygiene index was the same as that of the general population of the country, while people in the younger age groups had a better periodontal status. With regard to caries distribution, the results showed that in the younger age groups the number of decayed tooth was higher, while in the older age groups the number of filled teeth increased accordingly.
59% of the survivors experienced crown defects, with hypoplasia being the defect most frequently seen. Microdontia followed, while all other defects presented in ≤10%. In the age distribution of clinically recorded lesions it was characteristic that at younger ages the rate of caries was increased while in the older age groups the prevalence of crown lesions increased. High incidence of crown lesions is associated with the following factors: older age at examination, combination treatment protocols, high radiation dose (>50Gy) and high doses of administered cyclophosphamide.
Radiographic findings were more common with root defects presented in 62% of patients. The most common lesion with 57% was the incomplete root growth followed by the fused conical roots (44%). Arrested root growth, microdontia and narrow roots were recorded in 1/3 of the participants. Corresponding factors that increase the risk of developing lesions in the root were: older age at the examination, longer post-treatment periods, high doses of cyclophosphamide and administration of steroid drugs.
The results also recorded reduced mouth opening in the vast majority of survivors compared to the average maximum opening in the growth curves for children (50th percentile). The deviations recorded in both sexes and different age groups were statistically significant, underlining a trend towards reduced opening in survivors.
Regard stimulated salivary flow rate and its buffer capacity, it was found that 46% of participants had normal flow rate with only 5% very low. Similarly, 71% had high buffer capacity and only 4% low. Multivariate analysis showed that time since the end of antineoplastic treatment was the only risk factor for changing the qualitative and quantitative characteristics of saliva. Almost half of the survivors reported not feeling any of the symptoms of the dry mouth index, pointing out that there is no statistically significant correlation between objective and subjective perception.
The average dental age of patients was overestimated by almost 4 months compared to their chronological age. The distribution of the estimated difference was broad and ranged from an underestimation of 4.03 years to an overestimate of 2.54 years.
At least one lesion was recorded in 62% of patients. The average severity index was 17.46, with 28% of survivors showing severe defects. Multivariate analysis showed that patients diagnosed with leukemia, patients who have undergone a combination of anineoplastic treatment protocols, patients treated with cyclophosphamide and steroids, and patients for whom more time has elapsed since the end of treatment are more likely to experience severe dental defects.
In conclusion the percentage of patients who experience dental defects as a result of the disease and its treatment is large. It is evident that root defects occur more often and their effect is important in the longevity of affected teeth. It is clear that lesions occur in teeth that are under development during the treatment period with the severity of the effect being influenced by factors related to the disease and its treatment. However, the data to date do not allow conclusions to be drawn regarding the individual action of each antineoplastic drug in the cells under development as the effect of the combination action of the treatment regimens outweighs monotherapy.
We could therefore say that the role of the dentist in this special group of patients is important both for the timely and valid diagnosis of possible lesions and for the proper resolution of problems that arise as well as the information and guidance of patients. It should therefore be an integral part of the oncology team with the ultimate aim of optimizing the quality of life of these children.