In our cohort of children who had received anticancer therapies, 46% had at least one malformed tooth; and 13% had more than five malformed teeth. Defects in enamel development and alterations in tooth size were equally distributed among the patients (17%). Future dental aberrations may be predicted to some extent by understanding them within the context of the developmental stage of tooth mineralization in which they occurred20. In the current study, 62 teeth of 21 patients (17%) displayed some form of hypocalcification and hypoplasia. Several studies indicated higher rates of this dental alteration than observed in our cohort 9,21−29. Twenty-one patients (17.4%) in the current study displayed microdontia in contrast to 0.8%-1.7%20 in healthy populations. Microdontia causes esthetic, functional and occlusal complications, which require professional dental treatment later in life. Alterations of tooth root was the most frequent malformation found in the current study (21%) compared to 86.4% and even 100% in the literature20. This compares with a range of 1.3%-5.6% in healthy populations. As tooth development is a relatively slow process, up to two years may be necessary before anomalies become evident on radiographs. Intensive, repetitive chemotherapy at the time of initial hard tissue formation may cause tooth agenesis15,20, which is the most severe impairment in dental development. Agenesis affects dental arches, and impairs tooth symmetry, esthetics and function. Hypodontia was seen in 11% of our patients, which compares with 2.8%-10% in healthy populations28.
Associations of various anticancer therapies with the development of dental anomalies
Thirty-one percent of our patients who received chemotherapy were treated with radiation in addition. More than half the patients (53%) who received radiation displayed malformed teeth, a higher percent than among those who received only chemotherapy (43%). This difference concurs with a previous study27. Acute damage from chemotherapy seems to be greater when the treatment is combined with cranial irradiation or total body irradiation, rather than administered as a monotherapy13. Notably, among our 15 patients who had received head or neck radiation, the prevalence of dental anomalies was higher than among patients who had received chemotherapy alone, or total body irradiation. This finding concurs with other studies4,14.
Associations of chemotherapy agents with developing dental anomalies
Many pediatric cancers are treated with a combination of multi-agent chemotherapy to create synergistic and additive effects. In the current study, 46 patients (38%) had received a combination of three chemotherapy agents; the maximum combination treatment comprised six agents. Multiple agents make it difficult to attribute specific defects in odontogenesis to any single agent or therapy18, and the odontogenic toxicities induced by individual chemotherapy agents remain obscure29. Individual differences may also present between patients; the same treatment may result in a variable number of teeth affected and in differences in severity of lesions between individuals. The cohort size of the current study was small for evaluating the effects of individual chemotherapeutic agents on dental developmental defects. We suggest that more studies will investigate associations of chemotherapy agents, according to their mechanisms of action, with dental anomalies.
Associations of age and gender with developing dental anomalies
Malformed teeth of all the types examined presented more frequently among children who received anticancer treatment at age 6 years or younger than among older children. Young age also remained a significant factor for the total number of malformed teeth among patients who received chemotherapy only (P-value = 0.001). Several publications suggest that children diagnosed with cancer between ages 3 and 5.5 years exhibited the most severe developmental dental anomalies11,15,20,22,29. This is because in this age interval, root formation is at an initial stage for all permanent teeth except the second and third molars. Treatment administered during the first 3.5 years of life was more likely to affect the dental lamina and crown formation, and to result in a small tooth. Anticancer therapy administered after age 5 years may still disturb root growth, especially in late developing premolars and permanent second molars. However, by this age, the roots in the early developing teeth have already reached a moderate length, which improves the final result34. In several studies, the most extensive dental developmental anomalies (agenesis, microdontia and root anomalies) were reported in children who were treated before ages 5–6 years1,4,14,22,29, due to the proliferation of dental stem cells during this period1,2,25,29.
Only minor differences were found between boys and girls in the current study. Two significant differences regarding gender were noticed: microdontia was higher amongst females (P-value = 0.037) and decayed teeth were more prevalent amongst males (P-value = 0.025).
Dental Caries- DMFT
The mean DMFT score for the study group was 6.69. This score is much higher than 1.66, which was reported for healthy 12-year-old children in Israel. In the present study, the 'DT' component was the highest. Our findings concur with other reports of higher incidence of caries in children who received antineoplastic therapy 15,29,21. For our patients who received radiotherapy, the DMFT was even higher, 8.37; this compared to a score of 5.93 among children who received only chemotherapy. Aggressive and extensive caries, commonly known as radiation caries (such as seen in Fig. 1D), have a rapid onset and progression. Radiation caries are not caused directly by irradiation but result from the sequelae of xerostomia and a cariogenic shift in microflora. Ultimately, the carious process causes increased friability and the breakdown of teeth12.
Our study has several limitations that should be considered when interpreting the results. First, differences between the patients in age, time lapsed from diagnosis and from treatment, and the presentation of other chronic health conditions could create bias in the results. Second, family history, hygiene patterns, and socioeconomic status play crucial roles in dental health, and can affect many variables and especially DMFT score.
In conclusion, treatment of childhood cancer is a success story of modern medicine, in which effective treatments have been identified for previously untreatable diseases. The growing population of child survivors of cancer, as well as young adult survivors, will require considerable attention from the medical and dental community in the decades to come. The work of pediatric dentists and oncologists is not done when cancer cells are gone, for the subsequent years may present challenges that may be recognized only in a later context. Radiation and chemotherapy are independent risk factors for adverse oral-dental sequelae among childhood cancer survivors. Mitigating the effects should be a goal when possible; and if not possible, the effects should be understood so that future treatment can account for such. The results of this study may help direct physicians to identify childhood cancer survivors at high risk of having tooth developmental anomalies. This highlights the importance of dental care for children who received oncology treatment at a young age (0–6 years), particularly if combined with radiotherapy, and especially in the head or the neck region. Data from our study and previous ones support restrictions of high caloric food and sweets by children with cancer. Dentists should play a significant role in the team that manages childhood cancer and long-term follow-up.