Journal of Pharmacy and Pharmacology 10 (2022) 288-293

doi: 10.17265/2328-2150/2022.11.002
D DAVID PUBLISHING

The Influence of Oncological Treatment on Tooth

Agenesis in Adult Patients after Childhood
Chemotherapy and Radiotherapy

Natalia Kazimierczak1, Wojciech Kazimierczak1,2 and Ewa Ziolkowska3

1. Heliodent Private Dental Practice, Bydgoszcz, Poland
2. Department of Radiology, Nicolaus Copernicus University in Torun, Poland
3. State University of Applied Sciences in Kalisz, Nowy Swiat 4, 62-800 Kalisz, Poland

Abstract: Malignant neoplasms are one of the main causes of death in developed countries. Thanks to the multidisciplinary approach
and treatments methods (surgical treatment, chemotherapy, radiotherapy) in pediatric oncology, the number of cancer survivors
among children is growing. The high survival rate obliges the medical community to monitor the long-term consequences of both the
cancer disease and the anticancer treatment used. The incidence and type of complications in oncological treatment vary. Their
presence and severity depend on the child‟s age, the nature of the malignant neoplasm, as well as the specificity and intensity of
therapy. Frequent complications of treatment may include serious maxillofacial defects resulting from developmental disorders of
bones, soft tissues and teeth. One of the dental complications of both radio- and chemotherapy is tooth agenesis. In this manuscript,
we highlight the dental complications of oncological treatment and the need of an interdisciplinary approach in dealing with them.

Key words: Dental complications, dental management, hypodontia, malignant neoplasm.

1. Introduction monitor the long-term consequences of both the

cancer disease and the anticancer treatment used.
Malignant neoplasms, after injuries and poisoning
The incidence and type of complications in
as well as congenital and developmental defects, are
oncological therapy vary. Their presence and severity
one of the main causes of death in children in
depend on the child's age, the nature of the malignant
developed countries [1]. Most of these neoplasms are
neoplasm, as well as the specificity and intensity of
cancers of the central nervous system (CNS) and
therapy. In the case of recovery from a malignant
leukemias. In recent years, the development of
tumor, oncological therapy has a significant impact on
pediatric oncology has resulted in a steadily increasing
the general health and quality of life of the patient [4,
number of cured patients [2]. This is due to the
5]. Frequent complications of treatment may include
improved availability of various treatment options [3].
Nowadays, the 5-year survival rate among children endocrine disorders (e.g. growth disorders,
with cancer is as high as 80–85% [2]. This translates hypothyroidism, infertility) [4], as well as sensory
into a growing population of cancer survivors. The impairment, problems with education and
high survival rate obliges the medical community to interpersonal relations [3]. Late complications may
also occur in the form of serious maxillofacial defects
Corresponding author: Wojciech Kazimierczak, Dr, resulting from developmental disorders of bones, soft
research fields: radiotheraphy, oncology, dentistry. Email:
[email protected]. tissues and teeth [6].
 The Influence of Oncological Treatment on Tooth Agenesis in Adult Patients after Childhood 289
Chemotherapy and Radiotherapy

2. Discussion lateral incisors of the maxilla, mandibular second

premolars and maxillary second premolars [13-15].
2.1 The Histological Development of the Tooth and
Dental Disorders of an Agenesis Nature 2.2 Effect of Chemotherapy and Radiotherapy on
Tooth Tissues
During the stages of shaping of the deciduous and
permanent tooth in prenatal life, and subsequently In the case of radiotherapy of the head and neck
after birth, the germs first increase in volume. In the region in pediatric oncology, complications are
following stage, their cells differentiate to form associated with damage to organs and cells due to
enamel, dentin, pulp and periodontium. Enamel and radiation [16]. Cell damage occurs in two ways: direct
dentin are formed from two tissue types, epithelial and (the so-called shield effect), through ionization of cell
ectodermal, which interact with each other. There are components, e.g. a collision of a radiation particle
four developmental stages of the permanent tooth: with the DNA strand, and indirect, as a result of the
dental plate, bud, cap and bell. Permanent teeth are interaction of water radiolysis products (free radicals)
formed from a secondary lingual dental lamina, in the in the cell nucleus containing DNA. This may result in
second row behind deciduous teeth, which arise from the disturbance of the normal cell cycle, especially of
the primary lamina. Their mineralization takes place cells with increased mitotic activity. The proportion
in strictly defined periods. Among permanent teeth, between the direct and indirect effects of radiation on
incisors, canines and premolars are initially formed. DNA depends on the type of radiation. In the case of
This happens between the 20th week of gestation and radiation with a low density of ionization, e.g. X-rays,
the 10th month after birth. The first molars are formed 70–90% of DNA damage is caused by indirect action.
in the 20th week of fetal life; the third molars are With a high density of ionization, caused by neutrons,
formed at the age of 5 years [7]. protons and alpha particles, over 90% of damage to
One of the most common dental disorders in adult DNA is of direct nature [17].
patients with a history of pediatric oncological Radiotherapy of the developing tissues of the head
treatments is tooth agenesis, i.e. the absence of one or and neck causes osteocyte death, microangiopathies,
more tooth buds. Depending on the number of missing periosteal damage, marrow fibrosis and tissue
teeth, three types of defect are distinguished: hypoplasia [3]. The degree of damage depends on the
hypodontics, oligodontics and anodontics [8]. Authors radiation dose, the patient's age and the type of
of the available publications use different definitions irradiated tissues. The affected structures include skin
of the above anomalies. Nodal [9] and Sarnäs [10] tissues, mucous membranes, subcutaneous tissue,
claim that the basis for the diagnosis of oligodontics is bones, muscles and salivary glands. Vascular damage
the lack of 4 or more teeth (except wisdom teeth). plays a key role, which reduces the viability of
Sarnas [10] and Schalk van der Weide [11] indicate irradiated tissues. In the course of radiotherapy,
that only the absence of 6 or more teeth allows the irradiation of normal tissues and the secondary
diagnosis of oligodontics. A condition involving fewer presence of radiation reaction are inevitable.
missing teeth is defined as hypodontics. Anodontics, Abnormal tooth development caused by
i.e. the complete absence of tooth buds, is rarely radiotherapy and/or chemotherapy causes disturbances
observed [12]. According to the latest scientific in amelogenesis (enamel formation), dentinogenesis
reports, dental agenesis not related to chemotherapy (dentin formation) and cementogenesis (formation of
and/or radiotherapy most often affects the third molars, dental cement) [18]. Animal studies have shown that a
290 The Influence of Oncological Treatment on Tooth Agenesis in Adult Patients after Childhood
Chemotherapy and Radiotherapy

dose of 2 to 50 Gy can cause dental anomalies [18]. chemotherapy on the development of dental disorders.
The minimum dose that can produce such effects in A study by Gawade et al [21] showed that people who
humans is not known; however, there are studies that were treated with radiotherapy and chemotherapy or
have confirmed the effect of a 4 Gy dose on late hematopoietic cell transplantation in childhood
dental abnormalities. Lindvall et al [18] revealed that showed an increased tendency for dental caries and
even the smallest regular dose of radiation causes developmental dental disorders in the oral cavity.
changes in enamel, but rarely in dentin. The Kaste et al [22] analyzed pantomograms of patients
amelogenesis process is more radiosensitive than who received oncological treatment for
dentinogenesis. In addition, it has been found that rhabdomyosarcoma (RMS) of the head and neck in
with an appropriate dose of radiation, odontoblasts childhood. The authors showed that as many as 77%
(dentinogenic cells) die regardless of the phase of the of people in the studied group developed dental
cell cycle [3]. For radiotherapy, it has been confirmed disorders in adulthood. In addition, they confirmed
that enamel always shows morphological that chemotherapy for malignant tumors alone can
abnormalities, regardless of the dose used in the induce dental disorders as well.
oncological treatment. In the case of dentin, the There is agreement in the literature as to the
radiation dose plays a significant role, i.e. the higher influence of the patient's age on the degree of dental
the dose, the higher the level of irreversible disorders [23-25]. The study by Owosho et al [26]
morphological disorders. Additionally, after confirmed the significant effect of radiochemotherapy
radiotherapy, the time of formation of enamel (from on tooth and craniofacial development disorders in
preameloblasts) and, to some extent, dentin (from pediatric patients treated for RMS. As a complication
preodontoblasts), is significantly longer compared of the therapy, 9 out of 13 patients developed
with non-irradiated dental tissues [18]. In patients, the secondary craniofacial disorders. Significantly, all of
therapeutic dose is estimated individually. Exposure these patients were under the age of 7 years. Trismus
of the oral cavity and dentition of a child aged < 5 and xerostomia were the dominant abnormalities in
years to an irradiation dose equal to or greater than 20 older children.
Gy is associated with an increased risk of dental It is worth noting that in children who have
disorders [3]. The risk of dental disorders in patients undergone aggressive oncological treatment, the lack
who received head and neck radiotherapy was higher of a tooth rarely appears as a single anomaly, more
in a statistically significant manner than in patients often it is one of many disorders in the oral cavity. A
who were treated only with chemotherapy [6]. The use large follow-up study published by Kaste et al [6],
of radiotherapy causes qualitative and quantitative which included 9,308 patients treated for malignant
disturbances in enamel and dentin, unlike tumors in childhood, showed a significant effect of
chemotherapy, which results only in a qualitative oncological therapy on dental development disorders
disturbance [18, 19]. Chemotherapy is a treatment in this group of patients compared with their healthy
method that targets rapidly dividing cancer cells. siblings. Among many different correlations, that
Ameloblasts (cells that create enamel) and between the treatment history of malignant neoplasms
odontoblasts (cells responsible for the formation of and the occurrence of agenesis was confirmed, with
dentin) are the most sensitive to cytostatics during the odds ratio (OR) of 1.7 (95% confidence interval
tooth formation [20]. [CI], 1.4–2.0) in the case of hypodontics. The
There are a number of independent studies that researchers also showed the effect of the total dose of
show a significant effect of radiotherapy and radiotherapy on the degree of disorders. It was noted
 The Influence of Oncological Treatment on Tooth Agenesis in Adult Patients after Childhood 291
Chemotherapy and Radiotherapy

that more serious side effects were seen in patients chemotherapy alone, dental redundancy may occur as
treated with higher doses of radiotherapy. It was well [3].
proven that the risk of developing at least one dental
2.3 Dental Treatment
abnormality (hypodontia, microdontia, enamel
hypoplasia, root development disorder, more than 6 In patients with tooth agenesis after radio- and/or
missing teeth) is related to the dose of radiotherapy in chemotherapy in childhood, a common symptom is
patients undergoing radiotherapy in the mandibular unsatisfactory smile esthetics. It is this symptom that
area compared with the group of patients treated with usually prompts the patient to visit the dentist. Visual
radiochemotherapy without irradiating the mandible. defects in the form of gaps, reduced circumference of
When a 0–20 Gy dose was used, there was a the dental arch as well as rotations, migrations or other
significant increase in the risk of the above-mentioned displacement of teeth [28], which disturb the harmony
disorders – OR: 1.3; 95% CI 1.2–1.5 – compared with of the smile, are often noticeable. The above
the control group. For doses > 20 Gy, the correlation abnormality is most often diagnosed at the age of
was much stronger – OR: 5.6; 95% CI: 3.7–8.5. 6–12 years. Dental examination of a patient who
Radiochemotherapy during childhood causes a reports this problem should be based on the
number of complex developmental anomalies in the assessment of functionality, aesthetics and periodontal
structure of the oral cavity. The lack of dental buds condition. In order to plan comprehensive dental
may coexist with bone and soft tissue disorders and therapy, thorough diagnostics should be performed.
other dental abnormalities. The most common bone Precise analysis should be based on the systematic
defects include delays in bone development (facial collection of information based on the medical history
asymmetry, hypoplasia) and impaired repair processes (including the patient's age, specificity and intensity of
of bone cells. Soft tissue disorders include, among oncological treatment) and dental interviews, thorough
other, reduced salivation (sialopenia), which develops intra- and extraoral examination, careful radiography
indirectly, through reduced salivation due to the [28] and intra- and extraoral photography [29]. The
atrophy of receptors located on the surface of the basic diagnostic tool used to diagnose hypodontia,
tongue, and directly, through damage to the cells of oligodontia or anodontics is pantomographic X-ray.
the salivary glands. The result is dryness (xerostomia) The diagnosis of agenesis requires the confirmation of
and recurrent stomatitis and tooth decay. Other soft the absence of calcified substances in the tooth in the
tissue abnormalities are trismus, dysgeusia (most often pantomogram and the absence of evidence of tooth
a lack of taste due to the destruction of taste buds), extraction in a clinical examination, as well as
severe inflammation or necrosis of soft tissues, scar interview obtained from the patient [30]. For a broader
tissue formation and facial deformity [6]. The effect of assessment, a cephalometric image aimed at the apical
radiotherapy on the reduction of the mobility of the area, as well as Cone Beam Computed Tomography
temporomandibular joint has also been confirmed [27]. (CBCT) can be used [14, 28].
The developmental anomalies coexisting with Most studies emphasize that dental treatment
agenesis after radiotherapy and chemotherapy include: should be interdisciplinary, conducted in consultation
enamel/dentin hypoplasia, anatomical loss/thinning or with an orthodontist, prosthetist, dental surgeon,
stunting of the root, premature loss of teeth due to periodontist and pediatrician [14, 29, 31-33].
caries, microdontics, taurodontism, delayed loss of Treatment of systemic defects following oncological
deciduous teeth and/or decay of permanent teeth and therapy, in which dental agenesis is one of several
malocclusion [6]. In the case of treatment with comorbid complications, should involve physicians of
292 The Influence of Oncological Treatment on Tooth Agenesis in Adult Patients after Childhood
Chemotherapy and Radiotherapy

other specialties, such as a pediatrician, hematologist, and/or chemotherapy in childhood should be

oncologist, endocrinologist, ophthalmologist, comprehensive and always individualized [31]. For
cardiologist, otolaryngologist and psychiatrist. When this reason, physicians in charge of treatment and
dental diagnostics requires precise measurements from monitoring of minor patients should inform their
CBCT, a radiologist should participate in the parents about the possible dental complications, and in
treatment as well [14]. Regardless of the choice of the event of disturbing symptoms, refer the child to
treatment method, the team of the above-mentioned competent specialists at reference centers.
physicians must be in perfect communication, because
Conflict of Interest
it translates into the future outcome of treatment [33].
It is very important that the dental effect achieved The authors declare no conflict of interest.
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