Clinical Article CROSS-SECTIONAL

530 ANTI CANCER THERAPY AND ECTOPI C ERUPTI ON

PEDI ATRI C DENTI STRY V 35
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Effect of Anticancer Therapy on Ectopic Eruption of Permanent First Molars
Yoonsik Ko, DDS
1

Kitae Park, DDS, PhD
2

Ji-Yeon Kim, DDS, PhD
3

In recent years, advances in the treatment of childhood cancer
have led to long-term cures and a high survival rate.
1,2
As the
number of pediatric cancer survivors increases, however, so does
the incidence of delayed adverse efects of anticancer treatment.
Tese adverse efects include damage to the gonadal, pulmonary,
cardiac, and nervous systems.
3
Given that developing odontogenic
cells are susceptible to chemotherapeutic agents, dental defects
can potentially occur, such as arrested root development, inhibition
of dentine formation, and enamel defects.
4
An increase in the
prevalence of dental caries and deterioration of jaw development
have also been described.
5-8
Developmental disturbances may also
result in complicated tooth eruption disorders, such as ectopic
eruption (defned as a tooth erupting in an abnormal position),
which is most frequently observed in the permanent frst molars
(PFMs); (Figure 1).
9
The prevalence of ectopic eruption of PFMs is between
two percent and six percent.
10
Two thirds of ectopically erupting
PFMs, however, correct spontaneously from a locked position and
erupt into occlusion. Otherwise, PFMs can cause exfoliation of
primary second molars, which may result in mesial migration of
the PFMs. This provokes a decrease in arch length and delays
the eruption of the permanent second premolar.
11
Therefore,
early diagnosis and treatment precludes more complicated ortho-
dontic problems later in life.
The causes of ectopic eruption of the PFMs are not well
known.
11,12
Te disturbance of bone growth and delayed calcif-
cation, however, may afect their eruption.
11
In patients receiving
anticancer therapy, developmental disturbance of the teeth and
jaw may infuence ectopic eruption of PFMs. Yet, there currently
is no method of quantitative analysis of the relationship between
anticancer therapy and ectopic eruption of PFMs.
Te purpose of this study was to investigate the association
between anticancer therapy and ectopic eruption of permanent
frst molars.
Methods
Tis study was reviewed and approved by the Institutional Review
Board of Samsung Medical Center, Seoul, South Korea. Tis study
evaluated patients who had visited the Department of Pediatric
Dentistry at Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, between October 1, 2009 and Sep-
tember 30, 2010. A total of 601 fve- to seven-year-olds who had
radiographs taken during this period were initially enrolled.
One investigator analyzed electronic medical records (EMRs)
and radiographs, including bitewing, periapical, and panoramic
radiographs. Trough EMRs, cases of ectopic eruption were diag-
nosed, and the history of ectopic correction was investigated. From
radiographs, the root resorption of the primary second molar and
the position of the PFMs were investigated.
Patients who received anticancer drugssuch as cortico-
steroids for nonmalignant diseases, including hemangioma and
idiopathic thrombocytopenic purpurawere excluded from the
study. Patients whose radiographs clearly did not include or show
permanent first molars were also excluded. Among the 601 pa-
tients, 37 children were excluded based on these exclusion criteria
(six from the anticancer therapy group, mean age=fve years, 10
months old; 31 from the control group, mean age=six years, one
month old). Finally, 76 children who had been treated for ped-
iatric cancer were selected as the anticancer therapy group and
488 healthy children served as the control group (Table 1). All
76 children who had anticancer therapy received chemotherapy.
Among these, 49 also received hematopoietic stem cell transplant-
ation (HSCT) and 20 had both HSCT and radiation therapy.
Diagnostic criteria of ectopic eruption were cases in which
the PFMs were impacted in the primary second molar with or
without root resorption of the primary second molar. Te prev-
alence of ectopic eruption was compared between the anticancer
therapy group and control group. In the former, the relationship
between ectopic eruption and HSCT, radiation therapy, and age
1
Dr. Ko is a Captain, Korean Army Medical Corps,
5
th Infantry Division, Gyeonggido;
2
Dr. Park is a professor and chair, Department of Pediatric Dentistry, The Institute of
Oral Health Science, Samsung Medical Center, at Sungkyunkwan University School of
Medicine at Seoul; and
3
Dr. Kim is an associate professor, Department of Pediatric
Dentistry School of Dentistry, Pusan National University, Dental Research Institute, at
Busan, all in South Korea.
Correspond with Dr. Kim at jychaee@gmail.com or jychaee@pusan.ac.kr
Abstract: Purpose: The purpose of this study was to investigate the association between anticancer therapy and ectopic eruption of permanent
rst molars (PFMs). Methods: This study evaluated 564 ve- to seven-year-old patients (anticancer therapy group=76; control group=488) who
had radiographs taken between October 1, 2009 and September 30, 2010. The prevalence of ectopic eruption of PFMs was compared between
the anticancer therapy group and control group. In the anticancer therapy group, the association between ectopic eruption and radiation
therapy, hematopoietic stem cell transplantation (HSCT), and age at the start of treatment was also evaluated. Results: The overall prevalence
of ectopic eruption was approximately six percent, with a signicantly higher rate in the anticancer therapy group (~16 percent) than in the
control group (~ve percent; P<.001). Supplementary radiation therapy and HSCT did not signicantly inuence the prevalence. Patients who
started anticancer therapy after three years old, however, had a lower rate of ectopic eruption than patients who started earlier (P<.05).
Conclusions: The prevalence of ectopic eruption of permanent rst molars increased in patients with anticancer therapy. This effect was
greater in children who started anticancer therapy before they were three years old. (Pediatr Dent 2013;35:530-3) Received July 1, 2012
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Last Revision December 13, 2012
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Accepted December 15, 2012
KEYWORDS: ANTINEOPLASTIC AGENTS, MOLAR, TOOTH ERUPTION, ECTOPIC
PEDI ATRI C DENTI STRY V 35
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ANTI CANCER THERAPY AND ECTOPI C ERUPTI ON 531
at the start of treatment was also evaluated. Regarding radiation
therapy, local radiation therapy was excluded from the investiga-
tion because it did not focus on the maxillofacial region in any
patients in this study. Terefore, only patients who received sys-
temic radiation therapy were included.
Since anticancer therapy was started immediately after diag-
nosis, the date when the patients were diagnosed with cancer was
assumed to be the same as the start of treatment. Patients were
divided into four groups according to age at the start of treatment:
(1) less than one year; (2) greater than or equal to one and less
than two years; (3) greater than or equal to two and less than
three years; and(4) greater than or equal to three years.
Statistical methods. Statistical analyses were performed using
SAS 9.1.3 software (SAS Institute, Inc, Cary, N.C., USA). Fishers
exact test was used to investigate the relationship between two
specific variables, and Bonferronis correction was used to de-
termine the infuence of age at the start of treatment on ectopic
eruption. Statistical signifcance was defned as P.05.
Results
Ectopic eruption was found in 35 out of 564 patients (~6
percent), with a signifcantly higher prevalence in the anticancer
therapy group (~16 percent) than the control group (~5 percent;
P<.001; Table 2).
In the anticancer therapy group, approximately 20 percent
(10/49) of patients with HSCT and only approximately seven
percent (2/27) of patients without HSCT had ectopic eruption;
however, this diference was not statistically signifcant (P=.19).
Moreover, 15 percent (3/20) of patients who had radiation ther-
apy had ectopic eruption vs. approximately 16 percent (9/56)
who did not have radiation therapy, which did not present any
statistical signifcance (P=1.00).
The group who started anticancer therapy after three years
old showed a noticeable difference in the prevalence of ectopic
eruption vs. other age groups. There was no significant differ-
ence, however, among the other three groups (Table 3). Our data
showed that the prevalence of ectopic eruption of PFMs was rel-
atively lower when anticancer therapy was started after three years
old than in patients who started treatment before three years old
(P<.05).
Table 1. PATIENT DISTRIBUTION
Gender (%) Total Mean age
Male Female
Anticancer therapy

group
50 (66) 26 (34) 76 6 ys, 2 mos
Control group 281 (58) 207 (42) 488 6 ys, 7 mos
Figure 1. Radiographs and clinical photo of a patient receiving anticancer therapy
exhibiting bilateral ectopic eruption of the permanent maxillary frst molars. Note
the root resorption of the primary second molars.
* Fishers exact test was used to investigate the relationship between two specifc
variables.
Table 2. PREVALENCE OF ECTOPIC ERUPTION*
Group Ectopic eruption
(%)
P-value
No Yes
Control group (N=488) 465 (95) 23 (5) <.001
Anticancer therapy group (N=76) 64 (84) 12 (16)
Hematopoietic stem cell transplantation
.19
No (n=27) 25 (93) 2 (7)
Yes (n=49) 39 (80) 10 (20)
Radiation therapy
1.00
No (n=56) 47 (84) 9 (16)
Yes (n=20) 17 (85) 3 (15)
* Fishers exact test with Bonferronis correction was used to determine
the infuence of age at the start of treatment on ectopic eruption.
Signifcantly diferent from other age groups (P<.05).
Table 3. DISTRIBUTION OF ECTOPIC ERUPTION IN
ANTICANCER THERAPY GROUP ACCORDING
TO AGE*
Age at the start of
treatment (ys)
Ectopic eruption
(%)
Total
No Yes
>3 38 (100) 0 (0)

38
2-3 7 (70) 3 (30) 10
1-2 9 (60) 6 (40) 15
<1 10 (77) 3 (23) 13
Total 64 (84) 12 (16)
76
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The total number of teeth that ectopically erupted was 59.
Among them, 47 were on the maxilla and 12 were on the man-
dible. In the control group, approximately 89 percent (31/35) of
ectopic eruption cases occurred in the maxilla, and the remaining
approximately 11 percent (4/35) occurred in the mandible. In
the anticancer therapy group, approximately 67 percent (16/24)
of eruptions were in the maxilla, and approximately 33 percent
(8/24) occurred in the mandible (Table 4). Although there was
a higher prevalence of ectopic eruption on the mandible in the
anticancer therapy group than in the control group, the diference
was not signifcant (P=.05).
Discussion
Te causes of ectopic eruption of the PFMs are not well known,
and it is thought that multifactorial etiologies are involved.
11,12
In
1968, Pulver suggested six factors that influence the first molar
eruption
13
but could not find one specific factor that contrib-
utes to ectopic eruption, suggesting that a combination of factors
is involved. One such factor is alteration in the chronology of
bone growth in relation to calcifcation and eruption of the molar.
Previous studies have demonstrated that radiation therapy with
chemotherapy impairs odontogenesis and chemotherapy alone can
result in dental anomalies and developmental disturbances.
6,14-16

Growth retardation has a particularly profound impact on rapidly
growing tissues.
17
For this reason, the most severe interference in
skeletal development due to anticancer therapy occurs during the
periods of maximum bone growth from birth to six years old.
5
In
this study, all patients in the anticancer therapy group received
anticancer therapy before seven years old. Terefore, the increased
prevalence of ectopic eruption among patients with anticancer
therapy may arise from disturbance of tooth calcification and
underdevelopment of skeletal growth.
Analysis of cephalometric radiographs may be distinct evi-
dence for the assessment of skeletal growth retardation. Cephalo-
metric radiographs, however, were not taken routinely in this age
group unless for specifc purposes such as orthodontic necessity.
Taking cephalometry strictly for research purposes may cause
ethical problems. For these reasons, the current study is limited
in its analysis regarding the degree of growth retardation. Further
studies with quantitative and defnite analyses may be necessary in
the near future.
Since this studys fndings apply only to dental patients and
not to the general population, our results may have some limita-
tions. Nevertheless, our results correspond well to those of
previous studies. In the control group of this study, the preva-
lence of ectopic eruption of the PFMs was approximately fve per-
cent, similar to the prevalence reported by Bjerklin and Kurol in
healthy children.
18
Also, other studies have reported prevalence
ranging between two percent and six percent.
10
Several previous studies demonstrated that the severity of
dental malformation depends on the stage of tooth development
and type and dosage of anticancer agents employed.
5,19
In this
study, patients who started anticancer therapy after three years old
had a lower prevalence of ectopic eruption. Tis is probably be-
cause the roots of the primary second molar are fully developed
at approximately three years old, and the enamel of the PFMs
is completely formed at nearly the same age.
20,21
If anticancer
therapy is given before three years old, it can disturb the growth
of the teeth and disrupt the eruption pattern.
Regarding radiation therapy in this study, the same dose of
systemic radiation therapy was used (9.9 Gy over three days).
Patients receiving local radiation therapy were excluded from the
investigation because the radiation did not focus on the maxillo-
facial region. As for chemotherapy, diferent dosages, durations of
treatment, and types of anticancer agents were used according to
each patients stage and type of cancer (eg, solid tumor vs. blood
cancer). Dosage of chemotherapy, however, was not classified
quantitatively in this study. Likewise, patients can be classified
according to transplantation type (allogenic vs autologous trans-
plantation) and/or the number of transplantations. Since these are
limitations of this study, further study regarding dosage and/or
classifcation of anticancer treatment is necessary in the near future.
In previous reports, chemotherapy with radiation therapy
resulted in severe dental disturbances, whereas chemotherapy alone
has not been reported to produce severe problems.
5,14,22
Since most
children receive more than one type of therapy, however, it is
difcult to completely distinguish the sequelae of chemotherapy
from radiation effects. Moreover, in this study, supplementary
radiation therapy and HSCT did not signifcantly infuence the
prevalence of ectopic eruption. Such results might be possible for
the following reasons. First, the supplementary radiation therapy
and HSCT were performed for a short period compared to chemo-
therapy. Second, none of this studys patients had local radiation
therapy focused on the maxillofacial region.
Though it was not statistically significant, the anticancer
therapy group showed a higher prevalence of ectopic eruption
on the mandible than the control group. In 1989, Berkowitz et al.
reported that growth retardation of the mandible is afected more
by anticancer therapy than the nasomaxillary complex.
7
It is not
clear, however, why growth of the mandible is more sensitive to
anticancer therapy, and Berkowitz et al. did not propose specifc
mechanisms to explain this observation. Further study into the
underlying mechanism is, therefore, necessary.
Conclusion
Based on this studys results, the following conclusions can be
made:
1. Te prevalence of ectopic eruption of permanent frst
molars increased in patients with anticancer therapy,
especially in children who started anticancer therapy be-
fore they were three years old.
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* Fishers exact test was used to investigate the relationship between
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Table 4. DISTRIBUTION OF ECTOPIC ERUPTION
ACCORDING TO MAXILLA AND MANDIBLE*
Control
group
(%)
Anticancer
therapy
group (%)
P-value
Maxilla (n=47) 31 (89) 16 (67) .05
Mandible (n=12) 4 (11) 8 (33)
Total (N=59) 35 (100) 24 (100)
PEDI ATRI C DENTI STRY V 35
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Abstract of Electronic Publication in this Issue
Scientic Article IN VITRO
Microbial Microleakage Assessment of a New Hydrophilic Fissure Sealant:
A Laboratory Study
Ali Bagherian, DDS, MS
1

Mahsa Ahmadkhani, DDS
2

Mahmood Sheikhfathollahi, PhD
3

Reza Bahramabadinejad, MSc
4

Abstract: Purpose: The purpose of this study was to compare microbial leakage of a new hydrophilic sealant with that of a conventional hydro-
phobic resin-based sealant. Methods: One hundred extracted, caries-free, human maxillary premolars were randomly divided into ve groups.
Those in Groups 1, 2, and 3 had dry, wet, and articial saliva-contaminated occlusal surfaces, respectively, and were sealed with a hydrophilic
sealant, while those in Groups 4 and 5 had dry and wet occlusal surfaces, respectively, and were sealed with a hydrophobic sealant. A newly
designed microbial penetration method utilizing Streptococcus mutans as an indicator was tested for leakage assessment. Data were analyzed
using SPSS 15.0 software, and the signicance level was set at =0.05. Results: The log rank test indicated a statistically signicant difference
in leakage rates among the ve groups. Mantel-Cox log-rank test ndings showed that Group 3 had the highest leakage rate, with Groups 2
and 4 having the lowest. There was no statistically signicant difference in leakage rate between Groups 2 and 4. Conclusions: With respect to
the limitations of an in vitro study, our ndings suggest that hydrophilic sealants are an acceptable alternative to hydrophobic sealants.
(Pediatr Dent 2013;35:E194-E198) Received September 22, 2012
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Last Revision March 5, 2013
|
Accepted March 11, 2013
KEYWORDS: PIT AND FISSURE SEALANTS, DENTAL LEAKAGE, HYDROPHILICITY