A review of the literature

Ó 2015 CEO Published by / E´dite´ par Elsevier Masson SAS All rights reserved / Tous droits re´serve´s

rature Revue de la litte

Cervico-facial irradiation and orthodontic treatment Irradiation cervicofaciale et traitement orthodontique Rajae ELHADDAOUIa,*, Loubna BAHIJEb, Saliha CHBICHEBc, Fatima ZAOUIb a

Faculte de medecine dentaire, universite Mohamed V Souissi, Rabat Institut, avenue Allal Al Fassi, BP 6212, Rabat, Morocco b Service d’orthopedie dento-faciale, faculte de medecine dentaire, universite Mohamed V Souissi, Rabat Institut, avenue Allal Al Fassi, BP 6212, Rabat, Morocco c Service d’odontologie chirurgicale, faculte de medecine dentaire, universite Mohamed V Souissi, Rabat Institut, avenue Allal Al Fassi, BP 6212, Rabat, Morocco Available online: 16 May 2015 / Disponible en ligne : 16 mai 2015

Summary

sume  Re

Cancers during infancy and childhood affect 1 to 3% of children under the age of 15. Among these cancers the most frequent are malignant hemopathies, and in particular, acute lymphoblastic leukemia, which represents 80% of infant leukemias, with a peak of incidence around the age of 3–4. The overall prognosis for infant malignant hemopathies has improved significantly thanks to progress made in chemotherapy and radiotherapy. However, these anti-cancer treatments, particularly radiotherapy, when performed early, generally before 5 years of age, can have harmful effects that interfere with overall growth and particularly cranio-facial growth, and also with the child’s oro-dental development. Some effects such as mandibular retrognathia, macrodontia, microdontia, agenesis and delayed eruption could increase the need for orthodontic treatment, while other complications, particularly the reduced height of the alveolar processes, short thin roots and modification of the superficial and profound periodontium, are likely to make such treatment more difficult. The aim of this review of the literature is to identify the essential factors that must be analyzed before orthodontic treatment is proposed for subjects who have undergone radiotherapy at an early age, and the precautions to be taken before and during orthodontic treatment.

Les cancers chez l’enfant et l’adolescent avant 15 ans  representent de 1 a` 3 % de l’ensemble des cas de cancers.  Parmi ces cancers, les hemopathies malignes sont les plus   frequentes, notamment la leucemie lymphoblastique aigue€   qui represente 80 % des leucemies infantiles, avec un pic d’incidence qui se situe vers 3–4 ans. Le pronostic global des   e nettement amelior  e,  hemopathies malignes de l’enfant a et ^ aux progres  en matiere  de chimiotherapie  grace et de radio  therapie. Toutefois, ces traitements antineoplasiques, notam  ee  a` un age ^   e ment la radiotherapie, realis precoce, gen  ralement avant 5 ans, auraient des effets nefastes qui inte  erale  rferent avec la croissance gen et craniofaciale en particu lier, ainsi qu’avec le developpement buccodentaire de l’enfant.  Certains effets, tels le retrognathisme mandibulaire, les macro esies   donties, les microdonties, les agen et le retard d’eruption, pourraient augmenter les besoins de traitement orthodontique,  alors que d’autres complications, notamment la hauteur reduite  alveolaires,  des proces la morphologie radiculaire courte et  amincie, et l’alteration du parodonte superficiel et profond, sont en mesure de compliquer un tel traitement. Cette revue de   litterature a eu comme objectif de preciser les aspects essentiels a` analyser avant d’indiquer un traitement orthodontique  edents   chez un sujet ayant des antec de radiotherapie a` un ^ precoce,   age ainsi que les precautions a` prendre avant et en cours du traitement orthodontique.

Correspondence and reprints / Correspondance et tires a` part. e-mail address / Adresse e-mail : [email protected] (Rajae Elhaddaoui) *

International Orthodontics 2015 ; 13 : 139-148 http://dx.doi.org/10.1016/j.ortho.2015.03.017

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Ó 2015 CEO. Published by Elsevier Masson SAS. All rights reserved

Ó 2015 CEO. E´dite´ par Elsevier Masson SAS. Tous droits re´serve´s

Keywords

s Mots-cle

·· ··

Pediatric cancers. Hemopathy. Radiotherapy. Orthodontic treatment.

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diatrique. Cancer pe mopathie. He rapie. Radiothe Traitement orthodontique.

Introduction

Introduction

One to 3% of children are affected by cancer, which represents the second cause of mortality before age 15. It is currently estimated that 1 in every 900 young adults aged 16 to 44 has previously undergone anti-cancer treatment for childhood cancer [1,2]. Among these cancers the most frequent are malignant hemopathies, and particularly acute lymphoblastic leukemia (ALL) [1,2].

s par le cancer qui Un a` 3 % des enfants sont affecte sente la deuxie me cause de mortalite  avant 15 ans. On repre ^ ge s estime actuellement que 1 sur 900 des jeunes adultes a alablement subi un traitement antide 16 a` 44 ans a pre oplasique pour un cancer de l’enfance [1,2]. Parmi ces ne mopathies malignes sont les plus rencontre es, cancers, les he rement la leuce mie lymphoblastique aigue € particulie (LLA) [1,2]. s prometteurs en termes de traitements antiLes progre reux par chimiothe rapie et radiothe rapie ont permis cance liorer le pronostic global des he mopathies malignes d’ame chez l’enfant avec un taux de survie de 50 a` 70 %. es apre s leur traitement, ces patients ayant pre sente  Des anne matologique et malgre  leurs proble mes de une pathologie he  chroniques, aspirent a` avoir, dans la mesure du possisante s au traitement orthodontique a` l’instar des sujets ble, un acce . Or les traitements par radiothe rapie associe e en bonne sante rapie, applique s a` ces enfants en pe riode ou non a` la chimiothe quences ne fastes sur la croisde croissance, auront des conse  ne rale, ainsi que sur le de veloppement craniofacial et sance ge quences, manifestes buccodentaire en particulier. Ces conse es, peuvent apparaıˆtre des mois, voire des anne es ou nuance s la fin du traitement, et pourraient compliquer le traiteapre ment orthodontique [2–5]. tudier les effets de la radiothe raL’objectif de ce travail est d’e conise e a` un a ^ge pre coce sur le de veloppement crapie pre rence de ces effets avec le niofacial et buccodentaire, l’interfe gie the rapeutique la traitement orthodontique, et la strate e pour les ge  rer. mieux adapte

The promising advances in anti-cancer treatment by chemotherapy and radiotherapy have made it possible to improve the overall prognosis for malignant hemopathies in children, with a survival rate of 50 to 70%. Many years later, and despite their chronic health problems, these former hematological patients would like to benefit, as far as possible, from access to orthodontic treatment in the same way as subjects in good health. However, radiotherapy, in combination or not with chemotherapy and performed during the growth phase, has a harmful impact on growth generally and more particularly on cranio-facial and oro-dental development. These consequences, whether slight or evident, may appear months or even years after the end of treatment and may complicate orthodontic procedures [2–5]. The aim of this work is to review the effect of radiotherapy at an early age on cranio-facial and oro-dental development, the interference between these effects and orthodontic treatment, and the most appropriate strategy to overcome these problems.

Malignant hemopathies: treatments and consequences

mopathies malignes : traitements et Les he implications

Acute lymphoblastic leukemia (ALL) is the traditional form of infant leukemia and represents 80% of all cases. The peak of ALL incidence occurs around 3–4 years of age, with no gender differences. Warning signs include asthenia, unexplained fever, diffuse pain in bones, increased susceptibility to ulcers, bruising and petechia, and sometimes adenopathy and hepatosplenomegaly [2].

mie lymphoblastique aigue € (LLA) est la forme classiLa leuce mies infantiles dont elle repre sente 80 %. Le pic que des leuce rence entre d’incidence de LLA se situe vers 3–4 ans sans diffe nie, la les deux sexes. Les signes d’alerte comportent l’asthe vre inexplique e, les douleurs osseuses diffuses, une susfie e leve e aux ulce rations, ecchymoses et pe te chies, et ceptibilite nopathies et he patosple nome galies [2]. parfois des ade

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Cervico-facial irradiation and orthodontic treatment Irradiation cervicofaciale et traitement orthodontique

Treatment of ALL involves intensive chemotherapy (prednisone, vincristine, asparaginas, daunorubicin) and a bone marrow graft. Radiotherapy recommended for treatment of ALL takes the form of irradiation of the head, either prophylactically or to eliminate cancer cells from the central nervous system (CNS) at doses of up to 50 grays (Gy), or total body irradiation at 10 Gy as conditioning before a bone marrow graft [2]. Because most growth in children occurs before the age of 4 and then during puberty, the effects of radiotherapy on the skeleton will be more marked during these periods of rapid growth, just when the incidence of ALL is at its highest [2–6].

rapie intensive Le traitement de LAA consiste en une chimiothe (prednisone, vincristine, asparaginase, daunorubicine) ainsi conise e qu’une greffe de moelle osseuse. L’irradiation pre ^ nidans le traitement de LLA consiste en une irradiation cra enne en tant que traitement prophylactique ou permettant  liminer les cellules cance reuses du syste me nerveux cend’e tral (SNC), a` des doses pouvant atteindre 50 grays (Gy), ou une irradiation corporelle totale de conditionnement (ICT) alablement a` une greffe de moelle osseuse [2]. a` 10 Gy pre   que l’essentiel de la croissance chez un enfant Etant donne ^ge de 4 ans et au cours de la puberte , les s’effectue avant l’a rapie sur le squelette seront donc plus effets de la radiothe s au cours de ces pe riodes de croissance rapide, prononce leve e [2–6]. ou` l’incidence de LLA est la plus e

Impact of radiotherapy on skeletal growth and oro-dental development

percussions de la radiothe rapie sur la Re veloppement croissance du squelette et le de buccodentaire

Radiotherapy leads to alterations in skeletal growth, notably cranio-facial growth, and the oro-dental development of the child, the severity of which depends on two main factors: — the age of the patient at the time of treatment: the most severe consequences are noted when treatment is begun early, generally before the age of 6; — the radiation dose: doses of between 10 and 30 Gy have a significant impact on bone growth and tooth development. Thirty grays (30 Gy) is potentially harmful for the development of cranio-facial structures; 4 Gy modifies soft tissue development [2,4,5].

rapie entraıˆne des alte rations de la croissance La radiothe rement squelettique, particulie craniofaciale, et du veloppement buccodentaire de l’enfant, dont la se  ve rite  de pend de deux principaux facteurs : de ^ge du patient au moment du traitement : les manifesta— l’a ve res sont rapporte es lorsque le traitement est tions les plus se  pre cocement, en ge  ne ral avant 6 ans ; commence — la dose d’irradiation : des doses entre 10 et 30 Gy influencent significativement la croissance osseuse et le veloppement dentaire. Une dose de 30 Gy est potentiellede veloppement des structures craniofament nocive pour le de re le de veloppement des tissus mous [2,4,5]. ciales, 4 Gy alte

The effects of radiotherapy on the growing skeleton

rapie sur le squelette en Les effets de la radiothe croissance

Several different studies [2,7–9] on the effect of radiation on skeletal growth all agree that growth is suppressed by radiation, as in the case of irradiation of the head prescribed for the treatment of ALL. This suppressive effect is due to a deficit in growth hormone and affects the whole of the growing skeleton, including the cranio-facial complex. In fact, irradiation not only diminishes vascularization but also has a direct cytotoxic effect on epiphyseal chondrocytes. The reduction in height observed in irradiated children can also be explained by an early onset of puberty and a shortening of the accompanying growth spurt [2–6].

tudes [2,7–9] consacre es a` l’effet de l’irradiation sur la Les e croissance du squelette sont diverses et sont toutes en accord  par les irrasur l’effet suppresseur de la croissance provoque ^ nienne prescrite diations, comme dans le cas d’irradiation cra pour le traitement de la LLA. Cet effet suppresseur est duˆ a` un ficit en hormone de croissance (GH), et qui affecte l’ensemde ble du squelette en croissance y compris le complexe craniofacial. En effet, l’irradiation est non seulement a` l’origine d’une diminution de la vascularisation mais elle a aussi un effet piphysaires. La cytotoxique direct sur les chondrocytes e e chez enfants irradie s peut diminution de la taille observe ^tre explique e par le de but pre coce de la puberte  et aussi e e plus courte de la pousse e de croissance pubertaire la dure [2–6]. tudie  la croissance faciale dans un Dahllof et al. [8] ont e chantillon de 17 enfants chez lesquels on avait diagnostique  e e par transplantation de cellules une LLA et qu’on avait traite niques avec irradiation corporelle totale souches (TCS) alloge moins sains, les enfants (ICT). Par comparaison avec des te

Dahllof et al. [8] studied facial growth in a sample of 17 children in whom ALL had been diagnosed and who had been treated by allogenic stem cell transplant (SCT) and total body irradiation (TBI). In comparison with healthy controls, the subjects receiving SCT presented a reduction in the

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vertical dimensions of the face and the alveolar processes, and also the sagittal dimensions of the bony bases. Posterior facial height was reduced by 10%, anterior facial height and mandibular length by 5%, while maxillary length was reduced by only 2%. The length of the anterior base of the skull was almost unchanged. The most severe effect of radiotherapy was the impact on the alveolar processes, the height of which was reduced by almost 50% in the upper jaw [8]. In a sample of 97 children diagnosed with ALL before the age of 10 and treated by chemotherapy combined with cranial irradiation, who were followed up for at least 5 years after the diagnosis, the main observation was that patients under 5 at the moment of anti-cancer treatment, including 24 Gy cranial irradiation, had a much higher risk of mandibular retrognathism [9].

duction des dimensions recevant une TCS montraient une re s alve olaires, ainsi que des verticales de la face et des proce dimensions sagittales des bases osseuses. rieure e tait re duite de 10 %, la hauteur La hauteur faciale poste rieure et la longueur mandibulaire de 5 %, alors faciale ante tait re duite que de 2 %. La longque la longueur maxillaire n’e rieure du cra ^ ne e tait presque inchange e. ueur de la base ante rapie affecte les proce s L’effet le plus marquant de la radiothe olaires dont la hauteur e  tait re duite de presque 50 % alve rieure [8]. a` l’arcade supe chantillon de 97 enfants chez lesquels on avait Dans un e  une LLA avant l’a ^ge de 10 ans, traite s par chidiagnostique rapie associe e a` une irradiation cra ^ nienne, et suivis miothe s le diagnostic, la constatation pendant au moins 5 ans apre tait que les patients de moins de 5 ans au moment principale e reux, incluant une irradiation cra ^ nidu traitement anticance rablement accru de enne de 24 Gy, avaient un risque conside  trognathisme mandibulaire [9]. re

The effects of radiotherapy on tooth development

rapie sur le de veloppement Les effets de la radiothe dentaire

Radiotherapy leads to disturbances in tooth development characterized by: — shape abnormalities: macrodontia, microdontia, taurodontism; — quantitative abnormalities: hypodontia, anodontia, agenesia; — abnormalities of eruption: delayed shedding of temporary teeth and eruption of permanent dentition; — structural abnormalities: poor mineralization of enamel, cream-white opacities; — alterations in root formation, including: halting of root development and thinning of roots, which have a shortened ‘V’ shape. This is explained by the harmful effect of irradiation on root construction (root sheath, predontoblasts). This short narrow root morphology exposes the roots to a higher risk of resorption following orthodontic treatment;

rapie La radiothe entraıˆne des perturbations du veloppement dentaire qui sont caracte rise es par : de — des anomalies de forme : macrodonties, microdonties, taurodontisme ; — des anomalies de nombre : hypodonties, anodonties, ne sies dentaires ; age  ruption : retards d’exfoliation des dents — des anomalies d’e  ruption des dents permanentes ; temporaires et d’e ralisa— des anomalies de structure : perturbations de mine mail, opacite s en blanc cre  me ; tion de l’e rations de la formation radiculaire incluant : — des alte ^ t de de veloppement et amincissement des racines avec l’arre  par l’effet ne faste une forme en « V » court. Ceci est explique dification radiculaire (la gaine e pithe liale de l’irradiation sur l’e odontoblastes). Cette morphologie radicude Hertwing, pre troite expose les racines aux risques e leve s laire courte et e sorptions suite au traitement orthodontique ; de re  mature e provoque e par formation la fermeture apicale pre odentine dans cette re gion [10]. d’oste e a` la La morphologie en « V » court des racines, associe s alve olaires, perte de plus de 50 % de la hauteur des proce  lude a` la perte dentaire pre coce. De me ^me, la re duction de pre la taille des racines serait responsable de la diminution de la e a` 19 % pour les incisives taille totale des dents qui est estime mes molaires [2–5,11,12]. et 39 % pour les deuxie veloppement radiculaire e tant affecte  par l’irradiation Le de reuse, les re sultats de Niucha et al. [11], e valuant anticance ^ge dentaire chez un groupe d’enfants de 5 a` 12 ans atteints l’a s par chimiothe rapie et radiothe rapie, ont montre  de LLA, traite ^ge dentaire e tait significativement avance  par rapport que l’a ^ge chronologique. Ceci prouve que l’a ^ge dentaire ne peut a` l’a ^tre exploitable dans cette cate gorie de patients pour pas e ^ge biologique pre alablement a` une the rapeul’estimation de l’a dique. tique orthope

premature apical closure caused by the formation of osteodentine in this region [10]. The shortened ‘V’ shape of the roots and the loss of more than 50% of alveolar process height presage early tooth loss. Similarly, reduced root size could be responsible for the overall reduction in tooth size, which is estimated to be 19% for incisors and 39% for the second molars [2–5,11,12]. Since root development is affected by anti-cancer radiotherapy, the results of Niucha et al. [11], who evaluated dental age in a group of children aged 5 to 12 suffering from ALL and treated by chemotherapy and radiotherapy, showed that dental age was significantly in advance of chronological age. This proves that dental age cannot be used in this group of patients to estimate biological age prior to orthopedic treatment.

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The effects of radiotherapy on bone and soft tissue

rapie sur l’os et les tissus Les effets de la radiothe mous

When living tissue is irradiated, most cells survive, but with damage to their DNA, RNA, membranes and enzyme systems. These cells, and mainly the stem cells, vascular endothelium cells and fibroblasts responsible for healing, are altered and are not replaced by other cells. Consequently, tissues contain fewer cells; they are less well vascularized and less well oxygenated. This triad of hypocellularity, hypovascularization and hypoxia develops over time: soft tissue, bone, skin and mucosa become avascular, fibrotic and inelastic, with poor healing qualities in the event of lesions or surgical procedures. In irradiated subjects, the risk of osteoradionecrosis and soft tissue necrosis increases over time [1].

nergie du rayonnement passe a` travers les tissus Lorsque l’e vivants, la plupart des cellules survivent, mais avec des dommes enzymages au niveau de leurs ADN, ARN et les syste matiques et membranaires. Ces cellules, principalement les lium vasculaire et cellules souches, les cellules de l’endothe  re es fibroblastes responsables de la cicatrisation, sont alte es par de nouvelles cellules. Par et ne sont remplace quent, les tissus deviennent moins cellulaires, moins conse  ne s. Cette triade – hypocellularite , vasculaires, et moins oxyge veloppe dans le temps, hypovascularisation et hypoxie – se de les tissus comme l’os, la peau et les muqueuses deviennent lastiques, avec une faible avasculaires, fibrotiques et ine  de cicatrisation en cas de le sion ou apre s intervencapacite , le risque d’oste o-radio-ne crose et la tion. Chez le sujet irradie crose des tissus mous augmentent avec le temps [1]. ne En outre, d’autres manifestations buccales sont induites par la rapie cervicofaciale, et incluent des radiomucites, une radiothe rostomie, une dysphagie, une cariosusceptibilite e leve e et xe une inflammation gingivale [1–5,12]. Ces manifestations rement vulne rable qui risque constituent un terrain particulie ^tre aggrave  par le traitement orthodontique. d’e

Furthermore, cervico-facial radiotherapy causes other oral problems including radio-mucitis, xerostomia, dysphagia, greater susceptibility to dental caries, and gingival inflammation [1–5,12]. The terrain is therefore extremely vulnerable, with a risk of aggravation during orthodontic treatment.

Orthodontic treatment and cervicofacial irradiation

Traitement orthodontique et irradiation cervicofaciale

Infants or teenagers treated by radiotherapy for childhood cancers should benefit from the same access to orthodontic treatment as children in good health. Orthodontists are very likely to encounter such patients; sometimes cancer is diagnosed during active orthodontic treatment [2–5].

 te  traite s par radiothe rapie Les enfants ou adolescents ayant e ^me acce s au pour un cancer de l’enfance doivent avoir le me . Le traitement orthodontique que les enfants en bonne sante ^tre plus vraisemblable est que les orthodontistes peuvent e s a` recevoir ces patients ; parfois me ^me, un cancer amene ^tre diagnostique  au cours d’un traitement orthodontique peut e actif [2–5]. valuer les besoins de traitement orthodontique, une Afin d’e tude transversale a e  te  mene e par Akharzouz et al. [12] et a e  une population fran¸caise d’enfants ayant re¸cu un concerne rapie cervicofaciale. Les re sultats ont traitement par radiothe sentaient des conclu que suite a` l’irradiation, ces enfants pre trie faciale dans 74 % des retards de croissance, une dissyme s dans cas, un recouvrement et surplomb incisifs augmente respectivement 70 % et 61 % des cas. Les anomalies de veloppement dentaire (microdonties, fermetures apicales de  mature es et hypoplasies) sont retrouve es chez 83 % des pre  te  patients. Enfin, le besoin de traitement orthodontique a e  re  pour 61 % des patients, et mode  re  dans 17 % des cas. Il ave  a` l’absence ou la re  tention des dents et a` l’augmentation est lie du surplomb incisif [12]. ne ral affaibli par l’irradiation, avec des Face a` un terrain ge perturbations diverses de la croissance craniofaciale et du veloppement dentaire qui augmentent les besoins de traitede ment orthodontique, l’orthodontiste devrait tenir compte des rations spe ciales afin d’e  laborer un plan de traitement conside

In order to evaluate the needs for orthodontic treatment, a study was carried out by Akharzouz et al. [12] on a horizontal sample of French children who had undergone treatment including cervico-facial radiotherapy. The conclusion was that, following irradiation, these children suffered from delayed growth, with facial dissymmetry in 74 % of cases, and increased incisal overbite and overjet in 70% and 61% of cases respectively. Tooth development abnormalities (microdontia, premature apical closure and hypoplasia) were encountered in 83% of patients. Finally, there was a clear need for orthodontic treatment in 61% of patients and a moderate need in 17 %. It was linked to the absence or retention of teeth and the increased incisal overjet [12]. Faced with a terrain globally weakened by irradiation, with various modifications to cranio-facial growth and tooth development, which increase the need for orthodontic treatment, the orthodontist has to bear in mind a series of special considerations when drawing up a treatment plan that takes into

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account the chronic health problems of these patients. Possible harmful effects of orthodontic treatment should also be foreseen.

mes de sante  chroglobal qui prenne en mesure les proble fastes e ventuels du niques chez ces patients, les effets ne ^tre e galement anticipe s. traitement orthodontique doivent e

Start and duration of orthodontic treatment

but et dure e du traitement orthodontique De

Sheller and Williams [3] suggested that orthodontic treatment should be begun or resumed after the anti-cancer treatment, following a period of at least 2 years of incident-free survival. This advice is based on problems of recurrence of the disease as well as the risk of a second malignant neoplasia (SMN). Factors such as chemotherapy, radiotherapy and immunosuppression to prevent graft-versus-host disease during SCT, and genetic predisposition, have all been implicated in increased risk of SMN [13].

 de commencer ou de Sheller et Williams [3] ont conseille reprendre le traitement orthodontique a` la fin du traitement reux et apre s un minimum de deux ans de survie anticance  sur les proble mes de du patient sans incident. Cela est fonde currence de la maladie autant que sur le risque d’une re oplasie maligne (SNM). Des facteurs, tels la radioseconde ne rapie, la chimiothe rapie, l’immunosuppression pour pre  vethe actions du greffon contre l’ho ^te lors d’une TCS et la nir les re disposition ge  ne tique, ont tous e  te  implique s dans un rispre que accru de SNM [13]. tude de Dahllof et al. [2] a e  te  mene e sur dix enfants, Une e tous survivants au long terme a` la suite d’une TCS, ou` sept te  sensibilise s par une irradiation corporelle enfants avaient e totale (ICT) de 10 Gy avant la TCS. Les auteurs estiment que, sultats parfaits n’aient pas toujours e  te  atteints, bien que des re ne ralement pas le traitement orthodontique ne produisait ge fastes, a` condition de : d’effets secondaires ne  ge  res ; — utiliser des forces le ^t que normalement ; — terminer le traitement plus to thode la plus simple qui re  pond aux besoins — choisir la me rapeude traitement tout en acceptant des compromis the olie ou supraclusie non corrige es totalement, tiques (proalve siduels, overjet re siduel apre s traiteespaces proximaux re ment par activateurs. . .). Plusieurs raisons obligent a` l’accepsultat the rapeutique moins parfait, tels le pic tation d’un re cocement atteint qui compromet le traitement pubertaire pre dique, ainsi que l’e tat de sante  ge ne ral du patient de ja` orthope reux et qui a un impact affaibli par le traitement anticance gatif sur sa coope ration ; ne — ne pas traiter l’arcade mandibulaire dans la mesure du o-radio-ne crose et possible pour diminuer le risque d’oste duire la dure e du traitement [2]. re

Dahllof et al. [2] studied ten children who were all long-term survivors after SCT and of whom seven had been conditioned by total body irradiation (TBI) at 10 Gy before the SCT. The authors considered that, although the results obtained were not always perfect, orthodontic treatment generally did not produce adverse effects provided that: — light forces were used; — the treatment was stopped earlier than usual; — the method chosen was the simplest that matching treatment goals with acceptance of certain compromises (alveolar protrusion or deep bite not fully corrected, residual proximal spaces, residual overjet after treatment with activators, etc.). There were several reasons for accepting a less-than-perfect therapeutic result, such as the early onset of the growth spurt at puberty that compromises orthodontic treatment and the general state of health of patients already weakened by an anti-cancer treatment that also has a negative impact on their cooperation; — the upper arch was not treated, if possible, so as to reduce the risk of osteoradionecrosis and shorten treatment time [2].

Extractions

Les extractions

In subjects undergoing radiotherapy of the head and neck, the incidence of osteoradionecrosis (ORN) is 8.2% [14]. ORN is generally localized in the body of the mandible, and the main risk factor is radiotherapy before or after tooth extractions, which are responsible for 50% of all cases of ORN [15]. Orthodontic treatment should not be begun until 2 years after the end of anti-cancer treatment, and extractions for orthodontic reasons should also be postponed until the end of this period [3]. However, since the risk of osteonecrosis in irradiated areas increases with time, extractions should be performed according to the standard protocol with hyperbaric

rapie de la te ^te et du cou, Chez les sujets recevant une radiothe o-radio-ne crose (ORN) est de 8,2 % l’incidence d’une oste e dans le corps de la [14]. L’ORN est le plus souvent localise mandibule, et ayant comme facteur de risque principal la rapie avant ou apre s des extractions dentaires, ces radiothe res se sont re  ve  le es responsables de 50 % de l’ensemdernie ble des cas d’ORN [15]. Le traitement orthodontique ne doit ^tre commence  avant que 2 anne es ne se soient pas e coule es apre s la fin du traitement anticance reux, les extrace ^tre tions pour des indications orthodontiques doivent aussi e  re es jusqu’a` cette pe riode [3]. Toutefois, e tant donne  que diffe

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Cervico-facial irradiation and orthodontic treatment Irradiation cervicofaciale et traitement orthodontique

oxygen therapy (HBOT), which consists of 20 sessions of administration of 100% oxygen at a pressure of 2.4 absolute atmospheres for 90 minutes before the extraction, and 10 sessions afterwards. In addition, tooth development problems (short roots, resorption of alveolar processes, etc.) may modify the normal pattern of extractions to treat malocclusion; similarly, extractions should be avoided as far as possible so as to minimize tooth displacement and the associated risk of root resorption [1–3].

one crose dans un terrain irradie  augmente le risque d’oste ^tre re alise es selon le avec le temps, les extractions doivent e nothe rapie hyperbare (OHB), qui protocole standard d’oxyge ances d’administration d’oxyge ne 100 % consiste en 20 se a` une pression de 2,4 ATA, pendant 90 minutes, avant ances apre s. l’extraction, et 10 se veloppement dentaire Par ailleurs, les perturbations du de sorption des proce s alve olaires. . .) peu(racines courtes, re ma conventionnel des extractions de la vent modifier le sche ^me, les extractions doivent e ^tre malocclusion ; de me pargne es autant que possible pour minimiser les e placements dentaires et donc le risque de re sorptions radide culaires [1–3].

Tooth displacement in irradiated zones

placement dentaire en terrain irradie  Le de

King et al. [16] used histological methods and tracings to study the pathophysiological modifications of irradiated bone (tibia) in rats. Bone remodeling was quantified using ultraviolet microscopy. Results showed that damage due to irradiation was related to vascular wall modifications and resulting changes in blood flow. Histological study of cortical bone led to the following descriptions of remodeling phenomena:

 des me thodes d’histologie et de King et al. [16] ont utilise  tudier les modifications physiopathologiques tra¸cage pour e  (tibia) chez les rats ; le remodelage osseux a de l’os irradie  te  quantifie  a` l’aide d’un microscope a` rayons ultraviolets. Les e sultats ont montre  que le dommage produit par l’irradiation re ration de la paroi vasculaire et de l’os est en rapport avec l’alte bit sanguin qui en de coulent. L’e tude le changement du de crit les phe nome nes de remohistologique de l’os cortical de delage comme suit : s l’irradiation : augmentation du — de 8 heures a` 5 jours apre lement volume sanguin au niveau de l’os et de la moelle paralle  inflammatoire de re sorption ; a` l’augmentation de l’activite s l’irradiation : diminution significative de la — 1 mois apre abilite  vasculaire avec e  le vation de l’activite  de remoperme domine e par la re sorption. L’e  le vation de l’activite  delage pre de remodelage se manifeste par l’apparition de nouveaux sorptions osseuses ; foyers de formations et de re s l’irradiation : la perme abilite  vasculaire atteint — 3 mois apre son niveau initial, et le remodelage osseux atteint son maxidominance de l’activite  de re sorption ; mum avec la pre s l’irradiation : la perme abilite  vasculaire est — 6 mois apre toujours proche du niveau initial que chez le groupe de moins, le bilan de remodelage est toujours plus e leve  avec te dominance de l’activite  formation comparativement a` la pre sorption ; re s l’irradiation : le bilan de remodelage est — 12 mois apre ge  rement plus e leve  par rapport a` l’os non irradie , avec le dominance de l’activite  de formation, toutefois, l’activite  pre sorption exce de toujours celle de l’os non irradie  [16]. de re es sugge  rent que le potentiel de remodelage Ces donne cupe  re  progressivement au niveau de l’os irradie  osseux est re lement au re  tablissement de la perme abilite  vasculaire paralle s l’arre ^ t de l’irradiation. apre sultats de King et al. [16] sugge  rent que la Si les re abilite  vasculaire de l’os irradie  est presque entie rement perme cupe  re e en 6 mois, Marx et al. [1] estiment que l’irradiation re  ponse inflammatoire aigue € due produit initialement une re mie vasculaire qui se normalise au bout de 4 mois ; a` l’hyperhe lium vasculaire demeure endommage , toutefois, l’endothe

— 8 hours to 5 days after irradiation: increase in blood volume in the bone and the marrow in parallel with an increase in resorptive inflammatory activity; — 1 month after irradiation: significant drop in vascular patency with an increase in remodeling activity dominated by resorption. The increase in remodeling activity takes the form of new foci of bone formation and resorption; — 3 months after irradiation: vascular patency returns to its initial level and bone remodeling reaches a maximum, still dominated by resorption; — 6 months after irradiation: vascular patency remains close to its initial level in the control group; remodeling is still more intense, with formation now taking precedence over resorption; — 12 months after irradiation: remodeling, dominated by bone formation, is still slightly more active than in non-irradiated bone; however, the level of bone resorption is still higher than in non-irradiated bone [16]. These data suggest that the potential for bone remodeling is progressively recovered in irradiated bone, in parallel with restoration of vascular patency after cessation of radiation therapy. While the results of King et al. [16] suggest that vascular patency in irradiated bone is almost entirely recovered after 6 months, Marx et al. [1] consider that irradiation initially triggers an acute inflammatory response due to vascular hyperemia which returns to normal after about 4 months. However, the vascular endothelium remains damaged, leading

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to thrombosis with alteration of the fibroblasts. Consequently, the bone becomes progressively more hypovascularized. Thus, irradiated bone is a particularly high-risk terrain on account of its hypovascularization which increases over time, and the greater degree of bone resorption than in non-irradiated bone. The data in the literature recommend postponing orthodontic treatment until at least 2 years after radiotherapy, while the data shown above [1,16] highlight the risk of root resorption and argue in favor of the use of light forces.

ration des cellules fibroblasinduisant une thrombose avec alte quent, l’os devient de plus en plus tiques. Par conse . hypovascularise  constitue donc un terrain particulie rement a` risque L’os irradie du fait de son hypovascularisation qui augmente avec le  de re sorption qui exce de celle de l’os temps, et de l’activite . Si les donne es de la litte rature recommandent le non irradie s la report du traitement orthodontique au moins 2 ans apre rapie, les donne es pre  ce dentes [1,16] constituent un radiothe  ge  res, et la prise en argument pour l’utilisation de forces le leve  de re sorptions radiculaires. compte du risque e

Root resorption

sorptions radiculaires Les re

Radiotherapy leads to a halt in root construction, resulting in short roots with a predisposition towards resorption. Orthodontic treatment should therefore minimize any additional risk of resorption. General recommendations are to:

rapie entraıˆne un arre ^ t de l’e dification radiculaire La radiothe dispose aux qui se manifeste par des racines courtes et pre sorptions radiculaires. Le traitement orthodontique devrait re sorption radiculaire supdonc minimiser le risque d’une re mentaire. Les recommandations ge  ne rales consistent a` : ple  ge  res ; — utiliser des forces le placements dentaires ; — minimiser les de aliser une radiographie apicale apre s 6 mois de traite— re  ve le une progression de la ment actif. Si la radiographie re sorption, le traitement doit e ^tre interrompu pendant 3 mois. re ^tre de pose  mais les arcs doivent L’appareillage ne doit pas e ^tre passifs de fa¸con qu’il n’y ait pas de de placements dene taires [2–6,17–19]. Le type de la malocclusion et la morphologie des dents avant sorption le traitement, en tant que variables contribuant a` la re radiculaire, ne sont pas clairs. Il y a davantage de consensus e du traitement ; un temps de en ce qui concerne la dure  te  associe  au risque e leve  de re sorptions traitement long a e mentaire radiculaires [19]. Ceci constitue un argument supple duire la dure e du traitement orthodontique chez le pour re alablement traite  par radiothe rapie. patient pre

— use light forces; — minimize tooth movements; — perform root X-rays after 6 months of active treatment. If the X-ray reveals increased resorption, treatment should be suspended for 3 months. Brackets should not be debonded but archwires should be rendered passive so as to avoid any tooth movement [2–6,17–19]. The role of malocclusion type and pre-treatment tooth morphology as variables contributing to root resorption is not clear. There is a greater degree of consensus concerning treatment duration: long treatment time is associated with a greater risk of root resorption [19]. This is an additional argument in favor of reducing the length of orthodontic treatment in patients previously treated by radiotherapy.

Prevention of oro-dental complications

vention des complications buccodentaires Pre

Anti-cancer treatment by radiotherapy leads to reduced resistance to infections and atrophy of the oral mucosa. Consequently, irradiated patients are highly vulnerable to any irritation of the mucosal surface. Even a slight irritation can give rise to serious ulceration on account of the reduced regenerative capacity of the oral mucosa [2–5,9–13]. Special precautions need to be envisaged to minimize this risk, namely:

reux par radiothe rapie se traduit par Un traitement anticance sistance diminue e aux infections et une atrophie de la une re quent, les patients irradie s sont muqueuse buccale. Par conse s vulne rables a` toute irritation de la surface muqueuse. Une tre ^me minime, peut conduire a` une ulce ration grave irritation, me s de re  ge ne ration re duites de la en raison des capacite muqueuse buccale [2–5,9–13]. Pour minimiser ce risque, cautions particulie res doivent e ^tre prises en conside rades pre tion, a` savoir : ne buccodentaire ; — une motivation continue a` l’hygie

— continuing encouragement to maintain good oro-dental hygiene; — appropriate prescription of toothbrushes, interdental brushes, dental floss and toothpaste, with fluorine or chlorhexidine mouthwashes in the event of gingival inflammation; — excipients, such as polishing agents (silica, sodium bicarbonates, calcium phosphates), detergent-based moistening

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e de brosses a` dents, brossettes, fil — une prescription adapte s ou a` la interdentaire, dentifrices et bains de bouche fluore chlorhexidine en cas d’inflammation gingivale ; — les excipients, tels que les agents polissants (silice, bicarbonates de sodium, phosphates de calcium), humectants,

International Orthodontics 2015 ; 13 : 139-148

Cervico-facial irradiation and orthodontic treatment Irradiation cervicofaciale et traitement orthodontique

and foaming agents, thickeners, preservatives, coloring agents, sweeteners and artificial flavorings can promote allergies in patients suffering from mucitis; — regular rinsing with artificial saliva; — daily applications of fluorides by means of individual treatment trays, used for ten minutes per day. The trays can be replaced by regular applications of fluoride varnish every three months; — filling of grooves, pits and cracks to prevent or halt the development of dental caries; — careful check of orthodontic appliances: brackets with rounded, polished edges, use of protective orthodontic wax, archwires properly adjusted to follow arch contours, elastomeric ligatures, appropriate non-traumatic design of all fixed and removable appliances; — on-going surveillance of any irritation of the oral mucosa caused by orthodontic appliances; — if the patient requires additional chemotherapy or radiotherapy during the active orthodontic treatment, appliances should be removed so as to minimize possible oral complications. Once the patient is in remission and the prognosis is considered favorable orthodontic treatment can be resumed [2–5,11].

paississants, les moussants a` base de tensioactifs, et e dulcorants, et aro ^ mes artificiels conservateurs, colorants, e peuvent favoriser l’apparition d’allergies chez les patients atteints de mucite ; gulier avec de la salive artificielle ; — un rin¸cage re res de fluorures par le port de — des applications journalie res individuelles, 10 minutes par jour. Les gouttie res gouttie ^tre remplace es par l’application re gulie re de vernis peuvent e  tous les 3 mois ; fluore  venir ou — le scellement des sillons, puits et fissures pour pre ^ ter le de veloppement de caries ; arre ^ le des dispositifs orthodontiques : brackets de — le contro bords arrondis et polis, utilisation de cire de protection orthos correctement aux dontique, arcs orthodontiques ajuste lastome riques, conception contours des arcades, ligatures e e et non traumatisante des appareillages fixes et adapte amovibles ; — une surveillance continue de toute irritation de la muqueuse buccale par des appareillages orthodontiques ; rapie ou — au cas ou` le patient aurait besoin d’une chimiothe rapie comple mentaire lors de son traitement d’une radiothe ^tre de pose s pour orthodontique actif, les appareils doivent e minimiser les complications orales potentielles. Une fois que  mission et que le pronostic est conside  re  le patient est en re comme bon, le traitement orthodontique peut reprendre [2–5,11].

Conclusion

Conclusion

Radiotherapy prescribed at an early age can have long-term consequences affecting cranio-facial and oro-dental development, increasing the need for orthodontic treatment.

rapie pre conise e a` un a ^ge pre coce Les effets de la radiothe quences a` long terme qui peuvent se traduire par des conse veloppement craniofacial et buccodentaire, et affectent le de qui augmentent les besoins du traitement orthodontique. rement vulne rable, l’orthodontiste Face a` un terrain particulie gie de traitement globale qui prenne devrait suivre une strate ration les proble mes de sante  chroniques chez les en conside s, tout en acceptant des compromis the rapeupatients irradie  viter les complications. L’information du patient tiques pour e quant aux risques pouvant survenir au cours du traitement et cautions a` prendre, ainsi que la surveillance des signes aux pre  ve lateurs de rechute sont aussi d’une importance buccaux re capitale.

The orthodontist will be dealing with a particularly vulnerable terrain and should adopt an overall treatment strategy that takes into account the chronic health problems of irradiated patients and admits therapeutic compromises so as to avoid complications. It is also extremely important to inform patients of the risks that may be encountered during treatment and the precautions to be taken, and to be alert for any signs in the mouth of possible relapse.

Disclosure of interest

claration d’inte re ^ts De

The authors declare that they have no conflicts of interest concerning this article.

clarent ne pas avoir de conflits d’inte  re ^ ts en Les auteurs de relation avec cet article.

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References/References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

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Marx RE, Ehler WJ, Tayapongzak P, Pierce LW. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg 1990;160:519–24. Dahllof G, Jonsson A, Ulmner M, Huggare J. Orthodontic treatment in long-term survivors after pediatric bone marrow transplantation. Am J Orthod Dentofac Orthop 2001;120:459– 65. Sheller B, Williams B. Orthodontic management of patients with hematologic malignancies. Am J Orthod Dentofac Orthop 1996;109:575–80. Ioannidou-Marathiotou. Long term chemoradiotherapy-related dental and skeletal complications in a young female with nasopharyngeal carcinoma. Int J Gen Med 2010;3:187–96. Najafi SH, et al. The long-term effects of chemo radiotherapy on oral health and dental development in childhood cancer. J Dent (Tehran) 2011;8(1):39-43. Sklar C, Constine LS. Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 1995;31:1113–21. Blatt J, Bercu BB, Gillin JC, Mendelson WB, Poplack DG. Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukaemia. J Pediatr 1984;104:182–6. Dahllof G, Forsberg CM, Ringden O, Bolme P, Borgstrom B, Nasman M, et al. Facial growth and morphology in long-term survivors after bone marrow transplantation. Eur J Orthod 1989;11:332–40. Sonis AL, Tarbell N, Valachovic RW, Gelber R, Schwenn M, Sallan S. Dentofacial development in long-term survivors of acute lymphoblastic leukemia. A comparison of three treatment modalities. Cancer 1990;66:2645–52. Alpaslan G, Alpaslan C, Gogen H, Oguz A, Cetiner S, Karadeniz C. Disturbances in oral and dental structures in patients with pediatric lymphoma after chemotherapy. A preliminary report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:317–21. Vasconcelos NPS, Caran EMM, Lee ML, Lopes NNF, Weiler RME. Dental maturity assessment in children with acute lymphoblastic leukemia after cancer therapy. Forensic Sci Int 2009;184(1–3):10–4. Akharzouz C, Chauty S, Bodard AG. Children who received a radiotherapy treatment of the cranio-cervico-facial region: appraisal of the orthodontic treatment need. Orthod Fr 2013;84:157–68. Green DM. Late effects of treatment for cancer during childhood and adolescence. Curr Probl Cancer 2003;27:127–42. Reuther T, Schuster T, Mende U, Kubler A. Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients – a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 2003;32:289–95. Sulaiman F, Huryn JM, Zlotolow IM. Dental extractions in the irradiated head and neck patient: a retrospective analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria, and end results. J Oral Maxillofac Surg 2003;61:1123–31. King MA, Casarett GW, Weber DA. A study of irradiated bone: I. Histopathologic and physiologic changes. J Nucl Med 1979;20:1142–9. Levander E, Malmgren O, Eliasson S. Evaluation of root resorption in relation to two orthodontic treatment regimens. A clinical experimental study. Eur J Orthod 1994;16:223–8. Taithongchai R, Sookkorn K, Killiany DM. Facial and dentoalveolar structure and the prediction of apical root shortening. Am J Orthod Dentofac Orthop 1996;110:296-302. Burden D, Mullally B, Sandler J. Orthodontic treatment of patients with medical disorders. Eur J Orthod 2001;23:363–72.

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Cervico-facial irradiation and orthodontic treatment.

Cancers during infancy and childhood affect 1 to 3% of children under the age of 15. Among these cancers the most frequent are malignant hemopathies, ...
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