/home/opencode/cpanel/stomaeduj_hacked/uploads/2018/03/Article_5_3_5.pdf MAXILLOFACIAL SURGERY EFFICACY OF A DENTAL EXTRACTION POLICY DESIGNED TO PREVENT Original Article OSTEORADIONECROSIS: A RETROSPECTIVE STUDY IN 100 ORAL CANCER PATIENTS TREATED WITH INTENSITY-MODULATED RADIOTHERAPY Constantinus Politis1a* , Paul Deckers1b, Matthias Schol1b, Daan Nevens2c, Sandra Nuyts2d, Joseph Schoenaers1e, Reinhilde Jacobs1f 1 OMFS-IMPATH research group, Department of Imaging & Pathology, Faculty of Medicine, KU Leuven and Oral and Maxillofacial Surgery, University Hospitals Leuven, BE-3000 Leuven, Belgium 2 Department of Oncology, KULeuven - University of Leuven, University Hospitals Leuven - Radiation Oncology, BE-3000, Leuven, Belgium a MD, DDS, MHA, MM, PhD, Professor b DDS c MD d MD, PhD, Professor e MD, DDS, Professor f DDS,PhD, Professor ABSTRACT DOI: 10.25241/stomaeduj.2018.5(3).art.5 Introduction: The aim was to determine the efficacy of an extraction policy OPEN ACCESS This is an Open Access article under the CC BY-NC 4.0 license. designed to prevent osteoradionecrosis (ORN) in dentate areas of the jaw after Peer-Reviewed Article intensity-modulated radiotherapy (IMRT). A secondary aim was to establish whether our extraction policy risked unnecessary tooth extractions for areas designated to Citation: Politis C, Deckers P, Schol M, Nevens D, Nuyts S, Schoenaers J, Jacobs R. Efficacy of a dental extraction be not-at-risk of ORN. policy designed to prevent osteoradionecrosis: a Methodology: Data were retrospectively collected from 100 oral cancer patients, retrospective study in 100 oral cancer patients treated with intensity-modulated radiotherapy. Stoma Edu J. including the fate of 1430 individual teeth, from diagnosis to follow-up. 2018;5(3):173-178 Results: Eight percent of IMRT-treated patients developed ORN; spontaneous cases Academic Editor: Nardi Casap-Caspi, DMD, MD, (5) outnumbered those provoked by dental issues (3). All cases of ORN arose in regions Professor and Head, Hebrew University Hadassah Jerusalem, Jerusalem, Israel irradiated with > 60 Gy, with the posterior mandible as preferred location, with non- spontaneous cases primarily due to progressive periodontitis. No correlation was Received: September 03, 2018 Revised: September 19, 2018 found between the likelihood of extraction and cancer stage. Acccepted: September 24, 2018 Conclusions: A more robust extraction policy of teeth affected with periodontitis Published: September 25, 2018 and pocket depths of 4 - 5 mm might be advocated in molar areas predicted to *Corresponding author: Prof. Dr. Constantinus receive > 60 Gy. Unfortunately, our study's retrospective design precluded any Politis, MD, DDS, MHA, MM, PhD, Department of Oral and Maxillofacial Surgery, University Hospitals Leuven, detailed analyses of the underlying reasons for the 88 extractions that occurred at Kapucijnenvoer 33, Leuven, BE-3000 Belgium Tel: +32 16 332464; Fax: +32 16 332437, e-mail: lower radiation dose thresholds; a more conservative approach may therefore be constantinus.politis@uzleuven.be warranted for these low-risk areas. orcid.org/0000-0003-4772-9897 Keywords: osteoradionecrosis, intensity-modulated radiotherapy, dosimetric Copyright: © 2018 the Editorial Council for the distribution, tooth extraction, oral cancer. Stomatology Edu Journal. 1. Introduction Frequently, these screens are based on the presumption Osteoradionecrosis (ORN) of the jaw is a serious that conventional external beam radiation therapy will complication that can arise following radiotherapy for be used, as is the case in our Department of Oral and head and neck cancers [1]. ORN is defined as a slow- Maxillofacial Surgery, University Hospitals of Leuven healing radiation-induced ischemic necrosis of the (Leuven, Belgium). However, with the introduction bone, associated with varying degrees of soft tissue of intensity-modulated radiotherapy (IMRT), a necrosis in the absence of local primary tumor necrosis, significantly higher proportion of normal tissue is recurrent, or metastatic disease [1]. When radiation is spared from high-dose radiation [4], with these high delivered in standard fractions, bone irradiated at doses doses restricted to a smaller area. This leads us to in excess of 60 Gy appears to be the most vulnerable suggest that a modified extraction policy might be to ORN lesions [1]. However, occasionally, lesions arise appropriate for IMRT patients [5]. in bone exposed to lower doses (usually above 50 Gy To determine which teeth should be left in situ versus but below 60) [2]. Furthermore, ORN lesions may occur those that should be extracted (as a precautionary spontaneously after radiotherapy, or after trauma, measure in terms of ORN prevention), clinicians in particularly after dental extractions [1]. our department base their decision-making on the Pre-treatment dental screens aim to reduce the risk outcome of a "single tooth risk assessment" (Table 1), of developing ORN following radiation therapy by which is used for areas of the mouth at a low risk of removing teeth predicted to be at an increased risk developing ORN (i.e. areas < 50 Gy). of harboring infection or becoming infected [3]. Teeth which are designated "irrational to treat" in Table Stomatology Edu Journal 173 EFFICACY OF A DENTAL EXTRACTION POLICY DESIGNED TO PREVENT OSTEORADIONECROSIS: A RETROSPECTIVE STUDY IN 100 ORAL CANCER PATIENTS TREATED WITH INTENSITY-MODULATED RADIOTHERAPY 1) are extracted (leaving those with good prognoses in- Original Article situ. The fates of teeth with doubtful prognoses are then Table 1. Single tooth risk assessment. Prognosis Dental field Criteria based on levels of oral hygiene, any limitation in the Good - - ability to open the mouth, and the clinical experience of the supervising surgeon: whenever possible these Furcation involvement (levels II and III) teeth are treated and retained. Periodontal Angular bone defects For those areas at a high risk of developing ORN (> 50 “Horizontal” bone loss exceeding 2/3 of Gy), extractions are completed whenever the tooth the root Doubtful Incomplete root canal therapy demonstrates one of the signs/conditions listed in Table 2 [6]. Some teeth are also necessarily sacrificed as Endodontal Periapical pathology part of the surgical resection procedure. Presence of voluminous posts/screws The main objective of this study was to determine the Dental Extensive root caries efficacy of the tooth extraction policy in preventing ORN Recurrent periodontal abscesses at the Department of Oral and Maxillofacial Surgery, Periodontal Periodontic-endodontic lesions University Hospitals of Leuven (Leuven, Belgium). A high- Attachment loss to the apex performance extraction policy would accurately target Root perforation in the apical half of only those teeth that constitute a risk of promoting the root ORN. However, two other scenarios, should they be Endodontic Periapical pathology in the presence of identified, would be of concern as these would indicate Irrational to obturating post and core failings in the current preventative extraction protocol. treat Vertical fracture of the root These scenarios include a failure to extract teeth that Oblique fracture in the middle third of subsequently provoke ORN, or the identification of Dental the root extractions in the absence of risk (i.e. non irradiated Caries lesions that extend into the root teeth, teeth irradiated with < 50 Gy radiation, or teeth canal with none of the indications in Table 1). Functional Third molars without antagonist and with periodontitis/caries 2. Materials and Methods Table 2. Tooth extraction policy for areas predicted to receive a radiation dose > 50 Gy. 2.1. Subjects Our 100-patient cohort (with 1430 individual teeth under Lesions induced by deep caries that could expose the pulp during treatment consideration) comprised patients diagnosed with cancer pockets > 6 mm of the oral cavity between January 2012 and September furcation involvement > = level I 2016, at the Department of Oral and Maxillofacial Surgery, mobility > level I University Hospitals of Leuven (Leuven, Belgium). These gingival recession > = 6 mm patients were subsequently treated with IMRT at the Active periodontitis Department of Radiotherapy and Oncology, University with: any combination of these periodontal criteria Hospitals of Leuven (Leuven, Belgium). in patients that demonstrate poor All patients underwent pre-IMRT dental screening, cooperation, any tooth with active after which extractions of compromised teeth were periodontitis in the field of radiation is extracted performed: the “irrational to treat” as listed in Table 1, the indications as listed in Table 2, and extractions deemed Non-restorable teeth with large and/or subgingival restorations necessary because of the planned resection procedure. Root caries Since clinical, radiographic, and radiotherapeutic Teeth with large restorations, combined with severe erosion and documentation were available for all patients, we could abrasion retrospectively determine which teeth remained in- Teeth with a periapical granuloma situ and were present at the time of IMRT. These teeth Avital teeth were subsequently denoted as "not being considered a Partially impacted or partially erupted teeth that are not fully risk factor for ORN development after IMRT". covered by bone, or those showing a radiolucency above the crown Using the individual IMRT plans for each patient, all teeth Teeth with cyst formation (including those that were, and were not extracted) were subdivided according to maximum dose, with Teeth showing radiographic abnormalities categories of < 50 Gy (1), 50 - 60 Gy (2), and > 60 Gy (3). Teeth with cracked tooth syndrome This distinction was made because there is still a risk of ORN, albeit reduced [2], even if the total radiation dose delivered by standard fractionation is below 60 Gy [1]. 2.2. Statistical Analyses Patients who developed ORN prior to February 2017 The primary objective of this study was analyzed were categorized according to two types of ORN: statistically by evaluating patient subsets with spontaneous ORN that occurred post IMRT, and ORN percentages and confidence intervals, as well as plots caused by a dental issue. of an empirical distribution function. Statistical analyses The following data were also collected: patient were supervised by a certified statistician. identification number, date of cancer diagnosis, start date for IMRT, the cause of ORN and its date of Ethical Approval diagnosis. To avoid bias, clinicians involved in gathering This study was approved by the ethical committee of and processing data were not involved in treatment. UH Leuven (S54701). 174 Stoma Edu J. 2018;5(3):173-178 http://www.stomaeduj.com EFFICACY OF A DENTAL EXTRACTION POLICY DESIGNED TO PREVENT OSTEORADIONECROSIS: A RETROSPECTIVE STUDY IN 100 ORAL CANCER PATIENTS TREATED WITH INTENSITY-MODULATED RADIOTHERAPY Original Article Table 3. Details of all extractions. 3. Results Number of In 100 patients, 1770 teeth were absent at intake (Table Area Tooth status teeth 3). Management decisions for the 1430 remaining Absent at intake 1770 teeth were then made prior to surgery and/or radiation Present at intake 1430 therapy. In total 1031 teeth were left in situ, with 399 Peroperative removal in Resection site 136 extractions. The respective dose predictions for the 399 the resection specimen extracted teeth were as follows: 156 were destined to Irradiated area > Left in situ 397 50 Gy receive a radiation dose of < 50Gy; 59 were projected Irradiated area > Extracted for ORN to receive > 50Gy but < 60 Gy; and 48 extractions 50 Gy prevention 76 were in an area that would receive a dose of > 60 Gy. Irradiated area > Extracted for a dental Another 136 teeth were removed during the surgical 31 50 Gy reason procedure due to their position in the resection zone or Non-irradiated or Left in situ 634 immediately opposite the free flap. <50 Gy In those areas predicted to receive a radiation dose of Non-irradiated or Extracted for a dental 75 <50 Gy reason less than 50 Gy, 156 teeth were also extracted: 75 for dental reasons (indications listed in Table 1), and 81 for Noni-rradiated or Extracted, reasons not 81 <50 Gy specified (other) reasons that could not be established following review of the medical files. Due to the retrospective character of this study, it was impossible to identify the relevant decision-making criteria for these 81 extractions (i.e. limited cooperation of the patient, predictions of poor oral hygiene, or limited ability to open the mouth). Irrespective of the underlying reasons, the extraction policy in these areas more closely resembled the extraction policy used to prevent ORN. Collectively, 22 patients underwent 81 extractions from areas that were either not destined for irradiation, or were destined to be irradiated with a dose of < 50 Gy. One hypothesis that was tested was whether patients with an advanced stage of cancer would undergo more extractions in areas not prone to exhibit ORN of dental origin? Figure 1 shows a scatterplot depicting the correlation between Figure 1. Scatter plot showing the relationship between the number of tooth extraction (in each patient) and cancer staging at teeth removed and tumor size. the tumor level. A linear correlation could not be found. The Spearman’s rank correlation coefficient was -0.0314 (p-value = 0.7557). If only those patients that underwent tooth extractions were included, the Spearman’s rank correlation coefficient was 0.285 (p-value = 0.1465). Consequently, no correlation was found to exist between the stage of the oral cancer and the tooth extraction policy. The patients in this study had an average follow-up period of 815 days, or close to 2 years and 3 months after starting IMRT. In total, 8 out of 100 patients developed an ORN lesion, 5 spontaneously, and 3 after an extraction. For the five spontaneous cases (with no link to dental problems), 1 lesion occurred in the maxilla and the other 4 cases were in the mandible. All lesions arose in the body of the mandible, in areas where radiation levels Figure 2. Empirical distribution function showing the follow-up period exceeded 60 Gy. Lesion incidence showed a preference prior to developing ORN. for the posterior parts of the jaw in areas corresponding or higher. The causal teeth for these lesions were canine to (6) molars, (3) bicuspids, and (1) canine. (1), bicuspid (3), and molar (2). The medical files did Three patients developed ORN lesions caused by not mention any specific pathological findings at the dental problems from the retention of 6 teeth that canine or bicuspids at intake. The molars showed signs were presumed to pose (at the time of the extraction of periodontitis with pocket depths of 4 and 5 mm, decision-making) no risk of ORN. respectively, at intake. Eventually, these teeth had to be The average period between commencing IMRT and removed as periodontitis had progressed. Either this developing ORN was 438 days, or just over 1 year and infection, or the subsequent extraction, triggered ORN. 2 months; onset data for individuals (all 8 patients that developed ORN) with follow-up periods for the entire cohort are shown in Figure 2. 4. Discussion All three ORN lesions of dental origin arose in the As early as 1922, the first case of ORN was described mandible in areas exposed to a radiation dose of 60 Gy by Regaud [7]. In 1926, Ewing followed with an article Stomatology Edu Journal 175 EFFICACY OF A DENTAL EXTRACTION POLICY DESIGNED TO PREVENT OSTEORADIONECROSIS: A RETROSPECTIVE STUDY IN 100 ORAL CANCER PATIENTS TREATED WITH INTENSITY-MODULATED RADIOTHERAPY describing bone changes associated with radiation clarify this aspect of the decision-making process. For Original Article therapy that were termed “radiation osteitis" [8]. those areas not destined to receive > 60 Gy by IMRT, a Despite the extensive research provoked by these early more heuristic approach might be beneficial in terms reports, ORN still poses a substantial threat in patients of improving decision-making without bias. that have undergone radiation therapy in the head Due to the elevated incidence of oropharyngeal cancers and neck region, especially given the absence of any caused by the human papilloma virus (HPV) [17,18], the standard conservative treatment [9], and the frequent number of patients at risk of ORN is predicted to rise. requirement for extensive surgery [10]. The highest doses of radiation will be in the oropharynx The first category of ORN that should be addressed itself [19], with a smaller amount affecting the anterior is the spontaneous lesion. These can, by definition, area of the mandible. Therefore, there should be a focus not be prevented, even with an adequate extraction on maintaining the strict extraction criteria for ORN policy, as their origin is unrelated to trauma [1]. In this prevention [6] for posterior teeth, particularly those study, all but one spontaneous lesion arose in the in the mandible, whereas areas with a low risk of ORN mandible, with these results in line with the higher should be treated with the less austere general practice susceptibility of the mandible to ORN versus (vs.) the guidelines as outlined in Table 1. maxilla [1, 10]. The overall ratio for ORN incidence for In total, 8 out of 100 patients developed an ORN lesion. the mandible vs. maxilla was 24:1 [11]. All spontaneous Recent studies have reported an overall incidence lesions in this study were found in the alveolar ridge, of ORN in IMRT patients treated for oral cavity and with a preference for more posterior regions. The oropharyngeal cancer of 25.5% (mean follow-up of 41 lesions occurred in areas corresponding to 6 molars, 3 months) [20] and 40% (after 5 years of follow-up) [21]. bicuspids, and 1 canine. These findings are also in line The 8% incidence reported in this study is therefore with the general consensus that the posterior regions much lower than average. However, the short average of the jaw are more susceptible to developing ORN follow-up period of 815 days (just under 2 years and lesions [1, 10]. 3 months) may explain this low incidence rate that is The second category of ORN lesion would appear to be predicted to increase with lengthier follow-up. preventable given that this category arises following an extraction or by dental infection that occurs in areas of bone exposed to a high level of radiation [1]. The 5. Conclusions risk of developing ORN because of dental problems This study revealed that, in spite of an existing in highly irradiated alveolar bone persists for life [12]. extraction policy, ORN lesions caused by dental Furthermore, there is an increased risk of developing problems still occurred. Since ORN in these patients dental caries [13], and periodontal defects [14] after only developed in areas in receipt of > 60 Gy, primarily radiation therapy. Teeth predicted to lie in the path of in the molar areas, a more robust extraction policy high doses of radiation (> 50 Gy) should be in good could be warranted for these areas. condition in order to satisfy the criteria for being left in This study made a distinction between areas receiving situ without posing a risk of developing ORN [6, 15, 16]. a radiation dose of between 50 and 60 Gy, and those In this study, ORN caused by dental problems still areas that received a higher radiation dose. The results developed, with three cases identified. This finding show that all ORN lesions caused by a dental problem indicates that more teeth should have been extracted occurred in areas of 60 Gy or higher. As such, a cut-off from the area of high radiation in order to prevent value of 60 Gy of radiation may be a good guideline to ORN. These findings point to periodontal disease as establish for decision-making processes. The overall the greatest hazard, with periodontal pockets of 4-5 incidence of 8% (8/100) ORN after IMRT for oral and mm present at dental screening that subsequently oropharyngeal cancer, after a follow-up period of 2.3 progressed during follow-up. yrs., is considered to be low, although this figure is It was noted that ORN lesions caused by extractions expected to increase with time. Spontaneous ORN showed a slight preference to develop in the posterior (5 patients) was more common than ORN caused by regions of the alveolar bone, although not to the dental problems (3 patients). same extent as spontaneous ORN lesions. The teeth As for extractions in areas not destined for irradiation, that provoked ORN in the 3 patients were a canine, 3 or predicted to receive less than 50 Gy, a heuristic bicuspids, and 2 molars. approach to extraction decision-making is warranted. Given that IMRT spares many teeth from high doses Future prospective studies could clarify the reasoning of radiation when compared to conventional external for those extractions that failed to meet the expected beam radiation therapy [4], less teeth are predicted extraction criteria. We anticipate that this approach will to be at risk to develop ORN lesions. However, the benefit patients given that the loss of multiple teeth is findings of this study fail to account for the higher debilitating to the irradiated patient, both physically number of extractions in areas considered to pose no and emotionally. risk of developing ORN (81) vs. the 76 teeth that were at risk (Table 3). It is unclear, due to the retrospective design of this study, as to what triggered the extraction Author contributions decisions in these scenarios. However, possibilities CP, PD, MS: Substantial contributions to the design of include poor oral hygiene, future prospects of a limited the work; JS: Drafting the work; SN, DN: Substantial ability to open the mouth, poor surgical access, an contributions to the acquisition of data; RJ: reviewed uncooperative patient, or a mistaken evaluation of the the manuscript. area of high radiation. 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A review of the literature]. [Article in French]. Schweiz Monatsschr Zahnmed. 1994;104(3):271-277. Google Scholar (34) Scopus (19) Constantinus POLITIS MD, DDS, MHA, MM, PhD, Professor and Chairperson Department of Oral and Maxillofacial Surgery University Hospitals Leuven Kapucijnenvoer 33, Leuven, Belgium CV Constantinus Politis is an Oral and Maxillo-Facial Surgeon. He is currently Full Professor and Chairperson of the Department of Oral and Maxillofacial Surgery at Leuven University Hospitals, KULeuven, Belgium. He is an invited Lecturer at the EHSAL in Brussels. He graduated from the Catholic University of Leuven in medicine (MD, summa cum laude), in dentistry (DDS, magna cum laude). He specialized in oral and maxillofacial surgery at the Catholic University of Leuven. His professional field of interest is in orthognathic and orthodontic surgery and trigeminal nerve dysfunction. His clinical research projects include prevention and repair of iatrogenic trigeminal nerve injury, transplantation of teeth and orthognathic surgery. He has been elected as member of the Belgian Royal Academy of Medicine. Stomatology Edu Journal 177 EFFICACY OF A DENTAL EXTRACTION POLICY DESIGNED TO PREVENT OSTEORADIONECROSIS: A RETROSPECTIVE STUDY IN 100 ORAL CANCER PATIENTS TREATED WITH INTENSITY-MODULATED RADIOTHERAPY Questions Original Article 1. ORN occurred in areas irradiated with: qa. < 40 Gy; qb. < 50 Gy; qc. < 60 Gy; qd. > 60 Gy. 2. IMRT causes ORN in irradiation of oral and oropharyngeal cancer: qa. within the first 3 months after irradiation; qb. within the first 6 months after irradiation; qc. within the first 12 months after irradiation; qd. usually after the 1st year of irradiation. 3. ORN usually does not occur in: qa. in the upper jaw; qb. in the ascendic ramus of the lower jaw; qc. in the dentate area of the lower jaw; qd. in the area of the lower jaw where extractions have been done. 4. The following teeth need not to be extracted if they occur in a zone with 72 Gy of irradiation: qa. mobility > 6 mm; qb. periodontal pocket of 2 mm; qc. furcation > 1 mm; qd. root caries. https://2018acoms.com/cms-user/ 178 Stoma Edu J. 2018;5(3): 173-178 http://www.stomaeduj.com