Clin Oral Invest DOI 10.1007/s00784-013-1134-9
REVIEW
Oral rehabilitation with dental implants in irradiated patients: a meta-analysis on implant survival E. Schiegnitz & B. Al-Nawas & P. W. Kämmerer & K. A. Grötz
Received: 11 June 2013 / Accepted: 31 October 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Objectives The aim of this comprehensive literature review is to provide recommendations and guidelines for dental implant therapy in patients with a history of radiation in the head and neck region. For the first time, a meta-analysis comparing the implant survival in irradiated and non-irradiated patients was performed. Material and methods An extensive electronic search in the electronic databases of the National Library of Medicine was conducted for articles published between January 1990 and January 2013 to identify literature presenting survival data on the topic of dental implants in patients receiving radiotherapy for head and neck cancer. Review and meta-analysis were performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses statement. For meta-analysis, only studies with a mean follow-up of at least 5 years were included. Results After screening 529 abstracts from the electronic database, we included 31 studies in qualitative and 8 in quantitative synthesis. The mean implant survival rate of all examined studies was 83 % (range, 34–100 %). Meta-analysis of the current literature (2007–2013) revealed no statistically significant difference in implant survival between non-
irradiated native bone and irradiated native bone (odds ratio [OR], 1.44; confidence interval [CI], 0.67–3.1). In contrast, meta-analysis of the literature of the years 1990–2006 showed a significant difference in implant survival between nonirradiated and irradiated patients ([OR], 2.12; [CI], 1.69– 2.65) with a higher implant survival in the non-irradiated bone. Meta-analysis of the implant survival regarding bone origin indicated a statistically significant higher implant survival in the irradiated native bone compared to the irradiated grafted bone ([OR], 1.82; [CI], 1.14–2.90). Conclusions Within the limits of this meta-analytic approach to the literature, this study describes for the first time a comparable implant survival in non-irradiated and irradiated native bone in the current literature. Grafted bone combined with radiotherapy was identified as a negative prognostic factor on implant survival. Clinical relevance The evolution of implant hardware and improvement of treatment strategies during the last years have affirmed dental implant-supported concepts as a valuable treatment option for patients with a history of radiation in the head and neck region. Keywords Dental implants . Radiation therapy . Oral cancer . Survival rate . Bone augmentation
There are no commercial or other associations that might create a duality of interests in connection with the article. E. Schiegnitz (*) : B. Al-Nawas : P. W. Kämmerer Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre of the Johannes Gutenberg-University Mainz, Augustusplatz 2, 55131 Mainz, Germany e-mail: [email protected] P. W. Kämmerer Harvard Medical School, Boston, MA, USA K. A. Grötz Department of Oral and Maxillofacial Surgery, Dr. Horst Schmidt Clinic Wiesbaden, Wiesbaden, Germany
Introduction Cancer of the head and neck region is one of the most common malignancies and continues to be a major health concern as the 5-year survival rate still remains at approximately 50–60 % [1]. Early detection followed by correct treatment may increase cure rates and distinctly improve the quality of life [2, 3]. Besides surgery and chemotherapy, radiotherapy is an essential part of the treatment in patients suffering from cancer of the head and neck region. As a
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consequence of the cancer treatment, patients show reduced anatomical structure and physiologic functioning. Therefore, dental rehabilitation after head and neck cancer treatment and especially radiotherapy can be regarded as a highly challenging procedure. The effects of radiation on the bone tissue are an essential factor affecting the implant survival. Initial changes in bone caused by radiotherapy arise from direct injury to the remodeling system [4]. Radiation results in damage to the osteoclasts and decreases proliferation of bone marrow, collagen, and blood vessels [5]. Furthermore, vascular injury induces hyperemia, followed by endarteritis with decreasing microcirculation, thrombosis, and a progressive occlusion and obliteration of small vessels. With time, the bone marrow shows hypocellularity and hypovascularity, with marked fibrosis and fatty degeneration [4, 6]. All these lead to a compromised bone healing and a reduced viability that affects integration of the dental implant in the bone. Due to these adverse effects and altered anatomy, a complex dental rehabilitation is needed to restore function, speech, comfort, and quality of life. Although providing implantsupported prosthetics in patients with a history of radiation is a challenge and was once seen as a contraindication [7], it offers many benefits over the conventional tissue-born prostheses including improved retention, mastication, and patient acceptance. But to achieve a successful rehabilitation of patients receiving radiotherapy with dental implants, many different variables should be considered. Based on a comprehensive literature review, this study provides the basis for the development of the German guideline for dental implant therapy in irradiated patients. Furthermore, a meta-analysis comparing the implant survival in irradiated and non-irradiated patients was conducted for the first time.
Material and methods Protocol development and eligibility criteria A detailed protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement [8]. The following focused question in the Patient, Intervention, Comparison and Outcome (PICO) format was worked out [9]: “Is implant survival in irradiated jaw different to the non-irradiated jaw?” Inclusion criteria For the purpose of the present study, it was decided to include randomized controlled clinical trials, prospective clinical trials as well as retrospective studies presenting survival data on the topic of dental implants in patients receiving radiotherapy for
head and neck cancer. The following detailed inclusion criteria were defined: 1. Inclusion of greater than ten subjects 2. Published in English or German 3. Prospective studies: randomized controlled, non randomized controlled, cohort studies 4. Retrospective studies: controlled, case–control, “single cohort” 5. For meta-analysis, only studies with a follow-up higher than 5 years were considered. Studies that did not meet all the abovementioned inclusion criteria were excluded. Search strategy An extensive search in the electronic databases of the National Library of Medicine (http://www.ncbi.nlm.nih.gov) was carried out for articles published between January 1990 and January 2013. A detailed search strategy was applied using the following key words: “dental implants,” “radiation,” “quality of life,” “implant survival,” and “risk factors.” The literature research was completed using the following MeSH Terms (medical subject heading): (“dental implants” [Mesh] or “dental prosthesis, implant-supported” [Mesh], or “dental implantation” [Mesh] or “oral implants” [Mesh]) and (“head and neck neoplasms” [Mesh] or “head and neck neoplasms/ radiotherapy” [Mesh] or “oral squamous cell carcinomas (OSCC)” [Mesh] or “irradiated jaw” [Mesh]) and (“survival rate” [Mesh] or “implant survival” [Mesh]). Furthermore, the reference lists of related review articles and publications were systematically screened. Study selection Two independent reviewers (Peer W. Kämmerer [PK] and Eik Schiegnitz [ES]) initially screened the publication titles and abstracts as identified by the electronic as well as manual search for possible inclusion. For studies meeting the inclusion criteria, full-text manuscripts were obtained and evaluated further. Any disagreement between the reviewers regarding inclusion of a certain publication and data extraction was resolved by discussion and an additional review author was consulted when necessary. Kappa value as a measure of concordance was determined. The PRISMA flow diagram illustrates the flow of information through the different phases of the systematic review (Fig. 1). It depicts the number of records identified, included, and excluded and the reasons for exclusions. After a first search, there was obvious evidence that no prospective randomized studies could be found on the defined PICO question. Therefore, the possibly best available external evidence was described. The authors are aware that the risk of bias is higher compared with other reviews that
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Fig. 1 PRISMA flow diagram
include only randomized studies. Therefore, drawing definitive conclusions from this data is not recommended. To minimize the risk of bias, implant survival was selected as the objective main outcome criterion. In some studies, there was a difference between recorded numbers of dropouts and the implant survival. In these cases, implant survival was used for meta-analysis.
Statistical analysis The overall estimate effect was considered significant if p was 6 months ND postradiation (9.4)
ND
36
ND
Time of surgical reconstruction or after 3 months of healing 23 (5–203)
60 (12–140)
60
>6 months 2004–2006 postradiation
ND
ND
Squamous cell carcinoma, 41 months 1987–2008 postradiation adenoid cystic carcinoma, basal cell carcinoma, unknown primary head and neck carcinoma
ND
Squamous cell carcinoma, ameloblastoma, adenoid cystic carcinoma, keratocysts
Squamous cell carcinoma, 33 months 2000–2007 adenoid cystic carcinoma, postradiation basal cell carcinoma (12–96)
60
Time of Follow-up examination (months)
41 months 1987–2008 Squamous cell carcinoma, postradiation adenoid cystic carcinoma, basal cell carcinoma, unknown primary head and neck carcinoma
Jaw region Mean radiation Origin of malignancy dosage in Gy (range)
Table 1 Summary of studies on implant survival in the irradiated jaw
SLA: 96 % modSLA: 100 %
Grafted bone Max: 82.3 % Grafted bone Man: 98.1 %, Native bone Max: 79.8 % Native bone Man: 100 %
Overall: 89.4 % RT Max: 57.1 % RT Man: 98.4 % >50 Gy: 78.6 % 40 (12–70)
Yerit et al. [19]
103
186 RT: 124 C: 62 435 RT: 124
706
195 RT: 123 C: 72 190 RT>50 Gy: 61 C: 75
Man
Time of implant placement
1992–2004
1998–2002
1992–2005
1990–2003
>3 months 1996–2003 postradiation
Approx. 18 months postradiation
>12 months 1990–2000 postradiation
Postradiation
>12 months 1995–2010 postradiation (in 34 cases) 6 weeks 1998–2002 postradiation
Preradiation
Preradiation
1994–2006
78 %
Overall: 65 % RT: 49.44 % C: 77.8 %
60
120
RT: 75 % C: 87 %
97 % C: 100 %
Overall: 75 % (8-year) RT native bone: 72 % (8 years) RT grafted bone: 54 % (8 years) C native bone: 95 % (8 years)
93.9 % HBO: 85.2 %
Overall: 70 % (8 years) Overall: 69 % (13 years) RT: 84 % (3.8 years) RT: 54 % (13.5 years)
RT, native bone: 97 % C, native bone: 97 %
92.9 %
Overall: 82.6 % RT 50 Gy: 77.5 % C: 79.7 %
RT native bone: 89.4 % C native bone: 98.6 %
Overall: 85 % RT: 74.4 % C: 93.1 % RT, native bone: 76.9 % RT, grafted bone: 72.5 % C, native bone: 96.2 % C, grafted bone: 90.4 %
Implant survival rate
72 (6–276)
>30
60 (4–156)
36
120 (5–161)
18–24
108
60
60
41.1 (4–108)
Time of Follow-up examination (months)
Squamous cell carcinoma, Pre- and 1979–2004 adenoid cystic carcinoma, postradiation malignant ymphoma, other carcinoma ND 1994–2000 Squamous cell carcinoma, adenocarcinoma, fibrosarcoma, basal cell carcinoma Head and neck cancer >6 months 1987–2001 postradiation
Squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma
ND
squamous cell carcinoma
Malignancies and ameloblastomas
Squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma, ND tonsillar carcinoma, adenoid cystic carcinoma, rhabdomyosarcoma, osteosarcoma, unknown primary head and neck carcinoma
Jaw region Mean radiation Origin of malignancy dosage in Gy (range)
26 (60.1, 47–77)
RS
50 (61.5, 41–81) RT: 31 C: 19 93 (59, 26–89) RT: 29
111 (52, 13–79)
68 (55.7,
50 (61.5, 41–81)
206 RT: 90 C: 116
No. of implants
Schoen et al. [52] PS
Nelson et al. [51]
Schoen et al. [18] PS
RS
Salinas et al. [15]
44 (ND)
Study No. of patients type (age range, mean age)
Study
Table 1 (continued)
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RS
RS
RS
RS
Weischer et Mohr [56]
Schliephake et al. [57]
Werkmeister et al. [58]
Niimi et al. [59]
Keller et al. [60]
RS
59 (ND)
138
103
17 (67, 47–78)
26 (ND, 41–79)
221
98
409 RT: 145 C: 264 109 RT: 30 C: 79 228
175 RT: 83 C: 92
261
60 (ND)
19 (57, 24–84)
44 (ND)
138 (55, 35–79)
38 (51.9, 16–77) RT: 30
40 (55, 43–75) RT: 18 C: 22
197
No. of implants
50 (36–72)
60 (ND)
56 (27–70)
Man
50 (ND)
Max, Man ND
Man
Man
Max, Man ND (25–66)
Max, Man 54 (42–64)
Max, Man ND (32–60)
Man
Max, Man 40 (ND)
Max, Man ND (36–70)
ND (1–240) ND postradiation
>24 months 1991–1993 postradiation
20 months ND postradiation
48 months 1988–1997 postradiation (13–189)
36
21 (1–62)
60
120
9 months 1985–1995 postradiation ND 88 months ND postradiation (18–28) Squamous cell carcinoma Preradiation 1990–1996
ND
Squamous cell carcinoma
ND
Squamous cell carcinoma
Squamous cell carcinoma
ND
Jaw region Mean radiation Origin of malignancy dosage in Gy (range)
Native bone: 87.8 % Grafted bone: 58.3 %
Max: 92 % (1 year) Man: 97 % (1 year)
80 %
99 %
Japan: 88.9 % USA: 86 %
RT: 73 % C: 85 %
RT: 49.8 % C: 57.7 %
Overall: 91 % (3 years) RT: 75 % (7 years) C: 86 % (10 years)
77.8 %
72 %
Implant survival rate
RT radiotherapy group, C control group, Max maxilla, Man mandible, ND no data available or data cannot be separated, PS prospective study, RS retrospective study, CSS cross sectional study
Watzinger et al. [19]
Esser et Wagner RS [61] Jisander et al. [13] RS
PS
RS
Betz et al. [55]
RS
Grötz et al. [36]
47 (ND)
Study No. of patients type (age range, mean age)
Study
Table 1 (continued)
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Fig. 2 Forest plot of implant survival in the native irradiated jaw versus implant survival in the native non-irradiated jaw (literature, 2007–2013)
quality and level of evidence of the examined studies were low. Nearly all of the studies were retrospective analyses. Allocation concealment at high risk of bias, missing blind examiners to evaluate clinical outcomes, absence of reporting characteristics of dropouts, and lack of CONSORT adherence suggest to be careful with data interpretation and drawing general conclusions out of these studies. Study characteristics Altogether, in the investigated studies, 1,814 patients received a total of 8,177 implants. Hereof, 1,989 implants were part of control groups and were inserted in the non-irradiated jaw. The numbers of patients ranged between 17 and 207 and the age of patients between 12 and 90. The mean follow-up was 56±34 months (range, 3–120 months). Data on implant material was rarely given and could not be analyzed systematically. In most of the investigated studies, the implants were inserted in the maxilla and the mandible. Due to missing or inaccurate data, a systematic analysis concerning influence of the jaw region on implant survival was not possible. However, some studies point to a lower survival in the irradiated maxilla compared to the irradiated mandible [11–13]. Treatment
Fig. 3 Funnel plot calculated for selected studies (n =5) reporting on implants in native irradiated jaws versus implants in native non-irradiated jaws
outcomes and survival rates of the implant-retained prostheses were rarely declared, so that no conclusion could be drawn. The radiation dosage ranged between 25 and 75 Gy. In the majority of studies, the implants were inserted after radiation with a mean time of implant placement after radiotherapy of 28±24 months (range, 1–240 months). In four studies, implants were placed before radiation with a mean time of 52± 13 months (range, 36–60 months). In two studies, implants were inserted before and after radiation. Data about soft tissue conditions and soft tissue treatment in the studies were scarce. Therefore, conclusions concerning this issue were not possible.
Meta-analysis of implant survival in the irradiated jaw versus implant survival in the non-irradiated jaw A summary of all studies from the period between 1990 and 2013 examining the implant survival rate in irradiated patients is shown in Table 1. The survival rate of all studies with a follow-up between 5 and 10 years ranged between 49 and 99 %. The mean implant survival rate of all examined studies was 83±34 % (range, 33.96–100 %).
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Fig. 4 Forest plot of implant survival in the irradiated jaw versus implant survival in the non-irradiated jaw (literature, 1990–2006)
The investigated studies were divided into two time periods (1990 to 2006 and 2007 to 2013). These time periods were chosen because in the current literature, accurate data was provided about bone origin. Thus a comparison between the non-irradiated native bone and the irradiated native bone could be performed. In the literature of the years 1990 to 2006, information about bone origin was missing or incomplete. In addition, aim of this meta-analysis was to consider the evolution of implant hardware and improvement of treatment strategies during the last years. As the time of examination of some studies of the time period between 1990 and 2006 date back to end of the 1980s, the chosen cutoff was confirmed. In the current literature of the last 5 years (2007– 2013), three studies comparing implant survival between the non-irradiated native bone and the irradiated native bone with a follow-up of at least 5 years were found. Meta-analysis of these studies revealed no statistically significant difference in implant survival between the non-irradiated native jaw and the irradiated native jaw (odds ratio [OR], 1.44; confidence interval [CI], 0.67–3.1; Fig. 2). Begg and Mazumdar’s funnel plot indicated a low risk for publication bias for this meta-analysis (Fig. 3). The study of Mancha de la Plata et al. [25] was excluded from this meta-analysis by reason of missing exact Fig. 5 Funnel plot calculated for selected studies (n =4) reporting on implants in irradiated jaws versus implants in non-irradiated jaws (literature, 1990–2006)
data. Meta-analysis of the literature of the years 1990–2006 showed a significant difference in implant survival between non-irradiated and irradiated patients ([OR], 2.12; [CI], 1.69– 2.65; Fig. 4). Begg and Mazumdar’s funnel plot for this metaanalysis is shown in Fig. 5. Influence of bone origin on implant survival in the irradiated jaw Our systematic review showed the following implant survival rates in terms of bone origin: – – – –
Native bone, irradiated: 72–100 % [11, 14–20] Native bone, non-irradiated: 84–99 % [15–19, 21] Grafted bone, irradiated: 54–98 % [11, 14, 15, 17, 19, 20, 22, 23] Grafted bone, non-irradiated: 90–97 % [15, 23, 24]
Meta-analysis of the implant survival between the irradiated native bone and the irradiated grafted bone indicated a statistically significant higher implant survival in the irradiated native bone compared to the irradiated grafted bone ([OR], 1.82; [CI], 1.14–2.90; Fig. 6). In this meta-analysis, only studies with a follow-up of at least 5 years were considered.
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Fig. 6 Forest plot of survival of implants in irradiated grafted bone versus implants in irradiated local bone
A differentiation between the two periods 1990–2006 and 2007–2013 could be due to the small number of only two studies not performed. Begg and Mazumdar’s funnel plot showed a low risk for publication bias for this meta-analysis (Fig. 7).
Discussion Dental implants play an essential role in the therapy of patients receiving radiation of the head and neck region, improving their quality of life by allowing proper retention of removable prostheses, reconstruction of defects, and a reduction in the overload of vulnerable soft tissues. This study is the first metaanalysis describing a comparable implant survival between the non-irradiated native bone and the irradiated native bone in the current literature of the years 2007–2013. In this period, six studies regarding implant survival in the irradiated jaw compared to the non-irradiated jaw were published [15–18, 21, 25]. All of them showed no significant difference in implant survival between the irradiated and the nonirradiated jaw. Three of these six studies were included in meta-analysis as they showed a follow-up of at least 5 years. In addition, several current literature reviews indicated that implants can integrate into bone and remain functionally Fig. 7 Funnel plot calculated for selected studies reporting on implants in irradiated grafted bone versus implants in irradiated local bone
stable in the long-term in the irradiated jaw [4, 26–29]. In contrast, meta-analysis of the literature between 1990 and 2006 showed a significant difference in implant survival between the irradiated and the non-irradiated jaw. However, the period of patient treatment in these studies ranged between 1979 and 2004. The introduction of three-dimensional planning, guided implant surgery, improvements in implant surface features and shifts in treatment concepts in recent years may explain the fundamental changes regarding implant survival in irradiated patients. Consequently, dental implants seem to be a favorable treatment alternative for oral rehabilitation of patients with a history of radiation in the head and neck region. Generally, a multidisciplinary approach to patient care is critical for best treatment outcomes and may significantly improve patient survival [30, 31]. Concerning the influence of bone origin on implant survival, our meta-analysis showed a statistically significant higher implant survival in the irradiated native bone compared to the irradiated grafted bone. Hence, a coincidence of grafted bone and radiotherapy as a negative prognostic factor regarding implant survival is possible. These findings are confirmed by numerous studies [11, 14, 15, 19, 20, 32]. However, in our meta-analysis, only two studies were included as other studies showed follow-ups below 5 years. Therefore, definitive conclusions from this data should be drawn with caution.
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The reduced survival of implants in the grafted bone may be explained by differences in bone quality, bone volume, and revascularization compared with the original local bone. Therefore, implant placement in native bone should be preferred. Although a meta-analytic approach to examine the influence of the jaw region on implant survival was not feasible, some studies indicated a lower implant survival in the irradiated maxilla compared to the irradiated mandible [11–13]. The higher bone density of the mandible providing better initial primary implant stability could explain this higher survival rates in the mandible [33]. A dependency of implant survival on radiation dose was systematically documented in animal experiments [34]; clinically contradictory results were published in the literature [12, 17, 35, 36]. A systematic metaanalysis to evaluate this issue was due to lacking data not possible. The timing of implant placement in relation to the end of radiation therapy is another point that may contribute to the success or failure of osseointegration. In most of the studies investigated in this review, implants were inserted after radiation. There is no scientific evidence for the optimal timing of secondary implant placement, but the literature cumulatively supports implant placement between 6 and 12 months after irradiation [26, 28, 29, 32]. Another treatment concept is to insert the implants during or immediately after ablative surgery before radiation. There were promising results published in the literature [16, 18, 37]. Advantages of this approach are the following points: implant surgery in a based on radiation-compromised region is avoided, early rehabilitation of speech and mastication is possible, and another surgical intervention is obviated. However, this concept compromises the risk of interference with or delay of the oncological therapy including radiation. Assuming that bone healing and osseointegration in irradiated bone occur at a slower rate than in non-irradiated bone, an unloaded healing time of more than 6 months after implant placement is recommended [28, 32]. This is in contrast to progressive and immediate loading protocols, but this extra time assists in achieving successful osseointegration in the irradiated jaw. Soft tissues around the implant play a vital role in implant success and long-term periodontal health is often associated with the existence of keratinized gingiva. In the irradiated jaw, implant survival is particularly related to soft tissue reaction and peri-implant soft tissue inflammation is seen more frequently [38, 39]. Soft tissue conditions in tumor patients often require vestibuloplasties, but statistical evaluations of the outcome of vestibuloplasties with grafts are scarce [40, 41]. The technique of a vestibuloplasty by the use of a split-thickness skin graft from the upper thigh and an implant-retained splint showed promising results [42]. To decrease the likelihood for ORN onset, hyperbaric oxygen treatment (HBO) has been advised in conjunction with implant placement. The protocol of HBO used after RT in the head and neck region
compromises 20 to 30 sessions prior and 10 min after implant placement with 100 % oxygen [43]. There are contradictory results in the literature concerning effectiveness of HBO; however, a Cochrane review reported no additional benefit with the use of HBO on implant success in irradiated bone [44]. To date, some studies address the problem of recurrence of malignancy next to dental implants, most often via presentation of a solitary or several implant-related carcinomas [45–48]. Thus, patients with a history of previous OSCC profit from individualized recall intervals and careful clinical evaluations. Scalpel biopsy of persisting macroscopic lesions for these patients should be mandatory to rule out an invasive carcinoma [45].
Conclusion Within the limits of this meta-analytic approach to the literature, we demonstrated a comparable implant survival between the non-irradiated native bone and the irradiated native bone in the current literature. Therefore, patients with a history of radiation in the head and neck region can be successfully treated with dental implants. However, the coincidence of grafted bone and radiotherapy as a negative prognostic factor on implant survival must be considered. Generally, the patient and the attending clinician must be aware of potential risks and complications relevant to implant therapy in the irradiated patient to provide safe and predictable treatment.
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25. Mancha de la Plata M, Gias LN, Diez PM, Munoz-Guerra M, Gonzalez-Garcia R, Lee GY, Castrejon-Castrejon S, RodriguezCampo FJ (2012) Osseointegrated implant rehabilitation of irradiated oral cancer patients. J Oral Maxillofac Surg 70(5):1052–1063. doi: 10.1016/j.joms.2011.03.032 26. Anderson L, Meraw S, Al-Hezaimi K, Wang HL (2013) The influence of radiation therapy on dental implantology. Implant Dent 22(1): 31–38. doi:10.1097/ID.0b013e31827e84ee 27. Pace-Balzan A, Rogers SN (2012) Dental rehabilitation after surgery for oral cancer. Curr Opin Otolaryngol Head Neck Surg 20(2):109– 113. doi:10.1097/MOO.0b013e32834f5fef 28. Grötz KA, Schmidt BLJ (2013) Onko II: supportive TU-Betreuung. Handbuch MKG Update 1:17–20 29. Javed F, Al-Hezaimi K, Al-Rasheed A, Almas K, Romanos GE (2010) Implant survival rate after oral cancer therapy: a review. Oral Oncol 46(12):854–859. doi:10.1016/j.oraloncology.2010.10. 004 30. Friedland PL, Bozic B, Dewar J, Kuan R, Meyer C, Phillips M (2011) Impact of multidisciplinary team management in head and neck cancer patients. Br J Cancer 104(8):1246–1248. doi:10.1038/bjc. 2011.92 31. Cawood JI, Stoelinga PJ (2006) International academy for oral and facial rehabilitation–consensus report. Int J Oral Maxillofac Surg 35(3):195–198. doi:10.1016/j.ijom.2005.09.008 32. Dholam KP, Gurav SV (2012) Dental implants in irradiated jaws: a literature review. J Cancer Res Ther 8(Suppl 1):S85–S93. doi:10. 4103/0973-1482.92220 33. Kovacs AF (2000) Clinical analysis of implant losses in oral tumor and defect patients. Clin Oral Implants Res 11(5):494–504 34. Asikainen P, Klemetti E, Kotilainen R, Vuillemin T, Sutter F, Voipio HM, Kullaa A (1998) Osseointegration of dental implants in bone irradiated with 40, 50 or 60 gy doses, An experimental study with beagle dogs. Clin Oral Implants Res 9(1):20–25 35. Granstrom G (2005) Osseointegration in irradiated cancer patients: an analysis with respect to implant failures. J Oral Maxillofac Surg 63(5):579–585. doi:10.1016/j.joms.2005.01.008 36. Grotz KA, Wahlmann UW, Krummenauer F, Wegener J, Al-Nawas B, Kuffner HD, Wagner W (1999) [Prognosis and prognostic factors of endosseous implants in the irradiated jaw]. Mund Kiefer Gesichtschir 3(Suppl 1):S117–S124 37. Schepers RH, Slagter AP, Kaanders JH, van den Hoogen FJ, Merkx MA (2006) Effect of postoperative radiotherapy on the functional result of implants placed during ablative surgery for oral cancer. Int J Oral Maxillofac Surg 35(9):803–808. doi:10.1016/j.ijom.2006.03. 007 38. Eckert SE, Desjardins RP, Keller EE, Tolman DE (1996) Endosseous implants in an irradiated tissue bed. J Prosthet Dent 76(1):45–49 39. Kämmerer PW, Lehmann KM, Karbach J, Wegener J, Al-Nawas B, Wagner W (2011) Prevalence of peri-implant diseases associated with a rough-surface dental implant system 9 years after insertion. Int J Oral Imp Clin Res 3(3):135–139 40. Froschl T, Kerscher A (1997) The optimal vestibuloplasty in preprosthetic surgery of the mandible. J Craniomaxillofac Surg 25(2):85–90 41. Kao SY, Lui MT, Fong J, Wu DC, Wu CH, Tu HF, Hung KF, Yeung TC (2005) A method using vestibulo-sulcoplasty combining a splitthickness skin graft and a palatal keratinized mucosa graft for periimplant tissue secondary to oral cancer surgery. J Oral Implantol 31(4):186–191. doi:10.1563/1548-1336(2005)31[186:AMUVCA]2. 0.CO;2 42. Heberer S, Nelson K (2009) Clinical evaluation of a modified method of vestibuloplasty using an implant-retained splint. J Oral Maxillofac Surg 67(3):624–629. doi:10.1016/j.joms.2008.09.029 43. Marx RE, Johnson RP, Kline SN (1985) Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc 111(1):49–54
Clin Oral Invest 44. Coulthard P, Patel S, Grusovin GM, Worthington HV, Esposito M (2008) Hyperbaric oxygen therapy for irradiated patients who require dental implants: a Cochrane review of randomised clinical trials. Eur J Oral Implantol 1(2):105–110 45. Moergel M, Karbach J, Kunkel M, Wagner W (2013) Oral squamous cell carcinoma in the vicinity of dental implants. Clin Oral Investig. doi:10.1007/s00784-013-0968-5 46. Shaw R, Sutton D, Brown J, Cawood J (2004) Further malignancy in field change adjacent to osseointegrated implants. Int J Oral Maxillofac Surg 33(4):353–355. doi:10.1016/j.ijom.2003.09.017 47. Schache A, Thavaraj S, Kalavrezos N (2008) Osseointegrated implants: a potential route of entry for squamous cell carcinoma of the mandible. Br J Oral Maxillofac Surg 46(5):397–399. doi:10.1016/j. bjoms.2007.09.009 48. De Ceulaer J, Magremanne M, van Veen A, Scheerlinck J (2010) Squamous cell carcinoma recurrence around dental implants. J Oral Maxillofac Surg 68(10):2507–2512. doi:10. 1016/j.joms.2010.01.023 49. Heberer S, Kilic S, Hossamo J, Raguse JD, Nelson K (2011) Rehabilitation of irradiated patients with modified and conventional sandblasted acid-etched implants: preliminary results of a splitmouth study. Clin Oral Implants Res 22(5):546–551 50. Cuesta-Gil M, Ochandiano Caicoya S, Riba-García F, Duarte Ruiz B, Navarro Cuéllar C, Navarro Vila C (2009) Oral rehabilitation with osseointegrated implants in oncologic patients. J Oral Maxillofac Surg 67(11):2485–2496 51. Nelson K, Heberer S, Glatzer C (2007) Survival analysis and clinical evaluation of implant-retained prostheses in oral cancer resection patients over a mean follow-up period of 10 years. J Prosthet Dent 98(5):405–410 52. Schoen PJ, Raghoebar GM, Bouma J, Reintsema H, Vissink A, Sterk W, Roodenburg JL (2007) Rehabilitation of oral function in head and
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neck cancer patients after radiotherapy with implant-retained dentures: effects of hyperbaric oxygen therapy. Oral Oncol 43(4):379–388 Cao Y, Weischer T (2003) Comparison of maxillary implant-supported prosthesis in irradiated and non-irradiated patients. J Huazhong Univ Sci Technolog Med Sci 23(2):209–212 Visch LL, van Waas MA, Schmitz PI, Levendag PC (2002) A clinical evaluation of implants in irradiated oral cancer patients. J Dent Res 81(12):856–859 Betz T, Purps S, Pistner H, Bill J, Reuther J (1999) Oral rehabilitation of tumor patients with enosseous dental implants – success rate taking into account the peri-implant hard and soft tissues. Mund Kiefer GesichtsChir 3(Suppl 1): S99–S105 Weischer T, Mohr C (1999) Ten-year experience in oral implant rehabilitation of cancer patients: treatment concept and proposed criteria for success. Int J Oral Maxillofac Implants 14(4):521–528 Schliephake H, Neukam FW, Schmelzeisen R, Wichmann M (1999) Long-term results of endosteal implants used for restoration of oral function after oncologic surgery. Int J Oral Maxillofac Surg 28(4): 260–265 Werkmeister R, Szulczewski D, Walteros-Benz P, Joos U (1999) Rehabilitation with dental implants of oral cancer patients. J Craniomaxillofac Surg 27(1):38–41 Niimi A, Ueda M, Keller EE, Worthington P (1998) Experience with osseointegrated implants placed in irradiated tissues in Japan and the United States. Int J Oral Maxillofac Implants 13(3):407–411 Keller EE, Tolman DE, Zuck SL, Eckert SE (1997) Mandibular endosseous implants and autogenous bone grafting in irradiated tissue: a 10-year retrospective study. Int J Oral Maxillofac Implants 12(6):800–813 Esser E, Wagner W (1997) Dental implants following radical oral cancer surgery and adjuvant radiotherapy. Int J Oral Maxillofac Implants 12(4):552–557
REVIEW
Oral rehabilitation with dental implants in irradiated patients: a meta-analysis on implant survival E. Schiegnitz & B. Al-Nawas & P. W. Kämmerer & K. A. Grötz
Received: 11 June 2013 / Accepted: 31 October 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Objectives The aim of this comprehensive literature review is to provide recommendations and guidelines for dental implant therapy in patients with a history of radiation in the head and neck region. For the first time, a meta-analysis comparing the implant survival in irradiated and non-irradiated patients was performed. Material and methods An extensive electronic search in the electronic databases of the National Library of Medicine was conducted for articles published between January 1990 and January 2013 to identify literature presenting survival data on the topic of dental implants in patients receiving radiotherapy for head and neck cancer. Review and meta-analysis were performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses statement. For meta-analysis, only studies with a mean follow-up of at least 5 years were included. Results After screening 529 abstracts from the electronic database, we included 31 studies in qualitative and 8 in quantitative synthesis. The mean implant survival rate of all examined studies was 83 % (range, 34–100 %). Meta-analysis of the current literature (2007–2013) revealed no statistically significant difference in implant survival between non-
irradiated native bone and irradiated native bone (odds ratio [OR], 1.44; confidence interval [CI], 0.67–3.1). In contrast, meta-analysis of the literature of the years 1990–2006 showed a significant difference in implant survival between nonirradiated and irradiated patients ([OR], 2.12; [CI], 1.69– 2.65) with a higher implant survival in the non-irradiated bone. Meta-analysis of the implant survival regarding bone origin indicated a statistically significant higher implant survival in the irradiated native bone compared to the irradiated grafted bone ([OR], 1.82; [CI], 1.14–2.90). Conclusions Within the limits of this meta-analytic approach to the literature, this study describes for the first time a comparable implant survival in non-irradiated and irradiated native bone in the current literature. Grafted bone combined with radiotherapy was identified as a negative prognostic factor on implant survival. Clinical relevance The evolution of implant hardware and improvement of treatment strategies during the last years have affirmed dental implant-supported concepts as a valuable treatment option for patients with a history of radiation in the head and neck region. Keywords Dental implants . Radiation therapy . Oral cancer . Survival rate . Bone augmentation
There are no commercial or other associations that might create a duality of interests in connection with the article. E. Schiegnitz (*) : B. Al-Nawas : P. W. Kämmerer Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre of the Johannes Gutenberg-University Mainz, Augustusplatz 2, 55131 Mainz, Germany e-mail: [email protected] P. W. Kämmerer Harvard Medical School, Boston, MA, USA K. A. Grötz Department of Oral and Maxillofacial Surgery, Dr. Horst Schmidt Clinic Wiesbaden, Wiesbaden, Germany
Introduction Cancer of the head and neck region is one of the most common malignancies and continues to be a major health concern as the 5-year survival rate still remains at approximately 50–60 % [1]. Early detection followed by correct treatment may increase cure rates and distinctly improve the quality of life [2, 3]. Besides surgery and chemotherapy, radiotherapy is an essential part of the treatment in patients suffering from cancer of the head and neck region. As a
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consequence of the cancer treatment, patients show reduced anatomical structure and physiologic functioning. Therefore, dental rehabilitation after head and neck cancer treatment and especially radiotherapy can be regarded as a highly challenging procedure. The effects of radiation on the bone tissue are an essential factor affecting the implant survival. Initial changes in bone caused by radiotherapy arise from direct injury to the remodeling system [4]. Radiation results in damage to the osteoclasts and decreases proliferation of bone marrow, collagen, and blood vessels [5]. Furthermore, vascular injury induces hyperemia, followed by endarteritis with decreasing microcirculation, thrombosis, and a progressive occlusion and obliteration of small vessels. With time, the bone marrow shows hypocellularity and hypovascularity, with marked fibrosis and fatty degeneration [4, 6]. All these lead to a compromised bone healing and a reduced viability that affects integration of the dental implant in the bone. Due to these adverse effects and altered anatomy, a complex dental rehabilitation is needed to restore function, speech, comfort, and quality of life. Although providing implantsupported prosthetics in patients with a history of radiation is a challenge and was once seen as a contraindication [7], it offers many benefits over the conventional tissue-born prostheses including improved retention, mastication, and patient acceptance. But to achieve a successful rehabilitation of patients receiving radiotherapy with dental implants, many different variables should be considered. Based on a comprehensive literature review, this study provides the basis for the development of the German guideline for dental implant therapy in irradiated patients. Furthermore, a meta-analysis comparing the implant survival in irradiated and non-irradiated patients was conducted for the first time.
Material and methods Protocol development and eligibility criteria A detailed protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement [8]. The following focused question in the Patient, Intervention, Comparison and Outcome (PICO) format was worked out [9]: “Is implant survival in irradiated jaw different to the non-irradiated jaw?” Inclusion criteria For the purpose of the present study, it was decided to include randomized controlled clinical trials, prospective clinical trials as well as retrospective studies presenting survival data on the topic of dental implants in patients receiving radiotherapy for
head and neck cancer. The following detailed inclusion criteria were defined: 1. Inclusion of greater than ten subjects 2. Published in English or German 3. Prospective studies: randomized controlled, non randomized controlled, cohort studies 4. Retrospective studies: controlled, case–control, “single cohort” 5. For meta-analysis, only studies with a follow-up higher than 5 years were considered. Studies that did not meet all the abovementioned inclusion criteria were excluded. Search strategy An extensive search in the electronic databases of the National Library of Medicine (http://www.ncbi.nlm.nih.gov) was carried out for articles published between January 1990 and January 2013. A detailed search strategy was applied using the following key words: “dental implants,” “radiation,” “quality of life,” “implant survival,” and “risk factors.” The literature research was completed using the following MeSH Terms (medical subject heading): (“dental implants” [Mesh] or “dental prosthesis, implant-supported” [Mesh], or “dental implantation” [Mesh] or “oral implants” [Mesh]) and (“head and neck neoplasms” [Mesh] or “head and neck neoplasms/ radiotherapy” [Mesh] or “oral squamous cell carcinomas (OSCC)” [Mesh] or “irradiated jaw” [Mesh]) and (“survival rate” [Mesh] or “implant survival” [Mesh]). Furthermore, the reference lists of related review articles and publications were systematically screened. Study selection Two independent reviewers (Peer W. Kämmerer [PK] and Eik Schiegnitz [ES]) initially screened the publication titles and abstracts as identified by the electronic as well as manual search for possible inclusion. For studies meeting the inclusion criteria, full-text manuscripts were obtained and evaluated further. Any disagreement between the reviewers regarding inclusion of a certain publication and data extraction was resolved by discussion and an additional review author was consulted when necessary. Kappa value as a measure of concordance was determined. The PRISMA flow diagram illustrates the flow of information through the different phases of the systematic review (Fig. 1). It depicts the number of records identified, included, and excluded and the reasons for exclusions. After a first search, there was obvious evidence that no prospective randomized studies could be found on the defined PICO question. Therefore, the possibly best available external evidence was described. The authors are aware that the risk of bias is higher compared with other reviews that
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Fig. 1 PRISMA flow diagram
include only randomized studies. Therefore, drawing definitive conclusions from this data is not recommended. To minimize the risk of bias, implant survival was selected as the objective main outcome criterion. In some studies, there was a difference between recorded numbers of dropouts and the implant survival. In these cases, implant survival was used for meta-analysis.
Statistical analysis The overall estimate effect was considered significant if p was 6 months ND postradiation (9.4)
ND
36
ND
Time of surgical reconstruction or after 3 months of healing 23 (5–203)
60 (12–140)
60
>6 months 2004–2006 postradiation
ND
ND
Squamous cell carcinoma, 41 months 1987–2008 postradiation adenoid cystic carcinoma, basal cell carcinoma, unknown primary head and neck carcinoma
ND
Squamous cell carcinoma, ameloblastoma, adenoid cystic carcinoma, keratocysts
Squamous cell carcinoma, 33 months 2000–2007 adenoid cystic carcinoma, postradiation basal cell carcinoma (12–96)
60
Time of Follow-up examination (months)
41 months 1987–2008 Squamous cell carcinoma, postradiation adenoid cystic carcinoma, basal cell carcinoma, unknown primary head and neck carcinoma
Jaw region Mean radiation Origin of malignancy dosage in Gy (range)
Table 1 Summary of studies on implant survival in the irradiated jaw
SLA: 96 % modSLA: 100 %
Grafted bone Max: 82.3 % Grafted bone Man: 98.1 %, Native bone Max: 79.8 % Native bone Man: 100 %
Overall: 89.4 % RT Max: 57.1 % RT Man: 98.4 % >50 Gy: 78.6 % 40 (12–70)
Yerit et al. [19]
103
186 RT: 124 C: 62 435 RT: 124
706
195 RT: 123 C: 72 190 RT>50 Gy: 61 C: 75
Man
Time of implant placement
1992–2004
1998–2002
1992–2005
1990–2003
>3 months 1996–2003 postradiation
Approx. 18 months postradiation
>12 months 1990–2000 postradiation
Postradiation
>12 months 1995–2010 postradiation (in 34 cases) 6 weeks 1998–2002 postradiation
Preradiation
Preradiation
1994–2006
78 %
Overall: 65 % RT: 49.44 % C: 77.8 %
60
120
RT: 75 % C: 87 %
97 % C: 100 %
Overall: 75 % (8-year) RT native bone: 72 % (8 years) RT grafted bone: 54 % (8 years) C native bone: 95 % (8 years)
93.9 % HBO: 85.2 %
Overall: 70 % (8 years) Overall: 69 % (13 years) RT: 84 % (3.8 years) RT: 54 % (13.5 years)
RT, native bone: 97 % C, native bone: 97 %
92.9 %
Overall: 82.6 % RT 50 Gy: 77.5 % C: 79.7 %
RT native bone: 89.4 % C native bone: 98.6 %
Overall: 85 % RT: 74.4 % C: 93.1 % RT, native bone: 76.9 % RT, grafted bone: 72.5 % C, native bone: 96.2 % C, grafted bone: 90.4 %
Implant survival rate
72 (6–276)
>30
60 (4–156)
36
120 (5–161)
18–24
108
60
60
41.1 (4–108)
Time of Follow-up examination (months)
Squamous cell carcinoma, Pre- and 1979–2004 adenoid cystic carcinoma, postradiation malignant ymphoma, other carcinoma ND 1994–2000 Squamous cell carcinoma, adenocarcinoma, fibrosarcoma, basal cell carcinoma Head and neck cancer >6 months 1987–2001 postradiation
Squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma
ND
squamous cell carcinoma
Malignancies and ameloblastomas
Squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma, ND tonsillar carcinoma, adenoid cystic carcinoma, rhabdomyosarcoma, osteosarcoma, unknown primary head and neck carcinoma
Jaw region Mean radiation Origin of malignancy dosage in Gy (range)
26 (60.1, 47–77)
RS
50 (61.5, 41–81) RT: 31 C: 19 93 (59, 26–89) RT: 29
111 (52, 13–79)
68 (55.7,
50 (61.5, 41–81)
206 RT: 90 C: 116
No. of implants
Schoen et al. [52] PS
Nelson et al. [51]
Schoen et al. [18] PS
RS
Salinas et al. [15]
44 (ND)
Study No. of patients type (age range, mean age)
Study
Table 1 (continued)
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RS
RS
RS
RS
Weischer et Mohr [56]
Schliephake et al. [57]
Werkmeister et al. [58]
Niimi et al. [59]
Keller et al. [60]
RS
59 (ND)
138
103
17 (67, 47–78)
26 (ND, 41–79)
221
98
409 RT: 145 C: 264 109 RT: 30 C: 79 228
175 RT: 83 C: 92
261
60 (ND)
19 (57, 24–84)
44 (ND)
138 (55, 35–79)
38 (51.9, 16–77) RT: 30
40 (55, 43–75) RT: 18 C: 22
197
No. of implants
50 (36–72)
60 (ND)
56 (27–70)
Man
50 (ND)
Max, Man ND
Man
Man
Max, Man ND (25–66)
Max, Man 54 (42–64)
Max, Man ND (32–60)
Man
Max, Man 40 (ND)
Max, Man ND (36–70)
ND (1–240) ND postradiation
>24 months 1991–1993 postradiation
20 months ND postradiation
48 months 1988–1997 postradiation (13–189)
36
21 (1–62)
60
120
9 months 1985–1995 postradiation ND 88 months ND postradiation (18–28) Squamous cell carcinoma Preradiation 1990–1996
ND
Squamous cell carcinoma
ND
Squamous cell carcinoma
Squamous cell carcinoma
ND
Jaw region Mean radiation Origin of malignancy dosage in Gy (range)
Native bone: 87.8 % Grafted bone: 58.3 %
Max: 92 % (1 year) Man: 97 % (1 year)
80 %
99 %
Japan: 88.9 % USA: 86 %
RT: 73 % C: 85 %
RT: 49.8 % C: 57.7 %
Overall: 91 % (3 years) RT: 75 % (7 years) C: 86 % (10 years)
77.8 %
72 %
Implant survival rate
RT radiotherapy group, C control group, Max maxilla, Man mandible, ND no data available or data cannot be separated, PS prospective study, RS retrospective study, CSS cross sectional study
Watzinger et al. [19]
Esser et Wagner RS [61] Jisander et al. [13] RS
PS
RS
Betz et al. [55]
RS
Grötz et al. [36]
47 (ND)
Study No. of patients type (age range, mean age)
Study
Table 1 (continued)
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Fig. 2 Forest plot of implant survival in the native irradiated jaw versus implant survival in the native non-irradiated jaw (literature, 2007–2013)
quality and level of evidence of the examined studies were low. Nearly all of the studies were retrospective analyses. Allocation concealment at high risk of bias, missing blind examiners to evaluate clinical outcomes, absence of reporting characteristics of dropouts, and lack of CONSORT adherence suggest to be careful with data interpretation and drawing general conclusions out of these studies. Study characteristics Altogether, in the investigated studies, 1,814 patients received a total of 8,177 implants. Hereof, 1,989 implants were part of control groups and were inserted in the non-irradiated jaw. The numbers of patients ranged between 17 and 207 and the age of patients between 12 and 90. The mean follow-up was 56±34 months (range, 3–120 months). Data on implant material was rarely given and could not be analyzed systematically. In most of the investigated studies, the implants were inserted in the maxilla and the mandible. Due to missing or inaccurate data, a systematic analysis concerning influence of the jaw region on implant survival was not possible. However, some studies point to a lower survival in the irradiated maxilla compared to the irradiated mandible [11–13]. Treatment
Fig. 3 Funnel plot calculated for selected studies (n =5) reporting on implants in native irradiated jaws versus implants in native non-irradiated jaws
outcomes and survival rates of the implant-retained prostheses were rarely declared, so that no conclusion could be drawn. The radiation dosage ranged between 25 and 75 Gy. In the majority of studies, the implants were inserted after radiation with a mean time of implant placement after radiotherapy of 28±24 months (range, 1–240 months). In four studies, implants were placed before radiation with a mean time of 52± 13 months (range, 36–60 months). In two studies, implants were inserted before and after radiation. Data about soft tissue conditions and soft tissue treatment in the studies were scarce. Therefore, conclusions concerning this issue were not possible.
Meta-analysis of implant survival in the irradiated jaw versus implant survival in the non-irradiated jaw A summary of all studies from the period between 1990 and 2013 examining the implant survival rate in irradiated patients is shown in Table 1. The survival rate of all studies with a follow-up between 5 and 10 years ranged between 49 and 99 %. The mean implant survival rate of all examined studies was 83±34 % (range, 33.96–100 %).
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Fig. 4 Forest plot of implant survival in the irradiated jaw versus implant survival in the non-irradiated jaw (literature, 1990–2006)
The investigated studies were divided into two time periods (1990 to 2006 and 2007 to 2013). These time periods were chosen because in the current literature, accurate data was provided about bone origin. Thus a comparison between the non-irradiated native bone and the irradiated native bone could be performed. In the literature of the years 1990 to 2006, information about bone origin was missing or incomplete. In addition, aim of this meta-analysis was to consider the evolution of implant hardware and improvement of treatment strategies during the last years. As the time of examination of some studies of the time period between 1990 and 2006 date back to end of the 1980s, the chosen cutoff was confirmed. In the current literature of the last 5 years (2007– 2013), three studies comparing implant survival between the non-irradiated native bone and the irradiated native bone with a follow-up of at least 5 years were found. Meta-analysis of these studies revealed no statistically significant difference in implant survival between the non-irradiated native jaw and the irradiated native jaw (odds ratio [OR], 1.44; confidence interval [CI], 0.67–3.1; Fig. 2). Begg and Mazumdar’s funnel plot indicated a low risk for publication bias for this meta-analysis (Fig. 3). The study of Mancha de la Plata et al. [25] was excluded from this meta-analysis by reason of missing exact Fig. 5 Funnel plot calculated for selected studies (n =4) reporting on implants in irradiated jaws versus implants in non-irradiated jaws (literature, 1990–2006)
data. Meta-analysis of the literature of the years 1990–2006 showed a significant difference in implant survival between non-irradiated and irradiated patients ([OR], 2.12; [CI], 1.69– 2.65; Fig. 4). Begg and Mazumdar’s funnel plot for this metaanalysis is shown in Fig. 5. Influence of bone origin on implant survival in the irradiated jaw Our systematic review showed the following implant survival rates in terms of bone origin: – – – –
Native bone, irradiated: 72–100 % [11, 14–20] Native bone, non-irradiated: 84–99 % [15–19, 21] Grafted bone, irradiated: 54–98 % [11, 14, 15, 17, 19, 20, 22, 23] Grafted bone, non-irradiated: 90–97 % [15, 23, 24]
Meta-analysis of the implant survival between the irradiated native bone and the irradiated grafted bone indicated a statistically significant higher implant survival in the irradiated native bone compared to the irradiated grafted bone ([OR], 1.82; [CI], 1.14–2.90; Fig. 6). In this meta-analysis, only studies with a follow-up of at least 5 years were considered.
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Fig. 6 Forest plot of survival of implants in irradiated grafted bone versus implants in irradiated local bone
A differentiation between the two periods 1990–2006 and 2007–2013 could be due to the small number of only two studies not performed. Begg and Mazumdar’s funnel plot showed a low risk for publication bias for this meta-analysis (Fig. 7).
Discussion Dental implants play an essential role in the therapy of patients receiving radiation of the head and neck region, improving their quality of life by allowing proper retention of removable prostheses, reconstruction of defects, and a reduction in the overload of vulnerable soft tissues. This study is the first metaanalysis describing a comparable implant survival between the non-irradiated native bone and the irradiated native bone in the current literature of the years 2007–2013. In this period, six studies regarding implant survival in the irradiated jaw compared to the non-irradiated jaw were published [15–18, 21, 25]. All of them showed no significant difference in implant survival between the irradiated and the nonirradiated jaw. Three of these six studies were included in meta-analysis as they showed a follow-up of at least 5 years. In addition, several current literature reviews indicated that implants can integrate into bone and remain functionally Fig. 7 Funnel plot calculated for selected studies reporting on implants in irradiated grafted bone versus implants in irradiated local bone
stable in the long-term in the irradiated jaw [4, 26–29]. In contrast, meta-analysis of the literature between 1990 and 2006 showed a significant difference in implant survival between the irradiated and the non-irradiated jaw. However, the period of patient treatment in these studies ranged between 1979 and 2004. The introduction of three-dimensional planning, guided implant surgery, improvements in implant surface features and shifts in treatment concepts in recent years may explain the fundamental changes regarding implant survival in irradiated patients. Consequently, dental implants seem to be a favorable treatment alternative for oral rehabilitation of patients with a history of radiation in the head and neck region. Generally, a multidisciplinary approach to patient care is critical for best treatment outcomes and may significantly improve patient survival [30, 31]. Concerning the influence of bone origin on implant survival, our meta-analysis showed a statistically significant higher implant survival in the irradiated native bone compared to the irradiated grafted bone. Hence, a coincidence of grafted bone and radiotherapy as a negative prognostic factor regarding implant survival is possible. These findings are confirmed by numerous studies [11, 14, 15, 19, 20, 32]. However, in our meta-analysis, only two studies were included as other studies showed follow-ups below 5 years. Therefore, definitive conclusions from this data should be drawn with caution.
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The reduced survival of implants in the grafted bone may be explained by differences in bone quality, bone volume, and revascularization compared with the original local bone. Therefore, implant placement in native bone should be preferred. Although a meta-analytic approach to examine the influence of the jaw region on implant survival was not feasible, some studies indicated a lower implant survival in the irradiated maxilla compared to the irradiated mandible [11–13]. The higher bone density of the mandible providing better initial primary implant stability could explain this higher survival rates in the mandible [33]. A dependency of implant survival on radiation dose was systematically documented in animal experiments [34]; clinically contradictory results were published in the literature [12, 17, 35, 36]. A systematic metaanalysis to evaluate this issue was due to lacking data not possible. The timing of implant placement in relation to the end of radiation therapy is another point that may contribute to the success or failure of osseointegration. In most of the studies investigated in this review, implants were inserted after radiation. There is no scientific evidence for the optimal timing of secondary implant placement, but the literature cumulatively supports implant placement between 6 and 12 months after irradiation [26, 28, 29, 32]. Another treatment concept is to insert the implants during or immediately after ablative surgery before radiation. There were promising results published in the literature [16, 18, 37]. Advantages of this approach are the following points: implant surgery in a based on radiation-compromised region is avoided, early rehabilitation of speech and mastication is possible, and another surgical intervention is obviated. However, this concept compromises the risk of interference with or delay of the oncological therapy including radiation. Assuming that bone healing and osseointegration in irradiated bone occur at a slower rate than in non-irradiated bone, an unloaded healing time of more than 6 months after implant placement is recommended [28, 32]. This is in contrast to progressive and immediate loading protocols, but this extra time assists in achieving successful osseointegration in the irradiated jaw. Soft tissues around the implant play a vital role in implant success and long-term periodontal health is often associated with the existence of keratinized gingiva. In the irradiated jaw, implant survival is particularly related to soft tissue reaction and peri-implant soft tissue inflammation is seen more frequently [38, 39]. Soft tissue conditions in tumor patients often require vestibuloplasties, but statistical evaluations of the outcome of vestibuloplasties with grafts are scarce [40, 41]. The technique of a vestibuloplasty by the use of a split-thickness skin graft from the upper thigh and an implant-retained splint showed promising results [42]. To decrease the likelihood for ORN onset, hyperbaric oxygen treatment (HBO) has been advised in conjunction with implant placement. The protocol of HBO used after RT in the head and neck region
compromises 20 to 30 sessions prior and 10 min after implant placement with 100 % oxygen [43]. There are contradictory results in the literature concerning effectiveness of HBO; however, a Cochrane review reported no additional benefit with the use of HBO on implant success in irradiated bone [44]. To date, some studies address the problem of recurrence of malignancy next to dental implants, most often via presentation of a solitary or several implant-related carcinomas [45–48]. Thus, patients with a history of previous OSCC profit from individualized recall intervals and careful clinical evaluations. Scalpel biopsy of persisting macroscopic lesions for these patients should be mandatory to rule out an invasive carcinoma [45].
Conclusion Within the limits of this meta-analytic approach to the literature, we demonstrated a comparable implant survival between the non-irradiated native bone and the irradiated native bone in the current literature. Therefore, patients with a history of radiation in the head and neck region can be successfully treated with dental implants. However, the coincidence of grafted bone and radiotherapy as a negative prognostic factor on implant survival must be considered. Generally, the patient and the attending clinician must be aware of potential risks and complications relevant to implant therapy in the irradiated patient to provide safe and predictable treatment.
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