Viability of dental implants in head and neck irradiated patients: A systematic review Manuscript: HED-15-0043
Edson Virgílio Zen Filho, DDS, MSc1 Elen de Souza Tolentino, DDS, PhD2 Paulo Sérgio Silva Santos, DDS, PhD1
1 – Department of Stomatology, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil 2 – Department of Dentistry, Maringá State University, Maringá, Paraná, Brazil
Address correspondence: D.D.S, PhD Elen de Souza Tolentino Department of Dentistry, Maringá State University, Av. Mandacaru, 1550. Bloco S08 Maringá – PR - Brazil C.E.P: 87083-170 Tel: +55 (44) 2101-9051 - E-mail: [email protected]
Running title: Dental implants in irradiated head and neck Key words: Dental implant, osseointegration, radiotherapy, endosseous implant, radiation therapy
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/hed.24098 This article is protected by copyright. All rights reserved.
Manuscript: HED-15-0043 Viability of dental implants in head and neck irradiated patients: A systematic review
Edson Virgílio Zen Filho, DDS, MSc1 Elen de Souza Tolentino, DDS, PhD2 Paulo Sérgio Silva Santos, DDS, PhD1
1 – Department of Stomatology, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil 2 – Department of Dentistry, Maringá State University, Maringá, Paraná, Brazil
Address correspondence: D.D.S, PhD Elen de Souza Tolentino Department of Dentistry, Maringá State University, Av. Mandacaru, 1550. Bloco S08 Maringá – PR - Brazil C.E.P: 87083-170 Tel: +55 (44) 2101-9051 - E-mail: [email protected]
Running title: Dental implants in irradiated head and neck Key words: Dental implant, osseointegration, radiotherapy, endosseous implant, radiation therapy
This article is protected by copyright. All rights reserved.
Summary Based on the reviewed studies, the interval time between radiotherapy and implant placement as well as the radiation doses are not associated with significant implant failure rates. The placement of osseointegrated dental implants in irradiated bone is viable, and head and neck radiotherapy should not be considered as a contraindication for dental rehabilitation with implants.
Abstract Background: This systematic review aimed to evaluate the safety of dental implants placed in irradiated bone and to discuss their viability when placed post-radiotherapy. Methods: A systematic review was performed to answer the questions: “Are dental implants in irradiated bone viable?” and “What are the main factors that influence the loss of implants in irradiated patients?”. Results: The search strategy resulted in 8 publications. A total of 331 patients received 1237 implants, with an overall failure rate of 9.53%. The osseointegration success rates ranged between 62.5% and 100%. The optimal time interval between irradiation and dental implantation varied from 6 to 15 months. Conclusions: The interval time between radiotherapy and implant placement and the radiation doses are not associated with significant implant failure rates. The placement of implants in irradiated bone is viable, and head and neck rasdiotherapy should not be considered as a contraindication for dental rehabilitation with implants.
This article is protected by copyright. All rights reserved.
Introduction Radiotherapy is an established treatment modality in the management of malignant diseases of the head and neck. It is often applied prior to or following oral cancer surgery to improve the therapeutic outcome. Patients that undergo radiotherapy may require implant-supported oral rehabilitation and, in some cases, these implants are placed after the antineoplastic therapy. However, tissue damage invariably follows the course of radiotherapy, and this may interfere with the success of the implants’ osseointegration1.
Irradiation
causes
endarteritis,
leading
to
tissue
hypoxia,
hypocellularity, hypovascularity, and reduces the proliferation of bone marrow, collagen, and periosteal and endothelial cells2. The reduced viability of irradiated bone may not be capable of promoting osseointegration, compromising implant survival. Furthermore, there is an increased risk of osteoradionecrosis in the irradiated bone2. Despite the high quantity of studies, several questions persist regarding the osseointegration and functional stability of dental implants in head- and neck-irradiated patients. The aim of this systematic review was to evaluate the safety of dental implants placed in irradiated bone and to discuss if these implants are viable when placed post-radiotherapy.
Material and methods
Focused question A systematic review of the best evidence available in the literature was performed to answer the following clinical questions: “Are osseointegrated dental implants in irradiated bone viable?” and “What are the main factors that influence the loss of implants in irradiated patients?”
This article is protected by copyright. All rights reserved.
Search strategy An initial electronic search was performed using Pubmed (all years to October 2014). Further search was performed through Embase, Web of Science, Scopus and The Cochrane Library database. A broad search strategy was undertaken using the following keywords: (Oral OR Dental OR Endosseous OR Osseointegrated) AND (Implant(s)) AND (Radiotherapy OR Irradiation OR Radiation Therapy OR Radiated bone). The search was conducted using the separate terms, and then the results were merged with AND. Two independent observers made a quality assessment of the studies according to fixed eligibility criteria. The title and abstract (when available) of each result of the search were examined separately. For studies appearing to be relevant, and for those with insufficient data in the title and abstract, to make a clear decision the full article was obtained. Both reviewers evaluated the full text of all articles independently. Articles selected after the full-text assessment were submitted to final eligibility assessment for inclusion in the review. If both readers considered the article relevant, it was included in the study. When there was no agreement between the two reviewers, a third reviewer read the article and performed the decision.
Eligibility criteria The criteria described below were used to determine eligibility: 1) They had to be original clinical studies based on humans (randomized controlled clinical trials, cohort, prospective, retrospective, case series, and case-control studies); 2) Intervention: patients having undergone dental implant placement after head and neck radiotherapy (radiotherapy affecting mandible, maxilla or both); 3) Implants placed in irradiated native bone (maxilla and mandible) and not in
This article is protected by copyright. All rights reserved.
bone grafts; 4) Minimum sample size of 10 irradiated patients; 5) Patients must not have been submitted to hyperbaric oxygen adjuvant therapy; 6) Articles published in English. The exclusion criteria were lack of information about the number of patients, number of placed implants, radiation dose, irradiated region, interval between the radiotherpay and implant placement, number of implants lost, and follow-up period. Case reports, reviews, systematic reviews, letters to editor, annals and presentations in congresses were also excluded.
Quality assessment The quality assessment of the included studies was undertaken independently and in duplicate by the two reviewers as part of the data extraction process. It was performed by taking into account factors that could introduce bias to the results. The following variables were evaluated: (Adapted from Papadopoulos et al.3) 1. Study design (Randomized and/or controlled clinical trials = 3 points; Prospective study = 2 points; Retrospective study = 1 point; Case series = 0 points); 2. Sample size (Adequate = 2 points (31 patients or more); Partly adequate = 1 point (21-30 patients); Acceptable = 0 points (10-20 patients)); 3. Selection description and inclusion/exclusion criteria (Adequate = 2 points; Partly adequate = 1 point; Acceptable = 0 points); 4. Follow-up (Adequate = 3 points (48 months or more); Partly adequate = 2 points (23-47 months); Acceptable = 1 point (11-23 months); Inadequate = 0 points (1-11 months));
This article is protected by copyright. All rights reserved.
5. Measurement methods (Clear = 2 points; Acceptable = 1 point; Unclear = 0 points); 6. Use of method error analysis (YES = 1 point; NO = 0 points); 7. Blinding measurements (YES = 1 point; NO = 0 points); 8. Adequate statistics provided (YES = 1 point; NO = 0 points); 9. Confounding factors estimated in analysis (YES = 1 point; NO = 0 points); In summary, the studies could maximally score 16 points and were classified as low (0-5 points), medium (6-11 points), or high (12-16 points) quality. Papers classified as High or Medium quality were included in the systematic review.
Evaluated parameters The following variables were assessed: number of patients, gender, age, type of implant, number of placed implants, number of lost implants, site of implant placement (mandible/maxilla), site of implant failure, survival rate, success rate, radiation dose, type of radiation, irradiated region, implant length and surface, adjuvant therapy (i.e. antibiotics, chemotherapy) delay from radiotherapy to implant placement, and follow-up time. The main outcome considered was implant failure, defined as implant mobility, and implant removal needed by progressive marginal bone loss or infection (biologic failure implying failure to establish or to maintain osseointegration)4. The presence of periimplantitis or a buried implant was not considered as a negative outcome.
Results The database search identified 4487 studies: 1272 duplicates were removed and 3215 records were screened by title and abstract. Fifty full-text articles were
This article is protected by copyright. All rights reserved.
selected on the basis of the title and abstract review. Forty-two were excluded, as they did not completely meet the eligibility criteria (Appendix S1). The eligibility process (Figure 1) and the quality assessment resulted in 8 studies (Table 1). Authors, study design, number of patients, number of implants inserted, implant failure, follow-up duration, and study conclusion are summarized in Table 2. Two studies
were
randomized
controlled
trials10,11,
two
were
retrospective
(one
multicenter)6,7 and four were prospective5,8,9,12. Four papers did not mention the gender and the age of the irradiated patients6,7,9,12. The other studies included a total of 113 men and 64 women, with ages ranging from 34 to 87 years. All patients received radiation in the head and neck region to treat malignances in the jaws, oral soft tissues or oropharynx. Three studies5,9,11 mentioned the use of adjuvant chemotherapy. The follow-up period ranged from 1 month6 to 14 years8 (Table 2). A total of 331 patients received 1237 implants, with an overall failure rate of 9.53% (118 implants) (Table 2). The exact times of the implant failure were not specified. Only Landes and Kovacs9 and Andersson et al.5 have reported that the implants that failed were lost early9. In the study of Landes and Kovacs9, one irradiated patient had early loss of one implant at the time of loading. The causes of implant loss were not always repoed. Andersson et al.5 reported that both patients who lost implants were heavy smokers. Moreover, one lost implant was in the only patient who received chemotherapy during radiotherapy. In the study of Wagner et al.7, osteoradionecrosis occurred in one patient, with a loss of 5 implants. Table 3 summarizes the osseointegration success rates regarding the site of placement, time delay from radiotherapy to implant placement and radiation dose. The osseointegration success rates ranged between 62.5%6 and 100%6,11. In one study, this value was not specified7. From 1237 implants, 259 (21%) were placed in maxilla and 978 (79%) in mandible. In three studies7,9,10, implants were placed only in
This article is protected by copyright. All rights reserved.
mandible. The reported rate of implant failure in the maxilla was 25% (65/259) and 5.4% in mandible (53/978) (Table 3). The time delay from radiotherapy to implant placement ranged from one month to 20 years6 (Table 3). The direct association between this variable and implant failures has been reported in 7 studies5,6-9,10,12. The optimal time interval between irradiation and dental implantation varied from 68 to 15 months7. The radiation doses varied from 50Gy have a significantly lower survival rate (73%) than implants in locations that were irradiated with 50Gy dosage treated patients and 93.6% with
Edson Virgílio Zen Filho, DDS, MSc1 Elen de Souza Tolentino, DDS, PhD2 Paulo Sérgio Silva Santos, DDS, PhD1
1 – Department of Stomatology, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil 2 – Department of Dentistry, Maringá State University, Maringá, Paraná, Brazil
Address correspondence: D.D.S, PhD Elen de Souza Tolentino Department of Dentistry, Maringá State University, Av. Mandacaru, 1550. Bloco S08 Maringá – PR - Brazil C.E.P: 87083-170 Tel: +55 (44) 2101-9051 - E-mail: [email protected]
Running title: Dental implants in irradiated head and neck Key words: Dental implant, osseointegration, radiotherapy, endosseous implant, radiation therapy
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/hed.24098 This article is protected by copyright. All rights reserved.
Manuscript: HED-15-0043 Viability of dental implants in head and neck irradiated patients: A systematic review
Edson Virgílio Zen Filho, DDS, MSc1 Elen de Souza Tolentino, DDS, PhD2 Paulo Sérgio Silva Santos, DDS, PhD1
1 – Department of Stomatology, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil 2 – Department of Dentistry, Maringá State University, Maringá, Paraná, Brazil
Address correspondence: D.D.S, PhD Elen de Souza Tolentino Department of Dentistry, Maringá State University, Av. Mandacaru, 1550. Bloco S08 Maringá – PR - Brazil C.E.P: 87083-170 Tel: +55 (44) 2101-9051 - E-mail: [email protected]
Running title: Dental implants in irradiated head and neck Key words: Dental implant, osseointegration, radiotherapy, endosseous implant, radiation therapy
This article is protected by copyright. All rights reserved.
Summary Based on the reviewed studies, the interval time between radiotherapy and implant placement as well as the radiation doses are not associated with significant implant failure rates. The placement of osseointegrated dental implants in irradiated bone is viable, and head and neck radiotherapy should not be considered as a contraindication for dental rehabilitation with implants.
Abstract Background: This systematic review aimed to evaluate the safety of dental implants placed in irradiated bone and to discuss their viability when placed post-radiotherapy. Methods: A systematic review was performed to answer the questions: “Are dental implants in irradiated bone viable?” and “What are the main factors that influence the loss of implants in irradiated patients?”. Results: The search strategy resulted in 8 publications. A total of 331 patients received 1237 implants, with an overall failure rate of 9.53%. The osseointegration success rates ranged between 62.5% and 100%. The optimal time interval between irradiation and dental implantation varied from 6 to 15 months. Conclusions: The interval time between radiotherapy and implant placement and the radiation doses are not associated with significant implant failure rates. The placement of implants in irradiated bone is viable, and head and neck rasdiotherapy should not be considered as a contraindication for dental rehabilitation with implants.
This article is protected by copyright. All rights reserved.
Introduction Radiotherapy is an established treatment modality in the management of malignant diseases of the head and neck. It is often applied prior to or following oral cancer surgery to improve the therapeutic outcome. Patients that undergo radiotherapy may require implant-supported oral rehabilitation and, in some cases, these implants are placed after the antineoplastic therapy. However, tissue damage invariably follows the course of radiotherapy, and this may interfere with the success of the implants’ osseointegration1.
Irradiation
causes
endarteritis,
leading
to
tissue
hypoxia,
hypocellularity, hypovascularity, and reduces the proliferation of bone marrow, collagen, and periosteal and endothelial cells2. The reduced viability of irradiated bone may not be capable of promoting osseointegration, compromising implant survival. Furthermore, there is an increased risk of osteoradionecrosis in the irradiated bone2. Despite the high quantity of studies, several questions persist regarding the osseointegration and functional stability of dental implants in head- and neck-irradiated patients. The aim of this systematic review was to evaluate the safety of dental implants placed in irradiated bone and to discuss if these implants are viable when placed post-radiotherapy.
Material and methods
Focused question A systematic review of the best evidence available in the literature was performed to answer the following clinical questions: “Are osseointegrated dental implants in irradiated bone viable?” and “What are the main factors that influence the loss of implants in irradiated patients?”
This article is protected by copyright. All rights reserved.
Search strategy An initial electronic search was performed using Pubmed (all years to October 2014). Further search was performed through Embase, Web of Science, Scopus and The Cochrane Library database. A broad search strategy was undertaken using the following keywords: (Oral OR Dental OR Endosseous OR Osseointegrated) AND (Implant(s)) AND (Radiotherapy OR Irradiation OR Radiation Therapy OR Radiated bone). The search was conducted using the separate terms, and then the results were merged with AND. Two independent observers made a quality assessment of the studies according to fixed eligibility criteria. The title and abstract (when available) of each result of the search were examined separately. For studies appearing to be relevant, and for those with insufficient data in the title and abstract, to make a clear decision the full article was obtained. Both reviewers evaluated the full text of all articles independently. Articles selected after the full-text assessment were submitted to final eligibility assessment for inclusion in the review. If both readers considered the article relevant, it was included in the study. When there was no agreement between the two reviewers, a third reviewer read the article and performed the decision.
Eligibility criteria The criteria described below were used to determine eligibility: 1) They had to be original clinical studies based on humans (randomized controlled clinical trials, cohort, prospective, retrospective, case series, and case-control studies); 2) Intervention: patients having undergone dental implant placement after head and neck radiotherapy (radiotherapy affecting mandible, maxilla or both); 3) Implants placed in irradiated native bone (maxilla and mandible) and not in
This article is protected by copyright. All rights reserved.
bone grafts; 4) Minimum sample size of 10 irradiated patients; 5) Patients must not have been submitted to hyperbaric oxygen adjuvant therapy; 6) Articles published in English. The exclusion criteria were lack of information about the number of patients, number of placed implants, radiation dose, irradiated region, interval between the radiotherpay and implant placement, number of implants lost, and follow-up period. Case reports, reviews, systematic reviews, letters to editor, annals and presentations in congresses were also excluded.
Quality assessment The quality assessment of the included studies was undertaken independently and in duplicate by the two reviewers as part of the data extraction process. It was performed by taking into account factors that could introduce bias to the results. The following variables were evaluated: (Adapted from Papadopoulos et al.3) 1. Study design (Randomized and/or controlled clinical trials = 3 points; Prospective study = 2 points; Retrospective study = 1 point; Case series = 0 points); 2. Sample size (Adequate = 2 points (31 patients or more); Partly adequate = 1 point (21-30 patients); Acceptable = 0 points (10-20 patients)); 3. Selection description and inclusion/exclusion criteria (Adequate = 2 points; Partly adequate = 1 point; Acceptable = 0 points); 4. Follow-up (Adequate = 3 points (48 months or more); Partly adequate = 2 points (23-47 months); Acceptable = 1 point (11-23 months); Inadequate = 0 points (1-11 months));
This article is protected by copyright. All rights reserved.
5. Measurement methods (Clear = 2 points; Acceptable = 1 point; Unclear = 0 points); 6. Use of method error analysis (YES = 1 point; NO = 0 points); 7. Blinding measurements (YES = 1 point; NO = 0 points); 8. Adequate statistics provided (YES = 1 point; NO = 0 points); 9. Confounding factors estimated in analysis (YES = 1 point; NO = 0 points); In summary, the studies could maximally score 16 points and were classified as low (0-5 points), medium (6-11 points), or high (12-16 points) quality. Papers classified as High or Medium quality were included in the systematic review.
Evaluated parameters The following variables were assessed: number of patients, gender, age, type of implant, number of placed implants, number of lost implants, site of implant placement (mandible/maxilla), site of implant failure, survival rate, success rate, radiation dose, type of radiation, irradiated region, implant length and surface, adjuvant therapy (i.e. antibiotics, chemotherapy) delay from radiotherapy to implant placement, and follow-up time. The main outcome considered was implant failure, defined as implant mobility, and implant removal needed by progressive marginal bone loss or infection (biologic failure implying failure to establish or to maintain osseointegration)4. The presence of periimplantitis or a buried implant was not considered as a negative outcome.
Results The database search identified 4487 studies: 1272 duplicates were removed and 3215 records were screened by title and abstract. Fifty full-text articles were
This article is protected by copyright. All rights reserved.
selected on the basis of the title and abstract review. Forty-two were excluded, as they did not completely meet the eligibility criteria (Appendix S1). The eligibility process (Figure 1) and the quality assessment resulted in 8 studies (Table 1). Authors, study design, number of patients, number of implants inserted, implant failure, follow-up duration, and study conclusion are summarized in Table 2. Two studies
were
randomized
controlled
trials10,11,
two
were
retrospective
(one
multicenter)6,7 and four were prospective5,8,9,12. Four papers did not mention the gender and the age of the irradiated patients6,7,9,12. The other studies included a total of 113 men and 64 women, with ages ranging from 34 to 87 years. All patients received radiation in the head and neck region to treat malignances in the jaws, oral soft tissues or oropharynx. Three studies5,9,11 mentioned the use of adjuvant chemotherapy. The follow-up period ranged from 1 month6 to 14 years8 (Table 2). A total of 331 patients received 1237 implants, with an overall failure rate of 9.53% (118 implants) (Table 2). The exact times of the implant failure were not specified. Only Landes and Kovacs9 and Andersson et al.5 have reported that the implants that failed were lost early9. In the study of Landes and Kovacs9, one irradiated patient had early loss of one implant at the time of loading. The causes of implant loss were not always repoed. Andersson et al.5 reported that both patients who lost implants were heavy smokers. Moreover, one lost implant was in the only patient who received chemotherapy during radiotherapy. In the study of Wagner et al.7, osteoradionecrosis occurred in one patient, with a loss of 5 implants. Table 3 summarizes the osseointegration success rates regarding the site of placement, time delay from radiotherapy to implant placement and radiation dose. The osseointegration success rates ranged between 62.5%6 and 100%6,11. In one study, this value was not specified7. From 1237 implants, 259 (21%) were placed in maxilla and 978 (79%) in mandible. In three studies7,9,10, implants were placed only in
This article is protected by copyright. All rights reserved.
mandible. The reported rate of implant failure in the maxilla was 25% (65/259) and 5.4% in mandible (53/978) (Table 3). The time delay from radiotherapy to implant placement ranged from one month to 20 years6 (Table 3). The direct association between this variable and implant failures has been reported in 7 studies5,6-9,10,12. The optimal time interval between irradiation and dental implantation varied from 68 to 15 months7. The radiation doses varied from 50Gy have a significantly lower survival rate (73%) than implants in locations that were irradiated with 50Gy dosage treated patients and 93.6% with
