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Menapace DC, Van Abel KM, Jackson RS, Moore EJ. Primary vs Secondary Endosseous Implantation After Fibular Free Tissue Reconstruction of the Mandible for Osteoradionecrosis. JAMA Facial Plast Surg. 2018;20(5):401–408. doi:10.1001/jamafacial.2018.0263
Is it effective and cost efficient to perform primary dental implantation during fibula free tissue transfer for treatment of osteoradionecrosis and osteonecrosis?
In this cohort study of 23 patients, which includes those who underwent fibula free tissue transfer for osteoradionecrosis or osteonecrosis and dental implantation, primary implantation did not affect flap complication, flap viability, or implantation viability. Dental implantation performed primarily can be used sooner and is associated with decreased nonvariable costs than when it is performed secondarily.
It is both effective and cost efficient to perform primary implantation; earlier implant use and decreased cost should prompt surgeons to consider this treatment option.
The clinical and financial implications of the timing of dental rehabilitation after a fibula free tissue transfer (FFTT) for osteoradionecrosis (ORN) and osteonecrosis (ON) of the mandible have yet to be established.
To compare the outcomes of primary implantation vs secondary implantation after FFTT for ORN and ON of the mandible.
Design, Setting, and Participants
A retrospective review was conducted of 23 patients at a single tertiary academic referral center undergoing primary implantation or secondary implantation after FFTT for ORN and ON from January 1, 2006, to November 10, 2015.
All patients underwent FFTT with primary implantation (n = 12) or secondary implantation (n = 11).
Main Outcomes and Measures
Outcomes of FFTT, dental implantation, implant use, diet, speech, and disease-free survival were reviewed. Fixed unit costs were estimated based on the mean cost analysis.
Twenty-three patients (7 women and 16 men; mean [SD] age, 62.4 [8.2] years [range, 24-81 years]) met the inclusion criteria. Of these, 18 had ORN and 5 had ON. Dental implantation was performed at the time of FFTT for 12 patients and was performed secondarily for 11 patients. There were a mean of 5.2 implants per patient performed, for a total of 121 implants. There was 1 complete flap failure in the primary implantation group. Neither flap nor implant complications were affected by the timing of the implantation. Overall, the implant survival rate was 95% (55 of 58) in the primary implantation group and 98% (62 of 63) in the secondary implantation group. Time from FFTT to abutment placement (primary implantation, 19.6 weeks; secondary implantation, 61.0 weeks) was significantly shorter after primary implantation (P < .001). There was no clinical difference in postoperative complications and implant outcomes for ORN vs ON. Improvement in speech and oral competence in the primary implantation group vs the secondary implantation group was not statistically significant, given an experiment-adjusted P = .001 set as significant (normal speech, 9 vs 3; P = .02; and normal oral competence, 9 vs 3; P = .02). Disease-free survival was 91% (20 of 22 patients) overall. Fixed unit (U) costs were 1.0 U for primary implantation and 1.24 U for secondary implantation.
Conclusions and Relevance
Patients undergoing primary implantation after FFTT for ORN and ON had a similar rate of complications compared with those undergoing secondary implantation. However, primary implantation allowed a faster return than secondary implantation to oral nutrition and prosthesis use. The fixed unit cost was reduced for those undergoing primary implantation. Although dental implantation was safe and effective in both groups, the decreased time to use and the decreased overall cost should prompt surgeons to consider primary implantation after FFTT for ORN and ON.
Level of Evidence
Osteoradionecrosis (ORN) of the mandible is a well-described, progressive disease in which radiotherapy leads to the insidious devitalization of the soft tissue, cartilage, dentition, and bone of the mandible.1 Radiotherapy is thought to lead to endarteritis and reduced osteoclastic activity.2-5 Local trauma after radiotherapy, commonly in the form of dental extractions, has been associated with the development of ORN.6,7 Osteonecrosis (ON) of the mandible represents a similar spectrum of disease most commonly associated with prior exposure to antiresorptive and antiangiogenic bone therapies such as bisphosphonates and the receptor activator of nuclear κ B ligand inhibitor medication denosumab.8 Both ORN and ON present the treating surgeon with a complex disease process that can result in hostile, often infected, host tissue and the potential for progressive disease. However, these conditions are considered benign and are often present in patients who are either in remission or considered cured of their oncologic disease but are struggling with the sequela of their treatment.
The goals of surgical management for ORN and ON with fibula free tissue transfer (FFTT) are to remove dead and infected tissue, restore the structural integrity of the mandible, replace diseased soft tissue, and provide a scaffold for dental implantation. Dental rehabilitation has the potential to restore effective mastication, maintain or improve swallowing, and improve speech and aesthetic outcomes, thus improving oral function and quality of life.9,10 However, while dental implantation after FTTT has been proven relatively safe and effective, the clinical effect, timing, and cost of dental implantation for patients with ORN and ON has yet to be fully elucidated.11 The purpose of this study was to gain a better understanding of both the clinical outcomes and cost of primary implantation (primary implantation) vs secondary implantation (secondary implantation) after FFTT for ORN and ON of the mandible.
Patients treated from January 1, 2006, to November 10, 2015, were identified by searching the terms osteoradionecrosis and osteonecrosis (International Classification of Diseases, Ninth Revision [ICD-9] code 526.89) with the procedure code for mandibulectomy (Current Procedural Terminology code 21047; ICD-9 codes 76.31, 76.41, and 76.42). A diagnosis of ORN or ON required the presence of pain or trismus for 3 months or more and radiographic findings of osteolysis of the mandible with or without pathologic fracture in the absence of tumor recurrence. Stage of ORN was defined based on the classification system of Urken et al.12 Patients with recurrent or active oral cavity cancer were excluded. In general, dental implantation is offered, in the preoperative setting, to all patients for whom mandibulectomy resulted in loss of dentition critical to mastication and/or oral competence and who were interested in undergoing additional procedures, willing to accept the risks associated with implantation, able to finance this additional procedure, and did not have a contraindication to implantation such as significant trismus or nonreversible dysphagia resulting in a permanent nonoral diet. The decision for primary implantation vs secondary implantation was made on a case-by-case basis considering the patient’s overall general health, the patient’s preference, and the availability of multidisciplinary team members. Study data were collected and managed using REDCap electronic data capture tools hosted by the Mayo Clinic (REDCap, version 4.13.17; Vanderbilt University). The Mayo Clinic institutional review board approved this study (15-008484) and granted waiver of informed consent to collect these deidentified data.
Clinical and surgical outcomes were qualified based on review of patients’ medical records. Data on oral competence and speech intelligibility were obtained from objective reports documented by the evaluating speech pathologist or clinical notes when available. Normal oral competence was defined as lack of abnormal lip pucker or retraction with normal tongue elevation and protrusion. Mild dysfunction was defined as abnormal lip pucker. Moderate and severe dysfunction was defined as abnormal lip pucker and abnormal tongue elevation and protrusion. Normal speech was defined as understandable speech with no dysarthria. Mild dysfunction, moderate speech impairment, and severe speech impairment were subjectively qualified based on the level of articulation distortion and speech intelligibility. Diet was also recorded as full, soft, puree, liquid, supplementation via a percutaneous endoscopic gastrostomy (PEG) tube, and dependence on a PEG tube.
Fixed unit (U) cost analysis was performed by the Mayo Clinic’s Patient Financial Services. The fixed unit cost for primary implantation was estimated based on the mean cost of “mandibulectomy with fibula free tissue transfer with dental implantation.” The fixed unit cost for secondary implantation was estimated based on the mean cost of “mandibulectomy with fibula free tissue transfer” with a second procedure including “dental implantation.” Both implantation scenarios were estimated using a mean cost of 5 implants placed with a mean postoperative hospital stay after FFTT of 5 days. In the secondary implantation scenario, a second anesthetic cost was considered, and the procedure cost was calculated as an outpatient surgical procedure. Variable costs (eg, supplies, need for additional surgery owing to secondary complications, extended hospital stays) were not included. Power calculations were performed with the recognition that 60 patients would be needed in each group to reach statistical significance with standard P values (P = .05) during population proportion comparisons. Therefore, when performing 2-tailed z tests for population proportions and 2-tailed t tests for independent means, a Bonferroni correction was calculated to account for the multiple comparisons performed in this study. To reduce the chance for error in the conclusions, the experiment-wide α was lowered to P = .001 accordingly. Similarly, owing to small patient numbers, multivariate analysis was not possible. Data were analyzed using JMP, version 10, statistical analysis software (SAS Institute Inc).
All patients underwent vascularized FFTT for reconstruction of a segmental mandibulectomy defect, as previously described.11 Patients undergoing primary implantation received implantation after inset at the time of surgery. Primary implantation was performed after flap harvest and plating but before flap inset. After implantation, patients typically had a 3-month waiting period to allow for osseointegration. The implants would then be surgically uncovered for abutment placement and use. Patients who underwent secondary implantation would receive implants approximately 3 months after the initial FFTT to allow for bony union across fibula segment osteotomy sites. Implantation was followed by a 3- to 5-month osseointegration period before the implants were uncovered and the abutments placed. Abutment placement correlates closely with time of implantation use at the Department of Otorhinolaryngology, Mayo Clinic.
A total of 110 patients with ORN and ON were identified, of whom 52 patients underwent FFTT. Twenty-three patients (7 women and 16 men; mean [SD] age, 62.4 [8.2] years [range, 24-81 years]) underwent dental implantation and therefore met the inclusion criteria. Of these patients, 19 underwent treatment for ORN and 4 for ON. Thirteen of the 23 patients overlap with the previously published data.11 In the initial study, of those with ORN, 5 underwent primary implantation and 8 underwent secondary implantation. We now have 12 patients who underwent primary implantation and 11 who underwent secondary implantation, with at least 6 months of follow-up time. We think that this is a much larger pool of patients who underwent primary implantation. More important, the analysis focuses on ORN and ON and is not diluted by inclusion of other indications for FFTT. The most common ORN stage was stage III, defined by full thickness devitalization of bone, resorption of the inferior border of the mandible, fistula, or a pathologic fracture.12 Comorbidities and preoperative patient factors are outlined in Table 1.
A total of 121 implants were placed, with a mean of 5.2 implants per patient (range, 1-11 implants per patient). All patients received implantation to the FFTT neomandible; however, 13 patients also received implantation in their maxilla, and 7 patients received implantation in their native mandible as well. The mean number of mandibular segments and implants per mandibular segment was 2 for both groups (Table 2). Patients who received primary implantation began using their implants a mean of 41.4 weeks earlier than those in the secondary implantation group on average (P < .001). At last follow-up (primary implantation, 80 weeks; secondary implantation, 126 weeks), all patients were using their implants.
Flap-related complications and implant-related complications are reported in Table 3. One patient developed a complete flap failure secondary to arterial and venous insufficiency attributed to infection. Conservative revascularization was unsuccessful. The most common complications otherwise were skin paddle dehiscence and plate or screw extrusion. This patient ultimately required contralateral FFTT. There was 1 partial flap failure. Six patients developed a postoperative infection, with no difference in implantation timing. Thirteen patients required a return to the operating room at some point during their treatment course, with no difference between the primary implantation group (n = 7) and secondary implantation group (n = 6). One patient in the primary implantation group died 1 day after hospital discharge. The event was sudden and thought to be related to a cardiopulmonary or obstructive event after decannulation; autopsy was declined by the family. Overall, excluding the single mortality, we report a 95% (21 of 22) FFTT survival rate.
Implants were well tolerated, with no clinical difference between the primary implantation and secondary implantation groups for implant-related complications (Table 3). The most common implant-related complication was the formation of granulation tissue (3 patients in the primary implantation group and 2 patients in the secondary implantation group). One patient in each group had bone exposure adjacent to the implant. One patient in each group also had infection adjacent to the implant. Three patients in the secondary implantation group required implant revision, compared with 4 in the primary implantation group. There were a total of 11 implants removed (6 in the primary implantation group and 5 in the secondary implantation group), 7 of which were immediately replaced. The implant survival rate at last known follow-up was 94.9% in the primary implantation group and 98.4% in the secondary implantation group.
Patients in the primary implantation group had their nasogastric tube removed a mean of 16.6 days after surgery (range, 5-67 days), whereas those in the secondary implantation group maintained their nasogastric tube for a mean of 26.0 days (range, 7-108 days) (P = .26). Of the patients alive at last follow-up, 91% (20/22) maintained an oral diet (Table 4). In the primary implantation group, the diet was full oral for 6 of 11 patients (55%), mechanical soft for 3 (27%), and liquid for 1 (9%). In this group, only 1 patient required a PEG tube and remained dependent on the PEG tube despite oral rehabilitation. This was thought to be secondary to severe oral incompetence from previous subtotal glossectomy for oral cavity cancer.
In the secondary implantation group, the diet was full oral for 3 of 11 patients (27%) and mechanical soft for 7 (64%). Two patients in the secondary implantation group had a history of preoperative placement of a PEG tube. Both patients had their PEG tubes removed after treatment and graduated to a soft oral diet. Three patients in the secondary implantation group, however, after reconstruction, required placement of a PEG tube to maintain nutritional needs during their postoperative course (2 preabutment and 1 postabutment). One patient in the secondary implantation group remains dependent on a PEG tube. Although there are clinical differences in diet consistency and use of a PEG tube between the primary implantation and secondary implantation groups, these data were not statistically significant and likely multifactorial in origin. The trismus data set was incomplete and therefore not reported. The mean time from surgical resection to implantation use was significantly shorter for patients undergoing primary implantation (19.6 weeks) compared with those undergoing secondary implantation (61.0 weeks) (P < .001).
Oral competence and speech outcome are reported in Table 4. Overall, oral competence was superior for patients undergoing primary implantation than those undergoing secondary implantation (normal oral competence, 9 vs 3; P = .02). Speech impairment was also improved after primary implantation compared with after secondary implantation (normal speech, 9 vs 3; P = .02). However, with the adjusted P value, neither of these observations were statistically significant. No patient was reliant on tracheostomy at last follow-up.
At last follow-up, 20 patients were alive. One patient in the primary implantation group died suddenly after hospital discharge. Two patients in the secondary implantation group died of other causes. Nineteen of these patients (83%) were alive with no evidence of disease. One patient in the secondary implantation group continues to experience diffuse ON of the maxilla with no associated FFTT or implant complications. Disease-free survival was 91% (20 of 22) overall at last follow-up.
The fixed unit cost of primary implantation was approximately $100 000.00 (1 U), whereas the cost of secondary implantation was $124 000 (1.24 U). The cost of mandibulectomy and FTTT was $75 000.00 (0.75 U). This cost does not include variable costs, including supplies, subsequent trips to the operating room, or complications. However, complication rates and subsequent trips to the operating room were not significantly different between groups (Table 3).
Surgical management of advanced ORN and ON of the mandible requires a surgeon to consider not only resection of disease and restoration of structure, but also the restoration of function and quality of life. Alleviating pain and infection and improving speech, swallowing, oral competence, and overall quality of life in an expedient and cost-effective manner are of critical importance. Segmental mandibulectomy with FFTT has been shown to result in excellent outcomes for patients with ORN.1,13,14 However, FFTT alone may fail to optimally rehabilitate the patient. If dentition goes unrestored, the patient may experience ineffective mastication, decreased oral competence, and poor speech intelligibility. Although dental implantation in FFTT has been shown to be safe and effective, in the cohort of patients with ORN and ON, the potential for complications increased given the poor vascularity of the host tissue, malnutrition, and chronic inflammation.11 The question then when considering dental rehabilitation in this high-risk group is whether there is a functional benefit or cost benefit to primary implantation vs secondary implantation.
The fibula easily accommodates osteotomies for mandible contouring and contains a large bone stock, making it a not only a versatile flap but also a reliable option to support dental implantation. In this study, excluding 1 patient who died, we report a 95% (21 of 22) FFTT success rate. This result is consistent with the rates of 94% to 100% previously reported in the literature.12,15-19 It appears that dental implantation, even in patients with a history of ORN, does not affect FFTT survival.
Patients undergoing primary implantation did not experience increased flap failure rates or flap complications compared with those undergoing secondary implantation. Similarly, there was no difference in implant-related complications, with an implant survival rate of 98.4% among those undergoing primary implantation and 94.9% among those undergoing secondary implantation. This success rate is consistent with previously published rates of 91.7% to 95.1%.19-24 Implantation at the time of surgery for patients with ORN and ON does not appear to increase the rate of implant complications or implantation success. We report a 91% resolution of ORN in both groups (primary implantation, 10 of 11; secondary implantation, 10 of 11), which is consistent with the literature.19,20 These data support dental implantation, regardless of timing, as an effective procedure for rehabilitating patients with ORN or ON.
The data reported highlight technical details while obscuring the functional and financial outcomes associated with the timing of dental rehabilitation with FFTT. When counseling patients, it is important for them to understand how the surgical plan may affect their ability to eat and speak. This analysis found that when patients undergo primary implantation, they can begin using their implants sooner and return to an oral diet faster than when patients undergo secondary implantation. Additionally, fewer PEG tubes were used after treatment in the primary implantation group, which, although not statistically significant, may be of clinical importance. These conclusions should be considered with caution, however, as the implementation of a PEG tube is likely multifactorial and may depend on previous therapies, including ablative therapy and radiotherapy. With regard to functional outcomes, oral rehabilitation outcomes such as oral competence and speech articulation were similarly more likely to be graded as normal in the primary implantation group. Although our data suggest improved functional outcomes in patients undergoing primary implantation, overall it did not reach statistical significance with the experiment-adjusted P value. Patients in both groups benefited from and actively used their reconstruction.
Although oral rehabilitation is discussed with all patients undergoing FFTT, the decision to pursue implantation is most often based on financial and personal factors. In some cases, the status of remaining dentition also plays a factor as patients are satisfied with their remaining dentition or postoperative diet restrictions. However, as previously noted, cost can be a significantly limiting factor for patients seeking restoration to their premorbid oral competence and quality of life. This has led many insurers to deny coverage for dental rehabilitation, leaving patients with potential aesthetic deformity, speech distortion, and clinically significant alterations in oral intake. After FFTT, it is not routinely possible to use a denture, eliminating this option for our patients. At the Mayo Clinic, we have found that primary implantation reduces surgical costs by 24%, or $24 000 (primary implantation fixed unit cost, 1.0 U; secondary implantation fixed unit cost, 1.24 U), based on our fixed unit cost analysis. When taken in context with the data presented regarding time to oral intake, time to prosthesis use, and potential increased use of PEG tube placement and feedings, this analysis likely underestimates the true cost of secondary implantation to the patient. The more evidence built supporting objective improvements in outcomes and decreased overall costs with primary implantation may help to justify to insurers covering these costs. It is important to keep in mind, however, that the functional outcomes in reconstruction are often hard to predict and may change over time. Because cancer recurrence is the predominant obstacle to completion of oral rehabilitation, an argument can be made for delaying implant placement. However, to maximize patient outcomes after FFTT for ORN and ON, primary implantation may allow patients more expedient oral restoration.
To our knowledge, this study represents the largest cohort currently available for this disease process and treatment plan; however, both the retrospective nature of this study and the small number of patients limit the quality of the data and the strength of our conclusions. Multi-institutional study or meta-analysis will be needed to verify these findings. Furthermore, our cost analysis does not take into account variable supply, patient- and surgeon-related costs, and extended hospital stays, nor does it consider the coverage offered by various insurance plans.
Patients undergoing primary implantation after FFTT for ORN and ON had a similar rate of complications compared with those undergoing secondary implantation. However, primary implantation allowed patients to return to oral nutrition and begin using their prostheses sooner in recovery than secondary implantation. Importantly, primary implantation also resulted in a 24% reduction of cost associated with the procedures. Dental implantation in both the primary implantation and secondary implantation setting did not appear to compromise flap outcomes; however, primary implantation showed a more rapid return to function at a decreased cost, which should prompt surgeons to consider primary implantation after FFTT for ORN and ON. Further study is needed to assess the patient-reported effect of these efforts.
Accepted for Publication: February 19, 2018.
Corresponding Author: Deanna C. Menapace, MD, Department of Otorhinolaryngology, Mayo Clinic Rochester, 200 1st St SW, Rochester MN, 55905 (email@example.com).
Published Online: May 3, 2018. doi:10.1001/jamafacial.2018.0263
Author Contributions: Drs Menapace and Moore had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Menapace, Van Abel.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Menapace.
Study supervision: Van Abel, Jackson, Moore.
Conflict of Interest Disclosures: None reported.
Funding/Support: Funding was provided internally by the Mayo Clinic Department of Otorhinolaryngology. Statistical analysis software was enabled by grant UL1 TR000135 from the Center for Clinical and Translational Science.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Meeting Presentation: This paper was presented at the Annual Meeting of the American Head and Neck Society; July 16, 2016; Seattle, Washington.
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