|Year : 2022 | Volume
| Issue : 1 | Page : 32-39
Transcutaneous osseointegration for oncologic amputees with and without radiation therapy: An observational cohort study
Jason Shih Hoellwarth1, Kevin Tetsworth2, Muhammad Adeel Akhtar3, Atiya Oomatia4, Munjed Al Muderis4
1 Limb Salvage and Amputation Reconstruction Center, Hospital for Special Surgery, New York, NY, USA
2 Department of Orthopaedic Surgery, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
3 NHS Fife, Hayfield Rd, Kirkcaldy, United Kingdom
4 Limb Reconstruction Centre, Macquarie University Hospital, Macquarie University, Macquarie Park, Australia
|Date of Submission||02-May-2022|
|Date of Decision||23-May-2022|
|Date of Acceptance||24-May-2022|
|Date of Web Publication||30-Jun-2022|
Jason Shih Hoellwarth
535 East 70th Street, New York 10021, NY
Source of Support: None, Conflict of Interest: None
Context: Transcutaneous osseointegration for amputees (TOFA) consistently confers significant improvement in mobility and quality of life (QOL) for amputees using a traditional socket prosthesis. Limb radiation therapy (XRT) Has traditionally been considered hard contraindication against TOFA but has never actually been examined. Aims: This study evaluated the changes in mobility and QOL, and also the complications, for oncologic amputees provided TOFA: 9 with XRT, and 23 with no radiation therapy (NRT). Settings and Design: A retrospective registry review of all oncologic amputees was performed. Subjects and Methods: The patients' mobility (daily prosthesis wear hours, K-level, Timed Up and Go, and 6-min walk test [6MWT]) and QOL survey data (Questionnaire for Persons with a Transfemoral Amputation) were compared before TOFA and at the latest follow-up. Statistical Analysis Used: Fisher's exact test for frequencies, and Student's t-test for means (significance, P < 0.05). Results: Regarding mobility, the cohorts were similar to one another before and after TOFA, and both cohorts improved following osseointegration (statistically significant: XRT wear hours [P = 0.029], NRT K-level [P < 0.001], and NRT 6MWT [P = 0.046]). Both cohorts' QOL was also similar before and after TOFA, and both cohorts again improved following osseointegration (significant differences: XRT problem score [P = 0.021], NRT problem score [P < 0.001], and NRT global score [P < 0.001]). Three XRT patients (33%) and one NRT patient (4%) required removal (P = 0.048). Conclusions: While radiation therapy may be associated with increased risk of postoperative implant loosening, it seems unjustifiable to flatly contraindicate osseointegration for oncologic amputees solely because of prior limb irradiation.
Keywords: Oncologic amputee, oncologic osseointegration, osseointegration, radiation osseointegration, radiation therapy, sarcoma
|How to cite this article:|
Hoellwarth JS, Tetsworth K, Akhtar MA, Oomatia A, Al Muderis M. Transcutaneous osseointegration for oncologic amputees with and without radiation therapy: An observational cohort study. J Limb Lengthen Reconstr 2022;8:32-9
|How to cite this URL:|
Hoellwarth JS, Tetsworth K, Akhtar MA, Oomatia A, Al Muderis M. Transcutaneous osseointegration for oncologic amputees with and without radiation therapy: An observational cohort study. J Limb Lengthen Reconstr [serial online] 2022 [cited 2022 Aug 9];8:32-9. Available from: https://www.jlimblengthrecon.org/text.asp?2022/8/1/32/349413
| Introduction|| |
Amputation is an uncommon management strategy for extremity sarcoma in financially prosperous nations, regardless whether the disease is primary or metastatic. Limb salvage is generally favored because disease-specific survival following limb salvage or amputation is equal, so long as the tumor can be completely removed and the primary cancer can be treated. Amputation to address sarcoma may still be necessary when the disease is not amenable to limb salvage or when a health-care system does not have resources to provide the necessary limb reconstruction. Transfemoral and transtibial oncologic amputees require a prosthetic limb for rehabilitation and ambulation, most often a traditional socket prosthesis (TSP). Unfortunately, mobility and quality of life (QOL) using a TSP are often poor. More than half of patients may experience dermatologic problems., Residual limb size fluctuation can impair fit and mobility,, leading the majority of patients to seek frequent refitting. Approximately one in four patients report a poor or extremely poor QOL.
Transcutaneous osseointegration [Figure 1] has increasingly provided improved mobility and QOL for amputees compared to TSP,, including oncologic amputees. Prior radiation therapy has traditionally been considered an absolute contraindication for osseointegration,,,, but there has never been clinical substantiation of this theoretical risk.
|Figure 1: Overview of transcutaneous osseointegration. (a) Exploded view of an OPL implant, with the components arranged at approximately the proximal-distal levels in which they would be once assembled and implanted in a patient with a femoral amputation. (1) proximal cap screw; (2) OPL body; (3) safety screw; (4) dual-cone abutment adapter; (5) permanent locking screw; (6) proximal connector; and (7) prosthetic connector. (b) Radiograph of OPL in a transfemoral amputee. (c) Clinical photograph of a transfemoral amputee demonstrating a healthy transcutaneous stoma for the prosthetic connection. (d) Activity representative of the stability osseointegrated limbs can provide for amputees. OPL: Osseointegrated prosthetic limb|
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The primary purpose of this study was to evaluate that concern, comparing the mobility, QOL, and complications between two cohorts of osseointegrated oncologic amputees: nine who had prior local radiation therapy (XRT) versus 23 who had no local radiation therapy (NRT). Our hypothesis was that there would be no significant differences between the two groups, suggesting that osseointegration could be considered a safe and effective procedure in sarcoma patients regardless of whether they have previously undergone local irradiation.
| Subjects and Methods|| |
Following institutional ethics review, we retrospectively reviewed our prospectively maintained osseointegration database. In general, patients considered for osseointegration are skeletally mature adults who either (1) report pain or mobility dissatisfaction with their TSP; (2) have an intact limb with incapacitating pain, complex deformity, or profound distal weakness, whose functional capacity is considered likely to be improved by amputation; or (3) are recent amputees preferring osseointegration to TSP rehabilitation. Specific inclusion criteria for this study were patients who had a history of sarcoma on the amputated extremity and at least 1 year of postoperative follow-up. Patients were excluded if they did not have a history of sarcoma on the amputated extremity or if they did not have at least 1 year of postoperative follow-up (ten patients). These criteria yielded 32 patients with unilateral transfemoral amputation who were categorized into two cohorts: nine who had at least one session of XRT at the amputation site and 23 who had NRT. [Table 1] identifies each cohort's primary oncology. Chart review focused on demographic information, preoperative and postoperative mobility and QOL survey outcomes, and postoperative complications, which were defined as any unplanned surgery to manage problems such as infection or implant loosening. Of the nine XRT patients, seven (78%) had their care performed more than 5 years before presentation, and all at other institutions. These seven patients' charting was on paper records which were no longer retrievable. Given the very limited potential XRT treatment data available, the number of cycles and dosage of XRT was not evaluated in this study.
The preoperative assessment, operative technique, and postoperative follow-up routines are previously detailed, and summarized as follows. At the first consultation, patients interested in osseointegration are asked to complete QOL surveys (Questionnaire for Persons with a Transfemoral Amputation, and other questions asked by our practice) and perform validated mobility tests (Timed Up and Go and 6-min walk test [6MWT]); their K-level is determined by the surgeons during examination. Press-fit osseointegration implants included the integrated limb prosthesis (ILP, Orthodynamic, Lubeck, Germany) or osseointegrated prosthetic limb (OPL, Permedica Medical Manufacturing, Lecco, Italy). Patients are encouraged to remain local for at least 3 months postoperatively for focused rehabilitation. The patients are asked to complete the same questionnaires and mobility tests at annual follow-up visits where their K-level is also reassessed. Not all patients completed the formal mobility tests and surveys at both the preoperative and postoperative visits, even though this was requested. We do not deny patients osseointegration based on their willingness to complete research data metrics. Therefore, in situations where both preoperative and postoperative data are not available, both values are omitted from the analysis. The patients are still included in the study because there is value in understanding potential complications.
Statistical calculations were performed using Google Sheets (Google LLC, Mountain View, CA, USA) and Graphpad QuickCalcs (GraphPad Software, San Diego, CA, USA). Frequencies were compared using Fisher's exact test. Means were compared using Student's t-test. Statistical significance was set as P < 0.05.
| Results|| |
[Table 2] presents the demographic summary of each cohort. The two cohorts are generally similar: there were no statistically significant differences for age, gender, laterality, body mass index, years from amputation to osseointegration, surgical stages, implant brand, or follow-up years.
[Table 3] presents the mobility evaluations, grouped by cancer therapy cohort (XRT vs. NRT) and also by status (preoperative vs. postoperative). The XRT and NRT cohorts were similar to one another at each treatment point (no P values achieved significance). Both cohorts improved following osseointegration, with the following improvements statistically significant: XRT wear hours (P = 0.029), NRT K-level (P < 0.001), and NRT 6MWT (P = 0.046). These are shown graphically in [Figure 2].
|Figure 2: The patients' mobility metrics are presented, grouped by XRT versus NRT cohort (red vs. blue) and also by preoperative versus postoperative status (dark vs. light). Asterisk (*) indicates statistical significance. The XRT and NRT cohorts were similar to one another at the preoperative and postoperative time points (no asterisk between red and blue columns). All mobility metrics improved after osseointegration, as visualized by all light colors being taller than dark colors; the difference was statistically significant for XRT wear hours, NRT K-level, and NRT 6MWT. XRT: radiation therapy, NRT: No radiation therapy, 6MWT: 6-min walk test|
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|Table 3: Mobility performance, enumerated by cancer therapy cohort and by osseointegration status|
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[Table 4] presents the QOL survey data, also enumerated by cancer therapy cohort (XRT vs. NRT) and by status (preoperative vs. postoperative). The cohorts were similar to one another with no significant differences for any of the pre- or postosseointegration metrics. Comparing a cohort's preoperative to postoperative QOL (a pair of vertical pre- and postcells for a single metric), the cohort's average improved in every category measured, with significant differences identified for XRT problem score (P = 0.021), NRT problem score (P < 0.001), and NRT global score (P < 0.001). These are shown graphically in [Figure 3].
|Figure 3: The patients' quality of life surveys metrics are presented, grouped by XRT versus NRT cohort (red vs. blue) and also by preoperative versus postoperative status (dark vs. light). Asterisk (*) indicates statistical significance. The XRT and NRT cohorts were similar to one another at the preoperative and postoperative time points (no asterisk between red and blue columns). All quality of life metrics improved after osseointegration, as visualized by all light colors being better than dark colors (mobility and global higher is better, problem lower is better); the difference was statistically significant for NRT patients in all three areas. XRT: radiation therapy, NRT: No radiation therapy|
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|Table 4: Questionnaire for Persons with a Transfemoral Amputation survey data, enumerated by cancer therapy cohort and by osseointegration status|
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[Table 5] presents the complications requiring additional surgery, categorized by cohort. The rates of refashioning were low and not statistically different between the cohorts. Refashioning is a soft tissue debulking procedure (similar to the plastic surgery procedures of tissue tightening or redraping,) in which redundant fat and skin which sag and lead to stoma site irritation are debulked and stabilized. Debridement is performed to manage soft or bony tissue infectious symptoms. No patient in either cohort required debridement. Implants may require removal for various reasons. Three XRT patients and one NRT patient required removal, all for different reasons. The rate of removal was statistically greater in the XRT versus NRT cohort (33% vs. 4%, P = 0.048).
The situations prompting removal are summarized as follows. A female was diagnosed with right distal femur osteosarcoma at age 13 with management featuring local resection, XRT, and bilateral fibular autograft with subsequent lengthening. Upon presentation, she reported persistent frequent recurrent infections, and was therefore provided transfemoral amputation with simultaneous OPL osseointegration at age 37. She experienced persistent pain and radiographs identified loosening, so she had staged removal with antibiotic nail placement followed by revision osseointegration with an ILP. This also became infected and she had repeat removal with antibiotic spacer followed by second revision osseointegration with a large diameter OPL, which has been stable for 15 months [Figure 4]. A male was diagnosed with rhabdomyosarcoma at age 15 with management featuring XRT and right through-knee amputation. He presented to us at age 45 and had osseointegration with an ILP. He had loading pain which persisted through 1 year, suggesting that the implant probably either did not achieve integration or loosened without apparent infection. At surgical explantation, the implant was grossly loose without evidence of infection, and was removed and the incision was closed. One month later, he had revision osseointegration with an OPL and has done well in the 5 years since. A male had right distal femur osteosarcoma diagnosed at age 52 with management featuring XRT and tumor excision with total knee megaprosthesis. This became infected and he presented to us at age 58, and was managed with transfemoral amputation with placement of an antibiotic nail, followed 2 months later by osseointegration with an OPL. Three years later, he developed a deep infection which required implant removal and antibiotic nail placement. His infection persisted, and 4 months later, he had additional debridement with another antibiotic nail. Two months later, he had antibiotic implant removal with revision osseointegration using an OPL. He has done well in the 4 months since. A female who had amputation without radiation (NRT) at age 11 years to manage osteosarcoma had osseointegration at age 41 years with an ILP. Four years later, the implant fractured at the distal portion and dislodged. She had remnant implant extraction with prophylactic antibiotic spacer insertion, followed by revision osseointegration using an OPL, and has done well in the 8 months since [Figure 5].
|Figure 4: Radiographic storyline for a female who had distal femur osteosarcoma diagnosed at age 13 with management featuring local resection, XRT, and bilateral fibula autograft with subsequent lengthening. Upon presentation (a), she reported persistent frequent recurrent infections, and was therefore provided transfemoral amputation with simultaneous OPL osseointegration at age 37 (b-d). She experienced persistent pain and radiographs identified loosening, so she had staged removal with antibiotic nail placement (e) followed by revision osseointegration with an ILP (f). This also became infected and she had repeat removal with antibiotic spacer followed by second revision osseointegration with a large diameter OPL (g), which has been stable for 15 months. XRT: radiation therapy, OPL: Osseointegrated prosthetic limb, ILP: Integrated limb prosthesis|
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|Figure 5: Radiographic storyline for a patient who had osteosarcoma managed without radiation at age 11. She presented at age 41 (a) and was reconstructed with an ILP (b). Four years later, the implant fractured at the distal portion and dislodged (c). She had remnant implant extraction with prophylactic antibiotic spacer insertion (d), followed by revision osseointegration using an OPL (e and f), and has done well in the 8 months since. OPL: Osseointegrated prosthetic limb, ILP: Integrated limb prosthesis|
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| Discussion|| |
The most important finding of this study was that oncologic amputees achieve similar mobility and QOL benefit following osseointegration regardless of their prior exposure to XRT. While the implant revision rate was significantly higher in the XRT cohort compared to the NRT cohort, there were no observable differences between the XRT and NRT cohorts regarding either the patients' measured mobility improvement or their opinion of the benefit of osseointegration.
Traditionally, radiation exposure has been considered a major contraindication to transcutaneous osseointegration.,,, This judgment was based on early animal studies, suggesting that irradiation impaired the quality and strength of osseointegration;, however, this impairment is not always identified. Since those early animal studies, investigations have been performed regarding the use of XRT to prevent heterotopic ossification in cementless total hip and knee arthroplasty, which also relies on bone ingrowth to achieve implant stability. This use of XRT for heterotopic ossification prevention has been identified to not be a significant risk factor for loosening or revision for total joint arthroplasty, when administered at prophylactic doses and shielding the implant's textured areas for bone ingrowth. These caveats of dosage and region are important points: XRT for sarcoma palliation or treatment versus heterotopic ossification prophylaxis features substantially higher dosage which is potentially enough to impair the bone's ability to osseointegrate and heterotopic prophylaxis shields the implant far more than therapeutic radiation shields the bone. Perhaps the most frequently referenced article directly investigating this topic evaluated Ti6Al4V textured implants inserted bilaterally in dog humeri, with one limb being irradiated with either 500 (14 dogs) or 1000 (21 dogs) rads over 1 week postsurgery and the other limb serving as nonirradiated control. Five hundred rads did not significantly alter the bone ingrowth or fixation strength through 8 weeks. One thousand rads reduced ingrowth around 50% through 8 weeks and fixation through 2 weeks, but at 4 and 8 weeks, fixation was not significantly different. A recent study evaluated 33 patients who had total hip arthroplasty using titanium acetabular components, an average of 5 years following pelvic XRT for malignancy (mean 6300 rad) and followed for an average of 5 years. They reported a 10-year survivorship free of aseptic loosening (100%), any revision (89%), and any reoperation (89%). One notable difference of these patients versus most press-fit transcutaneous osseointegration for amputees (TOFA) is that TOFA is usually performed without retention aids such as screws, whereas 87% of the acetabular cups had screws. Therapeutic radiation dosage for extremity sarcoma is often 5000–6600 rads divided over several weeks to months, whereas prophylactic heterotopic ossification radiation dosage is around 600 rads (~10%) administered one time soon after the primary surgery,, and the implant is shielded from that radiation.
Taking all this into consideration, post-XRT amputees seeking TOFA were counseled with the following risk–benefit analysis. No prior studies have evaluated the clinical effect of XRT on transcutaneous extremity osseointegration, so there is no direct clinical precedent to indicate the potential success rate for limbs irradiated with such a high dose. Further, given that almost all the patients had amputation as tumor management, it may be that the radiation dosage to the residual limb bone and soft tissue was much lower than therapeutic malignancy XRT and perhaps closer to that of heterotopic ossification prophylaxis (depending on exact tumor location versus amputation level). In addition, whether XRT was administered pre- or postamputation can substantially alter the dosage because of the field of radiation., However, given the lack of patient record availability, this could only be guessed. However, because the patients had such poor QOL, they were willing to accept some potential risks. If the osseointegration process worked, which we expected would be the outcome, they were likely to have improved mobility and QOL as nearly all osseointegrated amputees have experienced. Should the procedure fail, the expected worst outcome would be a return to their existing status as a TSP user. It was considered medically safe, and ethically sound based on the principle of patient autonomy, to provide them the opportunity for an enhanced QOL.
In our opinion, the results of this study suggest that XRT should be considered an increased risk of implant removal, but not an absolute contraindication against osseointegration. All patients eventually achieved stable TOFA, and their objective functional performance and subjective reported outcomes document consistent improvement in both domains. Two of the XRT loosenings occurred for patients early in our osseointegration experience, and, in our opinion, several specific technical considerations could potentially mitigate this risk. The first is to use a titanium alloy implant, rather than cobalt-chrome. Titanium facilitates osseointegration better than cobalt-chrome and its mechanical properties are more similar to bone. The second is to achieve an appropriate fit with an implant that fills the medullary canal completely, while simultaneously avoiding an intraoperative fracture. Finally, while osseointegration between healthy bone and titanium is nearly always achieved without adjuncts, for irradiated or other biologically impaired bone, it may be beneficial to use a biological adjunct. Although at this time, there is no data to confirm any putative benefits, potential options include biophysical stimulation such as pulsed electric fields or low-intensity ultrasound,, bone marrow derivatives,, and hyperbaric oxygen., Infection remains the most common complication for osseointegration requiring removal, but to date, no one has identified specific techniques that eliminate or sufficiently minimize this clinical issue. It is worth specifically mentioning that the two XRT patients who developed infection had a history of local infection prior to osseointegration; these two potential risks of prior infection and XRT could be confounding variables. Limited data regarding osseointegration following prior local infection suggest that osseointegration is safe and appropriate following bacterial eradication,, but these studies represent patients without additional XRT.
The most significant limitation of this study is the uncertainty of XRT treatment details, specifically dose and field. Without such details, it is admittedly difficult to estimate the direct effect of XRT on osseointegration, and it is even conceivable that since almost all XRT patients had amputation, their residual limb radiation exposure was rather low, which could render the dichotomization of the cohorts clinically moot. Future investigations regarding the impact of XRT on osseointegration should strive to include such information. In addition, some XRT patients had prior local infection prior to eradication followed by osseointegration; these patients' subsequent infection could be confounded by the two variables of prior infection and XRT. Further, this investigation has the limitations inherent to the study design: an observational cohort study with a small sample size. The retrospective nature is susceptible to possible biases of selection and data availability. The patients had a variety of primary pathologies, with necessary differences in treatment regimen. It is also reiterated that these patients were treated as they presented, and it is not possible to endorse their prior treatment regimen. Further, because some patients' mobility and QOL data were incomplete despite our best efforts to collect it, the reported improvements may be either positively or negatively biased versus the truth. In addition, these procedures were all performed at a dedicated osseointegration tertiary referral center, limiting the generalizability of these results. The greatest strength of this study is that the XRT and NRT cohorts were very similar to one another in demographics, preoperative mobility and QOL, and postoperative mobility and QOL, suggesting that the two cohorts are reasonably comparable, albeit of different case numbers. Another strength is the relatively long follow-up, suggesting that the lack of any significant differences in these outcomes will most likely continue to be maintained. Also notable is that complications are most likely fully represented (patients needing help returned), and the benefits observed were more likely under-represented (satisfied patients may not have made the effort to return).
| Conclusions|| |
This study's hypothesis was partially supported and partially refuted. There was a statistically increased rate of implant removal among XRT patients versus NRT patients. However, the cohorts experienced a similar improvement in their preoperative versus postoperative mobility and QOL. Therefore, it does not seem appropriate to contraindicate osseointegrated reconstruction for oncologic amputees simply because they had prior limb irradiation. Future studies with more specific XRT exposure details are necessary and warranted to help better understand the potential risk–benefit relationship for oncologic amputees, and perhaps eventually more exactly identify a potential “safe limit” for local XRT and successful TOFA.
Financial support and sponsorship
Conflicts of interest
Munjed Al Muderis owns the rights and patents to the OPL implant system worldwide, which is an implant discussed in this article.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]