Aim: Limb salvage is the treatment of choice for lower extremity bone sarcomas in children. To date, peers have not described algorithms for soft tissue reconstruction of these defects. This paper is to report a large single center series of lower extremity salvage after sarcoma treatment, with algorithm.
Methods: The authors performed a retrospective review of patients undergoing resection of lower extremity bone sarcomas at a single center over 12 years.
Results: In total, 65 children (29 girls, 36 boys) with a mean age of 13 years (range 2.9-23.3 years) underwent resection of a lower leg sarcoma with limb-salvage. Tumors types included 50 osteosarcomas, and 15 Ewing sarcoma family of tumors. The types of reconstruction utilized included: 34 primary closures, 22 gastrocnemius and soleus flaps, 3 bipedicled flaps, 2 sural artery flaps, 1 pedicled anterolateral thigh flap, 3 pedicled posterior thigh flaps for subsequent above-knee amputations. No free flap based reconstructions were performed. An algorithm for reconstruction of leg defects in the setting of limb-salvage surgery is presented. Successful limb salvage rate was 95.4%. Limb salvage failed in 3 patients and they required amputation. Finally, 56 patients were able to ambulate without assistance at last follow-up.
Conclusion: The authors present an algorithm for the reconstruction soft tissue after resection of lower extremity bone sarcomas. The use of these techniques helps to decrease complications and maximize function in children with these tumors.
Keywords: Pediatric, bone sarcoma, limb-salvage surgery, reconstruction
Primary bone cancers which include osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) represent approximately 2,400 cases or 0.2% of new cancers diagnosed in the United States each year.[1,2] Malignant bone tumors account for 6% of neoplasms among children and 57% of those tumors occur in bones of the lower extremities.
Limb sparing resections have evolved with advances in reconstructive surgery, orthopedic oncologic surgery, medical oncology, and radiation oncology.[4-7] Limb-sparing surgery is now the treatment of choice for 90% of children. Limb-sparing resections provide the advantage of avoiding amputation but often results in a defect of bone and soft-tissue and function disability. Reconstruction of these defects and mitigating these functional disabilities is critical to achieving limb salvage.
Allografts,[9-12] autografts,[13-16] or endoprostheses[17-20] are used to reconstruct bony defects depending on the type and circumstance with much debate in the literature. Soft tissue reconstruction is equally mired in controversy. Some authors describe primary closure,[21-24] while others recommend local flaps[25-28] or free flaps.[29-32] Small patient cohorts, a variety of tumor types, and different treatment protocols, complicate data on this subject.[33-35] The purpose of this study is to report clinical characteristics and management in the largest single-center series of lower extremity limb sparing surgeries after treatment for bone sarcomas in children and adolescents. An algorithm based on this extensive patient population is also presented.
Patients and data collection
Our institutional review board approved all components of this study. We performed a retrospective review of children who underwent composite resection with limb-salvage for lower extremity bone sarcomas at our single center over a 12-year period, from January 1, 2000, to December 31, 2011. All patients were discussed at our multidisciplinary solid tumor conference before definitive treatment. Analyzed variables included: tumor location; gender; age; tumor size; tumor pathology; last follow-up date; radiotherapy; age at diagnosis; chemotherapy; number and extent of resections; number and site of tumor recurrence(s); pathologic margins of disease; and perioperative and long-term complications. Recurrences were defined as lesions that were biopsy-proven recurrent tumors.
Adjuvant therapy was provided per any protocol under which the patient was enrolled at the time of treatment and as judged appropriate by the care team. External beam radiotherapy was the only technique used for radiation therapy, in the setting of ESFT, with median dose of 58.4 Gy. Chemotherapy drugs most frequently included doxorubicin, cisplatin, methotrexate, and/or Bevacizumab.
Time to local failure and recurrence-free survival were calculated from the time of surgery performed at our institution to the first diagnosis of a local recurrence. Children who did not have a recurrence on or before their date of last contact or death were censored at this date.
At the time of the ablative procedure, tumors were resected to clear margins. Bony reconstruction was performed with a variety of techniques, including allografts and endoprostheses. The reconstruction of soft tissue varied from patient to patient and included primary closure, skin grafts, local and pedicled flaps. No free flaps were utilized in this series. For wound healing complications, various techniques were used. For superficial wound healing issues local debridement was performed either at bedside or under local. After debridement a wound vacuum-assisted closure (VAC) device was usually placed until the wound healed. For deep wound complications including dehiscence we returned to the operating room for debridements, implant revision/ replacement, re-closure, skin grafting, and/or flap reconstruction.[30-33] The choice of flap reconstruction was made based on the orientation and type of wound as well as availability of donor tissue. Flap donor sites were either skin grafted or closed primarily. All patients underwent rehabilitation per our predefined protocols.[36,37]
All data was analyzed with JMP® Pro 10.0 (Chicago, IL). Medians were generated to show the central tendency of continuous variables. Categorical data was presented with Frequencies and proportions. Continuous variables were compared with the Mann-Whitney U test. Significance was defined as a 2-tailed P value of less than 0.05.
Patient and disease characteristics
Eighty-two patients were evaluated for lower extremity bone sarcoma at SJCRH during the study period. Nine patients did not have any surgery, and 8 patients underwent primary amputation, leaving 65 patients included for analysis. With respect to upper leg/ thigh tumors, 9 patients had proximal femur tumors; 4 patients had mid-femur tumors; 24 had distal femur tumors; and 4 patients had tumors that involving the entire femur. With regard to leg tumors, 21 patients had proximal tibial tumors; 1 patient had a distal tibial tumor; and 2 patients had proximal fibula tumors. Patients with primary pelvic tumors were excluded from analysis. Patients with mid-shaft tibial tumors were classified either as proximal or distal tibial tumors, depending on the relative location of the primary tumor.
There were 65 primary limb-salvage surgeries. There were an additional 61 procedures during the perioperative/adjuvant therapy timeframe; and 130 long-term procedures (including non-invasive expansions). Excluding non-invasive expansions, the total number of procedures during the post-treatment period was 87. Characteristics of the patient cohort are detailed in Table 1.
Table 1: Patient and disease characteristics at baseline (n = 65)Click here to view
Patients at presentation had a median age of 13 years with a range of 2.9 to 23.3 years. Thirty-six were male and 29 were female. All patients had a history of an incisional biopsy of their primary tumor and any metastatic sites.
Fifty patients’ pathology was consistent with OS the remaining 15 had ESFT. The majority of children, 50 (78.5%), was presented with localized disease. Three had regional spread on presentation. An additional 12 presented with metastatic disease. A single child had regional spread and lung metastases. The most common metastatic site at time of presentation was the lung. OS or ESFT was the primary neoplasm in all patients. Patients with metastatic disease underwent resection of the primary tumor, as well as any metastatic sites.
Details of management
A multidisciplinary solid tumor board met to discuss each case before the initiation of treatment. All children underwent a curative surgical resection (n = 65) [Table 2]. Only 1 child needed additional resection for local control of the primary tumor [this patient underwent above-knee amputations (AKA) secondary to local recurrence]. For patients presenting with metastatic disease, treatment included resection of the primary tumor, as well as any metastatic sites.
Table 2: Treatment characteristics (n = 65)Click here to view
The median bone and soft tissue defect volume was 799 cm3 with a range of range 197 to 3,697 cm3. Osteotomy length had a median length of 23.7 cm with a range of 8.5 to 62.5 cm. The longest specimen in the series was a total femur tumor, including resection from the femoral head to mid-tibia. At the time of the index procedure, soft tissue reconstruction was performed with primary closure in 45 patients. Gastrocnemius or soleus flaps with patellar tendon reconstruction was utilized in 20 patients. Primary closure was most often utilized in proximal- and mid-femur tumors, and distal tibial lesions [Figures 1 and 2]. Gastrocnemius or soleus flap techniques were most often used in distal femur and proximal tibial lesions [Figure 3].
Figure 1: Proximal femoral resection and reconstruction with endoprosthesis. A: proximal femoral resection site; B: resection specimen and endoprosthesis; C: site after placement of endoprosthesis; D: soft tissue fascial and muscular closure over endoprosthesis; E: primary closure of soft tissue defect is possible, given anatomic orientation of soft tissue defect and reconstructionClick here to view
Figure 2: Bone and soft tissue reconstruction of distal tibia defect. A: bone reconstruction is performed with Phenix™ bone transport rod; B: endoprosthesis is covered in muscular and soft tissue envelope, and skin is closed with primary closure; C: photo at 3-month follow-upClick here to view
Figure 3: Proximal tibia osteosarcoma resection and reconstruction with endoprosthesis. A: resection site after en bloc tumor resection; B: tumor specimen with hinged endoprosthesis for bone reconstruction; C and D: placement of endoprosthesis; E: total implant coverage with gastrocnemius and soleus muscle flaps; F: proximal and distal primary closure; G and H: central portion with exposed muscle flap and skin graftClick here to view
Pathological margin status was evaluated for all resections. Sixty-two cases had negative margins (R0); 1 patient had microscopic margins positive at the time of resection (R1); and 2 patients had macroscopic positive tumor margins at the time of resection (R2). The incidence of an R0 margin was not significantly different between patients who had local (48 of 51, 94.1%), locoregional (2 of 2, 100%), or metastatic disease at the time of presentation (11 of 12, 91.7%) (P = 0.94, Pearson’s chi-squared test). Sixty-two of the 65 children received systemic chemotherapy at during their treatment. Fifty-six received preoperative chemotherapy, and 59 patients received postoperative chemotherapy. Five patients underwent for ESFT with a mean dose 58.4 Gy.
Bone reconstruction consisted of modular endoprosthesis in 42 patients; allograft in 7 patients; bone transport rod in 3 patients; expandible endoprosthesis (Repiphysis) in 12 patients; and 1 patients had no bone reconstruction (for fibula-only resection) [Figures 4 and 5]. Details of soft tissue reconstruction are discussed below.
Figure 4: Mid-femur bone replacement with allograft. A: proximal and distal bone segments are held in place with steinman pins and skeletal traction; B and C: bone allograft is placed in segmental femoral defect, and held in place with spanning plate (lateral and oblique views, respectively)Click here to view
Figure 5: Proximal tibia osteosarcoma reconstructed with Repiphysis expandable endoprosthesis and muscle flap coverage. A: surgical defect and en bloc tumor resection; B: tumor specimen and Repiphysis endoprosthesis in situ; C: placement of Repiphysis implant; D, E, and F: soft tissue reconstruction with muscle flaps, proximal and distal primary closure, skin grafting and incisional wound vacuum-assisted closureClick here to view
Management of complications during cancer treatment
We divided complications into three major categories based on how they were temporally related to surgery. The initial post operative period of 30 days, followed by the period they were undergoing adjuvant therapy and finally after the completion of their therapy. Then they were further subdivided into patients with soft-tissue, implant and long term functional complications.
Eighteen of 65 patients had an initial 30-day postoperative complication. Four patients had cellulitis treated with oral or intravenous antibiotics; 5 patients had a nonoperative wound complication; 7 patients had a deep wound dehiscence requiring operative debridement; and 3 suffered a popliteal artery thrombosis, 1 of these had a successful thombectomy, 2 resulted in AKA (1 patient had multiple complications). No patients had bone or implant related complications during the 30-day perioperative period. All patients were able to successfully resume planned adjuvant therapy postoperatively despite any immediate complications. A single patient had a protocol alteration due to surgical pathology, which found a low-grade OS and did not require further adjuvant therapy as planned.
Twenty-eight patients did not have any complications during their treatment period. Sixteen patients had a nonoperative minor wound complication (e.g. cellulitis, superficial wound dehiscence/ eschar). Twenty-nine patients had an operative complication, requiring a total of 52 procedures. Of these 52 procedures, 38 (73.1%) were soft tissue complications requiring surgery; 14 (26.9%) were bone/implant-related complications. There were an additional 11 metastatectomies (not counted as complications). Of 29 patients requiring surgery during the adjuvant therapy period, adjuvant therapy was delayed in 26; 2 patients did not delay therapy; and 1 patient did not require adjuvant therapy since the limb was amputated secondary to vascular injury. During the combined 30-day postoperative and adjuvant therapy treatment periods, soft tissue closure was achieved with primary closure in 37 cases. Two cases required bipedicled lower leg flap; 1 case required sural artery flap; 1 pedicled anterolateral thigh (ALT) flap; 2 pedicled gastrocnemius flaps; 2 pedicled posterior thigh flaps (for amputations); and split thickness skin graft was utilized in 3 cases. No patients required free flap closure.
Recurrence and overall survival
Median follow-up was 37 months with a range of 6 months to 6.8 years. After conclusion of the study, 22 of the 65 patients did not have any further surgical complications. The 43 remaining patients had a total of 130 procedures during the post-adjuvant therapy period. Endoprosthesis expansions were performed utilizing a non-invasive Repiphysis device, and were not counted as additional procedures. Fourteen procedures (10.7%) were for soft tissue/wound healing issues necessitating operative intervention; 51 (39.2%) were implant/bone-related (not including implant expansions, as noted above); there were 20 metastatectomies; there was 1 AKA secondary to local recurrence; and there was 1 neuroma resection secondary to phantom limb pain after AKA. With regard to soft tissue closure, 1 posterior thigh flap was used after an AKA; and primary closure was utilized in the remaining 65 cases. Table 3 reports the final reconstruction technique utilized for patients, as recorded at the time of their last follow-up.
Table 3: Long term outcomes (n = 65)Click here to view
At the conclusion of the period being evaluated 54 children had successfully completed their oncologic therapy. A remaining 8 were still receiving therapy and an addition three failed to complete their full course. At the most recent follow-up available, 43 had no evidence of any disease; 9 patients had stable disease; 4 patients had progressive disease; 6 patients had died of their disease; and 3 patients had been lost to follow up. With regard to recurrences, there was one local recurrence (as described above); one locoregional recurrence; 6 lung metastases; 3 spinal metastases; and 1 each of kidney, chest wall, and skull metastases. The median time to a recurrence was 13 months with a range of 2 months to 3.8 years. At the time of last available follow-up, 3 patients had had amputations; 56 patients were able to ambulate without any assistance; 7 patients required an assist device (e.g. brace, ankle foot orthosis, crutch, prosthesis); and 2 patients were completely non-ambulatory.
Limb-sparing surgery is now the standard of care for primary bone tumors, especially in the pediatric population.[3,4,6,7] Wide en bloc resection of bone and soft tissue is needed to avoid local recurrence and long term need for amputation. Large resections result in large bone and soft tissue defects, which can leave large functional deficits and require reconstruction. This paper presents an algorithm for both bone and soft tissue reconstruction that is effective in over 95% of patients [Figure 4].[34,38]
Three patients who underwent hinged knee endoprostheses suffered popliteal artery thrombosis, which resulted in 2 AKA’s. These cases were reviewed and are thought to be most likely due to a traction injury that occurred during implant placement. This phenomenon has been described in the literature and we now place these implants with direct visualization of the neurovascular bundle. In addition care is taken to prevent excess traction on the lower leg, with judicious use of a tourniquet. Vascular exams are also performed preoperatively, intraoperatively, and postoperatively. Aside from these events, perioperative complications were acceptable with only 10 of 65 patients requiring operative intervention. Most wound complications could be managed with a bedside debridement and negative pressure wound therapy.
Wound complications were common during the period when patients received adjuvant therapy. Our institutional protocols for these tumors feature early, aggressive multi-agent adjuvant chemotherapy. Experience during this treatment period has been especially instructive. Wound complications that were superficial and did not have any evidence of deep dehiscence or implant exposure could be managed with non-operative intervention. This included bedside debridement with placement of a wound VAC. More severe wound complications were successfully treated with our institutional protocol with a 95% successful limb salvage rate. For wounds around the knee and anterior incision, we elevated a bipedicled anterior leg fasciocutaneous flap. We transposed this to the defect and then skin grafted the donor site. This fasciocutaneous tissue was widely undermined during the index procedure and so it is a delayed flap and tolerates mobilization well. If a patient had a wound along the posterior portion of a knee incision, we elevated a sural artery fasciocutaneous flap. We found this procedure successful, as the large sural artery perforators are not generally injured during the initial reconstruction. Additional options include distally-based ALT flaps and free flaps. Femoral defects could typically be closed primarily since bone sarcoma resections in this region usually spared the majority of the soft tissue. In rare cases where soft tissue was required, defects were closed with proximally- and distally-based ALT flaps. Other options include pedicled rectus flaps and free flaps. While it is often taught that mid- to distal-tibial lesions require free tissue transfer for wound coverage, we found that these soft tissue defects were often small and frequently amenable to primary closure. For recurrent or complicated wounds, gastrocnemius and freestyle propeller-type flaps were adequate in our study. Other options include keystone flaps, pedicled flaps from the distal leg and foot, and free flaps.[35,40] An algorithm outlining our approach to soft tissue coverage is shown in Figure 6.
Figure 6: Algorithm for lower extremity reconstruction after composite resection for bone sarcoma. Defects of the proximal and mid-femur were successfully closed with primary closure in the majority of cases; backup options included pedicled ALT, and rectus abdominis flaps, and free flaps. Defects of the distal femur and proximal tibia were successfully closed with pedicled gastrocnemius flaps, often with inclusion of the soleus muscle. Backup options include distally-based pedicled ALT flaps, anterior bipedicled fasciocutaneous flaps, pedicled sural artery flaps, and free flaps. Defects of the mid- to distal tibia were successfully closed with primary closure in the majority of cases. Backup options include pedicled gastrocnemius and soleus flaps, propeller or keystone flaps, and free flaps. ALT: anterolateral thighClick here to view
One novel finding of our study pertains the timing of complication types, and need for reoperation. We observed that early complications were usually soft tissue related, whereas late complications were usually related to bone reconstruction. Specifically, in the 30-day postoperative period, 10 of 10 operative complications were soft-tissue related; in the adjuvant therapy period, 38 of 52 were soft tissue related, and 11 of 52 were implant related; and in the post-adjuvant period, 14 of 130 were soft tissue related, while 51 of 130 were implant related (chi-square test, P < 0.001). Based on these findings, we propose 2 primary soft-tissue reconstructive goals: facilitation of adjuvant therapy, and the ability to re-operate for late implant-related issues.
In many patients, we use unique implants that obviate multiple operating room trips for expansion, including Repiphysis, which is an expandable endoprosthesis in addition to the Phoenix bone transport intramedullary rod.[26-28] Each of these devices, while significantly more expensive than their standard counterparts, decrease the need for subsequent surgeries by allowing for non-invasive bone lengthening. A more detailed analysis of these devices is forthcoming.
The majority of patients in the cohort did not suffer an infection or hardware exposure. There was only one patient who had a late limb loss secondary to local recurrence. Nearly all attained excellent functional results including ambulation with full active and passive range of motion of the ankle, hip and knee joints.
From the perspective of their oncologic treatment outcomes were superb with a single local recurrence. Six patients died secondary to metastatic disease. This mortality rate (i.e. 9%) is low relative to established 10-year follow-up mortality rates for OS and ESFT, and may be a consequence of our short follow-up (3.1 years). Overall, 62 (95.4%) of limbs were successfully salvaged, with 43 (66.2%) of patients free of disease at last follow-up. Although invaluable for limb salvage surgery, microsurgical reconstruction was not utilized in any of these pediatric cases. The most likely reason for this is an institutional bias towards minimizing the magnitude of the surgery in this young (i.e. pediatric) demographic. While our long-term results are excellent using the algorithm described, the authors recognize that many of our patients would likely benefit from microsurgical techniques. Patients who are known to need frequent implant revisions could benefit from a more robust flap skin paddle that would better tolerate multiple reoperations. Futures studies identifying and evaluating those at risk could prove useful.
In conclusion, lower extremity limb sparing surgery is difficult, demanding extensive bone, tendon, and soft tissue reconstruction. We have found a number of techniques for soft tissue reconstruction that ultimately result in successful limb salvage in nearly all patients. Early complications are usually soft tissue related, and late complications are usually related to bone reconstruction. Thus, operative goals should provide for soft tissue reconstructive options that allow for immediate continuation of adjuvant therapy, the potential for long-term implant revision, and the optimization of oncologic safety and soft tissue integrity. Together, these options provide dependable bony and soft tissue reconstruction essential for successful limb salvage surgery.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Baylor Scott & White Health’s institutional review board approved all components of this study.
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