Ilizarov Distraction Osteogenesis for Reconstruction of Long Bone Defects Following Primary Malignant Bone Tumour Resection

Neal Jacobs¹, David Stubbs², Martin McNally²

Introduction

Primary malignant tumours of long bones (PMTLB) are rare and pose considerable reconstructive challenges [1]. Successful treatment usually requires en-bloc resection, plus chemotherapy for high grade tumours. Contemporary chemotherapy and surgical strategies have resulted in improved survival rates compared with earlier outcomes and limb salvage is now the gold standard with no survival differences between amputation and limb salvage provided adequate resection is undertaken [2].

Following tumour resection, reconstruction options include nonbiological and biological techniques as well as amputation. The choice of reconstruction can determine cosmetic and functional outcome. According to Tsuchiya (1997), the ideal reconstruction “should have biological affinity, resistance to infection, sufficient biomechanical strength, and durability” [3]. Due to the predilection of these tumours for periarticular sites, reconstruction is most commonly achieved with endoprostheses. Despite advances with this technology, long term outcomes remain complicated by prosthetic loosening, wear and infection [4-6]. For intercalary reconstruction, prostheses play a smaller role [7], and alternative strategies have focused on the use of allografts, devitalized tumour-bearing autograft bone, vascularised bone flaps or combinations of allograft or autograft with vascularised flaps [8-12]. The free vascularised fibular graft (FVFG) has become a workhorse for biological intercalary reconstruction, but in the lower limb particularly is associated with high rates of fracture, non-union and return to theatre [11-13].

An alternative biologic reconstruction option is distraction osteogenesis [14]. When undertaken with a stable fixation construct, distraction osteogenesis permits immediate mobilisation, weight bearing and functional rehabilitation, and fulfils the above requirements for an ideal reconstruction in that it is truly biological, strong, durable, resilient, resists infection and responds normally to subsequent physiological trauma. Distraction osteogenesis has been increasingly applied in the management of bone defects due to trauma and infection, however application for the primary reconstruction of PMTLB is rare and little is reported regarding indications, contraindications and outcomes. We present a systematic literature review of the use of distraction osteogenesis for primary reconstruction of long bone defects resulting from resection of PMTLB. This review aims to identify the number of cases reported along with outcomes including tumour recurrence. In addition, we report the experience from our institution of bone transport reconstruction in a series of 8 patients with primary malignant tumours of long bones.

Patients and Methods

Literature review

A systematic literature review was undertaken in compliance with PRISMA-P guidelines [15] to evaluate global experience of bone transport reconstruction following resection of PMTLB.Specific questions asked include: What is the number of cases reported? What is the tumour recurrence rate? Are high grade tumours or chemotherapy a contraindication?In April 2017, a search of the PubMed (1950 to present), Ovid Medline (1946 – present) and Embase (1974 – present) databases was made for all English language papers, articles, books and book chapters containing the following search terms within the title or abstract and Boolean operators; ((Ilizarov OR bone transport OR distraction osteogenesis OR distraction histiogenesis OR callotasis) AND (tumor OR sarcoma)).The abstracts and papers were all read by the first author(NJ) and assessed against the following inclusion criteria. Only articles regarding human cases of primary malignant tumours of long bones were included. Maxillofacial cases, benign tumours and conditions including Giant cell tumours and osteofibrous dysplasia were excluded as were cases of secondary deformity correction or limb lengthening procedures plus salvage procedures following failed alternate tumour reconstructions. Cases were also excluded if insufficient detail was provided to determine exact diagnosis or treatment. In addition to pure bone transport techniques, cases utilizing Ilizarov compressiondistraction techniques were also included, provided distraction was undertaken within the bone affected by the malignant tumour. Thus, cases of medial fibular transport were excluded, as were cases of arthrodesis with distraction osteogenesis undertaken on the other side of the original joint from the tumour. Initial search identified 127 articles, which was reduced to 21 after screening for inclusion criteria. Individual cases satisfying the inclusion criteria were mined from 058-068.

the various studies identified, and care was taken to avoid duplicate inclusion of cases where reported in more than one paper.

Case series from our institution

We retrospectively reviewed a consecutive series of eight patients managed with bone transport reconstruction of an intercalary defect arising from resection of a PMTLB during a 13-year-period between January 2002 and May 2015. All except one of the patients (case 1) presented to our institution via the multidisciplinary sarcoma board, and reconstructive surgery was performed by one of the 2 senior authors in all cases. Initial tumour workup confirmed that the patients had an isolated diaphyseal bone tumour without metastatic spread, and the reconstructive surgery was undertaken simultaneously with the tumour resection in all but one case (case 1). All primary malignant tumours regardless of grade were included, and adjuvant therapies were not Ilizarov circular frame constructs (Smith & Nephew, Memphis, USA) were used for bone transport in all but one case, in whom an LRS rail (Orthofix, Verona, Italy) mono lateral external-fixator was used. A latent period of 1 week was prescribed before commencing distraction at a rate of 1mm per day in 4 increments of 0.25mm. Bone transport was performed over an intramedullary nail in 3 cases. At the time of frame removal, patients were put into a protective brace or cast and partial weight bearing prescribed for 2 weeks.

Histological diagnosis was confirmed by a specialist osteoarticular pathologist. All patients were contacted to determine final status according to ASAMI [16] plus MSTS outcomes [17].

Complications of the Ilizarov treatment were classified using the system defined by Paley (1990), as ‘problems’ if they were resolved by the end of treatment with non-operative intervention, ‘obstacles’ if they were resolved by the end of treatment using operative intervention and true ‘complications’ if they resulted from intraoperative injury or were not resolved by the end of treatment [18].

Results

Literature review

Twenty-one papers met our inclusion criteria as illustrated in (Figure 1). Seven were single case reports, while 14 were case series. Within these series, not all reported patients had undergone distraction osteogenesis for a primary malignant bone tumour. In total, 67different cases of clearly documented distraction osteogenesis for the primary reconstruction of a defect resulting from resection of a PMTLB were identified [3,19-39]. Full details of these cases are provided as a table in the supplementary (Table S1).

Of the 67 cases, 34 were male (51%), mean age 21 years (range 4 - 72 years). Histological diagnosis was osteosarcoma in 43 cases (64%), Ewing’s sarcoma in 11 (16%), adamantinoma in 5 (7%), chondrosarcoma in 5 (7%) and MFH in 3 (4%). Use of chemotherapy was documented in 43 cases (64%).

The mean defect size reconstructed was 12.4cm (range 4.5 - 24cm), with a mean external-fixator index of 36.3 days/ cm (range 12.4 - 191 days/ cm). At least 57 cases were reconstructed using bone transport and at least 8 utilised bifocal compression distraction techniques. In 2 cases, it was not completely clear whether the distraction osteogenesis technique was bone transport or bifocal compression-distraction. Adjuvant use of IM nail was documented in 7 cases and locking plate

in 3. There were 14 documented cases of mono-lateral and 42 cases of circular external-fixation, while the method of stabilisation was not made clear in 11 cases. Median follow-up was 48 months (range 10 - 237 months). MSTS functional outcome scores were provided in 35 cases, with a mean score of 91% (range 60% - 100%).

Eighteen cases (27%) had a documented pin site infection, 15 (22%) had significant contracture/ stiffness of the knee or ankle joint, 15 (22%) experienced delayed-union or non-union of the docking site requiring a docking site procedure, 13 (19%) had delayed consolidation, 6 cases (10%) suffered deep infection, and 2 (3%) experienced hardware failure (one broken IM nail, one broken external-fixator pin). Nine cases (13%) had a resultant leg length discrepancy (reported range 2cm – 6cm), 4 (7%) had a reported malunion, and 1 patient suffered a peroneal nerve palsy. There were 5 cases (7%) of reported fractures, one involving an adjacent bone segment and one the result of a road traffic accident 4 years post-surgery. Among the 67 cases identified, there was only one documented case of local recurrence (1.5%) at 5 years following resection of intracortical osteosarcoma. Nine further cases (13%) developed systemic disease leading to death in 7 at mean time following surgery of 38 months (range 13 - 84 months).

058-068.

Case series

Eight cases were identified (7 female and 1 male), with average age 40 years (range 23 - 60 years).Details are provided in (Table 1). One case (case 1) had undergone a previous allograft reconstruction elsewhere at the time of tumour resection, but was referred to our institution with infected non-union. None of the patients required chemotherapy during their treatment. Mean follow up was 82.6 months (range 18 – 174 months). There were 2 true complications: one case of knee stiffness which resolved after quadriceps plasty, and one case of local tumour recurrence. There were no cases of deep infection or fracture.

The case with local recurrence (case 5) initially presented as pathological fracture and, after assessment by the sarcoma board and biopsy, was incorrectly diagnosed as an aneurysmal bone cyst (ABC). Attempted fracture fixation failed and she was referred to our unit. Segmental resection was undertaken with bone transport over an IM nail. All histology up until this point supported the diagnosis of ABC and so the resection was as for a benign tumour. Subsequent histological analysis confirmed grade 1 MFH. The sarcoma board decided to continue close observation and after completion of bone transport and locking of the IM nail, the transport segment was noted to undergo osteolysis in keeping with local recurrence. Despite plans for a staged total femoral replacement, she later underwent throughhip disarticulation. She completed chemotherapy and remains alive and disease free.

The remaining 7 cases all healed without recurrence or metastases. They achieved excellent ASAMI outcomes for bone reconstruction, excellent or good ASAMI outcomes for function, and MSTS functional outcomes of 90%and greater (Table 1). At final follow-up, these patients were satisfied with their reconstructions and would recommend the treatment to other patients with similar problems. No patient has required further reconstructive surgery. Radiographs and photographs illustrating the reconstructions and outcomes for cases 3 and 7 are provided in figure 2A-G and figure 3A-C respectively.

Discussion

Our literature review revealed only 67 clearly reported cases of distraction osteogenesis for the primary reconstruction following resection of PMTLB. Although these are rare cases, this most likely represents a significant under-reporting as some centres may have undertaken this type of surgery but not published due to low numbers.

We perceive there is anxiety regarding use of distraction osteogenesis immediately after malignant tumour resection, not only due to unfamiliarity with Ilizarov reconstruction methods and principles, but also due to fear of mitogenicity with this technique. This is a reasonable fear, although there is only one published report of malignancy arising in a bone regenerate, in a single case of Ilizarov lengthening through an area of fibrous dysplasia [40]. Our review of the literature demonstrates a local recurrence rate of only 1.5% among the 67 cases reported, which include a large proportion of high grade tumours. However, given the considerable heterogeneity of the different cases including follow-up periods, direct comparisons and analysis are difficult and extrapolation should be undertaken with caution.

Our own series includes one case of recurrence with catastrophic Ad - Adamantinoma, CS - Chondrosarcoma, MFH - Malignant Fibrous Histiocytoma, MPNST – Intra-Osseous Malignant Peripheral Nerve Sheath Tumour BT - Bone Transport, CF - Circular Frame, IM - Intramedullary, ML - Monolateral External Fixator. DS - Docking Site Non-Union, PF - Premature Fusion, PSI - Pin Site Infection, BGDS - Bone Graft Of Docking Site, DSP - Docking Site Procedure. MSTS – Revised Musculoskeletal Tumor

Av 40 13.5 365 26.8 Society functional outcome score (Enneking et al. 1993) outcome necessitating amputation. Initial incorrect diagnosis on biopsy, followed by intra-lesional surgery and subsequent inadequate resection contributed to this outcome. This is in keeping with recent conclusions by Gaston, et al. [41].

Potential adverse effects of adjuvant chemotherapy on the quality of bone regenerate is a particular issue of concern for distraction osteogenesis. Chemotherapy was not indicated in any of our successful salvage cases but was in 64% of the literature cases identified, with mixed results. Ozaki, et al. [31] reported poor regenerate in their series with prolonged frame index (average 95 days/ cm), although this was a challenging series with 4 of the 5 cases requiring chemotherapy and several needing wide resection of knee joint and 2 cases also requiring vascular reconstruction of popliteal vessels. Similarly, both Dormans, et al. [22] and Yang, et al. [38] also reported poor quality regenerate with chemotherapy necessitating a reduced distraction rate. In contrast, the Kanazawa group report little concern with bone regenerate quality despite chemotherapy for high grade sarcomas [3,35-37,42], as do Demiralp, et al. [21]. Animal studies specifically investigating the effects of chemotherapy 058-068.

Outcomes

Further Follow up ASAMI ASAMI MSTS

Complications

surgery (months) Bone Function (%) Quadsplasty, Lack of knee removal of 174 Excellent Good 90 flexion IM nail Revision Breakage of corticotomy transport & transport 144 Excellent Excellent 90 mechanism, PF mechanism, BGDS PSI with ulcer, SSG to ulcer, 115 Excellent Excellent 100 DS DSP soft tissue PSI, skin release, 75 Excellent Excellent 97 tethering, DS BGDS PSI, local Amputation 61 n/a n/a n/a recurrence skin tethering, soft tissue wire breakage, release, 30 Excellent Excellent 93 DS BGDS PSI, DS DSP 44 Excellent Excellent 93 Replacement Pin cut-out of pin with from transport 18 Excellent Good 93 transport segment cable, BGDS 82.6 93.7 on distraction osteogenesis have also been mixed in their findings and conclusions. Monsell, et al. [43] used a rabbit model to test effects of adriamycin and cisplatinum regimens on bone regenerate. They found that isolated pre-operative chemotherapy resulted in reduced bone mineral content and density, without altering the mechanical properties, while peri-operative chemotherapy produced no observed effect on mineralisation but did alter the mechanical properties of the bone regenerate [43]. In contrast, Jarka, et al. [44] were unable to demonstrate any histologically or radiologically apparent effect of methotrexate on distraction osteogenesis in their rabbit model [44]. This is clearly a multifactorial issue which is likely dependent on the specific chemotherapy regimen utilized, which may account for some of the clinical differences observed between different centres.

There were 7 documented uses of IM nail to reduce externalfixation time in the literature case series, including cases of high grade osteosarcoma and MFH. In 3 of our cases bone transport was undertaken over an intramedullary nail. This is a well described technique [45,46] to reduce frame time, however may be considered controversial in the setting of malignant bone tumour. If the tumour

regenerate formation and consolidation up to 15 months. Frame was

limb from Case 3 at 22 months (4 months post frame removal).

surgeon and pathologist are confident that successful resection has been achieved then we believe there is no contraindication to the use of an IM nail, however this decision must be made on an individual case basis and in discussion with the sarcoma board. As our experience with case 5 demonstrates, if diagnosis is incorrect or resection inadequate, then use of IM nail may contribute to poor outcome. Among the 7 cases of IM nail use in the literature, there was no local recurrence, but 2 cases of systemic disease.

Our own case series demonstrates outcomes comparable with the literature, although our external fixation indices appear shorter than average. The small size of our case series limits the study, however this is a rare solution for an uncommon problem and our eight cases equate to 11% of the published experience. Only 4 groups worldwide

have reported similar sized series [3,21,23,25,35-37]. The Kanazawa group in Japan appear to have the greatest experience of this technique and have producedseveral of the case series included in our literature review. These were among the largest series and, despite considerable overlap of the cases and repeated reporting, account for 23 of the included cases (34%) [3,35-37]. This centre also reports the longest follow-up, up to 237 months, in one of its series focusing purely on osteosarcoma cases with a minimum follow-up of ten years [37].

In conclusion, we have presented a systematic review of distraction osteogenesis for reconstruction of bone defects following PMTLB, along with a case series from our own institution. Distraction osteogenesis by Ilizarov principles offers an effective but rarely usedbiological reconstruction option in the management of PMTLB. In selected cases, excellent long term functional outcomes can be achieved, and chemotherapy for high grade tumours need not be a contraindication.

058-068.

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Supplimentary Table: Systematic review: Defect size Diagnosis/ Case Author(s) Age Sex Bone [length Surgery Chemo stage gained] (cm) ApornchaIntracortical 1 yanon, 21 F DT 14 CF, BT - OS 2011 Staged CF, Demir, + (prior to 2 36 M MFH PT 12 BT along 2016 reconstruction) LP Staged CF, Demir, + (prior to 3 42 M OS DT 14 BT along 2016 reconstruction) LP Staged CF, Demir, + (prior to 4 34 M ES MT 15 BT along 2016 reconstruction LP Demiralp, Parosteal OS 5 14 F MT 9 CF, BT - 2014 (G1T1M0) Demiralp, OS 6 15 F MT 21 CF, BT + 2014 (G1T1M0) Demiralp, OS 7 24 M DF 24 CF, BT + 2014 (G1T1M0) Demiralp, ES 8 7 M DF 11 CF, BT + 2014 (G1T1M0) Demiralp, ES 9 10 M DF 16 CF, BT + 2014 (G2T1M0) Demiralp, OS 10 19 M DF 14 CF, BT + 2014 (G1T1M0) Demiralp, ES 11 10 F DF 12 CF, BT + 2014 (G1T1M0) Demiralp, OS 12 33 M DT 17 CF, BT + 2014 (G1T1M0) Demiralp, OS 13 17 M DT 14 CF, BT + 2014 (G1T1M0) Demiralp, OS 14 21 M DT 15 CF, BT + 2014 (G1T1M0) Dormans, 15 13 F ES Tibia 13 ML, BT + 2005 16 Erler, 2005 14 F OS/ IA MT 9 CF, BT + 17 Erler, 2005 15 F OS/ IA MT 21 CF, BT + 18 Erler, 2005 24 M OS /IB DF 24 CF, BT + 19 Erler, 2005 21 M OS/ IA Ulna 8 ML, BT - 20 Erler, 2005 7 M ES/ IIA DF 11 CF, BT + 21 Erler, 2005 10 M ES/ IIA DF 16 CF, BT + 058-068. F/U DI EFI Reported Recurr- Further time (days/ (days Outcome Complications ence? treatment (moncm) /cm) ths) Repeat resection, chemotherapy, 32.1 LR, 5yrs >84 strut graft and ankle arthrodesis ASAMI Bone - ORIF & bone Excellent graft DS at 11.8 12.7 EC 71 ASAMI frame removal, Function - TAL Good ASAMI ORIF & bone Bone - graft DS at Excellent Exposed frame removal, ASAMI metalwork r/o metal and Function - reapplication Excellent of CF ASAMI Bone - ORIF & bone 11.5 12.5 PSI graft DS at 22 ASAMI frame removal, function - Exellent 11.11 31.6 MSTS 93% PSI 11.19 22.8 MSTS 90% DOD 84 11 22.5 MSTS 90% PSI, SI, EC, MU 11.7 40 MSTS 86% PSI, DC 11.25 18.8 MSTS 90% PSI, DS, DC, LLD 10.42 24 MSTS 86% EC 11.4 29.8 MSTS 93% LLD 10.5 31.7 MSTS 90% TE, DC 11.4 26.7 MSTS 96% PSI, TE 10.6 26 MSTS 83% TE PR, DS, LLD Bone graft 16.2* 53.8 MSTS 80% DOD 41 3.6cm docking site Enneking 11.1 31.6 (1987) - PSI 128 Enneking PSI, # distal 11.1 22.8 (1987) - ORIF fracture 53 femur Enneking Soft tissue 11 22.5 (1987) - PSI, SI, MU, EC 44 release Poor ORIF DS, R/o Enneking metal, bone 11.2 26.2 (1987) - PSI, DS, Inf 34 graft & DBM to DS non-union Enneking 11.7 40 (1987) - PSI, DC 31 Good Enneking 11.2 18.7 (1987) - PSI, DS, DC 27 Good Futani, 22 11 M small cell OS PT 13 CF, BT + 2012 Kapukaya, 23 17 M CS PF 20 ML, BT - 2000 Kapukaya, 24 8 F OS DF 12 CF, BT + 2000 Kapukaya, 25 7 F ES DF 13 CF, BT + 2000 Kapukaya, 26 37 M CS PF 11 ML, BT - 2000 Kapukaya, 27 8 F OS DF 12 CF, BT + 2000 Kapukaya, 28 13 M OS DF 10 ML, BT + 2000 Kitsoulis, 29 31 F Ad DT 5.8 ML, BT - 2009 Lammens, 30 20 M Parosteal OS Ulna 10 CF, BT 1992 31 Lee, 2006 8 F Ad MT CF, BT - 32 Lee, 2006 11 F Ad MT CF, BT - McCoy, 33 16 M CS MT 18 CF, BT - 2013 McCoy, ML, BT 34 18 F Parosteal OS Femur 11.7 - 2013 over IM nail ML, BT, Ouyang, 35 23 M CS DT [8] tibiotalar - 2015 arthrodesis Ozaki, Wide 1998 excision 36 11 F OS DF 23 [18] + Ozaki, knee. CF, 1998a trifocal BT Ozaki, CF, trifocal 37 6 M ES Tibia 10 + 1998a BT Ozaki, CF, trifocal 38 44 M CS Femur 19 [ 7] - 1998a BT Ozaki, CF, trifocal 39 26 F OS Femur 14 [12] + 1998a BT, VR Ozaki, 18 CF, trifocal 40 27 F OS Femur + 1998a [15.5] BT, VR CF, CD 41 Said, 1995 41 F MFH DF 11 [9] - arthrodesis Stoffelen, Distal 42 18 M Parosteal OS 10 CF, BT 1993 Ulna 43 17 M OS/ IIIB PT 11.8 BT + 1997 Tsuchiya, Low grade 44 15 F MT 13.5 ML, BT - 1997 OS 058-068. ORIF and bone 32 MSTS 73% DS, LLD 3cm graft DS at 48 frame removal 13 32 30 14.5 33.4 Inf 21 15.7 32.5 DOD 20 14.5 34.5 SI 20 31.0* 36 24.0* DS 18 PSI, EC, DS 39 PSI, Inf 37 ASAMI Bone - IM nail and 22.5 Excellent DS, LLD 2.3cm plating docking ≥36 MSTS site 100% ASAMI Bone - I&D abscess, Excellent Exchange PSI, HF, DS, 24.2 ASAMI IM nail, LLD2cm, EC Function - QuadricepsGood MSTS plasty 90% 11.1 36 MSTS 94% LLD 36 Enneking PSI, PR, TE, Removal of pin, 32.2 (1987) - DOD 66 LLD6cm MUA Poor FVFG, pedicled PR, SN, Enneking skin flap, pseudarthrosis n/a (1987) - centralisation 48 of subsequent Poor of ipsilateral FVFG fibular Enneking PR, TE, SN, TAL, AKA for 191 (1987) - 45 #, Inf osteomyelitis Poor Enneking 104 (1987) - PR, PSI, HF Insertion of pin 43 Fair By-pass of Enneking popliteal Thrombosis, 53 (1987) - vessels, valgus 40 MU, TE, DS Fair osteotomy, TAL, IM nail 18* 10 DS, stiffness 11 25 of forearm - 36 rotation Enneking 8.5 27.9 (1987) - DOD 13 Fair Enneking 10.3 28.6 (1987) - 62 1997 SubartiTsuchiya, cular 45 43 F OS PT 5.5 + 2002 reconstrn., Tsuchiya, CF, BT 2006 1997 2002 Low grade 46 20 M PT 5.5 CF, BFCD - Tsuchiya, OS 2006 Watanabe, 2013 1997 47 13 F OS DF 15 BFCD + 2002 2006 48 10 F ES PF 8 BFCD + 1997 49 72 M MFH/ IIIB MF 8 ML, IM nail - 1997 1997 Tsuchiya, MR, CF, BT, 50 38 M OS/ IIIB DF 15 + 2002 IM nail 2006 1997 Tsuchiya, ER, CF, 51 22 M OS DF 9.2 + 2006 BFCD Watanabe, 2013 1997 2002 ML, BFCD 52 34 F Parosteal OS DF 6.6 - Tsuchiya, over IM nail 2006 Watanabe, 2013 Tsuchiya 2002 53 15 M OS/ IIB PT 12.5 CF, BT + 2006 Watanabe, 2013 Tsuchiya 2002 Tsuchiya, ML, BFCD 54 9 F OS/ IIB DF 7 [9] + 2006 over IM nail Watanabe, 2013 Tsuchiya 2002 55 26 F low grade OS DF 9 CF, BT - 2006 Watanabe, 2013 058-068. MSTS 17.6 63.5 TE 94 100% DU, SN, bone graft, 10.1 32.7 MSTS 93% 231 Peroneal NP tendon transfer #, EC, knee 7.3 34.8 MSTS 77% 103 instability Enneking 10.8 34.8 (1987) - DOD 32 Good Enneking 21.1 24.8 (1987) - AWD 32 Enneking 14.9 15.9 (1987) - Inf DOD 13 Fair IM nail at 14.2 39.4 MSTS 83% DC, EC time of frame 237 removal MSTS 100% Resection of infected docking site with compression Inf, LLD 2cm, MSTS distraction. 20.6 39.7 MU,Tibial 218 100% Ilizarov # plateau # 4yrs fixation and residual deformity correction MSTS 100% 9.7 30.8 MSTS 90% 211 Ad – Adamantinoma, CS - Chondrosarcoma, ES - Ewings Sarcoma, MFH - Malignant Fibrous Histiocytoma, OS - Osteosarcoma, DF - Distal Femur, DT - Distal Tibia, MT- Mid-Tibia, PF - Proximal Femur, PT - Proximal Tibia, BT- Bone Transport, BFCD - Bifocal Compression-Distraction, CD - Compression-Distraction, CF - Circular Frame, ML - Monolateral External, Fixator, ER - Epiphyseal Reconstruction, LP – locking plate, MR - Metaphyseal Reconstruction, VR - Vascular Reconstruction, Chemo - Neoadjuvant / Adjuvant Chemotherapy, + Received Chemotherapy, - did not Receive Chemotherapy, DI - Distraction Index, EFI - External Fixator Index, * Estimated From Available Data, MSTS – Revised Musculoskeletal Tumor Society Functional Outcome Score (Enneking et al. 1993), DC - Delayed Consolidation, DS - Docking Site Non-Union/ Delayed Union, DU - Delayed Union, EC - Extension Contracture, HF - Hardware Failure, Inf - Deep Infection, LLD - Leg Length Discrepancy, MU - Malunion, NP - Nerve Palsy, PR - Poor Regenerate Formation, PSI - Pin Site Infection, SI - Skin Invagination, SN – Skin Necrosis, TE - Talipes Equinus, # - fracture, TAL - Tendoachilles lengthening, AKA - Above Knee Amputation, LR - local Recurrence, AWD - Alive With Systemic Disease (Metastases), DOD - Died Of Disease, DUC - Died From Unrelated Cause. Tsuchiya 2002 56 13 F OS PT 5.7 ER, CF, BT + 2006 Tsuchiya 2002 57 9 M OS DF 12.6 CF, BT + 2006 Watanabe, 2013 Watanabe, Low grade 58 52 F MF 9 BFCD - 2013 OS Watanabe, 59 8 M ES MT 9.5 BT + 2013 Watanabe, Low grade 60 14 F MT 13.5 BT - 2013 OS Watanabe, 61 4 M Ad MT 7.8 BT - 2013 Watanabe, 62 71 F Ad MT 4.5 BT - 2013 Watanabe, 63 18 F OS DF 14 BT + 2013 Watanabe, 64 46 F OS PT 5.5 BT + 2013 Watanabe, 65 17 F OS PT 5.7 BT + 2013 66 Yang, 2016 29 M Parosteal OS PT 11 ML, BT + 67 Yang, 2016 16 F OS DT 15 ML, BT + Av 21 12.4 058-068. MSTS 20 56.5 43 100% Bone graft 8.8 25.7 MSTS 93% DS DUC 125 docking site MSTS 15.3 17.7 DC Bone graft 145 100% MSTS 13.4 31.7 DS AWD bone grafting 180 100% MSTS 100% MSTS 100% MSTS 18.4 72.9 PSI 175 100% 8.8 37.4 MSTS 83% regenerate # re-fixation 187 MSTS 17.3 100.4 DC, EC bone graft 192 100% MSTS 20 56.5 131 100% MSTS 43.6* 51.2* PR Bone graft 51 73.3% Bone graft and 56* 62* MSTS 60% PR, NU internal fixation 56 with plates Med- 36.3 MSTS 91% ian 48