Tag Archive for: limb salvage surgery

Rehabilitation following Limb-Salvage Surgery in Sarcoma

Volume 2 | Issue 2 | May-Aug 2016 | Page 20-24 | Vincent S Paramanandam, Anuradha A Daptardar, Ashish Gulia

Authors: Vincent S Paramanandam [1], Anuradha A Daptardar [1], Ashish Gulia [2].

1Physiotherapy Department, Tata Memorial Hospital, Mumbai
2Orthopedic Oncology Services, Department of Surgical Oncology, Tata Memorial Hospital, Mumbai.

Address of Correspondence
Dr. Paramanandam V
Technichal Officer C, Physiotherapy Department, Tata Memorial Hospital, Mumbai
Email: vinsu24@gmail.com

Abstract

Introduction: Limb salvage after tumor resection has become a norm in today’s era. There are number of biological and non biological reconstruction options available for the reconstruction of these bone defects. The success story of these surgical procedures is mainly based on their excellent functional outcome. Post surgical rehabilitation plays an important role in achieving optimal functional outcome and good quality of life. The rehabilitation protocol following limb salvage surgery is complex and it differs with type of reconstruction procedure. Present articles discusses in detail the various rehabilitation protocols required to achieve above goals.

Keywords: Limb salvage surgery, rehabilitation, sarcoma

Introduction

Until 1970, amputation was the primary surgical treatment offered to bone and soft tissue sarcomas. However, from that time the treatment options have evolved dramatically and now approximately 90% of these cases undergo Limb Salvage Surgery (LSS)[1]. LSS has become the main line of treatment option for bone and soft tissue sarcomas along with adjuvant and/or neo adjuvant treatment modalities (Chemotherapy/ radiotherapy). The overall survival rate has been estimated as 55%-65%, based on the age of diagnosis, and it is considered to be comparable to that of amputation.
LSS is considered to be less invasive, provides better function and quality of life than amputation [2]. Moreover, it has been proposed that patients’ acceptability of LSS is high in view of the fact that it restores the body image better than amputation[3]. Nevertheless, LSS, unlike amputation, is associated with more peri-operative complications, prolonged hospital stay and requires repeated surgeries due to various reasons such as infection and prosthetic failure. LSS demands high surgical skills, whereas, amputation is a simple surgical procedure. Additionally, recent progress in prosthetic limbs, for example microprocessor based joints and endo-skeletal prosthetic reconstructions, have improved the functional outcome and cosmetic outlook following amputation [4]. A systematic review conducted by Bekkering et al [5] reported that the quality of life outcome from current available evidence is inconclusive in supporting LSS or amputation. Another recent systematic review and meta-analysis concluded that both surgical procedures provides similar functional recovery and quality of life [6].Despite the fact that early physical rehabilitation is the key to achieve good functional outcome and quality of life after LSS, rehabilitation techniques following LSS is largely neither tested nor documented in detail [7]. Lack of adequate early rehabilitation measures following LSS could be one of the rationales for conflicting interests reported by various studies examining the quality of life in LSS vs amputation.Hence, we have attempted to summarise basic principles and site specific considerations one must utilise to develop individual case specific rehabilitation protocol.

Common rehabilitation principles in LSS
In a recent paper, Shehadeh et al. [7] attempted to standardize the rehabilitation protocol for LSS following high grade bone and soft tissue sarcomas. They reported that following a standardized rehabilitation protocol produced improved functional outcome in group of 59 patients with LSS. Their conclusion, however, is based on small observational study with heterogeneous population who received different type of LSS for different anatomical sites. Following set protocol in LSS, unlike general orthopaedic procedure, will be counterproductive. In general orthopaedic procedures, more or less,
specific anatomical structures are involved with minimal damage to the bone, joint and soft tissue structures. In contrast, in LSS following sarcomas, these structures are extensively resected and may not be identical between two individuals undergoing similar procedures for a particular site. For example, resection length for distal end of femur osteogenic sarcoma may depend on the extent of disease in two individuals [4].  Following are common rehabilitation prospectives that need to be considered to formulate comprehensive rehabilitation protocol for LSS. 
Bone and joint reconstructions: Stability and mobility following LSS largely depends on the bone and joint structure loss and the type of reconstruction. For example, megaprosthetic distal femur replacement with cementing will allow the patient to be ambulated full weight bearing (FWB), whereas, if it is a bone graft , like in most of biological reconstructions, weight bearing needs to be delayed till the osteosynthesis is confirmed by radiographical evaluation.
Neuromuscular loss: Oncology resection demands large resections, which will also include a part of uninvolved soft tissue cover as surgical margin. Large resection may require additional rotational or free flaps for soft tissue coverage. In addition, nearby neuro-vascular bundle may need to be excised or repaired, hence, complete evaluation of neuro-motor loss would be necessary to plan the dynamic strength training and external support requirements.
Skin involvement: Donor sites of free flaps often receive split thickness skin graft which may hinder the early mobilisation of nearby joint. Moreover, scar development following open biopsy and LSS may need special attention from the rehabilitation team to prevent any future functional loss.
External supports: Temporary or permanent external support in the form of static or dynamic splinting may be required to provide support to the limb. To exemplify, prophylactic use of abduction brace along with derotation boot to prevent hip dislocation following proximal femur replacement and dynamic cock-up splint for radial nerve palsy needs to be the integral part of rehabilitation service.
Oncology treatments: Deranged blood count often hinders with the intensity of rehabilitation; hence, it prolongs the overall rehabilitation(8). Radiation induced fibrosis could cause severe restrictions in the joint range of motion. Thus, rehabilitation professionals must plan around the chemotherapy cycles and add prophylactic measures to prevent any impending radiation induced joint and soft tissue dysfunction.
Multidisciplinary approach: Limb salvage surgery is complex and demands close concordance in treatment specific outcomes between various health professional working in the rehabilitation team. This team may comprise of surgeons, medical oncologists, radiation therapists, nurses, physiotherapists, occupational therapists, prosthetics orthotics and medical social workers. Prehabilitation, rehabilitation even before starting the primary cancer therapy and surgery, such as crutch muscles strengthening, would be greatly beneficial in post-treatment functional outcome. Although in the field of LSS evidence of prehabilitation is lacking, there are considerable evidence to show beneficial effects in overall rehabilitation following cancer therapies [9–11].
Rehabilitation prescriptions and follow-up: Rehabilitation protocol for LSS must be tailor made considering the general principles and site specific modification, hence specific and also progressive. However, some negative effects of adjuvant therapies, such as the deranged blood counts and infection, may alter the course of rehabilitation process. Thus, frequent follow-up and close monitoring may be required during adjuvant therapy till they are functionally independent. 

Rehabilitation consideration for specific sites
Site specific rehabilitation principles following LSS have been presented below for few common sites.
Mega prosthetic replacement for distal femoral resection:
Distal femur is the commonest site for primary high grade sarcoma and giant cell tumors. Overall strengthening other than the affected site, in all possibility, should begin preoperatively. Limb elevation and ankle toe movement should be encouraged from post operative day one to prevent deep vein thrombosis. Cemented and semiconstrained (allows rotations and flexion/extension) knee joint endoprosthetic replacement permits early joint mobilization and FWB walking. Unlike other centres [4,7], in our centre knee joint mobilisation starts from day one with the help of continuous passive motion units (Fig.1) and active assisted methods within the pain tolerance level unless tight suturing. Close communication between the surgical team and the rehabilitation team helps in personalising the rehabilitation protocol as per the patients’ requirements. With adequate pain relief through appropriate medical management, active exercises could be started from day one to three. Full weight bearing walking could be started from day one initially with walker and later without any support if patient could effectively extend the knee “locking the knee”. Prior to ambulation, one leg standing and spot marching must be encouraged with appropriate support. After acute inflammation subsides slow progressive muscle strengthening exercises must be encouraged with the goal of achieving 900knee flexion, complete knee extension and muscle strength equivalent to the contra lateral lower limb by end of three months. Active passive motion devices, such as the one shown in Fig. 2, may help in joint mobilisation and strengthening.  Summary of rehabilitation protocol is tabulated in Table 1.
Mega prosthetic replacement for proximal tibial resection:
Proximal tibia and knee joint is the second most common site for primary high grade sarcoma and giant cell tumors. It is indeed a challenging location for rehabilitation in view of the fact that the extensor mechanism have to be reconstructed in these cases [4]. In most of the cases a gastrocnemius flap is done to provide a dynamic anchorage and direct anchorage to prosthesis provide a static attachment to help reattaching extensor mechanism to proximal tibial prosthesis. Protecting the extensor mechanism reconstruction till it attaches through fibrosis along with the surrounding soft tissue structures are crucial to prevent quadriceps lag. Hence, knee bending and quadriceps strengthening will be delayed for six weeks until then the knee is protected with the help of long knee brace. Re-attached gastrocnemius flap could lead to protective muscle spasm of plantar flexors and if not mobilised early it may create plantar flexors contracture. Thus, achieving/maintaining dorsi flexion of the ankle joint in the early post operative period is crucial for appropriate weight bearing.  Mobilisation of knee joint and quadriceps strengthening could be started after six weeks; however, therapist must consider that immobilisation of the knee joint in long knee brace leads to severe restriction of patella mobility. Unless adequate patella mobility is achieved, especially the medial lateral movement, knee flexion exercises could prevent smooth gliding of patella over the femoral condyle. This will increase strain on the reconstructed patella ligament. Therefore, our institute follows a unique mobilisation protocol following proximal tibia and knee replacement which is depicted in the Table 2. In few cases quadriceps lag could be evident due to patella tendon overstretch/avulsion, this could be due to improper patella mobilisation or forceful knee bending. Fig. 3 a, b and c depicts the patella tendon overstretch.
Mega prosthetic replacement for proximal and total femoral resection:
Resection of proximal femur and prosthetic replacement may be done for proximal femur tumor or as a part of total femoral resection and reconstruction. Partial or complete loss of joint capsule and dynamic stabilisers of hip joint during tumor resection may leave the hip joint vulnerable to dislocation. This may get potentiated with certain combination movements, if these joint movements are allowed beyond a certain limit. This restriction largely depends upon the surgical approach. Postero-lateral approach being most common in the LSS of this site, hip rotations, especially internal rotation and, flexion more than 600 and adduction of the hip joint needs to be prevented up to 6 weeks [4,7]. These movement restrictions could be achieved using hip abduction pillow/brace and de-rotation splint. Before the patient gets discharged from the hospital, training them for bed transfer, supine to standing, standing to supine and sitting in a chair/commode becomes paramount important in the early phase of rehabilitation. Knee joint mobilisation must be started early either by the edge of bed with hip joint well supported or in side lying with pillows between legs. Any restriction of knee joint range would adversely affect the overall function since hip joint function of the ipsilateral leg has already been compromised. Early FWB ambulation could be started from post operative day one initially with walker, then with walking stick. Later most of them would be trained to walk without any walking aid. Total femoral resections may require more intense rehabilitation with additional emphasis on knee strengthening as discussed earlier (Table 2). Patients may life long need to use walking aids in view of the fact that large motor loss in these cases.
Mega prosthetic replacement for proximal humeral resections:
Proximal humerus and the shoulder girdle are the third common place for primary bone sarcomas [4]. Despite endoprosthetic replacements for functional shoulder girdle structures, such as reverse glenoid prosthesis, are available, lack of muscular structures post excision and damage to the axillary nerve often prevent their use. Frequently, the proximal end of the humerus is replaced with the endoprosthesis and suspended by the remaining muscles and soft tissue structures by suturing around the proximal end of the prosthesis. The objective of the procedure is to achieve a stable shoulder to facilitate good elbow and hand function.
To prevent the weight of the endoprosthesis and the limb acting on the newly formed pseudo joint, shoulder sling and elbow pouch are provided for 4 – 6 weeks. Early post operative rehabilitation consists of elbow and hand range of motion (ROM) and strengthening exercises within pain limit. Again these exercises must be performed in supine position only to avoid undue stress on the shoulder. After six weeks, shoulder joint limited ROM exercise in the form of pendular movements and vigorous strengthening of shoulder girdle, elbow and hand complex should be commenced. Additionally, postural correction must be included in the rehabilitation program.

Biological reconstructions
Wherever feasible, biological reconstructions are preferred over endoprosthetic implants in order to provide a stable and permanent solution for reconstruction of defects after tumor resection. However, rehabilitation following biological reconstructions needs careful considerations regarding weight bearing and joint mobilization. Utmost importance to surgical notes and communication with operative surgeon is of prime importance. Early joint mobilisation is the key to prevent joint stiffness and functional loss; nevertheless, often protective functional braces may be required to prevent damage. For example, curettage and bone grafting of the lower end of femur close to the joint demands hinge knee brace to avoid varus and valgus stress. Strengthening exercises also could be started early with functional knee brace (Fig. 4).
Patients are taught to walk non-weight bearing with brace generally from post operative day one with the help of axillary crutches up to 8 weeks. Once, osteosynthesis is confirmed through radiological evaluation, progressive weight bearing walking could be started. FWB walking and complete joint range and strength are expected to be achieved by the end of 3 months to 4 months.

conclusions

Although limb salvage surgery for primary malignant tumours have achieved commendable advancement in surgical techniques and endo-prosthetic design and manufacturing, without optimal and timely peri and post-operative physical rehabilitation, achieving the desired quality of life outcome may not be feasible. This paper has highlighted few important rehabilitation principles and we have summarised rehabilitation protocol for specific area. Most of the oncology resection and reconstruction vary from one individual to another even in one particular site and needs tailor made rehabilitation protocol; nevertheless, this summary will be a guide for necessary foundation to design individual rehabilitation program.

References

1. Chopra BK. Health related quality of life studies in Indian patients after limb salvage surgery: Need of the hour. Med J Armed Forces India. 2013 Jul;69(3):209–10.
2. Ottaviani G, Robert RS, Huh WW, Palla S, Jaffe N. Sociooccupational and physical outcomes more than 20 years after the diagnosis of osteosarcoma in children and adolescents. Cancer. 2013;119(20):3727–36.
3. Frieden RA, Ryniker D, Kenan S, Lewis MM. Assessment of patient function after limb-sparing surgery. Arch Phys Med Rehabil. 1993 Jan;74(1):38–43 6p.
4. Oren R, Zagury A, Katzir O, Kollender Y, Meller I. Principles of rehabilitation after limb-sparing surgery for cancer. In: Musculoskeletal Cancer Surgery [Internet]. Springer; 2001 [cited 2014 Sep 3]. p. 583–93. Available from: http://link.springer.com/chapter/10.1007/0-306-48407-2_36
5. Bekkering WP, Vliet Vlieland TPM, Fiocco M, Koopman HM, Schoones JW, Nelissen RGHH, et al. Quality of life, functional ability and physical activity after different surgical interventions for bone cancer of the leg: A systematic review. SurgOncol. 2012 Jun;21(2):e39–47.
6. Mei J, Zhu X-Z, Wang Z-Y, Cai X-S. Functional outcomes and quality of life in patients with osteosarcoma treated with amputation versus limb-salvage surgery: a systematic review and meta-analysis. Arch Orthop Trauma Surg. 2014 Nov;134(11):1507–16.
7. Shehadeh A, Dahleh ME, Salem A, Sarhan Y, Sultan I, Henshaw RM, et al. Standardization of rehabilitation after limb salvage surgery for sarcomas improves patients’ outcome. HematolOncol Stem Cell Ther. 2013 Sep;6(3–4):105–11.
8. Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvão DA, Pinto BM, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010 Jul;42(7):1409–26.
9. Singh F, Newton RU, Galvão DA, Spry N, Baker MK. A systematic review of pre-surgical exercise intervention studies with cancer patients. SurgOncol. 2013 Jun;22(2):92–104.
10. Silver JK. Cancer Prehabilitation and its Role in Improving Health Outcomes and Reducing Health Care Costs. SeminOncolNurs. 2015 Feb;31(1):13–30.
11. Silver JK. Cancer prehabilitation and its role in improving health outcomes and reducing health care costs. SeminOncolNurs. 2015 Feb;31(1):13–30.

How to Cite this article: Paramanandam VS, Daptardar AA, Gulia A. Rehabilitation Following Limb-Salvage Surgery In Sarcoma. Journal of Bone and Soft Tissue Tumors May- Aug 2016;2(2):20-24.

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                                          (Abstract    Full Text HTML)      (Download PDF)

How important are surgical margins in Osteosarcoma?

 Volume 2 | Issue 1 | Jan-Apr 2016 | Page 22-26 |Thomas P Cloake, Lee M Jeys.

Authors: Thomas P Cloake[1], Lee M Jeys[2].

[1]The Royal Orthopaedic Hospital, Bristol Road South, Birmingham, B31 2AP, UK.
[2]School of Health and Life Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.

Address of Correspondence
Professor Lee M. Jeys
Professor of Health and Life Sciences
Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
E-mail: lee.jeys@nhs.net

Abstract

Surgical resection combined with chemotherapy is the mainstay of treatment of osteosarcoma. Traditionally, surgical margins were based upon tumour grade and classified into marginal, wide or radical resection. The definition of these margins, however, remains subjective and recent research has questioned the need for wide or radical margins. Advances in surgical technique and the use of neo-adjuvant chemotherapy have led to an improvement in outcome. By reducing tumour burden, chemotherapy has provided surgeons with the option of limb salvage surgery rather than radical resection. Surgical margins and response to chemotherapy are now considered the two most important predictors of outcome in osteosarcoma. This review focuses on surgical margins with respect to limb salvage surgery and discusses the importance of response to chemotherapy.
Keywords: osteogenic sarcoma, osteosarcoma, surgical margins, chemotherapy, limb salvage surgery.

Introduction
Osteosarcoma is a high grade, primary tumour of bone in which the tumour cells produce osteoid [1]. It is the most common primary bone tumour, with an annual incidence rate of 5.0 per million [2]. Osteosarcoma is predominantly a disease of the young with a peak incidence in the second decade and displays a male predominance which is most pronounced at a younger age [3]. The treatment of osteosarcoma is challenging. The use of neo-adjuvant chemotherapy regimes combined with surgical resection has led to an improvement in outcome. Nevertheless, despite recent advances in surgical technique and chemotherapy agents, the survival rate has plateaued over the last 30 years [4]. There has been much research into prognostic factors that may help predict outcome in osteosarcoma, a number of these have been identified (see Table 1). Authors have suggested the most important, independent risk factors are the response to adjuvant chemotherapy and resection margins [5-7]. This review considers the impact of resection margins with a focus on limb salvage surgery and discusses the significance of response to chemotherapy.

Table 1

Resection margins
There has been much debate around the margin of clearance required for surgical treatment of osteosarcoma.  Enneking et al. were the first group to formally stage osteosarcoma into three distinct grades according to biologic aggressiveness, tumour site and distant metastases [8].  The authors suggested this system be used in surgical planning and inform the use of marginal, wide or radical resection margins. Nonetheless the definition of marginal or wide resection remains subjective and may vary between surgeons or units and has never been objectively defined (Fig 1).  Kawaguchi et al. developed this concept by giving distinct numerical values for desired resection margin according to the grade to tumour suggesting a 2cm margin was required for low-grade tumours and a 3cm margin was needed for high-grade neoplasms such as osteosarcoma [9].More contemporary studies have failed to reach a consensus on a numerical value for an adequate resection margin. Li et al. reported there was no difference in local recurrence when wide (>5mm) margins and close (<5mm) margins were used [10]. Bispo et al. failed to detect a difference in local recurrence using a margin of 2mm [11]. Betrand et al. found surgical margin to be the only independent risk factor for local recurrence and suggested a margin of 1mm may be adequate [12].  These papers suggest resection does not require a strict numerical margin, however efforts should be made to ensure no margins are intralesional. However, international consensus is in equipoise regarding margins, and this has made interpreting research articles very difficult. Even within units, tumour clear margins and ‘wide’ margins have become interchangeable when in reality they may be completely different and may lead to inappropriate treatment for patients. In the oncological world, the concept of patient specific treatment or ‘personalised medicine’ is gaining popularity and what is correct for one patient, may not be suitable for another patient, even with the same tumour type.

Figure 1

Limb salvage surgery

Prior to the advent of effective chemotherapy, the surgical treatment for osteosarcoma involved early radical amputation or disarticulation of the affected limb. Whilst ensuring complete removal of the tumour, performing this radical surgery on young patients caused loss of function and permanent disability, without improving patient survival. Limb salvage surgery (LSS) aims to resect the tumour, whilst maintaining function of the preserved limb, all with minimal risk to the patient (Fig 2).


Figure 2 Figure 3

 

The emergence of efficacious chemotherapy regimes, which acted to reduce tumour burden and reduce metastatic spread, and enhanced imaging techniques such as CT and MRI have led to the increased use of LSS [13-15]. By definition, the use of LSS requires preservation of limb neurovascular structures and narrower surgical margins when compared to amputation. Preservation of tissue during tumour resection has led to the inevitable decrease in resection margins, which potentially risks causing an increase in local recurrence (Fig 3). There are conflicting reports on the rate of local recurrence in LSS with some studies reporting an increase [15-17] and others a decrease [18], when compared to amputation. Considering local recurrence is associated with poor outcome, much work has been done to examine the impact of LSS on survival. Simon et al. were one of the first groups to investigate outcomes following LSS in a multi-centre retrospective review of 227 patients. They reported LSS had a comparable survival rate with amputation at 5 years follow up [19] and provided the impetus for increased uptake of LSS amongst surgeons. A large study by Bacci et al. retrospectively compared the outcome in patients who underwent LSS to amputation. The authors report that whilst LSS was associated with reduced resection margins, local recurrence and 5-year disease free survival were comparable to amputation [20]. These results are confirmed by a number of other groups, with each describing a survival rate equal to or better than that of amputation [15,17,18,21-27].It is important to consider, however, these studies are limited by their retrospective nature. Without robust methods of randomisation, treatment decisions have been based on individual patient and tumour characteristics, local practice and patient choice, leaving them open to the influence of selection bias. Postoperative quality of life is an important outcome measure in osteosarcoma. As patients with osteosarcoma are young and can expect a prolonged period of survival following treatment, the demands put upon a salvaged limb or prosthesis can be great. It is essential, therefore to ensure there is minimal risk of technical failure, the limb provides adequate function for the individual patient and has an acceptable cosmesis for both the patient and their care givers. Measurement of quality of life in children is difficult and there have been relatively few studies assessing this outcome measure. Using objective quality of life scores, LSS and amputation groups report reduced quality of life compared to population norms [29,30]. A meta-analysis comparing quality of life in patients who underwent LSS and amputation found there was no significant difference between the 2 groups. Taking into consideration all the above evidence LSS remains a safe and effective management option and when used in combination with adjuvant chemotherapy offers a good survival outcome.

Chemotherapy/chemonecrosis

The introduction of chemotherapy regimes alongside surgical resection has led to a dramatic improvement in survival. The use of chemotherapy in the treatment of osteosarcoma began in the 1970s with the use of doxorubicin and high dose methotrexate regimens [31]. Administration of chemotherapy agents before surgical resection as neo-adjuvant therapy enhanced survival from10 – 20% to 70% [32].Current modern chemotherapy regimes are based on combination therapy using methotrexate, adriamycin/doxirubicin and cisplatin. Poor response to chemotherapy has been identified as an important independent risk factor for poor prognosis. Histological evaluation of surgical resection specimens permits the classification of response to chemotherapy as good (>90% tumour necrosis) and poor (<90% tumour necrosis). Patients who display poor response are consistently reported to have worse outcome [33,34]. A number of strategies have been employed to improve results in poor responders. Evidence suggests modification of chemotherapy regime may improve results. Several groups have showed intensification of pre-operative chemotherapy enhances tumour response [35-37] and may improve survival [38-40]. This benefit however, is limited and intensification of chemotherapy beyond a certain level does not improve outcome [36,41-43]. The use of high dose, intensive treatment to induce a good response early in the disease process has also been shown not to convey overall survival benefit [38,42-44]. Further work is therefore required to optimize tumour response and improve outcome in patients with poor chemotherapy response. A recent, large, multi-national study EURAMOS-1 investigated the effect of adding the additional agents, ifosfamide and etoposide, to salvage poor response to chemotherapy, as well as evaluating the addition of pegylated interferon for good responding tumours [45]. The published initial results suggest that the addition of interferon for good responding tumours appears beneficial, however, it was poorly tolerated and frequently refused by patients. Current practice involves assessing tumour response using resection specimens following surgery, after the completion of neo-adjuvant chemotherapy, to advise further treatment[45]. Considering tumour response to chemotherapy is such a significant prognostic factor, measuring response early in the disease process may inform further management choices. Non-invasive imaging techniques such as CT [46], MRI [47-49] and F-FDG PET [50,51] have all be used to investigate response to neo-adjuvant chemotherapy. A combination of F-FDG PET and CT (F-FDG PET-CT) scanning is widely used for the detection of many cancers. Meta-analysis of the current evidence for its use in osteosarcoma has shown F-FDG PET-CT to be a valuable modality to assess chemotherapy-induced necrosis [52]. Newer techniques for evaluating response to chemotherapy prior to surgery, such as functional MRI (fMRI) are also promising and may inform surgeon’s decisions in planning surgical margins.
Patients with poor response to chemotherapy present a complex management challenge. There have been few studies presenting evidence to guide the surgical management of these patients. Bacci et al. suggested that amputation should be considered in the setting of poor response to chemotherapy due to its significant correlation with local recurrence rates [20]. Recent work in Birmingham investigated the influence of resection margins on survival in patients with poor response to chemotherapy [28]. The authors showed there was no survival benefit gained from amputation when compared to LSS with close margins, irrespective of the risk of developing local recurrence [28]. These data demonstrate resection with preservation of the limb to be a safe surgical option even in patients with poor chemonecrosis.

Predicting outcome
The current classification systems used to grade osteosarcoma, pioneered by Enneking, incorporate tumour characteristics including the presence of metastases to guide surgical management and predict prognosis [8]. However, despite the widely accepted importance of response to chemotherapy in prognosis, the current classification fails to reflect this.  In a recent presentation at International Society of Limb Salvage (ISOLS 2015), Jeys et al introduced The Birmingham Classification, which uses numerically defined tumour margins and response to chemotherapy to predict both local recurrence and survival. In this series, chemotherapy response was reported to show a significant effect on the rate of local recurrence and overall survival. It was also reported that a margin of 2mm was a statistically significant cut off value for predicting local recurrence.  Furthermore, combining resection margins (greater or lesser then 2mm) with response to chemotherapy (good, >90% or poor, <90%) was more effective in predicting local recurrence and survival than other staging systems.  This classification, however, requires further validation on a multi-centre basis.

Conclusion

Osteosarcoma continues to present a number to treatment challenges. Although surgical resection margins are an important predictor of outcome, limb salvage surgery with close margins has been shown to be a safe and effective surgical option.  Response to chemotherapy is an important independent predictor of survival.  A distinct group of poor responders exist, who despite modification to chemotherapy regimes and complete surgical excision of the tumour continue to have a poor outcome.  Current classification systems have so far failed to reflect important prognostic indicators, the Birmingham Classification represents a new, robust system for classifying osteosarcoma and predicting outcome.

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How to Cite this article: Cloake T, Jeys L.How important are surgical margins in Osteosarcoma? . Journal of  Bone and Soft Tissue Tumors Jan-Apr 2016;2(1):22-26.

Dr. Thomas P Cloake

Dr. Thomas P Cloake

Prof Lee M Jeys

Prof Lee M Jeys

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