Author: Neetin P Mahajan [1], Pranay Pravin Kondewar[1], Sudip Subhash Chavan[1], Habung Chobing[1], Lalkar Gadod [1]

[1] Department of Orthopaedics, Grant Govt. Medical College and Sir J.J. Hospital, Mumbai, Maharashtra, India.

Address of Correspondence
Dr. Pranay Pravin Kondewar,
Department of Orthopaedics, Grant Govt. Medical College and Sir J.J. Hospital, Mumbai, Maharashtra, India.
E-mail: pranaypk1@gmail.com

Abstract

Introduction: Pathological fractures of femur are rare and are difficult to manage. Proximal weight bearing portion is more common site for these fractures and are least common in distal third of shaft. Depending on the location and origin of primary tumor or benign lesion, we decide the management. At risk, bone with impending fracture can be managed conservatively. Displaced fractures need surgical intervention. MIREL scoring is used to decide plan of management. Closed technique like intramedullary nailing is preferred over the open technique and gives good results without post-operative morbidity. Radiological investigations are necessary to find out the primary tumor source in metastatic lesions these includes plain radiographs, CT scan, MRI and PET scan. Lab investigations also aid in finding source of primary tumor.
Case Report: This is a case series of 3 patients who had a pathological fracture of the distal third shaft of femur. These patients had metastasis from primary tumor elsewhere in body. All the patients were operated with intramedullary nailing and fixation was done with the aim of reducing pain, avoiding complications such as bed sore, infection, deep venous thrombosis, and regaining the functional outcome as much as possible and improves the quality of life.
Conclusion: All 3 patients with a pathological femur fracture operated with intramedullary nailing were shown to have a significant reduction of pain, regaining of the range of motion of the knee joint and a better quality of life with improvement in performance of activities of daily living.

Keywords: Bony metastasis, pathological fracture, intra-medullary nail, palliative surgery.

References:

1. Feng H, Wang J, Xu J, Chen W, Zhang Y. The surgical management and treatment of metastatic lesions in the proximal femur: A mini review. Medicine (Baltimore) 2016;95:e3892.
2. Issack PS, Barker J, Baker M, Kotwal SY, Lane JM. Surgical management of metastatic disease of the proximal part of the femur. J Bone Joint Surg Am 2014;96:2091-8.
3. Coleman RE. Bone cancer in 2011: Prevention and treatment of bone metastases. Nat Rev Clin Oncol 2012;9:76-8.
4. Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, et al. TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest 1999;103:197-206.
5. Piccioli A, Ventura A, Maccauro G, Spinelli MS, Del Bravo V, Rosa MA. Local adjuvants in surgical management of bone metastases. Int J Immunopathol Pharmacol 2011;24 Suppl 1:129-32.
6. Heisterberg L, Johansen TS. Treatment of pathological fractures. Acta Orthop Scand 1979;50:787-90.
7. Feng H, Feng J, Li Z, Feng Q, Zhang Q, Qin D, et al. Percutaneous femoroplasty for the treatment of proximal femoral metastases. Eur J Surg Oncol 2014;40:402-5.
8. Hunt KJ, Gollogly S, Randall RL. Surgical fixation of pathologic fractures: An evaluation of evolving treatment methods. Bull Hosp Jt Dis 2006;63:77-82.
9. Ruggieri P, Mavrogenis AF, Casadei R, Errani C, Angelini A, Calabrò T, et al. Protocol of surgical treatment of long bone pathological fractures. Injury 2010;41:1161-7.
10. Willeumier JJ, van der Linden YM, van de Sande MA, Dijkstra PS. Treatment of pathological fractures of the long bones. EFORT Open Rev 2016;1:136-45.
11. Sarahrudi K, Greitbauer M, Platzer P, Hausmann JT, Heinz T, Vécsei V. Surgical treatment of metastatic fractures of the femur: A retrospective analysis of 142 patients. J Trauma 2009;66:1158-63.

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Author: V.R.Ganesan[1], T.C.Prem Kumar[1], Sanjay.C[1], Roopesh Kumar.S[1]

[1]Department of Orthopaedic Surgery & Traumatology,
Madurai Medical College & GRH, Madurai, Tamilnadu. India.

Address of Correspondence
Dr. V R Ganesan,
Department of Orthopaedic Surgery & Traumatology,
Madurai Medical College & GRH , Madurai, Tamilnadu. India.
E-mail: sphospital@hotmail.com

Introduction: Osteosarcoma (OS), the most common primary bone tumor, is known to be relatively a radioresistant tumor. Pathological fracture in OS denotes its aggressive biological response and so it was considered a contraindication to limb salvage in earlier days. Radiotherapy has its role only in cases that are inoperable or have poor prognostic factors. In recent years, there have been major advances in the management of pathological fractures in high-grade OS (HGOS). This case report is about the effect of combination chemotherapy and radiotherapy in the management of pathological fracture in HGOS with limb salvage procedure.
Case Report: A 19-year-old male with pain and swelling in his right lower third of thigh and inability to walk for 3 months was diagnosed as a case of OS right distal femur with a pathological fracture. Open biopsy was done which confirmed the diagnosis as HGOS, staged Enneking IIb. He was treated with a combination of chemotherapy, external beam radiotherapy, tumor resection, and modular resection prosthesis.
Results: There were no immediate, early, and late complications. At the end of 1½ years, his functional recovery is good and he has reached more than 70% of the right knee functions. He has no signs of recurrence at present. He has got a better quality of life and functional activity with the prosthesis compared to what an amputated limb can produce.
Conclusion: Pathological fracture in OS is not a contraindication to limb salvage. Radiotherapy can be used in combination with chemotherapy and limb salvage surgery in HGOS with a pathological fracture. This combination treatment helps in increasing the chances of limb sparing surgery with good local control and tumor necrosis rate. The new knowledge that radiotherapy can be effective when used with chemotherapy has shown good result in our case.
Keywords: Osteosarcoma, pathological fracture, external beam radiotherapy, limb salvage, custom modular prosthesis.

Reference:
1. Abudu A, Sferopoulos NK, Tillman RM, Carter SR, Grimer RJ. The surgical treatment and outcome of pathological fractures in localized osteosarcoma. J Bone Joint Surg Br 1996;78:694-8.
2. Ferguson PC, McLaughlin CE, Griffin AM, Bell RS, Deheshi BM, Wunder JS. Clinical and functional outcomes of patients with a pathologic fracture in high-grade osteosarcoma. J Surg Oncol 2010;102:120-4.
3. Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathologic fracture in osteosarcoma: Prognostic importance and treatment implications. J Bone Joint Surg Am 2002;84:49-57.
4. Glasser DB, Lane JM, Huvos AG, Marcove RC, Rosen G. Survival, prognosis and therapeutic response in osteogenic sarcoma: The Memorial Hospital experience. Cancer 1992;69:698-708.
5. Finn HA, Simon MA. Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature individuals. Clin Orthop Relat Res 1991;262:108-18.
6. Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited: Members of the Musculoskeletal Tumor Society. J Bone Joint Surg 1996;78:656-63.
7. Bacci G, Ferrari S, Longhi A, Donati D, Manfrini M, Giacomini S, et al. Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: Local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand 2003;74:449 54.
8. Kim MS, Lee SY, Lee TR, Cho WH, Song WS, Cho SH, et al. Prognostic effect of pathologic fracture in localized osteosarcoma: A cohort/case controlled study at a single institute. J Surg Oncol 2009;100:233 9.
9. Jaffe N, Spears R, Eftekhari F, Robertson R, Cangir A, Takaue Y, et al. Pathologic fracture in osteosarcoma. Impact of chemotherapy on primary tumor and survival. Cancer 1987;59:701-9.
10. Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age: State of the art. Cancer Treat Rev 2006;32:423-36.
11. Jeon DG, Lee SY, Kim JW. Bone primary sarcomas undergone unplanned intralesional procedures the possibility of limb salvage and their oncologic results. J Surg Oncol 2006;94:592-8.
12. Xie J, Diener M, Sorg R, Wu EQ, Namjoshi M. Cost-effectiveness of denosumab compared with zoledronic acid in patients with breast cancer and bone metastases. Clin Breast Cancer 2012;12:247-58.
13. Ebeid W, Amin S, Abdelmegid A. Limb salvage management of pathologic fractures of primary malignant bone tumors. Cancer Control 2005;12:57-61.
14. Natarajan MV, Govardhan RH, Williams S, Raja GT. Limb salvage surgery for pathological fractures in osteosarcoma. Int Orthop 2000;24:170-2.
15. Cui Q, Li DF, Liu C, Guo J, Liu SB, Liu YS, et al. Two case-reports of the limb salvage treatment of osteosarcoma consolidated with obvious pathological fractures. Pathol Oncol Res 2011;17:973-9.
16. Godley K, Watts AC, Robb JE. Pathological femoral fracture caused by primary bone tumour: A population-based study. Scott Med J 2011;56:5-9.
17. Chandrasekar CR, Grimer RJ, Carter SR, Tillman RM, Abudu AT, Jeys LM. Outcome of pathologic fractures of the proximal femur in nonosteogenic primary bone sarcoma. Eur J Surg Oncol 2011;37:532-6.
18. Yin K, Liao Q, Zhong D, Ding J, Niu B, Long Q, et al. Metaanalysis of limb salvage versusamputation for treating high grade and localized osteosarcoma in patients with pathological fracture. Exp Ther Med 2012;4:889-94.
19. Scully SP, Temple HT, O’Keefe RJ, Mankin HJ, Gebhardt M. The surgical treatment of patients with osteosarcoma who sustain a pathological fracture. Clin Orthop 1996;324:227-32.
20. Machak GN, Tkachev SI, Solovyev YN, Sinyukov PA, Ivanov SM, Kochergina NV, et al. Neoadjuvant chemotherapy and local radiotherapy for high-grade osteosarcoma of the extremities. Mayo Clin Proc 2003;78:147-55.
21. Caceres E, Zaharia M, Valdivia S, Hilsenbeck S. Tejada F. Local control of osteogenic sarcoma by radiation and chemotherapy. Int J Radiat Oncol Biol Phys 1984;10:35-9.
22. Dincbas FO, Koca S, Mandel NM, Hiz M, Dervişoğlu S, Seçmezacar H, et al. The role of preoperative radiotherapy in non-metastatic high-grade osteosarcoma of the extremities for limb-sparing surgery. Int J Radiat Oncol Biol Phys 2005;62:820-8.

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Authors: Zeeshan Khan [1], Shakir Hussain [1], Simon Carter[1].

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

Address of Correspondence
Dr. Ashish Gulia
Associate Professor, Orthopedic oncology, Department of Surgical Oncology, Tata Memorial Hospital, Mumbai.
Email: aashishgulia@gmail.com

Abstract

 Osteosarcoma is the commonest primary bone tumour with a bimodal age distribution. The survivorship of patients with osteosarcoma has improved with advances in chemotherapy making limb salvage surgery the commonest surgical procedure. Pathological fractures associated with osteosarcoma, however are rare and suggests the aggressiveness of the tumour. These patients are considered as a special group due to the variable outcomes reported in the literature due to some special characteristics, prompting the discussion between limb salvage surgery versus ablative surgery.
This article reviews the reasons why this group of patients are considered challenging and also the various outcomes reported in the literature.
Keywords: Pathological fracture, osteosarcoma, outcomes

Introduction

Primary bone and soft tissue sarcomas are rare tumours. Osteosarcoma is the commonest primary bone tumour with a bimodal age distribution and with a reported incidence of 2-3 per million population per year [1, 2]. With advances in chemotherapy, the survivorship of patients with osteosarcoma has improved significantly with various studies revealing similar results with limb salvage surgery when compared with amputation [5]. Contra indications to limb salvage surgery may include involvement of the neurovascular bundle, joint involvement, progression of disease whilst on treatment, patient choice, infection and a pathological fracture (Fig. 1).
A pathological fractureassociated with osteosarcoma at presentation or during treatment is even rarer with a reported incidence of 5-10% [3, 4]. A pathological fracture can be the mode of presentation for osteosarcomas in certain cases whereas it can occur during treatment in others. This is generally considered to be an aggressive biological behaviour of the disease which in turn, historically, has been considered as a poor prognostic factor in the outcome of this special group of patients [6].

Why is this group of patients special?
This select group of patients poses a challenge to the treating orthopaedic surgeon about the modality of surgical procedure. There has been a debate over the years whether these patients should have ablative or limb salvage surgery and if there is a difference in the outcome of both with varying results reported by different authors [8].

What makes these patients special is the associated hematoma with the pathological fracture which is considered to have tumour cells which spreads locally in the tissues [7]. The extent of spread also depends on the anatomic location of fracture and whether it is intra or extra capsular. The disruption of local microvasculature is also considered to be a risk factor for development of metastasis [7]. Understandably, extra articular resection for intra articular extension of tumours is a more challenging procedure particularly when limb salvage surgery is attempted with the reported outcomes of extra articular resections in limb salvage surgery considered to be compromised as well [9]. The local contamination of soft tissues with the tumour cells is also considered to be a risk factor for local recurrence. This prompted the thought that early and aggressive surgery in the form of ablative surgery will halt the progression and spread of disease any further. The presence of a pathological fracture in osteosarcoma, therefore, has been considered as a poor prognostic factor by some authors but not by all [8, 10, 11].

Initial treatment& work up
Perhaps the most important step in the management of this select group of patients is the early recognition of the aggressiveness of the lesion and prompt referral to a specialist unit. Failure of recognition of these fractures as being pathological can lead to inappropriate treatment and potentially worse outcomes (Fig. 2) [14]. The rest of the management in a multidisciplinary team setting involves a detailed history, examination of the involved limb and joints for any effusion, local and systemic staging, biopsy and neoadjuvant chemotherapy after confirmation of diagnosis of osteosarcoma.
It is also important to note that one of the most challenging issues with this group of patients is pain management and immobilisation during the pre-operative period whilst they wait for surgery and have neoadjuvant chemotherapy. 

Immobilisation
Immobilisation for pain relief can be challenging as this depends on the location of the fracture and may involve a plaster cast, simple sling, skin traction or in some cases external fixators [15]. Significant attention should be paid to the placement of the schanz pins if an external fixator is used due to the risk of tumour spread into non-involved compartments and risk of infection which would compromise limb sparing surgery.

Prognostic factors
A pathological fracture is independently considered a poor prognostic factor in osteosarcoma but was not considered one in cases of chondrosarcoma and Ewing’s sarcoma [8, 10]. A poor response to chemotherapy and local recurrence are also considered to be poor prognostic factors for survivorship [8, 10-13]. It is however, important to note that the efficacy of chemotherapy and healing of fracturesin these special cases are considered as supportive factors for limb salvage surgery [20].

Fracture consolidation
It has been noted that these fractures heal whilst patients are on chemotherapy and in most of the cases these patients have had significant post chemotherapy necrosis(Fig. 3) [8]. On the contrary some fractures might happen whilst patients are on chemo which depicts the aggressive nature of the disease.

What is the verdict?
Limb salvage surgery should be attempted, if possible, in these patients after neoadjuvant treatment but if clear surgical margins cannot be obtained during surgery or limb salvage will result in a poor functioning limb, then ablative surgery should be considered, particularly in the paediatric population where they can adapt to prosthetics earlier than adults [16]. It is however, also important to note that after wide resection of tumour, limb salvage is still a viable option with reconstruction performed with either arthrodesis or rotationplasty where appropriate.
Scully et al, suggested that a pathological was a poor prognostic factor but it is important to note that this study was performed over a 30 year period where some patients in their series had not received any chemortherapy and there have been advances in this field over the study time period [8]. Similarly Finn et al, suggested early amputation due to the risk of local and distant tumour spread [14]. In another study, the 5 year survival in patients with pathological fractures secondary to osteosarcoma was lower than those without a fracture [18]. On the contrary Bacci et al, and Abudu et al, showed that there was no difference in the survivorship of these patients when they were treated with neoadjuvant chemotherapy [7, 11]. In a recent meta-analysis comparing limb salvage with ablative surgery for pathological fractures in high grade osteosarcomas, no significant difference between local recurrence and 5 year survival was noted [19]. Adjuvant radiotherapy in these patients has not been shown to reduce the risk of local recurrence and in fact might increase the risk of these patients undergoing further surgical procedures compromising there outcomes [7].

Future direction
All the studies performed on this select group of patients are retrospective and contain a small number of patients over a prolonged period of time. The results are further effected by variables including the heterogeneity of the patient and fracture characteristics and also the advances in chemotherapy over a period of time. Improvements in surgical techniques have also resulted in improved outcomes. Most of these variables are un avoidable due to the rarity of these cases but in order to come to a definite conclusion, a multi central randomised trial will eradicate all these bias and should guide treatment.

References

1. 1.Bielack S, Carrle D, Jost L. ESMO guidelines working group osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow up. Annals of Oncology.2008; 19, supplement 2: 94-96.
2. Widhe B, Widhe T. Initial symptoms and clinical features in osteosarcoma and Ewing sarcoma. J Bone Joint Surg Am. 2000; 82:667-74.
3. Jaffe N, Spears R, Eftekhari F, Robertson R, Cangir A, Takaue Y, Carrasco H, Wallace S, Ayala A,Raymond K, et al. Pathologic fracture in osteosarcoma. Impact of chemotherapy on primarytumorand survival. Cancer. 1987; 59:701-09.
4. Mulder JO, Schutte HE, Kroon HM, Taconis WK. Radiologic atlas of bone tumors. Amsterdam:Elsevier Science. 1993. Intraosseous osteosarcoma: conventional type: 51-5.
5. Simon MA. Current concepts review. Limb salvage in osteosarcoma. J Bone Joint Surg Am.1988; 70:307-10.
6. Coley BL, Pool JL. Factors influencing the prognosis in osteogenic sarcoma. Ann Surg. 1940; 112:1114-28.
7. Abudu A, Sferopoulos NK, Tillman RM, Carter SR, Grimer RJ. The surgical treatment and outcome of pathological fractures in localised osteosarcoma. J Bone Joint Surg Br. 1996; 78:694-8.
8. Scully SP1, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. J Bone Joint Surg Am. 2002 Jan;84-A (1):49-57.
9. Hardes J1, Henrichs MP, Gosheger G, Gebert C, Höll S, Dieckmann R, Hauschild G, Streitbürger A. Endoprosthetic replacement after extra-articular resection of bone and soft-tissue tumours around the knee. Bone Joint J. 2013 Oct; 95-B (10):1425-31.
10. Bramer JAM, Abudu AA, Grimer RJ, Carter SR, Tillman RM. Do pathological fractures influence survival and local recurrence rate in bony sarcomas?. Eur J Cancer. 2007 Sep; 43(13):1944-51.
11. Bacci G1, Ferrari S, Longhi A, Donati D, Manfrini M, Giacomini S, Briccoli A, Forni C, Galletti S.Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local andsystemic control by amputation or limb salvage after preoperative chemotherapy. ActaOrthop Scand. 2003 Aug; 74(4):449-54.
12. Meyers PA, Heller G, Healey J, Huvos A, Lane J, Marcove R, ApplewhiteA, Vlamis V, Rosen G. Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J ClinOncol. 1992; 10:5-15.
13. Glasser DB, Lane JM, Huvos AG, Marcove RC, Rosen G. Survival, prognosis, and therapeutic response in osteogenic sarcoma. The Memorial Hospital experience. Cancer. 1992; 69:698-708.
14. Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited: Members of the Musculoskeletal Tumor Society. J Bone Joint Surg [Am] 1996; 78-A: 656–663.
15. Chandrasekar CR, Grimer RJ, Carter SR, et al. Pathological fracture of the proximal femur in osteosarcoma: need for early radical surgery? ISRN Oncol 2012; 2012:512389.
16. Hosalkar HS, Dormans JP. Limb sparing surgery for pediatric musculoskeletal tumors. Pediatr Blood Cancer 2004; 42:295–310.
17. Finn HA, Simon MA. Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature individuals. ClinOrthopRelat Res 1991; 262:108–118.
18. Ferguson PC, McLaughlin CE, Griffin AM, et al. Clinical and functional outcomesof patients with a pathologic fracture in high-grade osteosarcoma. J SurgOncol2010; 102:120–124.
19. Yin K, Liao Q, Zhong D, Ding J, Niu B, Long Q, Ding D. Meta-analysis of limb salvage versusamputation for treating high-grade and localized osteosarcoma in patients with pathological fracture. ExpTher Med. 2012 Nov; 4(5):889-894.
20. Scully SP, Temple HT, O’Keefe RJ, et al. The surgical treatment of patients with osteosarcoma who sustain a pathological fracture. ClinOrthop. 1996; 324:227-232.

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