search
for
 About Bioline  All Journals  Testimonials  Membership  News  Donations

Indian Journal of Surgery, Vol. 65, No. 4, July-Aug, 2003, pp. 354-360

Review Article

Limb salvage for malignant primary bone tumours: current status with a review of the literature

Manish G. Agarwal, Ajay Puri

Bone and Soft Tissue Service, Department of Surgery, Tata Memorial Hospital, Dr. E. Borges Road, Parel, Mumbai 400012.
Address for correspondence Dr. Manish Agarwal, Room No 41, Tata Memorial Hospital, Dr. E. Borges Road, Parel, Mumbai 400012. E-mail: mgagarwal@yahoo.com

How to cite this article: Agarwal MG, Puri A. Limb salvage for malignant primary bone tumours: current status with a review of the literature. Indian J Surg 2003;65:354-60.

Paper Received: March 2002. Paper Accepted: December 2002. Source of Support: Nil

Code Number: is03070

Abstract

Though primary malignant bone tumours form only about 1% of all cancers, their aggressive natural history makes disease control very difficult. Effective chemotherapy has improved survival and advances in imaging, engineering and surgical techniques have made limb salvage feasible and the world has moved from amputation to limb salvage in the majority of cases with non-metastatic disease at presentation. Indigenously developed technology and chemotherapy protocols have allowed our own results to be comparable to those reported in the Western literature. Newer biomaterials and fabrication methods have allowed us to develop indigenously a high-quality yet affordable customized megaprosthesis which forms the backbone of limb salvage surgery. This paper broadly reviews the literature and presents our own experience with the current limb salvage methods as carried out at the Tata Memorial Hospital.

Key words: Limb salvage, Endoprosthesis, Megaprosthesis, Rotationplasty, Osteosarcoma, Ewing's sarcoma, Biopsy, Neoadjuvant chemotherapy.

Introduction

Bone cancers are rare and form only about 1% of the cancer load at the Tata Memorial Hospital. These tumours have long been known to be very aggressive in their natural history and therefore for a very long time amputation was considered to be the only way to achieve local control of the tumour in the limb. Even after an amputation, only 10-20%survived,1,2 the rest succumbing to systemic disease.3,4

In the last 30 years a sea change has occurred in the outlook for these cancers. Chemotherapy has allowed better local and systemic control.5,6 Better imaging like CT and MRI have allowed the surgeon to accurately define the extent and therefore plan tumour resection. Advances in bioengineering have provided exciting options for reconstruction and the world has moved from amputation to limb salvage. In osteosarcoma, survival improved from a dismal 10-20% to 50-70%.7,8 Long-term studies showed that limb salvage operations, performed with wide margins and chemotherapy did not compromise the survival or local control compared to an amputation.9-14

Though all these exciting developments occurred in the west, in our own country, limb salvage was still a difficult proposition. Chemotherapeutic drugs were very expensive, endoprosthesis unaffordable, ignorance widespread and the patients poor. In the last decade cheaper yet equally effective chemotherapeutic regimens have been developed, bioengineering has developed indigenously and limb salvage has become a standard method of treatment at many centres. In this article we attempt to present our protocols and methods in the management of these challenging neoplasms.

Incidence

Approximately 200 new cases of primary malignant bone tumours present to the Tata Memorial Hospital every year. Osteosarcoma is the commonest primary bone tumour (approx 100 new cases every year) followed by chondrosarcoma and Ewing's sarcoma. 70% of primary bone tumours occur around the knee.

Evaluation

The patient is first assessed clinically and a mental impression formed whether the limb is salvageable, borderline or non-salvageable. All patients undergo an imaging work-up for local extent and distant spread. For suspected malignant tumours which are clinically borderline or salvageable, an MRI of the local area helps further define the extent and relationships to vital structures like the neurovascular bundle. The MRI helps to plan the margins of resection. The commonest site of distant metastases is the chest. An X-ray chest and where limb salvage is considered, a CT scan of the chest (if the X-ray is clear) helps to screen for pulmonary metastases. A bone scan is used to screen for skips and osseous metastases. Presence of distant metastases is generally indicative of a poor prognosis.

Biopsy

Irrespective of how typical the imaging appearance, a histopathological diagnosis is a vital step in the diagnostic work-up of bone tumours. Fine needle aspiration provides only cytological material and is not the preferred method for the diagnosis of primary bone tumours.15 For bone tumours, the cellular architecture as well as the quality of matrix has to be studied for a proper diagnosis which FNAC cannot provide. A tissue sample may be obtained either by an open incisional biopsy or a closed core biopsy. A sub-optimally performed biopsy may not only fail to provide a diagnosis but may also compromise limb salvage and even have a negative impact on overall survival.16-21 Open biopsy, commonly performed in the past, results in significant contamination of the surrounding soft tissues with tumour cells. It also carries a significant risk of infection as well as causing a pathological fracture. Percutaneous core biopsy of bone lesions provides early and definitive diagnosis and guides decisions on management. The biopsy should be performed in accordance with planned subsequent surgery.

The biopsy site chosen should be such that the tract can be excised en bloc with the tumour. The periphery of the tumour is the best site and the pre-biopsy MRI may help in localizing the most representative area. Necrotic or heavily calcified or ossified areas are avoided. In primary bone tumours, the soft tissue mass is adequately representative for a biopsy. Where necessary, an imaging C-arm or CT guidance is used. We have got representative tissue in more than 90% of the cases and an error in diagnosis was found in less than 5% of the cases.

Indications for Limb Salvage Surgery

Long-term clinical case studies have shown that a limb salvage procedure has the same survival as an amputation.9-14 Therefore, every patient with a malignant tumour of the extremity is considered for limb salvage if the tumour can be removed with an adequate margin and the resulting limb has satisfactory function. An adequate margin is one that results in an acceptably low rate of local recurrence of the tumour. An adequate margin is generally wide in most areas. It may be close in some areas, for example in the case of a distal femur resection, the popliteal vessels may be on the pseudocapsule but can be easily separated and experience has shown an acceptable low rate of local recurrence. After salvage the limb should have an acceptable degree of function and cosmetic appearance with a minimal amount of pain, and should be capable of withstanding the demands of normal daily activities. It must look and function comparable or better than an artificial limb after amputation. Balancing these sometimes conflicting requirements is what makes limb salvage surgery a complex and difficult, but rewarding process.

In selected cases, limb salvage can be combined with metastasectomy. For patients with uncontrollable disease, limb salvage should be considered if the surgery can be accomplished with minimum morbidity and rapid return to function. These patients can enjoy relief from pain, improved quality of life, and the intact body image that limb salvage can offer, even if they may not survive long.

Barriers to limb salvage

Barriers to limb salvage include poorly placed biopsy incisions, major vascular involvement, encasement of a major motor nerve, pathological fracture of the involved bone, infection and inadequate motors after resection. These adverse factors are barriers but not absolute contraindications. For example in pathological fractures, the fracture often heals with chemotherapy and the specimen can be removed with adequate margins. The ability to transfer motors, graft nerves and vessels and provide skin cover with microsurgical methods has allowed successful limb salvage despite many barriers. In our country, the inability to afford chemotherapy is a major barrier to salvage. Without cover of chemotherapy the local recurrence rate is higher22 and therefore amputation may give the best chance for survival.

Surgical resections and reconstruction

An adequate wide margin is a must for most sarcomas. For bone 3 cm away from the extent on T1-MRI image is adequate.23-28 The marrow is always sent from the cut end for frozen section evaluation for tumour. For the soft tissue 1-2 cm margin is preferred wherever possible. In practice, the line between a wide and a marginal margin is sometimes difficult to define as the surgeon strives to control the tumour while still leaving the patient with a useful limb. However, when in doubt, the surgeon errs on the side of excess tissue removal. The adequacy of the margin can be judged by bivalving the specimen. If there is any doubt about margins a decision for an amputation can be made on table. This is the reason that any patient undergoing a limb salvage procedure is forewarned about this possibility and consent for amputation always obtained.

After completion of the tumour resection, the surgeon must reconstruct the resulting surgical defect. The surgeon must eliminate potential deadspace and transfer tissues if necessary to allow an effective closure. Most bone sarcomas occur in the metaphyseal portion of the bone, so that typical resection involves the whole proximal or distal part of the bone. The gap remaining needs reconstruction either with metal or with bone or a composite of the two. Endoprosthesis is the most common method used as it provides immediate stability and mobility without interfering with any adjuvant treatment. An imported prosthesis, though of excellent quality, is very expensive (price Rs 3.5 lacs) and out of reach of most of our patients. We have therefore developed an indigenous stainless steel prosthesis at 10% of the cost of the imported joint. This joint has now been used in over 80 cases with excellent short-term results. We have also developed shoulder, hip and elbow megaprostheses. Recently, we have developed and used even total humerus, total femur and saddle pelvic prosthesis. The latter was used to reconstruct the defect after internal hemipelvectomy.

For tumours that involve the diaphyseal portion of a bone, an intercalary resection and reconstruction can be performed that saves the joints at either end. Small resected segments of bone are reconstructed using autogenous bone from the patient's iliac crest or other sites, but the available supply is strictly limited. In most cases the excised segment of bone must be replaced, either by a large internal prosthesis, a segment of allograft bone, a composite of an allograft and a prosthesis, or by other methods. The tissue bank at the Tata Memorial Hospital provides freeze- dried irradiated long segment allografts which we have used to reconstruct intercalary defects with good success.

At the Tata Memorial Hospital, the authors have designed and standardized a low-cost customized prosthesis called Tata Memorial Hospital New Indigenous Custmozed Endoprosthesis (TMH-NICE) (Figures 1 & 2). This prosthesis has been used in over 30 patients over the last 18 months with excellent early results (Figure 3). The functional score as assessed by the modified Enneking system (Table 1) We had an average score of 24 out of posssible 30 corresponding to 80% function score.

Osteosarcoma - guidelines

Osteosarcoma is the commonest primary malignant bone tumour. Approximately 100 cases present to our hospital every year. Almost 50% present with metastatic disease or with locally advanced disease. The prognosis is poor with metastatic disease. The commonest age is between 12-25 yrs with males outnumbering the females. The distal femur is the commonest site followed by the proximal tibia. Figure 4 shows the case of a 19-year old male treated with NICE prosthesis.

Preoperative chemotherapy

Once tissue diagnosis is made, chemotherapy is advised. This chemotherapy is given as per the established hospital protocols. Anterior chemotherapy is given for the following reasons:

- It controls micrometastases and improves survival5,6

- It allows time for the fabrication of a customized endoprosthesis

- The response to chemotherapy can be evaluated after surgery. This is the single most important prognostic factor29-31

- A good response to chemotherapy makes limb salvage surgery easier by:

- Decrease in tumour size and vascularity

- Pseudocapsule becomes thick and composed of mature fibrous tissue and finger-like projections of the tumour through the pseudocapsule disappear22

- Decrease in local recurrence rate22

The best chemotherapy results came initially from high dose methotrexate-based regimens.5-7,32 However, these regimens were expensive and toxic and a shift is occurring towards protocols without methotrexate.33-37 Adriamycin, cisplatinum, ifosfamide and etoposide are the effective drugs against osteosarcoma.

At the Tata Memorial Hospital, we are using a non-methotrexate-based chemotherapy protocol (Table 2). Adriamycin is given alternating with ifosfamide and cisplatinum for five cycles. Surgery is done after 5 cycles. After this adriamycin is replaced with etoposide for the next 4 cycles. Chemotherapy has to be given under expert supervision as toxicity is substantial (Table 3). Inadequate care during febrile neutropenia or cardiotoxicity can result in fatality. We have had two deaths related to chemotherapy toxicity. Fortunately, these patients are young with no systemic compromise and tolerate the chemotherapy well. The cost of chemotherapy is still high and many of our patients are unable to afford it.

3 to 5 cycles are given prior to surgery. During this time the customized joint is ordered. If metastases are present they are reevaluated after chemotherapy. Metastatectomy can be combined with limb salvage surgery in selected cases.

After surgery the specimen is sent for evaluation of chemotherapy response. It is cut into multiple sections, and each analyzed for percentage of necrosis. The pathologist then averages all sections to give the response in terms of percentage tumour necrosis. We use Huvos' grading 36 (Table 4 ).

The single best prognostic factor following preoperative chemotherapy has been > 90% necroses.29,37,38 For those with complete response (100% necrosis), 10-year survival is estimated to be 90%.30 In our series we have approximately 70% patients showing a good response to chemotherapy.

Following surgery, chemotherapy is started after suture removal. Patient is followed up periodically with CT scans. The commonest site of disease recurrence is the lung (70-80%) followed by the bone (15-20%). The local recurrence rate is around 5-10% for the limbs. 89% of the recurrences occur within 18 months of diagnosis.22

Ewing's family of tumours

The Ewing's family of tumours includes Ewing's sarcoma of bone, primitive neuroectodermal tumour (PNET) of the bone and soft tissues, and Ewing's tumour of the soft tissues. These are all small round cell tumours. For long, Ewing's tumours have been known to be extremely sensitive to radiation. While surgery or irradiation could provide local control in 50-70% of cases,39 more than 90% eventually died of metastatic disease.40,41 Like in osteosarcoma, multiagent chemotherapy developed in the 70s improved overall survival by controlling micrometastases and reducing local failure.41-44 The role of surgery is not yet precisely defined. Radiation had been the preferred method of local control due to the morbidity associated with surgery. Recent reports indicate that surgery combined with chemotherapy and with or without radiation may have better local control rates than chemotherapy with radiation alone.45-51

Management of round cell tumours, therefore, requires a team approach. All these patients are best discussed in a joint clinic involving medical oncologists, radiotherapists, orthopaedic surgeons and radiologists. The feasibility of wide resection without significant morbidity and loss of function is evaluated. The decision is made using various imaging modalities like plain radiographs, CT, MRI, bone scans, etc to determine size, extent, soft tissue mass and muscle involvement and neurological / vascular involvement.

Surgery is preferred wherever complete surgical excision is feasible without significant functional loss like in fibula or rib. Where margins are close or involved, radiation can be added postoperatively. The dose can be reduced, thereby also reducing the complications. Lesser tumour load also improves the efficacy of the administered dose.

Irrespective of the local treatment, multi-drug chemotherapy is always given and is the mainstay in the management of the Ewing's family of tumours. Ifosfamide, etoposide, vincristine, adriamycin, cyclophosphamide and actinomycin-D are the agents used in the protocol running at the Tata Memorial Hospital (Table 5). 4 cycles of induction therapy are used (each cycle lasts 3 weeks). After this a decision of modality for local control is made. Like in osteosarcoma, response to chemotherapy is an important prognostic factor.52-54 This information is available only in the operated cases. Chemotherapy is resumed soon after suture removal.

Complications

Massive and long surgical procedures in patients compromised by chemotherapy or radiotherapy make the patient prone to complications. Various complications, both intraoperative and postoperative are seen in limb salvage surgery. Minor wound complications like collection or haematoma or edge necrosis are seen in 5-8%. Deep infection rate is about 5% and can compromise the final outcome. Late infections are a lifelong hazard with maximum risk during postoperative chemotherapy. Intraoperative complications include arterial injury and nerve palsies but these are quite rare. Implant-related complications like breakage, loosening occur over a longer period of time. Local recurrence is seen in about 8-10% of cases and distant metastases in about 30-40%. It is because of this propensity to complications that the patient is forewarned about multiple surgical procedures or even amputation.

Conclusion

The first decade of the new millennium has been globally recognized by the orthopaedic fraternity as the decade of improvements in the treatment of bone and joint disorders. An ideal situation in the management of bone tumours is when the disease can be successfully removed without an amputation and the resulting loss of bone and muscle is compensated by a method which retains near normal limb function. Patient survivals have dramatically improved following the availability of newer chemotherapy drugs and this has accentuated the need for durable methods of reconstruction of large musculoskeletal defects. Orthopaedic surgeons have risen to the challenge and it is now possible to offer limb salvage to a large majority of patients with bone tumours. Ever-increasing advances in technology and biomaterials combined with a better understanding of biomechanics will further help in increasing the durability and refining limb salvage procedures. Though complications occur, the ultimate outcome is highly satisfactory in the majority of cases.

Acknowledgements

The authors acknowledge the help and intellectual input of Sushrut Surgicals in the design and fabrication of the TMH-NICE endoprosthesis.

References

1. Dahlin DC, Coventry MB. Osteosarcoma a study of 600 cases. J Bone Joint Surg 1967;49A:101-10.

2. Marcove RC, Mike V, Hajeh JV, Levin AG, Hutter RV. Osteosarcoma under the age of twenty one: A review of one hundred and forty five operative cases. J Bone Joint Surg 1970;52:411-23.

3. Huth JF, Eilber FR. Patterns of recurrence after resection of osteosarcoma of the extremity: strategies for treatment of metastases. Arch Surg 1989;124:122-6s.

4. Bacci G, Avella M, Picci P, Briccoli A, Dallari D, Campanacci M. Metastatic patterns in osteosarcoma. Tumori 1988;74:421-7.

5. Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, et al. The effect of adjuvant chemotherapy on relapse free survival in patients with osteosarcoma of the extremity. New Eng J Med 1986;314:1600-6.

6. Eilber F, Giuliano A, Eckhardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol 1987;5:21-6.

7. Meyers PA, Heller G, Healy J, Huvos A, Lane J, Marcove R, et al. Chemotherapy for non-metastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience J Clin Oncol 1992;10:5-15.

8. Baci G, Ferrari S, Bertoni F, Ruggieri P, Picci P, Longhi A, et al. Long term outcome for patients with non-metastatic osteosarcoma of the extremity treatment at the istituto ortopedico Rizzoli according to the istituto ortopedico Rizzoli / osteosarcoma-2 protocol: an updated report. J Clin Oncol 2000;18:4016-27.

9. Sim, FH, Ivins JC, Taylor WF, Chao EYS. Limb-sparing surgery for osteosarcoma: Mayo Clinic experience. Cancer Treat Sympos 1985;3:139-54.

10. Lane JM, Glasser DB, Duane K, Healey JH, McCormack RR, Rosen G, et al. Osteogenic sarcoma: two hundred thirty-three consecutive patients treated with neoadjuvant chemotherapy. Orthop Trans 1987;11:495.

11. Goorin AM, Perez-Atayde A, Gebhardt M, Andersen JW, Wilkinson RH, Delorey MJ, et al. Weekly high-dose methotrexate and doxorubicin for osteosarcoma: The Dana-Farber Cancer Institute / The Children's Hospital - Study III. J Clin Oncol 1987;5:1178-84.

12. Simon MA, Aschliman MA, Thomas N, Mankin HJ. Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg 1986;68:1331-7.

13. Winkler K, Beron G, Kotz R, Salzer-Kuntschik M, Beck J, Beck W, et al. Neoadjuvant chemotherapy for osteogenic sarcoma. Results of a cooperative German/Austrian Study. J Clin Oncol 1984;2:617-24.

14. Rougraff BT, Simon MA, Kneisl JS,Greenberg DB, Mankin HJ. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. A long-term oncological, functional, and quality-of-life study. J Bone Joint Surg 1994;76:649-56.

15. Van der Bijl AE, Taminiau AHM, Hermans J, Beerman H, Hogendoorn PCW. Accuracy of the Jamshidi trocar biopsy in the diagnosis of bone tumors. Clin Ortho Rel Res 1997;334:233-43.

16. Bickels J, Jelinek JS, Shmookler BM, Neff RS, Malawer MM. Biopsy of musculoskeletal tumors. Clin Ortho Rel Res 1999;368:212-9.

17. Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. J Bone Joint Surg 1996;78;656-63.

18. Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg 1982;64:1121-7.

19. Enneking WF. The issue of the biopsy. J Bone Joint Surg 1982;64:1119-20.

20. Simon MA. Current concepts review. Biopsy of musculoskeletal tumors. J Bone Joint Surg 1982;64:1253-7.

21. Springfield DS, Rosenberg A. Biopsy: complicated and risky. J Bone Joint Surg 1996;78:639-43.

22. Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M. Relationship of chemotherapy induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol 1994;12:2699-705.

23. Aisen AM, Martel W, Braunstein EM, McMillin KI, Phillips WA, Kling TF. MRI and CT evaluation of primary bone and soft-tissue tumors. Am J Roentgenol 1986;146:749-56.

24. Cohen MD, Weetman RM, Provisor AJ, Grosfeld JL, West KW, Cory DA, et al. Efficacy of magnetic resonance imaging in 139 children with tumors. Arch Surg 1986;121:522-9.

25. Gillespy T 3rd, Manfrini M, Ruggieri P, Spanier SS, Pettersson H, Springfield DS. Staging of intraosseous extent of osteosarcoma: Correlation of preoperative CT and MR imaging with pathologic macroslides. Radiology 1988;167:765-7.

26. Golfieri R, Baddeley H, Pringle JS, Leung AW, Greco A, Souhami R. MRI in primary bone tumors: Therapeutic implications. Eur J Radiol 1991;12:201-7.

27. O'Flanagan SJ, Stack JP, McGee HM, Dervan P, Hurson B. Imaging of intramedullary tumour spread in osteosarcoma: A comparison of techniques. J Bone Joint Surg 1991;73:998-1001.

28. Onikul E, Fletcher BD, Parham DM, Chen G. Accuracy of MR imaging for estimating intraosseous extent of osteosarcoma. Am J Roentgenol 1996;167:1211-5.

29. Goorin AM, Shuster JJ, Baker A, Horowitz ME, Meyer WH, Link MP. Changing pattern of pulmonary metastases with adjuvant chemotherapy in patients with osteosarcoma: results from the multiinstitutional osteosarcoma study. J Clin Oncol 1991;9:600-5.

30. Link MP, Goorin AM, Horowitz M. Adjuvant chemotherapy of high grade sarcoma of the extremity. Clin Orthop 1991;270:8-14.

31. Raney RB, Asmar L, Newton WA Jr, Bagwell C, Breneman JC, Crist W, et al. Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study. J Clin Oncol 1997;15:574-82.

32. Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, et al. Preoperative chemotherapy for osteogenic sarcoma. Selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 1982;49:1221-30.

33. Souhami RL, Craft AW, Van der Eijken JW, Nooij M, Spooner D, Bramwell VH, et al. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup. Lancet 1997;350:911-7.

34. Krailo M, Ertel I, Makley J, Fryer CJ, Baum E, Weetman R, et al. A randomized study comparing high-dose methotrexate with moderate dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. Med Pediatr Oncol 1987;15:69-77.

35. Bramwell VH, Burgers M, Sneath R, Souhami R, van Oosterom AT, Voute PA, et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. J Clin Oncol. 1992;10:1579-91.

36. Huvos A, Rosen G, Marcove RC. Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy, en bloc resection and prosthetic bone replacement. Arch Pathol Lab Med 1977;101:14.

37. Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol 1994;12:423-31.

38. Bacci G, Briccoli A, Mercuri M, Ferrari S, Bertoni F, Gasbarrini A, et al. Osteosarcoma of the extremities with synchronous lung metastases: long-term results in 44 patients treated with neoadjuvant chemotherapy. J Chemother 1998;10:69-76.

39. Pizzo AA, Poplack DG. Principles and Practice of Paediatric Oncology, 3rd edn. Lippincott Raven Publishers; 1997.

40. Dahlin DC, Coventy MD, Scanlon PW. Ewing's sarcoma: a critical analysis of 165 cases. J Bone Joint Surg Am 1962; 43:185.

41. Wang CC, Schultz MD. Ewing's sarcoma. N Engl J Med 1953;248:571.

42. Perez CA, Tefft M, Nesbit M, Burgert EO Jr, Vietti T, Kissane J, et al. The role of radiation therapy in the management of non-metastatic Ewing's sarcoma of bone: report of the Intergroup Ewing's Sarcoma Study. Int J Radiat Oncol Biol Phys 1981;7:141-9.

43. Cangir A, Vietti TJ, Gehan EA, Burgert EO Jr, Thomas P, Tefft M, et al. Ewing's sarcoma metastatic at diagnosis: results and comparisons of two intergroup Ewing's sarcoma studies. Cancer 1990;66:887-93.

44. Fernandez CH, Lindberg RD, Sutow WW, Samuels ML. Localized Ewing's sarcoma: treatment and results. Cancer 1974;34:143-8.

45. Nesbit ME Jr, Gehan EW, Burgert EO Jr, Vietti TJ, Cangir A, Tefft M, et al. Multimodal therapy for the management of primary nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the first intergroup study. J Clin Oncol 1990;8:1664-74.

46. Marcove RC, Rosen G. Radical en bloc excision of Ewing's sarcoma. Clin Orthop 1980;153:86-91.

47. Rosen G. Primary Ewing's sarcoma: the multidisciplinary lesion. Int J Radiat Oncol Biol Phys 1978;4:527.

48. Sailer SL, Harmon DC, Mankin HJ, Truman JT, Suit HD. Ewing's sarcoma: surgical resection as a prognostic factor. Int J Radiat Oncol Biol Phys 1988;15:43.

49. Conner MI, Pritchard DJ: Ewings Sarcoma. Clin Orthop Rel Res 1991;262:78.

50. Hoffmann C, Ahrens S, Dunst J, Hillmann A, Winkelmann W, Craft A, et al. Pelvic Ewing sarcoma: a retrospective analysis of 241 cases. Cancer 1999; 85:869-77.

51. Yaw KM: Pediatric bone tumors. Seminars Surg Oncol 1999;16:173-83.

52. Bacci G, Ferrari S, Bertoni F, Rimondini S, Longhi A, Bacchini P, et al. Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli. J Clin Oncol 2000;18:4-11.

53. Rosito P, Mancini AF, Rondelli R, Abate ME, Pession A, Bedei L, et al. Italian Cooperative Study for the treatment of children and young adults with localized Ewing sarcoma of bone: a preliminary report of 6 years of experience. Cancer 1999; 86:421-8.

54. Wunder JS, Paulian G, Huvos AG, Heller G, Meyers PA, Healey JH. The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma. J Bone J Surg 1998;80:1020-33.

© 2003 Indian Journal of Surgery. Also available online at http://www.indianjsurg.com


The following images related to this document are available:

Photo images

[is03070f4.jpg] [is03070f1.jpg] [is03070t5.jpg] [is03070t4.jpg] [is03070t1.jpg] [is03070f3.jpg] [is03070t2.jpg] [is03070t3.jpg] [is03070f2.jpg]


Indian Journal of Surgery
Medknow Publications on behalf of Association of Surgeons of India
ISSN: 0972-2068
Vol. 65, Num. 4, 2003, pp. 354-360
Home Faq Resources Email Bioline
© Bioline International, 1989 - 2019, Site last up-dated on 12-Jun-2019.
Site created and maintained by the Reference Center on Environmental Information, CRIA, Brazil
System hosted by the Internet Data Center of Rede Nacional de Ensino e Pesquisa, RNP, Brazil