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Re implantation of Sterilised tumour bone by Extra Corporeal Radiotherapy

May 10, 2015

Vol 1 | Issue 1 | May – August 2015 | page:37-39 | Subin Sugath[1*]. Author: Subin Sugath[1*]. [1]Department of Aster Orthopaedics, Aster DM Healthcare Pvt Ltd., Kochi 682 027, Kerala, India. Address of Correspondence Dr. Subin Sugath MS Orth. Department of Ortho Oncology. Aster DM Healthcare Pvt Ltd. Kuttisahib Road, Near Kothad Bridge, South Chittoor […]

Management of Ewing Sarcoma: Current Management and the Role of Radiation Therapy

May 10, 2015

Vol 1 | Issue 1 | May – August 2015 | page:18-22 | Monica Malik Irukulla[1,*], Deepa M Joseph[1]. Author: Monica Malik Irukulla[1,*], Deepa M Joseph[1]. [1]Department of Radiation Oncology, Nizam’s Institute of Medical Sciences, Hyderabad. India Address of Correspondence Dr. Monica Malik Irukulla, MD. Department of Radiation Oncology, Nizam’s Institute of Medical Sciences, Hyderabad. India. […]

Re implantation of Sterilised tumour bone by Extra Corporeal Radiotherapy

May 10, 2015

Management of Ewing Sarcoma: Current Management and the Role of Radiation Therapy

May 10, 2015

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Re implantation of Sterilised tumour bone by Extra Corporeal Radiotherapy

May 10, 2015

Vol 1 | Issue 1 | May – August 2015 | page:37-39 | Subin Sugath[1*].

Author: Subin Sugath[1*].

[1]Department of Aster Orthopaedics, Aster DM Healthcare Pvt Ltd., Kochi 682 027, Kerala, India.

Address of Correspondence
Dr. Subin Sugath MS Orth.
Department of Ortho Oncology. Aster DM Healthcare Pvt Ltd. Kuttisahib Road, Near Kothad Bridge, South Chittoor PO, Cheranallor, Kochi 682 027, Kerala, India.
Email: drsubin.sugath@dmhealthcare.com

Abstract

With the use of potent chemotherapeutic drugs, newer imaging modalities and improved surgical techniques limb preserving surgeries for malignant bone tumours have become the norm. Endoprosthesis still remains the commonest method of reconstruction after tumour resection. But when one is able to an oncologically safe intercalary resection for malignant bone tumours one method of reconstruction is reimplanting the resected tumour bone after sterilisation. Radiation given outside the body to sterilise the tumour bone is called Extra Corporeal Radiotherapy (ECRT). After resection the bone is cleaned of all its soft tissue and marrow contents and sent in a plastic container to the Radiotherapy department where it is subjected to 50 Gy of radiation which kills all cells including the tumour cells. The bone is brought back to the theatre and reimplanted after augmenting it with either bone cement or fibular grafts and stabilised by appropriate fixation devices. The advantage of reimplanting the same bone is that you get an exact match to the resected bone which is tumour free. Post operatively the joint is mobilised immediately and weight bearing started as appropriate to the fixation used. The diaphyseal end takes more time to unite than the metaphyseal end. In our series of 16 patients who had undergone ECRT and reimplantation for malignant bone tumours of the extremity and had completed two year follow up, the metaphyseal end took an average of 6.2 months (4 – 12 months) for union while the diaphyseal end united in 10.6 months (5 – 15 months). If the tumour has caused extensive destruction of the bone or has a pathological fracture, it may be mechanically not sound to reimplant it after ECRT. ECRT is an oncologically safe and mechanically stable procedure in biologically reconstructing bony defects after tumour resection.
Keywords: Extra Corporeal Radiotherapy, Bone tumour, intercalary resection.

Introduction

With the use of potent chemotherapeutic drugs, newer imaging modalities and improved surgical techniques limb preserving surgeries for malignant bone tumours have become the norm. Endoprosthetic replacement is the most commonest method used to bridge the bone defect after tumour resection [1]. Such resection commonly involve resection of the growth physis across the joint leading to limb length disparity as the child grows. To overcome this, one will have to use a growing prosthesis which can be lengthened post operatively either by invasive or non invasive techniques to compensate for the growth of the normal limb [2] These implants are expensive and are not affordable to majority of patients who undergo limb salvage surgery in our country
At times, especially in young children where the open physis can be taken as a wide margin the tumour can be resected with wide margins sparing the joint ant the physis. The bone defects after these resection can be bridged by intercalary implants or size matched allografts if one has access to good tissue bank. Biological method of reconstruction has the advantage that once it incorporates with the host bone it is a life long procedure and is not associated with the complications of using a prosthesis [3,4]. Alternative technique of biological reconstruction if one does not have access to a tissue bank would be to use a vacularised or non vascularised autograft like fibula. But at times it would be impossible to harvest enough autografts to bridge large bony defects [5]. Sterilising and reimplanting the resected tumour bone is a viable option in these situations.
The advantage of reimplanting the same bone is that you get an exact match to the resected bone which is tumour free. The different methods used to sterilise tumour bone are autoclaving, pasteurisation, liquid nitrogen and radiotherapy [6]. Autoclaving involves sterilising the bone at 1210 C for 20 minutes which kills all tumour cells. But it has got the disadvantage that it reduces the bone strength as well as destroys the Bone Morphogenic Protein (BMP) [7]. Sterilising the specimen in a water bath at 650 C for 30 minutes is called pasteurisation. It has the advantage it retains the bone strength and BMP but has the practical difficulty of maintain the sterility during the procedure [6,8]. The most common method of sterilisation technique used is radiotherapy. 50 Gy of single shot high dose radiotherapy is used to sterilise the tumor bone. The procedure of giving radiotherapy outside the human body is called Extra Corporeal Radiotherapy (ECRT). The dose of radiotherapy given is so high that it destroys all cells including the tumour cells which necessitates this dose to be given outside the human body. The mechanical strength of the bone is least affected by this procedure and there are enough publications in literature which show this to be an oncological safe procedure in sterilising tumour bone. 50 Gy of radiotherapy is sufficient in attain tumour kill [9,10,11] and any higher dose of radiation decreases the mechanical strength and revascularisation and delays graft union and incorporation. The resection is made as per the pre operative imagings (Fig 1a). Marrow curettings from both the proximal and distal cut ends are send for frozen study to ensure adequacy of tumour clearance. Intercalary resected specimen with soft tissue cover over the tumour. Now the bone is completely stripped of all its soft tissue, periosteum and medullary contents (Fig 1b). The soft tissue removed is oriented with suture tags so that adequacy of tumour clearance can be assessed by histopathological examination. The bone is thoroughly washed with Vacomycin saline using a pulse lavage (Fig 1c).

The vancomycin which gets absorbed by the graft is eluded over a period of time when it is reimplanted. The cleaned specimen is put in a plastic container and sent for radiotherapy (Fig 2a).

Care is taken to eliminate free space in the container with saline and cotton pads to eliminate air as air causes dispersion of radiation. Specimen is taken to the radiotherapy department and as described earlier 50 Gy of single shot radiotherapy is given to the specimen after planning CT scan (Fig 2b,2c). This procedure takes between 30 – 90 minutes depending on the radiation machine used. The specimen is then brought back to the theatre and cleaned and washed with Vancomycin saline (Fig 2d).

The medullary canal of the sterilised bone can either be filled with bone cement or fibular graft to add on to the osteoconductive property (Fig 3a). The graft is re-implanted and stabilised by appropriate plate and screw fixation (Fig 3b). Care must be taken to put only minimal screws in the re-implanted graft during fixation. In case of tibial lesions an additional medial gastrocnemius flap may be needed for covering the sub cutaneous implants (Fig 3c). Post operatively the joint is mobilised immediately and weight bearing started as appropriate to the the fixation used. Patients are followed up at the routine frequency practised for malignant bone tumours. Radiological, oncological and functional assessment are done at each visit. The diaphyseal end takes more time to unite than the metaphyseal end. In our series of 16 patients who had undergone ECRT and reimplantation for malignant bone tumours of the extremity and had completed two year follow up, the metaphyseal end took an average of 6.2 months (4 – 12 months) for union while the diaphyseal end united in 10.6 months ( 5 – 15 months) (Fig 3c, 3d).

There were two cases of non union at the diaphyseal end for which subsequent bone grafting was required to attain union.
ECRT can also be used in reconstruction of bony defects after Internal Hemipelvectomy for malignant tumours of the pelvis. Here like in the long bones the tumour can be resected with margins as per the pre chemotherapy imagings and reimplanted after ECRT and fixed with appropriate plate and screw fixation (Fig 4a-d).

ECRT and reimplantation is an inexpensive method of reconstruction which can be carried out even in hospitals without radiation facility. The specimen after resection can be transported to the nearby centre having radiation facility where ECRT can be done and brought back and reimplanted. This method eliminates the need to have a tissue bank in hospital for doing biological reconstruction and also is not associated with the complications of using massive allografts. This technique also has the advantage that it provides an exact size matched graft for reconstruction.
If the tumour has caused extensive destruction of the bone or has a pathological fracture, it may be mechanically not sound to reimplant it after ECRT and alternative methods of reconstruction like intercalary implants or allografts would be ideal. Graft fracture is one complication that can occur in this procedure. This can be reduced by using appropriate fixation devices which bridge the whole length of the graft and also augmenting the graft with bone cement or fibular graft.
ECRT is an oncologically safe and mechanically stable procedure in biologically reconstructing bony defects after tumour resection. But the success of the procedure depends on appropriate patient selection, meticulous preoperative planning, implementing these plans intra operatively and the infrastructure backup to support it.

References

1. Gosheger, G.; Gebert, C.; Ahrens, H.; Streitbuerger, A.; Winkelmann, W.; Hardes, J. Endoprosthetic reconstruction in 250 patients with sarcoma. Clin. Orthop. Relat. Res. 2006, 450, 164–171.
2. Kotz, R.I.; Windhager, R.; Dominkus, M.; Robioneck, B.; Muller-Daniels, H. A self-extending paediatric leg implant. Nature 2000, 406, 143–144.
3. Tsuchiya H, Tomita K, Minematsu K, et al. Limb salvage using distraction osteogenesis: a classification of the technique: J Bone Joint Surg [Br] 1997;79-B:403–11.
4. Plotz W, Rechl H, Burgkart R, et al. Limb salvage with tumor endoprostheses for malignant tumors of the knee: Clin Orthop 2002;405:207–15.
5. Ceruso M, Falcone C, Innocenti M, Delcroix L et al. Reconstruction with a free vascularized fibula graft associated to bone allograft after resection of malignant bone tumor of limbs. Handchir. Mikrochir. Plast. Chir. 2001, 33, 277–282.
6. Singh VA, Nagalingam J, Saad M, Pailoor J: Which is the best method of sterilization of tumour bone for reimplantation? A biomechanical and histopathological study : Biomed Engineering OnLine 2010, 9:48.
7.Kok Long Pan, Wai Hoong Chan, Gek Bee Ong, Shanmugam Premsenthil et al. Limb salvage in osteosarcoma using autoclaved tumor-bearing bone: Pan et al. World Journal of Surgical Oncology 2012,10:105
8.Jyoti Kode, Prasad Taur, Ashish Gulia, Nirmala Jambhekar, Manish Agarwal, and Ajay Puri. Pasteurization of bone for tumour eradication prior to reimplantation – An in vitro & pre-clinical efficacy study; Indian J Med Res. 2014 Apr; 139(4): 585–597.
9.Mondelaers W, Van Laere K, Uyttendaele D. Treatment of primary tumours ofbone and cartilage by extracorporeal irradiation with a low energy high power electron linac; Nuclear Instruments Methods in Physics Res 1993;70-B:898-900.
10.Hong A, Stevens G, Stalley P, et al. Extracorporeal irradiation for malignant bone tumours. Int J Radiat Oncol Biol Phys 2001;50:441-7
11.Sharma D N, Rastogi S, Bakhshi S, Rath G K, Julka P K, Laviraj M A, Khan S A, Kumar A. Role of extracorporeal irradiation in malignant bone tumors. Indian J Cancer 2013;50:306-9.

How to Cite this article: Sugath S. Re implantation of Sterilised tumour bone by Extra Corporeal Radiotherapy. Journal of Bone and Soft Tissue Tumors May-Aug 2015; 1(1):37-39.

Dr.Subin Sugath

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Management of Ewing Sarcoma: Current Management and the Role of Radiation Therapy

May 10, 2015

Vol 1 | Issue 1 | May – August 2015 | page:18-22 | Monica Malik Irukulla[1,*], Deepa M Joseph[1].

Author: Monica Malik Irukulla[1,*], Deepa M Joseph[1].

[1]Department of Radiation Oncology, Nizam’s Institute of Medical Sciences, Hyderabad. India

Address of Correspondence
Dr. Monica Malik Irukulla, MD.
Department of Radiation Oncology, Nizam’s Institute of Medical Sciences, Hyderabad. India.
Email: dr_monica11@yahoo.com

Abstract

The management of Ewing sarcoma has evolved over the last few decades with successive improvement in survival rates. Multidisciplinary management is the key to successful outcomes. Dose intensity of chemotherapy is of vital importance. Local control can be effectively achieved with surgery, radiation therapy or a combination of the two. The choice of appropriate local therapy should be individualized and depends on various factors such as site, size, resectability, expected morbidity, long term effects etc. Metastatic disease remains a significant challenge and optimal therapeutic strategies still need to be defined. Current management and the role of radiation therapy in Ewing sarcoma are reviewed.
Keywords: Ewing sarcoma, radiation therapy, management.

Introduction

Ewing sarcoma family of tumors (ESFT) are a group of small round cell tumors showing varying degrees of neuroectodermal differentiation with Ewing sarcoma being the least differentiated. Primitive neuroectodermal tumors (PNET) show neuroectodermal differentiation by light microscopy, immune histochemistry (IHC) or electron microscopy [1]. According to WHO classification of bone and soft tissue tumors, Ewings sarcoma/PNET is synonymous with Ewing tumor, peripheral neuroepithelioma, peripheral neuroblastoma and Askin tumor [1]. In most of the patients, a chromosomal translocation leads to the expression of the EWS-FLI1 chimeric transcription factor which is the major oncogene in this pathology [2].

Epidemiology
Ewing sarcoma is the second most common primary bone tumor of childhood and it most commonly occurs in the second decade of life with a slight male preponderance. The incidence of Ewing sarcoma has been reported to be low in Asian population as compared to Caucasians[3]. Data from Indian population show that it is not so uncommon[4]. The common sites of primary Ewing sarcoma are the long bones of the lower extremities (41%), pelvic bones (26%), and bones of the chest wall (16%)[5]. Extraosseous Ewing sarcoma is more commonly axial in location involving the trunk (32%), extremities (26%), head and neck (18%), the retroperitoneum (16%) etc[6]. Approximately 20-25% of patients present with metastasis at diagnosis. Common sites of metastases include lungs, bones and bone marrow.

Diagnostic Evaluation
Typical presenting symptoms include pain and swelling with occasional constitutional symptoms like fever, fatigue and loss of weight. Patients should be evaluated and managed by a multidisciplinary team of experts including pediatric oncologists, orthopedic surgeons, radiologists, pathologists and rehabilitation specialists. A biopsy should be performed in a way such that the track and scar can be included in the subsequent resection or radiation portal. Biopsy should be from soft tissue as often as possible to avoid increasing the risk of fracture and should be through rather than between muscle compartments avoiding the neurovascular bundles. A skilled pathologist should be available onsite to confirm adequacy of the material and review the frozen sections. A needle biopsy may be adequate if sufficient tissue can be obtained for histological, cytogenetic and molecular studies. The risk of diagnostic errors and complications increases by as much as 12-fold when the biopsy is improperly done [7]. Ewing sarcoma/PNETs usually strongly express the cell surface glycoprotein MIC2 (CD99) and this can be helpful in diagnosis of small blue round cell tumors. CD99 is however not exclusively specific for ES/PNET and is found in other tumors such as synovial sarcoma, NHL, GIST etc [8]. Approximately 85% patients have expression of EWS-FLI1 chimeric transcription factor resulting from translocation between EWS and FLI-1 gene t(11;22)(q24;q12) [9]. In most of the remaining patients, alternative translocations between EWS and another ETS- family member (ERG, FEV, ETV1, E1AF) are detected [2]. Molecular analysis for EWS-FLI 1 should be considered. The prognostic value of the same remains inconclusive until now[10]. This is being evaluated as potential therapeutic target [11]. Local imaging with MRI with or without CT scan is recommended. Conventional staging evaluation includes bilateral bone marrow aspiration and biopsy or MRI of spine and pelvis, bone scan and CT scan of the chest. Serum LDH is an important prognostic marker. Positron emission tomography (PET) combined with conventional imaging is a valuable tool in staging and restaging ESFT with a sensitivity of 96% and specificity of 92% [12]. FDG-PET can also serve as a non-invasive method to predict response to chemotherapy which is a useful prognostic marker.13 Whole-body MRI can be a useful radiation-free modality to detect metastatic lesions with a higher sensitivity than bone scintigraphy [14,15]. Fertility consultation should be done for patients desiring future child bearing before starting therapy.

Prognostic factors
5-year event free survival approaches around 70% with standard multimodality approach in localized disease [16]. Favorable prognostic factors include extremity tumors, tumor volume <100ml, normal LDH and absence of metastases at presentation. Common adverse prognostic factors include metastatic disease at presentation, extra skeletal presentation, pelvis as the primary site and poor response to induction chemotherapy. Metastatic disease is the most significant adverse prognostic factor. Those with isolated pulmonary metastasis have a slightly better outcome than those with bone or bone marrow metastasis [17]. Survival depends on the site and number of metastases and the tumor burden with 5 year survival rates ranging from approximately 30% with isolated lung metastasis to less than 20% with multiple bone metastases. Older patients do worse than patients younger than 15 years.18 Poor histologic response to chemotherapy is associated with worse outcomes in patients with localized disease [19].

Treatment
Treatment of Ewing sarcoma has evolved following evidence from large multinational trials over the past few decades with successive improvement in outcomes. Multimodality approach is the key in the management of nonmetastatic Ewing sarcoma.

Chemotherapy
The prognosis in Ewing sarcoma remained very poor until 1960s in spite of good initial response to local treatment. The introduction of chemotherapy into the treatment regimen dramatically improved the response rates and thus the cure rates. Patients are started on induction chemotherapy for 3-4 cycles followed by local therapy at 12weeks. Restaging should be done with a chest imaging and MRI of the local part before local therapy. Further adjuvant chemotherapy is continued for total treatment duration of about 10-12 months. Chemotherapy with Vincristine, Adriamycin/Actinomycin D, cyclophosphamide, (VAC) alternating with Ifosfamide and Etoposide (IE) administered at a three weekly fashion is the standard regimen. Maintaining adequate dose intensity of chemotherapy is of utmost importance. Interval compressed or dose dense chemotherapy improves DFS and has the potential to improve overall survival [20].

Local therapy
Local therapy is delivered at the completion of 3-4 cycles of chemotherapy at 12 weeks and comprises of surgery or radiotherapy or both. There are no randomized trials comparing the two modalities. The choice of local therapy depends on the site of the disease, age of the patient, expected functional outcomes and concern over the late morbidities. Although retrospective institutional series suggest superior local control and survival with surgery rather than radiation therapy, most of these studies are compromised by selection bias. A North American intergroup trial showed no difference in local control or survival based on local treatment modality – surgery, radiation therapy, or both [21]. In patients with localized Ewing sarcoma treated in cooperative intergroup studies there was no significant effect of local control modality (surgery, RT, or surgery plus RT) on OS or EFS rates. In the CESS 86 trial, although radical surgery and resection plus RT resulted in better local control rates (100% and 95%, respectively) than definitive RT (86%), there was no improvement in relapse free survival and overall survival [22]. Preoperative radiation therapy can achieve tumor shrinkage and surgical resection with negative margins in cases with borderline resectability and can potentially allow smaller fields and lower radiation doses [23].

Definitive Radiotherapy
Ewing sarcoma was described by James Ewing in 1921 as “diffuse endothelioma of bone”, a distinct entity from osteosarcoma due to its high response to radiation therapy. In the current scenario, definitive radiotherapy remains an effective local therapy strategy for patients with tumors in sites not amenable for surgical resection and in cases where resection is likely to result in unacceptable morbidity. Advances in imaging, tumor delineation, treatment planning and delivery is now allowing greater precision and sparing of normal tissues. Historically, patients were treated with whole bone irradiation. With the POG 8346 trial, adequate involved field RT with MRI based planning became the standard. Current guidelines recommend 1.5 to 2 cm margin from the gross tumor volume. A randomized study of 40 patients with Ewing sarcoma using 55.8 Gy to the prechemotherapy tumor extent with a 2 cm margin compared with the same total-tumor dose after 39.6 Gy to the entire bone showed no difference in local control or EFS [24]. Initial treatment volume include the pre-chemotherapy volume with margin up to a dose of 45Gy, further boost is delivered to the post chemotherapy volume upto a total dose of 55.8Gy to 60Gy. Tumor size and RT dose have been shown to be predictive of local control rates in patients with non-metastatic Ewing sarcoma treated with chemotherapy and definitive RT [25]. Role of hyperfractionated radiotherapy in management of Ewing sarcoma has been evaluated in the CESS 86 trial [22]. No significant advantage has been demonstrated over the standard fractionation and dose. Recent reports suggest that Proton beam therapy can potentially spare more amount of normal tissue but longer follow up is needed to determine its impact on morbidity and cure rates [26]. Radiation therapy is associated with the development of second malignant neoplasms. In a retrospective analysis, the incidence of second malignancy was 20% in patients who received doses of 60 Gy or more and 5% in those who received 48 Gy to 60 Gy. Those who received < 48 Gy did not develop a second malignancy [27]

Postoperative RT
Postoperative radiation (PORT) is recommended in cases of intralesional or marginal resection, intraoperative spill and poor pathological response to chemotherapy and is usually initiated at 6-8 weeks following surgery. Current Children’s Oncology Group (COG) protocols have more specifically defined adequate margin status. Complete resection is defined as a minimum of 1 cm margin and ideally 2–5 cm around the involved bone. The minimum soft tissue margin for fat or muscle planes is at least 5 mm and for fascial planes at least 2 mm. The Intergroup Ewing Sarcoma Study (INT-0091) recommends 45 Gy to the original disease site plus a 10.8 Gy boost for patients with gross residual disease and 45 Gy plus a 5.4 Gy boost for patients with microscopic residual disease. In the absence of gross residual disease there seems to be no clear benefit to doses over 45 Gy [28]. No radiation therapy is recommended for those who have no evidence of microscopic residual disease following surgical resection. Although not statistically significant, local relapse was least in the combined arm (10.5%) compared with 25% for either surgery or radiotherapy alone [21]. EICESS 92 evaluated the role of postoperative RT in patients with poor pathological response to induction chemotherapy (<90% necrosis). In their analysis there was reduction in local failures (5% vs.12%) in the poor responders if they received PORT [29 In the CESS and EICESS trials, the local failure rate for central primaries was reduced by 50% with PORT. However the role of adjuvant radiotherapy in poor responders and central tumors needs to be clearly defined and the benefits need to be balanced against potential risks of long term effects and second malignancies. For extraskeletal ES, PORT is generally recommended except in good prognosis superficial tumors [30].

Management of metastatic disease
Standard treatment guidelines for metastatic Ewing sarcoma recommend treatment similar to localized disease [30]. Different chemotherapy agents used are Vincristine, Adriamycin, Cyclophosphamide, Ifosphamide and Etoposide. Addition of IE to VAC does not seem to have additional benefit in this subset of patients [31]. Dose-intense treatment approach with high dose chemotherapy and autologous stem cell transplantation (HDT/SCT) was evaluated in the nonrandomized Euro-EWING 99 R3 study [32]. Even though this may have a potential to improve outcome, it has not become the standard of therapy.
Following induction chemotherapy, patients are reassessed with local and chest imaging and previously abnormal investigations are repeated. A progressive disease is treated with palliative intent and the good responders are managed with treatment of primary disease and metastatic sites. Timing of local therapy for both primary site and metastatic sites remain unclear.

Radiotherapy in metastatic disease
Whole lung irradiation (WLI) in patients with lung-only metastases has shown improved disease free and overall survival in various trials. Patients with lung metastasis should be considered for whole lung irradiation even after complete resolution following chemotherapy [33] Doses of 12 to 21 Gy have been used and are usually well tolerated [34]. Hemithoracic irradiation is recommended in patients with chest wall tumor with pleural nodules, pleural effusion or positive pleural cytology.
Bone metastases in Ewing sarcoma should be treated with similar doses as the primary site. They may be treated simultaneously or following completion of chemotherapy depending on the risk of marrow suppression. In the phase II POG/CCG trial which evaluated the role of intensive chemotherapy, local treatment for primary disease was done after completion of 21weeks of chemotherapy and that of metastatic disease was done after week 39 chemotherapy [35]. With the emergence of stereotactic body radiotherapy (SBRT), it is now possible to deliver ablative doses to sites of bone metastases with excellent sparing of normal tissues. SBRT delivered in one to five fractions can also minimize interruptions of systemic therapy.

Treatment of relapse
Outlook of patients who relapse remain unfavorable. Late onset relapse (>2years) and strictly localized disease has a favorable outcome [36]. Chemotherapy regimens in relapse settings are not standard. Two phase II studies have demonstrated upto 33% partial responses in relapsed refractory Ewing’s sarcoma with the combination of Topotecan and Cyclophosphamide [37]. The combination of Irinotecan and Temozolomide has demonstrated clinical responses.38 Gemcitabine in combination with Docetaxel has shown modest activity [39]. Newer drugs and targeted therapies are being evaluated. Radiotherapy and/or surgery may play a role in improving control rates.

Indian Data
There is paucity of data from Indian population. In a retrospective analysis, symptom duration >4 months, tumor diameter >8cm and baseline WBC >11×10(9)/L were predictive of poorer outcomes [40]. Optimal surgical margin in extra skeletal Ewing sarcoma in children was evaluated by Laskar et al who concluded that clear margins of resection correlated with local control irrespective of margin size[41] Survival rates in India remain dismal in spite of the advancement seen in the western world [42]. Patients tend to present with advanced stage disease and often default treatment due to socioeconomic factors.

Conclusion

The management of Ewing sarcoma has significantly evolved over the last few decades with consequent improvements in survival and functional outcomes. Treatment mandates multidisciplinary co-ordination involving Medical, Surgical and Radiation Oncologists, Orthopedic surgeons, Rehabilitation specialists, Pediatricians and others. Dose intensity of chemotherapy and optimal timing and modality of local therapy appear to significantly influence outcomes and survival rates. Metastatic disease represents a major challenge and optimal treatment strategies still need to be defined.

References

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How to Cite this article: Irukulla MM, Joseph DM. Management of Ewing Sarcoma: Current Management and the Role of Radiation Therapy. Journal of Bone and Soft Tissue Tumors May-Aug 2015;1(1):18-22.

: Dr. Monica M. Irukulla

: Dr. Deepa M Joseph

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Re implantation of Sterilised tumour bone by Extra Corporeal Radiotherapy

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Management of Ewing Sarcoma: Current Management and the Role of Radiation Therapy

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Re implantation of Sterilised tumour bone by Extra Corporeal Radiotherapy

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Management of Ewing Sarcoma: Current Management and the Role of Radiation Therapy

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