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ORIGINAL ARTICLE
Year : 2013  |  Volume : 50  |  Issue : 4  |  Page : 306-309
 

Role of extracorporeal irradiation in malignant bone tumors


1 Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Orthopedic Surgery, All India Institute of Medical Sciences, New Delhi, India
3 Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication24-Dec-2013

Correspondence Address:
D N Sharma
Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.123601

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 » Abstract 

Aims and Objectives: Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation, and re-implantation back in the body. We report our preliminary experience of using ECI for management of MBT. Materials and Methods: From year 2009 to 2010, 14 patients with primary MBT were enrolled into this study. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for limb preservation therapy. Surgery was performed about 4 weeks after completion of neoadjuvant chemotherapy. The affected bone segment was resected, irradiated extracorporeally with a dose of 50 Gy and reimplanted. Local control, complications and short-term survival were studied. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. Results: There were 10 males and four females with median age of 14 years. Histopthologically, nine patients had osteosarcoma (OS) and five had Ewing's sarcoma family of tumors (ESFT). Distribution of primary site was as follows: Femur eight patients, tibia five patients and humerus one patient. At a median follow-up was 22 months, three patients (two OS, one ESFT) had local recurrence. Two patients (14%) developed wound infection in the perioperative period. The 2 year local recurrence free survival was 73% and mean MSTS score was 88. Conclusion: Results of our study suggest that ECI is technically feasible in the management of MBT and provides decent local control and short-term survival rates.


Keywords: Extracorporeal irradiation, limb preservation, malignant bone tumors


How to cite this article:
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 URL:
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 [serial online] 2013 [cited 2020 May 28];50:306-9. Available from: http://www.indianjcancer.com/text.asp?2013/50/4/306/123601



 » Introduction Top


Primary malignant bone tumors (MBT) are relatively rare but common in children and adolescents. [1] Management of MBT has changed in last couple of years because of the advancement in the field of pathology, imaging, surgical techniques, chemotherapy, and radiation therapy (RT). [2],[3],[4],[5],[6],[7] About two decades back, most patients used to undergo amputation. Recent management strategies favor limb preservation therapy (LPT) in most patients rather than amputation. This has been possible because of the multidisciplinary treatment, which consists of optimal use of surgery, chemotherapy, and RT.

The aim of LPT is to achieve local control by completely resecting the tumor and to maintain the limb function by performing a reconstruction procedure using either prosthesis or a bone graft. Recently, there has been an interest in reimplanting the tumor bone itself after sterilizing it. The various methods of sterilization reported in the literature are boiling, autoclaving, irradiation, microwave, pasteurization and the use of liquid nitrogen. [8] Extracorporeal irradiation (ECI) and re-implantation is a useful, convenient, and cost effective method. It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor and the soft tissues from the bone, irradiation and re-implantation back in the body. [9] Though there are limited studies [10],[11],[12],[13],[14],[15],[16],[17] in the literature, but results have been encouraging so far. We hereby report our preliminary experience of using ECI in the management of MBT.


 » Materials and Methods Top


From year 2009 to 2010, 14 patients with primary MBT were enrolled into this phase II study after the Institutional Review Board approval. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for LPT. Consent was obtained from every patient.

The initial pre-treatment workup of the patients consisted of detailed clinical examination in the clinic by a team comprising of orthopedic surgeon, medical oncologist and radiation oncologist. Each patient was subjected to various investigations. Routine hematological tests like hemogram, liver and kidney function tests were done for each patient. Magnetic resonance imaging (MRI) of the affected limb was done to assess the local extent of disease and X-ray chest and bone scan were performed to rule out distant metastases. Computed tomography (CT) scan chest and Positron emission tomography scan were done if necessary. Bone marrow examination was done for Ewing's sarcoma family of tumors (ESFT) patients.

The treatment approach and sequence of treatment modalities was decided by the multidisciplinary team. The usual treatment policy contemplated for osteosarcoma (OS) and ESFT was neoadjuvant chemotherapy followed by surgery and further treatment according to pathological findings. The chemotherapy regimens were used as per our institutional protocol.

Surgical procedure

Limb preservation surgery was performed about 4 weeks after the completion of neoadjuvant chemotherapy. It consisted of en-bloc resection of the tumor and the involved bone along with soft-tissues. [Figure 1] demonstrates the radiological images and operative photographs of a patient who underwent this procedure. The bone segment was tightly wrapped in wet sterile drape and then sealed in two plastic bags before it was sent for ECI. The wrapping material was at least 3.0 cm thick and therefore, sufficient for the bolus effect for six Mega Voltage X-rays. While packing the bone segment, care was taken not to leave any air gaps that may affect homogenous radiation dose delivery. During the ECI, the operative site was prepared for re-implantation, and biopsy was performed at all osteotomy sites to assess the status of resection margins. After the completion of ECI, the sealed package containing the bone was opened in the operation theater. The bone was then re-implanted with fixation devices. During the post-operative period, immobilization was continued until the radiographic imaging showed the evidence of union. Full weight bearing was allowed according to the clinical and radiological progress.
Figure 1: Radiological images and operative photographs of a 10 year old boy diagnosed with osteosarcoma of lower end of right femur that underwent extracorporeal irradiation (ECI). (a) (plain radiograph) and (b) (reconstructed computed tomography scan) showing the tumor at the lower end of femur. (c) the resected bone segment from which the tumor has been removed. The same was packaged and sent for ECI. (d) the operated limb after the resection of the bone segment

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Technique of ECI

The sealed bone segment was sent for ECI on the Linear Accelerator, which is located in the adjacent block. The bone segment was placed on the treatment couch and immobility was ensured. Every segment was irradiated with a single session dose of 50 Gy prescribed at mid plane using 6 MV X-rays. Two parallel opposed Anteroposterior-Posteroanterior fields were used. Radiation field size was chosen which adequately covered the segment. After the completion of ECI, the bone segment was returned to operation theatre without any delay.

Follow-up

Patients were followed-up every month until 6 months and then every 3 months until 2 years. Plain radiograph and MRI of the local part were performed every 3 months and 6 months respectively. For detecting lung metastases, plain chest skiagram was done every month and chest CT scan was done whenever required. Local recurrence free survival (LRFS) was calculated using Kaplan Meier method. [18] The functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system [19] at the last follow-up visit.


 » Results Top


Between year 2009 and 2010, 14 patients with primary MBT underwent E CI. Various clinical characteristics of the patents are given in [Table 1]. There were 10 males and four females with median age of 14 years (range 7-20 years). Histopthologically, nine patients had OS and five had ESFT. Distribution of primary site was as follows: Femur eight patients, tibia five patients, and humerus one patient. The ECI time (including the transfer time) ranged from 40 min to 95 min (median 50 min). In all patients, the ECI dose was 50 Gy.
Table 1: Details of the patients with their demography, clinical, treatment and outcome characteristics

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Median follow-up was 22 months (range 13-38 months). Three patients (two OS, one ESFT) had local recurrence (LR) and all of them subsequently developed lung metastases [Table 1]. One more patient had lung metastases with primary site controlled. Thus, local control rate was 79% and systemic control rate was 71%. The 2-year LRFS was 73% [Figure 2].
Figure 2: The Kaplan Meier curve showing local recurrence free survival of all the patients

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Out of 14, two patients (14%) developed wound infection in the perioperative period [Table 1]. One of them healed with antibiotic therapy and did not require any surgical intervention. The other one required wound debridement and prolonged antibiotic therapy. It took 4 months to control the wound complication in this patient and therefore, the scheduled chemotherapy course was deferred till 4 months after surgery. There was no other surgery/ECI related complication observed in any other patient. The mean MSTS score was 88 at the last follow-up visit.


 » Discussion Top


Though the use of ECI in the management of MBT was first reported by Spira et al. [10] in 1968, there are limited reports [10],[11],[12],[13],[14],[15],[16],[17] available in the literature. ECI has several potential advantages. (1) The affected bone segment is removed from the body and irradiated and therefore, avoidance of radiation injury to the un-irradiated bone, muscles, joint, and other healthy tissues of the body. (2) The delivery of very high doses of radiation to tumor bearing bone by ECI, which is otherwise not possible in the intact bone. These higher doses in the range of 50-300 Gy are lethal to the remaining tumor cells and therefore, reduce the risk of recurrence. (3) It provides an anatomically size-matched graft for biological reconstruction. (4) It is cost effective as compared to the prosthetic devices and (5) it has psychological advantage as patients feel that their own bone is being used as prosthesis.

On the other hand, ECI has few limitations like wound infection, failure of the graft etc. Risk of wound infection in various ECI series [12],[16] has been reported to be up to 17%. Infection rate of 14% in our present study is comparable to that in the literature. Infection can result into delayed/non-union of the bone graft, failure of the graft, and delay in subsequent course of chemotherapy and therefore every effort should be done to minimize the infection.

It is difficult to compare the survival and local control rates reported in the literature since most series have small sample size with heterogenous bone malignancies (OS, ESFT etc.) having different biological behavior. Still, the local control rate of 79%, 2-year LRFS of 73% and wound complication rate of 14% in our series seems to be comparable with the literature. The studies by Davidson et al. [15] and Poffyn et al. [17] are two of the largest in the literature treating 50 or more patients and are worth discussing here. Davidson et al. [15] reported a series of 50 patients with different MBT mainly ESFT (21 patients) and OS (16 patients) using en bloc resection and ECI (50 Gy). The mean time of ECI process was 35 min. With a mean follow-up of 38 months (range 12-92), 84% patients were alive without any disease and only 8% developed LR. The mean MSTS score was 77. Poffyn et al. [17] recently published a retrospective analysis of 107 patients with 108 malignant or locally aggressive bone tumors treated by ECI with 300 Gy, and re-implantation of the bone as an orthotopic autograft. At 5 year follow-up, there was no LR and 64% of patients had well healed graft. The 0% LR rate could be due to relatively very high dose of ECI (300 Gy) used in their study.

Although, most studies including ours have used 50 Gy and have reported acceptable recurrence rates; the 0% recurrence rate in Poffyns' study [17] having largest patient population so far will require future studies to consider higher doses specially for OS, which is relatively radio-resistant. In our study, two of the three local failures were noticed in OS patients. We also plan to escalate the dose of ECI to 100 Gy or more for OS patients in the next phase. Puri et al. [16] recently reported their experience of treating 12 patients of ESFT employing ECI dose of 50 Gy. Although, the authors have opined that ECI dose of 50 Gy avoids graft factures but, as apparent from their results, 50% of the patients died due to disease. This again suggests that a higher dose of ECI needs to be tried in future trials.

Though, it is difficult to draw conclusions from our preliminary study, due our smaller sample size and shorter follow-up period, the overall results suggest that the ECI is technically feasible in our setup and provides decent local control and short-term survival rates. We suggest that a higher dose of ECI needs to be explored in future trials in order to further improve the local control rates.

 
 » References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]

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