Four year experience of sarcoma of soft tissues and bones in a tertiary care hospital and review of literature
© Ansari et al; licensee BioMed Central Ltd. 2011
Received: 20 January 2011
Accepted: 17 May 2011
Published: 17 May 2011
Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones.
This cross sectional study was carried out at Aga Khan University Hospital from 2004 to 2008. The patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted.
Out of 93 newly diagnosed patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed patients, 5 had soft tissue sarcoma and 9 had bone sarcoma. Mean age was 32.5 years. At presentation, approximately two third patients had localised disease while remaining one third had metastatic disease. The Kaplan Meier estimate of median recurrence free survival was 25 months, 35 months, and 44 months for Osteogenic sarcoma, Ewing's sarcoma and Chondrosarcoma respectively. For Leiomyosarcoma and Synovial sarcoma, it was 20 and 19 months respectively. The grade of the tumour (p = 0.02) and surgical margin status (p = 0.001) were statistically significant for determination of relapse of disease.
The median recurrence free survival of patients in our study was comparable to the reported literature but with significant lost to follow rate. Further large-scale, multi centre studies are needed to have a more comprehensive understanding of this heterogeneous disease in our population.
The skeleton and soft tissue comprise approximately 75% of the average body weight but the cancer arising from these parts represent 1% of adult and 15% of pediatric malignancies . The diversity and rarity of occurrence make their comprehensive understanding a difficult task. Broadly, sarcoma comprise of two distinct entities i.e. Bone sarcoma and Soft tissue sarcoma. Sarcomas have been associated with earlier radiation therapy, toxic exposure and genetic conditions but no clearly defined aetiology has been identified . The histological grade of the tumour is one of the most important prognostic variables for soft tissue sarcoma [1, 3, 4]. Complete staging and treatment planning by multidisciplinary team of cancer specialists is required to determine the optimal treatment for these patients . The role of chemotherapy is less well defined for soft tissue sarcoma while some bone sarcomas are chemo-sensitive and therefore, chemotherapy is an integral component of their treatment protocols. Bone sarcomas disseminate almost exclusively through the blood as bones lack a lymphatic system. Early lymphatic spread to regional nodes has only rarely been reported . It usually affects the younger age group, and hence the social burden of disability and morbidity is huge for any community.
With this background, we planned to under take a study to report our four year experience of dealing with sarcoma patients at a tertiary care hospital as data is limited from our country. Our population exhibits a very diverse behaviour in terms of tumour biology, disease manifestation and outcome and we wanted to explore these factors in our ethnically varied population.
Materials and methods
This descriptive, cross sectional study was conducted at Aga Khan University Hospital, Karachi. Our centre gets referral from all over the country. The method of referral is, however, not uniform. Sometimes primary physicians refer the patients and in other instances people make self-referrals.
The charts of the patients with diagnosis of the sarcoma were reviewed from a period of 2004 to 2008 after formal approval from the Institutional Ethical Review Board. Only adult patients with age of more than 16 years were included.
The data was analyzed in SPSS version 16.0. The descriptive analysis was done for the demographics and clinical characteristics of the patients. From the outset, two separate descriptive analyses were done, for relapsed and no relapsed cases. The further analysis was done on the basis of diagnosis whether soft tissue or bone sarcoma, localised versus metastatic disease and different modalities of treatment. The Chi square test was applied for univariate analysis for determining the significance of individual categorical variables for recurrence and Kaplan Meier survival curves were obtained for recurrence free survival.
The mean age group for the whole study population was 32.5 years with the range of 18 to 47 years. The stage of the disease at presentation was generally similar in both group of sarcoma patients with 67.8% of patients had localised disease and 34% had metastatic disease while staging details were missing for 2 patients with Ewing's sarcoma. The median follow up duration was 44 months (18-72 months).
There was unequal gender distribution in Osteogenic sarcoma with the male to female ration of 2.8:1. The diagnosis had been established by needle (trucut) biopsy for most of cases, but a few cases had excisional biopsies and exploratory surgeries as part of investigative work up.
The sub-group analysis of 22 patients with Osteogenic sarcoma showed that 16 had localised disease and 6 had metastatic disease at presentation. The long bones of the extremity were the main site of involvement in Osteogenic sarcoma with 17 cases (77%) of lower extremity and 4 cases (18%) of upper extremity location, while the site was not documented for one patient. Of these 16 patients with localised disease, twelve received neoadjuvant chemotherapy. Most patients tolerated the chemotherapy well and the commonly encountered side effects were nausea, vomiting, and mucositis. Only few patients had febrile neutropenia (grade 4 toxicity) but recovered fairly quickly with no definite localizing source of fever. Seven patients in the neo-adjuvant group had a good clinical response to the therapy while 2 had confirmed responsive disease radiologically as per RECIST criteria; however, the re-staging work up was missing for 3 patients.
Univariate Analysis of Categorical Variables for Relapse of the Disease
Number of Patients n (%)
Grade of the Tumour
Positive Surgical Margins
The gender distribution was 1:1 in Ewing's sarcoma. The neoadjuvant chemotherapy was given to 14 patients with Ewing's sarcoma and among them 3 had metastatic disease. The most commonly used chemotherapy regimen comprised of Cyclophosphamide, Vincristine, Adriamycin, Ifosfamide and Etoposide. The local treatment for localised disease was addressed at 12 - 14 weeks depending on the response to chemotherapy .
Patients with localised Chondrosarcoma had primary upfront surgery. Out of 14 patients 11 had localised disease and only one patient had positive margins postoperative and treated by adjuvant radiation.
Soft Tissue Sarcoma
The soft tissue sarcoma was under represented in our study and showed a trend towards female preponderance.
Majority of the patients i.e. 29 patients (31.2%) with soft tissue sarcoma had upfront surgery with negative margins in 21 patients and positive in 3 patients while margin status was not documented for 10 patients. Most patients had high grade tumour and five patients with Leiomyosarcoma received anthracyclines and Ifosfamide based adjuvant chemotherapy.
Outcome of Entire Cohort of Newly Diagnosed Sarcoma Patients
Alive with no recurrence
Alive with recurrence and taken treatment
Alive with recurrence/on supportive care
Lost to follow
Sarcomas represent the heterogeneous group of cancer with diverse tumour biology. Chemotherapy, being the main stay of treatment for certain sub-types of bone sarcoma e.g. Ewing's sarcoma, has proved to improve the recurrence free survival in adjuvant setting in Osteogenic sarcoma , but has a controversial role in soft tissue sarcomas. Wide adequate surgical resection with pathologically proven clear margins is the most effective therapeutic approach for management of soft tissue sarcoma.
Though the numbers of patients were small in our study but this was consistent with the overall incidence of the sarcoma and the rarity of the disease . The age group affected comprised of young adults with predominance of males in Osteogenic sarcoma as compared to females which was in contrast to the reported literature . It is not known whether this gender difference is related to epigenetic factors in our population or reflects a general social background of the community where men are more privileged than women and hence the greater access to medical facilities. One study from India has also reported a similar gender difference in the incidence of Osteogenic sarcoma [9, 10]. Nevertheless, female preponderance that had been shown in soft tissue sarcoma could be related to the significant number of cases of Leiomyosarcoma arising from the uterine muscle.
Successful management of sarcomas and localised Osteogenic sarcomas requires careful coordination and timing of staging studies, biopsy, surgery, and preoperative and postoperative chemotherapy. Majority of the cases of localised Osteogenic sarcomas did receive neoadjuvant chemotherapy in our study before proceeding with definitive surgery. It was in keeping with the revised standards for the management of Osteogenic sarcoma that had been established in 1990 . Limb-salvage surgery has now been considered a standard operation for selected cases. Approximately 95% of Osteogenic sarcomas can be treated successfully with this technique . Many studies have targeted the quality of life issues with limb salvage versus amputation but with conflicting results [11, 12].
Despite multidisciplinary involvement and appropriate planning of individual cases, the recurrence rate could not be compared between limb salvage and amputation; and also between two groups of limb salvage surgeries who relapse versus who do not relapse mainly because of smaller sample size. However, the recurrence free survival for Osteogenic sarcoma was comparable to few studies as per reported literature but definitely inferior for soft tissue sarcoma . Therefore, we need larger studies and longer follow up period before commenting on this any further.
The two most important determinant of local recurrence in previous studies were the surgical margins and the response to chemotherapy and our study corroborated these findings in emphasizing the importance of negative surgical margins for successful management of sarcoma . In our cohort, 3 patients had positive margins after limb salvage surgery. One of them is alive without recurrence but this patient had 90 percent necrosis on surgical specimen. One had local recurrence in 6 months time which had been treated with re-excision and the third one had multiple recurrences treated with surgery and chemotherapy and subsequently lost to follow. This patient had poor response to neo-adjuvant chemotherapy with significant residual tumour initially. This again highlights the importance of response to chemotherapy for recurrence free survival. The rest of the patients who relapsed had distant recurrences rather than local.
The soft tissue sarcoma group was, somewhat, under represented in our study mainly due to variable pattern of referrals i.e. most patients with low grade soft tissue sarcoma do not follow the oncologists after primary surgical resection. We primarily see patients with high grade tumours referred for adjuvant chemotherapy or for palliative chemotherapy in un-resectable cases. Adjuvant chemotherapy for high grade soft tissue sarcoma remains divisive but has been given to most patients with high grade tumours based on results of earlier meta-analyses which have demonstrated a reduction in local and distant recurrence rate and trend towards improved overall survival with adjuvant chemotherapy [14, 15]. Recent trials have also shown an advantage in disease free survival and overall survival with Ifosfamide and Adriamycin combination chemotherapy [16, 17]. Radiotherapy has also been used for improving the local control both before and after surgery depending on the individual case of high grade and large soft tissue sarcoma .
A major limitation of the study was the wide variation in treatment policies in small number of patients and hence, the analysis was based on small groups of heterogeneous sarcoma population. Also, the lost to follow rate was significantly high in our study for many reasons. The financial burden of the treatment is substantial, and people tend to disappear once the treatment is declared completed for the fear of more expenses associated with regular follow up visits. For the same reason significant number of patients have the tendency not to complete their treatment as soon as they start feeling better and then return later with extensive disease. Yet another factor is inadequate literacy level due to which many fail to understand the importance of follow up visits. Some people even argue about the significance of these visits once the treatment is deemed completed.
Sarcoma, though a rare cancer group, is associated with considerable morbidity and disability in younger group of the community. Our results showed the different characteristics of sarcoma patients, their course and outcome over a four year period. Multidisciplinary involvement is essential for appropriate and successful management of individual cases. The median recurrence free survival was comparable in our study to the reported literature but with significant lost to follow rate. Further large scale, multicentre prospective studies are needed to have a more comprehensive understanding of the behaviour and outcome of this heterogeneous disease in our population. Also, there is a need for increasing awareness among general public for meticulous follow up.
I would like to acknowledge the great efforts of my sisters Huda Ansari and Nida Ansari for making this a successful project, and rendering their constant support from scratch to final manuscript.
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