|Year : 2019 | Volume
| Issue : 5 | Page : 95-98
Metastatic synovial sarcoma: Experience from a tertiary care center from India
K Govind Babu, Rajesh Patidar, C Lakshmaiah Kuntegowdanahalli, Lokanatha Dasappa, Linu Abraham Jacob, Suresh Babu, AH Rudresha, Lokesh N Kadabur, LK Rajeev, Deepak Koppaka, Vikas Asati
Department of Medical Oncology, Kidwai Cancer Institute, Bengaluru, Karnataka, India
|Date of Web Publication||25-Jul-2019|
Room No. 214, PG Mens Hostel, Kidwai Cancer Institute, Near NIMHANS, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Synovial sarcoma represents 8% of all soft-tissue sarcoma (STS). It is a high-grade STS, and 50% of patients develop metastasis. The most common site of metastasis is the lungs, lymph nodes followed by bones. Ifosfamide-based chemotherapy is associated with improved outcome. In this study, we report our experience of metastatic synovial sarcoma according to primary sites, metastatic pattern, and their outcome. Materials and Methods: This was a retrospective observational study carried out at our institute from January 2013 to December 2016. The aim of our study was to evaluate the pattern of metastasis, response to chemotherapy, and survival in patients with metastatic synovial sarcoma. Results: Over a period of 4 years, 43 patients with metastatic synovial sarcoma were diagnosed with median age of 30 years. Nearly 70% of patients had lung metastasis, other site of metastasis were lymph node, bone, and liver. Thirty patients received chemotherapy with a combination of ifosfamide and doxorubicin. The overall response rate was 87% with median progression-free survival of 8 months. Patients with lung only metastasis had better survival compared with nonpulmonary metastatic site (18 months vs. 12 months). The median survival was 18 months. Conclusion: Metastatic synovial sarcoma is chemoresponsive tumor with lung being the most common metastatic site. Patients with lung only metastasis had a better outcome than nonpulmonary metastasis.
Keywords: Metastatic synovial sarcoma, sarcoma, synovial sarcoma
|How to cite this article:|
Babu K G, Patidar R, Kuntegowdanahalli C L, Dasappa L, Jacob LA, Babu S, Rudresha A H, Kadabur LN, Rajeev L K, Koppaka D, Asati V. Metastatic synovial sarcoma: Experience from a tertiary care center from India. Indian J Med Paediatr Oncol 2019;40, Suppl S1:95-8
|How to cite this URL:|
Babu K G, Patidar R, Kuntegowdanahalli C L, Dasappa L, Jacob LA, Babu S, Rudresha A H, Kadabur LN, Rajeev L K, Koppaka D, Asati V. Metastatic synovial sarcoma: Experience from a tertiary care center from India. Indian J Med Paediatr Oncol [serial online] 2019 [cited 2020 Jun 4];40, Suppl S1:95-8. Available from: http://www.ijmpo.org/text.asp?2019/40/5/95/263322
| Introduction|| |
Synovial sarcoma represents 8%–10% of all soft-tissue sarcoma (STS). Synovial sarcomas may be diagnosed at any age, but the mostly occurs in young adults, between 15 and 35 years of age, and more commonly in males. Although relatively rare, synovial sarcoma is the third-most common extremity STS. It affects mostly young adults, with a median age of 35 years. Despite its name, synovial sarcoma is a misnomer; it does not originate from synovial tissue. It may sometimes originate near the joint but never within it. Its cellular origin is undefined. Sometimes, it may be encountered in regions without apparent relationship to synovial structures, including the head and neck (<10%), thoracic and abdominal wall (<10%), or intrathoracic sites. Synovial sarcomas are of four subtypes – monophasic fibrous (spindle), monophasic epithelial, biphasic, and poorly differentiated and monophasic subtype being the most common. Biphasic subtype has both, epithelial and spindle cell components. Its unique t(X: 18)(p11.2; q11.2) translocation helps to define the diagnosis and to distinguishes this subtype from other STSs.
Synovial sarcoma is an aggressive STS with a higher propensity for recurrence and metastasis. Overall 50% of patients develop metastatic disease either at initial presentation or later in the disease course. The most common site of metastasis is the lungs (74%–81%), lymph nodes (3%–23%), and bones (10%–20%).,, In this study, we report our experience of metastatic synovial sarcoma according to primary sites, metastatic pattern, and their outcome.
| Material and Methods|| |
This was a retrospective descriptive study carried out at Kidwai Cancer Institute, a tertiary care center at Bengaluru, India.
Patients of metastatic synovial sarcoma (either at initial presentation or relapsed) evaluated at our institute from January 2012 and December 2016 were included in this study. Biopsy from the primary site or accessible metastatic site was performed. The diagnosis was made by histopathological examination and appropriate immunohistochemistry marker such as cytokeratin, epithelial membrane antigen, desmin, vimentin, smooth muscle antigen, and S-100. All patients underwent staging evaluation with computed tomography (CT) scan/magnetic resonance imaging of primary site and CT scan of thorax and abdomen.
Patients with the Eastern Cooperative Oncology Group performance status (PS) of 0–2 received chemotherapy. Combination of ifosfamide (1.8 g/m 2 days 1–3) and doxorubicin (75 mg/m 2 day 1) repeated every 21 days was used in all eligible patients. Maximum 6 cycles were planned depending on interim reassessment and tolerability.
Reassessment CT scan was performed at the end of 3 cycles of chemotherapy or on suspected clinical progression. The response evaluation was based on RESIST 1.1 criteria. All patients with stable disease, partial response, or complete response received another 3 cycles of chemotherapy.
SPSS software, version 23.0 (SPSS, Chicago, IL, USA) was used for all statistical analysis. The association of different variables was analyzed using the log-rank test. Multivariate analysis was done to test the correlation of different factors with survival. Overall survival analysis was done using the Kaplan–Meier method.
| Results|| |
Over a period of 4 years, 43 patients with metastatic synovial sarcoma were diagnosed at our institute.
The median age at diagnosis was 30 years (10–70 years). A female preponderance was seen with a male to female ratio being 1:1.15 [Table 1]. Extremity was the most common site of primary tumor seen in 76% (n = 32) of all patients. Retroperitoneum (7%) and neck (7%) were the next common site of primary tumor [Table 2].
The most common site of metastasis was lung (69.7%) followed by lymph node and bone with the incidence being 18.6% and 11.6%, respectively. Liver metastasis was uncommon and present in only 6.9% of patients.
Thirteen patients did not receive any chemotherapy in view of poor PS. Thirty patients received chemotherapy with a combination of ifosfamide and doxorubicin.
As expected synovial sarcoma being chemoresponsive malignancy overall response rate (ORR) was 87%. One patient showed a complete response to the chemotherapy. The median progression-free survival was 8 months [Table 3]. Second-line chemotherapy on progression was received by only 8 patients. The overall median overall survival was 18 months.
| Discussion|| |
Synovial sarcoma occurs most commonly in adolescent and young adults. It occurs most commonly in the soft tissues of the extremities, especially near large joints, but other sites such as head and neck, lung, heart, mediastinum, and abdominal wall sites also have been reported. Patients with synovial sarcoma have relatively high rates of response to chemotherapy. Ifosfamide-based chemotherapy has been associated with improved disease-specific survival with chemotherapy compared with no chemotherapy., Ifosfamide appears to be most active agent with ORR of around 30%–55%., We found that ORR with ifosfamide and doxorubicin 85% which is higher than as reported by Stefan Sleijfer et al. Patients with lung only metastasis had better survival 18 months and 12 months as shown in [Figure 1]. Similar observation reported by Salah et al.
|Figure 1: Survival curve comparing lung only metastasis versus other site of metastasis|
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Other newer drugs which showed some efficacy in metastatic synovial sarcoma are pazopanib and sunitinib., Pazopanib showed activity in a variety of STS including synovial sarcoma in various phase 2 and phase 3 clinical trials.,, Olaratumab is a recombinant human monoclonal antibody that specifically targets PDGFRα, blocking PDGF-AA, PDGF-BB, and PDGF-CC binding and receptor activation. The result of the phase 1b/2 study, randomizing 133 patients to receive olaratumab plus doxorubicin or doxorubicin alone, showed a median progression-free survival of 6.6 months and 4.1 months. Median survival was 26.5 months and 14.7 months in experimental versus doxorubicin arm.
Immunotherapy has been one of the major breakthroughs in oncology, for both solid and hematological tumors. In the SARC028 phase 2 study, pembrolizumab as a single agent showed activity in unselected STS of all types, with an ORR of 17.5%.
| Conclusion|| |
Metastatic synovial sarcoma is a chemoresponsive malignancy with good response to ifosfamide and doxorubicin. Patients with extrapulmonary metastasis have dismal prognosis. There is a need for better novel agents for achieving better treatment outcomes.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Corey RM, Swett K, Ward WG. Epidemiology and survivorship of soft tissue sarcomas in adults: A National Cancer Database report. Cancer Med 2014;3:1404-15.
Eilber FC, Dry SM. Diagnosis and management of synovial sarcoma. J Surg Oncol 2008;97:314-20.
Lewis JJ, Antonescu CR, Leung DH, Blumberg D, Healey JH, Woodruff JM, et al.
Synovial sarcoma: A multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol 2000;18:2087-94.
Fisher C. Synovial sarcoma. Ann Diagn Pathol 1998;2:401-21.
Kadoch C, Crabtree GR. Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell 2013;153:71-85.
Hajdu SI, Shiu MH, Fortner JG. Tendosynovial sarcoma: A clinicopathological study of 136 cases. Cancer 1977;39:1201-17.
Cadman NL, Soule EH, Kelly PJ. Synovial sarcoma; an analysis of 34 tumors. Cancer 1965;18:613-27.
Palmerini E, Staals EL, Alberghini M, Zanella L, Ferrari C, Benassi MS, et al.
Synovial sarcoma: Retrospective analysis of 250 patients treated at a single institution. Cancer 2009;115:2988-98.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al.
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
Rajeev LK, Patidar R, Babu G, Suresh Babu MC, Lokesh KN, Patil Okaly GV, et al.
A rare case of primary synovial sarcoma of lung. Lung India 2017;34:545-7.
] [Full text]
Jain A, Sajeevan KV, Babu KG, Lakshmaiah KC. Chemotherapy in adult soft tissue sarcoma. Indian J Cancer 2009;46:274-87.
] [Full text]
Eilber FC, Brennan MF, Eilber FR, Eckardt JJ, Grobmyer SR, Riedel E, et al.
Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma. Ann Surg 2007;246:105-13.
Spurrell EL, Fisher C, Thomas JM, Judson IR. Prognostic factors in advanced synovial sarcoma: An analysis of 104 patients treated at the Royal Marsden hospital. Ann Oncol 2005;16:437-44.
Bokemeyer C, Franzke A, Hartmann JT, Schöber C, Arseniev L, Metzner B, et al.
A phase I/II study of sequential, dose-escalated, high dose ifosfamide plus doxorubicin with peripheral blood stem cell support for the treatment of patients with advanced soft tissue sarcomas. Cancer 1997;80:1221-7.
Sleijfer S, Ouali M, van Glabbeke M, Krarup-Hansen A, Rodenhuis S, Le Cesne A, et al.
Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: An exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). Eur J Cancer 2010;46:72-83.
Salah S, Yaser S, Salem A, Al Mousa A, Abu Sheikha A, Sultan I, et al.
Factors influencing survival in metastatic synovial sarcoma: Importance of patterns of metastases and the first-line chemotherapy regimen. Med Oncol 2013;30:639.
Schöffski P. Pazopanib in the treatment of soft tissue sarcoma. Expert Rev Anticancer Ther 2012;12:711-23.
George S, Merriam P, Maki RG, Van den Abbeele AD, Yap JT, Akhurst T, et al.
Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas. J Clin Oncol 2009;27:3154-60.
Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schöffski P, et al.
Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: A phase II study from the European Organization for Research and Treatment of Cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol 2009;27:3126-32.
Deeks ED. Pazopanib: In advanced soft tissue sarcoma. Drugs 2012;72:2129-40.
van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, et al.
Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012;379:1879-86.
Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, et al.
Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: An open-label phase 1b and randomised phase 2 trial. Lancet 2016;388:488-97.
Tawbi HA, Burgess MA, Crowley J, Van Tine BA, Hu J, Schuetze S, et al
, and for SARC028 Investigators. Safety and efficacy of PD-1 blockade using pembrolizumab in patients with advanced soft tissue (STS) and bone sarcomas (BS): Results of SARC028—A multicenter phase II study. Journal of Clinical Oncology 2016;34(Suppl 15);11006-11006. ASCO Journals.
[Table 1], [Table 2], [Table 3]