Patients with metastatic synovial sarcoma to lungs should be assessed for pulmonary metastasectomy if the metastases are resectable and the primary tumor is controlled although the level of evidence behind that concept is lower than other sarcomas like osteosarcoma. Nevertheless, there may be a chance for long term survival with such surgical approach. Patients with unresectable metastatic synovial sarcoma should be managed with palliative chemotherapy if they have adequate performance status. Synovial sarcoma is characterized by heightened sensitivity to chemotherapy with overall response rates in the range of 40-50% depending on the regimen. In fact, achievement of objective response in patients with metastatic synovial sarcoma correlated with improved survival ( 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 Mar;16(3):437-44), nevertheless; the optimal first line chemotherapy regimen is not well defined.

In our retrospective study we concluded that ifosfamide should be an integral component of the first-line chemotherapy regimen of patients with metastatic synovial sarcoma because it made significant difference in outcomes (Salah S, Yaser S, Salem A, Al Mousa A, Abu Sheikha A, Sultan I. Factors influencing survival in metastatic synovial sarcoma: importance of patterns of metastases and the first-line chemotherapy regimen. Med Oncol. 2013;30(3):639); however, confirmation of that finding in other studies is warranted. The most common chemotherapy regimen that we use for this disease in the metastatic setting at our center is the combination ifosfamide (12 g/m2/cycle), doxorubicin, and Mesna uroprotection. Other centers use other regimens that are based on ifosfamide or doxorubicin.

Pazopanib may be a promising agent for patients who progress following ifosfamide or doxorubicin- based therapy as it resulted in suppression of synovial sarcoma cells in xenograft models (Hosaka S, Horiuchi K, Yoda M, et al. A novel multi-kinase inhibitor pazopanib suppresses growth of synovial sarcoma cells through inhibition of the PI3 K-AKT pathway. J Orthop Res.

2012;30(9):1493–8). Furthermore, pazopanib has shown activity in sarcomas including synovial sarcoma in phase 2/ 3 clinical trials (Sleijfer S, Ray-Coquard I, Papai Z, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the

European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol. 2009;27(19):3126–32), (van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, doubleblind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829): 1879–86).

Synovial sarcoma is characterized by unique t(X;18)(p11.2;q11.2) translocation resulting in the fusion of the SYT gene on chromosome 18 to either of two closely related genes; SSX1 and SSX2 on chromosome X. The presence of this specific translocation may serve as a rationale for evaluating targeted therapies and we hope that the prognosis of patients with metastatic synovial sarcoma will improve by introduction of new active agents in the future.

Finally, I attach to you the most important publication in the field by Dr Spurrel.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Prognostic+factors+in+advanced+synovial+sarcoma%3A+an+analysis+of+104+patients+treated+at+the+Royal+Marsden+Hospital

Thanks Samer for your input. Rolando.

Dear Rolando,

You are more than welcome