A Synovial Sarcoma-Specific Preoperative Nomogram Supports a Survival Benefit to Ifosfamide-Based Chemotherapy and Improves Risk Stratification for Patients

Sarcoma Disease Management Program, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA.
Clinical Cancer Research (Impact Factor: 8.72). 01/2009; 14(24):8191-7. DOI: 10.1158/1078-0432.CCR-08-0843
Source: PubMed


To identify prognostic factors related to outcome in 255 patients with synovial sarcoma and to construct a preoperative nomogram to predict the risk of disease-specific death.
Between July 1982 and June 2006, 301 patients underwent treatment at our institution for primary synovial sarcoma of all anatomic sites and 255 patients with localized disease at presentation were resected with curative intent. Data were collected prospectively and analyzed retrospectively.
Five-, 10-, and 15-year disease-specific survival (DSS) was 72%, 60%, and 53%, respectively. Multivariate analysis revealed size and primary tumor site as the only independent adverse predictors of disease-specific death. A nomogram based on preoperative data for surgical patients not receiving anthracycline-ifosfamide (AI) chemotherapy (n = 196) estimates 3- and 5-year DSS with a concordance index of 77.3%. For the first 3 years following diagnosis, the observed DSS for patients treated with AI chemotherapy (n = 59) was greater than that predicted by the preoperative nomogram based on patients not receiving AI chemotherapy. SYT-SSX fusion transcript data were available for 132 patients. Multivariate analysis of this subset showed that SYT-SSX1 fusion type was predictive of early, but not late, distant recurrence.
Size and location govern prognosis in primary synovial sarcoma resected with curative intent. A nomogram based on preoperative variables provides individualized patient survival estimates and shows an early survival benefit to chemotherapy that may dissipate over time. This nomogram may improve decision-making with regards to selecting patients most likely to benefit from neoadjuvant/adjuvant chemotherapy.

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    • "Many studies have reported the prognostic impact of SS18 – SSX fusion type on synovial sarcomas , but it still remains a matter of debate ( Kawai et al . 1998 ; Ladanyi et al . 2002 ; Guillou et al . 2004 ; Skytting 2000 ; Nilsson et al . 1999 ; Hill et al . 2003 ; Canter et al . 2008 ; Panago - poulos et al . 2001 ; Mezzelani et al . 2001 ; Takenaka et al . 2008 ; ten Heuvel et al . 2009 ; Sun et al . 2009 ; Krieg et al . 2011 ; Charbonneau et al . 2013 ; Ren et al . 2013 ) . One of"
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    ABSTRACT: SS18–SSX (formerly called SYT–SSX) fusion gene has been established clinically as a molecular diagnostic test for synovial sarcoma, but the prognostic value of the fusion gene variant for survival is controversial. The objective of this systematic review is to provide an up-to-date and unprecedented summary of the prognostic impact of SS18–SSX fusion type in synovial sarcoma. Studies evaluating SS18–SSX fusion type as a prognostic marker in synovial sarcoma were systematically searched for in MEDLINE, EMBASE, and Web of Science. Comparative analysis of the pooled hazard ratios (HR) between fusion types was carried out, in order to assess the likelihood of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and metastasis-free survival (MFS). A total of 10 studies comprising 902 patients with synovial sarcoma were considered for the meta-analysis. The pooled HR for eight eligible studies evaluating for OS or DSS was 1.28 (95% confidence interval: 0.81–2.00), suggesting no significant difference between SS18–SSX1 and SS18–SSX2 (P = 0.29). For seven studies which evaluated for PFS or MFS, the presence of SS18–SSX1 may indicate a lower survival probability than that of SS18–SSX2, although the effect did not reach a level of statistical significance (P = 0.09). There was no significant difference in OS or DSS between SS18–SSX1 and SS18–SSX2, but there were indications of SS18–SSX1 being an unfavorable prognostic factor of PFS or MFS. Further studies including cohorts with a longer follow-up period are needed. Electronic supplementary material The online version of this article (doi:10.1186/s40064-015-1168-3) contains supplementary material, which is available to authorized users.
    Full-text · Article · Jul 2015 · SpringerPlus
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    • "In the literature male sex is associated with decreased survival (Trassard et al., 2001). SYT-SSX1 fusion transcript has a higher prevalence in males and it has been shown that patients carrying this fusion type have an increased risk of early distant recurrence (Canter et al., 2008). One other explanation could be the slower clearance rate of chemotherapeutic agents in women (Sleijfer et al., 2010). "
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    ABSTRACT: Background: We aimed to evaluate prognostic factors and response rates to various treatment approaches to patients with synovial sarcoma in an advanced setting. Materials and methods: We retrospectively reviewed the medical records of 55 patients (18 pts; 32.7% women) diagnosed with synovial sarcomas. Twenty had metastatic disease at the time of diagnosis while the remainder of the study group consisted of patients who developed metastatic or inoperable locally advanced disease during follow up. Results: The median follow up time was 15 months (range: 1-53). Regarding outcomes for the 55 patients, 3 and 5 year overall survival rates were 26% and 14%, respectively. In univariate analyses among demographic factors female gender was associated with a better outcome (p=0.030). Patients with early progressing disease (<2 years) had a worse prognosis when compared to patient group with late relapse, but this difference did not reach statistical significance (p=0.056). According to multivariate Cox regression analysis patients who had undergone metastasectomy had a significant survival advantage (p=0.044). The overall response rate to different salvage chemotherapy regimens given as second line treatment was around 42.9-53.9% for all regimes. There were no statistically significant differences between chemotherapy regimens given in either second or third line settings in terms of overall survival. Conclusions: We observed no major differences in terms of response rate and survival between different salvage chemotherapy regimens. Although metastatic disease still carries a poor prognosis, metastasectomy was found to be associated with improved survival.
    Full-text · Article · Sep 2013 · Asian Pacific journal of cancer prevention: APJCP
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    • "Evidence of a welldefined role for chemotherapy remains uncertain in localized adult STS, but is more debatable in SS. Some series of SS support a survival benefit with chemotherapy [12] [13] [14], while others have reached the opposite conclusion [15] [16] [17] [18]. "
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    ABSTRACT: Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15–76) and 14 (range 0.4–18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.
    Full-text · Article · Apr 2011 · Sarcoma
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