National Cancer Intelligence Network Outcome and the effect of age in 1318 patients with synovial sarcoma: Report from the National Cancer Intelligence Network: Registered cases diagnosed in England between 1985 and 2009 Bernadette Brennan 1, Nicola Dennis 2, John Broggio 2, Matthew Francis 2 Institutions 1 Paediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK, 2 Public Health England Knowledge and Intelligence Team West Midlands, UK

BACKGROUND Synovial sarcoma - rare STS in children and TYA Crosses all age groups- peak incidence third decade 30% occur in age < 20 years Prognostic factors- site, size, stage, resectability Age significant in institutional series and SEER data IMD 2010 important in other diseases and Cancers OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

PURPOSE To further assess the role of age on outcome for synovial sarcoma, this study analysed a contemporary all-age population-based cohort of patients with synovial sarcoma treated in England and registered in the eight English cancer registry offices between 1985 and 2009 to examine the effect of age on outcome as well as other available prognostic factors including IMD. OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

Methods Population-1,318 SS English cancer registry all cases included Data available – age, sex, ethnicity, site, surgery or not, distant metastases or not, and IMD No data on chemotherapy, radiotherapy and size. Morphology subtype not used in analysis Analysis included incidence as ASR and effect of time period, patient characteristics and prognostic factors, comparison between age groups 0-19 years and 19 years plus for available characteristics, and the effect of characteristics and prognostic factors on the outcome of 5 year relative survival. OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

Patient Characteristics: Data on 1318 Patients Diagnosed From OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND Total Children/AdolescentsAdults No% % % Total p value Age %2514% 0% %15786% 0% % 0%23721% % 0%23921% % 0%20718%- >= % 0%45340%- Sex Female 62848%7943%54948%0.217 Male 69052%10357%58752% Location Head & neck665%148%525% Extremity86165%11463%74766% Lungs and pleura605%63%545% Trunk 19014%2715%16314% Others 14111%2112%12011%0.6928

Patient IMD scores: Data on 1318 Patients Diagnosed From OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND Deprivation quintile Least deprived %3620%22119% %3016%22620% %2916%23220% %4123%23721% Most deprived %4625%22019% Total Children/AdolescentsAdults No% % % Total P value

Patient Metastatic Stage and Surgery Status: Data on 819 Patients Diagnosed From OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND Total Children/AdolescentsAdults No% % %P value Stage Distant 12015%1211%10815% Other 69985%10189%59885% Surgery Status No Surgery 26933%2926%24034%0.08 Surgery55067%8474%46666%

Synovial Sarcoma age standardised incidence rates (3 year rolling average). England OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

Synovial Sarcoma age standardised incidence rates (3 year rolling average). England years, 20 years + 9 OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

Age specific incidence rates England OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND 25 cases < 10 years age

Proportion of synovial sarcomas diagnosed in each age group and anatomical site (England ) OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

Synovial sarcoma 5-year relative survival rates (5-year rolling average) 1985–2004 OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

Synovial sarcoma 5-year relative survival rates (5-year rolling average) 1985– years, 20 years + OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND

Survival Curves of Patients from 2000 Compared According to Metastatic Stage OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND P<0.001

Survival Curves of Patients from Compared According to Primary Tumour Site OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND P<0.001

Cox Proportional Hazards Regression for Cancer Mortality: Data on 1318 Patients Diagnosed From OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND Variable All patients Children/adolescents Adults Age category, y HR (95% CI)p-value HR (95% CI)p-value HR (95% CI)p-value 0 to to ( ) to ( ) ≥ ( ) < Sex Female 1.00 Male 1.43 ( ) ( ) ( )0.007 Ethnicity White 1.00 Black 0.70 ( ) ( )0.356 Unknown 1.20 ( ) ( ) ( )0.612 Others 0.45 ( ) ( )0.001 Primary site Extremity 1.00 Other 2.20 ( )< ( ) ( )<0.001

Cox Proportional Hazards Regression for Cancer Mortality: Data on 819 Patients Diagnosed From OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND Variable All patients Children/adolescents Adults HR (95% CI)p-value HR (95% CI)p-value HR (95% CI) p value Extent Mets 1.00 Other 0.17 ( )< ( )< ( ) < IMD quintile Least Deprived ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 0.28 Most Deprived ( ) ( ) ( ) 0.13

Conclusions The incidence of Synovial sarcoma has increased with time It is rarely diagnosed in patients under 10 years of age, the highest incidence in the age group years Children/adolescents have a similar clinical presentation to adults, but a significantly better outcome. For all ages survival has not increased with time Mortality is significantly higher in adults, male sex, non- extremity tumour location, patients with metastases and in children with the highest deprivation scores The lack of data on tumour size and treatment received stops further exploration of these findings currently but in the future the COSD will provide this OUTCOME AND THE EFFECT OF AGE IN 1318 PATIENTS WITH SYNOVIAL SARCOMA: REPORT FROM THE NATIONAL CANCER INTELLIGENCE NETWORK REGISTRY: REGISTERED CASES DIAGNOSED BETWEEN 1985 AND 2009 IN ENGLAND