1. Synovial sarcoma- which patients don’t need adjuvant treatment? Khan M, Rankin KS, Beckingsale TB, Todd R, Gerrand CH North of England Bone and Soft Tissue Tumour Service Newcastle upon Tyne, UK

2. Synovial sarcomas: background Wide range of presentation Varied anatomical location Outcomes can be poor Adjuvant chemo and/or radiotherapy Some patients are best treated with surgery only Small completely resected tumours in the paediatric population can have good outcomes Brennan B et al Synovial sarcoma in childhood and adolescence: a retrospective series of 77 patients registered by the Children’s Cancer and Leukaemia Group between 1991 and 2006. Pediatric Blood Cancer 2010

3. High versus Low Risk Groups Low risk Size <5cm Age <25 years No histological evidence of poor differentiation 88% versus 18% overall survival Bergh P et al, Synovial sarcoma: identification of low and high risk groups. Cancer 1999

4. Sites Distal extremity tumours associated with better 10 year survival 65% hand, ankle, foot 48% proximal extremity 0% truncal (all were >5cm) Deshmukh R et al. Synovial sarcoma: the importance of size and location for survival. Clin Orthop Relat Res 2004

5. Does chemotherapy improve outcomes? 42 cases Texas 1966-1999 (Paediatric) No difference in overall survival Okcu MF et al, Synovial sarcoma in children and adolescents: thirty three years of experience with multimodal therapy. Med Pediatric Oncology, 2001 237 cases France (Adults) No improvement in survival (OS, LRFS, DRFS) Italiano A et al, Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial sarcoma: A study of the French Sarcoma Group. Ann Oncol 2009 271 cases Italy (All ages) Adjuvant chemotherapy improved metastasis free survival in high risk group (tumours >5cm, age >= 17 years) Ferrari A et al, Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 2004 101 cases USA (Adults) Ifosfomide shown to have disease specific survival benefit in high risk group i.e. adults with tumours >5cm Eilber FC et al. Chemotherapy is associated with improved survival benefit in adults with primary extremity synovial sarcoma. Ann Surg 2007 No Yes

6. Methods Retrospective Database and case note review 1998-2013 Treatment approach: Neo-adjuvant chemotherapy (ifosfamide/doxorubicin) for “high risk” tumours Radiotherapy for all except widely excised superficial tumours Palliative treatment for patients with unresectable primary or metastatic tumours

7. Results 82 patients 42 female, 40 male Mean age 39 (range 8-78) Mean maximum diameter 8.5cm (1-26cm, SD 4.3) 9 patients (11%) had metastases at presentation No significant difference in tumour size between metastatic and non- metastatic patients

8. Anatomical location LocationNumberMean diameter Extremity587.2 (SD 4.4) Head & Neck56.2 (SD 1.3) Truncal1912.5 (SD 6.0) Total82

9. Treatment overview 9 surgery alone 18 surgery and radiotherapy alone 42 with chemotherapy in addition to local therapy (26 neo-adjuvant, 20 adjuvant only) 13 patients had no chemotherapy or radiotherapy. 6 surgical resection only 3 amputation 4 palliative supportive treatment only.

10. Who did we give chemotherapy to? Treatment modalityNo chemotherapy ChemotherapyPalliativeP value Gender Females Males 17 (40%) 13 (33%) 19 (44%) 23 (59%) 7 (16%) 3 (8%) 0.3 Mean Age (years)4134480.05 Location Extremity Head/Neck Truncal 26 (45%) 1 (20%) 3 (16%) 28 (48%) 4 (80%) 10 (52%) 4 (7%) 0 6 (32%) 0.015 Staging at presentation Non-metastatic Metastatic 26 (40%) 2 (22%) 38 (57%) 3 (33%) 2 (3%) 4 (45%) 0.004 Size of Tumour Unknown < 5 cm ≥ 5cm 6 (55%) 14 (70%) 10 (19%) 3 (27%) 6 (30%) 33 (63%) 2 (18%) 0 8 (18%) 0.001 Microscopic margins Negative Positive 27 (39%) 3 (30%) 32 (46%) 10 (70%) 10 (14%) 0 0.1 Radiotherapy No radiotherapy Radiotherapy 13 (35%) 17 (38%) 21 (57%) 21 (47%) 3 (8%) 7 (15%) <0.001

11. Are small tumours different? Tumour size< 5cm≥ 5cmUnknownP value Gender Females Males 11 (25%) 9 (23%) 28 (65%) 23 (59%) 4 (10%) 7 (18%) 0.5 Mean Age (years)2742390.005 Location Extremity Head/Neck Truncal 19 (32%) 0 1 (5%) 31 (53%) 4 (80%) 16 (84%) 8 (15%) 1 (20%) 2 (11%) 0.76 Chemotherapy Palliative Neo-adj No Neo-adj 1 (10%) 1 (4%) 18 (39%) 8 (72%) 23 (92%) 20 (43%) 2 (18%) 1 (4%) 8 (18%) 0.001 Microscopic margins Negative Positive 19 (28%) 1 (7.7%) 41 (60%) 10 (77%) 9 (12%) 2 (15.3%) 0.3 Radiotherapy No radiotherapy Radiotherapy 12 (32%) 8 (22%) 21 (57%) 25 (65%) 4 (11%) 5 (13%) 0.3

12. Disease-specific survival Mean 15 year survival 43% (Std Error 0.069)

13. Disease-specific survival by chemotherapy treatment group Mean Survival (months) No Chemotherapy (15 years)57% Chemotherapy (12 years)43% Palliative (9 years)13% Log Rank p value <0.001

14. Difference in survival of tumours more than 5cm size Mean Survival in weeks Without Neo-adj treatment (17 pts) 88 With Neo-adj treatment (20 pts) 50 No significant difference

15. Cox multivariate analysis VariableOverall Survival Hazard Ratio P value Location Extremity Head/Neck Truncal Reference 0.56 4.2 0.526 0.006 Tumour Size <5cm ≥5cm Reference 0.770.86 Metastasis at presentation No/Yes1.430.003 Treatment Modality Chemotherapy No Chemotherapy Palliative Reference 2.33 4.12 0.225 0.006

16. Local recurrence There were 10 local recurrences at a mean of 19 months 2 Head and Neck 2 Knees 2 Groin 1 Pelvis 1 Thorax 1 Shoulder 1 Intra-abdominal

17. Surgery only All alive – no evidence of disease Thigh 59 years old 2003 2.8cm Thigh 14 years 2006 2cm Elbow 19 years old 2006 3cm Knee (infrapatellar) 70 years old 2000 1.3cm Ankle 20 years old 2012 1.5cm Thigh 18 years 2000 1.5cm

18. Conclusion Aggressive disease Some patients with small tumours in the extremities can do well with surgery alone Chemotherapy did not appear to improve outcomes in our series