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  1. Tough to treat tumours in the  elderly: sarcomas Dr Michael Leahy The Christie The Christie Manchester, UK

  2. Sarcomas Sarcomas • Malignant tumours of mesenchymal origin g – Rare – Difficult to diagnose – Often late presenting – Anatomically unrestricted: involve diverse surgical teams – Require access to expert multi‐disciplinary teams Require access to expert multi disciplinary teams – Relatively less sensitive to radiotherapy – Relatively less sensitive to chemotherapy – Slow development of new therapies due to low trial  recruitment – Overall 5 years survival rate ~ 50% Overall 5 years survival rate   50% y g

  3. Sarcoma practice age profile Sarcoma practice age profile 25% 20% 15% 10% 5% 5% 0% 0 - 9 0 9 10 - 19 10 19 20 - 29 20 29 30 - 39 30 39 40 - 49 40 49 50 - 59 50 59 60 - 69 60 69 70 - 79 70 79 80 - 89 80 89 90 - 99 90 99

  4. Age related aspects in the  management of sarcoma • Late diagnosis – Patient delay – Physician delay • Access to specialist teams – Reluctance to refer (physician) – Reluctance to attend (patient) • Adherence compliance with therapeutic advice • Under‐representation in clinical trials • Generalisability of research findings • Possibly different biology Possibly different biology – host – PK, co‐morbidity, con meds – tumour biology • Danger of under or over treatment Danger of under or over treatment f

  5. Scenario 1:   Non‐metastatic soft  tissue sarcoma • Presentation: progressive mass in leg Presentation:  progressive mass in leg • Diagnosis: cross sectional imaging, biopsy, staging • Management plan: Wide local excision and post‐ Management plan:  Wide local excision and post operative radiotherapy • Expected outcome: Expected outcome:   – Local control: 80% – Severe functional impairment: rare – Metastatic relapse: ~20% in 5 years

  6. Points Points • Clinical outcomes generally good Clinical outcomes generally good • Ability to tolerate surgical resection and long  course RT may be reduced by frailty course RT may be reduced by frailty • Less radical therapy may have a worse  lli i palliative outcome • Options for tailoring – Immediate onco‐plastic reconstruction – Pre‐ vs post‐ op radiotherapy

  7. Scenario 2:  Metastatic soft tissue  sarcoma • Presentation: relapse after resection or metastatic Presentation:  relapse after resection or metastatic  at presentation • Diagnosis:  assessment of extent of disease and  g fitness for therapy • Management plan:  Doxorubicin, ifosfamide,  g p trabectedin cytotoxic chemotherapy • Expected outcome:   – Overall response rate: 25% or less – Average survival: 12 months

  8. Overall survival in advanced STS Overall survival in advanced STS

  9. Outcome from first line chemo Outcome from first line chemo

  10. Number of lines of chemotherapy Number of lines of chemotherapy Number of lines of therapy in advanced soft tissue sarcoma 40% 35% 30% 25% 20% 0% & 15% 10% 5% 0% 0 1 2 3 4 Lines Lines

  11. No chemo given at Christie No chemo given at Christie Patients not receiving chemotherapy for advanced soft tissue sarcoma 90% 80 80% 70 70 70% 60 60 60% 53 50 50% 40 0 % 37 40% 32 30 30% 24 20 20% 15 15 14 14 10 10% 0% 0 10 20 30 40 50 60 70 80 Age decade Age decade

  12. Survival in STS Survival in STS

  13. Points Points • Palliative therapy often ineffective and associated with  morbid toxicity – Both doxorubicin and ifosfamide known to be problematic in elderly  patients – Less known about trabectedin • Useful benefit in a minority • Honest disclosure and optimal patient involvement in decision Honest disclosure and optimal patient involvement in decision  making.  Early engagement of community supportive care  services • Options for tailoring • Options for tailoring – Avoid combination regimens – Less toxic chemotherapy regimens have been published but no RCTs to  compare compare

  14. Scenario 3:  Gastrointestinal stromal  tumour (GIST) • Presentation: mass +/‐ upper GI haemorrhage Presentation:  mass  / upper GI haemorrhage  or incidental • Diagnosis: Post‐op / radiological / biopsy Diagnosis:  Post op / radiological / biopsy • Management plan:   – Surgery Surgery – Tyrosine Kinase Inhibitor therapy (imatinib) • Expected Outcome Expected Outcome – Non‐metastatic presentation: 5 yr survival 90% – Survival from metastases: median 5 years Survival from metastases:  median 5 years ( )

  15. Lines of therapy in advanced GIST Lines of therapy in advanced GIST Number of lines of therapy in advanced GIST 50% 45% 40% 40% 35% 30% 25% 5% % 20% 15% 10% 5% 0% 0 1 2 3 4 Linbes Linbes

  16. Lines of therapy in advanced GIST Lines of therapy in advanced GIST Number of lines of therapy in advanced GIST by age 60% 50% 40% <65 years >65 ears >65 years 30% % 20% 10% 10% 0% 0 1 2 3 4 Lines Lines

  17. Points Points • Good outcomes can be obtained with correct Good outcomes can be obtained with correct  management • Tolerability of stomach resections is variable • Tolerability of stomach resections is variable • Use of TKIs has revolutionised the outlook for  i patients – Issues with drug‐drug interactions (CYP450)

  18. Scenario 4:  Childhood type tumours  presenting in the elderly • Presentation: Solitary destructive bone lesion Presentation:  Solitary destructive bone lesion • Diagnosis: Osteosarcoma / Ewing’s l • Management plan:  Intensive pre‐operative  cytotoxic chemo; radical surgery; extended  i h post‐operative chemo +/‐ radiotherapy • Expected outcomes:   – Osteo: 60 – 80 % cured – Ewings: 55 – 65 % cured h ld l i i / di h

  19. Points Points • Good outcomes can be achieved but is Good outcomes can be achieved but is  dependent on use of chemotherapy – treatment very morbid – treatment very morbid – age thought to be a poor prognostic factor applicability in older patients – applicability in older patients  • ? Different biology

  20. Conclusions Conclusions • Let age be no bar • Host and condition both  need careful assessment • Validated tools are required • Validated tools are required • Cross disciplinary dialogue  is very welcome • Organisational co‐ ordination may be more  effective than any clinical  intervention • Targeted therapies are  better tolerated but have  their own problems • Current avenues being Current avenues being  explored – Trabectedin – VEGF therapy (pazopanib) VEGF therapy (pazopanib) – mTOR inhibitors  (radiforalimus as  maintenance therapy) – Lower dose infusional  ifosfamide – Single sub‐type trials py