tough to treat tumours in the elderly: sarcomas · 2019. 6. 7. · sarcomas • malignant tumours...
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Tough to treat tumours in the elderly: sarcomas
Dr Michael LeahyThe ChristieThe Christie
Manchester, UK
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SarcomasSarcomas
• Malignant tumours of mesenchymal origing y g– Rare– Difficult to diagnose– Often late presenting– Anatomically unrestricted: involve diverse surgical teams– Require access to expert multi‐disciplinary teamsRequire 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%
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Sarcoma practice age profileSarcoma practice age profile25%
20%
15%
5%
10%
0%
5%
0 - 9 10 - 19 20 - 29 30 - 39 40 - 49 50 - 59 60 - 69 70 - 79 80 - 89 90 - 990 9 10 19 20 29 30 39 40 49 50 59 60 69 70 79 80 89 90 99
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Age related aspects in the fmanagement 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 biologyPossibly different biology
– host – PK, co‐morbidity, con meds– tumour biology
• Danger of under or over treatmentDanger of under or over treatment
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Scenario 1: Non‐metastatic soft tissue sarcoma
• Presentation: progressive mass in legPresentation: progressive mass in leg• Diagnosis: cross sectional imaging, biopsy, staging• Management plan: Wide local excision and post‐Management plan: Wide local excision and postoperative radiotherapy
• Expected outcome:Expected outcome: – Local control: 80%– Severe functional impairment: rare– Metastatic relapse: ~20% in 5 years
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PointsPoints
• Clinical outcomes generally goodClinical outcomes generally good• Ability to tolerate surgical resection and long course RT may be reduced by frailtycourse RT may be reduced by frailty
• Less radical therapy may have a worse lli ipalliative outcome
• Options for tailoring– Immediate onco‐plastic reconstruction– Pre‐ vs post‐ op radiotherapy
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Scenario 2: Metastatic soft tissue sarcoma
• Presentation: relapse after resection or metastaticPresentation: relapse after resection or metastatic at presentation
• Diagnosis: assessment of extent of disease and gfitness for therapy
• Management plan: Doxorubicin, ifosfamide, g ptrabectedin cytotoxic chemotherapy
• Expected outcome: – Overall response rate: 25% or less– Average survival: 12 months
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Overall survival in advanced STSOverall survival in advanced STS
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Outcome from first line chemoOutcome from first line chemo
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Number of lines of chemotherapyNumber of lines of chemotherapy
Number of lines of therapy in advanced soft tissue sarcoma
35%
40%
20%
25%
30%
&
10%
15%
0%
0%
5%
0 1 2 3 4
LinesLines
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No chemo given at ChristieNo chemo given at Christie
Patients not receiving chemotherapy for advanced soft tissue sarcoma
7080%
90%
70
80
60
53
50%
60%
70%
% 40
50
60
14
24
3237
1520%
30%
40%
20
30
0
14 15
0%
10%
10 20 30 40 50 60 70 80
Age decade
0
10
Age decade
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Survival in STSSurvival in STS
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PointsPoints• 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 decisionHonest 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
comparecompare
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Scenario 3: Gastrointestinal stromal ( )tumour (GIST)
• Presentation: mass +/‐ upper GI haemorrhagePresentation: mass / upper GI haemorrhage or incidental
• Diagnosis: Post‐op / radiological / biopsyDiagnosis: Post op / radiological / biopsy• Management plan:
– SurgerySurgery– Tyrosine Kinase Inhibitor therapy (imatinib)
• Expected OutcomeExpected Outcome– Non‐metastatic presentation: 5 yr survival 90%– Survival from metastases: median 5 yearsSurvival from metastases: median 5 years
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Lines of therapy in advanced GISTLines of therapy in advanced GIST
Number of lines of therapy in advanced GIST
40%
45%
50%
25%
30%
35%
40%
%
10%
15%
20%
5%
0%
5%
0 1 2 3 4
LinbesLinbes
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Lines of therapy in advanced GISTLines of therapy in advanced GIST
Number of lines of therapy in advanced GIST by age
50%
60%
30%
40%
%
<65 years>65 ears
10%
20%
>65 years
0%
10%
0 1 2 3 4
LinesLines
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PointsPoints
• Good outcomes can be obtained with correctGood 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
ipatients– Issues with drug‐drug interactions (CYP450)
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Scenario 4: Childhood type tumours h ld lpresenting in the elderly
• Presentation: Solitary destructive bone lesionPresentation: Solitary destructive bone lesion• Diagnosis: Osteosarcoma / Ewing’s
l i i• Management plan: Intensive pre‐operative cytotoxic chemo; radical surgery; extended
i h / di hpost‐operative chemo +/‐ radiotherapy• Expected outcomes:
– Osteo: 60 – 80 % cured– Ewings: 55 – 65 % cured
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PointsPoints
• Good outcomes can be achieved but isGood outcomes can be achieved but is dependent on use of chemotherapy– treatment very morbid– treatment very morbid– age thought to be a poor prognostic factorapplicability in older patients– applicability in older patients
• ? Different biology
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ConclusionsConclusions• Let age be no bar • Targeted therapies are • Host and condition both
need careful assessment• Validated tools are required
better tolerated but have their own problems
• Current avenues being• Validated tools are required• Cross disciplinary dialogue
is very welcome
Current avenues being explored– Trabectedin– VEGF therapy (pazopanib)• Organisational co‐
ordination may be more effective than any clinical
VEGF therapy (pazopanib)– mTOR inhibitors
(radiforalimus as maintenance therapy)
interventionpy
– Lower dose infusional ifosfamide
– Single sub‐type trials
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