Urinary system outflow obstruction and urinary system tumors
Rare cancers Medical oncologist Point of View€¦ · Rare Urinary system 2,5 0,0 12 693 8 18,5 0,4...
Transcript of Rare cancers Medical oncologist Point of View€¦ · Rare Urinary system 2,5 0,0 12 693 8 18,5 0,4...
Rare cancersMedical oncologist Point of View
Isabelle Ray-Coquard, MD PhD
Centre Léon Bérard – GINECO&
Université Claude Bernard Lyon I
Identified factors to explain medical practices
• Initial Medical school education
• Scientific data
• Continuous medical education
• Pharma industries
• Financial incitation's & Private or public system
• Organized networks?
Medical decision – for rare cancers?
Characteristics disease’s &
prognostic factors for survival
Social and cultural values:
• Practicians uses • Patient preferences
Evidence based Medicine
Organisational context
• Management care access• Economical context• Referent centers
Medical decision
??
Not Done !
Specific background for rare cancers
Few knowledge
No evidence based Medecine
& CPG’s
No clinical trials
No innovations No improvements for survival over
time
No interests from Agencies & Pharma
No financial supports
Incidence & prevalence by sites
Table 3. Incidence and prevalence of rare and common cancers by site in EU27
Incidence
rate per
100,000
Standard
error
Estimated
incident
cases in
EU27
Incidence
distribution
(%)
Prevalence per
100,000
Standard
error
Estimated
prevalent
cases in
EU27
Prevalence
distribution
(%)
Common Digestive tract 76,1 0,1 380 565 67 400,3 1,2 2 001 514 84
Rare Digestive tract 17,2 0,1 86 143 15 50,0 0,4 250 005 11
All Digestive tract 114,1 0,1 570 236 100 474,6 1,4 2 373 151 100
Common Respiratory tract 31,6 0,1 157 903 49 56,2 0,3 280 918 43
Rare Respiratory tract 13,6 0,0 68 125 21 60,2 0,4 300 876 46
All Respiratory tract 64,1 0,1 320 391 100 130,0 0,6 649 911 100
Common Skin 61,3 0,1 306 427 96 744,6 1,5 3 722 876 95
Rare Skin 1,5 0,0 7 487 2 14,8 0,3 74 116 2
All Skin 63,7 0,1 318 615 100 779,7 1,5 3 898 655 100
Common Breast 47,7 0,1 238 471 74 522,6 4,1 2 612 913 75
Rare Breast 4,9 0,0 24 415 8 56,9 0,7 284 484 8
All Breast 64,3 0,1 321 429 100 700,1 6,3 3 500 252 100
Common Female genital tract 9,6 0,0 47 779 32 126,7 0,6 633 546 38
Rare Female genital tract 16,1 0,0 80 669 55 176,2 0,8 881 107 53
All Female genital tract 29,5 0,1 147 597 100 331,7 1,1 1 658 589 100
Common Male genital tract 40,6 0,1 203 224 78 279,5 1,4 1 397 655 70
Rare Male genital tract 4,3 0,0 21 673 8 93,0 0,8 465 225 23
All Male genital tract 52,0 0,1 259 868 100 399,6 1,6 1 997 975 100
Common Urinary system 25,9 0,1 129 253 78 202,2 0,7 1 011 037 85
Rare Urinary system 2,5 0,0 12 693 8 18,5 0,4 92 689 8
All Urinary system 33,1 0,1 165 457 100 238,7 0,8 1 193 504 100
Common Haematopoietic system 11,1 0,0 55 273 50 59,0 0,5 295 022 48
Rare Haematopoietic system 9,6 0,0 48 077 44 62,5 0,5 312 462 50
All Haematopoietic system 21,9 0,1 109 721 100 123,9 0,7 619 550 100
Common All sites 309,6 0,2 1 548 036 61 2428,2 4,9 12 141 163 68
Rare All sites 97,1 0,1 485 697 19 797,3 2,0 3 986 679 22
All All sites 503,6 0,3 2 518 108 100 3565,4 7,2 17 826 767 100
Gatta G, Eur J Cancer 2011
Context
• Rare Gynecologic cancers = same problematic than
all other rare cancers:
– Absence of knowledge, curability, few therapeutic
options, no very few dedicated clinical trials….
– Organization of care pathway at all levels
• Regional, national European & international
×
National Network including3 national + 22 regional expert centers
➢Objectives ➢Management : medical strategy decided in dedicated regional multidisciplinary tumor boards➢Diagnosis: ➢systematic second review➢molecular diagnosis for all patients (ex: FOXL2, SMARCA4….). ➢Education: ➢workshops & continuing medical education. ➢information for patients, families and advocacy groups.➢To elaborate CPG’s
The French National Network dedicated to Rare gynecologic Malignant Tumors
ESMO PRECEPTORSHIP PROGRAM
Isabelle Ray-Coquard
Dedicated website - http:// www.ovaire-rare.org
8
ESMO PRECEPTORSHIP PROGRAM
Isabelle Ray-Coquard
Decision-making algorythmes are availableon web site for 8 types of tumors
- Stromal and sex-cord T
- Germ-cell T
- Serous&mucinous borderline
- Clear-cell adenocarcinoma
- Mucinous adenocarcinoma
- Low grade serous carcinoma
- Small cell carcinoma
- Carcinosarcoma
11
1st French Patient Advocacy group
IMAGYN
Published in the Official Journal of 31st May 2014
www.monimagyn.org
Support
Share and help
ClinicalResearch
Awareness
ESMO PRECEPTORSHIP PROGRAM
Isabelle Ray-Coquard
Yearly new cases of rare ovarian tumorsOvarian Tumor types 2011 2012 2013 2014 2015 2016 Cumulated
Sex cord-stromal tumor 128 202 191 235 216 298 1270
Germ cell tumor 95 93 102 113 125 127 655
Small cell carcinoma 6 8 8 12 7 12 53
Carcinosarcoma 30 42 50 42 36 67 267
Low-grade serous carcinoma 2 13 14 36 70 85 220
Clear cell carcinoma 42 77 83 105 123 100 530
Mucinous carcinoma 41 83 117 109 125 135 610
Borderline Tumors 172 182 355 450 472 429 2060
Malignant Brenner tumor 9 3 5 6 9 13 45
Other rare tumor 28 11 26 84 19 27 185
Total Ovary 553 714 951 1192 1202 1331 5943
Yearly progression of clinical and diagnosis review
128107
141
198
166
302
477
544
259
305333
450
0
100
200
300
400
500
600
2011 2012 2013 2014
-- Multidisciplinary staff meeting
-- Multidisciplinary staff meeting with expert pathologic review
-- Expert diagnosis review
Expert diagnosis review inducing medicaldecision change
Year #Yearlynewcases
# Casesdiagnosed by pathologistreferees
# Cases benefitingfrom both local and central review
# Minordiagnosisdiscrepancy
# Cases for whichdiagnosis modifiedtherapeutic strategy
2011 553 425 359 28 17 (17/359) (5%)
2012 714 607 355 52 28 (28/355) (8%)
2013 951 810 445 93 40 (40/445) (9%)
2014 1192 994 658 155 61 (61/658) (9%)
Total 3410 2383 1817 328 (18%) 146 (146/1817) (8%)
ALIENORENGOT- OV7
Avastin and weekly pacLItaxel use in sEx cord-stromalovariaN tumORs
A randomized, open label, phase II trial of bevacizumab plus weeklypaclitaxel followed by maintenance with bevacizumab monotherapy versusweekly paclitaxel followed by observation in patients with relapsed ovariansex-cord stromal tumors
National network and clinical research: an example
0
10
20
30
40
50
60
70
France Germany Italy
International Collaboration
AGO, 10
BGOG, 2
GINECO, 38
GOTIC, 2
MITO, 8
RANDOMISED PATIENTS
ALIENOR - GCIG June 1st 2017
ALIENOR
Clinical trials in Germ cell tumours
Novartis : ribociclib, CDK4/6 inh (pRb & cell cycle)
Background: CDK4 & CyclinD2 upregulated GCT
Randomized phase II with LEE011 for patients with immature teratoma in relapse after standard CT
Sarcoma – research program
• Epidemiology not well known (incidence, risk factors)
• Retrospective study on medical practices :
32% management conformed with CPG’s (Ray-Coquard, Ann Oncol 04)
problems for diagnosis, management, clinical trials
Dedicated research program for sarcoma tumours
Since 2005 – Prospective - Rhône-Alpes Region
Medical practice
evaluation for
STS
study
Incidence study
Exhaustive cohort of sarcoma in a specific region
Economical
study of sarcoma
management
costs
Concordance study for
histological diagnosis between initial and second
opinion
Overall survival and Conformity of Surgery
Surgical conformity and PFS for STS patients
Median PFS
Conformed surgery: NR
Non conformed surgery: 45.2
HR: conformed vs non conformed: 0.44
IC 95%: [0.32, 059]
p ≤0.0001
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102
Months
Adherent to CPG’s
Not adherent to CPG’s
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96102
Pro
bab
ilit
y o
f su
rviv
al
Months
University /conformedsurgery
Private +general S-
p=0.006
Key point: double organization within network (pathologists & clinicians dedicated to sarcoma)
▪ All new diagnosis of STS /GIST anddesmoid since 2010▪ systematic central review▪molecular biology▪ FFPE & frozen samples
▪ All patients with managementdiscussed in MS since 2010
▪ New incident patients▪ Patients in follow up or
relapse▪ clinical data▪ participation to clinical trial
Collect of indicators in real time
Shared databasis(https://netsarc.org)
Patients With 2nd
opinion without MS
Patients With MS
without 2nd
opinion
RRePSNETSARC Patients
☺
Pathologist included in the 2nd
opinion report (in conclusion), arecommendation to promote adedicated MS for managementof sarcoma patient «
Dedicated MS from NetSarcasked a systematic 2nd opinionfor initial diagnosis for sarcomapatients before to validateproposal of management care
National evaluation of medical practices
Regional organisation of experts centers
3 coordinator centers9 expert centrers17 delegate experts centers
RRePS – 22 centres(Pathologists)
NETSARC – 29 centres(Clinicians - MS)
Dedicated national network for rare cancers Sarcoma- 2010 - 2017
Quality of initial surgery:New operated sarcoma patients
24%
32%
25%24%
37%
23%24%
37%
22%
28%31%
24%
54%
28%
9%
56%
27%
6%
56%
27%
7%
58%
26%
8%
Incidents 2011 Incidents 2012 Incidents 2013 Incidents 2014
Incidents 2011 Incidents 2012 Incidents 2013 Incidents 2014
Résection R0 R1 R2
Outside Network
NetSarc network
Outside Network Outside Network Outside Network NetSarc networkNetSarc networkNetSarc network
Histological discordances
ESMO PRECEPTORSHIP PROGRAM
Isabelle Ray-Coquard
COST ECONOMIC IMPACT OF CENTRALIZED HISTOLOGICAL REVIEWS IN PATIENTS WITH SARCOMA,
GIST, AND DESMOID TUMORS
➢ Out of the 2,425 patients that underwent histological review, 341patients had a major discordance in their diagnosis (14%)
➢ N = 10 patients were excluded from the model due to missing data
Access to Expertise and innovation ? Territorial inequalities?
Cartography and flux of patients to MTB in France
– More favorable patients (screening, hygiene measures,
fighting vulnerabilities)
– More scientific guidelines (“evidence based guidelines”)
– Top level physicians (medical practices)
– Efficient structures (hospital volume, quality program)
– More specific drugs ‘Imatinib model’
How to improve survival in sarcoma (rare cancer) patients?
Scientific data and availability for routine ?Always coherence?
2007- academic study662 patientsBenefit in OSDrug expensiveNon available in France
1984- academic study70 patientsNo benefit in OSDrug non expensiveStandard of care
Negative spiral for rare cancersFew
knowledge
No evidence based Medicine no Standard of
Care
No clinical trials
No innovations No improvements for
survival over time
No interests from Agencies & Pharma
No financial supports
Rare Gynecologic cancers = same problematic than all other rare cancers
How to change the future?
• 5th OCCC GCIG in Tokyo 2015– Have fixed standard of care in 1st line & relapse – Have highlighted the need for investigational treatments – New prognostic factors including molecular factors
• New organizations for management & clinical research– Dedicated cancer network (eg French model)
• Education for physicians, care givers and public• Motivate Patients advocacy group
– European network for rare cancer (ENGOT, ESMO, ESO, EURACAN)
– International collaboration (GCIG, WSN)
RARE SOLID ADULT CANCERS
Melanoma Patient Network Europe
Rarity will be the future
Learning More in the 20th Century
Leukemias,
Blood
Cancers
Breast
Cancer
Lung
CancerColon
Cancer
Prostate
CancerOther
Cancers,
including
Sarcomas
Appreciating the Complexity of Cancers
in the 21st Century
Take home message
• Rare tumors are frequent!
– Prognosis & clinical presentation really different
– Thinking to rarity before surgery!
– Fertility & of adjuvant treatment
• Management decision making:
– Expert Pathologists
– Multidisciplinary expert staff
– Dedicated Rare Cancer Network French experience
• Physicians & patients advocacy groups parternship Autorities & gouvernements
• Tumoral minority is the future of the oncology
• European Cooperation +++++
• European networks of reference for rare diseases: we need you to be sure they will be dedicated to rare cancers!
http://ec.europa.eu/health/rare_diseases/european_reference_networks