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”Lærende succeshistorie”:Resultat af klassisk databasedrift og interaktion mellem forskning og kvalitetsmonitorering i DAHANCA
Jens OvergaardDanish Cancer Society, Department of Experimental Clinical
Oncology, Aarhus University Hospital, [email protected]
Regionernes nationale databasedag 2015København – 8 april
The Danish National Head and Neck Cancer Database
www.dahanca.dk
Jens OvergaardDanish Cancer Society, Department of Experimental Clinical
Oncology, Aarhus University Hospital, [email protected]
DAHANCA.dkDanish Head and Neck Cancer Group
Head and neck cancer
OropharynxLarynx
Epiglottic
EsophagusTrachea
Nasal cavity
Oral cavity
Supraglottic
Glottic
Subglottic
Nasopharynx
Laryngopharynx
Pharynx'
Head and Neck Cancer:
Probably the most diverse and heterogeneous cancer type in Europe
Major variations in:
IncidenceEpidemiologyEtiologyTreatmentPrognosis
1500 pts per year(4% of all cancer cases in Denmark)
Head and Neck cancer is a heterogeneous disease
… and so is the treatment strategy
established byTHE DANISH SOCIETY
FOR HEAD & NECK ONCOLOGY1976
DAHANCA.dkDanish Head and Neck Cancer Group
Organized by the Danish Society for Head and Neck Oncology
MULTIDICIPLINARY collaborative group involving
ALL relevant Danish departments and specialities
– and taking care of ALL head and neck cancer
patients in Denmark (and some in Norway)
National databaseRegistration and follow up of all H&N patientsNational treatment strategyNational (evidence-based) guidelinesClinical trials and studiesQuality assuranceBiobank Translational research infrastructureResearch projects (Ph.D students) Education and information (professionals – public)International collaboration (all issues above)
DAHANCA.dkDanish Head and Neck Cancer Group
DAHANCA.dk
DAHANCA –databaseIncludes: ICD-7 no. 141-148, 160-161,194.Since 1960: Larynx from 3 largest institutions (80%)
1971-91 Nat’l “official” larynx database (> 99%)
1992 - Nat’l “official” Head & Neck base (larynx, pharynx, oral cavity)
1996 - DATYRCA (thyroid cancer)
2000 - Unknown primary data base
2002 (1996)- DASPYTCA (salivary gland tumours)
2005- Biobank database (linked with clinical data)
2008- Nasal Sinus etc...
2010- Approved as “Nat’l Clinical Quality Database”
2010- Establisment of QA database for Radiotherapy DAHANCA.dk
per April 2015
>31.000 patient
s included
DAHANCA -databaseTYPE OF DATABASE.
Pre 1991 “Homemade” flat FORTRAN base (on the medical physicist’s computer).
DAHANCA.dk
DAHANCA -databaseTYPE OF DATABASE.
Pre 1991 “Homemade” flat FORTRAN base (on the medical physicist’s computer).
1991 Medlog (BMDP) Local recording with file to central collection
2003 - Internet based central database using Clarion on a Windows serverplatform.
Run from all computers (128 bit cryptation) Extractable to e.g. textfile, Excel, STATA (Bill Gates is the winner)
DAHANCA.dk
DAHANCA -databaseSTRUKTUR
DAHANCA.dk
Overordnet databaseansvarlig
(datatilsynet)
Onkol. center
RH
Onkol. center Herlev
Onkol. center SDU
Onkol. center Århus
Onkol. center Aalb
Onkol. center Oslo
DATHYRCA
Omfatter ICD-7 no. 141-148, 160-161,194
Lokaliseret: Afd. Eksp Klin Onkologi, AUH. (Aleks)
Tilknyttet: Kompetencecenter Nord (bruges ikke)
Dokumentationscenter for Kræftbehandling (KB)
Driftsprincip: entusiastisk, non-bureaukratisk
Økonomi: RKKP – resten forskningsfonde o.l.
DAHANCA -databaseWHY HAVE A DATABASE?
ResearchProtocols, pro- and retrospective studies attracts youngsters
Quality control (“law”)
Health care management
“Political reasons”. (knowledge is power)
DAHANCA.dk
DAHANCA -databaseWHAT DO WE RECORD
“Relevant” baseline data (> 300 variables)
“On Study, Treatment, Follow-up, Recurrence, Death”.
Flexible (ad hoc data if needed)
Longitudinal (time trends) – contineous variables
Exchange/International(AJC, UICC, ICD, EORTC, INKA, etc)
Data must be verified to be applicable and useful)
DAHANCA.dk
DAHANCA -databaseDATA MUST BE USED (updated and verified)
National Cancer Registry
(Eurocare, Nordcan)
Hospital records
CPR (unique personnumber)
EPJ, e-journal
Course of death registry
Pathology registry
Other …….
DAHANCA.dk
DAHANCA -databaseDATA MUST BE USED (and verified) and GOOD
> 99% coverage of national patient cohort (compared with Danish Cancer registry)
DAHANCA.dk
Problem:Den ”ægte” varevs. ”industrielt genbrug”
Problem:Vi kan ikke ”tilbagerette”forkerte data(så de går igen)
DAHANCA -databaseWHAT DO WE USE IT FOR?
A FEW EXAMPLES:
DAHANCA.dk
EXAMPLE 1
DAHANCA.dk
Time after treatment (months)0 6 12 18 24 30 36 42 48 54 60
Loco
-regi
onal
con
trol (
%)
0
20
40
60
80
100
27%
DAHANCA Database Stage 3-4 Larynx and Pharynx
5 fx/wk
The DAHANCA strategy: progression through consecutive clinical trials
Standard 1985
EXAMPLE 1
Primary RT of HN
Cancer
larger RT dose
Hyperfx
Neo-adjuvant Chemo-
RT
Smaller RTvolume
IMRT
Hypoxic modification
of RT
Basic “virtues”
Waiting time etc.
Con-commitant Chemo-RT
Reduced RT time
Accl fx
Changed RT-Surg balance
Better diagnosis
and imaging
Dahanca 2
Dahanca 5
Dahanca 10
Dahanca 1
Dahanca 9
Dahanca 11
Dahanca 13
Dahanca 15
Dahanca 6
Dahanca 7
Dahanca study
DAHANCA.dk
Hypoxic modification
of RT
Reduced RT time
Accl fx
Dahanca 14
Dahanca 18
Dahanca 19Dahanca 16
Con-commitant Chemo-RT
Dahanca 24
Dahanca 27
Dahanca 29
Dahanca 30
Dahanca 28
Comorbidity
Biological modifiers
Anti-EGFr
DAHANCA.dk
Time after treatment (months)0 6 12 18 24 30 36 42 48 54 60
Loco
-regi
onal
con
trol (
%)
0
20
40
60
80
100
27%
DAHANCA Database Stage 3-4 Larynx and Pharynx
5 fx/wk
5 fx/wk + NIM44%
Benefit of Hypoxic Modification
The DAHANCA strategy: progression through consecutive clinical trials
Standard 1985
DAHANCA.dk
Time after treatment (months)0 6 12 18 24 30 36 42 48 54 60
Loco
-regi
onal
con
trol (
%)
0
20
40
60
80
100
27%
DAHANCA Database Stage 3-4 Larynx and Pharynx
5 fx/wk
5 fx/wk + NIM44%
62% 6 fx/wk + NIM
Benefit of Hypoxic Modification
Benefit of Accelerated Fract.
The DAHANCA strategy: progression through consecutive clinical trials
Standard 1985
DAHANCA.dk
Time after treatment (months)0 6 12 18 24 30 36 42 48 54 60
Loco
-regi
onal
con
trol (
%)
0
20
40
60
80
100
27%
DAHANCA Database Stage 3-4 Larynx and Pharynx
5 fx/wk
5 fx/wk + NIM44%
62%
83%
6 fx/wk + NIM
6 fx/wk + NIM + cis-P
Benefit of Hypoxic Modification
Benefit of Accelerated Fract.
Benefit of Chemo-Radiotherapy
The DAHANCA strategy: progression through consecutive clinical trials
Standard 1985
Standard 2007
Larynx/oropharynx/ hypopharynx
HPV/p16 negativeStage III - IV (T1-4, N0-3)
RANDOMIZATION
Accl RT (70 Gy, 6 fx/wk) + cddp (40 mg/m2
weekly x 5 or 100 mg/m2 x 2)+ placebo (daily)
Stratification:•Institution•Localization•T-stage•N-stage•WHO-PS•Hypoxic gene-profile
+ Nimorazole (1.2 g/m2 daily)
Accl RT (70 Gy, 6 fx/wk) + cddp (40 mg/m2
weekly x 5 or 100 mg/m2 x 2)
1219 ROG-HNCG/DAHANCA 29: Study Design
DAHANCA.dk
Charlotte Rotbøl Bøje, MD PhD
Comorbidity among 12.623
Head and Neck Cancer patients from the
DAHANCA database:
EXAMPLE 2
ESTRO Barcelona 2012
The CPR Registry
Danish CancerRegistry
The National Patient Registry
Diabetes Registry
Registry ofCauses of Death
DAHANCA
Materials and methods
Prescription registry
National Health Insurance Registry
99.4%
ESTRO Barcelona 2012
• Resulted in more than 1.000.000 diagnoses on the 12.623 patients.
• Diagnoses from 10 years prior to the HNSCC diagnosis were included
Materials and methods
ESTRO Barcelona 2012
Comorbidity and overall survival
CCI=0 50%CCI=1 45%CCI=2 39%CCI=3+ 33%
P<0.001
Crude HR:CCI=1: HR=1.16 (1.08 - 1.25)CCI=2: HR=1.34 (1.22 - 1.46)CCI=3: HR=1.63 (1.51 - 1.80)
N= 12,596
025
5075
100
Ove
rall
surv
ival
(%)
1237 799 549 410 291 221Severe comorbidity1196 854 604 473 366 286moderate comorbidity2110 1582 1199 902 723 587mild comorbidity8013 6266 4843 3943 3330 2831no comorbidity
Number at risk
0 1 2 3 4 5Time after treatment (years)
Comorbidity and SurvivalN=12.623
Presence of comorbidity is associated with increased risk of death,
highly statistically significant
ESTRO Barcelona 2012
Comorbidity and disease specific survival
Crude HR:CCI=1: HR=1.00 (0.9 - 1.1)CCI=2: HR=1.04 (0.93 - 1.17)CCI=3: HR=1.00 (0.89 - 1.13)
N= 12,623
025
5075
100
Dis
ease
spe
cific
sur
viva
l(%)
1232 719 498 370 269 206Severe comorbidity1183 754 515 395 311 245moderate comorbidity2105 1387 1023 783 643 520mild comorbidity7980 5442 4171 3422 2891 2458no comorbidity
Number at risk
0 1 2 3 4 5Time after treatment (years)
Comorbidity and Survival
No association between comorbidity and disease specific survival
HPV in Head and Neck Squamous Cell Carcinoma (HNSCC)
• Oropharynx cancer
• Increasing incidence
• Non‐keratinizing SCC
• p16 expression, p53wt
• Younger age/more fit
• Less smoking
• Less alcohol
• N+ (advanced disease)
• Improved prognosis Updated from Lassen Radiother Oncol 2010
Year
1977 1982 1987 1992 1997 2002 2007 2012
Num
ber o
f pat
ient
s
0
50
100
150
200
250
300
350
400
Oropharynx
Larynx
55%
37%42%
33%
70%
74%
p16‐pos*
*
Denmark 1977‐2013DAHANCA database
EXAMPLE 3
Impact of HPV/p16 on RT‐outcome by tumor siteOropharynx N=1002
Time after treatment (months)0 6 12 18 24 30 36 42 48 54 60
Loco
-regi
onal
con
trol (
%)
0
20
40
60
80
100
81%
55%
DAHANCA DatabaseOropharyngeal tumors
HPV status
HPVneg
HPVpos
p<0.0001
432 pts
569 pts570pts
HR: 0.32 [0.25‐0.42]
Loco‐regional controlHPV/p16 neg
p<0.0001
HPV/p16 pos
0
25
50
75
100
Dis
ease
-spe
cific
sur
viva
l (%
)
0 12 24 36 48 60Time after treatment (months)
HR: 0.19 [0.14‐0.26]
88%
54%
Disease‐specific survival
HPV/p16 neg
p<0.0001
HPV/p16 pos
0
25
50
75
100
Ove
rall
surv
ival
(%)
0 12 24 36 48 60Time after treatment (months)
HR: 0.24 [0.19‐0.32]
80%
50%
Overall survival
Time after treatment (months)0 6 12 18 24 30 36 42 48 54 60
Loco
-regi
onal
con
trol (
%)
0
20
40
60
80
100
57%51%
DAHANCA DatabaseNon-oropharyngeal tumors
HPV status
HPVneg
HPVpos
p=0.34
528 pts
77 pts
HR: 0.89 [0.60‐1.30]
p=0.53
Impact of HPV/p16 on RT‐outcome by tumor site
Time after treatment (months)0 6 12 18 24 30 36 42 48 54 60
Loco
-regi
onal
con
trol (
%)
0
20
40
60
80
100
81%
55%
DAHANCA DatabaseOropharyngeal tumors
HPV status
HPVneg
HPVpos
p<0.0001
432 pts
569 pts
Loco‐regional controlLoco‐regional control
Oropharynx N=1002 Non‐Oropharynx N=604
HR: 0.32 [0.25‐0.42]
N=1606 stage III‐IV
6 marts 2007EXAMPLE 4
Year
1968 1978 1988 1998 2008
'Wai
ting
time'
in d
ays
7
14
21
28
35
”Ventetid” for start på strålebehandling ved hoved-hals kræft i Danmark 1968-2008
Konklusion 6 marts 2007:
Hvad har vi lært?
Der er ingen data der støtter at ventetid er harmløs og uden forringelse af prognosen – derimod er der stort set entydige data som klart viser at selv kort ventetid indebærer en risiko for en markant reduktion af mulighederne for helbredelse
– det er derfor videnskabeligt bevist (hvor det er undersøgt) at ventetid medfører en forringelse for helbredelsesmulighederne og dermed en dårligere prognose
– formodentlig skal en væsentlig del af det efterslæb vi har i Danmark vedrørende resultater af cancerbehandling ses i lyset heraf – både i form af ventetider for nydiagnostiserede patienter og pga. manglende udnyttelse af de screenings-muligheder der foreligger
Ventetid (d
er er ingen
nedre græ
nse) medfør
er
dårligere t
umor kontrol
og deraf d
årligere
overlevelse
- Cancer er e
n akut sygd
om – og skal beh
andles
som sådan
Politiken juli 2007
10 august 2007
Pakkeforløb
Year
1968 1973 1978 1983 1988 1993 1998 2003 2008 2013
Med
ian
"wai
ting
time"
in d
ays
7
14
21
28
35
Median time from 1st contact with oncological centerto 1st day of radiotherapy/surgery
DAHANCA -databaseJakob Axel Nielsen
Bent Hansen
DAHANCA -databaseWHAT’S IMPORTANT
COLLECTION with a “Carrot” – not a stick
Obviously benefit for the persons who input data
Only collect what will be used (we miss it anyway)
Access for the users (they “own” the data)
Alert and control system
Feedback (control, verification, revision)
(remember: a data base is a “living” thing)
DAHANCA.dk
DAHANCA -databaseWHAT’S IMPORTANT (cont..)
Easy input and (research) access (to own data)
Webbased – accessible from all computers
Flexible and not to big
Quality
Connected with biobank (DCB?)
Good clinical data from protocolized studies with associated biobank material is worth more than gold)
DAHANCA.dk
DAHANCA -databaseWHAT’S IMPORTANT (cont..)
USE IT(e.g. annual question)
Ph.d. studies, publications…
DAHANCA.dk
>150 publicationer based on the database4 DMSc and 18 (6 ongoing) Ph.d studies.
Web site for extract of database
Meget begrænset mulighed for elektronisk opfølgning af data!
Paradox: Vi har lov til at kende data, - vi har de praktiske og tekniske muligheder for at fådata - men det må vi ikke elektronisk (og de er ikke længere på papir).
Dette er de kliniske (kræft) databasers største trussel –og den er tæt på at være fatal.
Danish Head and Neck Cancer Group
DAHANCA
Thank you