Regionernes nationale databasedag 2015
København – 8 april
”Lærende succeshistorie”:
Resultat af klassisk databasedrift og
interaktion mellem forskning og
kvalitetsmonitorering i DAHANCA
Jens Overgaard
Danish Cancer Society, Department of Experimental Clinical
Oncology, Aarhus University Hospital, Denmark.
[email protected]
DAHANCA.dk
Danish Head and Neck Cancer Group
The Danish National Head and Neck
Cancer Database
www.dahanca.dk
Jens Overgaard
Danish Cancer Society, Department of Experimental Clinical
Oncology, Aarhus University Hospital, Denmark.
[email protected]
Head and neck cancer
Nasal cavity
Pharynx
'
Oral cavity
Epiglottic
Larynx
Supraglottic
Nasopharynx
Oropharynx
Laryngopharynx
1500 pts per year
Esophagus
Subglottic
(4% of
all cancer
cases in Denmark)
Trachea
Glottic
Head and Neck Cancer:
Probably the most
diverse and
heterogeneous
cancer type in Europe
Major variations in:
Incidence
Epidemiology
Etiology
Treatment
Prognosis
Head and Neck
cancer is a
heterogeneous
disease
… and so is the
treatment
strategy
DAHANCA.dk
Danish Head and Neck Cancer Group
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THE
DANISH SOCIETY
t
n
e
i
t
pa
FOR HEAD & NECK ONCOLOGY
1976
DAHANCA.dk
Danish Head and Neck Cancer Group
National database
Registration and follow up of all H&N patients
National treatment strategy
National (evidence-based) guidelines
Clinical trials and studies
Quality assurance
Biobank
Translational research infrastructure
Research projects (Ph.D students)
Education and information (professionals – public)
International collaboration (all issues above)
DAHANCA.dk
DAHANCA –database
Includes: 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 1996 2000 -
.
1
3
>
2002 (1996)2005-
5
1
0
2
l
i
d
r
e
p
d
A
(thyroid cancer) clu
r
n
i
peDATYRCA
s
t
n
e
Unknown
primary
data base
i
t
a
p
000
DASPYTCA (salivary gland tumours)
Nat’l “official” Head & Neck base
(larynx, pharynx, oral cavity)
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
DAHANCA -database
TYPE OF DATABASE.
Pre 1991
“Homemade” flat FORTRAN base (on the
medical physicist’s computer).
DAHANCA.dk
DAHANCA -database
TYPE 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 -database
STRUKTUR
Onkol.
center
RH
Onkol.
center
Herlev
Overordnet
databaseansvarlig
(datatilsynet)
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.dk
DAHANCA -database
WHY HAVE A DATABASE?
Research
Protocols, pro- and retrospective studies
attracts youngsters
Quality control (“law”)
Health care management
“Political reasons”.
(knowledge is power)
DAHANCA.dk
DAHANCA -database
WHAT 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 -database
DATA 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 -database
DATA MUST BE USED (and verified) and GOOD
> 99% coverage of national patient cohort
(compared with Danish Cancer registry)
Problem:
Den ”ægte” vare
vs. ”industrielt
genbrug”
Problem:
Vi kan ikke
”tilbagerette”
forkerte data
(så de går igen)
DAHANCA.dk
DAHANCA -database
WHAT DO WE USE IT FOR?
A FEW EXAMPLES:
EXAMPLE 1
DAHANCA.dk
The DAHANCA strategy:
progression through consecutive clinical trials
DAHANCA Database
Stage 3-4 Larynx and Pharynx
Loco-regional control (%)
100
80
EXAM
PLE
1
60
40
27% 5 fx/wk
20
Standard 1985
0
0
6
12
18
24
30
36
42
48
54
60
Time after treatment (months)
DAHANCA.dk
Dahanca 24
Dahanca 13
Dahanca 6
Dahanca 7
Reduced
RT time
Dahanca 30
Better
diagnosis
and
imaging
Comorbidity
Basic
“virtues”
Waiting
time etc.
Hypoxic
modification
Dahanca 10
of RT
Dahanca 5
Primary
RT of HN
Cancer
Dahanca 29
Dahanca 16
Dahanca 27
Changed
RT-Surg
balance
Dahanca 1
Smaller
RTvolume
Dahanca 11
IMRT
Accl fx
Dahanca 2
Dahanca
study
larger RT
dose
Dahanca 9
Hyperfx
Dahanca 28
Biological
modifiers
Neoadjuvant
ChemoRT
Concommitant
Chemo-RT
Anti-EGFr
Dahanca 15
Dahanca 19
Dahanca 14
Dahanca 18
DAHANCA.dk
The DAHANCA strategy:
progression through consecutive clinical trials
DAHANCA Database
Stage 3-4 Larynx and Pharynx
Loco-regional control (%)
100
80
60
44% 5 fx/wk + NIM
40
27%
20
Benefit of Hypoxic
5 fx/wk
Modification
Standard 1985
0
0
6
12
18
24
30
36
42
48
54
60
Time after treatment (months)
DAHANCA.dk
The DAHANCA strategy:
progression through consecutive clinical trials
DAHANCA Database
Stage 3-4 Larynx and Pharynx
Loco-regional control (%)
100
80
62% 6 fx/wk + NIM
60
Benefit of
Accelerated Fract.
44% 5 fx/wk + NIM
40
27%
20
Benefit of Hypoxic
5 fx/wk
Modification
Standard 1985
0
0
6
12
18
24
30
36
42
48
54
60
Time after treatment (months)
DAHANCA.dk
The DAHANCA strategy:
progression through consecutive clinical trials
DAHANCA Database
Stage 3-4 Larynx and Pharynx
100
Loco-regional control (%)
Standard 2007
Benefit
of Chemo+ NIM
+ cis-P
83% 6 fx/wk
80
Radiotherapy
62% 6 fx/wk + NIM
60
Benefit of
Accelerated Fract.
44% 5 fx/wk + NIM
40
27%
20
Benefit of Hypoxic
5 fx/wk
Modification
Standard 1985
0
0
6
12
18
24
30
36
42
48
54
60
Time after treatment (months)
DAHANCA.dk
HPV/p16 negative
Stage III - IV (T1-4,
N0-3)
Larynx/oropharynx/
hypopharynx
Stratification:
RANDOMIZATION
1219 ROG-HNCG/DAHANCA 29: Study Design
Accl RT (70 Gy, 6 fx/wk) + cddp (40 mg/m2
weekly x 5 or 100 mg/m2 x 2)
+ placebo (daily)
Accl RT (70 Gy, 6 fx/wk) + cddp (40 mg/m2
weekly x 5 or 100 mg/m2 x 2)
+ Nimorazole (1.2 g/m2 daily)
•Institution
•Localization
•T-stage
•N-stage
•WHO-PS
•Hypoxic gene-profile
DAHANCA.dk
EXAM
PLE
2
Comorbidity among 12.623
Head and Neck Cancer patients from the DAHANCA database: Charlotte Rotbøl Bøje, MD PhD
Materials and methods
Danish Cancer
99.4%
DAHANCA
Registry of
Causes of Death
Registry
The CPR Registry

National Health
Insurance Registry
The National Patient
Registry
Prescription registry
ESTRO Barcelona 2012
Diabetes Registry
Materials and methods
• Resulted in more than 1.000.000 diagnoses on the 12.623 patients.
• Diagnoses from 10 years prior to the HNSCC diagnosis were included
ESTRO Barcelona 2012
0
Overall survival (%)
25
50
75
100
Comorbidity and overall survival
Comorbidity and Survival
N= 12,596
N=12.623
CCI=0 50%
CCI=1 45%
CCI=2 39%
CCI=3+ 33%
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)
0
P<0.001
1
2
3
4
Time after treatment (years)
5
Presence
of comorbidity is associated with
Number at risk
increased risk of death,
highly statistically significant
no
mild
moderate
Severe
ESTRO Barcelona 2012
comorbidity 8013
comorbidity 2110
comorbidity 1196
comorbidity 1237
6266
1582
854
799
4843
1199
604
549
3943
902
473
410
3330
723
366
291
2831
587
286
221
Disease specific survival(%)
0
25
50
75
100
Comorbidity and disease specific survival
Comorbidity and Survival
N= 12,623
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)
0
1
2
3
4
Time after treatment (years)
5
Number at risk
No association between
comorbidity and disease specific survival
no comorbidity 7980
mild comorbidity 2105
moderate comorbidity 1183
Severe comorbidity 1232
ESTRO Barcelona 2012
5442
1387
754
719
4171
1023
515
498
3422
783
395
370
2891
643
311
269
2458
520
245
206
HPV in Head and Neck Squamous Cell Carcinoma (HNSCC)
• Oropharynx cancer
• Increasing incidence
Denmark 1977‐2013
DAHANCA database
400
74%*
EXAM
• Non‐keratinizing SCC
PLE
3
• p16 expression, p53wt
•
•
•
•
•
Younger age/more fit
Less smoking
Less alcohol
N+ (advanced disease)
Improved prognosis
Number of patients
350
Larynx
300
250
200
70%
55%
150
Oropharynx
33%
100
42%
50
*p16‐pos
37%
0
1977
1982
1987
1992
1997
2002
2007
2012
Year
Updated from Lassen Radiother Oncol 2010
Impact of HPV/p16 on RT‐outcome by tumor site
Disease‐specific survival
Oropharynx N=1002
HPV/p16 pos
DAHANCA Database
Loco‐regional control
Oropharyngeal tumors
HPV status
HPVpos
80
81%
569
pts
570pts
88%
75
HPV/p16 neg
p<0.0001
25
HR: 0.19 [0.14‐0.26]
0
60
12
24
36
48
60
Time after treatment (months)
55%
432 pts
54%
50
0
Overall survival
HPVneg
100
HPV/p16 pos
40
p<0.0001
20
HR: 0.32 [0.25‐0.42]
0
0
6
12
18
24
30
36
42
48
54
60
Overall survival (%)
Loco-regional control (%)
100
Disease-specific survival (%)
100
80%
75
HPV/p16 neg
50%
50
p<0.0001
25
Time after treatment (months)
0
HR: 0.24 [0.19‐0.32]
0
12
24
36
48
Time after treatment (months)
60
Impact of HPV/p16 on RT‐outcome by tumor site
N=1606 stage III‐IV
Loco‐regional control
DAHANCA Database
Loco‐regional control
DAHANCA Database
Oropharynx N=1002
Oropharyngeal tumors
HPV status
100
HPVpos
80
81%
569 pts
60
55%
432 pts
HPVneg
40
p<0.0001
20
0
6
12
18
24
30
36
80
HPVpos
77 pts
60
528 pts
57%
51%
HPVneg
40
p=0.34
p=0.53
20
HR: 0.89 [0.60‐1.30]
HR: 0.32 [0.25‐0.42]
0
Loco-regional control (%)
Loco-regional control (%)
100
Non-oropharyngeal tumors
Non‐Oropharynx N=604
HPV status
0
42
48
54
Time after treatment (months)
60
0
6
12
18
24
30
36
42
48
54
Time after treatment (months)
60
6 marts 2007
EXAM
PLE
4
”Ventetid” for start på strålebehandling ved hoved-hals
kræft i Danmark 1968-2008
35
'Waiting time' in days
28
21
14
7
1968
1978
1988
Year
1998
2008
Konklusion 6 marts 2007:
Hvad har vi lært?
r
e
Der er ingen data der støtter at ventetid er harmløs og
uden
r
ø
f
d
e
m entydige
forringelse af prognosen – derimod er der stort)set
e
s
n
e risiko for
data som klart viser at selv kort ventetid
indebærer
en
r
æ
r
e
g
g
i
l
e
r
r
å
en markant reduktion af mulighederne
for
helbredelse
d
d
e
n
f
a
s
n
r
e
l
e
e
d
g
d
n
n
i
a
g
h
o
r
e
e
l
– det er derfor
videnskabeligt
at
b
o bevist (hvor det keralundersøgt)
r
r
e
t
d
n
(
o
s
k
d
ventetid
medfører
en
forringelse
for
helbredelsesmulighederne
og
i
g
r
t
o
o
e
–
t
m
u
en
t
m
en
dårligere
prognose
o
Vdermed
e
d
r
e
yg
g
s
i
l
r
t
u
e
s
k
d–å formodentlig
l
a
e
v
nen væsentlig del af det efterslæb vi har i
skal
e
e
l
r
r
e
e
ov
r
Danmark
vedrørende
resultater af cancerbehandling ses i lyset
e
c
n
heraf
inform af ventetider for nydiagnostiserede
- Ca– både
a
d
åog pga. manglende udnyttelse af de screeningss
patienter
m
so
muligheder der foreligger
Politiken juli 2007
10 august 2007
Pakkeforløb
DAHANCA -database
Median "waiting time" in days
35
Bent
Hansen
Jakob
Axel
Nielsen
28
Median time
from 1st contact with oncological center
to 1st day of radiotherapy/surgery
21
14
7
1968
1973
1978
1983
1988
1993
Year
1998
2003
2008
2013
DAHANCA -database
WHAT’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 -database
WHAT’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 -database
WHAT’S IMPORTANT (cont..)
USE IT
(e.g. annual question)
Ph.d. studies, publications…
>150 publicationer based on the database
4 DMSc and 18 (6 ongoing) Ph.d studies.
DAHANCA.dk
Meget begrænset mulighed
for elektronisk opfølgning af
data!
Web site for extract of database
Paradox: Vi har lov til at kende
data, - vi har de praktiske og
tekniske muligheder for at få
data - 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.
Thank you
Danish Head and Neck Cancer Group
DAHANCA