Download The main purposes of childhood cancer registries are:

Improving the treatment of
children with cancer through
registry-driven research
Childhood Cancer Registries:
a “good” model
Franco Locatelli, MD, PhD
Department of Pediatric Hematology-Oncology,
IRCCS, Bambino Gesù Children’s Hospital, Roma
University of Pavia, Italy
[email protected]
Childhood Cancer is a rare disease…
Number
New Cases of Cancer in the U.S. in 2003
140000
120000
100000
80000
60000
40000
20000
0
130,000
125,000
105,000
12,500
Breast
Lung
Prostate
Cancer Type
Childhood
Cancers
Childhood cancers are significantly different
from adult cancers
PEDIATRIC ONCOLOGY
Causes of Death Children
congenital anomalies
cancer
other
accidents
cerebral palsy
suicide
pneumonia
meningitis
Heart disease
HIV
homicide
Five-year relative survival rates for selected
primary cancers according to year of diagnosis
(1975–2006) among patients younger than 20 years
Pui, C.-H. et al. Nat. Rev. Clin. Oncol. 2011;28;8:540-549
Today, in 2016,
a 20-year old young adult
in 800
is a subject cured
by a cancer suffered in childhood
PEDIATRIC ONCOLOGY
Important Steps in the History of
Childhood Cancer Research
 Multi-institution Cooperation
 Leukemia Chemotherapy refinements
 Conduction of Clinical Trials
 Treatment of Solid Tumors
 Multi-Disciplinary Team Care
 Stratification of patients in risk groups
 Use of information deriving from registries
The main purposes of childhood cancer
registries are:
• To monitor incidence, prevalence and survival
trends of cancer over time in different
geographical areas and social classes.
• To assess, by providing comparative data, the
quality and results of the diagnosis and
treatment of cancer.
• To investigate the differences in incidence,
survival and access to treatments.
• To evaluate the long-term outcome, through
monitoring of late sequels of cancer treatment.
• To support research into the causes of cancer.
Tumor Registries:
Worldwide distribution
526 Registries
Tumor Registries:
distribution and coverage in Europe
Automated Childhood Cancer Info.System (ACCIS)
225 Registries / 40 Countries
© European Union / ENCR, 2014 · JRC 90053
Eva Steliarova-Foucher et al. Lancet 2004
• To monitor incidence, prevalence
and survival trends of cancer over
the course of time in different
geographical areas and social
classes.
AIEOP: integrated framework
55 AIEOP Centers
Protocol’s
Follow-up
Mod. 1.01 Registry
52.406 pts
Unique
Patient
Number
TCSE
Registry
Anagraphic
Diagnosis
9.734 pts
11.633 TCSEs
Follow-up
Off-Therapy
Registry
Total pts: 19.820
SmartLab
Biologic
data base
ALL
Pts 11.591
AML
1525
SE
301
LH
2544
ID
2467
SM
140
AIEOP protocols
Clinical Data
Warehouse
DBA
236
RTB
59
IS
957
NBL
AIRTUM Registries (2003-2008, 0-19 years)
360.000 new cases/year in Italy (all ages)
269 new cases/year/million
in Italy, about 800 cases
(15-19 years)
164 new cases/year/million
in Italy, about 1.500 cases
(0-14 years)
AIRTUM Registries (2003-2008, 0-19 years)
Age-standardized rates (x 106)
by malignant cancer type and gender.
0-14 yrs
15-19 yrs
Tumor Registries (1978-2006, 0-19 years)
Age-standardized rates (x 106) in Europe, Italy and USA for
malignant cancer in children and adolescents.
USA, 0-19 yrs
Europe, 0-14 yrs
Kaatsch P et al, Eur J Cancer 42,1961–1971, 2006.
Smith MA et al, J Clin Oncol 28:2625-2634, 2010
Italy, 0-14 yrs
I tumori in Italia – Rapporto AIRTUM 2008 – Tumori infantili
Epidemiol Prev, 32 (2) suppl 2; 1-111, 2008.
• To assess, by providing comparative
data, the quality and results of the
diagnosis and treatment of cancer.
• To investigate the differences in
incidence, survival and access to
treatments.
There are still survival disparities between
Countries and European regions
AIEOP Mod.1.01 Registry
Cases treated with AIEOP protocols by age
Resident in Italy, period 2008-2010
100%
Non AIEOP Centers
92 %
(AIOM 192, SIE 224, ecc)
80%
60%
AIEOP Centers
AIEOP protocols
65 %
(0-14 yrs: 72%, 15-19 yrs: 63%)
40%
25 %
20%
15 %
0%
<15
1%
15-19
20-39
Age (Years)
AIEOP Mod.1.01 Registry
Survival by protocol
11144 cases (0-14 yrs: 10558, 15-19 yrs: 586) period 1989-1998
AIEOP
AIEOP
0-14 yrs
Non AIEOP
protocols
p = 0.000
Non AIEOP
protocols
p = 0.000
AIEOP
Overall
15-19 yrs
p = 0.003
Non AIEOP
protocols
Outcome of adolescents with cancer is inferior to that of children for many cancers
Secondary Malignant Neoplasms:
The snake in the bathtub
Risk of subsequent malignant neoplasms by radiation
dose for breast cancer.
Why we need innovative therapies for Pediatric Tumors?
Because the optimisation of
present treatments has reached its limits
Dose-intense multimodality
Multiagent approaches
Improved outcome for
childhood cancers
Unsolved
Issues
How to treat children with refractory
and relapsed malignancies?
Target Therapies
How to manage toxicities
related to intense chemo/radiation therapy?
CAR T Lymphocytes Targeting CD19 as a valid
clinical option for ALL relapsed patients
93% CR rate for relapsed/refractory ALL after CAR T cells CTL019
>200 patients with CLL, ALL, NHL, MM have received CTL019
• 59 r/r Pediatric ALL patients
–
–
–
–
–
55 in CR at 1 mo (93%) median f/u 12 mo
6 went to subsequent transplant, 1 to DLI
6 mo RFS: 76%
12 mo RFS: 55%
18 patients in remission beyond 1 year,
13 without further therapy
– 20 relapses, 7 CD19+ and 13 CD19-
• CNS
– 98% of pts have CTL019 detectable in CSF
– 0 CNS relapses
– 4 pts CNS2 on D-1, all CNS1 at D28
CAR T CELL THERAPY TRIALS FOR LEUKEMIA AND/OR LYMPHOMA:
WORLD DISTRIBUTION
Novartis (2/3)
Novartis
anti-CD19 CAR T cells
Novartis (1/2)
anti-CD19 CAR T cells
anti-CD19 CAR T cells
anti-CD19 CAR T cells
anti-CD20 CAR T cells
anti-CD7 CAR-pNK cells
anti-CD30 CAR T cells
anti-CD19 CAR T cells (21)
h anti-CD19 CAR T cells (1)
anti-CD22 CAR T cells (3)
anti-CD30 CAR T cells (2)
Novartis 1 (in 14 centers)
JUNO Therapeutics 2 (in 15 centers)
Kite Pharma 3 (in 20 centers)
anti-CD19 CAR T cells
Novartis
Take-home messages
 Treatment of childhood cancers represents one of the
greatest success of modern medicine.
 Registry-driven studies have significantly contributed to the
achievement of this result.
 Continuous refinements of therapies and risk-stratification
can further optimize long-term outcome.
 However, cancer survivors are subjects to be followed for
years after treatment discontinuation.
 EU efforts should be concentrated to the elimination of
outcome disparities, also through the support of the
activities of cancer registries in childhood.
 EU must invest on innovative, targeted therapies, developed
not only by industry, but also by academic institutions.