1. INCIDENCE AND SURVIVAL OF CENTRAL NERVOUS SYSTEM MALIGNANCIES ACCORDING TO HISTOLOGICAL SUBTYPES. RESULTS OF A POPULATION-BASED STUDY IN GIRONA (SPAIN)
Marcos-Gragera R1; Vilardell L1; Perez-Bueno F2; Osca G1; Cano A1; Fuentes-Raspall R3
1 Girona Cancer Registry, Oncology Coordination Plan. Department of Health. Autonomous Government of Catalunya. Catalan Institute of Oncology, Girona, Spain.
2Pathology Service, Hospital Universitari de Girona “Dr.Josep Trueta”, Girona, Spain
3Radiation Oncology Service, Catalan Isntitute of Oncology, Girona, Spain.
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2. INTRODUCTION
Primary malignant brain tumors represent a heterogenous group of diseases.
Risk Factors:
Hereditary syndromes
Tuberous sclerosis, neurofibromatosis, nevoid basal cell carcinoma syndrome, adenomatous polyposis syndromes, Li-Fraumeni cancer family syndrome
Family history of brain tumours
Ionizing radiation
Epidemiological data of Central nervous systems (CNS) malignancies by morphological groups in Europe are not frequently reported.

5. Fuente: Atlas Municipal de Mortalidad por Cáncer en España. 1989-1998

6. Primary malignant brain tumors:survival
Survival for these malignancies is generally low;
During last few years, new developments in the management of this tumours using different combinations of surgery, radiation therapy and chemotherapy have been translated into better outcomes.

7. Multicenter phase 3 trial To compare: Radiotherapy alone vs
Radiotherapy + Temozolomide (oral alkylating agent)
Treatment
5-y OS
Radiotherapy
1.9%
Combined
9.8%

8. OBJECTIVE
Estimate the population-based incidence and survival of primary brain tumours by
Histological subtypes
sex
age at diagnosis
Treatment (Temozolomide) in patients diagnosed by Glioblastoma.

9. Participants (period & person-years) Source: Girona Cancer Registry
Population (2007):
Period
1994
2007
Person-years
Inclusion
(ICD10)
C71 (Brain)
C72 (spinal cord, cranial nerves and other parts of the CNS)
Exclusion
Meningeal, soft tissue and spinal cord tumours were excluded, also primary CNS lymphoma

10. METHODS (2)
All pathological records were revised in order to classify them according to the 2007 WHO Classification.

11. METHODS (3)
Incidence
Incidence rates were calculated as the average annual number of cases per person-years.
Age-standardised rates (ASRs) were calculated by the direct method using the world standard population.
Incidence time-trends
Overall incidence trends were evaluated using Poisson models adjusted by age, sex and the presence of change-points in the trends was assessed with a Joinpoint analysis.
Survival
Follow-up until
Observed survival was calculated using Kaplan-Meier method and relative survival by Hakulinen method. DCO cases were excluded for survival analysis
RETOCAR AMB LES DADES NOSTRES 11

12. Primary malignant brain tumors, Girona (Spain) 1994-2007
Primary malignant brain tumors, Girona (Spain) Data quality indicators
Death certificate only (DCO)
4.9%
Microscopical verification (MV)
61.3%
Completeness
98.7%
Number of cases
658
RESULTS

13. Age-specific incidence rates (males and female) of primary brain tumours
Mean
(years)
Median
Rank ♂
57.71 63
0-93 ♀
59.02 64
1-92
♂ ♀
58.3
RESULTS

14. Incidence by hitological subtype and sex according to the WHO classification. Girona (Spain)
Histological subtype
Both sexes N % CR
ASRw
CI 95%
Astrocytic tumours
333
50.84
4.18
3.19
(2.81; 3.57)
Diffuse astrocytoma (WHO grade II) 87
13.28
1.09
0.98
(0.74; 1.21)
Anaplastic astrocytoma (WHO grade III) 31
4.73
0.39
0.30
(0.18; 0.41)
Glioblastoma (WHO grade IV)
215
32.82
2.70
1.92
(1.64; 2.20)
Oligodendroglial & oligoastrocytics 22
3.36
0.28
0.22
(0.13; 0.31)
Ependymal tumors 18
2.75
0.23
0.26
(0.12; 0.40)
Embryonal tumors 25
3.82
0.31
0.44
(0.25; 0.63)
Choroid plexus tumors 1
0.15 -
Without histological confirmation
256
39.08
3.21
1.58
(1.36; 1.80)
TOTAL
658
100
8.21
5.72
(5.21; 6.23)
RESULTS
Men: 6.53 (95% CI: 5.77;7.30) Women: 4.96 (95% CI: 4.28;5.64). Sex ratio: 1.32

15. Temporal incidence in malignant neuroepithelial tumors
Temporal incidence in malignant neuroepithelial tumors. Trends calculated using joinpoint analysis, Girona (Spain)
PCA: (CI95% ; 1.72)
RESULTS

16. Temporal incidence trends in glioblastoma tumors
Temporal incidence trends in glioblastoma tumors. Trends calculated using joinpoint analysis, Girona (Spain)
PCA: 0.99 (CI 95% ; 5.53)
RESULTS

17. Kaplan-Meier estimated of overall observed survival curves for patients diagnosed with a primary brain and central nervous system tumours, Girona (Spain)
All tumours
5-y OS
Median: 0.4 yr
15.5
5-y RS
16.3
No. at Risk
658
218
151
127 96 81

18. Kaplan-Meier estimated of overall observed survival curves for patients diagnosed with a primary brain and central nervous system tumours by sex. Girona (Spain)
Sig.
Log Rank (Mantel-Cox)
SEX
5-y OS
5-y RS
Men
16.1
17.2
Women
14.9
15.3
Men
Women
No. At Risc
Men
364
125 84 71 51 45
Woman
294 93 67 56 36

19. Kaplan-Meier survival estimates of overall survival by histological groups according to WHO classification groups. Girona (Spain)
Sig.
Log Rank (Mantel-Cox) < 0.001
Histological type
5-y OS
5-y RS
Astrocytic tumours
15.5
15.9
Oligodendroglial & oligoastrocytics
54.5
55.3
Ependymal tumours
48.5
49.4
Embryonal tumours
36.0
36.1
Without histological confirmation
7.7
8.7
Faltaria afegir una taula amb les medianes de supervivencia

20. Kaplan-Meier estimates of overall survival of astrocytic tumours according to WHO grades (Girona, Spain, )
Glioblastoma
Anaplastic astrocytoma
Diffuse astrocytoma
Years
Sig.
Log Rank (Mantel-Cox) < 0.001
Histological type
5-y OS
5-y RS
Diffuse astrocytoma
(WHO grade II)
42.5
43.4
Anaplastic astrocytoma
(WHO grade III)
4.8
5.0
Glioblastoma
(WHO grade IV)
5.8
6.1
No. at Risk
Diffuse astrocytoma 87 54 41 39 33 31
Anaplastic astrocytoma 14 6 4 2 1
Glioblastoma
215 60 29 20 12 9

21. Most Common Brain and CNS Tumors by Age
Age (years)
Most Common Histology
Second Most Common Histology
< 15
Diffuse astrocytoma
CNS without histological confirmation
15-44
Glioblastoma
45-64
65-74
> 75
Gliomatosis cerebri

22. Kaplan-Meier estimates of overall survival for patients diagnosed of a primary brain and central nervous system tumours by age groups. Girona (Spain)
< 15 years
15-44 years
65-74 years
45-64 years
>75 years
Sig.
Log Rank (Mantel-Cox) <0.001
Age group
5-y OS
5-y RS
<15 years
43.9
15-44 years
45.8
46.1
45-64 years
15.3
15.7
65-74 years
2.9
3.6
> 75 years
3.3
4.6
No. at Risk
<15 31 11 8 3
15-44
113 44 17 2
45-64
196 20 9
65-74
168 4
>75
150

23. Kaplan-Meier estimated of overall observed survival curves for patients diagnosed of a primary brain and central nervous system tumours by period of diagnosis. Girona (Spain)
Sig.
Log Rank (Mantel-Cox)
Period
5-y OS
5-y RS
10.9
11.5
14.9
16.1
Crec que aquesta gràfica no es correspon amb el total de casos
No. at Risk
441
145 97 79 68 62
217 73 54 48 28 19

24. Kaplan-Meier estimates of overall survival by treatment group
Kaplan-Meier estimates of overall survival by treatment group. Glioblastoma.
Treatment
5-y OS
5-y RS
Combined
(n=42)
7.1
7.4
Radiotherapy
(n=146)
2.6
2.7

25. NB: Patients older than 15 yrs
Hazard ratios (HRs) and 95% confidence intervals (CIs) for Glioblastomas (ICD-O3: 9440/3).
Cases, n HR
CI (95%)
Sex
Male
103 1
Female 85
1.086
(0.81 – 1.45)
Age (years)
15-44 20
45-64 77
2.90
(1.67 – 5.02)
65-74 71
2.71
(1.55 – 4.72)
>75 19
3.58
(1.80 – 7.11)
Period
113 75
0.83
(0.61 – 1.11)
Temozolomide Si 42 No
146
2.29
(1.60 – 3.27)
NB: Patients older than 15 yrs

26. Astrocytic tumours constituted over 50% of CNS tumours.
MAIN RESULTS
2007 WHO classification characterize homogeneous subgroups in brain tumours.
Astrocytic tumours constituted over 50% of CNS tumours.
Glioblastoma (WHO grade IV) constituted over 30% of malignant CNS tumours
Better diagnosis imaging is most probably the cause of an increasing number of patients without histological verification.

27. MAIN RESULTS
Survival of CNS tumours patients is strongly depenent on histological typing and grading.
Survival for ependymal and oligodendroglial tumours was more favourable in comparison to other tumours types.
Glioblastoma and anaplastic astrocytoma had worst survival.
Oligodendroglial & oligoastrocytics had relative good survival

28. MAIN RESULTS
Slightly better survival for men than women.
Age is a predictive factor.
The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a statiscally significant survival

29. Thank you
Gracias
Gràcies
Merci
Mulţumiri
Grazie
Obrigado

30. Kaplan-Meier estimates of overall survival by age groups (children vs adults). Girona (Spain)
Sig.
Log Rank (Mantel-Cox) < 0001
Age group
5-y OS
5-y RS
≤ 14 years
43.9
46.9
> 14 years
14.6
15.4
Afegir la supervivencia observada, relativa als 5 anys i les medianes de supervivencia segons els grups d’edat.