1. Improved survival in primary central nervous system lymphoma up to age 70: a population-based study on incidence, primary treatment and survival in the Netherlands,
Matthijs van der Meulen, A.G. Dinmohamed,
O. Visser, J.K. Doorduijn, J.E.C. Bromberg
Erasmus Medical Centre, the Netherlands
Netherlands comprehensive cancer organisation
June 24, 2017

2. Disclosures
No disclosures

3. Primary central nervous system lymphoma
Aggressive form of non-Hodgkin lymphoma
Brain, leptomeninges, eyes and/or spinal cord
3% of all brain tumors
Focal deficits, neuropsychiatric symptoms and headache
Mostly diffuse large B-cell lymphoma
Clinical presentation concerns mostly focal neurological deficits, neuropsychiatric symptoms and headache and, in contrast to glioma’s , in only a minority of the cases the patient will present with a seizure
MRI shows mostly a single or multiple space occupying lesions with homogenous contrast enhancement.
Batchelor TT, 2006; Colocci, 2004
Central Brain Tumor Registry of the US

4. Rationale
Findings from the few available prospective studies demonstrated improved outcome in PCNSL over the past decades1-4
However, the results from such studies may not reflect daily practice
Population-based studies are useful to complement prospective intervention studies by addressing a non-selected group of patients
May not reflect actual daily practice because of stringent inclusion criteria in prospective trials
A non selected group of patients from a specific geographic area
1Ferreri AJ et al. Lancet. 374: (2009); 2Thiel E et al. Lancet Oncol. 11: (2010); 3Omuro A et al. Lancet Haematol. 2: (2015); 4Fritsch K et al. Leukemia. Epub ahead of print (2016).

5. Rationale
Large representative population-based studies in PCNSL are scarce
Comprehensive information on incidence, treatment and survival at the population level are virtually lacking
We assessed trends in incidence, primary treatment and survival among adult PCNSL patients diagnosed in the Netherlands from 1989 to 2015 reported to the nationwide Netherlands Cancer Registry (NCR)

6. The Netherlands Cancer Registry
We selected all adult PCNSL patients diagnosed between from the NCR with survival follow-up through February 1, 2016
The NCR includes all newly diagnosed malignancies since 1989
all pathology laboratories in the Netherlands (PALGA)
Nationwide Registry of Hospital Discharges (LMR/LBZ)
Coverage >95%
The NCR contains
Dates of birth, sex and vital statistics
Diagnosis, stage, morphology and primary treatment
The primary central nervous system lymphoma’s has to be confirmed by pathology or cytology
NCR, founded in has access to the Nationwide Network of Histopathology and Cytopathology and the National Registry of Hospital Discharges. Earlier research showed an overall coverage of >95%
The registry contains age, sex, diagnosis, stage and primary treatment. Unfortunately details about the treatment administered are only available from 2014 onwards

7. Statistical methods
Patients divided into 4 periods ( , , and ) and 3 age groups (18-60, and >70 years)
Primary treatment was defined as: no anti-neoplastic therapy, chemo-therapy (CT), radiotherapy (RT), CT+RT, and other/unknown therapy
Relative survival as a measure of disease-specific survival
Patient survival corrected for the expected survival of a comparable group from the general population (i.e. sex, age and period matched)

8. Results Total Number of patients 1,673 Men 885 Women 788 Median age
65 years (19-87)

9. Age-specific incidence of PCNSL
Males and females together
Incidence per 100,000
Over the past 28 years there is a increasing incidence of PCNSL among patients over 60 years old only
The increase among women is slightly less
The incidence of PCNSL steadily increased for patients >60 years
In part due to improved diagnostic practices among the elderly over time, however the incidenc of glioma’s and lymphoma’s elsewhere in the body is not increasing a the speed. Changes in etiologic factors cannot be completely ruled out
So, the increase is not completely understood, bit is a clear trend of over a long period
Year of diagnosis

10. Primary therapy of PCNSL
% of patients
Among the youngest group
More patients received treatment
the administration of Chemoradiotherapy and chemotherpay has increased the most
Among elderly (over 60 years old)
More patienst were treated with chemotherapy, instead of radiotherapy
The question is, whether these changes in primary treatment has influenced their prognosis
Age and period at diagnosis

11. Relative survival of PCNSL
18-60 years
>70 years
% relative survival
Years after diagnosis
61-70 years
The 1-, 3 and 5 year relative survival has increased significantly over the past decades
The blue line is the first period
The pink line is the last period of our cohort
Unfortunately the prognosis of patients over 70 years old did not improve at all
Years after diagnosis

12. Relative excess risk of mortality (EMR)
Model without therapy
Covariate
EMR
95% CI p
Period of diagnosis 1
Reference
1.10
0.269
0.73
<0.001
0.59
Sex
Male
Female
1.05
0.451
Age at diagnosis
18-60
61-70
1.67
>70
3.11
Primary treatment
No anti-neoplastic therapy
CT+RT
CT alone
RT alone
Other/ unknown therapy
Model with therapy
EMR
95% CI p 1
Reference
1.18
0.076
1.04
0.650
0.86
0.100
0.98
0.774
1.26
<0.003
1.50
<0.001
0.08
0.14
0.22
0.28

13. Summary and conclusions
Incidence of PCNSL steadily increased for patients >60 years
Survival improved over the past decades for patients up to age 70
↑ chemoradiotherapy for patients age 18-60
↑ chemotherapy alone for patients age 61-70
Use of chemotherapy alone gradually ↑ for patients >70 years
Their survival remained poor and essentially unchanged
Specific trials for >70 years are needed to improve outcomes
Incidence
However, changes in etiologic factors cannot be completely ruled out
Although the use of chemotherapy alone is gradually increasing among patients above age 70, their survival remained poor and essentially unchanged over the past decades. Therefore, there is a need to design specific trials for patients above age 70 in order to improve their survival.

14. Acknowledgements
Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands
All data managers of the NCR X

18. Patient characteristics at diagnosis
Calendar period of diagnosis
Total
No.
(%)
Total No. of patients
300
316
416
641
1,673
Sex
Male
155
(52)
177
(54)
217
(53)
336
885
Female
145
(48)
139
(46)
199
(47)
305
788
Age, years
Median (range)
62 (20-87)
65 (19-87)
64 (25-87)
66 (21-87)
18-60
136
(45)
108
(34)
153
(37)
188
(29)
585
(35)
61-70 83
(28)
112
130
(31)
242
(38)
567
>70 81
(27) 96
(30)
133
(32)
211
(33)
521

19. Relative excess risk of mortality (EMR)
Model without therapy
Covariate
EMR
95% CI P
Period of diagnosis 1
Reference
1.10
0.269
0.73
<0.001
0.59
Sex
Male
Female
1.05
0.451
Age at diagnosis, years
18-60
61-70
1.67
>70
3.11
Primary therapy
No anti-neoplastic therapy
CT+RT
CT alone
RT alone
Other/unknown therapy
Model with therapy
EMRa
95% CI P
1.18
0.076
1.04
0.650
0.86
0.100 1
Reference
0.98
0.774
1.26
0.003
1.50
<0.001
0.08
0.14
0.22
0.28
Relative excess risk of mortality during first five years after diagnosis