Page 283 - 2021_02-Haematologica-web

Letters to the Editor
Primary therapy and survival in patients over 70 years old with primary central nervous system lymphoma: a contemporary, nationwide, population-based study in the Netherlands
Primary central nervous system lymphoma (PCNSL) is an uncommon, but aggressive non-Hodgkin lymphoma confined to the brain, leptomeninges, spinal cord, and eyes. Its incidence has increased substantially over the past decades among over 60-year-olds.1 The median age at diagnosis is around 65 years, and approximately one- third of newly diagnosed patients are >70 years.1 Nevertheless, elderly PCNSL patients, especially those over the age of 70 years, are frequently excluded from or under-represented in clinical trials due to concomitant comorbidities, poor performance status, or concerns regarding treatment-related sequelae.2,3 Prospective stud- ies specifically designed for elderly PCNSL patients are scarce.4-6 Furthermore, the few available, somewhat outdated series mostly included relatively small numbers of patients (range, 10-107). These studies congruently showed that the prognosis of elderly patients remained poor and unchanged over the past decades, with overall survival (OS) ranging between 14-37 months. Collectively, apart from omitting consolidation radiother- apy after chemotherapy, the optimal treatment for elder- ly PCNSL patients is ill-defined.1,6,7
Population-based studies can complement prospective trials, especially in settings where data from prospective trials are scarce. At present, contemporary population- based studies with detailed data regarding primary thera- py specifically among >70-year old PCNSL patients to inform clinical practice are lacking. Therefore, in this con- temporary, nationwide, population-based study, we assessed primary therapy and OS among >70 year old PCNSL patients diagnosed in the Netherlands.
Established in 1989, the nationwide Netherlands Cancer Registry (NCR) has an overall coverage of >95% of all malignancies in the Netherlands.8 We identified all >70-year old PCNSL patients diagnosed confirmed with cytology, histology, and/or flow cytometry between January 1st 2014 and December 31st 2017 from the NCR. Diffuse large B-cell PCNSL was defined using the International Classification of Diseases for Oncology morphology and topography codes (Online Supplementary Methods). Two patients diagnosed at autopsy were excluded. We included patients diagnosed from 2014 because the NCR has collected data on the therapeutic regimen from that year onwards. The NCR is based on comprehensive case notifications through the Nationwide Network of Histopathology and Cytopathology, and the National Registry of Hospital Discharges (i.e., outpatient and inpatient discharges). Information on dates of birth and diagnosis, sex, disease stage, topography, and morphology, performance score, and primary therapy was available for individual patients. This information is collected by trained regis- trars of the NCR through retrospective medical records review. Primary therapy was categorized into chemother- apy, radiotherapy only, and supportive care only. Corticosteroids are not standardly registered in the NCR and may have been given in all treatment groups. The category of chemotherapy was broken down by the exact therapeutic regimen. The Privacy Review Board of the NCR approved the use of anonymous data for this study.
The primary survival endpoint was OS, defined as the time from diagnosis until death. Patients were censored at emigration or end of follow-up (1st February 2019). OS
Table 1. Patients’ characteristics. Characteristic
Total n. of patients
Sex
Male
Female
Age at diagnosis, years
Median (range) 71-74
75-79
≥80
Performance score
0-1
2-4 Unknown
Prior malignancy No
Yes
Vital status
Alive
Death
Median follow-up, months (range)
Overall Alive Death
N (%)
145
73 (50)
72 (50)
75 (71-87)
55 (38) 58 (40) 32 (22)
24 (17) 52 (36) 69 (48)
113 (78) 32 (22)
27 (19)
118 (81)
4.1 (0.0-60.0) 31.7 (15.2-60.0) 2.6 (0.0-41.4)
was calculated for three age groups (71-74, 75-79, and ≥80 years) and according to primary treatment (chemotherapy, radiotherapy only, and supportive care only) using the Kaplan-Meier method. Survival distribu- tions were compared with the log-rank test. Multivariable Cox regression was conducted to assess co- variates (sex, age at diagnosis, a prior malignancy before PCNSL diagnosis, receipt of rituximab, and type of pri- mary therapy) associated with OS. P<0.05 was consid- ered statistically significant. Further details about the sta- tistical analyses are available in the Online Supplementary Appendix.
A total of 145 PCNSL patients >70 years old (50% males) were included in the study. Median age was 75 years (range, 71-87), with 55 (38%), 58 (40%), and 32 (22%) patients aged 71-74, 75-79, and ≥80 years at diag- nosis, respectively (Table 1).
Overall, 43% of patients received chemotherapy, 20% radiotherapy only, and 37% supportive care only (Table 2). Numbers of patients receiving chemotherapy decreased with older age (58%, 40%, and 22% respec- tively across the three age groups), while radiotherapy only or supportive care only increased (P=0.002) (Table 2 and Online Supplementary Table S1). All 62 (43%) chemotherapy-treated patients except one were treated with either methotrexate (MTX) monotherapy (n=25) or a variety of MTX-based regimens (n=36) (Table 2). MTX with teniposide, carmustine, and prednisolone (MBVP) was the most commonly applied MTX-based regimen (25 of 36; 69%). Rituximab was added to chemotherapy in 17 of 62 (27%) patients (Table 2). Of note, 6 of 7 chemotherapy-treated patients aged ≥80 years were treated with MTX-monotherapy.
During follow-up, 118 (81%) patients died. The medi-
haematologica | 2021; 106(2)
597