Primary central nervous system lymphoma (PCNSL) is a rare type of extranodal non-Hodgkin’s lymphoma (NHL), which is a rare and heterogeneous disease that accounts for approximately 1–3% of all central nervous system (CNS) tumors [
For decades, radiation and chemotherapy have gained wide recognition as the main treatments for cancer. Cancer-directed surgical procedures have become an unorthodox treatment [
The data source for this study is the SEER database from 1973 to 2014, which was released in November 2016. The SEER program provides clinical data, such as patient demographics and tumor characteristics, annually and openly. The National Center for Health Statistics is responsible for mortality data collection and updates [
The inclusion criteria for the study were as follows: patients who were diagnosed between 1973 and 2014 with complete clinical manifestations, patients who had CNS listed as the primary disease lesion (International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) topography codes C70.0–C72.9), and patients who were diagnosed as having NHL subtypes (ICD-O-3 histology codes 9590, 9591, 9670–9699, 9701–9705, 9714, 9719, and 9727–9729). All diagnoses were histologically confirmed. All patients included were regularly followed up. Immunological status was not provided directly in the SEER database, and it was presumed by cause of death. Thus, on some level, “uncertain criteria” were included in the inclusion criteria. Patients with an insufficient clinical profile, unknown cause of death, and unknown survival months were excluded. Finally, 5903 patients were enrolled. This study was conducted based on the Public Data Base, and all methods were carried out in accordance with the Declaration of Helsinki. No experiments on humans or the use of human tissue samples were used in this study.
Age at diagnosis, sex, race, lymphoma subtypes, tumor primary sites, tumor laterality, lymphoma stage, therapy modality, immunological status, insurance status, marital status, and overall survival (OS) were extracted from original data and considered primary variables. Age at diagnosis was categorized as less than 60 years and 60 years or older. Race was classified into African American, non-Hispanic Caucasian, and others. Lymphoma subtypes were dichotomized as diffuse large B cell lymphoma (DLBCL) and non-DLBCL. Primary sites were located in the brain, meninges/cranial nerves, spine, and other locations. Tumor laterality was defined as a binary variable, with a nonpaired site and a paired site (left/right—origin of primary). According to SEER research data record description, tumor laterality describes the side of a paired organ or side of the body on which the reportable tumor originated. Laterality is coded for select invasive, benign, and borderline primary intracranial and CNS tumors. Lymphoma stage was stratified according to the Ann Arbor stage [
OS was the observed indicator of outcomes. OS was determined by the “vital status,” which represents the time from the date of diagnosis to the date of death. Death was considered a separate event. Censored observations included patients who were still alive at the time of the last follow-up. We only performed analysis on OS because we found that the results for cancer-specific survival were the same as those obtained for OS in the univariate and multivariate analyses.
All statistical analyses were calculated by Statistical Package for the Social Sciences (SPSS) software version 22 (SPSS Inc., Chicago, IL, USA). Univariate and multivariate Cox proportional hazard models were used to estimate the association between various covariates and survival outcome. Kaplan-Meier curves and the log-rank (Mantel-Cox) test were used to compare the OS rates. Differences were considered statistically significant when
A total of 3353 males and 2550 female patients were included in the analysis. Of the total, 5138 patients were considered immunocompetent, and 765 were immunocompromised. The majority of them (4685, 79.4%) were diagnosed between 1996 and 2014. The median age at diagnosis was 61 years. Patients with ages ranging from 0 years to 98 years (Q25 47 years, Q75 71 years) were analyzed, in which patients with ages ≥ 60 years were the most common (53.7%). The immunocompromised cohort was substantially younger than the immunocompetent cohort was (for patients ≥ 60, 3.7% versus 61.1%). More blacks (28.2%) and males (88.9%) were included in the immunocompromised cohort than in the immunocompetent cohort (6% and 52%, resp.). DLBCL was the primary subtype in both cohorts. The tumor was usually located in the brain as the primary lesion. More azygous lesions than paired lesions were detected in patients. Patients had a larger proportion stratified as Ann Arbor stages I–II. More patients in the immunocompromised cohort (60.8%) underwent radiation than did those in the immunocompetent cohort (45.2%). In contrast, the patients in the immunocompetent cohort were more likely to receive chemotherapy than were those in the immunocompromised cohort (61.9% versus 19.2%). The insurance status of most patients was unknown. Most immunocompromised patients never got married (74%), while most immunocompetent patients were or ever got married. For immunocompromised patients, radiation only (49.3%) and neither but conservative treatment (30.5%) were the main therapeutic approaches. In contrast, most immunocompetent patients received chemotherapy treatments. The demographics and clinical characteristics are summarized in Table
Summary of characteristics for the patient population. SEER 1973–2014 (
Characteristic | All patients number (%) ( |
Immunocompromised patients number (%) ( |
Immunocompetent patients number (%) ( |
---|---|---|---|
Age | |||
<60 | 2735 (46.3) | 737 (96.3) | 1998 (38.9) |
≥60 | 3168 (53.7) | 28 (3.7) | 3140 (61.1) |
Sex | |||
Male | 3353 (56.8) | 680 (88.9) | 2673 (52.0) |
Female | 2550 (43.2) | 85 (11.1) | 2465 (48.0) |
Race | |||
Black | 523 (8.9) | 216 (28.3) | 307 (6.0) |
White | 4816 (81.5) | 525 (68.6) | 4291 (83.5) |
Other (American Indian/AK native, Asian/Pacific Islander) | 564 (9.6) | 24 (3.1) | 540 (10.5) |
Dates of diagnosis | |||
1973–1984 | 188 (3.2) | 5 (0.7) | 183 (3.6) |
1985–1995 | 1030 (17.4) | 386 (50.5) | 644 (12.5) |
1996–2006 | 2265 (38.4) | 250 (32.7) | 2015 (39.2) |
2007–2014 | 2420 (41.0) | 124 (16.1) | 2296 (44.7) |
Lymphoma subtypes | |||
DLBCL | 4342 (73.6) | 527 (68.9) | 3815 (74.3) |
Non-DLBCL | 1561 (26.4) | 238 (31.1) | 1323 (25.7) |
Primary site | |||
Brain | 4768 (80.8) | 684 (89.4) | 4084 (79.5) |
Meninges/cranial nerves | 110 (1.9) | 7 (0.9) | 107 (2.0) |
Spine | 364 (6.1) | 18 (2.4) | 346 (6.7) |
Other | 661 (11.2) | 56 (7.3) | 605 (11.8) |
Laterality | |||
Not a paired site | 4197 (71.7) | 662 (86.5) | 3535 (68.8) |
Paired site (left/right—origin of primary) | 1706 (28.9) | 103 (13.5) | 1603 (31.2) |
Lymphoma Ann Arbor stage | |||
I–II | 4324 (73.3) | 585 (76.5) | 3739 (72.8) |
III–IV | 116 (19.6) | 147 (19.2) | 1015 (19.8) |
Unknown | 417 (7.1) | 33 (4.3) | 384 (7.5) |
Radiation | |||
No | 3015 (51.1) | 289 (37.8) | 2726 (53.1) |
Yes | 2785 (47.2) | 465 (60.8) | 2320 (45.2) |
Unknown | 103 (1.7) | 11 (1.4) | 92 (1.8) |
Chemotherapy | |||
Yes | 3325 (56.3) | 147 (19.2) | 3178 (61.9) |
No | 2578 (43.7) | 618 (80.8) | 1960 (38.1) |
Immunological status | |||
Immunocompromised | 765 (13.0) | — | — |
Immunocompetent | 5138 (87.0) | ||
Vital status | |||
Dead | 4382 (74.2) | 765 (100.0) | 3617 (70.4) |
Alive | 1521 (25.8) | 0 (0.0) | 1521 (29.6) |
Insurance status | |||
Uninsured | 101 (1.7) | 12 (1.6) | 89 (1.7) |
Insured/any Medicaid | 2271 (38.5) | 107 (14.0) | 2164 (42.1) |
Insurance status unknown | 3531 (59.8) | 646 (84.4) | 2885 (56.2) |
Marital status | |||
Never married | 1409 (23.9) | 566 (74.0) | 843 (16.4) |
Married | 3170 (53.7) | 107 (14.0) | 3063 (59.6) |
Ever married (divorced, separated, and widowed) | 1142 (19.3) | 63 (8.2) | 1079 (21.0) |
Unknown | 182 (3.1) | 9 (3.8) | 153 (3.0) |
Multiple modalities | |||
Neither but conservative treatment | 1104 (18.7) | 233 (30.5) | 871 (17.0) |
Chemotherapy involving | 3270 (55.4) | 144 (18.8) | 3126 (60.8) |
Only radiation | 1426 (24.2) | 377 (49.3) | 1049 (20.4) |
Missing | 103 (1.7) | 11 (1.4) | 92 (1.8) |
SEER: Surveillance, Epidemiology, and End Results; DLBCL: diffuse large B cell lymphoma; PCNSL: primary central nervous system lymphoma. aData are presented as the number (percentage) of patients.
The variables that were validated as independent prognostic factors in immunocompromised patients with DLBCL included Ann Arbor stage (stages III–IV, hazard ratio (HR): 1.499, 95% CI: 1.187–1.892,
Univariate and multivariate survival analysis in immunocompromised patients with DLBCL.
Variable | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|
HR (95% CI) | HR (95% CI) | |||
Age (years) | ||||
<60 | Reference | |||
≥60 | 0.727 (0.453–1.166) | 0.186 | ||
Race | ||||
White | Reference | |||
Black | 1.194 (0.988–1.443) | 0.067 | ||
Other (American Indian/AK native, Asian/Pacific Islander) | 0.921 (0.573–1.480) | 0.734 | ||
Gender | ||||
Female | Reference | |||
Male | 1.185 (0.908–1.546) | 0.212 | ||
Dates of diagnosis | ||||
1973–1984 | Reference | Reference | ||
1985–1995 | 3.253 (1.027–10.304) | 0.045 | 2.701 (0.472–15.466) | 0.264 |
1996–2006 | 2.270 (0.718–7.179) | 0.163 | 1.881 (0.329–10.747) | 0.477 |
2007–2014 | 2.740 (0.858–8.756) | 0.089 | 2.376 (0.411–13.728) | 0.334 |
Primary site | ||||
Brain | Reference | Reference | ||
Meninges/cranial nerves | 0.313 (0.076–1.287) | 0.107 | 0.603 (0.073–5.004) | 0.640 |
Spine | 0.465 (0.254–0.852) | 0.013 | 0.487 (0.262–0.906) | 0.023 |
Other | 0.593 (0.709–1.541) | 0.824 | 1.052 (0.692–1.600) | 0.811 |
Laterality | ||||
Not a paired site | Reference | |||
Paired site (left/right—origin of primary) | 0.901 (0.709–1.145) | 0.393 | ||
Lymphoma Ann Arbor stage | ||||
I–II | Reference | Reference | ||
III–IV | 1.452 (1.157–1.824) | 0.001 | 1.499 (1.187–1.892) | 0.001 |
Unknown | 1.269 (0.833–1.935) | 0.267 | 1.177 (0.735–1.886) | 0.497 |
Radiation | ||||
No | Reference | Reference | <0.001 | |
Yes | 0.673 (0.562–0.806) | <0.001 0.569 | 0.662 (0.548–0.800) | 0.925 |
Unknown | 0.823 (0.422–1.607) | 0.968 (0.490–1.914) | ||
Chemotherapy | ||||
No | Reference | Reference | ||
Yes | 0.585 (0.465–0.735) | <0.001 | 0.554 (0.434–0.709) | <0.001 |
Insurance status | ||||
Uninsured | Reference | |||
Insured/any Medicaid | 0.708 (0.378–1.328) | 0.282 | ||
Insurance status unknown | 0.735 (0.403–1.339) | 0.315 | ||
Marital status | ||||
Never married | Reference | |||
Married | 0.847 (0.660–1.087) | 0.192 | ||
Ever married (divorced, separated, and widowed) | 0.877 (0.647–1.189) | 0.399 | ||
Unknown | 1.097 (0.731–1.646) | 0.654 |
OS: overall survival; HR: hazard ratio; CI: confidence interval; SEER: Surveillance, Epidemiology, and End Results; DLBCL: diffuse large B cell lymphoma; PCNSL: primary central nervous system lymphoma.
Univariate and multivariate survival analysis in immunocompetent patients with DLBCL.
Variable | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|
HR (95% CI) | HR (95% CI) | |||
Age (years) | ||||
<60 | Reference | Reference | ||
≥60 | 2.084 (1.916–2.267) | <0.001 | 1.834 (1.679–2.004) | <0.001 |
Race | ||||
White | Reference | Reference | ||
Black | 0.759 (0.628–0.918) | 0.004 | 0.854 (0.703–1.037) | 0.111 |
Other (American Indian/AK native, Asian/Pacific Islander) | 0.890 (0.788–1.006) | 0.062 | 0.912 (0.806–1.031) | 0.140 |
Gender | ||||
Female | Reference | |||
Male | 0.947 (0.878–1.021) | 0.153 | ||
Dates of diagnosis | ||||
1973–1984 | Reference | Reference | ||
1985–1995 | 1.937 (0.761–1.153) | 0.536 | 1.124 (0.912–1.386) | 0.272 |
1996–2006 | 0.727 (0.600–0.879) | 0.001 | 1.048 (0.861–1.275) | 0.642 |
2007–2014 | 0.636 (0.525–0.770) | <0.001 | 1.031 (0.841–1.265) | 0.767 |
Primary site | ||||
Brain | Reference | Reference | ||
Meninges/cranial nerves | 0.467 (0.312–0.698) | <0.001 | 0.470 (0.313–0.706) | <0.001 |
Spine | 0.403 (0.323--0.503) | <0.001 | 0.428 (0.342–0.535) | <0.001 |
Other | 0.682 (0.594–0.783) | <0.001 | 0.715 (0.620–0.824) | <0.001 |
Laterality | ||||
Not a paired site | Reference | Reference | ||
Paired site (left/right—origin of primary) | 0.885 (0.815–0.961) | 0.003 | 0.905 (0.825–0.994) | 0.036 |
Lymphoma Ann Arbor stage | ||||
I–II | Reference | |||
III–IV | 0.967 (0.877–1.067) | 0.504 | ||
Unknown | 1.254 (1.073–1.465) | 0.004 | ||
Radiation | ||||
No | Reference | |||
Yes | 1.038 (0.962–1.120) | 0.338 | ||
Unknown | 0.815 (0.615–1.081) | 0.156 | ||
Chemotherapy | ||||
No | Reference | Reference | ||
Yes | 0.402 (0.372–0.434) | <0.001 | 0.442 (0.407–0.480) | <0.001 |
Insurance status | ||||
Uninsured | Reference | |||
Insured/any Medicaid | 0.880 (0.646–1.198) | 0.416 | ||
Insurance status unknown | 1.090 (0.802–1.481) | 0.581 | ||
Marital status | ||||
Never married | Reference | Reference | ||
Married | 1.254 (1.118–1.406) | <0.001 | 1.070 (0.949–1.207) | 0.271< 0.001 0.472 |
Ever married (divorced, separated, and widowed) | 1.823 (1.603–2.074) | <0.001 | 1.354 (1.183–1.549) | |
Unknown | 1.632 (1.283–2.075) | <0.001 | 1.093 (0.857–1.394) |
OS: overall survival; HR: hazard ratio; CI: confidence interval; SEER: Surveillance, Epidemiology, and End Results; DLBCL: diffuse large B cell lymphoma; PCNSL: primary central nervous system lymphoma.
Univariate and multivariate survival analysis in immunocompromised patients with non-DLBCL.
Variable | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|
HR (95% CI) | HR (95% CI) | |||
Age (years) | ||||
<60 | Reference | |||
≥60 | 0.599 (0.305–1.176) | 0.136 | ||
Race | ||||
White | Reference | |||
Black | 1.029 (0.766–1.382) | 0.848 | ||
Other (American Indian/AK native, Asian/Pacific Islander) | 2.129 (0.936–4.841) | 0.071 | ||
Gender | ||||
Female | Reference | |||
Male | 0.874 (0.568–1.346) | 0.541 | ||
Dates of diagnosis | ||||
1973–1984 | Reference | |||
1985–1995 | 1.396 (0.344–5.661) | 0.641 | ||
1996–2006 | 1.056 (0.257–4.347) | 0.939 | ||
2007–2014 | 2.218 (0.518–9.505) | 0.283 | ||
Primary site | ||||
Brain | Reference | |||
Meninges/cranial nerves | 1.068 (0.439–2.598) | 0.885 | ||
Spine | 0.784 (0.363–1.690) 0.620 | 0.534 | ||
Other | (0.414–0.929) | 0.021 | ||
Laterality | ||||
Not a paired site | Reference | |||
Paired site (left/right—origin of primary) | 1.383 (0.905–2.115) | 0.134 | ||
Lymphoma Ann Arbor stage | ||||
I–II | Reference | |||
III–IV | 0.968 (0.708–1.322) | 0.836 | ||
Unknown | 0.938 (0.495–1.779) | 0.846 | ||
Radiation | ||||
No | Reference | |||
Yes | 0.803 (0.617–1.046) | 0.104 | ||
Unknown | 0.454 (0.111–1.846) | 0.270 | ||
Chemotherapy | ||||
No | Reference | Reference | ||
Yes | 0.384 (0.273–0.539) | <0.001 | 0.384 (0.273–0.539) | <0.001 |
Insurance status | ||||
Uninsured | Reference | |||
Insured/any Medicaid | 0.349 (0.046–2.631) | 0.307 | ||
Insurance status unknown | 0.222 (0.031–1.605) | 0.136 | ||
Marital status | ||||
Never married | Reference | |||
Married | 0.635 (0.430–0.936) | 0.022 | ||
Ever married (divorced, separated, and widowed) | 0.885 (0.531–1.477) | 0.641 | ||
Unknown | 2.138 (0.788–5.799) | 0.136 |
OS: overall survival; HR: hazard ratio; CI: confidence interval; SEER: Surveillance, Epidemiology, and End Results; DLBCL: diffuse large B cell lymphoma; PCNSL: primary central nervous system lymphoma.
Univariate and multivariate survival analysis in immunocompetent patients with non-DLBCL.
Variable | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|
HR (95% CI) | HR (95% CI) | |||
Age (years) | ||||
<60 | Reference | Reference | ||
≥60 | 2.399 (2.085–2.759) | <0.001 | 2.389 (2.052–2.780) | <0.001 |
Race | ||||
White | Reference | |||
Black | 0.777 (0.608–0.993) | 0.043 | ||
Other (American Indian/AK native, Asian/Pacific Islander) | 1.016 (0.793–1.300) | 0.902 | ||
Gender | ||||
Female | Reference | 0.946 | ||
Male | 1.005 (0.880–1.147) | |||
Dates of diagnosis | ||||
1973–1984 | Reference | |||
1985–1995 | 1.165 (0.876–1.549) | 0.294 | ||
1996–2006 | 0.761 (0.577–1.002) | 0.052 | ||
2007–2014 | 0.847 (0.633–1.135) | 0.266 | ||
Primary Site | ||||
Brain | Reference | Reference | ||
Meninges/cranial nerves | 0.358 (0.245–0.524) | <0.001 | 0.349 (0.238–0.511) | <0.001 |
Spine | 0.443 (0.355--0.553) | <0.001 | 0.452 (0.362–0.565) | <0.001 |
Other | 0.555 (0.463–0.666) | <0.001 | 0.515 (0.428–0.618) | <0.001 |
Laterality | ||||
Not a paired site | Reference | |||
Paired site (left/right—origin of primary) | 0.962 (0.804–1.150) | 0.670 | ||
Lymphoma Ann Arbor stage | ||||
I–II | Reference | |||
III–IV | 0.980 (0.835–1.152) | 0.810 | ||
Unknown | 1.008 (0.832–1.220) | 0.936 | ||
Radiation | ||||
No | Reference | |||
Yes | 0.894 (0.780–1.023) | 0.104 | ||
Unknown | 1.978 (1.198–3.267) | 0.008 | ||
Chemotherapy | ||||
No | Reference | Reference | ||
Yes | 0.684 (0.599–0.781) | <0.001 | 0.724 (0.633–0.828) | <0.001 |
Insurance status | ||||
Uninsured | Reference | |||
Insured/any Medicaid | 1.457 (0.685–3.096) | 0.328 | ||
Insurance status unknown | 1.522 (0.722–3.208) | 0.270 | ||
Marital status | ||||
Never married | Reference | Reference | ||
Married | 1.153 (0.961–1.383) | 0.126 | 0.821 (0.677–0.994) | 0.043 |
Ever married (divorced, separated, and widowed) | 1.689 (1.363–2.094) | <0.001 | 1.048 (0.833–1.319) | 0.689 |
Unknown | 1.206 (0.805–1.805 | 0.364 | 0.809 (0.538–1.217) | 0.309 |
OS: overall survival; HR: hazard ratio; CI: confidence interval; SEER: Surveillance, Epidemiology, and End Results; DLBCL: diffuse large B cell lymphoma; PCNSL: primary central nervous system lymphoma.
To compare the efficacy of different treatments, we grouped them as follows: received radiation only, received chemotherapy treatments (chemotherapy only or chemotherapy plus radiation), and received neither. In many countries, PCNSL patients first undergo chemotherapy. When the therapeutic response is good, the patients may be followed up without radiotherapy, but when complete remission is not obtained or the tumor recurs, radiation therapy may be added. Patients who receive chemotherapy plus radiation may thus have an apparently worse background than those who receive chemotherapy alone. Therefore, it is not appropriate to separate these two groups. Stratification analysis made the results more accurate. Survival analysis beyond different treatments was conducted according to different immunological statuses and dates of diagnosis. For immunocompromised patients, the median OS for those who received radiation only was 2 months (1985–1995), 4 months (1996–2006), and 2 months (2007–2014), respectively. The median OS for those who received neither was 0 months (1985–1995, 1996–2006, and 2007–2014). The median OS for those who received chemotherapy involving treatments was 2 months (1985–1995), 9 months (1996–2006), and 3 months (2007–2014). For immunocompetent patients, the median OS for those who received radiation only was 12 months (1973–1984), 6 months (1985–1995), 6 months (1996–2006), and 2 months (2007–2014). The median OS for those received neither was 0 months (1973–1984), 2 months (1985–1995), 1 month (1996–2006), and 1 month (2007–2014). The median OS for those who received chemotherapy treatments was 18 months (1973–1984), 20 months (1985–1995), 28 months (1996–2006), and 34 months (2007–2014). These differences were statistically significant (
Kaplan-Meier survival curves of immunocompromised patients with diffuse large B cell lymphoma (DLBCL) in 1985–1995 (a), 1996–2006 (b), and 2007–2014 (c) according to treatment options.
Kaplan-Meier survival curves of immunocompetent patients with DLBCL in 1973–1984 (a), 1985–1995 (b), 1996–2006 (c), and 2007–2014 (d) according to treatment options.
For immunocompromised patients, the median OS for those who received radiation only was 3 months (1985–1995), 2 months (1996–2006), and 1 month (2007–2014). The median OS for those who received neither was 1 month (1985–1995), 0 months (1996–2006), and 0 months (2007–2014). The median OS for those who received chemotherapy treatments was 5 months (1985–1995), 14 months (1996–2006), and 2 months (2007–2014). For immunocompetent patients, the median OS for those who received radiation only was 57 months (1973–1984), 11 months (1985–1995), 57 months (1996–2006), and 62 months (2007–2014). The median OS for those who received neither was 3 months (1973–1984), 3 months (1985–1995), 4 months (1996–2006), and 4 months (2007–2014). The median OS for those who received chemotherapy treatments was 18 months (1973–1984), 35 months (1985–1995), 74 months (1996–2006), and 46 months (2007–2014). These differences were statistically significant (
Kaplan-Meier survival curves of immunocompromised patients with non-DLBCL in 1985–1995 (a), 1996–2006 (b), and 2007–2014 (c) according to treatment options.
Kaplan-Meier survival curves of immunocompetent patients with non-DLBCL in 1973–1984 (a), 1985–1995 (b), 1996–2006 (c), and 2007–2014 (d) according to treatment options.
The median OS (months) of each group of patients in any periods are displayed using line charts: (a) immunocompromised patients with DLBCL, (b) immunocompromised patients with non-DLBCL, (c) immunocompetent patients with DLBCL, and (d) immunocompetent patients with non-DLBCL
Previous studies focused mostly on either immunocompetent patients or the impact of demographic factors [
In immunocompromised patients, regardless of whether they have been diagnosed with DLBCL or non-DLBCL, chemotherapy treatments could prolong survival in all time periods. It is better to choose this as the primary treatment. Additionally, some benefit could be observed in patients who received radiation only. Without these two approaches, immunocompromised patients have little chance of survival. It is obvious that the immunocompromised patients who received neither chemotherapy nor radiation had a median OS of 0 months. How could this occur? Detailed analysis showed that this population of patients was mainly male (possibly homosexual), black, single, young, or having poor economic and education conditions, which may prevent them from receiving further treatment. Furthermore, faint medical awareness, which can lead to a long duration before seeking medical assistance and concerns about basic immunodeficiency diseases (almost HIV), from the physician may also be a cause. This type of patient unexpectedly represents one-third of all immunocompromised patients, and it has been a general social phenomenon in the US. The results became more interesting in immunocompetent patients. Chemotherapy treatments provide more benefits over time in DLBCL patients, which is mainly attributed to the improvement of chemotherapy drugs and regimens. Only radiation therapy is below the therapeutic need and may cause central neurotoxicity. The relevant survival time is relatively shorter than that in those who received chemotherapy treatments in recent years. However, the results were the reverse in non-DLBCL patients. Although great advancements have been made in chemotherapy treatments, it was still seen that the efficacy of radiation therapy was not inferior to that of chemotherapy treatments and became even better in the last 7 years. It is well known that non-DLBCL has a less aggressive evolution than DLBCL does, so less radical therapeutic approaches may be associated with favorable survival. In any case, receiving neither chemotherapy nor radiation is not recommended. We observed that most patients were at Ann Arbor stages I–II, which is considered an early stage of NHL, but only less than 30% cases survived, regardless of treatment. There is still a long way to go in cancer control.
Previous studies have collected relevant results based on a limited population. Chalise et al. [
The latest data and the relatively large cohort are the major strengths of this study, which closely represents the current situation in the US. Conclusions about mortality and the outcomes of rare malignancies could be found only in studies of large populations but not for collaborative or single institutions. However, the known limitations of the study may weaken these conclusions. Our effort to identify immunocompromised patients has inherent flaws, although there are no better methods. In addition, this classification scheme relies primarily on the causes of death. A few surviving immunocompromised patients might be classified as immunocompetent. The inability to accurately classify immunocompromised patients in the SEER data has the potential to introduce bias. However, this situation cannot be solved until a marker of immunological status, such as HIV and transplantation status, is clearly labelled in the SEER database. In addition, detailed information about chemotherapy and radiation was not captured. This information is not currently available from the SEER database.
In summary, these data indicate that radiation alone should not be recommended as the primary therapeutic approach for PCNSL patients with the DLBCL subtype. In non-DLBCL cases, it may provide an excellent outcome. Receiving neither chemotherapy nor radiation led to poor survival. The use of proper chemotherapy regimens greatly improved survival over time. Novel adjuvant therapies should be developed.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare no conflicts of interest.
Yudong Shan wrote the main manuscript text, and Yilan Hu prepared Figures