Improved survival outcomes despite older age at diagnosis: an era‐by‐era analysis of patients with primary central nervous system lymphoma treated at a single referral centre in the United Kingdom

2021 ◽  
Author(s):  
Furqaan A. Kaji ◽  
Nicolas Martinez‐Calle ◽  
Mark J. Bishton ◽  
Rocio Figueroa ◽  
Joanne Adlington ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
United Kingdom ◽  
Central Nervous System Lymphoma ◽  
Older Age ◽  
Age At Diagnosis ◽  
Survival Outcomes ◽  
Referral Centre ◽  
The United Kingdom

scholarly journals Primary Central Nervous System Lymphoma: A Retrospective Study of the Population of Texas and Florida with an Emphasis on Survival Outcomes on Hispanics Vs Non-Hispanics

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1443-1443
Author(s):  
Kana Tai Lucero ◽  
Lakene Raissa Djoufack Djoumessi ◽  
Joel E Michalek ◽  
Qianqian Liu ◽  
Adolfo Enrique Diaz Duque
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retrospective Study ◽  
Research Funding ◽  
Central Nervous System Lymphoma ◽  
Survival Outcomes ◽  
P Value ◽  
Poverty Index ◽  
Significant Difference ◽  
The U.S

Abstract Introduction Primary central nervous system lymphoma (PCNSL) is a devastating subtype of extranodal non-Hodgkin's lymphoma (NHL) that accounts for ~4% of newly diagnosed central nervous system (CNS) tumors. (NeuroOncol PMID: 21915121) The age-adjusted incidence of PCNSL in the U.S. has increased since the 1970s. (ACS PMID: 19273630) despite advances in the treatment of lymphoma, and clinical outcomes remain poor with an estimated 5- year survival for immunocompetent patients at 30%. (NCBIPMID:31424729) Trends in outcomes of PCNSL have been reported, but sub-analyses for minorities like Hispanics (HI), have not been widely studied. Understanding ethnic disparities on outcomes and patterns of care in PCNSL are crucial given the rapid growth of HI in the U.S. This study aims to examine the demographics, treatment patterns, and survival outcomes of PCNSL in HI compared to Non-Hispanics (NH) in Texas (TX) and Florida (FL). Methods This is a retrospective study of a cohort of patients diagnosed with lymphoma (Hodgkin and Non-Hodgkin) from the TX Cancer Registry (TCR) and the FL Cancer Data System (FCDS) from 2006-2017. Patients with PCNSL were identified by the International Classification of Diseases for Oncology Third Edition (ICD-O-3) code list. Standard demographic variables collected include gender, ethnicity, dates at diagnosis and death, primary payer at diagnosis, type of treatment and poverty index (PI). The significance of variation in the distribution of categorical outcomes with ethnicity (HI and NH) was assessed with Fisher's Exact tests or Pearson's Chi-square tests as appropriate; age was assessed with T-tests or Wilcoxon tests as appropriate. Survival distributions were described with Kaplan-Meier curves and significance of variation in median survival with ethnicity was assessed with log rank testing. All statistical testing was two-sided with a significance level of 5%. Results The study included 1969 patients (TX: n=297 HI, n= 708 NH; FL: n=149 HI, n=415 NH). PCNSL was diagnosed at younger median age in HI (TX: 59,FL:59) compared to NH (TX: 62, FL:63),with a significant difference noted within each state (TX: p= 0.005; FL: p=0.007). HI in TX were identified primarily as Mexican, Spanish or NOS/Hispanic. There was a significant predominance of overall males (M) in TX (p=0.009). There was a non-significant predominance of M in FL. Regarding poverty index (PI), there were more HI (TX:51% and FL: 35%) in the 20-100% bracket than NH (TX: 25%; FL: 22%). Conversely there were more NH in all other PI in TX and FL. Government sponsored insurance was the most common insurance in all subgroups. This reached a significant predominance in HI (54%) and NH (54%) in TX (p<0.001). There was no significant difference in insurance types between HI and NH in FL(p=0.772). Regarding chemotherapy there was a trend to either use multiple agents [(TX: 34% in HI vs 32% in NH; p=0.68); (FL: 33% in HI vs 67% in NH; p=0.042)] or to not offer chemotherapy at all [(TX: 26% in HI vs 29% in NH; p= 0.68); (FL: 44% in HI vs 33% in NH; p=0.042)] with significant differences noted in FL only. (Table 1) The median survival (MS) for HI and NH in TX was similar in years (y) at 0.8 while the MS time in FL for HI vs NH was higher (1.3 vs 0.6 respectfully) Thus, the MS for HI in FL was higher compared to NH in FL and HI and NH in both TX and FL. (Table 2) The survival probability for HI was shorter at 2 and 5 years compared to NH in TX with a non-significant overall survival (OS) probability (p-value=0.19) seen in Figure 1. Significantly, the survival probability of HI in FL at 2, 5 and 10 years was higher compared to NH with an OS probability (p-value=0.0063) seen in Figure 2. Conclusion This retrospective study showed a statistically significant difference in OS probabilities at all years between HI and NH in FL with PCNSL. The OS probability also remained higher in HI in FL compared to both HI and NH in TX. In addition, the study demonstrated a longer MS in HI in FL compared to not only HI in TX, but also both NH in TX and FL. Sociodemographic differences like gender and insurance types were noted between HI in TX and FL. HI origin groups are also a subject of interest. The primary HI origin group in TX were Mexican and not otherwise specified (NOS). This data was missing for FL HI. Future studies should be conducted to uncover any further disparities between these two HI populations to explore the impact of access to care and disease biology on PCNSL survival outcomes. Figure 1 Figure 1. Disclosures Diaz Duque: Incyte: Consultancy; Morphosys: Speakers Bureau; Astra Zeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Epizyme: Consultancy; ADCT: Consultancy.

scholarly journals Primary Central Nervous System Lymphoma in a Community Academic Oncology Practice: Aggressive Disease with Suboptimal Outcomes Regardless of the Available Management Options

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5046-5046
Author(s):  
Ramya Pinnamaneni ◽  
Musharraf Navaid ◽  
Darla Liles ◽  
Laura Hanson ◽  
Ridas Juskevicius
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Radiation Therapy ◽  
Patient Population ◽  
Standard Treatment ◽  
Central Nervous System Lymphoma ◽  
Proliferation Rate ◽  
Age At Diagnosis ◽  
Treatment Regimens ◽  
Aggressive Disease

Abstract Introduction: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extra-nodal lymphoma which has historically shown to be therapeutically challenging. Currently, the standard treatment remains to be high dose methotrexate (HD-MTX)-based combination chemotherapy with or without whole-brain radiotherapy. The rarity of this disease has precluded large and randomized controlled trials from taking place. In this retrospective study performed at our tertiary care academic medical center, we report our experience and characterize the nature of this disease in our patient population in a predominantly rural area of North Carolina. We demonstrate the reality and challenges of the therapeutic approaches in an attempt to achieve more durable responses and better outcomes with available treatment regimens in our patient population. Methods: After approval from our Institutional Review Board, medical records and pathology data base at our institution were reviewed to identify patients diagnosed with PCNSL between the years of 2004 and 2014. Eleven cases with no radiographic or other evidence of systemic disease who fulfilled the criteria for PCNSL according to the most recent WHO classification were included in the study. Patients' demographics, clinical presentation, radiographic and pathologic findings and treatment details and outcomes were collected and analyzed. Results: The median age at diagnosis was 60. Most patients were Caucasians (90%) with a slight predominance of males (54% males, 45% females). Clinically, most patients presented with neurologic symtpoms and deficits rather than with 'B' symptoms. Radiographically, all patients had supratentorial and multifocal involvement mostly with frontotemporal lesions. The lesions were seen crossing the corpus callosum mimicking glioblastoma multiforme in 4 patients. The pathologic features in all patients were consistent with diffuse large B-cell lymphoma (DLBCL) characterized by a diffuse intraparenchymal growth pattern. At least focal perivascular distribution of tumor cells was present in 3 cases. CD20 expression was present in all cases and 10 of 11 cases were negative for CD10, consistent with non-germinal center (non-GC) phenotype. Most tumors showed a high Ki67 proliferation rate (80-100%). Six of eleven patients had cytological assessment of the cerebrospinal fluid (CSF) at the time of diagnosis. No patients had lymphoma cells in the CSF indicating lack of leptomeningeal involvement. A total of 2 patients received induction chemotherapy based on the CALBG 50202 protocol including HD-MTX, Temozolamide and Rituxumab. Of the remaining 9 patients, 4 received HD-MTX alone, 3 received HD-MTX with concomitant intrathecal cytarabine, 1 received HD-MTX plus rituximab and 1 received Pemetrexed alone. A total of 2 patients received radiation therapy (WBRT). Five patients died of disease with time to death of disease ranging from 1.5 to 8 months. Three patients are alive at months ranging from 8 months to 3.5 years after diagnosis. One patient has been cured of their PCNSL but developed a secondary systemic DLBCL seven years later. The remaining 2 patients were lost to follow up. We were unable to determine any impact of the individual treatment modalities on the overall survival due to the small number of patients in our study. Conclusion: Our patients were predominantly Caucasian with a median age at diagnosis of 60 years. The tumors were exclusively CD20+ DLBCLs with a high Ki67 proliferation rate and a predominantly non-GC phenotype, indicating an aggressive disease pattern. Majority of the patients were unable to complete standard chemotherapy regimens previously described in the literature. Factors contributing to incomplete therapy included age more than 65 and adverse events from chemotherapy including acute kidney failure and neurotoxicity. We conclude that although HD-MTX with or without radiation therapy is the current standard treatment, it is not necessarily feasible nor appropriate in all patient populations. In our population, success was seen in patients who were younger, less than 65 years, in those who received methotrexate doses of 4g/m2 rather than the standard 8g/m2 and those who received Rituximab as part of their regimen. Larger multicenter retrospective studies may provide better insight into finding more optimal treatment regimens. Disclosures No relevant conflicts of interest to declare.

scholarly journals Increased Serum Beta-2 Microglobulin during Induction Chemotherapy Associated with Poor Prognosis in Primary Central Nervous System Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2995-2995
Author(s):  
Jaewon Hyung ◽  
Jung Yong Hong ◽  
Dok Hyun Yoon ◽  
Shin Kim ◽  
Jung Sun Park ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Factors ◽  
Induction Chemotherapy ◽  
Poor Prognosis ◽  
Central Nervous System Lymphoma ◽  
Survival Outcomes ◽  
Induction Treatment ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Abstract Introduction Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma that exclusively involves the brain, leptomeninges, eyes, or spinal cord. Due to the rare incidence of PCNSL, therapeutic decisions and predictions of outcomes rely on phase 2 clinical trials and retrospective studies. Indeed, it is important to continuously search potential prognostic factors. Serum beta-2 microglobulin (B2MG) is thought to be associated with prognosis in several lymphomas and multiple myeloma. Previous study in our center showed that increased serum B2MG of ≥ 1.8 μg/mL at diagnosis was associated with poor prognosis in PCNSL. In this study, we investigated association of serum B2MG level changes with survival outcomes in PCNSL patients during induction chemotherapy who had elevated serum B2MG level at diagnosis. Methods We retrospectively reviewed prospectively collected PCNSL registry data for patients treated from March 1993 to May 2017 at Asan Medical Center in Seoul, Korea. Patients with serum B2MG of ≥ 1.8 μg/mL at diagnosis who had at least two or more measurement of serum B2MG including at diagnosis, 6 weeks, and 3 months from the initiation of induction chemotherapy were included in the analysis. Two weeks of window period was allowed for measured B2MG at 6 weeks and 3 months from the beginning of treatment. Overall survival (OS) was defined as the time from the initiation of induction treatment to death from any cause, and progression-free survival (PFS) was defined as the time from the initiation of induction treatment to disease progression or death. Univariate analyses were performed to compare survival outcomes using log-rank tests. Multivariate analyses were performed to identify independent prognostic factors for PFS and OS using a Cox proportional hazards model. Results Among 241 patients with diagnosis of PCNSL, 42 patients were included in the study. Median follow-up period was 4.0 years (range, 0.1-9.7). Median OS and PFS was 2.3 years (95% CI 1.9-2.6), and 1.2 years (95% CI 0.6-1.8), respectively. Median age was 67 years old (range, 28-85) and 26 patients (61.9%) were male. All patients received methotrexate-based combination chemotherapy as induction treatment and 31 patients (88.6%) showed complete response or partial response as best responses. Ten patients (23.8%) received consolidation treatment with high-dose chemotherapy followed-by autologous stem cell transplantation. Patients were classified into two groups according to serum B2MG level difference compared to B2MG level at diagnosis with the B2MG level at 6 weeks and 3 months from the initiation of induction treatment. Median B2MG at diagnosis, 6 weeks, and 3 months was 2.4 μg/mL (range, 1.9-11.7), 2.5 μg/mL (range, 1.3-8.7), and 2.6 μg/mL (range, 1.4-8.7), respectively. There was no statistically significant difference in terms of OS between patients with increased B2MG level at 6 weeks (16 patients) and patients with no increment (10 patients) with median OS of 1.4 years (95% CI 0.1-2.8) and 3.0 years (95% CI 1.1-4.9), respectively (P = 0.065). Patients with increased B2MG level at 3 months (23 patients) significantly poor prognosis in terms of OS compared to patients with same or decreased level (13 patients). Median OS was 1.4 years (95% 0.6-2.3) for the increased patients and not reached in patients with no increment (P < 0.001). Multivariate analysis with other factors showed significantly poor outcomes in patients with increased serum B2MG level at 3 months from the initiation of induction treatment in terms of OS with hazard ratio of 14.3 (95% CI 2.1-100.0, P = 0.007). Conclusion Among PCNSL patients who had serum B2MG level of ≥ 1.8 μg/mL at diagnosis, which was associated with poor prognosis in our previous study, patients with no increment of serum B2MG level at 3 months from the initiation of induction chemotherapy was associated with better survival outcomes in terms of OS compared to those with increased level. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effect of Tumor Microenvironment and Angiogenesis on Clinical Outcomes of Primary Central Nervous System Lymphoma

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hui-Ching Wang ◽  
Hui-Hua Hsiao ◽  
Jeng-Shiun Du ◽  
Shih-Feng Cho ◽  
Tsung-Jang Yeh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Microenvironment ◽  
Induction Chemotherapy ◽  
Central Nervous System Lymphoma ◽  
Survival Outcomes ◽  
Short Term ◽  
Genomic Alterations ◽  
Baseline Characteristics

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma, and the disease course is often aggressive with poor prognosis outcomes. PCNSL undergoes germinal center reactions and impairs B-cell maturation. However, angiogenesis is also involved in the tumorigenesis and progression of PCNSL. This study investigated the effects of the tumor microenvironment and angiogenesis-associated genomic alterations on the outcomes of PCNSL. The analysis also evaluated the influence of treatment modality and timing on PCNSL survival using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and disease outcomes with a small sample of measurements and structural models. A total of 19 immunocompetent PCNSL samples were analyzed by exome sequencing. Our results suggest that the timing of radiotherapy and mutations of ROBO1 and KAT2B are potential indicators of PCNSL outcomes and may be affected by baseline characteristics such as age and sex. Our results also showed that patients with no mutations of ROBO1 and KAT2B, SubRT subgroup showed favorable survival outcomes compared with no SubRT subgroup in short-term follow-up. All SubRT patients have received high-dose methotrexate induction chemotherapy in the initial treatment. Therefore, initial induction chemotherapy combined with subsequent radiotherapy might improve survival outcomes in PCNSL patients who have no ROBO1 and KAT2B somatic mutations in short-term follow-up. The overall findings suggest that the tumor microenvironment and angiogenesis-associated genomic alterations and treatment modalities are potential indicators of overall survival and may be affected by the baseline characteristics of PCNSL patients.

Sign in / Sign up

Export Citation Format

Share Document