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.

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.

Cognitive Outcomes and Long-term Follow-up Results after Enhanced Chemotherapy Delivery for Primary Central Nervous System Lymphoma

Neurosurgery ◽  
2000 ◽  
pp. 51-61 ◽  
Author(s):  
Leslie D. McAllister ◽  
Nancy D. Doolittle ◽  
Paul E. Guastadisegni ◽  
Dale F. Kraemer ◽  
Cynthia A. Lacy ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Cognitive Outcomes ◽  
Long Term Follow Up

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&lt;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 Autologous Stem Cell Transplantation with Thiotepa, Busulfan, and Cyclophosphamide Conditioning in Patients with Primary Central Nervous System Lymphoma: A Remarkable Outcome Form Single-Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3462-3462 ◽  
Author(s):  
Seyoung Seo ◽  
Jung Yong Hong ◽  
Dok Hyun Yoon ◽  
Jeong Hoon Kim ◽  
Young Hyun Cho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Prognostic Score ◽  
Central Nervous System Lymphoma ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Baseline Characteristics

Abstract Introduction High dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has been adopted as an effective treatment in patients with relapsed or refractory primary central nervous system lymphoma (PCNSL) and also has been proposed as a consolidative treatment option for newly diagnosed PCNSL. HDC-ASCT may overcome chemoresistance mediated by blood-brain barrier by affording higher drug concentrations in the central nervous system. We investigated the feasibility of thiotepa, busulfan, and cyclophosphamide (TBC) conditioning followed by ASCT in patients with PCNSL. Method Between December 2012 and July 2015, a total of 27 patients with PCNSL underwent TBC conditioning followed by ASCT. Those with a complete or partial response after induction chemotherapy or salvage chemotherapy proceeded with TBC conditioning followed by ASCT. TBC conditioning consists of thiotepa 250 mg/m2 on days -9 to day -7, busulfan 3.2 mg/kg on days -6 to day -4 and cyclophosphamide 60 mg/kg on days -3 to day -2. The event free survival (EFS) was defined from the date of transplant to the date of relapse, progression or any cause of death, while overall survival (OS) was calculated from the date of transplant to death. Result Baseline characteristics were summarized in table 1. Twenty patients received TBC conditioning followed by ASCT as a consolidative therapy after high-dose methotrexate-based induction chemotherapy and the other 7 patients received TBC conditioning followed by ASCT after salvage chemotherapy due to relapsed or refractory disease. The median time to neutrophil recovery (absolute neutrophil count >500/uL) and platelet recovery (>20000 x103/uL) were 8 (range, 7-9) and 8 (range, 4-15) days, respectively. All 27 patients experienced febrile neutropenia and 33.3% of patients (9/27) and 7.4% of patients (2/27) had documented bacterial and viral infection, respectively. Commonly observed nonhematologic grade 3 or 4 toxicities were mucositis (63%), diarrhea (59.3%) and nausea (25.9%). The 100-day transplant-related mortality rate was 0%. With median follow-up duration of 27.8 months (range 6.7-42.6), median EFS and OS were not reached. The 2-year EFS and OS estimates were 76.8% (95% CI: 68.4-85.2) and 88.9% (95% CI: 82.9-94.9), respectively (Figure 1). Conclusion ASCT with TBC conditioning appears to be feasible in patients with PCNSL. Although survival outcomes are encouraging, longer follow-up is required. Further studies are warranted to investigate the role of ASCT with TBC conditioning in both clinical settings of consolidative treatment of newly diagnosed PCNSL and salvage treatment of relapsed or refractory PCNSL. Table 1 Baseline characteristics (n=27) *Conventional cytology; flow cytometry not performed $The cutoff for normal CSF protein concentration was 45 mg/dL in patients ¡Â 60 years old and 60 mg/dL in patients more than 60 years old. *MSK RPA, Memorial Sloan-Kettering prognostic score determined by recursive partitioning $Periventricular, basal ganglia, brainstem and cerebellar lesion Table 1. Baseline characteristics (n=27). / *Conventional cytology; flow cytometry not performed. / $The cutoff for normal CSF protein concentration was 45 mg/dL in patients ¡Â 60 years old. / and 60 mg/dL in patients more than 60 years old. / *MSK RPA, Memorial Sloan-Kettering prognostic score determined by recursive partitioning. / $Periventricular, basal ganglia, brainstem and cerebellar lesion Figure 1 Event-free survival and overall survival. Figure 1. Event-free survival and overall survival. Disclosures No relevant conflicts of interest to declare.

IMMUNE CHECKPOINT INHIBITOR SALVAGE THERAPY IN PATIENT WITH REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

2019 ◽  
Vol 65 (2) ◽  
pp. 294-297
Author(s):  
Kirill Lepik ◽  
Aleksey Polushin ◽  
Ye. Kondakova ◽  
K. Yakimovich ◽  
I. Tsygankov ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Tumor Microenvironment ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Central Nervous System Lymphoma ◽  
Therapeutic Strategies ◽  
Disease Relapse ◽  
Resistance To Therapy

Despite the progress in the therapy of a primary central nervous system lymphoma (PCNSL) the rates of disease relapse and resistance to therapy are high. Development of new effective therapeutic strategies is needed. One of the key mechanisms in the pathogenesis of PCNSL is the suppression of the immune response in the tumor microenvironment. Recent studies have demonstrated the increased expression of PD-L1 in the tumor cells of PCNSL and therefore the use of PD-1 blockade might be effective. This report includes the description of a case of the successful use of PD-1 inhibitor nivolumab as monotherapy in a severely pretreated young patient with refractory PCNSL.

scholarly journals Primary central nervous system lymphoma and 5-aminolevulinic acid

2020 ◽  
Vol 11 ◽  
pp. 122 ◽  
Author(s):  
Pierre Ferrer ◽  
Pablo Barbero ◽  
Gonzalo Monedero ◽  
Anna Lo Presti ◽  
Bartolome Bejarano ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Central Nervous System Lymphoma ◽  
High Grade Glioma ◽  
Complete Resection ◽  
Neurological Deficits ◽  
Pathological Examination

Background: Despite surgical resection of primary central nervous system lymphomas (PCNSL) having been always discouraged, recent evidence supports that it might improve prognosis in this patient population. Five- aminolevulinic acid-derived fluorescence is widely used for the resection of malignant gliomas, but its role in PCNSL surgery remains unclear. Case Description: We present two patients with a solitary solid intraparenchymal mass. As high-grade glioma leaded the list of differential diagnosis (other possibilities were metastasis, abscess, and PCNSL), a five- aminolevulinic acid-guided complete resection (with strong fluorescence in both cases) was done. Surgery was uneventfully carried on with complete resection until five-aminolevulinic acid-induced fluorescence was no longer evident. After surgery, patients have no neurological deficits and had good recovery. Pathological examination revealed that both tumors were PCNSL. Adjuvant radiotherapy and chemotherapy were started. After 1 year of follow-up, patients have good evolution and have no recurrences. Conclusion: These cases add to the growing literature which shows that surgery might play an important role in the management of PCNSL with an accessible and single lesion. Five-aminolevulinic acid could also be a useful tool to achieve complete resection and improve prognosis in this group of patients.

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