First-line temozolomide therapy and MGMT status in elderly patients with primary CNS lymphoma

Abstract Introduction The optimal follow-up strategy for primary CNS lymphoma (PCNSL) patients in remission after first line therapy is not clear. The goal of this study is to determine the utility of planned brain surveillance imaging in the detection of relapse in a large cohort of PCNSL patients. Methods Patients were from consecutive PCNSL cases (N=209) included in Leon Berard Cancer Centre registry (Lyon, France), from 1987 to 2011 (date of diagnosis). Patients were all treated by chemotherapy, 92% of them by high-dose methotrexate containing chemotherapy followed by brain radiotherapy for 107 patients (51%). All patients were followed for relapse, retreatment and death. Patient clinical records were reviewed for details at relapse and relationship to planned follow-up visits and brain surveillance imaging. Results Among the 209 PCNSL patients, 28 (13%) presented toxic death, one patient died from another reason and 41 patients (20%) had a progressive disease during first-line therapy. The remaining 139 patients (66%) entered in post-treatment observation, 128 of them in complete remission (92%) and 11 in partial remission (8%). The median follow up was 36 months for the patients who entered in post-treatment observation. Among these 139 patients, 7 (5%) were lost of follow-up, 62 (45%) patients are still in remission and 70 (50%) relapsed. Among these 70 relapses, 15 (21%) were detected by planned brain surveillance imaging but 53 (76%) patients were symptomatic and presented earlier than a planned follow-up visit; two patients (3%) had no information at time of relapse. If we consider only patients in complete remission who entered in post-treatment observation, 13 (20%) relapses were detected by brain surveillance imaging and 50 (80%) patients presented symptoms between planned visits and imaging. Among the 7/11 patients considered in partial remission after initial treatment who relapsed, two (29%) relapses were detected by brain surveillance imaging and five (71%) by symptoms between planned visits and imaging. Among the 53 symptomatic patients at relapse, 41 (77%) presented a brain tumor relapse, six had an isolated leptomeningeal relapse, one a spinal cord localization and five an extra-cerebral relapse (three abdominal nodes, one soft-tissue mass, one testis). The most common symptoms at relapse were cognitive troubles, motor or sensitive deficits, epilepsy, and alteration of performance status. We did not observe any difference between asymptomatic relapse patterns before and after 2 years with 54% relapses before the two years of follow-up (brain imaging mainly every 4 months) and 46% relapses after 2 years of follow-up (brain imaging mainly every 6 months). Conclusions This study showed that PCNSL relapses frequently occurred outside of planned follow-up visits and were notably detected by symptoms between two brain surveillance imaging. Even during the two first years of follow-up with a closed brain imaging monitoring, planned surveillance imaging seemed not efficient. Disclosures: No relevant conflicts of interest to declare.

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First-line therapy with temozolomide induces regression of primary CNS lymphoma

Neurology ◽

10.1212/wnl.58.10.1573 ◽

2002 ◽

Vol 58 (10) ◽

pp. 1573-1574 ◽

Cited By ~ 29

Author(s):

U. Herrlinger ◽

W. Kuker ◽

M. Platten ◽

J. Dichgans ◽

M. Weller

Keyword(s):

Primary Cns Lymphoma ◽

Cns Lymphoma ◽

First Line ◽

First Line Therapy ◽

Line Therapy

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Diagnosis-to-Treatment Interval Is an Important Prognostic Factor with a Time-Dependent Effect Predicting Event-Free Survival after 12 Months from First-Line Treatment in Newly Diagnosed Diffuse Large B-Cell Primary CNS Lymphoma

Blood ◽

10.1182/blood-2020-138789 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 43-45

Author(s):

Marie-Charlotte Laude ◽

Edith Julia ◽

Emmanuelle Nicolas-Virelizier ◽

Gabriel Antherieu ◽

Violaine Safar ◽

...

Keyword(s):

Board Of Directors ◽

Cox Model ◽

Primary Cns Lymphoma ◽

Time Dependent ◽

Cns Lymphoma ◽

First Line ◽

Advisory Committees ◽

Dependent Effect ◽

Prognostic Effect ◽

Time Dependent Effect

Background: Diagnostic-to-treatment interval (DTI) was recently described as a strong prognostic factor for newly diagnosed systemic diffuse large B-cell lymphoma patients (DLBCL) with an improvement of event-free survival (EFS) for patients with a longer DTI. These results have some implications for patient selection and result interpretations in clinical trials. This association has not been previously evaluated in DLBCL Primary CNS Lymphoma (PCNSL) patients who also present a clinically aggressive disease. Patients and Methods: The cohort constited of all consecutive DLBCL PCNSL patients treated in two Hematology Departments of the University of Lyon between 1984 and 2018 (N=244). All patients had DLBCL histology at diagnosis, obtained by brain biopsy (N=235, 96%), vitrectomy (N=4, 2%) or CSF evaluation (N=5, 2%). As first line treatments, all patients but 5 (2%) received high-dose (HD) methotrexate-based chemotherapy, associated with intra-venous rituximab for 154 patients (63%) and HD cytarabine for 182 patients (75%). Consolidation treatment by whole-brain radiotherapy was performed in seventy-six patients (31%). DTI was defined as the number of days between the date of diagnosis (i.e. biopsy) and the date of treatment initiation. Association between DTI and patient characteristics was assessed by chi-square tests or Student t-tests. EFS was defined from the start of therapy to progression, relapse, or death from any cause. As we previously described, prognostic factors such as age and performance status (PS) demonstrate a time-dependent effect on overall survival (OS) in PCNSL limiting the validity of traditional Cox proportional hazard models. We thus used a piecewise Cox model to allow assessment of prognostic effect over different time periods. All survival analyses were done in univariate and multivariate settings and stratified on rituximab use during first-line therapy. Results: With a median follow-up of 73.5 months, the 5-year EFS and OS rates were 31.6% and 48.4% for whole cohort, respectively. Median DTI was 16 days (range, 1 to 67 days). Short DTI (≤16 days) was associated with a poor PS (ECOG PS 2-4, 53.3% versus 38.5%), altered Karnofsky score (<70%, 49.2% versus 32.0%) but not median of age (63 versus 64 years), CSF level, deep brain involvement, type of symptoms at diagnosis, diagnosis modality, treatment period, inclusion in clinical trial and rituximab used. However, patients with elevated LDH level presented more frequently a longer DTI (41.8% versus 32.0%). DTI was associated with MSKCC risk score but not IELSG score. For prognostic analyses, 205 patients were considered (39 patients with missing data [LDH or PS]). The 5-year EFS rates were 24.6% versus 39.4% for patients with DTI ≤ and > 16 days, respectively (Figure 1). Using a standard cox model, in univariate analyses, PS (2-4 vs. 0-1) (HR: 1.40, 95%CI, 1.00 - 1.94, P=0.045) and age (per 10-year increase) (HR: 1.19, 95%CI, 1.05-1.36, P=0.006) were associated with EFS but not DTI (≤ or > 16 days) (HR: 0.80, P=0.19), deep involvement (HR: 0.97, P=0.85) and LDH level (HR=1.02, P=0.91). In multivariate analysis, only age was associated with EFS (HR: 1.27, 95%CI, 1.11-1.46, P=0.001). Using a piecewise Cox model over two periods of time (before and after 12 months), we confirmed in multivariate analyses, the time varying effect of PS and age on EFS with a high-risk period before 12 months and no prognostic effect after 12 months (Table 1). We also observed a time-dependent effect for DTI as shown by a significant interaction with time (P=0.02) (Table 1). Indeed, longer DTI was not associated with EFS before 12 months (HR: 1.14, 95%CI, 0.74-1.76, P=0.56) however, it had a strong protective effect after 12 months (HR: 0.44, 95%CI, 0.24-0.86, P=0.02). Conclusions: In this large cohort of DLBCL PCNSL, a short DTI was mainly associated with poor PS at diagnosis. We confirmed that prognostic factors for PCNSL outcome such as age and PS had time-varying effects with a good predictability of EFS only before 12 months. However, DTI allows prediction of long-term EFS (>12 months) after first line treatment. These results could be related to different biological patterns of tumor aggressiveness. If confirmed in independent PCNSL cohorts, DTI should also be taken in consideration for patient selection and the interpretation of clinical trial results especially for long-term outcome. Disclosures Karlin: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Sanofi: Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Personal fees. Salles:Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria. Bachy:Amgen: Research Funding; Roche, Gilead: Consultancy; Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria.

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Treatment of elderly patients with primary CNS lymphoma

Annals of Lymphoma ◽

10.21037/aol-20-30 ◽

2021 ◽

Vol 5 ◽

pp. 2-2

Author(s):

Nicolas Martinez-Calle ◽

Lisa K. Isbell ◽

Kate Cwynarski ◽

Elisabeth Schorb

Keyword(s):

Elderly Patients ◽

Primary Cns Lymphoma ◽

Cns Lymphoma

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ACTR-23. MAINTENANCE TREATMENT WITH IBRUTINIB FOLLOWING FIRST LINE METHOTREXATE-BASED IMMUNO-CHEMOTHERAPY IN ELDERLY PATIENTS WITH PRIMARY CNS LYMPHOMA (PCNSL). A PHASE 2 OPEN-LABEL STUDY

Neuro-Oncology ◽

10.1093/neuonc/noz175.066 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi17-vi18

Author(s):

Osnat Bairey ◽

Alexandra Benouaich-amiel ◽

Shlomit Yust-Katz ◽

Ronit Gurion ◽

Tali Siegal

Keyword(s):

Maintenance Treatment ◽

Fungal Infections ◽

Randomized Study ◽

Primary Cns Lymphoma ◽

Progression Free Survival ◽

Cns Lymphoma ◽

High Dose ◽

Newly Diagnosed ◽

First Line ◽

Open Label

Abstract BACKGROUND Patients older than 60 years account for up to 70% of all PCNSL cases. Elderly PCNSL patients have median overall survival (OS) under 2 years and progression free survival (PFS) ranging between 6–16 months. Older patients have multiple comorbidities associated with low tolerability to high-dose (HD) chemotherapy. As maintenance treatment prolongs PFS and\or OS in several hematological malignancies we sought to investigate whether Ibrutinib maintenance may benefit elderly PCNSL patients. Ibrutinib was selected for maintenance since it has an impressive tolerability and activity in a range of systemic B-cell lymphomas. METHODS Single arm, open label, non-randomized study aiming to accrue 30 newly diagnosed PCNSL patients aged 60–85 years who received HD-methotrexate–based first line chemotherapy and have a documented response which is either partial (PR) or complete response (CR). The primary end-point is one and 2-year PFS and ibrutinib dose is 560mg/day. All patients undergo pre-maintenance neurocognitive evaluation which is repeated every 6 months. RESULTS Of the 16 patients screened for the study 2 were excluded due to relapse while on screening. 14 patients have been enrolled with a median age of 74 (61–80) years. The median interval between PCNSL diagnosis and start of ibrutinib maintenance is 7.6 (5.6–11.5) months. Currently, the median PFS is 22.5 (12–31.5) months. The adverse effects are largely grade 1/2 with rare grade 3/4 events. One patient discontinued treatment due to skin rash at 4.5 months. Two patients relapsed while on maintenance after 4 and 15 months of treatment. 3 patients with PR at enrolment improved to CR/CRu during maintenance. No invasive fungal infections have been observed. CONCLUSIONS Ibrutinib maintenance is feasible and well tolerated in newly diagnosed elderly PCNSL patients after first-line HD-MTX based treatment. The toxicity is mild to moderate. Enrollment is ongoing and updated outcomes will be presented at the meeting.

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Primary CNS Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2017.72.7602 ◽

2017 ◽

Vol 35 (21) ◽

pp. 2410-2418 ◽

Cited By ~ 119

Author(s):

Christian Grommes ◽

Lisa M. DeAngelis

Keyword(s):

Primary Cns Lymphoma ◽

Phase Iii ◽

Cns Lymphoma ◽

High Dose ◽

First Line ◽

Phase Iii Trial ◽

Non Hodgkin Lymphoma ◽

Systemic Spread ◽

Line Setting ◽

The Brain

Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. To our knowledge, no randomized trial has been conducted for recurrent/refractory disease, leaving many questions unanswered about optimal first-line and salvage treatments. This review will give an overview of the presentation, evaluation, and treatment of immunocompetent patients with PCNSL.

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Patterns of Treatment and Survival in Elderly Patients with Primary CNS Lymphoma; An 11-Year Population-Based Analysis

Blood ◽

10.1182/blood-2020-137300 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 2-3

Author(s):

Yazan Samhouri ◽

Moaath Mustafa Ali ◽

Thejus Jayakrishnan ◽

Chelsea Peterson ◽

Veli Bakalov ◽

...

Keyword(s):

Elderly Patients ◽

Elderly Population ◽

Primary Cns Lymphoma ◽

The Elderly ◽

Population Based ◽

Rank Test ◽

Cns Lymphoma ◽

Younger Patients ◽

To Receive ◽

Wilcoxon Rank Test

Introduction Primary CNS lymphoma (PCNSL) is an aggressive form of lymphoid malignancy that occurs exclusively in the brain, meninges, spinal cord, and eyes. The incidence of PCNSL has been increasing, particularly in the elderly population, with a median age at diagnosis of 66 years (Olson J.E. et al., Cancer 2002). The primary modality of treatment for this deadly disease is systemic chemotherapy that includes high-dose methotrexate (HD-MTX), with or without whole-brain radiation. Due to the toxicity of HD-MTX, physicians tend to avoid using it in the elderly population. This was confirmed in previous reports from the 1990s (Panageas K.S. et al., Cancer 2007). In this comprehensive population-based analysis, we sought to examine the patterns of treatment and survival in elderly patients in the 2000s and sought to investigate clinical and socioeconomic predictors of treatment selection. Methods We conducted a retrospective cohort analysis using de-identified data accessed from the national cancer database (NCDB). The NCDB provided records of 2985 patients diagnosed with PCNSL between 2004 and 2015. We excluded patients who are younger than 65 years old, those who tested positive for HIV, and those who started treatment >120 days since diagnosis to account for immortal time bias. Patients were divided into four groups based on treatment received: combined modality treatment (CMT), chemotherapy alone, radiation alone, and no treatment. Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Multivariate regression models were used to analyze predictors of the selection of any treatment versus no treatment and for selecting chemotherapy versus no chemotherapy. To account for variable baseline characteristics, we used propensity score weighting methodology to calculate estimates of interest. Survival estimates were performed using the Kaplan-Meier method, and survival differences were tested using the wilcoxon-rank test. Results We identified 1096 patients with PCNSL who fulfilled the inclusion criteria. The median age was 73 (IQR: 68-79). There were 52% males. The majority of the patients were whites (92%), lived in a metropolitan area (78%), treated at an academic/research center (57%). The most common treatment modality used was chemotherapy alone (48%), followed by CMT (22%), no treatment (16%), and radiation alone (13%). On multivariate analysis, age (OR: 0.94, 95% CI 0.92-0.96) and comorbidity score (OR: 0.63, 95% CI 0.52-0.76) significantly predicted receiving any type of treatment. Both age (OR: 0.91, 95% CI 0.89-0.94) and distance (OR: 1.006, 95% CI 1.001-1.01) were predictors of receiving chemotherapy. Median follow up was 12 months (IQR: 3-44). Median OS in months for the four groups was: 43.1 for CMT, 19.4 for chemotherapy alone, 17.2 for radiation alone, and 2.3 for no treatment. (wilcoxon-rank test p-value: <0.001). Median OS for the whole population was 17 months (IQR: 12-26). Patients >75 year old had lower median OS in general, but receiving CMT had a survival advantage as well. (Figures 1 and 2) Conclusions The majority of PCNSL patients in our analysis received treatment. Our results showed an increased trend of chemotherapy use in elderly patients compared with earlier reports, where radiation alone was the most common treatment modality. The median OS of patients was longer compared with the 1990s data (17 vs. 7 months). CMT was associated with better OS compared with no treatment and chemotherapy alone. Although this was numerically better compared with radiation alone, it was not statistically significant. Younger patients and patients with lower comorbidity scores were more likely to receive treatment. Younger patients and patients who live further from the treating facility were more likely to receive chemotherapy. Longer distance may have led to less radiation use due to the need for complex planning and frequent visits associated with radiation therapy. Our study is limited by its retrospective nature, which makes it at risk of selection bias. Using propensity score weighting methodology strengthens our results. Also, the NCDB lacks certain pertinent variables, such as details of chemotherapy regimens, and toxicity information especially for radiation in the CMT arm which will have practical implications. Disclosures Fazal: Glaxosmith Kline: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau. Kahn:Genetech: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Seattle Genetics: Honoraria; Abbvie: Honoraria; Celgene: Honoraria; AstraZeneca: Honoraria; Beigene: Honoraria.

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Combination of Rituximab with Chemotherapy Improved Outcome of Newly Diagnosed Primary CNS Lymphoma: A Retrospective Study of 209 Unselected Patients Referred to a Single Institution

Blood ◽

10.1182/blood.v126.23.1544.1544 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1544-1544

Author(s):

Herve Ghesquieres ◽

Celine Segura-Ferlay ◽

Gaelle Fossard ◽

Francois Ducray ◽

Violaine Safar ◽

...

Keyword(s):

Multivariate Analysis ◽

Protein Level ◽

Primary Cns Lymphoma ◽

Daily Practice ◽

Cns Lymphoma ◽

High Dose ◽

First Line ◽

First Line Therapy ◽

Meningeal Involvement ◽

Consolidation Radiotherapy

Abstract Introduction: Treatment of first-line therapy of primary CNS lymphoma (PCNSL) is based on high-dose methotrexate and cytarabine combination chemotherapy. Consolidation radiotherapy is mainly withdrawal for patients older than 60 years old regarding the excessive rate of neurological toxicity. Rituximab improved outcome of systemic diffuse large B-cell lymphoma but no data from randomized phase III trial is available to prove such outcome improvement for PCNSL. We introduced in daily practice intravenous rituximab in combination with chemotherapy for B-cell PCNSL in first-line therapy in 2004. The goal of this study is to determine whether such therapeutic modification improves PCNSL patient's outcome. Methods: Patients were from consecutive PCNSL cases (N=209) included in Leon Berard Cancer Centre registry (Lyon, France), from 1987 to 2011 (date of diagnosis). Median age of patients was 63 years (range, 26-87), 56% were male, 51% had a performance status (PS) >1, 63% had an involvement of deep structures of brain, 66% a high CSF protein level, 12% a meningeal involvement and 42% a high LDH level. Of the 171 available patients, 16% had 0-1, 60% had 2-3, and 24% had 4-5 adverse IELSG prognostic scores, respectively. Patients were all treated by chemotherapy, 92% and 63% of them by high-dose methotrexate and cytarabine containing chemotherapy, respectively followed by brain radiotherapy for 108 patients (58%). Intravenous rituximab was used in combination with chemotherapy in 61 patients (29%) between 2004 and 2011. Results: No difference in term of clinical characteristics (median age, PS, tumor site, CSF protein level, meningeal involvement, LDH level) was observed between patients treated with or without rituximab in combination with chemotherapy. With the median of 86.3 months (18.2-259), the median progression free survival (PFS) and overall survival (OS) for whole series were 17.3 months (95%CI, 10.7-25.9) and 35.6 months (95%CI, 22.7-50.0), respectively. The 3-year PFS were 55.5% (95%CI, 43-67) and 31.1% (95%CI, 24-39) for patients treated or not with rituximab, respectively (P=0.001). The 3-year OS were 73.6% (95%CI, 61-83) and 39.9% (95%CI, 32-48) for patients treated or not with rituximab, respectively (P<0.0001). A multivariate analysis was performed to test the impact of the addition of rituximab over clinical prognostic factors (age, PS, tumor site, CSF protein level, meningeal involvement, LDH level, IELSG score). Age>60 years (HR=1.74; 95%CI, 1.22-2.46; P=0.002), meningeal involvement (HR=2.33; 95%CI 1.42-3.85; P=0.0009) and used of rituximab (HR=0.50; 95%CI, 0.32-0.78; P=0.002) were identified as independent predictors of PFS. OS was significantly influenced by age>60 years (HR=1.94; 95%CI, 1.36-2.77; P=0.0002), PS (HR=1.76; 95%CI, 1.26-2.46; P=0.001), meningeal involvement (HR=2.17; 95%CI, 1.30-3.61; P=0.003) and used of rituximab (HR=0.39; 95%CI, 0.24-0.62; P=0.0001) in multivariate analysis. In a prognostic model integrating the IELSG score (0-1 vs. 2-3 vs. 4-5) (P=0.0002 for PFS and P<0.0001 for OS), used of rituximab was independently associated with the improvement of PFS (HR=0.60; 95%CI, 0.39-0.91; P=0.02) and OS (HR=0.44; 95%CI, 0.26-0.72; P=0.001). Disease free survival including patients who reached a complete response at the end of the first-line treatment was also improved by the used of rituximab (not reached versus 3.2 years, P=0.04). We also observed in this daily practice study, a reduction of the used of radiotherapy as first-line consolidation treatment (69% vs. 34%, P<0.001) before (1987-2003) and after (2004-2011) rituximab period. Conclusion: In this retrospective analysis, we showed that PCNSL patients treated with intravenous rituximab in combination with first-line chemotherapy had a better outcome. The frequency of consolidation radiotherapy was reduced for these patients treated at rituximab era. In multivariate analysis, CSF involvement was an independent adverse prognostic factor that inclines to improve meningeal explorations and propose new therapeutic options for CSF positive PCNSL patients. Disclosures No relevant conflicts of interest to declare.

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The Trend of Combined Modality Treatment and its Outcomes in Elderly Patients With Primary CNS Lymphoma; A 12-Year Population-Based Analysis Using Propensity Score

10.21203/rs.3.rs-651578/v1 ◽

2021 ◽

Author(s):

Yazan Samhouri ◽

Moaath K Mustafa Ali ◽

Thejus Jayakrishnan ◽

Veli Bakalov ◽

Salman Fazal ◽

...

Keyword(s):

Propensity Score ◽

Elderly Patients ◽

Primary Cns Lymphoma ◽

Population Based ◽

Treatment Selection ◽

Cns Lymphoma ◽

P Value ◽

Combined Modality Treatment ◽

Factors Affecting ◽

Combined Modality

Abstract BackgroundThe addition of radiation to chemotherapy in elderly patients with PCNSL remains controversial. Our objective was to assess the trend of combined modality treatment (CMT) and compare its survival with chemotherapy alone and radiation alone in non-HIV patients. MethodsWe identified 6,537 patients who received single treatment modality, combined modality treatment, or no treatment at all between 2004 and 2015 from the National Cancer Database. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of CMT use. A propensity score weighting methodology was used to compare survival outcomes. FindingsOnly 12.8% of patients received CMT, and this proportion steadily declined between 2004 (17.7%) and 2015 (8.7%), with APC of -6.0% (95% CI -8.0 to -4.0, p-value <0.001) during the 12 years. Apart from classical prognostic factors (age and comorbidities), treatment selection was significantly influenced by sex, facility type, degree of urbanization, and type of insurance. CMT had improved survival (median overall survival 19.5 months (95% CI 15.7-22.8)) compared with single-modality treatment. This effect was more prominent in the first year. Conclusion Socioeconomic factors affect the selection of treatment in elderly patients with PCNSL that can alter outcomes. CMT is falling out of favor in this patient population due to the risks of neurotoxicity. Further work should focus on developing strategies that minimize toxicity and access disparities without compromising survival

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