scholarly journals Sarcopenia Measured by Temporalis Muscle Thickness Independently Predicts Early Relapse and Short Survival in Primary CNS Lymphoma

2021 ◽  
Author(s):  
Alipi Bonm ◽  
Anthony Menghini ◽  
Jerome J. Graber
Keyword(s):  
Univariate Analysis ◽  
Primary Cns Lymphoma ◽  
Muscle Thickness ◽  
Early Mortality ◽  
Cns Lymphoma ◽  
First Year ◽  
High Dose ◽  
Temporalis Muscle ◽  
Short Survival ◽  
Early Progression

Abstract Introduction: Primary CNS lymphoma (PCNSL) outcomes diverge between a majority of patients who achieve long term remission and a smaller minority who have aggressive disease course and die in the first year. Sarcopenia is increasingly recognized as a powerful predictor of mortality in brain and systemic cancers. Temporalis muscle thickness (TMT) is a validated radiographic measure of sarcopenia. We hypothesized that patients with TMT less than one standard deviation below the mean (“very thin TMT”) would go on to have shorter survival. Methods: Two blinded operators retrospectively measured TMT in 99 consecutive pretreatment brain MRIs from patients that were subsequently diagnosed with PCNSL. Results: On univariate analysis TMT predicted early progression (HR 4.25, 95% CI 1.95 – 9.29, p<0.001) and early mortality (HR 4.38, 95% CI 2.25 – 8.53, p<0.001), and these effects were maintained in subgroups of patients both <65 and ³65 years of age. Very thin TMT predicted mortality more robustly than IELSG or MSKCC scores. Patients with very thin TMT received fewer cycles of high-dose methotrexate (HD-MTX) and were less likely to receive consolidation. On multivariate analysis which included the covariates age, sex, TMT, ECOG, BMI, lifetime doses of HD-MTX, and consolidation, very thin TMT was independently associated with both early progression (HR = 7.87, 95% CI = 3.55 – 17.45, p<0.001) and short survival (HR 4.49, 95% CI = 1.94 – 10.40, p<0.001). Conclusions: We conclude that PCNSL patients with very thin TMT are at high risk for relapse and early mortality. Future trials should stratify patients by TMT to avoid potential confounding.

NIMG-68. SARCOPENIA AS MEASURED BY TEMPORALIS MUSCLE WIDTH IS A PREDICTOR OF SURVIVAL IN PRIMARY CNS LYMPHOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi145-vi145
Author(s):  
Alipi Bonm ◽  
Anthony Menghini ◽  
Jerome Graber
Keyword(s):  
Clinical Trials ◽  
Standard Deviation ◽  
Intraclass Correlation ◽  
Primary Cns Lymphoma ◽  
Muscle Thickness ◽  
Important Variable ◽  
Cns Lymphoma ◽  
Routine Practice ◽  
Temporalis Muscle ◽  
Increased Risk

Abstract Sarcopenia refers to a loss of skeletal muscle mass, which has been associated with increased risk of injury and decreased ability to perform activities of daily living. In multiple cancers including systemic lymphomas, sarcopenia has been strongly associated with survival and may be an important way to risk stratify patients in clinical trials as well as routine practice. Temporalis muscle width has been reported as an indicator of sarcopenia and independent predictor of outcomes in multiple settings including glioblastoma, brain metastases and subarachnoid hemorrhage. We evaluated temporalis width in primary CNS lymphoma (PCNSL) patients at presentation and outcomes. Using an institutional database of immunocompetent PCNSL patients treated at the University of Washington, two independent readers reviewed the initial MRIs for 104 patients who presented from 2011-2021 and measured the width of the temporalis muscle on axial T1 images. Median duration of follow up was 42.2 months (range 0.59-125.9 months). Median age at diagnosis was 65 (range 19-90 years), and patients were 42.8% male, 57.2% female. Interrater variability was acceptable with an average intraclass correlation coefficient of 0.934. Temporalis measurements were normally distributed, with mean 0.79 cm and standard deviation 0.18 cm. We divided patients into two groups, those with temporalis width less than or greater than 1 standard deviation below the mean (absolute value 0.60 cm). Temporalis width was strongly associated with survival among all patients (χ2=15.5, p&lt; 0.001) as well as patients 65 years or older (χ2=4.5, p=0.03). We conclude that sarcopenia as measured by temporalis muscle thickness is associated with survival in PCNSL and may be an important variable to consider in clinical trials and routine practice.

P14.48 Extracerebral relapses of primary CNS lymphoma (PCNSL): a LOC network retrospective study

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii47-ii47
Author(s):  
J Dufour ◽  
S Choquet ◽  
A Schmitt ◽  
G Ahle ◽  
R Houot ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Molecular Mechanisms ◽  
Univariate Analysis ◽  
Primary Cns Lymphoma ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cns Relapse ◽  
Systemic Relapse ◽  
Work Up

Abstract BACKGROUND Classically PCNSL remain confined within the CNS throughout their evolution for reasons still unknown (&gt; 80% cerebral relapses). The aim of this study was to describe the characteristics and outcomes of the rare extracerebral relapses of PCNSL. MATERIAL AND METHODS This is a multicenter, retrospective study. We included all immunocompetent patients newly diagnosed with diffuse large B-cell PCNSL registered in the national LOC network database since 2010 and followed prospectively, who presented an extracerebral relapse, pure (extracerebral only site) or associated with concomitant CNS relapse (mixed). All had body scan and/or TEP -CT at diagnosis work up. RESULTS Of the 1968 PCNSL included in the database, 29 (1.5%) patients presented a systemic relapse [median age 71 years, median KPS 70% at relapse], either pure (n=19) or mixed (n=10), with a histological confirmation in 19 cases (66%). The median delay between initial diagnosis and systemic relapse was 15 months [2–49 months], with 5 very early relapses (&lt;8 months) and 10 late relapses (&gt;21 months). 27 patients had symptoms, 21 related to the location of relapse and 6 with only general symptoms. The localization was thoracic (n=11), abdominal/pelvic (n=14), head/neck (n=6) and limbs (n=9). We found visceral (n=24, 83%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n=12, 41%) and peripheral nervous system (PNS) (n=8, 28%; 4 plexus and 4 extradural roots) involvement. 27 patients were treated with chemotherapy, either with only systemic target (n=8) (R-CHOP alone) or mixed systemic and CNS target (n=19) (R-CHOP-MTX, R-ICE, GEMOX, RDHAC) and consolidated by high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) in 4 cases [median age 55 years, median KPS 80%], with 34% of complete response. After systemic relapse, median progression-free survival was 8 months and overall survival (OS) was 9 months, 15 months for pure systemic and 4.5 months for mixed relapses. KPS&gt;70%, pure systemic relapses and complete response were significantly associated with higher OS in univariate analysis. CONCLUSION Extracerebral PCNSL relapses are very rare, mainly extranodal and involve a large spectrum of anatomical sites, the most frequent being testis, breast and PNS. Prognosis was worse in case of mixed relapse than in pure systemic relapse that was similar to non PCNSL lymphomas. Very early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic work up that should include systematically a FDG PET-CT. More studies are needed to refine their treatment and to specify the role of HCT-ASCT. Paired tumor tissues at diagnosis (CNS)/relapse (extracerebral) analysis would provide a better understanding of underlying molecular mechanisms.

scholarly journals P14.45 Primary diffuse large B-cell CNS lymphoma over 80 years: an analysis of 110 patients from the french Oculo-Cerebral Lymphoma (LOC) network

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii77-iii77
Author(s):  
A MAAREK ◽  
D Maucort-Boulch ◽  
C Houillier ◽  
K Hoang-Xuan ◽  
C Soussain ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Primary Cns Lymphoma ◽  
National Database ◽  
Cns Lymphoma ◽  
High Dose ◽  
Chemotherapy Response ◽  
First Line ◽  
Cerebral Lymphoma ◽  
Elevated Liver Enzymes

Abstract BACKGROUND in large unselected series, the median age of Primary CNS Lymphoma (PCNSL) patients (pts) is about 70 years. In one USA cancer registry study for PCNSL patients older than 65 years, 14% of them are older than 80 years. Data on clinical characteristics, therapeutical management, toxicity of treatment and outcome of these very elderly pts are limited. MATERIAL AND METHODS we reviewed PCNSL pts aged of 80 years or older included in the database of the French Oculo-Cerebral lymphoma (LOC) network. From January 2011, this network prospectively recorded all newly diagnosed PCNSL from 22 regional expert centers in France. RESULTS 110 pts with a DLBCL PCNSL aged of 80 years or older were diagnosed between January 2011 and January 2018 representing 8% of pts available in the LOC database. The clinical characteristics were as follows: 63% of females; median age: 83y (80–92); performance status (PS) ≥3, 55% of pts. Median creatinine clearance (CKD.EPI) was 70ml/min. Treatment was initiated either by a neuro-oncology or a hematology team in 35% and 65% of cases, respectively. First line treatment was high-dose (HD) methotrexate (MTX) based chemotherapy (CT) in 85 pts (77%), other chemotherapy regimen in 13 pts (12%) and palliative care in 12 pts (11%). Interestingly, no difference of distribution for the main clinical and biological characteristics was observed between these three groups. After first-line induction chemotherapy, response rate for evaluable patients (n=85) were as follows: 37% of complete response, 9% of partial response, 54% of stable or progressive disease. Rituximab was used in combination with CT in 53/98 treated pts (54%). For toxicity, among the 351 infusions performed for the 85 pts who received MTX-based CT, grade 3–4 toxicities were: 46% of any events, 15% of infection, 13% of cytopenia, 11% of acute renal failure and 8% of elevated liver enzymes. 13% of pts presented toxic death. Median progression free survival (PFS) and overall survival (OS) were 5 months and 8 months, respectively. Pts treated with MTX-based CT had a significantly prolonged PFS and OS. In the univariate analysis performed for the 85 pts treated with MTX-based CT, no initial clinical and biological influenced PFS or OS. Intravenous rituximab used in first line therapy significantly improved PFS and OS. CONCLUSION in this large series of consecutive PCNSL pts aged of 80y or over prospectively recorded in a national database, we showed that the prognosis remains poor with major toxicity under conventional treatment. No clinical predictor of survival was highlighted in our series. Patients initially treated with MTX-based CT in combination with rituximab had an improved outcome. The development of target and innovative therapies is needed for this category of patients representing 8% of all PCNSL in the database of the LOC network.​

scholarly journals SS-4 High dose chemotherapy with autologous hematopoietic stem cell transplantation for CNS lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii2
Author(s):  
Eisei Kondo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Hematopoietic Stem

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is listed as a consolidation therapy option for primary central nervous system (CNS) lymphoma in the guidelines of western countries. The advantages of HDT-ASCT for primary CNS lymphoma as consolidation are believed to be high rates of long-term remission and lower neurotoxicity, even though its eligibility is limited to younger fit patients. In the Japanese guideline, HDT-ASCT for primary CNS lymphoma is however not recommended in daily practice, mainly because thiotepa was unavailable since 2011. The Japanese registry data for hematopoietic transplantation have shown that primary CNS lymphoma patients were treated with various HDT regimens and thiotepa-containing HDT was associated with better progression free survival (P=.019), lower relapse (P=.042) and a trend toward a survival benefit (Kondo E et al, Biol Blood Marrow Transplant 2019). A pharmacokinetic study of thiotepa(DSP-1958) in HDT-ASCT for lymphoma was conducted in 2017, and thiotepa was approved for HDT-ASCT in lymphoma this March, meaning that optimal HDT regimen for CNS lymphoma is now available in Japan. The treatment strategy of CNS lymphoma needs further development to improve survival and reduce toxicity.

scholarly journals Treatment of HIV-associated primary CNS lymphoma with antiretroviral therapy, rituximab, and high-dose methotrexate

Blood ◽  
2020 ◽  
Vol 136 (19) ◽  
pp. 2229-2232
Author(s):  
Kathryn Lurain ◽  
Thomas S. Uldrick ◽  
Ramya Ramaswami ◽  
Mark N. Polizzotto ◽  
Priscila H. Goncalves ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junyao Yu ◽  
Huaping Du ◽  
Xueshi Ye ◽  
Lifei Zhang ◽  
Haowen Xiao
Keyword(s):  
Meta Analysis ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Dose Methotrexate

AbstractWith the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

First Results of the Acsé Pembrolizumab Phase II in the Primary CNS Lymphoma (PCNSL) Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Khe Hoang-Xuan ◽  
Roch Houot ◽  
Carole Soussain ◽  
Marie Blonski ◽  
Anna Schmitt ◽  
...  
Keyword(s):  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Moderate Activity ◽  
Multicentric Study ◽  
First Results ◽  
Duration Of Response

Background: AcSé Pembrolizumab is a Phase 2, open-label, single-arm, multi-cohort, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with advanced rare cancers (NCT03012620). Here, we report the first results of Pembrolizumab in the cohort of Primary Central Nervous System Lymphoma (PCNSL). Methods: Main inclusion criteria were: relapsed or refractory PCNSL after one or several lines of treatment including high dose Methotrexate based chemotherapy, pathologically confirmed diffuse large B cell lymphoma, age&gt;18, HIV negative, concurrent steroid medication at a dose no greater than prednisone 20 mg/day or equivalent. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycles for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to IPCG at 84 day after the start of treatment. Secondary endpoints included best response (ORR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. Analysis used all enrolled patients. Results: 50 patients suffering from PCNSL, including 9 primary vitreoretinal lymphoma (PVRL) were included from July, 2017 to October, 2019. Median age was 72 years (range: 43 to 83), Median PS (ECOG) was 1 (range 0-1). The median number of cycles was 4 (range 1-35). At 84 days from start of treatment, 6 patients responded (4 CR+2PR). Overall, 3 patients whose response was not assessed were considered as failures, and the rates of ORR (CR+PR), stable disease (SD), progressive disease (PD) were 26% (13/50, 8 CR + 5 PR), 10% (5/50), 58% (29/50), respectively. ORR was 29% (12/41) and 11% (1/9) in primary cerebral lymphoma and PVRL respectively. After a median follow-up of 6.7 months (range 0.2-27.4), median PFS was 2.6 months, with 6-month PFS of 29.8% and 6-month OS of 60.4%. In responders, median duration of response was estimated at 10 months (95%CI, 2.7 to 12.5). Grade III and IV toxicities related to the drug were observed in 4 patients (8%) and one patient (2%) respectively. No related toxic death was reported. Conclusion: Pembrolizumab shows moderate activity in relapsed/ refractory PCNSL with acceptable toxicity, supporting further studies evaluating its use in combination therapies. Disclosures Hoang-Xuan: BTG: Consultancy, Research Funding. Houot:Bristol-Myers Squibb: Honoraria; MSD: Honoraria; Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Schmitt:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen: Honoraria. Ahle:Roche: Honoraria; Novartis: Honoraria; Biogene: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria. Bories:Abbvie: Consultancy; Celgen: Consultancy; Gilead: Consultancy; BMS: Honoraria; Novartis: Honoraria. Houillier:BTG: Consultancy.

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