A prospective phase II trial of response adapted whole brain radiotherapy after high dose methotrexate based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma-analysis of acute toxicity profile and early clinical outcome

Adhikari, Narayan Prasad; Biswas, Ahitagni; Gogia, Ajay; Sahoo, Ranjit Kumar; Garg, Ajay; Nehra, Ashima; Sharma, Mehar Chand; Bhasker, Suman; Singh, Meharban; Sreenivas, Vishnubhatla; Chawla, Rohan; Joshi, Garima; Kumar, Lalit; Chander, Subhash

doi:10.1007/s11060-018-2856-y

Cited by 24 publications

(21 citation statements)

References 23 publications

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“…HD-MTX-based chemotherapy combined with radiotherapy is a traditional treatment strategy for PCNSL. Although some studies have reported that the combination of MTX-based regimens with WBRT has promising effects, it leads to an increased incidence of advanced neurotoxicity ( 12 , 13 ). Hence, WBRT is no longer a routinely recommended treatment for patients with newly diagnosed PCNSL.…”

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confidence: 99%

The Efficacy and Safety of Cytarabine on Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

et al. 2020

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Background: The role of cytarabine on newly diagnosed primary central nervous system lymphoma (PCNSL) remains controversial. The present study mainly aimed to assess the efficacy and safety of cytarabine in the induction treatment of PCNSL. Methods: We systematically searched PubMed, Embase, and the Cochrane library for randomized controlled trials comparing treatment of PCNSL patients with or without cytarabine. A meta-analysis was conducted to compare the odds ratios (ORs) with corresponding 95% confidence intervals (95% CI) for complete remission (CR) rate, overall response rate (ORR), grade 3-4 toxic effects, hazard ratios (HRs) with 95% CIs for progression-free survival (PFS), and overall survival (OS) using Stata 12.0. Results: In total, three randomized clinical trials were analyzed in this study. The result of our statistical analysis demonstrated that the application of cytarabine was closely correlated with a higher CR (OR: 2.27, 95% CI: 1.29-3.99, P < 0.01) and ORR (OR: 2.11, 95% CI: 1.14-3.93, P = 0.02). No significant difference was found in OS (HR: 0.75, 95% CI: 0.50-1.13, P = 0.17), but PFS had been improved (HR: 0.66, 95% CI: 0.45-0.97, P = 0.04) when cytarabine was added to the treatment regimen. The grade 3-4 side effect rate of the cytarabine group was higher (overall OR: 2.95, 95% CI: 1.37-6.34, P < 0.01) than that of the cytarabine-free group. Conclusions: This meta-analysis verifies that adding cytarabine to the therapeutic regimen is helpful for newly diagnosed PCNSL patients in terms of CR, ORR, and PFS. Moreover, it should be noted that the grade 3-4 toxic effects, especially hematological toxicity, are higher in the cytarabine group than in the cytarabine-free group. The results indicate that cytarabine plays an important role in the induction therapy of PCNSL. Large-sample and high-quality RCTs should be conducted to verify our results and confirm the effects of cytarabine on newly diagnosed PCNSL.

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Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Cytarabine on Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

et al. 2020

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“…No severe late neurocognitive morbidity was observed in this cohort. However, a similar treatment approach of response-adapted WBRT led to a significantly inferior PFS in newly diagnosed patients with PCNSL with a CR to HDMTX-based induction chemotherapy at our institute [18]. Hence the consolidation strategy in the illustrative patient was partially reduced-dose WBRT (36 Gy) followed by 2 cycles of high-dose cytarabine and rituximab-based chemoimmunotherapy.…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Primary Central Nervous System Lymphoma in an Adolescent Female Treated with High-Dose Methotrexate and Rituximab-Based Chemoimmunotherapy and Consolidation Whole Brain Radiotherapy

et al. 2019

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Primary central nervous system lymphoma (PCNSL) is a rare pediatric brain tumor. A 16-year-old female patient presented to the clinic with complaints of multiple episodes of generalized tonic clonic seizures, nystagmus, and weakness on the left side of the body for 3 weeks. She had similar symptoms, waxing and waning for the last 2 years, responding to corticosteroids. Repeat magnetic resonance imaging (MRI) of the brain showed multiple areas of signal abnormalities involving the left temporal lobe, the basal ganglion, the thalamus, and the right frontal and occipital lobes with contrast enhancement in bitemporal lesions. With a clinico- radiological diagnosis of demyelinating disorder, she underwent an image-guided right frontal lobe biopsy, which revealed sheets of atypical lymphoid cells diffusely immunopositive for CD20 but negative for CD3, CD10, BCL-6, and MUM-1, suggesting diffuse large B-cell lymphoma, germinal center B-cell subtype. The systemic lymphoma workup was essentially normal. She received 5 cycles of chemoimmunotherapy with rituximab, high-dose methotrexate (HDMTX), vincristine, and procarbazine and had a complete radiological response (CR). This was followed by whole brain radiotherapy (WBRT) to a dose of 36 Gy in 20 fractions over 4 weeks. Subsequently she received 2 cycles of consolidation chemoimmunotherapy with rituximab and high-dose cytarabine. Serial brain MRI done 1, 4, and 8 months after completion of treatment showed persistence of the CR. At the last follow-up visit, 15 months from the date of diagnosis, she was disease free and asymptomatic. This report underlines the fact that PCNSL in adolescents may be effectively treated with a combination of HDMTX- and rituximab-based chemoimmunotherapy followed by consolidation with WBRT.

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“…The standard dose of WBRT was 45 Gy in 25 fractions over 5 weeks (n = 50) by bilateral parallel opposed skull fields using a German Helmet portal with cobalt-60 gamma rays; the procedure is described in detail elsewhere. 17 In a few patients (n = 10), reduced-dose WBRT (23.4 Gy in 13 fractions over 2.5 weeks) was administered, because these patient experienced complete response (CR) as part of a study protocol. 4,17,18…”

Section: Methodsmentioning

confidence: 99%

Primary CNS Lymphoma in India: A 17-Year Experience From the All India Institute of Medical Sciences

Patekar

Adhikari

Biswas

et al. 2019

JGO

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PURPOSE The information about the outcome of primary CNS lymphoma (PCNSL) in India is scarce, because there is no population-based or large hospital-based data. MATERIALS AND METHODS This is a retrospective study that spanned 17 years (2001 to 2017) to study the outcome of PCNSL at the All India Institute of Medical Sciences (AIIMS), which is a tertiary care center in Northern India. RESULTS Only one of 99 patients was positive for HIV serology. Diffuse large B-cell lymphoma was the most common histology (97.7%). The median patient age was 50 years (range, 13 to 70 years), and the ratio of men to women was 1.9. The median duration of symptoms before diagnosis was 3.5 months (range, 0.5 to 48 months), and 58.5% had a performance status (PS) of 3 or more. Multiple intracranial lesions were present in 81.8% of patients. Surgical resection was performed in 45%, and approximately 22% of patients were ineligible for treatment. Most patients (n = 73) were treated with high-dose methotrexate (HDMTX)–based regimens (ie, methotrexate, vincristine, and procarbazine with or without rituximab). Pharmacokinetic monitoring of methotrexate was not available at our center. HDMTX-related mortality was 3.9%. The median follow-up duration, event-free survival (EFS), and overall survival (OS) were 34 months, 20.4 months, and 31.7 months, respectively. Addition of rituximab (n = 27) to MVP resulted in a higher objective response rate (88.9% v 73.9% without rituximab; P = .12), complete remission (81.5% v 56.5%; P = .03), 2-year EFS (57.3% v 40.4%; P = .02), and 2-year OS (61.6% v 53.4%; P = .056). CONCLUSION This is the largest study of PCNSL from India. The patients were immunocompetent and young but presented with a high-burden disease that precluded treatment in approximately 22%. The treatment with HDMTX appears safe without pharmacokinetic monitoring. The outcome is comparable to those observed in the West, and rituximab use showed additional benefit. There are notable barriers with respect to management of PCNSL in the real world, and efforts are required to improve the outcome more.

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A prospective phase II trial of response adapted whole brain radiotherapy after high dose methotrexate based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma-analysis of acute toxicity profile and early clinical outcome

Abstract: In patients with PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due to higher risk of recurrence, progression and early death. Trial Registration No CTRI/2015/10/006268.

Cited by 24 publications

References 23 publications

The Efficacy and Safety of Cytarabine on Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

The Efficacy and Safety of Cytarabine on Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

A Rare Case of Primary Central Nervous System Lymphoma in an Adolescent Female Treated with High-Dose Methotrexate and Rituximab-Based Chemoimmunotherapy and Consolidation Whole Brain Radiotherapy

Primary CNS Lymphoma in India: A 17-Year Experience From the All India Institute of Medical Sciences

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