Journal of Neuro-Oncology

, Volume 139, Issue 1, pp 153–166 | Cite as

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

  • Narayan Adhikari
  • Ahitagni Biswas
  • Ajay Gogia
  • Ranjit Kumar Sahoo
  • Ajay Garg
  • Ashima Nehra
  • Mehar Chand Sharma
  • Suman Bhasker
  • Manmohan Singh
  • Vishnubhatla Sreenivas
  • Rohan Chawla
  • Garima Joshi
  • Lalit Kumar
  • Subhash Chander
Clinical Study



The treatment of primary CNS lymphoma (PCNSL) comprises high dose methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy (WBRT), the major drawback of which is long term neurotoxicity. We intended to assess the feasibility of response adapted WBRT in PCNSL in the Indian setting.


We screened 32 patients and enrolled 22 eligible patients with PCNSL from 2015 to 2017 in a prospective phase II trial. The patients underwent five 2-weekly cycles of induction chemotherapy with rituximab, methotrexate, vincristine, procarbazine. Patients with complete response(CR) to induction chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks while those with partial response (PR), stable or progressive disease (SD or PD) were given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter two cycles of consolidation chemotherapy with cytarabine were given. The primary endpoints of the study were assessment of response rate (RR) and progression free survival (PFS). The secondary endpoints of the study were assessment of overall survival (OS), toxicity profile of treatment and serial changes in quality of life and neuropsychological parameters.


Out of 19 patients who completed HDMTX based chemotherapy, 10 (52.63%) patients achieved CR, 8 (42.11%) patients had PR and 1 patient had PD. After a median follow-up period of 11.25 months, the estimated median OS was 19 months. The actuarial rates of PFS and OS were respectively 94.1 and 68.2% at 1 year and 50.2 and 48.5% at 2 years. Three patients in reduced dose WBRT arm had recurrence and two of them died of progressive disease, whereas there was no recurrence or disease related death in standard dose WBRT arm. On univariate analysis of PFS, age ≤ 50 years and use of standard dose WBRT (45 Gy) led to significantly improved outcome (p value 0.03 and 0.02 respectively).


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


Primary CNS lymphoma High dose methotrexate Whole brain radiotherapy 



Financial assistance for research received from Indian Council of Medical Research (ICMR).


Dr. N. Adhikari received financial assistance for research from Indian Council of Medical Research (ICMR). This was an investigator initiated prospective phase II trial. The cost of imaging(MRI) and other investigations, chemotherapy (but not Rituximab) and radiotherapy in patients in this clinical trial was exempted by the competent authority at All India Institute of Medical Sciences, New Delhi.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Research involving human and animal participants

This article does not contain any study with animals performed by any of the authors.

Supplementary material

11060_2018_2856_MOESM1_ESM.docx (1 mb)
Supplementary material 1 (DOCX 1054 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Narayan Adhikari
    • 1
  • Ahitagni Biswas
    • 1
  • Ajay Gogia
    • 2
  • Ranjit Kumar Sahoo
    • 2
  • Ajay Garg
    • 3
  • Ashima Nehra
    • 4
  • Mehar Chand Sharma
    • 5
  • Suman Bhasker
    • 1
  • Manmohan Singh
    • 6
  • Vishnubhatla Sreenivas
    • 7
  • Rohan Chawla
    • 8
  • Garima Joshi
    • 4
  • Lalit Kumar
    • 2
  • Subhash Chander
    • 1
  1. 1.Department of Radiation OncologyAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of Medical OncologyAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.Department of NeuroradiologyAll India Institute of Medical SciencesNew DelhiIndia
  4. 4.Department of Clinical NeuropsychologyAll India Institute of Medical SciencesNew DelhiIndia
  5. 5.Department of PathologyAll India Institute of Medical SciencesNew DelhiIndia
  6. 6.Department of NeurosurgeryAll India Institute of Medical SciencesNew DelhiIndia
  7. 7.Department of BiostatisticsAll India Institute of Medical SciencesNew DelhiIndia
  8. 8.Department of OphthalmologyAll India Institute of Medical SciencesNew DelhiIndia

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