230 - A 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

Background

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 patients with PCNSL.

Methods

We screened 35 patients & enrolled 24 patients with PCNSL in a phase II trial. They underwent 5 two-weekly cycles of MVP chemotherapy with HDMTX, Vincristine & Procarbazine. Rituximab was added in 16 patients as per their preference & affordability. Patients with complete response (CR) to induction chemotherapy were given reduced dose WBRT 23.4Gy/13fractions/2.5weeks while those with partial response (PR), stable or progressive disease(PD) were given standard dose WBRT 45Gy/25fractions/5 weeks. Thereafter 2 cycles of consolidation chemotherapy with Cytarabine was given. The primary endpoints of the study were assessment of response rate & progression free survival (PFS). The secondary endpoints were assessment of overall survival (OS), toxicity profile, serial changes in quality of life & neuropsychological parameters.

Results

The median age at diagnosis was 50 years. Out of 20 patients who completed induction chemotherapy, 10(50%) achieved CR, 9(45%) had PR & 1 patient had PD. After a median follow-up period of 21.05 months, the median OS and PFS had not been reached. The actuarial rates of 3 year PFS & OS were 51% & 51.4% respectively. 4 patients in reduced dose WBRT arm had recurrence & 2 of them died of PD, whereas there was one recurrence and no cancer related death in standard dose WBRT arm. On univariate analysis of PFS, age≤60 years(p = 0.004) & use of standard dose WBRT (p = 0.047) led to significantly improved outcome. Serial neuropsychological assessments showed marked improvement in general cognition, verbal fluency & motor speed after induction chemotherapy & treatment completion.

Conclusions

In patients with newly diagnosed PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due to higher risk of recurrence, progression & early death.

Editorial acknowledgement

Clinical trial identification

Clinical Trial Registry India: CTRI/2015/10/006268.

Legal entity responsible for the study

The authors.

Funding

All India Institute of Medical Sciences, New Delhi, Indian Council of Medical Research.

Disclosure

All authors have declared no conflicts of interest.