Treatment outcome and prognostic factors in PCNSL

Abstract

Objectives Standard treatment with a thiotepa-based regimen in countries with a limited resource is less feasible. Aims of the study were to evaluate the treatment outcome, and identify the prognostic factors in patients with primary central nervous system lymphoma (PCNSL). Methods We conducted a retrospective study of 43 patients diagnosed with PCNSL, DLBCL subtype, who were treated with either HDMTX-based regimen, whole brain radiotherapy (WBRT), or both between 2010 and 2017. Results There were 43 patients with a median age of 65 years (range 34–89 years). Protein expression of CD10, Bcl6, MUM1, Bcl2 and MYC were found in 19, 86, 91, 91 and 23%, respectively. Both germinal center B cell (GCB) and double-expressor (MYC+/Bcl2+) lymphomas were found in 21%. Multiple brain lesions and maximum tumor diameter (MTD) ≥5 cm were seen in 27 and 10 patients, respectively. Chemotherapy combined with WBRT, chemotherapy and WBRT were given to 20, 14 and 9 patients, respectively. Overall complete remission (CR) rate was 55.8%. Those receiving a combined-modality therapy had a higher CR rate than those treated with either chemotherapy (75% versus 36%, p = 0.036) or WBRT (75% versus 44%, p = 0.109). Median follow-up time was 17 months, and a 7-year overall survival (OS) was 40%. Features associated with a prolonged OS were an ECOG score ≤ 2 ( p = 0.001), multiple brain lesions ( p = 0.010), multiple area of brain involvement ( p = 0.023), MTD < 5 cm ( p = 0.004), GCB subtype ( p = 0.003) and positive CD10 staining ( p = 0.007). Expression of Bcl2 protein was associated with a significantly worse OS in the non-GCB DLBCL patients. Discussion The factors affecting treatment outcomes in PCNSL were cell of origin of DLBCL, lesion characteristics, patients’ status and treatment regimen.

New genetic prognostic biomarkers in primary central nervous system lymphoma (PCNSL)

“…BCL2 expression not related to t(14;18) (q32;q21) is frequent (Deckert, Brunn, et al., 2014; Deckert, Brunn, et al., 2014). Similar to literature, in this cohort most patients presented overexpression of BCL2 protein (80%), which a tendency for association with poor prognosis (worse OS and PFS; p values = .067 and 0.083, respectively) (Cai et al., 2019; Montesinos‐Rongen et al., 2008; Niparuck et al., 2019). In pre‐rituximab era, BCL2 expression was considered a poor prognostic factor in NHL; however, the overexpression of BCL2 in the post‐rituximab era in DLBCL has shown no prognostic value (Mounier et al., 2003).…”

Apparent diffusion coefficient as a valuable quantitative parameter for predicting clinical outcomes in patients with newly diagnosed primary CNS lymphoma

“…Performing WBRT after chemotherapy yields a better survival rate than chemotherapy alone. However, the incidence of radiotherapy-induced neurotoxicity increases in patients who have undergone combined therapy [ 7 - 9 ]. Therefore, precise prognostic factors are needed to develop improved risk-adapted treatment strategies, such as high-dose chemotherapy with autologous stem cell transplantation (auto-SCT) or chemotherapy, followed by WBRT in high-risk patients with PCNSL.…”

MYD88 L265P mutation in primary central nervous system lymphoma is associated with better survival: A single centre experience

“…Interestingly, our data suggest that among treated PCNSL cases, a combined-modality therapy may be better at prolonging survival. A recent study of PCNSLs reported that a significantly prolonged survival could be achieved with a combined-modality therapy, although unlike in our study, autologous stem cell therapy was excluded 36 . Current treatment regimens for PCNSL remain ineffective partly because CNS is inaccessible to many drugs.…”