Background. To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL)... Show moreBackground. To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL).Methods. One hundred and ninety-nine patients from a phase Ill trial (HOVON 105/ALLG NHL 24), randomized to standard chemotherapy with or without rituximab, followed in patients <= 60 years old by 30-Gy whole-brain radiotherapy (WBRT), were asked to participate in a neuropsychological evaluation before and during treatment, and up to 2 years posttreatment. Scores were transformed into a standardized z-score; clinically relevant changes were defined as a change in z-score of >= SD.The effect of WBRT was analyzed in irradiated patients. All M Rls were centrally assessed for white matter abnormalities and cerebral atrophy, and their relation with neurocognitive scores over time in each domain was calculated.Results. 125/199 patients consented to neurocognitive evaluation. Statistically significant improvements in neurocognition were seen in all domains. A clinically relevant improvement was seen only in the motor speed domain, without differences between the arms. In the follow-up of irradiated patients (n = 43), no change was observed in any domain score, compared to after WBRT. Small but significant inverse correlations were found between neurocognitive scores over time and changes in white matter abnormalities (regression coefficients: -0.048 to -0.347) and cerebral atrophy (-0.212 to -1.774).Conclusions. Addition of rituximab to standard treatment in PCNSL patients did not impact neurocognitive functioning up to 2 years posttreatment, nor did treatment with 30-Gy WBRT in patients <= 60 years old. Increased white matter abnormalities and brain atrophy showed weak associations with neurocognition. Show less
Meulen, M. van der; Dirven, L.; Bakunina, K.; Bent, M.J. van den; Issa, S.; Doorduijn, J.K.; Bromberg, J.E.C. 2021
Introduction To assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients. Methods In... Show moreIntroduction To assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients. Methods In the HOVON 105/ ALLG NHL 24 phase III study patients with newly-diagnosed PCNSL were randomized between high-dose methotrexate-based chemotherapy with or without rituximab. Data on potential (MMSE-score), and known baseline prognostic factors (age, performance status, serum LDH, cerebrospinal fluid total protein, involvement of deep brain structures, multiple cerebral lesions, and the IELSG-score) were collected prospectively. Multivariable stepwise Cox regression analyses were used to assess the prognostic value of all factors on progression-free survival (PFS) and overall survival (OS) among patients with available MMSE score at baseline. Age was analyzed as continuous variable, the MMSE-score both as a continuous and as a categorical variable. Results In univariable analysis, age, MMSE-score and whether the patient received rituximab were statistically significantly prognostic factors for PFS. Age and MMSE-score were statistically significantly associated with OS. In a multivariable analysis of the univariately significant factors only MMSE-score was independently associated with the survival endpoints, as a continuous variable (HR for PFS 1.04, 95% CI 1.01-1.08; OS 1.06 (95% CI 1.02-1.10) and as categorical variable HR (< 27 versus >= 27 for PFS 1.55 (1.02-2.35); OS 1.68 (1.05-2.70). In our population, performance status, serum LDH, and CSF protein level were not of prognostic value. Conclusion Neurocognitive disturbances, measured with the MMSE at baseline, are an unfavorable prognostic factor for both PFS and OS in adult PCNSL patients up to 70 years-old. Show less
Meulen, M. van der; Bakunina, K.; Nijland, M.; Minnema, M.C.; Cull, G.; Stevens, W.B.C.; ... ; Dirven, L. 2020
Background: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to... Show moreBackground: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial.Patients and methods: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients <= 60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences >= 10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients.Results: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: -3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months -7.4 and -8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570.Conclusion: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impact HRQoL over time. WBRT did not result in deterioration of HRQoL in the first 2 years. Show less
