scholarly journals Hippocampal Avoidance and Memantine for Whole-Brain Radiotherapy: Long-Term Follow-Up Warranted

2020 ◽  
pp. JCO.20.00747
Author(s):  
Nicolaus Andratschke ◽  
José Belderbos ◽  
Michael Mayinger ◽  
Sanne B. Schagen ◽  
Dirk De Ruysscher
2006 ◽  
Vol 24 (28) ◽  
pp. 4570-4574 ◽  
Author(s):  
Igor T. Gavrilovic ◽  
Adília Hormigo ◽  
Joachim Yahalom ◽  
Lisa M. DeAngelis ◽  
Lauren E. Abrey

Purpose We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity. Patients and Methods Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations. Results The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy. Conclusion Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.


2020 ◽  
Author(s):  
Wen-Chi Yang ◽  
Ya-Fang Chen ◽  
Chi-Cheng Yang ◽  
Pei-Fang Wu ◽  
Hsing-Min Chan ◽  
...  

Abstract Background Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function. Methods This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test–Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was −8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well. Conclusion Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.


2013 ◽  
Vol 31 (31) ◽  
pp. 3971-3979 ◽  
Author(s):  
Patrick G. Morris ◽  
Denise D. Correa ◽  
Joachim Yahalom ◽  
Jeffrey J. Raizer ◽  
David Schiff ◽  
...  

Purpose A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma. Patients and Methods Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor. Results Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33). Conclusion R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.


Neurology ◽  
2020 ◽  
Vol 95 (23) ◽  
pp. e3138-e3144
Author(s):  
Sabine Seidel ◽  
Hendrik Pels ◽  
Sabine Schlömer ◽  
Annika Kowoll ◽  
Klaus Fliessbach ◽  
...  

ObjectiveTo determine whether a fraction of patients with primary CNS lymphoma (PCNSL) had been cured by systemic and intraventricular methotrexate- and cytarabine-based chemotherapy (Bonn protocol) after a very long-term follow-up of nearly 20 years.MethodsSixty-five patients (median age 62 years, range 27–75; median Karnofsky performance score 70, range 20–90) had been treated with systemic and intraventricular polychemotherapy without whole brain radiotherapy from September 1995 until December 2001. All patients still alive in 2019 were contacted and interviewed on their current life situation.ResultsMedian follow-up for surviving patients was 19.6 years (17.5–23.3 years). Out of 65 patients, 11 (17%) were still alive. Six of those never experienced any relapse. For the whole study population, median overall survival (OS) was 4.4 years (95% confidence interval [CI] 2.9–5.9); for patients ≤60 years, 11.0 years (95% CI 4.8–17.0). The 10-year OS rate for the entire cohort was 29% and the estimated 20-year OS rate was 19%. Four late relapses were observed after 9.8, 10.3, 13.3, and 21.0 years.ConclusionAt a median follow-up of 19.6 years, 17% of patients were alive and free of tumor; however, even after response for decades, an inherent risk of relapse, either systemic or cerebral, characterizes the biology of PCNSL.Classification of evidenceThis work provides Class III evidence that PCNSL treatment with methotrexate-based polychemotherapy including intraventricular therapy is associated with long-term disease control in some patients.


2019 ◽  
Vol 5 (suppl) ◽  
pp. 124-124
Author(s):  
Buhai Wang ◽  
Shiwei Fu ◽  
Yuxiang Huang

124 Background: To investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Methods: For the retrospective analysis, 50 patients diagnosed with brain metastases were selected and divided into two groups from 2015-01-01 to 2017-12-31 at the Department of Oncology, Jiangsu Subei People's Hospital. Group A (n=27) was hippocampal avoidance whole-brain radiotherapy group; group B (n=23) was whole brain radiation therapy (WBRT) group. Neurocognitive function was statistically analyzed at 3, 6, 9, 12, and 24 months after radiotherapy, as scored by the MMSE (Mine-Mental State Examination) scales and the MoCA (Montreal Cognitive Assessment) scales. The OS, PFS and tumor recurrence sites of the two groups was also analyzed. Results: After 12, 24 months after radiotherapy, there was a significant difference between the two groups. The cognitive function of the hippocampal protection group was significantly higher than that of the non-hippocampal protection group (P<0.05). There was no significant difference in OS (P=0.2) and PFS (P=0.18) between the two groups. 14 patents in group A and 12 patents in group B had brain tumor recurrence after radiation, only one patient in group A occurred 5 mm within the edge of the hippocampus (P>0.05). Conclusions: First, HA-WBRT has a protective effect on long-term neurocognitive function. Second, there was no statistically significant different on OS and PFS in patients who underwent HA-WBRT or WBRT. Third, HA-WBRT didn’t increase the risk of brain tumor recurrence within the edge of the hippocampus.


2021 ◽  
Vol 20 ◽  
pp. 153303382110342
Author(s):  
Buhai Wang ◽  
Shiwei Fu ◽  
Yuxiang Huang ◽  
Liqin Liu ◽  
Yichen Liang ◽  
...  

Whole-brain radiotherapy (WBRT) is the mainstay of therapy in treating cancer patients with brain metastases, but unfortunately, it might also lead to decline in neurocognitive function. This study aims to investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Retrospectively, 47 patients diagnosed with brain metastases of non-small cell lung cancer (NSCLC) between 2015-01-01 and 2017-12-31 at the Department of Oncology, XXX Hospital were selected and divided into 2 groups. Group A (n = 27) received HA-WBRT, whereas group B (n = 20) received WBRT. Neurocognitive function was analyzed at baseline and at 3, 6, 9, 12 and 24 months after radiotherapy, using Mine-Mental State Examination (MMSE) scales and Montreal Cognitive Assessment (MoCA) scales. The OS, PFS and tumor recurrence sites were also analyzed. When evaluated at 12 and 24 months after radiotherapy, the cognitive function scores of the hippocampal avoidance group were significantly higher than those of the non-hippocampal avoidance group ( P < 0.001). In terms of patient survival, there was no significant difference in OS ( P = 0.2) and PFS (P = 0.18) between these 2 groups. Fourteen patients in group A and 12 patients in group B had brain tumor recurrence after radiation, only one patient in group A occurred within 5 mm from the edge of the hippocampus ( P > 0.05). In conclusion, HA-WBRT might have a protective effect on long-term neurocognitive function and did not affect patient survival.


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