Matthijs van der Meulen1, Linda Dirven2,3, Esther J J Habets3,4, Katerina Bakunina5, Marion Smits6, Hakim C Achterberg6, Tatjana Seute7, Gavin Cull8,9, Harry Schouten10, Josée M Zijlstra11, Dieta Brandsma12, Roelien H Enting13, Max Beijert14, Martin J B Taphoorn2,3, Martin J van den Bent1, Samar Issa15, Jeanette K Doorduijn16, Jacoline E C Bromberg1. 1. Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands. 2. Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. 3. Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands. 4. Department of Medical Psychology, Haaglanden Medical Center, The Hague, The Netherlands. 5. HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 6. Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 7. Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands. 8. Haematology Department, Sir Charles Gairdner Hospital and PathWest Laboratory Medicine, Nedlands, Western Australia, Australia. 9. University of Western Australia, Crawley, Western Australia, Australia. 10. Department of Hematology, University Medical Center, Maastricht, The Netherlands. 11. Department of Hematology, Amsterdam UMC-Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands. 12. Department of Neuro-oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands. 13. Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 14. Department of Radiotherapy, University Medical Center Groningen, Groningen, The Netherlands. 15. Department of Hematology, Middlemore Hospital, Auckland, New Zealand. 16. Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract
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). METHODS: One hundred and ninety-nine patients from a phase III 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 ≥1 SD. The effect of WBRT was analyzed in irradiated patients. All MRIs 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.
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). METHODS: One hundred and ninety-nine patients from a phase III 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 ≥1 SD. The effect of WBRT was analyzed in irradiated patients. All MRIs 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.
Authors: Wim van der Elst; Martin P J van Boxtel; Gerard J P van Breukelen; Jelle Jolles Journal: J Clin Exp Neuropsychol Date: 2006-08 Impact factor: 2.475
Authors: Nancy D Doolittle; Agnieszka Korfel; Meredith A Lubow; Elisabeth Schorb; Uwe Schlegel; Sabine Rogowski; Rongwei Fu; Edit Dósa; Gerald Illerhaus; Dale F Kraemer; Leslie L Muldoon; Pasquale Calabrese; Nancy Hedrick; Rose Marie Tyson; Kristoph Jahnke; Leeza M Maron; Robert W Butler; Edward A Neuwelt Journal: Neurology Date: 2013-05-17 Impact factor: 9.910
Authors: Linda Douw; Martin Klein; Selene Saa Fagel; Josje van den Heuvel; Martin Jb Taphoorn; Neil K Aaronson; Tjeerd J Postma; W Peter Vandertop; Jacob J Mooij; Rudolf H Boerman; Guus N Beute; Jasper D Sluimer; Ben J Slotman; Jaap C Reijneveld; Jan J Heimans Journal: Lancet Neurol Date: 2009-08-07 Impact factor: 44.182
Authors: L O Wahlund; F Barkhof; F Fazekas; L Bronge; M Augustin; M Sjögren; A Wallin; H Ader; D Leys; L Pantoni; F Pasquier; T Erkinjuntti; P Scheltens Journal: Stroke Date: 2001-06 Impact factor: 7.914
Authors: Denise D Correa; Erica Braun; Maria Kryza-Lacombe; Ka-Wai Ho; Anne S Reiner; Katherine S Panageas; Joachim Yahalom; Craig S Sauter; Lauren E Abrey; Lisa M DeAngelis; Antonio Omuro Journal: J Neurooncol Date: 2019-08-03 Impact factor: 4.130
Authors: Andrés J M Ferreri; Kate Cwynarski; Elisa Pulczynski; Christopher P Fox; Elisabeth Schorb; Paul La Rosée; Mascha Binder; Alberto Fabbri; Valter Torri; Eleonora Minacapelli; Monica Falautano; Fiorella Ilariucci; Achille Ambrosetti; Alexander Roth; Claire Hemmaway; Peter Johnson; Kim M Linton; Tobias Pukrop; Jette Sønderskov Gørløv; Monica Balzarotti; Georg Hess; Ulrich Keller; Stephan Stilgenbauer; Jens Panse; Alessandra Tucci; Lorella Orsucci; Francesco Pisani; Alessandro Levis; Stefan W Krause; Hans J Schmoll; Bernd Hertenstein; Mathias Rummel; Jeffery Smith; Michael Pfreundschuh; Giuseppina Cabras; Francesco Angrilli; Maurilio Ponzoni; Martina Deckert; Letterio S Politi; Jürgen Finke; Michele Reni; Franco Cavalli; Emanuele Zucca; Gerald Illerhaus Journal: Lancet Haematol Date: 2017-10-17 Impact factor: 18.959
Authors: Fayez Estephan; Xiaobu Ye; Omar Dzaye; Nina Wagner-Johnston; Lode Swinnen; Douglas E Gladstone; Rich Ambinder; David Olayinka Kamson; Sebastian Lambrecht; Stuart A Grossman; Doris D M Lin; Matthias Holdhoff Journal: J Neurooncol Date: 2019-10-16 Impact factor: 4.130