Extent of radiological response does not reflect survival in primary central nervous system lymphoma

Matthijs van der Meulen; Alida A Postma; Marion Smits; Katerina Bakunina; Monique C Minnema; Tatjana Seute; Gavin Cull; Roelien H Enting; Marjolein van der Poel; Wendy B C Stevens; Dieta Brandsma; Aart Beeker; Jeanette K Doorduijn; Samar Issa; Martin J van den Bent; Jacoline E C Bromberg

doi:10.1093/noajnl/vdab007

Extent of radiological response does not reflect survival in primary central nervous system lymphoma

Neurooncol Adv. 2021 Feb 15;3(1):vdab007. doi: 10.1093/noajnl/vdab007. eCollection 2021 Jan-Dec.

Authors

Matthijs van der Meulen¹, Alida A Postma², Marion Smits³, Katerina Bakunina⁴, Monique C Minnema⁵, Tatjana Seute⁶, Gavin Cull^{7

8}, Roelien H Enting⁹, Marjolein van der Poel¹⁰, Wendy B C Stevens¹¹, Dieta Brandsma¹², Aart Beeker¹³, Jeanette K Doorduijn¹⁴, Samar Issa¹⁵, Martin J van den Bent¹, Jacoline E C Bromberg¹

Affiliations

¹ Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
² Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, School for Mental Health and Sciences, Maastricht, The Netherlands.
³ Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴ Department of Hematology, HOVON Data Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
⁵ Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁶ Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁷ Haematology Department, Sir Charles Gairdner Hospital and PathWest Laboratory Medicine, Nedlands, Australia.
⁸ University of Western Australia, Crawley, Australia.
⁹ Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁰ Department of Hematology, University Medical Center, Maastricht, The Netherlands.
¹¹ Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
¹² Department of Neuro-Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
¹³ Department of Hematology, Spaarne Gasthuis, Haarlem, The Netherlands.
¹⁴ Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁵ Department of Haematology, Middlemore Hospital, Auckland, New Zealand.

Abstract

Background: In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival.

Methods: All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis.

Results: Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment.

Conclusions: Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.

Keywords: MRI; central radiology review; complete response; response evaluation; survival.