Prospective Multicenter Study for Evaluating Cognitive Disorders in Hematology-Oncology: A Pilot Study of 118 Patients
Authors: Rossi Jean François , Laurier Laurence , Misset Jean-Louis , Spaeth Dominique , Uwer F. , Soubeyran Pierre , Largiller Remy , Metges Jean-Philippe , Blay Jean- Yves , Attal Michel , Facon Thierry , Hermine Olivier , Bugat Roland , Spano Jean-Philippe , Cals Laurent , Cure Hervé , Atlan Dan , Gjoklaj Mario 
Published: April 2020

Abstract
Introduction: Cognitive impairment occurs in a subset of cancer survivors and is generally subtle. Most evidence suggests that chemotherapy may be a cause, although other factors associated with the diagnosis and treatment of cancer may contribute. Recently, recommendations for future research in evaluating cognitive disorders have been suggested though different published studies. Nevertheless, there is a need to standardize this evaluation, particularly for neuropsychological tests. The various domains to be explored include memory disorders, decrease in oral fluency, care and concentration, slowing down of information processing. The main objective of this prospective study was to assess the feasibility for evaluating cognitive disorders with neuropsychological tests in different groups of homogeneous patients. The secondary objectives were to evaluate the cognitive disorders in these groups of patients and the impact of disease and therapeutic strategies with a follow-up period of 48 weeks.
Patients and Methods: 124 previously untreated patients were included by 13 centers. 5 subgroups were defined: group 1, breast cancer T1N0 treated by local radiotherapy (n=24); group 2, breast cancer T1–T2, N+ treated by adjuvant chemotherapy and radiotherapy (n=52); group 3, diffuse large B-cell lymphoma treated by chemotherapy plus rituximab (n=8); group 4 colon cancer treated by adjuvant chemotherapy (n=11); group 5, multiple myeloma treated by 4–5 cycles of VAD followed by high dose therapy and autologous transplantation (n=23). Exclusion criteria included previous cognitive disorders or neurological diseases, HIV patients, other cancers, previous vascular disease or head trauma, sleep apnea, brain metastasis, metabolic disorders or neuropsychiatric drug intake. Hetero-evaluation was performed three times by neuropsychologists, at inclusion (pre-therapeutic, except for group 5 where inclusion corresponded to the pre-transplantation period), second evaluation, (24 weeks after 1st visit (V) for groups 1–4 and 12 weeks for group 5), and 3rd evaluation (48 weeks or 24 weeks respectively for groups 1–4 or 5). Intra- and inter-comparisons were made. Neuropsychological tests were performed in similar order and included: Brown Petterson test; Grober and Buschke (16 items) test; Double work; letter, number sequence; D2 test; code test; trail-making test; Stroop test; oral fluency. Statistical analysis included Mantel Haenszel tests.
Results : Mean age was 57.14 years (range 31–85), with a sex ratio F:M=5.3. Body mass index and blood pressure were not significantly different between groups. Performance status was different among groups particularly for groups 3–5. Baseline evaluation included other co-morbidities and anxiety/depression status which was slightly abnormal in 7% of the patients. Test feasibility was good for the majority of them but was dependent on the group of patients, particularly for oral fluency test (not performed in 27.3% of patients in group 4). In addition, the percentage of patients who did not have other controls (V 2 and 3) varied from one group to another, but concerned less than 24% of the patients (particularly for groups 3,4 and 5). A significant increase of the number of patients presenting an alteration at V 2 and 3 but normal at V1 was observed, particularly in the trail making test (altered in 26.2% of the patients) and Brown Petterson test altered particularly after 12 months of radiotherapy (37% of patients). The Empan test was improved at visit 3 particularly for group 2.
Conclusion: This pilot prospective multicenter study allows to
define and validate neuro-psychological tests for evaluating cognitive disorders and estimate the percentage of patients having impaired cognitive functions due to treatment.