Tablee-1. Treatment Summary

Treatment / No. of Patients (%)
Total*† / 80
Chemotherapy only / 65 / (81)
High-dose methotrexate-based / 32 / (40)
High-dose methotrexate-based (i.a.) with BBBD / 25 / (31)
High-dose methotrexate-based followed by HDCHT with ASCT / 8 / (10)
Chemotherapy followed by WBRT / 15 / (19)
High-dose methotrexate-based / 10 / (13)
High-dose methotrexate-based followed by HDCHT with ASCT / 5 / (6)
Abbreviations: i.a., intra-arterial; BBBD, blood-brain barrier disruption;
HDCHT, high-dose chemotherapy; ASCT, autologous stem-cell transplantation;
WBRT, whole brain radiotherapy.
*High-dose methotrexate was administered intravenously unless otherwise specified.
†Seventeen patients (21%) received intraventricular administration of chemotherapy into an Ommaya reservoir. The primary regimen used was methotrexate, prednisolone and cytarabine (ARA-C). Three patients received intrathecal ARA-C alone. For the management of ocular lymphoma (n=2), one patient was treated with intravitreal rituximab and one with ocular irradiation.

Table e-2. Number (%) of primary CNS lymphoma survivors with cognitive impairment overall and according to treatment group

No. and type of neuropsychological domains showing impairment* / Total
(n = 80) / HDMTX-based
CHT alone
(n = 32) / HDMTX (IA)-based CHT with BBBD
(n = 25) / HDMTX-based CHT
f/b HDCHT with ASCT
(n = 8) / HDMTX-based CHT f/b WBRT
(n = 15)
No. pts / % / No. pts / % / No. pts / % / No. pts / % / No. pts / %
No. of Impaired Domains
0 domain / 33 / 41 / 16 / 50 / 10 / 40 / 4 / 50 / 3 / 20
1 domain / 32 / 40 / 13 / 41 / 11 / 44 / 3 / 38 / 5 / 33
2 domains / 9 / 11 / 3 / 9 / 3 / 12 / 0 / 0 / 3 / 20
3 domains / 6 / 8 / 0 / 0 / 1 / 4 / 1 / 13 / 4 / 27
Domains
Attention/Executive Function / 12 / 15 / 3 / 9 / 1 / 4 / 1 / 13 / 7 / 47
Verbal Memory / 23 / 29 / 5 / 16 / 8 / 32 / 3 / 38 / 7 / 47
Motor Skills† / 33 / 45 / 11 / 35 / 11 / 46 / 2 / 29 / 9 / 75
Composite score / 21 / 26 / 6 / 19 / 4 / 16 / 3 / 38 / 8 / 53
Abbreviations: HDMTX, high-dose methotrexate; CHT, chemotherapy; IA, intra-arterial; BBBD, blood-brain barrier disruption; f/b, followed by;
HDCHT with ASCT, high-dose chemotherapy with autologous stem cell transplantation; WBRT, whole brain radiotherapy
*Cognitive Impairment is defined as a z-score greater than or equal to 1.5 SD worse than the normative mean.
†Six survivors were missing scores in the motor skills domain (3 survivors in the WBRT group and 1 survivor in each of the other treatment groups), thus for the motor skills domain, the overall n = 74.

Table e-3. Long-term quality of life scores of primary CNS lymphoma survivors overall and according to treatment group

Questionnaire/Scale / Total
(n = 80) / HDMTX-based
CHT alone
(n = 32) / HDMTX (IA)-based
CHT with BBBD
(n = 25) / HDMTX-based CHT f/b HDCHT with ASCT
(n = 8) / HDMTX-based CHT
f/b WBRT
(n = 15)
No. / Mean / SD / No. / Mean / SD / No. / Mean / SD / No. / Mean / SD / No. / Mean / SD
EORTC QLQ-C30*
Functional Scales
Physical function / 71 / 75.28 / 26.76 / 29 / 71.14 / 25.72 / 25 / 85.60 / 25.65 / 6 / 83.33 / 19.21 / 11 / 50.45 / 20.22
Role function / 70 / 70.48 / 33.95 / 28 / 63.69 / 36.87 / 25 / 84.00 / 26.56 / 6 / 86.11 / 16.39 / 11 / 48.48 / 34.52
Emotional function / 71 / 69.64 / 26.92 / 29 / 65.71 / 26.32 / 25 / 76.67 / 26.68 / 6 / 81.94 / 13.35 / 11 / 57.32 / 30.16
Cognitive function / 71 / 65.73 / 29.80 / 29 / 66.09 / 26.53 / 25 / 73.33 / 29.66 / 6 / 72.22 / 22.77 / 11 / 43.94 / 34.38
Social function / 71 / 64.32 / 36.98 / 29 / 55.75 / 38.13 / 25 / 79.33 / 33.08 / 6 / 88.89 / 20.18 / 11 / 39.39 / 29.13
Global health status/QOL / 71 / 68.19 / 24.33 / 29 / 62.36 / 21.08 / 25 / 82.67 / 23.93 / 6 / 72.22 / 20.86 / 11 / 48.48 / 15.73
Symptom Scales/Items
Fatigue / 71 / 32.47 / 28.01 / 29 / 29.31 / 22.85 / 25 / 23.56 / 29.28 / 6 / 31.48 / 22.68 / 11 / 61.62 / 23.50
Nausea and vomiting / 71 / 6.81 / 16.32 / 29 / 6.32 / 12.92 / 25 / 6.67 / 20.97 / 6 / 0.00 / 0.00 / 11 / 12.12 / 16.82
Pain / 71 / 23.47 / 32.44 / 29 / 18.97 / 29.45 / 25 / 21.33 / 31.74 / 6 / 16.67 / 27.89 / 11 / 43.94 / 39.63
Dyspnea / 71 / 14.55 / 25.03 / 29 / 18.39 / 26.10 / 25 / 8.00 / 17.43 / 6 / 5.56 / 13.61 / 11 / 24.24 / 36.79
Insomnia / 69 / 34.78 / 37.68 / 27 / 30.86 / 38.03 / 25 / 29.33 / 36.41 / 6 / 27.78 / 25.09 / 11 / 60.61 / 38.92
Appetite loss / 71 / 14.55 / 26.86 / 29 / 16.09 / 30.37 / 25 / 13.33 / 23.57 / 6 / 0.00 / 0.00 / 11 / 21.21 / 30.81
Constipation / 70 / 14.29 / 27.55 / 29 / 11.49 / 25.63 / 25 / 13.33 / 27.22 / 6 / 5.56 / 13.61 / 10 / 30.00 / 36.68
Diarrhea / 70 / 4.76 / 16.34 / 28 / 4.76 / 19.70 / 25 / 5.33 / 12.47 / 6 / 0.00 / 0.00 / 11 / 6.06 / 20.10
Financial difficulties / 71 / 22.07 / 32.34 / 29 / 21.84 / 29.92 / 25 / 22.67 / 34.32 / 6 / 11.11 / 27.22 / 11 / 27.27 / 38.92
EORTC QLQ-BN20
Symptom Scales
Future uncertainty / 71 / 27.54 / 28.86 / 29 / 31.61 / 26.01 / 25 / 18.00 / 25.76 / 6 / 5.56 / 8.61 / 11 / 50.51 / 34.06
Visual disorder / 71 / 16.90 / 25.88 / 29 / 15.71 / 21.72 / 25 / 11.11 / 22.45 / 6 / 1.85 / 4.54 / 11 / 41.41 / 35.52
Motor dysfunction / 71 / 22.85 / 28.91 / 29 / 24.90 / 28.74 / 25 / 12.00 / 19.49 / 6 / 11.11 / 22.22 / 11 / 48.48 / 35.58
Communication deficit / 71 / 23.00 / 23.03 / 29 / 21.84 / 20.03 / 25 / 17.33 / 22.92 / 6 / 22.22 / 18.59 / 11 / 39.39 / 27.83
Items
Headaches / 71 / 18.78 / 29.13 / 29 / 17.24 / 29.03 / 25 / 16.00 / 23.80 / 6 / 22.22 / 40.37 / 11 / 27.27 / 35.96
Seizures / 71 / 0.94 / 5.55 / 29 / 2.30 / 8.60 / 25 / 0.00 / 0.00 / 6 / 0.00 / 0.00 / 11 / 0.00 / 0.00
Drowsiness / 71 / 26.76 / 27.38 / 29 / 25.29 / 22.98 / 25 / 16.00 / 21.77 / 6 / 27.78 / 38.97 / 11 / 54.55 / 26.97
Hair loss / 71 / 11.74 / 26.49 / 29 / 12.64 / 25.84 / 25 / 6.67 / 21.52 / 6 / 11.11 / 17.21 / 11 / 21.21 / 40.20
Itchy skin / 71 / 17.37 / 30.27 / 29 / 19.54 / 33.94 / 25 / 12.00 / 23.33 / 6 / 16.67 / 27.89 / 11 / 24.24 / 36.79
Weakness of legs / 70 / 20.48 / 32.74 / 29 / 19.54 / 31.52 / 24 / 9.72 / 20.80 / 6 / 5.56 / 13.61 / 11 / 54.55 / 42.88
Bladder control / 71 / 16.43 / 29.21 / 29 / 13.79 / 27.48 / 25 / 14.67 / 25.60 / 6 / 16.67 / 27.89 / 11 / 27.27 / 41.68

Abbreviations: HDMTX, high-dose methotrexate; CHT, chemotherapy; IA, intra-arterial; BBBD, blood-brain barrier disruption; f/b, followed by;

HDCHT with ASCT, high dose chemotherapy with autologous stem cell transplantation; WBRT, whole brain radiotherapy; EORTC QLQ, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; BN20, brain cancer-specific questionnaire.

*EORTC QLQ-C30, EORTC-BN20 scores range from 1 to 100. Higher scores on the Functional Scales represent a higher level of functioning. Higher scores on the Symptom Scales/Items represent more perceived symptoms