Article Figures & Data
Figures
- Figure 1
Survival outcomes of the study patients. The Kaplan-Meier curves of progression-free survival (PFS) (A) and overall survival (OS) (B). Forest plot of PFS (C) and OS (D) per patient subgroup.
- Figure 2
Distribution of genomic alterations with regard to response to treatment and survival analysis based on Kaplan-Meier curve in GBM patients in secondary analysis. (A) Mutational landscape of patients with glioblastoma multiforme (GBM) detected by whole exome sequencing (WES). (B) The frequency of gene variants between relapse and non-relapse patients. PFS in patients harboring RP1L1 (C) and HEG1 (D) alterations and wild-type. OS in patients with harboring RP1L1 (E) and HEG1 (F) alterations and wild-type.
Tables
- Table 1
Demographic and baseline characteristics of the patients and those detected by WES
Patients included in the trial (n = 33) Patients included in the WES analysis (n = 21) Characteristic Age, years Median 52 54 Range 32–69 32–68 Gender Male 17 (52) 11 (52) Female 16 (49) 10 (48) KPS score Median 90 90 ≥ 90 22 (67) 15 (71) 60–80 11 (33) 6 (29) RPA class III 7 (21) 3 (14) IV 13 (39) 10 (48) V 13 (39) 8 (38) Co-morbidities No 25 (76) 17 (81) Yes 8 (24) 4 (19) Hypertension and diabetes 2 (6) 2 (10) Hypertension 6 (18) 2 (10) BMI, kg/m2 < 18.5 2 (6) 2 (10) 18.5 ≤ BMI < 24 15 (45) 9 (43) ≥ 24 16 (49) 10 (48) Extent of surgical resection Gross total resection 10 (30) 7 (33) Near-total resection 6 (18) 4 (19) Subtotal resection 17 (52) 10 (18) Ki-67 index ≤ 30% 15 (45) 11 (52) > 30% 13 (39) 7 (33) Unknown 5 (15) 3 (14) MGMT promotor methylation status Methylated 11 (33) 11 (52) Unmethylated 20 (61) 8 (38) Undetermined 2 (6) 2 (10) IDH1/2 mutation status Mutant 2 (6) 2 (10) Wild-type 31 (94) 19 (91) BMI, body mass index; IDH, isocitrate dehydrogenase; KPS, Karnofsky performance status; MGMT, methylguanine-DNA methyltransferase; RPA, recursive partitioning analysis; WES, whole exome sequencing. Data are expressed as the number (%) unless otherwise specified. IDH1/2 mutation and MGMT promoter methylation status are based on the surgical pathology reports.
Variables Progression-free survival Overall survival Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis HR (95% CI) P value HR (95% CI) P value HR (95% CI) P value HR (95% CI) P value Age (> 54 vs. ≤ 54), years 1.1 (0.4–3.2) 0.873 0.5 (0.1–3.9) 0.546 1.6 (0.5–5.2) 0.399 0.3 (0.0–3.6) 0.365 Gender (female vs. male) 0.8 (0.3–2.3) 0.635 1.7 (0.5–5.8) 0.428 1.1 (0.4–3.5) 0.827 2.6 (0.6–10.1) 0.184 KPS (≥ 90 vs. 60–80) 1.2 (0.4–3.7) 0.810 0.8 (0.2–4.7) 0.849 1.6 (0.5–5.3) 0.458 1.4 (0.1–12.5) 0.792 Resection 0.787 0.500 0.414 0.140 NTR vs. GTR 1.2 (0.3–5.4) 0.796 2.1 (0.4–10.8) 0.396 2.2 (0.4–10.9) 0.357 5.1 (0.7–34.9) 0.330 STR vs. GTR 1.6 (0.4–5.5) 0.495 2.6 (0.5–13.9) 0.250 2.4 (0.6–9.7) 0.218 5.9 (0.9–38.5) 0.681 HEG1 (mutant vs. wild-type) 5.6 (1.3–23.7) 0.021 6.0 (1.2–28.8) 0.026 2.8 (0.7–10.3) 0.132 2.5 (0.6–10.1) 0.210 RP1L1 (mutant vs. wild-type) 11.1 (2.2–57.2) 0.004 12.5 (2.1–74.3) 0.005 33.8 (3.4–334.5) 0.003 33.4 (3.2–351.4) 0.003 GTR, gross total resection; KPS, Karnofsky performance status; NTR, near-total resection; OS, overall survival; PFS, progression-free survival. One hypermutator case with tumor mutational burden (TMB) = 327.7 was excluded from analysis.
Treatment-emergent AEs Concomitant therapy Adjuvant therapy Any grade Grade 3–4 Any grade Grade 3–4 Hypertriglyceridemia 19 (58) 2 (6) 22 (67) 1 (3) Hypercholesterolemia 15 (46) 0 (0) 9 (27) 0 (0) Hypoalbuminemia 15 (46) 0 (0) 7 (21) 0 (0) Leukopenia 11 (33) 0 (0) 24 (73) 1 (3) Elevated g-glutamyl transferase 11 (33) 0 (0) 11 (33) 0 (0) Neutropenia 10 (30) 0 (0) 17 (52) 0 (0) Elevated aspartate transaminase 8 (24) 0 (0) 4 (12) 0 (0) Elevated alanine aminotransferase 6 (18) 0 (0) 6 (18) 0 (0) Hypertension 5 (15) 0 (0) 5 (15) 0 (0) Fatigue 5 (15) 0 (0) 15 (46) 0 (0) Thrombocytopenia 4 (12) 0 (0) 9 (27) 3 (6) Nausea 4 (12) 0 (0) 6 (18) 0 (0) Vomiting 4 (12) 0 (0) 5 (15) 0 (0) Proteinuria 1 (3) 0 (0) 14 (42) 0 (0) Seizure 1 (3) 0 (0) 4 (12) 0 (0) Hypothyroidism 0 (0) 0 (0) 10 (30) 0 (0) Palmar–plantar erythrodysaesthesia syndrome 0 (0) 0 (0) 4 (12.1) 0 (0) Data are expressed as a number (%).
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