Clinical predictors of radiation-induced lymphopenia in patients receiving chemoradiation for glioblastoma: clinical usefulness of intensity-modulated radiotherapy in the immuno-oncology era

Table 2 Univariate and multivariate Cox regression analyses for overall survival

	Univariate HR (95% CI)	P	Multivariate HR (95% CI)	P
Patient-related factor
Age (per 1 year)	1.01 (1.00–1.02)	0.005	1.02 (1.01–1.03)	0.003
Sex (Male vs. Female)	1.02 (0.80–1.30)	0.889
KPS
(80 vs. ≤70)	1.06 (0.79–1.42)	0.697
(≥90 vs. ≤70)	0.78 (0.58–1.06)	0.112
Baseline TLC (< 1000/μL vs. ≥1000/μL)	1.25 (0.94–1.64)	0.119
Tumor-related factor
Extent of resection
(Subtotal/Partial vs. Total)	1.78 (1.38–2.31)	<.001	1.75 (1.33–2.31)	<.001
(Biopsy vs. Total)	1.69 (1.06–2.70)	0.028	1.50 (0.93–2.43)	0.095
IDH1 mutation
(Yes vs. No)	0.25 (0.11–0.55)	<.001	0.30 (0.13–0.69)	0.005
(Unknown vs. No)	1.14 (0.86–1.52)	0.360	0.97 (0.71–1.31)	0.818
MGMT (Methylated vs. Unmethylated)	0.46 (0.35–0.60)	<.001	0.48 (0.37–0.63)	<.001
Subventriclular zone (Involved vs. Uninvolved)	1.57 (1.23–2.01)	<.001	1.52 (1.17–1.96)	0.001
Treatment-related factor
The cumulative dose of temozolomide (per 100 mg/m²)	1.00 (0.99–1.00)	0.260	1.00 (0.99–1.01)	0.597
PTV1 volume (per 10 cm³)	1.01 (1.00–1.01)	0.132
PTV2 volume (per 10 cm³)	1.02 (1.00–1.03)	0.029	1.01 (0.99–1.02)	0.305
Radiotherapy modality (IMRT vs. 3D-CRT)	0.91 (0.71–1.17)	0.483
Total dose (per 1 Gy)	0.98 (0.95–1.01)	0.187
No. of fractionation (per 1)	0.99 (0.94–1.05)	0.845
Acute severe lymphopenia (Yes vs. No)	1.32 (1.03–1.69)	0.028	1.04 (0.81–1.35)	0.756

Abbreviations: 3D-CRT three-dimensional conformal radiotherapy, CI confidence interval, HR hazard ratio, IMRT intensity-modulated radiotherapy, KPS Karnofsky performance status, PTV planning target volume, TLC total lymphocyte count

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