Abnormal preoperative haematological parameters in Endometrial cancer; reflecting tumour aggressiveness or reduced response to radiotherapy?

Figures & data

Figure 1. Study flowchart.

Table 1. Baseline clinicopathological characteristics.

Patient characteristics		Total (n = 894)
Age (years)		65.9 (27.2–93.8)
BMI (kg/m^2)		29.7 (16.4–60.9)
Serum values
Haemoglobin mmol/L		8.4 (3.9–10.6)
Haemoglobin <7.45 mmol/L		103 (11.3)
Platelets ×10^9 /L		298.3 (13.9–781.0)
Platelets >400×10^9		79 (8.6)
Leukocytes ×10^9/L		8.1 (2.2–33.5)
Leukocytes >10×10^9/L		114 (12.5)
Final tumour histology
Tumour Grade	1–2	620 (69.4)
	3	274 (30.6)
Histology	Endometrioid	735 (82.2)
	Non-endometrioid	159 (17.8)
LVSI	Yes	177 (19.8)
	No	717 (80.2)
FIGO stage	Early (I–II)	806 (90.2)
	Advanced (III–IV)	88 (9.8)
Lymph node status	Positive (N1)	34 (3.8)
	Negative (N0)	171 (19.1)
	Unknown† (Nx)	689 (77.1)
ESGO/ESTRO/ESP risk groups	Low	409 (45.7)
	Intermediate	159 (17.8)
	High-intermediate	162 (18.1)
	High	140 (15.7)
	Advanced/metastatic	24 (2.7)
Adjuvant treatment
None		550 (61.5)
RT	VBT	132 (14.8)
	EBRT (+/− VBT)	107 (11.9)
CT + CRT		100 (11.2)
Other		5 (0.6)
Outcome
Recurrence	Yes	124 (13.9)
	No	770 (86.1)
Mortality	Overall	160 (17.9)
	EC-related	99 (11.1)

Data is presented in numbers (%) or median (IQR).

Abbreviations: Number (n), Federation International Gynaecology Obstetric (FIGO), European Society of Gynaecological Oncology (ESGO), European SocieTy for Radiotherapy and Oncology (ESTRO), European Society of Pathology (ESP), Radiotherapy (RT), Vaginal brachytherapy (VBT), External beam radiation therapy (EBRT), Chemotherapy (CT), Chemoradiation (CRT), Endometrial cancer (EC).

^† No lymphadenectomy performed.

Table 2. Clinicopathological characteristics in relation to haemoglobin-, leukocytes- and thrombocytosis-level.

		Normal haemoglobin (n = 791)	Anaemia (n = 103)	P	Normal platelets (n = 642)	Thrombocytosis (n = 79)	P	Normal leukocytes (n = 553)	Leucocytosis (n = 114)	P
Patient characteristics
Age		65.7 (27.2–91.0)	68.2 (33.8–93.8)	0.246	66.0 (31.2–93.8)	64.0 (27.2–90.7)	0.017*	66.0 (31.2–93.8)	65.0 (27.2–86.0)	0.386
Final tumour histology
Tumour grade	1–2	560 (70.8)	60 (58.3)	0.009*	448 (69.8)	52 (65.8)	0.471	383 (69.3)	81 (71.1)	0.705
	3	231 (29.2)	43 (41.7)		194 (30.2)	27 (34.2)		170 (30.7)	33 (28.9)
Endometrioid		656 (82.9)	79 (76.7)	0.120	531 (82.7)	62 (78.5)	0.353	455 (81.7)	94 (82.5)	0.856
Non-endometrioid		135 (17.1)	24 (23.3)		111 (17.3)	17 (21.5)		101 (18.3)	20 (17.5)
LVSI	Yes	149 (18.8)	28 (27.2)	0.046*	121 (18.8)	23 (29.1)	0.031*	109 (19.7)	26 (22.8)	0.454
	No	642 (81.2)	75 (72.8)		521 (81.2)	56 (70.9)		444 (80.3)	88 (77.2)
ESGO/ESTRO/ESP risk groups
Low risk		372 (47.0)	37 (35.9)	0.033*	309 (48.1)	31 (39.2)	0.135	270 (48.8)	53 (46.5)	0.650
Intermediate risk		146 (18.5)	12 (11.7)	0.088	105 (16.4)	7 (8.9)	0.083	77 (13.9)	17 (14.9)	0.782
High-intermediate risk		140 (17.7)	22 (21.4)	0.364	114 (17.8)	17 (21.5)	0.413	101 (18.3)	17 (14.9)	0.393
High risk		114 (14.4)	27 (26.2)	0.002*	97 (15.1)	19 (24.1)	0.041*	92 (16.6)	20 (17.5)	0.813
Advanced/metastatic		19 (2.4)	5 (4.9)	0.148	17 (2.6)	5 (6.3)	0.073	13 (2.4)	7 (6.2)	0.031*
Adjuvant treatment
None		499 (63.1)	51 (49.5)	0.009*	412 (64.2)	42 (53.2)	0.066	361 (65.2)	64 (56.1)	0.069
RT	VBT	122 (15.4)	10 (9.7)	0.124	87 (13.6)	3 (3.8)	0.013*	58 (10.5)	15 (13.2)	0.406
	EBRT (+/− VBT)	87 (11.0)	20 (19.4)	0.012*	75 (11.6)	14 (17.7)	0.124	69 (12.5)	17 (14.9)	0.480
CT + CRT		79 (10.0)	21 (20.4)	0.002*	65 (10.1)	19 (24.0)	<0.001*	62 (11.3)	17 (15.0)	0.260
Other		4 (0.5)	1 (1.0)	0.459	3 (0.5)	1 (1.3)	0.372	3 (0.5)	1 (0.8)	0.528

Data is presented in numbers (%), median (range).

Abbreviations: number (n), Lymphovascular space invasion (LVSI), European Society of Gynaecological Oncology (ESGO), European SocieTy for Radiotherapy and Oncology (ESTRO), European Society of Pathology (ESP), Radiotherapy (RT), Vaginal brachytherapy (VBT), External beam radiation therapy (EBRT), Chemotherapy (CT), Chemoradiation (CRT).

* P < 0.05.

Figure 2. (A–F) 5-year disease-specific survival (DSS) and recurrence-free survival (RFS) of patients with normal and abnormal haematological parameters. (A) 5-year DSS of patients with and without anaemia. (B) 5-year DSS of patients with and without thrombocytosis. (C) 5-year DSS of patients with and without leucocytosis. (D) 5-year RFS of patients with and without anaemia. (E) 5-year RFS of patients with and without thrombocytosis. (F) 5-year RFS of patients with and without leucocytosis.

Table 3. Cox regression univariable and multivariable analysis of disease-specific survival (DSS) and recurrence-free survival (RFS).

Variable	Univariable DSS		Multivariable DSS Event 66		Univariable RFS		Multivariable RFS Event 78
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Patient characteristics
Age (continuous)	1.04 (1.02–1.06)	<0.001*	1.03 (1.00–1.06)	0.009*	1.04 (1.01–1.05)	<0.001*	1.03 (1.00–1.05)	0.022*
Haematological parameters
Anaemia	3.19 (2.02–5.02)	<0.001*	2.31 (1.19–4.50)	0.013*	2.32 (1.49–3.60)	<0.001*	1.71 (0.91–3.19)	0.091
Thrombocytosis	1.90 (1.08–3.34)	0.025*	1.06 (0.49–2.30)	0.872	1.31 (0.73–2.36)	0.363	0.70 (0.32–1.55)	0.382
Leucocytosis	1.65 (0.95–2.86)	0.074	1.37 (0.74–2.55)	0.312	1.45 (0.85–2.44)	0.168	1.53 (0.84–2.74)	0.159
ESGO/ESTRO/ESP risk groups
Low	1		1		1		1
Intermediate	7.59 (3.01–19.12)	<0.001*	3.06 (0.98–9.53)	0.053	6.20 (3.06–12.55)	<0.001*	2.38 (0.88–6.39)	0.087
High-intermediate	3.90 (1.38–10.96)	0.010*	1.59 (0.44–5.65)	0.472	5.23 (2.56–10.89)	<0.001*	3.43 (1.44–8.16)	0.005*
High	32.66 (13.99–76.23)	<0.001*	18.3 (7.64–43.94)	<0.001*	22.21 (11.64–42.37)	<0.001*	16.78 (8.05–34.83)	<0.001*
Advanced/metastatic	101.97 (40.33–257.79)	<0.001*	72.1 (27.36–189.97)	<0.001*	36.59 (15.79–84.74)	<0.001*	33.68 (13.15–86.29)	<0.001*

Abbreviations: Disease-specific survival (DSS), Recurrence-free survival (RFS), Hazard ratio (HR), Confidence interval (CI), European Society of Gynaecological Oncology (ESGO), European SocieTy for Radiotherapy and Oncology (ESTRO), European Society of Pathology (ESP),.

* P < 0.05.

Figure 3. (A–F) 5-year disease-specific survival (DSS) and recurrence-free survival (RFS) of patients with normal and abnormal haematological parameters within patients with solely adjuvant radiotherapy (RT). (A) 5-year DSS of patients with and without anaemia in patient with adjuvant RT. (B) 5-year DSS of patients with and without thrombocytosis in patients with adjuvant RT. (C) 5-year DSS of patients with and without leucocytosis in patients with adjuvant RT. (D) 5-year RFS of patients with and without anaemia with adjuvant RT. (E) 5-year RFS of patients with and without thrombocytosis with adjuvant RT. (F) 5-year RFS of patients with and without leucocytosis with adjuvant RT.

Data availability statement

The data that support the findings of this study are available from the corresponding author, SW, upon reasonable request.