Background
Methods
Settings and study population
Statistical analysis
Results
Patient characteristics
Non-diabetic patients (n = 299) | Diabetic patients (n = 89) | ||
---|---|---|---|
Good Glycemic Control (n = 35) | Poor Glycemic Control (n = 54) | ||
Age, median (range) (years) | 52 (24–80) | 52 (28–72) | 52 (26–66) |
Body mass index (kg/m2) | 23.2 (20.0–28.5) | 23.2 (19.4–26.7) | 23.6 (20.8–30.1) |
Serum creatinine, median (range) (μmol/l) | 69 (43–100) | 71 (52–103) | 72 (44–121) |
Smoking status, n (%) | |||
Never | 278 (93.0) | 33 (94.3) | 51 (94.4) |
Former | 9 (3.01) | 0 (0.0) | 1 (1.9) |
Current | 1 (0.3) | 0 (0.0) | 1 (1.9) |
Missing data | 11 (3.7) | 2 (5.7) | 1 (1.9) |
Regular cervical cancer screening, n (%) | |||
No | 264 (88.3) | 29 (82.9) | 45 (83.3) |
Yes | 14 (4.7) | 4 (11.4) | 7 (13.0) |
Missing data | 21 (7.0) | 2 (5.7) | 2 (3.7) |
Cell type, n (%) | |||
Squamous cell carcinoma | 253 (84.6) | 30 (85.7) | 41 (75.9) |
Non-squamous cell carcinoma | 46.0 (15.4) | 5.0 (14.3) | 13.0 (24.1) |
FIGO stage, n (%) | |||
IB2 | 253 (84.6) | 30 (85.7) | 41 (75.9) |
IIA2 | 46 (15.4) | 5 (14.3) | 13 (24.1) |
Grade, n (%) | |||
G1–2 | 274 (91.6) | 33 (94.3) | 49 (90.7) |
G3 | 25 (8.4) | 2 (5.7) | 5 (9.3) |
Lymph node status, n (%) | |||
Negative | 202 (67.6) | 17 (48.6) | 28 (51.9) |
Positive | 97 (32.4) | 18 (51.4) | 26 (48.2) |
Parametrial status, n (%) | |||
Negative | 291 (97.3) | 33 (94.3) | 50 (92.6) |
Positive | 8 (2.7) | 2 (5.7) | 4 (7.4) |
Resection margin, n (%) | |||
Negative | 292 (97.7) | 32 (91.4) | 48 (88.9) |
Positive | 7 (2.3) | 3 (8.6) | 6 (11.1) |
LVSI, n (%) | |||
Negative | 156 (52.2) | 18 (51.4) | 26 (48.2) |
Positive | 143 (47.8) | 17 (48.6) | 28 (51.9) |
Deep stromal invasion, n (%) | |||
No | 97 (32.4) | 8 (22.9) | 11 (20.4) |
Yes | 202 (67.6) | 27 (77.1) | 43 (79.6) |
Hypertension, n (%) | |||
No | 241 (80.6) | 19 (54.3) | 38 (70.4) |
Yes | 58 (19.4) | 16 (45.7) | 16 (29.6) |
Cardiovascular disease, n (%) | |||
No | 281 (94.0) | 30 (85.7) | 46 (85.2) |
Yes | 18 (6.0) | 5 (14.3) | 8 (14.8) |
Metformin use, n (%) | |||
No | 262 (87.6) | 31 (88.6) | 37 (68.5) |
Yes | 37 (12.4) | 4 (11.4) | 17 (31.5) |
Complete response, n (%) | |||
No | 96 (32.1) | 12 (34.3) | 21 (38.9) |
Yes | 203 (67.9) | 23 (65.7) | 33 (61.1) |
Survival outcomes
Recurrence-free survival | Cancer-specific survival | Overall survival | |||||||
---|---|---|---|---|---|---|---|---|---|
HR | 95% CI |
P value | HR | 95% CI |
P value | HR | 95% CI |
P value | |
Age (years) | 1.01 | 0.98–1.04 | 0.505 | 1.01 | 0.98–1.04 | 0.390 | 1.01 | 0.98–1.03 | 0.642 |
Body mass index (kg/m2) | 1.14 | 0.99–1.31 | 0.064 | 1.12 | 0.98–1.29 | 0.105 | 1.05 | 0.92–1.19 | 0.470 |
Serum creatinine (μmol/l) | 1.00 | 0.98–1.02 | 0.810 | 1.01 | 0.99–1.03 | 0.618 | 1.00 | 0.99–1.02 | 0.737 |
Tumor stage (IIA2 vs. IB2) | 1.15 | 0.73–1.83 | 0.541 | 1.15 | 0.71–1.84 | 0.576 | 0.97 | 0.64–1.47 | 0.873 |
Histology (non-squamous vs. squamous) | 1.69 | 0.98–2.91 | 0.059 | 1.84 | 1.06–3.19 | 0.029 | 1.91 | 1.19–3.08 | 0.008 |
Tumor differentiation (G3 vs. G1–2) | 1.49 | 0.72–3.11 | 0.285 | 1.81 | 0.90–3.65 | 0.098 | 1.50 | 0.78–2.90 | 0.228 |
Deep stromal invasion (yes vs. no) | 1.95 | 1.09–3.50 | 0.025 | 2.09 | 1.16–3.77 | 0.014 | 2.19 | 1.30–3.68 | 0.003 |
LVSI (yes vs. no) | 2.10 | 1.29–3.41 | 0.003 | 2.04 | 1.25–3.35 | 0.005 | 1.62 | 1.06–2.48 | 0.025 |
Positive margins (yes vs. no) | 9.37 | 5.19–16.91 | <0.0001 | 10.2 | 5.59–18.63 | <0.0001 | 7.92 | 4.41–14.22 | <0.0001 |
Positive nodes (yes vs. no) | 7.13 | 4.09–12.44 | <0.0001 | 7.55 | 4.25–13.42 | <0.0001 | 4.81 | 3.07–7.54 | <0.0001 |
Positive parametrium (yes vs. no) | 10.88 | 5.68–20.87 | <0.0001 | 11.83 | 6.11–22.87 | <0.0001 | 9.19 | 4.81–17.55 | <0.0001 |
Diabetes | |||||||||
No | Reference | Reference | Reference | Reference | Reference | Reference | Reference | Reference | Reference |
HbA1c < 7% | 2.66 | 1.32–5.37 | 0.006 | 2.79 | 1.31–5.97 | 0.008 | 3.33 | 1.78–6.24 | <0.0001 |
HbA1c ≥ 7% | 6.02 | 3.63–9.96 | <0.0001 | 7.13 | 4.17–12.17 | <0.0001 | 7.01 | 4.44–11.06 | <0.0001 |
Hypertension (yes vs. no) | 1.37 | 0.82–2.27 | 0.227 | 1.36 | 0.78–2.37 | 0.273 | 1.31 | 0.83–2.09 | 0.248 |
Cardiovascular disease (yes vs. no) | 1.09 | 0.47–2.52 | 0.837 | 0.47 | 0.18–1.19 | 0.109 | 1.11 | 0.54–2.31 | 0.770 |
Metformin (yes vs. no) | 1.21 | 0.65–2.24 | 0.552 | 0.88 | 0.46–1.68 | 0.705 | 1.86 | 1.13–3.07 | 0.015 |
Complete response (yes vs. no) | 0.52 | 0.33–0.82 | 0.005 | 0.50 | 0.31–0.83 | 0.007 | 0.69 | 0.45–1.06 | 0.089 |
Recurrence-free survival | Cancer-specific survival | Overall survival | |||||||
---|---|---|---|---|---|---|---|---|---|
HR | 95% CI |
P value | HR | 95% CI |
P value | HR | 95% CI |
P value | |
Age (years) | |||||||||
Body mass index (kg/m2) | 1.04 | 0.90–1.19 | 0.621 | 1.03 | 0.89–1.20 | 0.680 | |||
Serum creatinine (μmol/l) | |||||||||
Tumor stage (IIA2 vs. IB2) | |||||||||
Histology (non-squamous vs. squamous) | 1.28 | 0.70–2.35 | 0.427 | 1.30 | 0.68–2.47 | 0.430 | 1.28 | 0.51–3.21 | 0.602 |
Tumor differentiation (G3 vs. G1–2) | 4.16 | 1.93–8.97 | <0.0001 | ||||||
Deep stromal invasion (yes vs. no) | 0.77 | 0.40–1.49 | 0.433 | 0.83 | 0.42–1.63 | 0.586 | 1.21 | 0.68–2.16 | 0.516 |
LVSI (yes vs. no) | 1.26 | 0.73–2.15 | 0.405 | 1.16 | 0.66–2.04 | 0.616 | 0.91 | 0.56–1.48 | 0.708 |
Positive margins (yes vs. no) | 3.70 | 1.86–7.35 | <0.0001 | 4.42 | 2.15–9.08 | <0.0001 | 3.26 | 1.69–6.28 | <0.0001 |
Positive nodes (yes vs. no) | 5.21 | 2.82–9.62 | <0.0001 | 6.67 | 3.47–12.80 | <0.0001 | 3.47 | 2.09–5.78 | <0.0001 |
Positive parametrium (yes vs. no) | 3.37 | 1.67–6.82 | 0.001 | 3.14 | 1.54–6.41 | 0.002 | 2.84 | 1.41–5.73 | 0.004 |
Diabetes | |||||||||
No | Reference | Reference | Reference | Reference | Reference | Reference | Reference | Reference | Reference |
HbA1c < 7% | 1.49 | 0.69–3.22 | 0.307 | 1.57 | 0.68–3.62 | 0.290 | 2.06 | 1.04–4.07 | 0.039 |
HbA1c ≥ 7% | 3.33 | 1.89–5.88 | <0.0001 | 3.60 | 1.96–6.61 | <0.0001 | 4.35 | 2.64–7.17 | <0.0001 |
Hypertension (yes vs. no) | |||||||||
Cardiovascular disease (yes vs. no) | 0.57 | 0.22–1.48 | 0.245 | ||||||
Metformin (yes vs. no) | 1.13 | 0.41–3.11 | 0.807 | ||||||
Complete response (yes vs. no) | 0.58 | 0.36–0.95 | 0.031 | 0.52 | 0.31–0.87 | 0.013 | 0.78 | 0.50–1.22 | 0.279 |
Univariate analysis | Univariate analysis | Univariate analysis | |||||||
---|---|---|---|---|---|---|---|---|---|
HR | 95% CI |
P value | HR | 95% CI |
P value | HR | 95% CI |
P value | |
Age (years) | 1.00 | 0.96–1.04 | 0.875 | 1.01 | 0.97–1.05 | 0.681 | 0.99 | 0.96–1.03 | 0.698 |
Body mass index (kg/m2) | 1.17 | 0.99–1.39 | 0.065 | 1.18 | 1.00–1.39 | 0.055 | 1.08 | 0.92–1.26 | 0.361 |
Serum creatinine (μmol/l) | 1.00 | 0.98–1.02 | 0.872 | 1.02 | 0.99–1.04 | 0.211 | 1.01 | 0.98–1.03 | 0.610 |
Tumor stage (IIA2 vs. IB2) | 2.04 | 1.07–3.90 | 0.031 | 1.85 | 0.96–3.57 | 0.065 | 1.44 | 0.82–2.54 | 0.207 |
Histology (non-squamous vs. squamous) | 1.31 | 0.62–2.77 | 0.485 | 1.27 | 0.58–2.80 | 0.549 | 1.40 | 0.71–2.76 | 0.332 |
Tumor differentiation (G3 vs. G1–2) | 0.79 | 0.19–3.30 | 0.751 | 0.90 | 0.22–3.76 | 0.888 | 1.07 | 0.33–3.44 | 0.913 |
Deep stromal invasion (yes vs. no) | 1.49 | 0.62–3.58 | 0.371 | 1.55 | 0.68–3.55 | 0.300 | 1.79 | 0.86–3.70 | 0.119 |
LVSI (yes vs. no) | 1.16 | 0.61–2.24 | 0.647 | 1.26 | 0.65–2.44 | 0.503 | 0.96 | 0.54–1.70 | 0.890 |
Positive margins (yes vs. no) | 3.69 | 1.71–7.97 | 0.001 | 4.14 | 1.88–9.13 | <0.0001 | 3.04 | 1.42–6.47 | 0.004 |
Positive nodes (yes vs. no) | 4.81 | 2.19–10.56 | <0.0001 | 4.12 | 1.87–9.07 | <0.0001 | 3.07 | 1.63–5.78 | <0.0001 |
Positive parametrium (yes vs. no) | 5.55 | 2.27–13.55 | <0.0001 | 4.76 | 1.95–11.59 | 0.001 | 3.71 | 1.55–8.89 | 0.003 |
Diabetic status (HbA1c ≥ 7% vs. HbA1c < 7%) | 2.24 | 1.08–4.63 | 0.030 | 2.45 | 1.15–5.22 | 0.020 | 2.17 | 1.15–4.11 | 0.017 |
Hypertension (yes vs. no) | 0.90 | 0.46–1.77 | 0.763 | 0.94 | 0.47–1.86 | 0.854 | 0.90 | 0.50–1.62 | 0.723 |
Cardiovascular disease (yes vs. no) | 0.61 | 0.22–1.73 | 0.355 | 0.51 | 0.18–1.46 | 0.211 | 0.68 | 0.30–1.52 | 0.343 |
Metformin (yes vs. no) | 0.77 | 0.34–1.75 | 0.531 | 0.79 | 0.33–1.90 | 0.595 | 1.22 | 0.62–2.40 | 0.563 |
Complete response (yes vs. no) | 0.56 | 0.29–1.07 | 0.077 | 0.49 | 0.25–0.94 | 0.033 | 0.74 | 0.41–1.33 | 0.316 |
Recurrence-free survival | Cancer-specific survival | Overall survival | |||||||
---|---|---|---|---|---|---|---|---|---|
HR | 95% CI |
P value | HR | 95% CI |
P value | HR | 95% CI |
P value | |
Age (years) | |||||||||
Body mass index (kg/m2) | 1.16 | 0.94–1.44 | 0.171 | 1.12 | 0.90–1.38 | 0.312 | |||
Serum creatinine (μmol/l) | |||||||||
Tumor stage (IIA2 vs. IB2) | 1.64 | 0.78–3.48 | 0.195 | 1.55 | 0.71–3.37 | 0.267 | |||
Histology (non-squamous vs. squamous) | |||||||||
Tumor differentiation (G3 vs. G1–2) | |||||||||
Deep stromal invasion (yes vs. no) | 1.16 | 0.54–2.52 | 0.702 | ||||||
LVSI (yes vs. no) | |||||||||
Positive margins (yes vs. no) | 2.25 | 0.94–5.39 | 0.070 | 3.21 | 1.31–7.90 | 0.011 | 2.16 | 1.00–4.68 | 0.050 |
Positive nodes (yes vs. no) | 3.64 | 1.49–8.85 | 0.004 | 3.44 | 1.42–8.35 | 0.006 | 2.73 | 1.37–5.45 | 0.004 |
Positive parametrium (yes vs. no) | 3.50 | 1.31–9.32 | 0.012 | 2.71 | 1.00–7.35 | 0.049 | 2.16 | 0.88–5.30 | 0.093 |
Diabetic status (HbA1c ≥ 7% vs. HbA1c < 7%) | 2.18 | 1.02–4.63 | 0.044 | 2.00 | 0.89–4.49 | 0.092 | 2.29 | 1.20–4.35 | 0.012 |
Hypertension (yes vs. no) | |||||||||
Cardiovascular disease (yes vs. no) | |||||||||
Metformin (yes vs. no) | |||||||||
Complete response (yes vs. no) | 0.82 | 0.39–1.72 | 0.599 | 0.64 | 0.30–1.36 | 0.247 |
Factors predicting CR after NACT
Complete response | ||||||
---|---|---|---|---|---|---|
Univariate analysis | Multivariate analysis | |||||
OR | 95% CI |
P value | OR | 95% CI |
P value | |
Age (years) | 1.01 | 0.99–1.04 | 0.286 | |||
Body mass index (kg/m2) | 1.19 | 1.01–1.39 | 0.037 | 1.27 | 1.04–1.55 | 0.020 |
Serum creatinine (μmol/l) | 0.97 | 0.95–0.99 | 0.001 | 0.99 | 0.97–1.02 | 0.573 |
Tumor stage (IIA2 vs. IB2) | 1.60 | 1.12–2.30 | 0.010 | 0.99 | 0.73–1.35 | 0.956 |
Histology (non-squamous vs. squamous) | 1.55 | 0.64–3.71 | 0.329 | |||
Tumor differentiation (G3 vs. G1–2) | 0.91 | 0.45–1.84 | 0.784 | |||
Diabetes | ||||||
No | Reference | Reference | Reference | Reference | Reference | Reference |
HbA1c < 7% | 0.05 | 0.02–0.14 | <0.0001 | 0.06 | 0.02–0.17 | <0.0001 |
HbA1c ≥ 7% | 0.04 | 0.02–0.10 | <0.0001 | 0.04 | 0.02–0.11 | <0.0001 |
Hypertension (yes vs. no) | 0.34 | 0.20–0.59 | <0.0001 | 0.38 | 0.20–0.74 | 0.004 |
Cardiovascular disease (yes vs. no) | 0.84 | 0.35–2.04 | 0.700 | |||
Metformin (yes vs. no) | 0.64 | 0.34–1.22 | 0.174 |