Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Laboratory Assays
2.3. Statistical Analysis
3. Results
3.1. Descriptive Characteristics of the Study Population
3.2. Clinical and Biochemical Thyroid Dysfunction at Baseline
3.3. Overall Survival Outcomes
3.4. Recurrence-Free and Cancer-Specific Survival Outcomes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Number (% of Total) |
---|---|
Age at diagnosis (years) | Median (IQR)—66 (50, 82) |
<50 years | 42 (12.6%) |
50–70 years | 178 (53.5%) |
>70 years | 113 (33.9%) |
Body Mass Index (kg/m2) | Median (IQR)—33 (19, 47) |
Underweight | 3 (0.9%) |
Normal weight | 45 (13.5%) |
Overweight | 70 (21.0%) |
Obese | 215 (64.6%) |
Social deprivation quintile (n = 331) | |
1 (Most deprived) | 125 (37.8%) |
2 | 69 (20.9%) |
3 | 41 (12.4%) |
4 | 52 (15.7%) |
5 (Least deprived) | 44 (13.3%) |
History of hypothyroidism | |
Yes | 51 (15.3%) |
No | 282 (84.7%) |
History of diabetes mellitus | |
Yes | 59 (17.7%) |
No | 274 (82.3%) |
Histological subtype | |
Endometrioid | 268 (80.5%) |
Serous | 24 (7.2%) |
Carcinosarcoma | 21 (6.3%) |
Clear cell | 12 (3.6%) |
Other | 8 (2.4%) |
FIGO (2009) Stage | |
I | 256 (76.9%) |
II | 29 (8.7%) |
III | 43 (12.9%) |
IV | 5 (1.5%) |
Grade | |
1 | 164 (49.3%) |
2 | 75 (22.5%) |
3 | 94 (28.2%) |
LVSI (n = 332) | |
No | 239 (72%) |
Yes | 93 (28%) |
Depth of myometrial invasion (n = 332) | |
<50% | 217 (65.4%) |
≥50% | 115 (34.6%) |
Primary treatment | |
Surgery | 268 (80.5%) |
Hormonal (Fertility sparing) | 25 (7.5%) |
Hormonal (Not fit for surgery) | 37 (11.1%) |
Radiotherapy | 3 (0.9%) |
Adjuvant treatment | |
Yes | 132 (39.6%) |
No | 201 (60.4%) |
Recurrence (n = 326) | |
Yes | 38 (11.7%) |
No | 288 (88.3%) |
Overall survival status at end of follow-up | |
Alive | 283 (85.0%) |
Cancer-specific mortality | 33 (9.9%) |
Non-cancer related mortality | 17 (5.1%) |
Variable | Women with No History of Hypothyroidism n = 282 (84.7%) | Women with History of Hypothyroidism n = 51 (15.3%) | All Women n = 333 (100%) |
---|---|---|---|
Biochemical thyroid patterns, n (%) | |||
Euthyroid (Normal TSH, normal FT4) | 240 (88.2%) | 28 (58.3%) | 268 (83.8%) |
Hypothyroid | 23 (8.5%) | 13 (27.1%) | 36 (11.3%) |
Subclinical (High TSH, normal FT4) | |||
Overt (High TSH, low FT4) | - | 2 (4.2%) | 2 (0.6%) |
Secondary (Normal TSH, low FT4) | 1 (0.4%) | 1 (2.1%) | 2 (0.6%) |
Hyperthyroid | 7 (2.6%) | 2 (4.2%) | 9 (2.8%) |
Subclinical (Low TSH, normal FT4) | |||
Overt (Low TSH, high FT4) | 1 (0.4%) | 1 (2.1%) | 2 (0.6%) |
High FT4, normal TSH | - | 1 (2.1%) | 1 (0.3%) |
Total | 272 (100%) | 48 (100%) | 320 (100%) |
Biochemical tests, n (%) | |||
TSH (mU/L) (n = 329) | median (IQR) 2.1 (0.12, 9.1) n = 279 | median (IQR) 2.2 (0.003, 40.0) n = 50 | median (IQR) 2.1 (0.003, 40.0) |
<0.4 | 8 (2.9%) | 3 (6.0%) | 11 (3.30%) |
0.4–4.5 | 247 (88.5%) | 32 (64.0%) | 279 (84.8%) |
>4.5 | 24 (8.6%) | 15 (30.0%) | 39 (11.9%) |
FT4 (pmoL/L) (n = 323) | median (IQR) 14.0 (7.3, 27.2) n = 274 | median (IQR) 15.7 (7.7, 31.0) n = 49 | median (IQR) 14.2 (7.3, 31.0) |
<9.0 | 1 (0.4%) | 3 (6.1%) | 4 (1.2%) |
9–25 | 272 (99.3%) | 44 (89.8%) | 316 (97.8%) |
>25 | 1 (0.4%) | 2 (4.1%) | 3 (0.9%) |
TT3 (nmoL/L) (n = 331) | mean (SD) 1.73 (0.33) n = 280 | mean (SD) 1.53 (0.37) n = 51 | mean (SD) 1.70 (0.34) |
<1.2 | 8 (2.9%) | 9 (17.7%) | 17 (5.1%) |
1.2–2.6 | 267 (95.4%) | 41 (80.45) | 308 (93.1%) |
>2.6 | 5 (1.8%) | 1 (2.0%) | 6 (1.8%) |
TPOAb (IU) (n = 321) | |||
<60 (negative) | 252 (92.6%) | 34 (69.4%) | 286 (89.1%) |
≥60 (positive) | 20 (7.4%) | 15 (30.6%) | 35 (10.9%) |
TSH prognostic categories (n = 329) | |||
≤4.5 mU/L | 255 (91.4%) | 35 (70.0%) | 290 (88.1%) |
>4.5 mU/L | 24 (8.6%) | 15 (30.0%) | 39 (11.9%) |
Total | 282 (100%) | 51 (100%) | 333 (100%) |
Variable | One Year Survival % (95% CI) | Three-Year Survival % (95% CI) | Five-Year Survival % (95% CI) | Hazard Ratio (95% CI) | p-Value |
---|---|---|---|---|---|
Age (years) | |||||
<50 | 100 | 95 (72, 99) | 95 (72, 99) | 1.00 | |
50–70 | 96 (92, 98) | 87 (81, 92) | 80 (70, 88) | 5.49 (0.74, 40.6) | 0.095 |
>70 | 93 (87, 97) | 77 (67, 84) | 69 (54, 81) | 10.57 (1.43, 78.0) | 0.021 |
BMI categories | |||||
Normal weight | 100 | 95 (82, 98) | 85 (49, 96) | 1.00 | |
Overweight | 96 (87, 99) | 76 (63, 85) | 71 (56, 81) | 3.08 (1.03, 9.22) | 0.045 |
Obese | 95 (91, 97) | 85 (79, 90) | 80 (72, 87) | 1.84 (0.65, 5.24) | 0.254 |
Social deprivation quintile | |||||
Quintile 1 (Most deprived) | 96 (90, 98) | 85 (79, 90) | 80 (72, 87) | 1.00 | |
Quintile 2 | 93 (83, 97) | 86 (76, 92) | 84 (74, 90) | 1.40 (0.64, 3.04) | 0.401 |
Quintile 3 | 100 | 82 (69, 90) | 82 (69, 90) | 1.08 (0.42, 2.78) | 0.878 |
Quintile 4 | 96 (85, 99) | 83 (66, 92) | 83 (66, 92) | 1.06 (0.43, 2.61) | 0.895 |
Quintile 5 (Least deprived) | 95 (81, 99) | 89 (75, 95) | 77 (53, 90) | 2.19 (1.00, 4.76) | 0.049 |
History of diabetes mellitus | |||||
No | 96 (93, 98) | 88 (83, 92) | 83 (75, 89) | 1.00 | |
Yes | 93 (82, 97) | 68 (52, 80) | 55 (34, 72) | 2.84 (1.58, 5.11) | <0.001 |
History of hypothyroidism | |||||
No | 95 (91, 97) | 83 (79, 88) | 76 (67, 83) | 1.00 | |
Yes | 100 | 93 (78, 98) | 93 (78, 98) | 0.34 (0.11, 1.10) | 0.072 |
Baseline TSH (mU/L) | |||||
≤4.5 | 95 (92, 97) | 84 (79, 88) | 77 (68, 84) | 1.00 | |
>4.5 | 97 (82, 100) | 89 (69, 96) | 89 (69, 96) | 0.49 (0.15, 1.59) | 0.237 |
Histological subtype | |||||
Endometrioid | 97 (94, 98) | 89 (84, 92) | 85 (78, 90) | 1.00 | |
Non-endometrioid | 91 (80, 96) | 68 (54, 79) | 46 (17, 70) | 3.37 (1.90, 5.97) | <0.001 |
FIGO (2009) Stage | |||||
Early Stage (I/II) | 98 (95, 99) | 88 (83, 92) | 82 (74, 88) | 1.00 | |
Late stage (III/IV) | 83 (69, 91) | 66 (49, 78) | 57 (39, 72) | 3.45 (1.92, 6.20) | <0.001 |
Grade | |||||
1 | 97 (93, 99) | 91 (84, 95) | 86 (76, 92) | 1.00 | |
2 | 97 (89, 99) | 89 (78, 95) | 87 (75, 93) | 1.20 (0.52, 2.80) | 0.666 |
3 | 92 (85, 96) | 72 (60, 80) | 55 (33, 72) | 3.72 (1.95, 7.11) | <0.001 |
LVSI | |||||
No | 97 (94, 99) | 89 (84, 93) | 83 (73, 89) | 1.00 | |
Yes | 92 (84, 96) | 73 (62, 81) | 68 (55, 79) | 2.59 (1.48, 4.50) | 0.001 |
Depth of myometrial invasion | |||||
≤50% | 97 (94, 99) | 90 (84, 93) | 83 (73, 90) | 1.00 | |
>50% | 93 (86, 96) | 75 (64, 82) | 70 (58, 79) | 2.43 (1.39, 4.24) | 0.002 |
Thyroid Marker | Hazard Ratio (95% CI) | p-Value |
---|---|---|
Overall Survival | ||
History of Hypothyroidism | ||
No | 1.00 | |
Yes | 0.22 (0.06, 0.74) | 0.02 |
Baseline TSH (mU/L) | ||
≤4.5 | 1.00 | |
>4.5 | 0.48 (0.14, 1.65) | 0.25 |
Recurrence-free Survival | ||
History of Hypothyroidism | ||
No | 1.00 | |
Yes | 0.17 (0.04, 0.77) | 0.02 |
Baseline TSH (mU/L) | ||
≤4.5 | 1.00 | |
>4.5 | 0.57 (0.16, 2.05) | 0.39 |
Cancer-Specific Survival | ||
History of Hypothyroidism | ||
No | 1.00 | |
Yes | 0.21 (0.05, 0.98) | 0.04 |
Baseline TSH (mU/L) | ||
≤4.5 | 1.00 | |
>4.5 | 0.38 (0.08, 1.82) | 0.23 |
Variable | One Year Survival % (95% CI) | Three-Year Survival % (95% CI) | Five-Year Survival % (95% CI) | Hazard Ratio (95% CI) | p-Value |
---|---|---|---|---|---|
Age | |||||
<50 | 100 | 97 (82, 99) | 97 (82, 99) | 1.00 | |
50–70 | 91 (85, 95) | 84 (76, 89) | 79 (69, 86) | 6.32 (0.86, 46.8) | 0.071 |
>70 | 94 (87, 98) | 85 (74, 92) | 74 (47, 89) | 6.03 (0.78, 46.4) | 0.084 |
BMI categories | |||||
Normal weight | 100 | 92 (76, 97) | 81 (50, 94) | 1.00 | |
Overweight | 87 (75, 94) | 81 (65, 90) | 71 (44, 86) | 2.15 (0.67, 6.85) | 0.166 |
Obese | 94 (90, 97) | 87 (80, 91) | 84 (75, 90) | 1.34 (0.46, 3.89) | 0.701 |
Social deprivation quintile | |||||
Quintile 1 (Most deprived) | 94 (87, 97) | 84 (75, 90) | 84 (75, 90) | 1.00 | |
Quintile 2 | 94 (84, 98) | 84 (70, 92) | 84 (70, 92) | 1.03 (0.45, 2.44) | 0.944 |
Quintile 3 | 91 (75, 97) | 83 (63, 93) | 83 (63, 93) | 1.01 (0.37, 2.78) | 0.986 |
Quintile 4 | 100 | 95 (72, 99) | 88 (57, 97) | 0.29 (0.07, 1.25) | 0.097 |
Quintile 5 (Least deprived) | 86 (69, 94) | 86 (69, 94) | 56 (17, 83) | 1.50 (0.07, 1.25) | 0.380 |
History of diabetes mellitus | |||||
No | 94 (90, 97) | 89 (84, 93) | 82 (72, 89) | 1.00 | |
Yes | 87 (74, 94) | 67 (47, 81) | 67 (47, 81) | 2.49 (1.26, 4.94) | 0.009 |
History of hypothyroidism | |||||
No | 93 (89, 95) | 85 (79, 89) | 78 (67, 85) | 1.00 | |
Yes | 98 (84, 100) | 94 (78, 99) | 94 (78, 99) | 0.28 (0.07, 1.16) | 0.078 |
Baseline TSH (mU/L) | |||||
≤4.5 | 93 (89, 96) | 85 (80, 90) | 79 (69, 86) | 1.00 | |
>4.5 | 94 (79, 99) | 88 (64, 96) | 88 (64, 96) | 0.66 (0.20, 2.16) | 0.495 |
Histological subtype | |||||
Endometrioid | 96 (92, 97) | 91 (85, 94) | 89 (82, 93) | 1.00 | |
Non-endometrioid | 83 (71, 90) | 67 (49, 79) | 33 (6.4, 64) | 4.56 (2.39, 8.69) | <0.001 |
FIGO (2009) Stage | |||||
Early Stage (I/II) | 97 (93, 98) | 90 (85, 94) | 84 (74, 91) | 1.00 | |
Late stage (III/IV) | 71 (55, 83) | 59 (41, 73) | 59 (41, 73) | 5.55 (2.89, 10.7) | <0.001 |
Grade | |||||
1 | 99 (95, 100) | 96 (88, 99) | 93 (78, 98) | 1.00 | |
2 | 97 (89, 99) | 88 (76, 94) | 88 (76, 94) | 3.22 (0.94, 11.0) | 0.062 |
3 | 80 (70, 88) | 67 (54, 77) | 49 (26, 69) | 13.64 (4.75, 39.2) | <0.001 |
LVSI | |||||
No | 97 (93, 98) | 93 (88, 96) | 88 (76, 94) | 1.00 | |
Yes | 84 (75, 91) | 67 (54, 77) | 62 (46, 74) | 5.54 (2.83, 10.84) | <0.001 |
Depth of myometrial invasion | |||||
≤50% | 97 (93, 99) | 92 (86, 96) | 86 (74, 93) | 1.00 | |
>50% | 86 (77, 91) | 72 (60, 81) | 68 (53, 79) | 3.82 (1.98, 7.40) | <0.001 |
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Barr, C.E.; Njoku, K.; Hotchkies, L.; Ryan, N.A.J.; Wan, Y.L.; Davies, D.A.; Razvi, S.; Crosbie, E.J. Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study. Cancers 2021, 13, 5444. https://doi.org/10.3390/cancers13215444
Barr CE, Njoku K, Hotchkies L, Ryan NAJ, Wan YL, Davies DA, Razvi S, Crosbie EJ. Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study. Cancers. 2021; 13(21):5444. https://doi.org/10.3390/cancers13215444
Chicago/Turabian StyleBarr, Chloe E., Kelechi Njoku, Leo Hotchkies, Neil A. J. Ryan, Y. Louise Wan, David A. Davies, Salman Razvi, and Emma J. Crosbie. 2021. "Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study" Cancers 13, no. 21: 5444. https://doi.org/10.3390/cancers13215444