Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Chemotherapy
2.3. Response Evaluation
2.4. Follow-Up and Overall Survival
2.5. Molecular Analysis
2.6. Statistical Analysis
3. Results
3.1. Sex/Age and Association with Patient Characteristics and Response to Chemotherapy
3.2. Sex/Age and Survival of the Patients
3.3. Sex/Age and Frequency of Molecular Subgroups and Association with Patient Characteristics and Response to Chemotherapy
3.4. Sex-Specificity of the Molecular Subgroups and Survival of the Patients
3.5. Multivariable Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Category | Value | Female n (%) | Male n (%) | p-Value 1 | <55 Years n (%) | ≥55
Years n (%) | p-Value 1 |
---|---|---|---|---|---|---|---|
Cases | Total | 188 (100) | 529 (100) | 174 (100) | 543 (100) | ||
Tumor localization | Proximal | 75 (39.9) | 298 (56.3) | 0.001 | 94 (54.0) | 279 (51.4) | 0.581 |
Middle | 52 (27.7) | 116 (21.9) | 39 (22.4) | 129 (23.7) | |||
Distal | 47 (25.0) | 92 (17.4) | 36 (20.7) | 103 (19.0) | |||
Total/linitis | 14 (7.4) | 16 (3.6) | 5 (2.9) | 28 (5.2) | |||
n/a | - | 4 (<1) | - | 4 (<1) | |||
Proximal versus non-proximal | Proximal | 75 (39.9) | 298 (56.3) | <0.001 | 94 (54.0) | 279 (51.4) | 0.604 |
Non-proximal | 113. (60.1) | 227 (42.9) | 80 (46.0) | 260 (47.9) | |||
n/a | - | 4 (<1) | - | 4 (<1) | |||
Laurén classification | Intestinal | 82 (43.6) | 315 (59.5) | <0.001 | 81 (46.6) | 316 (58.2) | 0.007 |
Non-intestinal | 106 (56.4) | 214 (40.5) | 93 (53.4) | 227 (41.8) | |||
Tumor grade | G1/2 | 36 (19.1) | 111 (21.0) | 0.485 | 27 (15.5) | 120 (22.1) | 0.061 |
G3/4 | 131 (69.7) | 347 (65.6) | 124 (71.3) | 354 (65.2) | |||
n/a | 21 (11.2) | 71 (13.4) | 23 (13.2) | 69 (12.7) | |||
Clinical tumor stage | cT2 | 46 (24.5) | 103 (19.5) | 0.123 | 29 (16.7) | 120 (22.1) | 0.135 |
cT3/cT4 | 138 (73.4) | 422 (79.8) | 142 (81.6) | 418 (77.0) | |||
n/a | 4 (2.1) | 4 (<1) | 3 (1.7) | 5 (<1) | |||
(y)pT 2 | (y)pT0 | 5 (2.7) | 4 (0.8) | 0.030 | 4 (2.3) | 5 (0.9) | 0.293 |
(y)pT1 | 19 (10.1) | 48 (9.1) | 14 (8.1) | 53 (9.8) | |||
(y)pT2 | 24 (12.8) | 70 (13.2) | 17 (9.8) | 77 (14.2) | |||
(y)pT3 | 85 (45.2) | 297 (56.1) | 99 (56.9) | 283 (52.1) | |||
(y)pT4 | 53 (28.2) | 110 (20.8) | 39 (22.4) | 124 (22.8) | |||
n/a | 2 (1.1) | - | 1 (<1) | 1 (<1) | |||
(y)pN 2 | Negative | 60 (31.9) | 179 (33.8) | 0.695 | 48 (27.6) | 191 (35.2) | 0.069 |
Positive | 126 (67.0) | 350 (66.2) | 125 (71.8) | 351 (64.6) | |||
n/a | 2 (1.1) | - | 1 (<1) | 1 (<1) | |||
Metastasis status | No | 156 (83.0) | 442 (83.6) | 0.920 | 136 (78.2) | 462 (85.1) | 0.040 |
Yes | 30 (15.9) | 87 (16.4) | 37 (21.3) | 80 (14.7) | |||
n/a | 2 (1.1) | - | 1 (<1) | 1 (<1) | |||
Resection category | R0 | 148 (78.7) | 402 (76.0) | 0.319 | 130 (74.7) | 420 (77.3) | 0.524 |
R1 | 38 (20.2) | 127 (24.0) | 43 (27.7) | 122 (22.5) | |||
n/a | 2 (1.1) | - | 1 (<1) | 1 (<1) | |||
Neoadjuvant CTx | No | 98 (52.1) | 193 (36.5) | <0.001 | 50 (28.7) | 241 (44.4) | <0.001 |
Yes | 90 (47.9) | 336 (63.5) | 124 (71.3) | 302 (55.6) | |||
Response 3 | Responder (TRG1) | 12 (13.3) | 33 (9.8) | 0.336 | 16 (12.9) | 29 (9.6) | 0.314 |
Non-responder (TRG2/3) 4 | 78 (86.7) | 303 (90.2) | 108 (87.1) | 273 (90.4) | |||
Total 3 | 90 (100) | 336 (100) | 124 (100) | 302 (100) | |||
MSI status | MSS | 159 (84.6) | 454 (85.8) | 0.278 | 162 (93.1) | 451 (83.1) | 0.004 |
MSI-L | 7 (3.7) | 30 (5.7) | 5 (2.9) | 32 (5.9) | |||
MSI-H | 22 (11.7) | 45 (8.5) | 7 (4.0) | 60 (11.0) | |||
EBV status | EBV negative | 186 (98.9) | 502 (94.9) | 0.016 | 163 (93.7) | 525 (96.7) | 0.080 |
EBV positive | 2 (1.1) | 27 (5.1) | 11 (6.3) | 18 (3.3) |
Patient Cohort and Subgroups | Sex | No. | Events | Survival Probability (%) | Median Survival (Months) | HR | p-Value 1 | ||
---|---|---|---|---|---|---|---|---|---|
1 Year | 3 Years | 5 Years | (95% CI) | (95% CI) | |||||
All tumor specimens | Female | 188 | 78 | 79.7 | 61.4 | 55.2 | 75.8 (42.6–109.0) | 0.77 (0.60–0.99) | 0.035 |
Male | 529 | 266 | 78.4 | 51.4 | 43.8 | 41.7 (29.8–53.6) | 1 ref. | - | |
Total | 717 | 344 | 78.8 | 54.0 | 46.8 | 46.3 (33.1–59.5) | - | - | |
Tumors with neoadjuvant CTx | Female | 90 | 41 | 79.8 | 61.1 | 53.4 | 71.6 (42.4–100.9) | 0.72 (0.51–1.01) | 0.054 |
Male | 336 | 181 | 77.7 | 46.4 | 38.9 | 31.4 (22.1–40.7) | 1 ref. | - | |
Total | 426 | 222 | 78.1 | 49.7 | 42.0 | 35.9 (27.2–44.6) | - | - | |
Tumors without neoadjuvant CTx | Female | 98 | 37 | 79.8 | 61.9 | 57.2 | nr | 0.90 (0.61–1.32) | 0.587 |
Male | 193 | 85 | 79.8 | 59.9 | 52.4 | 77.3 (36.7–117.9) | 1 ref. | - | |
Total | 291 | 122 | 79.7 | 60.5 | 54.0 | 85.0 (51.7–118.3) | - | - |
Patient Cohort and Subgroups | Sex and MSI Status | No. | Events | Survival Probability (%) | Median Survival (Months) | HR | p-Value 1 | ||
---|---|---|---|---|---|---|---|---|---|
1 Year | 3 Years | 5 Years | (95% CI) | (95% CI) | |||||
All tumor specimens | 0.031 | ||||||||
Female, MSI-H | 22 | 6 | 81.8 | 77.0 | 71.1 | nr | 0.39 (0.18–0.89) | 0.024 | |
Female, MSS/EBV(−) | 158 | 69 | 79.7 | 59.1 | 52.6 | 66.9 (33.9–99.9) | 0.79 (0.61–1.04) | 0.095 | |
Male, MSI-H | 45 | 18 | 78.5 | 62.6 | 59.3 | 87.5 (-) | 0.69 (0.43–1.11) | 0.126 | |
Male, MSS/EBV(−) | 428 | 222 | 78.5 | 49.3 | 41.4 | 33.8 (24.1–43.5) | 1 ref. | - | |
Total 2 | 653 | 315 | 78.9 | 53.6 | 46.5 | 45.3 (31.5–59.1) | - | - | |
Tumors with neoadjuvant CTx | 0.056 | ||||||||
Female, MSI-H | 8 | 1 | 100 | 100 | 83.3 | 0.13 (0.02–0.94) | 0.043 | ||
Female, MSS/EBV(−) | 78 | 39 | 78.1 | 56.7 | 49.7 | 44.9 (14.2–75.6) | 0.75 (0.53–1.07) | 0.114 | |
Male, MSI-H | 24 | 10 | 82.4 | 57.7 | 51.3 | nr | 0.66 (0.35–1.25) | 0.198 | |
Male, MSS/EBV(−) | 274 | 156 | 76.3 | 43.4 | 36.1 | 29.1 (25.2–33.0) | 1 ref. | - | |
Total 2 | 384 | 206 | 77.8 | 48.5 | 40.9 | 33.8 (25.5–42.1) | - | - | |
Tumors without neoadjuvant CTx | 0.898 | ||||||||
Female, MSI-H | 14 | 5 | 71.4 | 63.5 | 63.5 | nr | 0.76 (0.30–1.88) | 0.548 | |
Female, MSS/EBV(−) | 80 | 30 | 81.7 | 62.1 | 56.1 | 89.5 (-) | 0.94 (0.61–1.45) | 0.772 | |
Male, MSI-H | 21 | 8 | 73.9 | 68.2 | 68.2 | 87.5 (-) | 0.82 (0.39–1.72) | 0.604 | |
Male, MSS/EBV(−) | 154 | 66 | 81.7 | 59.9 | 51.2 | 61.1 (25.5–96.7) | 1 ref. | - | |
Total 2 | 269 | 109 | 80.5 | 61.5 | 54.9 | 87.5 (-) | - | - |
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Kohlruss, M.; Ott, K.; Grosser, B.; Jesinghaus, M.; Slotta-Huspenina, J.; Novotny, A.; Hapfelmeier, A.; Schmidt, T.; Gaida, M.M.; Weichert, W.; et al. Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer. Cancers 2021, 13, 1048. https://doi.org/10.3390/cancers13051048
Kohlruss M, Ott K, Grosser B, Jesinghaus M, Slotta-Huspenina J, Novotny A, Hapfelmeier A, Schmidt T, Gaida MM, Weichert W, et al. Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer. Cancers. 2021; 13(5):1048. https://doi.org/10.3390/cancers13051048
Chicago/Turabian StyleKohlruss, Meike, Katja Ott, Bianca Grosser, Moritz Jesinghaus, Julia Slotta-Huspenina, Alexander Novotny, Alexander Hapfelmeier, Thomas Schmidt, Matthias M. Gaida, Wilko Weichert, and et al. 2021. "Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer" Cancers 13, no. 5: 1048. https://doi.org/10.3390/cancers13051048