Prolonged Exposition with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) May Provide Survival Benefit after Cytoreductive Surgery (CRS) in Advanced Primary Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Study Design
2.2. Details of CRS + HIPEC
2.3. Clinical Characteristics
2.4. Statistical Analysis
3. Results
3.1. Interval vs. Upfront HIPEC
3.2. Does the Duration of HIPEC Affect Clinical Parameters and Patient Survival?
3.3. Analysis of Other Parameters on Patient Survival Data
4. Discussion
Limitations of the Study
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical Characteristics | Total (n = 85) | Upfront HIPEC (n = 37) | Interval HIPEC (n = 48) | Crude p-Value | p-Value | 60 min HIPEC (n = 60) | 90 min HIPEC (n = 25) | Crude p-Value | p-Value |
---|---|---|---|---|---|---|---|---|---|
Age (year) | 62.16 ± 10.29 | 61.98 ± 12.33 | 62.52 ± 8.57 | 1.0000 | 62.50 ± 10.87 | 61.77 ± 9.01 | 1.0000 | ||
Body mass index (kg/m2) | 26.28 ± 5.39 | 26.74 ± 5.51 | 25.91 ± 5.29 | 1.0000 | 26.12 ± 5.00 | 26.62 ± 6.28 | 1.0000 | ||
ASA score | 1.0000 | 1.0000 | |||||||
| 20 (23.53%) | 9 (24.32%) | 11 (22.92%) | 13 (21.67%) | 7 (28%) | ||||
| 65 (76.47%) | 28 (75.68%) | 37 (77.08%) | 47 (78.33%) | 18 (72%) | ||||
Histology | 1.0000 | 1.0000 | |||||||
| 61 (71.76%) | 27 (72.97%) | 34 (70.83%) | 42 (70.00%) | 19 (76%) | ||||
| 21 (24.71%) | 9 (24.32%) | 12 (25%) | 15 (25.00%) | 6 (24%) | ||||
| 1 (1.18%) | 0 (0%) | 1 (2.08%) | 1 (1.67%) | 0 (0%) | ||||
| 1 (1.18%) | 1 (2.7%) | 0 (0%) | 1 (1.67%) | 0 (0%) | ||||
| 1 (1.18%) | 0 (0%) | 1 (2.08%) | 1 (1.67%) | 0 (0%) | ||||
FIGO Stage | 0.0025 | 0.1496 | 1.0000 | ||||||
| 11 (12.94%) | 5 (13.51%) | 6 (12.5%) | 9 (15.00%) | 2 (8%) | ||||
| 55 (64.71%) | 19 (51.35%) | 36 (75%) | 36 (60.00%) | 19 (76%) | ||||
| 3 (3.53%) | 0 (0%) | 3 (6.25%) | 3 (5.00%) | 0 (0%) | ||||
| 16 (18.82%) | 13 (35.14%) | 3 (6.25%) | 12 (20.00%) | 4 (16%) | ||||
Cause of FIGO IV | |||||||||
| 7 (8.24%) | 5 (13.51%) | 2 (4.17%) | 1.0000 | 4 (6.67%) | 3 (12%) | 1.0000 | ||
| 2 (2.35%) | 1 (2.7%) | 1 (2.08%) | 1.0000 | 2 (3.33%) | 0 (0%) | 1.0000 | ||
| 6 (7.06%) | 6 (16.22%) | 0 (0%) | 0.0053 | 0.3136 | 6 (10.00%) | 0 (0%) | 1.0000 | |
| 1 (1.18%) | 1 (2.7%) | 0 (0%) | 1.0000 | 1 (1.67%) | 0 (0%) | 1.0000 | ||
| 3 (3.53%) | 1 (2.7%) | 2 (4.17%) | 1.0000 | 3 (5.00%) | 0 (0%) | 1.0000 | ||
| 1 (1.18%) | 1 (2.7%) | 0 (0%) | 1.0000 | 0 (0%) | 1 (4%) | 1.0000 | ||
| 1 (1.18%) | 0 (0%) | 1 (2.08%) | 1.0000 | 1 (1.67%) | 0 (0%) | 1.0000 | ||
Cycles of carboplatin/TAX NACT | – | 0.1273 | 1.0000 | ||||||
| 17 (20%) | 0 (0%) | 17 (35.42%) | 9 (15.00%) | 8 (32%) | ||||
| 9 (10.59%) | 0 (0%) | 9 (18.75%) | 7 (11.67%) | 2 (8%) | ||||
| 22 (25.88%) | 0 (0%) | 22 (45.83%) | 13 (21.67%) | 9 (36%) | ||||
Peritoneal carcinomatosis index | 11.41 ± 6.45 | 15.00 ± 4.96 | 8.60 ± 5.79 | <0.0001 | 12.92 ± 5.65 | 7.72 ± 6.29 | 0.0009 | 0.0593 | |
CC score | 1.0000 | 1.0000 | |||||||
| 67 (78.82%) | 30 (81.08%) | 37 (77.08%) | 44 (73.33%) | 23 (92%) | ||||
| 16 (18.82%) | 6 (16.22%) | 10 (20.83%) | 14 (23.33%) | 2 (8%) | ||||
| 2 (2.35%) | 1 (2.7%) | 1 (2.08%) | 2 (3.33%) | 0 (0%) | ||||
Cisplatin (mg) | 132 ± 16.46 | 134.34 ± 17.37 | 130.20 ± 15.67 | 1.0000 | 130.69 ± 14.75 | 135.16 ± 19.97 | 1.0000 | ||
Doxorubicin (mg) | 26.58 ± 3.10 | 27.01 ± 3.17 | 26.11 ± 2.91 | 1.0000 | 26.28 ± 2.54 | 27.04 ± 4.00 | 1.0000 | ||
Duration of HIPEC (min) | 0.0298 | 1.0000 | – | ||||||
| 60 (70.59%) | 31 (83.78%) | 29 (60.42%) | – | – | ||||
| 25 (29.41%) | 6 (16.22%) | 19 (39.58%) | – | – | ||||
Type of HIPEC | – | 0.0298 | 1.0000 | ||||||
| 37 (43.53%) | – | – | 31 (51.67%) | 6 (24%) | ||||
| 48 (56.47%) | – | – | 29 (48.33%) | 19 (76%) | ||||
Length of surgery excl. HIPEC (min) | 317 ± 94 | 353 ± 77 | 290.38 ± 97.59 | 0.0015 | 0.0892 | 336.87 ± 74.26 | 270.80 ± 118.43 | 0.0145 | 0.8676 |
Surgical procedures | |||||||||
| 74 (87.06%) | 34 (91.89%) | 40 (83.33%) | 1.0000 | 52 (86.67%) | 22 (88%) | 1.0000 | ||
| 74 (87.06%) | 31 (83.78%) | 43 (89.58%) | 1.0000 | 54 (90.00%) | 20 (80%) | 1.0000 | ||
| 24 (28.24%) | 15 (40.54%) | 9 (18.75%) | 0.0317 | 1.0000 | 15 (25.00%) | 9 (36%) | 1.0000 | |
| 58 (68.24%) | 30 (81.08%) | 28 (58.33%) | 0.0345 | 1.0000 | 41 (68.33%) | 17 (68%) | 1.0000 | |
| 35 (41.18%) | 19 (51.35%) | 16 (33.33%) | 1.0000 | 30 (50%) | 5 (20%) | 0.0149 | 0.8814 | |
| 12 (14.12%) | 4 (10.81%) | 8 (16.67%) | 1.0000 | 9 (15.00%) | 3 (12%) | 1.0000 | ||
| 7 (8.24%) | 3 (8.11%) | 4 (8.33%) | 1.0000 | 5 (8.33%) | 2 (8%) | 1.0000 | ||
| 2 (2.35%) | 0 (0%) | 2 (4.17%) | 1.0000 | 2 (3.33%) | 0 (0%) | 1.0000 | ||
| 25 (29.41%) | 14 (37.84%) | 11 (22.92%) | 1.0000 | 19 (31.67%) | 6 (24%) | 1.0000 | ||
| 3 (3.53%) | 3 (8.11%) | 0 (0%) | 1.0000 | 3 (5.00%) | 0 (0%) | 1.0000 | ||
| 39 (45.88%) | 21 (56.76%) | 18 (37.50%) | 1.0000 | 29 (48.33%) | 10 (40%) | 1.0000 | ||
| 7 (8.24%) | 4 (10.81%) | 3 (6.25%) | 1.0000 | 5 (8.33%) | 2 (8%) | 1.0000 | ||
| 3 (3.53%) | 3 (8.11%) | 0 (0%) | 1.0000 | 3 (5.00%) | 0 (0%) | 1.0000 | ||
| 25 (29.41%) | 16 (43.24%) | 9 (18.75%) | 0.0159 | 0.9220 | 23 (38.33%) | 2 (8%) | 0.0080 | 0.5015 |
| 46 (54.12%) | 29 (78.38%) | 17 (35.42%) | 0.0055 | 38 (63.33%) | 8 (32%) | 0.0097 | 0.5947 | |
| 15 (17.65%) | 7 (18.92%) | 8 (16.67%) | 1.0000 | 11 (18.33%) | 4 (16%) | 1.0000 | ||
| 43 (50.59%) | 27 (72.97%) | 16 (33.33%) | 0.0260 | 36 (60.00%) | 7 (28%) | 0.0091 | 0.5635 | |
| 13 (15.29%) | 7 (18.92%) | 6 (12.50%) | 1.0000 | 11 (18.33%) | 2 (8%) | 1.0000 | ||
| 1 (1.18%) | 0 (0%) | 1 (2.08%) | 1.0000 | 1 (1.67%) | 0 (0%) | 1.0000 | ||
| 48 (56.47%) | 21 (56.76%) | 27 (56.25%) | 1.0000 | 37 (61.67%) | 11 (44%) | 1.0000 | ||
| 13 (15.29%) | 8 (21.62%) | 5 (10.42%) | 1.0000 | 9 (15.00%) | 4 (16%) | 1.0000 | ||
| 1 (1.18%) | 1 (2.70%) | 0 (0%) | 1.0000 | 1 (1.67%) | 0 (0%) | 1.0000 | ||
| 76 (89.41%) | 34 (91.89%) | 42 (87.50%) | 1.0000 | 53 (88.33%) | 23 (92%) | 1.0000 | ||
| 34 (40%) | 19 (51.35%) | 15 (31.25%) | 1.0000 | 25 (41.67%) | 9 (36%) | 1.0000 | ||
| 9 (10.59%) | 6 (16.22%) | 3 (6.25%) | 1.0000 | 7 (11.67%) | 2 (8%) | 1.0000 | ||
| 6 (7.06%) | 3 (8.11%) | 3 (6.25%) | 1.0000 | 5 (8.33%) | 1 (4%) | 1.0000 | ||
| 60 (70.59%) | 25 (67.57%) | 35 (72.92%) | 1.0000 | 45 (75.00%) | 15 (60%) | 1.0000 | ||
| 65 (76.47%) | 28 (75.68%) | 37 (77.08%) | 1.0000 | 43 (71.67%) | 22 (88%) | 1.0000 | ||
Length of hospital stay (day) | 22.76 ± 12.29 | 24.16 ± 9.33 | 21.79 ± 14.37 | 1.0000 | 24.38 ± 13.39 | 19.08 ± 8.89 | 1.0000 | ||
Length of ICU stay (day) | 5.23 ± 5.25 | 5.46 ± 5.28 | 5.06 ± 5.37 | 1.0000 | 5.72 ± 5.72 | 4.08 ± 3.99 | 0.0361 | 1.0000 | |
Blood transfusion | |||||||||
| 1.46 ± 2.20 | 1.30 ± 2.26 | 1.46 ± 2.00 | 1.0000 | 1.60 ± 2.28 | 0.88 ± 1.54 | 0.0511 | 1.0000 | |
| 3.45 ± 3.98 | 4.22 ± 5.03 | 2.73 ± 2.53 | 1.0000 | 3.73 ± 4.11 | 2.52 ± 3.14 | 1.0000 | ||
| 3:4:1 (3.53:4.71:1.18%) | 0:1:0 (0:2.70:0%) | 3:3:1 (6.25:6.25:2.08%) | 1.0000 | 0:0:0 (0:0:0%) | 3:4:1 (12:16:8%) | 0.0015 | ||
Pleura punction | 8 (9.41%) | 4 (%) | 4 (8.33%) | 1.0000 | 5 (8.33%) | 3 (12%) | 1.0000 | ||
Dialysis | 3 (3.53%) | 1 (2.70%) | 2 (4.17%) | 1.0000 | 2 (3.33%) | 1 (4%) | 1.0000 | ||
Complication grade (Clavien–Dindo) | 1.0000 | 1.0000 | |||||||
| 37 (43.53%) | 18 (48.65%) | 19 (39.58%) | 29 (48.33%) | 8 (32%) | ||||
| 22 (25.88%) | 12 (32.43%) | 10 (20.83%) | 14 (23.33%) | 8 (32%) | ||||
| 3 (3.53%) | 1 (2.70%) | 2 (4.17%) | 2 (3.33%) | 1 (4%) | ||||
| 2 (2.35%) | 0 (0%) | 2 (4.17%) | 2 (3.33%) | 0 (0%) | ||||
Complications | |||||||||
| 2 (2.35%) | 2 (5.41%) | 0 (0%) | 1.0000 | 1 (1.67%) | 1 (4%) | 1.0000 | ||
| 7 (8.24%) | 2 (5.41%) | 5 (10.42%) | 1.0000 | 6 (10.00%) | 1 (4%) | 1.0000 | ||
| 4 (4.71%) | 2 (5.41%) | 2 (4.17%) | 1.0000 | 4 (6.67%) | 0 (0%) | 1.0000 | ||
| 20 (23.53%) | 10 (27.03%) | 10 (20.83%) | 1.0000 | 15 (25.00%) | 5 (20%) | 1.0000 | ||
| 21 (24.71%) | 11 (29.73%) | 10 (20.83%) | 1.0000 | 16 (26.67%) | 5 (20%) | 1.0000 | ||
| 3 (3.53%) | 1 (2.70%) | 2 (4.17%) | 1.0000 | 2 (3.33%) | 1 (4%) | 1.0000 | ||
| 7 (8.24%) | 2 (5.41%) | 5 (10.42%) | 1.0000 | 3 (5.00%) | 4 (16%) | 1.0000 | ||
| 10 (11.76%) | 7 (18.92%) | 3 (6.25%) | 1.0000 | 9 (15.00%) | 1 (4%) | 1.0000 | ||
| 2 (2.35%) | 0 (0%) | 2 (4.17%) | 1.0000 | 2 (3.33%) | 0 (0%) | 1.0000 | ||
| 12 (14.12%) | 5 (13.51%) | 7 (14.58%) | 1.0000 | 8 (13.33%) | 4 (16%) | 1.0000 | ||
Median overall survival (month) | 42.58 | 43.00 | 47.44 | – | 31.16 | 58.41 | – | ||
Median DSS (month) | 45.24 | 45.24 | 47.44 | – | 41.92 | 58.41 | – | ||
Median RFS (month) | – 1 | – 1 | 59.73 | – | 59.73 | – 1 | – |
Clinical Characteristics | DSS | OS | RFS | |||
---|---|---|---|---|---|---|
Univariate p-Value | Multivariate p-Value | Univariate p-Value | Multivariate p-Value | Univariate p-Value | Multivariate p-Value | |
Age (years) | 0.0307 | 0.0113 | 0.0088 | 0.0416 | 0.6850 | 0.4184 |
Body mass index (kg/m2) | 0.0230 | 0.0004 | 0.0301 | 0.0044 | 0.6630 | 0.7968 |
ASA score | <0.0001 | <0.0001 | 0.2821 | 0.1319 | <0.0001 | <0.0001 |
FIGO Stage | 0.4550 | <0.0001 | 0.3085 | 0.2154 | <0.0001 | <0.0001 |
CC score | 0.0921 | 0.1617 | 0.0888 | 0.2351 | 0.3446 | 0.1521 |
Peritoneal carcinomatosis index | 0.0724 | < 0.0001 | 0.1040 | 0.0062 | 0.7090 | 0.1075 |
Type of HIPEC (upfront vs. interval) | 0.3670 | < 0.0001 | 0.2410 | 0.0016 | 0.8240 | 0.1865 |
Duration of HIPEC (60 vs. 90 min) | 0.0538 | 0.0030 | 0.0330 | 0.0012 | 0.2070 | 0.0959 |
Complication grade (Clavien–Dindo) | 0.1340 | – 1 | 0.0018 | 0.0041 | <0.0001 | <0.0001 |
Any incomplete tumor removal surgery prior CRS + HIPEC | 0.4300 | 0.0655 | 0.4290 | 0.2552 | 0.8740 | 0.9810 |
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Acs, M.; Herold, Z.; Szasz, A.M.; Mayr, M.; Häusler, S.; Piso, P. Prolonged Exposition with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) May Provide Survival Benefit after Cytoreductive Surgery (CRS) in Advanced Primary Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer. Cancers 2022, 14, 3301. https://doi.org/10.3390/cancers14143301
Acs M, Herold Z, Szasz AM, Mayr M, Häusler S, Piso P. Prolonged Exposition with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) May Provide Survival Benefit after Cytoreductive Surgery (CRS) in Advanced Primary Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer. Cancers. 2022; 14(14):3301. https://doi.org/10.3390/cancers14143301
Chicago/Turabian StyleAcs, Miklos, Zoltan Herold, Attila Marcell Szasz, Max Mayr, Sebastian Häusler, and Pompiliu Piso. 2022. "Prolonged Exposition with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) May Provide Survival Benefit after Cytoreductive Surgery (CRS) in Advanced Primary Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer" Cancers 14, no. 14: 3301. https://doi.org/10.3390/cancers14143301