Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Data Collection and Outcome Assessments
2.3. Statistical Analyses
3. Results
3.1. Patient Demographics
3.1.1. Complete OCCC Cohort
3.1.2. Relapse Cohort
3.2. Grading Platinum Sensitivity by PFI
3.3. PFI-Associated Factors
3.4. Stage-Associated Factors
3.5. Clinical Outcomes
3.5.1. Stage-Associated and Treatment-Associated Survival
3.5.2. Survival Curves following the First Relapse
3.6. Univariate and Multivariate Analyses
3.6.1. Complete OCCC Cohort
3.6.2. Early-Stage OCCC Cohort
3.6.3. Relapsed OCCC Cohort
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | OCCC Patients (n = 536) |
---|---|
Age, years, mean ± SD | 50.0 ± 9.9 |
Menarche age, years, median ± IQR (range) | 13.0 ± 1.0 (10.0–18.0) |
CA125 level at diagnosis, U/mL, median ± IQR (range) | 101.5 ± 324 (6.0–16,659.0) |
Nulliparity | 141 (30.4) |
Parity, mean ± SD | 1.5 ± 1.3 |
Menopause | 279 (52.1) |
Most common symptoms, n (%) | |
Asymptomatic | 43 (8.0) |
Abdominal pain | 112 (20.9) |
Abdominal bloating | 132 (24.6) |
Abnormal uterine bleeding | 17 (3.2) |
Other symptoms | 101 (18.8) |
Endometriosis present pathologically | 209 (39.0) |
FIGO stage, n (%) | |
I | 308 (57.5) |
II | 63 (12.3) |
III | 116 (21.1) |
IV | 34 (6.2) |
Unknown | 15 (2.8) |
Primary staging/cytoreduction, n (%) | |
RD < 1 cm | 429 (80.0) |
RD ≥ 1 cm | 61 (11.4) |
Unknown | 46 (8.5) |
Front-line chemotherapy, n (%) | |
Pt-PTX | 354 (66.0) |
Pt-CTX | 120 (22.4) |
Other platinum-based regimens, n (%) | 29 (5.4) |
None | 33 (6.2) |
Cycles of front-line chemotherapy, median ± IQR (range) | 6.0 ± 1.0 (1–11) |
<6, n (%) | 134 (26.6) |
≥6, n (%) | 369 (73.4) |
PFI after primary chemotherapy, n (%) | |
≥12 months | 320 (63.6) |
6–12 months | 56 (11.1) |
<6 months | 127 (25.2) |
Surgical resection after the first relapse, n (%) | 67 (36.0) |
Chemotherapy after the first relapse, n (%) | |
None | 35 (18.8) |
Pt-PTX | 55 (29.6) |
Pt-CTX | 2 (1.1) |
Other | 87 (46.8) |
PFI after Front-Line Chemotherapy to the First Relapse (Months) | No. of Patients with Pt-Based Chemotherapy | No. of Patients with the Second Relapse | Median PFS2-PFS (Months) | HR | 95% CI |
---|---|---|---|---|---|
<6 | 38 | 34 | 6.8 | 1.00 | – |
≥6 | 47 | 32 | 20.9 | 0.41 | 0.25–0.68 |
6–12 | 16 | 15 | 9.2 | 0.76 | 0.41–1.40 |
≥12 | 31 | 16 | 24.4 | 0.27 | 0.15–0.50 |
<7 | 41 | 37 | 6.8 | 1.00 | – |
≥7 | 44 | 28 | 21.0 | 0.37 | 0.22–0.61 |
7–12 | 13 | 12 | 11.2 | 0.68 | 0.35–1.31 |
≥12 | 31 | 16 | 24.4 | 0.27 | 0.14–0.49 |
7–14 | 18 | 16 | 14.9 | 0.53 | 0.29–0.97 |
≥14 | 26 | 12 | 24.4 | 0.26 | 0.13–0.50 |
7–16 | 20 | 18 | 11.2 | 0.57 | 0.32–1.01 |
≥16 | 24 | 10 | NR | 0.22 | 0.11–0.45 |
7–18 | 23 | 21 | 11.2 | 0.60 | 0.35–1.03 |
≥18 | 21 | 7 | NR | 0.17 | 0.07–0.38 |
<8 | 46 | 41 | 8.5 | 1.00 | – |
≥8 | 39 | 24 | 23.0 | 0.38 | 0.23–0.65 |
8–16 | 15 | 14 | 8.6 | 0.65 | 0.35–1.21 |
≥16 | 24 | 10 | NR | 0.24 | 0.12–0.49 |
<10 | 49 | 44 | 8.5 | 1.00 | – |
≥10 | 36 | 21 | 24.4 | 0.35 | 0.20–0.60 |
10–18 | 15 | 14 | 8.6 | 0.64 | 0.35–1.19 |
≥18 | 21 | 7 | NR | 0.18 | 0.08–0.41 |
<12 | 54 | 49 | 8.6 | 1.00 | – |
≥12 | 31 | 16 | 24.4 | 0.30 | 0.16–0.54 |
12–18 | 10 | 9 | 8.5 | 0.57 | 0.27–1.18 |
>18 | 21 | 7 | NR | 0.18 | 0.08–0.41 |
Variables | PFI ≥7 Months n = 366 | PFI <7 Months n = 137 | p | PFI ≥12 Months n = 318 | PFI <12 Months n = 185 | p |
---|---|---|---|---|---|---|
Age >50 years | 179 (48.9) | 60 (43.8) | 0.271 | 154 (48.4) | 85 (45.9) | 0.584 |
Menopause | 192 (52.5) | 68 (49.6) | 0.516 | 162 (50.9) | 98 (53.0) | 0.667 |
CA125 level ≥114.5 U/mL | 126 (34.4) | 88 (64.2) | <0.001 | 103 (32.4) | 111 (60.0) | <0.001 |
Endometriosis present | 147 (40.1) | 52 (38.0) | 0.628 | 132 (41.5) | 67 (36.2) | 0.424 |
FIGO stage | <0.001 | <0.001 | ||||
I | 248 (67.8) | 41 (29.9) | 225 (70.8) | 64 (34.6) | ||
II | 43 (11.7) | 17 (12.4) | 39 (12.3) | 21 (11.4) | ||
III | 46 (12.6) | 64 (46.7) | 31 (9.7) | 79 (42.7) | ||
IV | 18 (4.9) | 13 (9.5) | 12 (3.8) | 19 (10.3) | ||
Primary cytoreduction | <0.001 | <0.001 | ||||
Optimal (RD <1 cm) | 316 (86.3) | 94 (68.6) | 278 (87.4) | 132 (71.3) | ||
Suboptimal (RD ≥1 cm) | 17 (4.6) | 35 (25.5) | 11 (3.5) | 41 (22.2) | ||
Front-line chemotherapy | 0.192 | 0.121 | ||||
Pt-PTX | 250 (68.3) | 104 (75.9) | 214 (67.3) | 140 (75.7) | ||
Pt-CTX | 95 (26.0) | 25 (18.2) | 85 (26.7) | 35 (18.9) | ||
Other | 21 (5.7) | 8 (5.8) | 19 (6.0) | 10 (5.4) | ||
Cycles of front-line chemotherapy | 0.005 | 0.068 | ||||
<6 | 85 (23.2) | 49 (35.8) | 76 (23.9) | 58 (31.4) | ||
≥6 | 281 (76.8) | 88 (64.2) | 242 (76.1) | 127 (68.6) | ||
Response to primary chemotherapy | <0.001 | <0.001 | ||||
CR/PR | 335 (91.5) | 68 (49.6) | 298 (93.7) | 105 (56.8) | ||
SD/PD | 22 (6.0) | 64 (46.7) | 11 (3.5) | 75 (40.5) | ||
Tumour resection after the first relapse | 0.076 | 0.034 | ||||
No | 114 (79.2) | 67 (69.1) | 98 (81.0) | 83 (69.2) | ||
Yes | 30 (20.8) | 30 (30.9) | 23 (19.0) | 37 (30.8) | ||
Chemotherapy after the first relapse | <0.001 | <0.001 | ||||
Pt-PTX | 33 (54.1) | 16 (21.6) | 29 (70.7) | 20 (21.3) | ||
Other | 28 (45.9) | 58 (78.4) | 12 (29.3) | 74 (78.7) |
Variables | HR for the First Progression (95% CI) | HR for Death (95% CI) |
---|---|---|
Age (≥50 vs. <50 years) | 0.89 (0.62–1.27) | 2.98 (1.60–5.57) |
CA125 level at diagnosis (≥ 114.5 versus <114.5 U/mL) | 1.57 (1.03–2.40) | 0.71 (0.34–1.47) |
Endometriosis present (yes versus no) | 1.00 (0.69–1.44) | 0.93 (0.52–1.64) |
FIGO stage (advanced versus early) | 3.21 (1.98–5.22) | 1.41 (0.67–2.95) |
Primary staging/cytoreduction (RD ≥ 1 cm versus <1 cm) | 1.30 (0.81–2.08) | 1.12 (0.59–2.34) |
Front-line chemotherapy (Pt-PTX versus Pt-CTX) | 0.69 (0.41–1.16) | 0.71 (0.25–2.03) |
Cycles of chemotherapy (≥6 versus <6) | 0.88 (0.59–1.33) | 1.04 (0.51–2.10) |
Response to chemotherapy (SD/PD versus CR/PR) | 4.56 (2.88–7.23) | 1.47 (0.79–2.73) |
Progression-free interval (<7 months versus ≥7 months) | - | 7.85 (3.63–16.94) |
Surgical resection after the first relapse (yes versus no) | - | 0.60 (0.29–1.23) |
Chemotherapy after the first relapse (others versus Pt-PTX) | - | 1.23 (0.52–2.89) |
Variables | HR for the First Progression (95% CI) | HR for Death (95% CI) |
---|---|---|
Age (≥50 versus <50 years) | 0.72 (0.39–1.31) | 2.39 (0.67–8.50) |
CA125 level at diagnosis (≥ 114.5 versus <114.5 U/mL) | 2.63 (1.48–4.67) | 0.61 (0.17–2.19) |
Endometriosis present (yes versus no) | 0.74 (0.41–1.33) | 0.44 (0.14–1.35) |
Primary staging/cytoreduction (RD ≥ 1 cm versus <1 cm) | 1.38 (0.39–4.92) | 0.81 (0.09–7.81) |
Front-line chemotherapy (Pt-PTX versus Pt-CTX) | 0.61 (0.34–1.09) | 0.48 (0.12–1.99) |
Cycles of chemotherapy (≥6 versus <6) | 0.76 (0.41–1.41) | 2.22 (0.57–8.61) |
Response to chemotherapy (SD/PD versus CR/PR) | 22.77 (11.64–44.56) | 1.83 (0.44–7.57) |
PFI after primary chemotherapy (<7 versus ≥7 months) | - | 4.82 (1.32–17.60) |
Surgical resection after the first relapse (yes versus no) | - | 0.23 (0.06–0.91) |
Chemotherapy after the first relapse (other versus Pt-PTX) | - | 1.64 (0.41–6.62) |
Variables | HR for the Next Progression (95% CI) | HR for Post- Progression Death (95% CI) |
---|---|---|
Age (≥50 versus <50) | 1.49 (0.97–2.30) | 2.26 (1.37–3.72) |
FIGO stage (advanced versus early) | 1.50 (0.95–2.37) | 1.73 (1.01–2.96) |
Response to chemotherapy (SD/PD versus CR/PR) | 1.33 (0.85–2.08) | 1.26 (0.76–2.10) |
Progression-free interval (<7 versus ≥7 months) | 2.46 (1.54–3.93) | 3.86 (2.15–6.96) |
Surgical resection after the first relapse (yes versus no) | 0.83 (0.52–1.32) | 0.83 (0.50–1.41) |
Chemotherapy after the first relapse (other versus Pt-PTX) | 1.04 (0.62–1.75) | 0.95 (0.51–1.78) |
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Chou, C.-Y.; Cheng, W.-F.; Chen, M.-Y.; Lin, H.; Ho, C.-M.; Hung, Y.-C.; Huang, L.-W.; Wang, P.-H.; Yu, M.-H.; Huang, Y.-F. Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study. Cancers 2022, 14, 1746. https://doi.org/10.3390/cancers14071746
Chou C-Y, Cheng W-F, Chen M-Y, Lin H, Ho C-M, Hung Y-C, Huang L-W, Wang P-H, Yu M-H, Huang Y-F. Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study. Cancers. 2022; 14(7):1746. https://doi.org/10.3390/cancers14071746
Chicago/Turabian StyleChou, Cheng-Yang, Wen-Fang Cheng, Min-Yu Chen, Hao Lin, Chih-Ming Ho, Yao-Ching Hung, Lee-Wen Huang, Po-Hui Wang, Mu-Hsien Yu, and Yu-Fang Huang. 2022. "Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study" Cancers 14, no. 7: 1746. https://doi.org/10.3390/cancers14071746