Correlating the KELIM (CA125 elimination rate constant K) score and the chemo-response score as predictors of chemosensitivity in patients with advanced ovarian carcinoma.

BACKGROUND: The objective of this study is to assess the correlation between the pre-operative CA125 Elimination rate constant K(KELIM) score and the intraoperative chemo-response score (CRS) in patients with advanced high grade serous ovarian cancer(HGSC) treated with neoadjuvant chemotherapy(NACT). METHODS: This is a retrospective cohort study of patients with Stage III-IV HGSC treated with NACT from March 2010 to December 2019 at Princess Margaret Cancer Center, Toronto, Canada. KELIM scores were calculated based on the tool devised by You et al. available online. CRS was assessed using an established 3-tier scoring system. An association analysis was performed to determine if the KELIM score assessed during NACT can predict CRS score at the time of interval cytoreductive surgery(ICS). RESULTS: 172 patients were included in this analysis. Patients with CRS 1-2 had a lower median Platinum Free Interval(PFI) (9.24 vs 13.64 months, p = 0.005), lower median progression free survival(PFS) (14.99 vs 20.29 months, p = 0.003) and lower 5-year overall survival(OS) (63.8% vs 69.7%, p = 0.54) compared to patients with CRS3. Among patients with CRS 1-2(n = 115), 68.7% had KELIM <1, while 56.2% of patients with CRS3 had KELIM ≥1(56.2%), p = 0.0017, suggesting a correlation between the KELIM and CRS scores. Furthermore, patients with KELIM ≥1 and CRS3 had significantly higher PFS compared to other groups(median PFS 28.27 months vs 17.66 months for KELIM ≥1/CRS 1/2; 17.13 months for KELIM <1/CRS 3; and 14.53 months for KELIM <1/CRS 1-2, p = 0.003). CONCLUSION: The biochemical KELIM score correlated with the surgical pathologic CRS score and may predict pathological response to chemotherapy. This information can be utilized to tailor and personalize treatment in patients with advanced ovarian malignancy.

CA-125 KELIM as an Alternative Predictive Tool to Identify Which Patients Can Benefit from PARPi in High-Grade Serous Advanced Ovarian Cancer: A Retrospective Pilot Diagnostic Accuracy Study.

BRCA mutation and homologous recombination deficiency (HRD) are the criteria for the administration of PARP inhibitor (PARPi) maintenance therapy. It is known that PARPi efficacy is related to platinum sensitivity and that the latter can be demonstrated from the CA-125 elimination rate constant (KELIM). This study aims to investigate if KELIM can be another tool in the identification of patients that could be benefit from PARPi therapy. Retrospective analysis of patients with high-grade serous advanced ovarian cancer that underwent cytoreduction and was further tested for HRD status. The HRD status was tested either by myChoice HRD CDx assay or by RediScore assay. KELIM score was measured in both neoadjuvant and adjuvant settings with the online tool biomarker-kinetics.org. A total of 39 patients had available data for estimating both HRD status and KELIM score. When assuming KELIM as a binary index test with the value 1 as the cut-off point, the sensitivity was 0.86, 95% CI (0.64-0.97) and the specificity was 0.83, 95% CI (0.59-0.96). On the other hand, when assuming KELIM as a continuous index test, the area under the curve (AUC) was 81% and the optimal threshold, using the Youden index, was identified as 1.03 with a sensitivity of 85.7% and a specificity of 83.3%. KELIM score seems to be a new, cheaper, and faster tool to identify patients that can benefit from PARPi maintenance therapy.

Validation of the KELIM score as a predictor of response to neoadjuvant treatment in patients with advanced high grade serous ovarian cancer.

OBJECTIVE: The objective of this study is to externally validate the KELIM (rate of elimination of CA-125 elimation) score in patients with high grade serous ovarian cancer(HGSC)undergoing NACT and determine its relation to outcome of cytoreduction, platinum sensitivity, progression free(PFS) and overall survival(OS). METHODS: This is a retrospective cohort study of patients with Stage III-IV HGSC diagnosed between January 1, 2010 and December 31, 2019 and treated with NACT. KELIM score was calculated using at least 3 CA-125 values within the first 100 days of chemotherapy. Demographic parameters were collected and Kaplan Meier survival analyses were performed for PFS and OS. This study was approved by local ethics board. RESULTS: 217 patients met inclusion criteria. Median follow-up was 28.93 months(range 2.86-135.06). There was no significant difference in stage, functional status, cytoreductive outcome or BRCA status(germline or somatic) between patients with a KELIM ≥ 1 and <1. Patients with a KELIM<1 had a lower median PFS (13.58 vs 19.69, p < 0.001), median platinum free interval(PFI) (7.66 vs 13.64, p < 0.001) and 5-year OS (57% vs 72%, p = 0.0140) compared to patients with KELIM≥1 . After adjusting for stage, treatment delays, bevacizumab or poly adenosine diphosphate-ribose polymerase(parp)-inhibitor use, and BRCA status, patients with KELIM<1 had a high risk of disease progression(HR = 1.57 (95% CI 1.08-2.28) and death(HR = 1.99 (95% CI 1.01-3.95) compared to KELIM≥1. BRCA status was independently associated to an increase on KELIM score (OR = 1.917, 95% CI 1.046-3.512, p = 0.035). CONCLUSION: Patients with advanced HGSC undergoing NACT with a KELIM <1 were more likely to have platinum-resistant disease, worse PFS and worse OS when compared to patients with KELIM≥1. The KELIM score can be a helpful tool to predict chemo-response and aid in treatment decision making.

The Use of CA-125 KELIM to Identify Which Patients Can Achieve Complete Cytoreduction after Neoadjuvant Chemotherapy in High-Grade Serous Advanced Ovarian Cancer.

(1) Background: Neoadjuvant chemotherapy followed by interval debulking surgery is used in the treatment of advanced ovarian cancer. However, no tool can safely predict if complete cytoreduction after 3-4 cycles can be achieved. This study aims to investigate if the KELIM score can be a triage tool in the identification of patients that will be ideal candidates for interval debulking surgery (IDS). (2) Methods: We retrospectively analyzed the records of patients with high-grade serous advanced ovarian cancer that were treated in the 1st Department of Obstetrics-Gynecology, 2012-2022, with neoadjuvant chemotherapy followed by IDS. Patient characteristics, oncological outcome and follow-up information were collected. The primary outcome was the association of the KELIM score with residual disease. (3) Results: 83 patients were categorized into two groups: Group A (51 patients) with favorable (≥1) and Group B (32 patients) with unfavorable (<1) KELIM scores. A statistically significant correlation between KELIM and residual disease (p < 0.05) exists, showing that patients with a favorable KELIM score can achieve a complete IDS. Furthermore, there was a statistically significant difference in overall survival (p = 0.017), but no difference was observed in progression-free survival (p = 0.13); (4) Conclusions: KELIM seems to safely triage patients after neoadjuvant chemotherapy and decide who will benefit from IDS.

The Gustave Roussy immune score as a novel scoring system for predicting platinum resistance in advanced high-grade serous ovarian cancer.

OBJECTIVE: This study was designed to investigate the relationship between the Gustave-Roussy immune score (GRIm-score) and platinum resistance in patients with advanced high-grade serous ovarian cancer (HGSOC). METHODS: We conducted a retrospective study of patients diagnosed with advanced HGSOC between January 2017 and December 2020. A nomogram was developed to predict the risk of platinum resistance. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the nomogram. Bootstrap analysis was utilized for internal validation. Additionally, we analyzed the risk factors for platinum resistance in patients who received neoadjuvant chemotherapy (NACT). RESULTS: A total of 232 patients with advanced HGSOC were included, 52 (22.4 %) of whom experienced relapse with platinum resistance. Multivariate logistic regression analysis revealed that high GRIm-score (OR = 4.174, P < 0.001), NACT (OR = 2.706, P = 0.017), PLT > 260 (OR = 2.233, P = 0.037) and non-R0 (OR = 2.526, P = 0.012) were independent risk factors for platinum resistance. The area under the curve (AUC) of the model was 0.802 (95 % CI 0.736-0.868), and the internally validated AUC of 1000 bootstrap samples was 0.798 (95 % CI 0.725-0.862). In NACT-treated patients, univariate and multivariate logistic regression analyses revealed that a low KELIM score (OR = 10.405, P = 0.001) and PLT > 260 (OR = 4.611, P = 0.014) were independent risk factors for platinum resistance. CONCLUSION: The GRIm-score and PLT count are important prognostic factors in patients with HGSOC. For precision treatment, the status of partially platinum-sensitive patients should also be considered.

KELIM score predicts outcome in patients with platinum-resistant/refractory recurrent ovarian cancer.

Aim: To assess the prognostic role of the CA-125 elimination rate constant K (KELIM) score in platinum-resistant/refractory ovarian cancer patients receiving second-line treatment. Methods: A retrospective study was carried out including 117 patients with advanced-stage platinum-resistant/refractory ovarian cancer treated with liposomal doxorubicin ± bevacizumab. The KELIM score, calculated using CA-125 measurements within the first 100 days of chemotherapy, was used. Survival analyses were performed for overall survival (OS) and progression-free survival (PFS). Results: Higher KELIM scores were associated with a superior PFS and OS. Multivariate analysis confirmed the independent prognostic value of the KELIM score for OS. Validation cohorts showed consistent results. Conclusion: KELIM score may serve as a valuable prognostic marker for predicting OS and PFS in platinum-resistant/refractory ovarian cancer patients receiving second-line treatment. Prospective studies are needed for validation.

This study aimed to investigate the usefulness of a scoring system called CA-125 elimination rate constant K (KELIM) in predicting the outcomes of ovarian cancer patients who are resistant to or have not responded to platinum-based treatments and are receiving a second-line treatment. The researchers conducted a retrospective (backwards looking) study involving 117 patients with advanced-stage ovarian cancer. They analyzed the patients' CA-125 levels within the first 100 days of chemotherapy to calculate the KELIM score. The results showed that higher KELIM scores were associated with better progression-free survival (the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not get worse) and overall survival (the length of time from either the date of diagnosis or the start of treatment for a disease that patients diagnosed with the disease are still alive). Further analysis confirmed that the KELIM score was an independent predictor of overall survival. The findings were consistent when validated with additional patient groups. In conclusion, the KELIM score has the potential to be a useful tool for predicting the outcomes of ovarian cancer patients undergoing second-line treatment. However, further prospective studies are necessary to validate these findings.