Biomarkers Kinetics : Is it a favorable decrease?

Changes in serum tumor biomarkers may indicate treatment efficacy. Mathematical modeling is a promising tool for analyzing serum tumor marker declines. Indeed it allows calculation of the mathematical equations describing the longitudinal tumor biomarker time-changes (Almufti & You, et al. Annals of Oncology 25: 41–56, 2014). The model-based population kinetic approach is particularly relevant as it enables determination of individual kinetic profiles parameters based on a few timepoints, with limited impact of inter- and intra-individual variability of timepoints and assays.

We have used these approaches to assess the kinetic profiles of different serum tumor markers, such as prostate specific antigen (PSA), human chorionic gonadotrophin (hCG), alfa fetoprotein (AFP), CA-125, circulating tumor cells,…, during cancer treatments. In these studies, mathematical modeling of tumor marker individual kinetics was feasible. Moreover modeled kinetic parameters harboring strong reproducible predictive values regarding treatment efficacy were extracted (Almufti & You, et al. Annals of Oncology 25: 41–56, 2014). Based on a few timepoints analyzed with these models, it is easily possible for any clinician to calculate modeled kinetic parameters able to inform early on the risk of failure.

In the present site, 4 of these tools are provided for clinicians/scientists:

• Modeled PSA clearance after radical prostatectomy in patients with low-risk prostate cancers (pT2-pT3aN0R0; no lymph node or seminal vesicle involvement, no positive margins). In a prospective validation study, this kinetic parameter calculated with 3 to 4 values of PSA measured during the first 30 days after positive prostatectomy was shown to be predictive of the risk of biochemical relapse without any adjuvant treatment (for more details).
  It informs clinicians on the risk of relapse in individual patients after radical prostatectomy, when they enter minimum 3 values of PSA during the post-operative first 30 days. Ideally these PSA values should have been performed on day 0 (surgery day); day 2; day 7; and day 27.
• Modeled hCGres in patients with low-risk gestational trophoblastic neoplasias treated with the 8-day Methotrexate regimen. In two large retrospective studies, modeled hCGres parameter calculated with weekly values of hCG measured during the first 50 treatment days after start of methotrexate was shown to be predictive of the risk of methotrexate resistance (for more details).
  It informs clinicians on the risk of resistance in individual patients, when they enter minimum 4 values of hCG during the first 50 days after methotrexate start.
• CA-125 during adjuvant chemotherapy: Modeled CA-125 KELIM (elimination rate) in patients with high grade serous ovarian carcinomas treated with first line chemotherapy (carboplatin-paclitaxel +/- bevacizumab) after primary cytoreductive surgery. This parameter, calculated with CA-125 values measured at each cycle during the first 100 days of chemotherapy (minimum 3 values including a CA-125 concentration just before the first cycle of chemotherapy), exhibits strong independent and reproducible prognostic value regarding progression-free survival and overall survival in the retrospective analysis of 3 large phase III trials (AGO-OVAR 7; AGO-OVAR 9, and ICON-7). Based on CA-125 concentrations measured at every 3-week cycle during the first chemotherapy 100 days, patients can be classified with “favorable CA-125 decline” associated with long overall survival > 60 months, or “unfavorable decline” associated with short overall survival < 40 months. Moreover the risk of subsequent platinum resistant relapse (< 6 months) value can be simulated based on patient KELIM value while the median expected survival associated with patient KELIM value can be simulated using AFT model. Of note, these data do not apply to patients receiving maintenance treatment with a PARP inhibitor following first line treatment.
• CA-125 during neo-adjuvant chemotherapy: Modeled CA-125 KELIM (elimination rate) in patients with stage III-IV high grade serous ovarian carcinomas treated with first line neo-adjuvant chemotherapy (carboplatin-paclitaxel every 3 weeks) before interval debulking cytoreductive surgery. This parameter, calculated with CA-125 values measured at each cycle during the first 100 days of chemotherapy (minimum 3 values including a CA-125 concentration just before the first cycle of chemotherapy), exhibits strong independent and reproducible prognostic & predictive value regarding tumor response rate, the likelihood of complete interval debulking surgery, progression-free survival and overall survival in the retrospective analysis of the randomized phase II trial CHIVA (NCT01583322). Based on CA-125 concentrations measured at every 3-week cycle during the first chemotherapy 100 days, patients can be classified with “favorable CA-125 decline” associated with higher chemo-sensitivity, higher response rate, higher likelihood of complete interval debulking surgery, lower risk of subsequent platinum-resistant relapse, longer progression free survival and overall survival, or “unfavorable decline”. Moreover the risk of subsequent platinum resistant relapse (< 6 months) value can be simulated based on patient KELIM value. Of note, these data do not apply to patients receiving maintenance treatment with a PARP inhibitor following first line treatment.

The kinetic parameters are calculated for information purpose only. The authors of this site do not take any responsibility or endorse treatment decisions.