The value of an initial drop in human Chorionic gonadotropin levels in predicting a response to methotrexate in women with low-risk gestational trophoblastic neoplasia
, 1, 2, 1
Abstract
Objectives: The early identification of patients who are being treated for low-risk gestational trophoblastic neoplasia (LRGTN) with single-agent chemotherapy, who are at high risk of developing chemoresistance, is of crucial importance. The aim of our research was to evaluate the pretreatment beta subunit of human chorionic gonadotropin (βhCG) concentration and its decrease after the administration of the first course of methotrexate (MTX) in predicting later chemo-resistance to single-agent chemotherapy.
Material and methods: A total of 46 patients diagnosed with LRGTN treated with a 5-day methotrexate (MTX) regimen were retrospectively studied. 24 of the patients were successfully cured with only MTX therapy (MTX group). The disease was considered resistant in the remaining 22 patients who, after MTX therapy, required further chemotherapy with an EMA/CO regimen (EMA/CO group). To compare changes in the βhCG concentrations between the two courses of treatment (and the two groups), we calculated the percentage of decline. We determined the specificity and sensitivity of the initial βhCG level and its percentage decline, as a potential predictor of the need for a future EMA/CO regimen. For diagnostic purposes, βhCG levels were measured before the first and second administrations of MTX with a commercial ELISA kit.
Results: In the EMA/CO group, we found the initial βhCG level before the first MTX dose was higher (median = 6275 mIU/mL, range: 21.53–192.610.0 mIU/mL) than in the MTX group (median = 532 mIU/mL, range: 56.5 mIU/mL–360.397.0 mIU/mL) (p = 0.034, Mann-Whitney test). The percentage decreases in the βhCG values relative to the initial concentrations were higher in the MTX group (median decrease = 82.7%, range: from 13.3% to 99.9%) than in the EMA/CO group (median de- crease = 71.1%, range: from an increase of 56.1% to a decrease of 97.1%) (p = 0.0079, Mann-Whitney test). An analysis of the ROC curves implied optimal cutoff values for the initial βHCG (6054 IU, sensitivity = 55%, specificity = 86%) and the percentage change in βhCG levels (decrease by 76.5%, sensitivity = 72%, specificity = 71%).
Conclusions:
- Women with initially higher βhCG levels have a greater risk of developing MTX chemo resistance.
- It would be advantageous to consider administering an EMA/CO regimen in women with LRGTN when their initial
βhCG levels are greater than 6000.
Keywords: methotrexatepredictive values of βhCGgestational trophoblastic neoplasms
References
- Uberti EM, Fajardo Md, da Cunha AG, et al. Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women. Rev Bras Ginecol Obstet. 2015; 37(6): 258–265.
- FIGO staging for gestational trophoblastic neoplasia 2000. International Journal of Gynecology & Obstetrics. 2002; 77(3): 285–287.
- Aminimoghaddam S, Nezhadisalami F, Anjidani S, et al. Outcome of treatment with EMA/EP (etoposide methotrexate and actinomycin-D/ etoposide and cisplatin) regimen in gestational trophoblastic neoplasia. Med J Islam Repub Iran. 2018; 32: 36.
- Foulmann K, Guastalla JP, Caminet N, et al. What is the best protocol of single-agent methotrexate chemotherapy in nonmetastatic or low-risk metastatic gestational trophoblastic tumors? A review of the evidence. Gynecol Oncol. 2006; 102(1): 103–110.
- Maestá I, Growdon WB, Goldstein DP, et al. Prognostic factors associated with time to hCG remission in patients with low-risk postmolar gestational trophoblastic neoplasia. Gynecol Oncol. 2013; 130(2): 312–316.
- Kanno T, Matsui H, Akizawa Y, et al. Treatment results of the second-line chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia treated with 5-day methotrexate and 5-day etoposide. J Gynecol Oncol. 2018; 29(6): e89.
- Gilani MM, Fariba B, Behtash N, et al. The WHO score predicts treatment outcome in low risk gestational trophoblastic neoplasia patients treated with weekly intramuscular methotrexate. J Cancer Res Ther. 2013; 9(1): 38–43.
- Chapman-Davis E, Hoekstra AV, Rademaker AW, et al. Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: factors associated with resistance to single-agent methotrexate chemotherapy. Gynecol Oncol. 2012; 125(3): 572–575.
- Hammond CB, Hertz R, Ross GT, et al. Primary chemotherapy for nonmetastatic gestational trophoblastic neoplasms. Am J Obstet Gynecol. 1967; 98(1): 71–78.
- Hammond CB, Soper JT, Weed JC, et al. Treatment of metastatic trophoblastic disease: good and poor prognosis. Am J Obstet Gynecol. 1973; 115(4): 451–457.
- Soper JT, Clarke-Pearson DL, Berchuck A, et al. 5-day methotrexate for women with metastatic gestational trophoblastic disease. Gynecol Oncol. 1994; 54(1): 76–79.
- van Trommel NE, Massuger LF, Schijf CP, et al. Early identification of resistance to first-line single-agent methotrexate in patients with persistent trophoblastic disease. J Clin Oncol. 2006; 24(1): 52–58.
- McGrath S, Short D, Harvey R, et al. The management and outcome of women with post-hydatidiform mole 'low-risk' gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l(-1). Br J Cancer. 2010; 102(5): 810–814.
- Soper JT, Clarke-Pearson DL, Berchuck A, et al. 5-day methotrexate for women with metastatic gestational trophoblastic disease. Gynecol Oncol. 1994; 54(1): 76–79.
- You B, Deng W, Hénin E, et al. Validation of the Predictive Value of Modeled Human Chorionic Gonadotrophin Residual Production in Low-Risk Gestational Trophoblastic Neoplasia Patients Treated in NRG Oncology/Gynecologic Oncology Group-174 Phase III Trial. Int J Gynecol Cancer. 2016; 26(1): 208–215.
- You B, Pollet-Villard M, Fronton L, et al. Predictive values of hCG clearance for risk of methotrexate resistance in low-risk gestational trophoblastic neoplasias. Ann Oncol. 2010; 21(8): 1643–1650.
- You B, Harvey R, Henin E, et al. Early prediction of treatment resistance in low-risk gestational trophoblastic neoplasia using population kinetic modelling of hCG measurements. Br J Cancer. 2013; 108(9): 1810–1816.
