Flat-dose versus weight or body surface area-based methotrexate dosing in low-risk gestational trophoblastic neoplasia.

BACKGROUND: Single-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus exists on the optimal treatment regimen to maximise complete hCG response (CR) and minimise relapse rates. Current regimens differ in the route of administration, dose scheduling, and use of flat-dose, body surface area (BSA)- or weight-based dosing. In the UK a methotrexate-folinic acid (MTX-FA) 8-day 50 mg intramuscular flat-dose regimen is used, with 15 mg oral folinic acid rescue. In LR-GTN patients, we aim to determine the effect of MTX dose adjustment by BSA and weight upon chemotherapy response and disease relapse. METHODS: Between January 1973 and August 2020, 935 LR-GTN patients treated with first-line MTX-FA were identified from a single UK specialist trophoblastic centre. Of these, 364 were included, of which 178 (49%) had a CR to first-line MTX-FA. Subgroup analyses were performed upon: (i) patients who changed chemotherapy due to MTX toxicity (n = 33); and (ii) patients with a FIGO score of 5-6 (n = 85). Logistic regression analysis explored the relationship between BSA or weight adjusted MTX dosing and: (i) CR to first-line chemotherapy; (ii) incidence of disease relapse. Linear regression analyses assessed the correlation of BSA and weight with the number of MTX-FA cycles required to achieve CR. RESULTS: In LR-GTN patients, BSA and weight adjusted MTX-FA dosing did not influence CR to first-line chemotherapy or the incidence of disease relapse. The number of MTX cycles required to achieve CR was not associated with BSA or weight. These findings were maintained in a subgroup analysis of FIGO 5-6 patients. The incidence of MTX toxicity was not influenced by BSA or weight. CONCLUSIONS: In the treatment of LR-GTN, dose individualisation using BSA or weight is not required, and fixed dosing continues to be preferred as the UK standard.

Comparison and optimisation of microRNA extraction from the plasma of healthy pregnant women.

Circulating microRNA (miRNA) biomarkers are implicated in the diagnosis, monitoring and prediction of various disease processes. Before embarking upon biomarker discovery, miRNA extraction techniques must first be optimised in the biofluid and population under study. Using plasma from a healthy pregnant woman, it was attempted to optimise and compare the performance of two commercially available miRNA extraction kits; Qiagen (miRNeasy Serum/Plasma) and Promega (Maxwell® RSC miRNA from Tissue or Plasma or Serum). Sample miRNA content (concentration and percentage) was assessed using Agilent Bioanalyzer Small RNA chips and reverse transcription­quantitative PCR (RT­qPCR) using four constitutively expressed miRNAs (hsa­miR­222­3p, hsa­let­7i­3p, hsa­miR­148­3p and hsa­miR­30e­5p). Quality control spike­ins monitored RNA extraction (UniSp2, 4 and 5) and cDNA synthesis (UniSp6, cel­miR­39­3p) efficiency. Optimisation approaches included: i) Starting volume of plasma; the addition of ii) Proteinase K; iii) a RNA bacteriophage carrier (MS2); and iv) a glycogen carrier. The two kits exhibited equivalence in terms of miRNA recovery based on Bioanalyzer and RT­qPCR ΔΔCq results. Optimisation attempts for both kits failed to improve upon miRNA content compared with standard methodology. Comparing the standard methodology, the Qiagen kit was more consistent (smaller variance of ΔCq values) compared with the Promega kit. The standard methodology of either kit would be suitable for the investigation of miRNA biomarkers in a healthy pregnant population.