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.

Early outcomes following EndoFLIP-tailored peroral endoscopic myotomy (POEM): the establishment of POEM services in two UK centers.

Peroral endoscopic myotomy (POEM) is a safe and effective minimally invasive treatment for achalasia. Postoperative reflux rates remain high. The functional luminal imaging probe (FLIP) allows intraoperative measurement of lower esophageal distensibility during POEM. In theory, this enables a tailoring of myotomies to ensure adequate distensibility while minimizing postoperative reflux risk. Two prospectively collected POEM databases were analyzed from two UK tertiary upper GI centers. The operators in each center used FLIP measurements to ensure adequate myotomy. Outcome measures included Eckardt score (where <3 indicated clinical success) and proton-pump inhibitor use (PPI), collected at the first postoperative appointment. Length of stay was recorded as were complications. In all, 142 patients underwent POEM between 2015 and 2019. Overall, 90% (128/142) had postoperative Eckardt scores of <3 at 6 weeks. Clinical success improved to 93% (66/71) in the latter half of each series with a significantly higher rate of complete symptom resolution (53 versus 26%, P = 0.003). In all, 79% of the poor responders had previous interventions compared with 55% of responders (P = 0.09). Median post-myotomy distensibility index was 4.0 mm2/mmHg in responders and 2.9 in nonresponders (P = 0.16). Myotomy length of <7 cm was associated with 93% clinical success and 40% post op PPI use compared with 60% PPI use with longer myotomies. There were two type IIIa, two type IIIb, and one IV Clavien-Dindo complications. This is the largest series of endoluminal functional lumen imaging probe (EndoFLIP)-tailored POEM in the UK to date. The shorter myotomies, allowed through EndoFLIP tailoring, remained clinically effective at 6 weeks. Complete symptom response rates improved in the latter half of each series. More data will be needed from high-volume collaborations to decipher optimal myotomy profiles based on EndoFLIP parameters.