Measuring 5-FU levels halved severe toxicity, and chemoimmunotherapy is confirmed as first line in oesophageal squamous cancer

The edition in brief

Six phase 3 trials of first-line PD-1 inhibitor-based therapy in advanced oesophageal squamous cell carcinoma were pooled: overall survival hazard ratio 0.68 (95% CI 0.63-0.74) with no statistical heterogeneity. The benefit looked larger in PD-L1-high disease, but biomarker data were too poorly harmonised to pool, so the size of any benefit in PD-L1-negative disease remains unknown. Immune-related toxicity was, as expected, commoner with the immunotherapy arms. Seven retrospective comparative studies covering 589 patients and 649 resection cavities compared single-fraction stereotactic radiosurgery with hypofractionated stereotactic radiotherapy after resection of brain metastases. Six-month local control marginally favoured single fraction (RR 1.05, 1.01-1.09), the 12-month difference was not significant (1.06, 0.99-1.14), and 12-month survival did not differ (1.08, 0.82-1.41). The authors attribute the early difference to hypofractionation being chosen for larger and more complex cavities. Across 70 studies of Bruton tyrosine kinase inhibitors in mantle cell lymphoma, pooled complete response was 76.5% in treatment-naive and 43.2% in relapsed or refractory disease. Zanubrutinib-containing first-line regimens reached 95.2% complete response and had the lowest pooled haematological toxicity; acalabrutinib monotherapy performed best in relapsed disease. The French Society of Childhood Cancer has published updated national recommendations for non-seminomatous germ cell tumours in children and adolescents, built on the TGM95 and TGM13-NS protocols, with risk-stratified surgery and platinum chemotherapy. Across five comparative studies and 809 patients, pharmacokinetically guided fluorouracil dosing halved severe toxicity (RR 0.50, 0.33-0.76) and raised objective response (RR 1.50, 1.24-1.80) compared with body surface area dosing.