IgA nephropathy after pembrolizumab therapy for mesothelioma.

The use of immune checkpoint inhibitors (CPIs), such as pembrolizumab, for the treatment of cancer, is now prevalent. CPIs are associated with a significant side effect profile, termed immune-related adverse events (irAEs). Renal irAEs, such as interstitial nephritis, are rare, and CPI-related glomerulonephritis even rarer. This is a case report of a 72-year-old man with mesothelioma of the left lung, whose serum creatinine rose during pembrolizumab treatment. Renal biopsy revealed IgA nephropathy. Withdrawal of therapy for 2 months saw no improvement in renal function, and following recommencement, serum creatinine fluctuated at approximately 1.4 times original baseline. This report will highlight the renal irAEs to be the aware of when starting CPIs, and the importance of early renal biopsy in management.

Radical accelerated radiotherapy for non-small cell lung cancer (NSCLC): A 5-year retrospective review of two dose fractionation schedules.

BACKGROUND AND PURPOSE: Numerous fractionation regimes are used for inoperable NSCLC patients not suitable for stereotactic ablative radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART, 54 Gy, 36 fractions over 12 days) and hypofractionated accelerated radiotherapy (55 Gy, 20 fractions over 4 weeks) are recommended UK schedules. In this single-centre retrospective analysis, we compare both fractionation schemes for patients treated at our institution from 2010 to 15. MATERIALS AND METHODS: Clinical demographic, tumour and survival data were collected alongside radiotherapy dosimetric data from the Varian Eclipse Scripting application programming interface. Differences were assessed using independent samples t-tests. Multivariate survival analysis was performed using Cox regression. RESULTS: We identified 563 eligible patients; 43% received CHART and 57% hypofractionated radiotherapy. Median age was 71 years, 56% were male, 95% PET staged with 53% WHO performance status 0-1. 30%, 14%, 50% and 6% were stage I, II, III and IV, respectively. 38% of patients underwent induction chemotherapy. 99% completed their prescribed radiotherapy treatment. Overall response rate was 50% with a 6.5% 90-day mortality rate. Median disease-free survival was 19 months, 50% recurred locally. Median overall survival was 22.5 months with 48% alive at 2 years. Multivariate analysis identified histology, stage, performance status, chemotherapy and radiotherapy response as independent predictors of survival; no significant differences between radiotherapy regimes were observed. CONCLUSION: In our centre, CHART and hypofractionated accelerated radiotherapy produce similar outcomes. Dose escalation studies are in progress to develop these schedules to match outcomes reported in concurrent chemo-radiation studies.