Real-world prevalence of PD-L1 expression in non-small cell lung cancer: an Australia-wide multi-centre retrospective observational study.

An investigator-initiated, Australia-wide multi-centre retrospective observational study was undertaken to investigate the real-world prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC). Multiple centres around Australia performing PD-L1 immunohistochemistry (IHC) were invited to participate. Histologically confirmed NSCLC of any stage with a PD-L1 IHC test performed for persons aged ≥18 years between 1 January 2018 and 1 January 2020, and eligible for review, were identified at each centre, followed by data extraction and de-identification, after which data were submitted to a central site for collation and analysis. In total data from 6690 eligible PD-L1 IHC tests from histologically (75%) or cytologically (24%) confirmed NSCLC of any stage were reviewed from persons with a median age of 70 years, 43% of which were female. The majority (81%) of tests were performed using the PD-L1 IHC SP263 antibody with the Ventana BenchMark Ultra platform and 19% were performed using Dako PD-L1 IHC 22C3 pharmDx assay. Reported PD-L1 tumour proportion score (TPS) was ≥50% for 30% of all tests, with 62% and 38% scoring PD-L1 ≥1% and <1%, respectively. Relative prevalence of clinicopathological features with PD-L1 scores dichotomised to <50% and ≥50%, or to <1% and ≥1%, were examined. Females scored ≥1% slightly more often than males (64% vs 61%, respectively, p=0.013). However, there was no difference between sexes or age groups (<70 or ≥70 years) where PD-L1 scored ≥50%. Specimens from patients with higher stage (III/IV) scored ≥1% or ≥50% marginally more often compared to specimens from patients with lower stage (I/II) (p≤0.002). Proportions of primary and metastatic specimens did not differ where PD-L1 TPS was ≥1%, however more metastatic samples scored TPS ≥50% than primary samples (metastatic vs primary; 34% vs 27%, p<0.001). Cytology and biopsy specimens were equally reported, at 63% of specimens, to score TPS ≥1%, whereas cytology samples scored TPS ≥50% slightly more often than biopsy samples (34% vs 30%, respectively, p=0.004). Resection specimens (16% of samples tested) were reported to score TPS ≥50% or ≥1% less often than either biopsy or cytology samples (p<0.001). There was no difference in the proportion of tests with TPS ≥1% between PD-L1 IHC assays used, however the proportion of tests scored at TPS ≥50% was marginally higher for 22C3 compared to SP263 (34% vs 29%, respectively, p<0.001). These real-world Australian data are comparable to some previously published global real-world data, with some differences noted.

Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted therapy with dabrafenib and trametinib-A case report.

BACKGROUND: Combination molecular targeted therapy with dabrafenib plus trametinib has been shown to improve progression-free survival and overall survival in patients with BRAF V600 mutated unresectable or metastatic melanoma. In general, these agents are well tolerated. Kidney related adverse events are uncommon with only three case reports of acute interstitial nephritis and one case of a serious acute kidney injury. We report another case of interstitial nephritis related to these drugs. CASE: A 37-year-old man diagnosed with metastatic melanoma (BRAF V600E mutation) who developed acute interstitial nephritis 5 years into his treatment with combination dabrafenib plus trametinib therapy. He presented with an asymptomatic acute kidney injury on routine surveillance pathology with a creatinine of 174 µmol/L (from baseline 80 µmol/L) and a corresponding estimated glomerular filtration rate (eGFR) of 42 ml/min/1.73 m2 (from a baseline >90 ml/min/1.73 m2 ) and microalbuminuria (albumin creatinine ratio [ACR] 8.5 mg/mmol). Renal biopsy revealed a granulomatous interstitial nephritis likely drug related. He was treated with prednisolone 1 mg/kg and ceased his targeted therapy with improvement in his renal function. CONCLUSION: Although rare, recognition of acute interstitial nephritis, a possible serious adverse outcome due to dabrafenib and trametinib is important and needs to be incorporated into current Australian cancer therapy guidelines.

Spontaneous expulsion of large submucosal uterine fibroid without embolisation - a case study.

Background: This case involved a 35-year-old G6P0 with multiple uterine fibroids detected at 12 weeks gestation. Fibroid growth was monitored throughout pregnancy, and intrauterine growth restriction (< 5th centile) was detected at 20 weeks. Fetal demise occurred at 22+ weeks gestation at which time the largest of fibroids measured 150 × 100 × 118 mm and labour was induced. Materials and methods: Serial ultrasounds following delivery showed features of reduced vascularity and separation of the fibroid from the myometrium, consistent with spontaneous degeneration. Our patient re-presented with severe pain and went on to expel the fibroid spontaneously 41 days post induction of labour. Histopathology confirmed fibroid degeneration. Conclusion: This case demonstrates spontaneous fibroid degeneration and expulsion without embolisation. This may have resulted from the hormonal and mechanical effects of induction of labour. This case also demonstrated the effects of large intrauterine fibroids on fetal growth and increased risk of fetal demise, highlighting the importance of closer monitoring of fetal growth in such pregnancies.