Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab.

There is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a fivefold higher than average mutation burden. We confirmed the association between germline loss-of-function variant in MBD4 and CI response. The patient experienced stable disease (10 months) and survived 2 years with metastatic disease, which is twice as long as median survival. Additionally, the frequency of MBD4 loss-of-function variants in reported UM cohorts was > 20 times higher than in an aggregated population genome database (P < 5 × 10-5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion of MBD4 in the screening of potential UM-prone families as well as stratification of immunotherapy.

Correction to: Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab.

The authors regret that the online version of this article contains an error. The MBD4 mutation in sample MM138 was given an incorrect dbSNP ID. The correct ID is rs769076971.

Posterior Reversible Encephalopathy Syndrome in Early-Stage Breast Cancer.

Wider use of chemotherapy and targeted agents can be associated with posterior reversible encephalopathy syndrome (PRES). This syndrome is most commonly found in metastatic adenocarcinoma treated with platinum-based analogs and is managed with cessation of the precipitating medication. We present the first case of PRES in early-stage breast cancer and discuss the further management of this condition. Recognition of this condition and correction of identifiable precipitating factor including cessation of relevant medications remains important in its management.

Estimating cancers attributable to physical inactivity in Australia.

OBJECTIVES: It was previously estimated that 1814 (1.6 % of incident cancers) were attributable to physical inactivity in Australia in 2010, when only three sites were considered. We estimated the burden of cancer due to physical inactivity in Australia for 13 sites. DESIGN: The population attributable fraction estimated site-specific cancer cases attributable to physical inactivity for 13 cancers. The potential impact fraction was used to estimate cancers that could have been prevented in 2015 if Australian adults had increased their physical activity by a modest amount in 2004-05. METHODS: We used 2004-05 national physical activity prevalence data, 2015 national cancer incidence data, and contemporary relative-risk estimates for physical inactivity and cancer. We assumed a 10-year latency period. RESULTS: An estimated 6361 of the cancers observed in 2015 were attributable to physical inactivity, representing 4.8 % of all cancers diagnosed. If Australian adults had increased their physical activity by one category in 2004-05, 2564 cases (1.9 % of all cancers) could have been prevented in 2015. CONCLUSIONS: More than three times as many cancers are attributable to physical inactivity than previously reported. Physical activity promotion should be a central component of cancer prevention programmes in Australia.

Clinicopathological report: bilateral choroidal metastases from papillary thyroid cancer.

Bilateral uveal metastases from papillary thyroid carcinoma are extremely rare. A 36-year-old woman with a 12-month history of papillary thyroid carcinoma presented with sudden loss of visual acuity and fields in the left eye. An examination and B-scan revealed a large, solid choroidal lesion in the left eye causing exudative retinal detachment. A small solid mass was also observed in the right eye fundus. Following left eye enucleation, immunohistopathology confirmed metastatic papillary thyroid carcinoma. The authors report the third known case of bilateral choroidal metastases.