The use of immune checkpoint inhibitor (ICI) therapy in the treatment of solid organ malignancies is becoming increasingly common. This has prompted the recognition of a new class of immune-related adverse effects (irAEs) stemming from the upregulation of T-cell activity causing autoimmunity. Neurological irAEs are a rare complication of ICIs that can lead to long-term morbidity. We report a rare case of encephalopathy after treatment with pembrolizumab, to which the patient achieved durable disease response despite discontinuation of therapy. We also review the pathophysiology, incidence, clinical presentation, diagnosis, and management of neurotoxicity secondary to ICIs. Treatment requires early administration of high-dose corticosteroids, and cessation of ICI therapy is often necessary after grade 3 or 4 irAEs. However, early data suggest that neurological irAEs correlate with a favorable disease response. Consideration should also be given to the optimal duration of ICI therapy to minimize the risk of toxicity and optimize health care expenditure.

Summary It has been suggested that the percentage of non-protein-bound or free oestradiol (E2) is abnormally high in patients with breast cancer. In this study, the serum oestradiol profiles of a large group of women were analysed to determine whether a significant correlation could be found between serum oestradiol and various breast diseases. In addition oestradiol levels were measured in relation to sex hormone binding globulin (SHBG), albumin levels, oestrogen receptor status and family history of breast cancer. Serum samples were taken from a total of 300 women who had either no breast disease, benign breast disease or breast cancer. The percentage of free oestradiol was found to be highest in women with breast cancer, lowest in the control group and intermediate for the women with benign breast disease. These differences were most marked in post-menopausal women. The absolute values for total and free oestradiol were not statistically different in the three groups studied. There did not appear to be a correlation between oestrogen receptor (ER) concentration in breast cancer tissue and free E2 percentage levels. Women who had a family history of breast cancer did not appear to have higher percentage levels of free E2 than those with no such history. The presence of elevated proportions of free oestradiol in the serum of women with breast cancer may be significant in regard to understanding the aetiology of breast neoplasia. There also may be important implications for the use of this measurement in the earlier diagnosis and detection of breast cancer.

The omentum is a rare metastatic site for prostatic adenocarcinoma. We present a case of metastatic castrate-resistant prostate cancer, with progressive omentum invasive prostate cancer identified on prostate-specific membrane antigen (PSMA) PET/CT scan. Omental biopsy revealed metastatic prostate adenocarcinoma, and cabazitaxel chemotherapy was instituted with a prostate-specific antigen biochemical response. Repeat PSMA PET/CT imaging revealed increased avidity in omental metastasis. Despite prostate-specific antigen response, PSMA PET/CT did not correlate with a therapeutic response.

Nivolumab, a human IgG4 anti-PD1 monoclonal antibody, has been shown to have promising results in patients with advanced non-small cell lung cancer (NSCLC) [1, 2]. Despite the improved outcomes compared to chemotherapy, only ∼20% of patients had a sustained favourable response, which highlights the need to identify measures that can augment the efficacy of immunotherapy in NSCLC [3]. Previous studies have demonstrated that radiation acts as an immune stimulus, facilitating immune mediators to enable antitumour responses within and outside the radiation field [4]. Multiple mechanisms have been shown to be involved in the systemic immune response from radiation therapy [5]. Preclinical studies also suggest that immune checkpoint inhibitors such as nivolumab can have a synergistic effect to radiation with enhancement of the antitumour T-cell activity [6], which should theoretically result in a greater clinical response in patients with NSCLC. There is also evidence to suggest an augmented abscopal effect from the combined treatment [7]. Despite the strong preclinical evidence, the impact of previous radiation therapy on the efficacy and safety of immunotherapy in real-world clinical practice in patients with NSCLC is less well defined. Here, we present the findings of a pilot case-controlled study investigating the impact of radiation therapy on outcomes with nivolumab in patients with advanced NSCLC in a large thoracic oncology unit in Brisbane, Australia. Consecutive patients with metastatic or progressive locally advanced NSCLC, who had previous radiation therapy to the chest and subsequently received nivolumab (RT group, n=23) were compared to a control group comprised of an age, sex, tumour histology and performance status matched cohort of patients who did not have previous radiation therapy prior to receiving nivolumab (non-RT group, n=23), between January 2015 and June 2017. Disease response was assessed with RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 [8]. The primary co-endpoints of the study were progression free survival (PFS) and overall survival (OS). The adverse effects of therapy were graded according to the CATCAE (Common Terminology Criteria for Adverse Event) classification. Ethical approval for this study was granted by the Queensland Metro South Human Research Ethics Committee (REC/17/QPAH/338). A total of 46 patients were included in the study with a median age of 62 years (IQR 55-67 years). All patients had metastatic or progressive locally advanced disease at baseline and the other clinical variables were equal between the two groups. The performance status at baseline was also very closely matched between the two groups. All patients had platinum-based chemotherapy before receiving nivolumab. The majority of patients had received one line of chemotherapy (84.8%, n/N=39/46). A total of 17.4% (n/N=4/ 23) of patients in the RT group and 13.0% (n/N=3/23) of patients in the non-RT group received more @ERSpublications This study investigated the effects of previous radiation...

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