Real-world experience of immune checkpoint inhibitors in patients with solid tumours in the Top End of the Northern Territory, Australia from 2016 to 2021: a retrospective observational cohort study.

BACKGROUND: Use of immune checkpoint inhibitors is growing, but clinical trial data may not apply to Indigenous patients or patients living in remote areas. AIMS: To provide real-world incidence of immune-related adverse events (irAE) in the Top End of the Northern Territory and compare incidence between demographic subgroups. METHODS: This retrospective, observational, cohort study collected data from electronic records of patients living in the Top End with solid organ cancer treated with immunotherapy between January 2016 and December 2021. The primary outcome was cumulative incidence of any-grade and severe irAE. Secondary outcomes were overall survival, treatment duration and reason for treatment discontinuation. RESULTS: Two hundred and twenty-six patients received immunotherapy. Forty-eight (21%) lived in a remote or very remote area, and 36 (16%) were Indigenous. Cumulative incidence of any-grade irAE was 54% (122/226 patients); incidence of severe irAE was 26% (59/226 patients). Rates were similar between Indigenous and non-Indigenous patients of any-grade (42% vs 56%, P = 0.11) and severe (11% vs 18%, P = 0.29) irAE. However, Indigenous patients had shorter treatment duration, more frequently discontinued treatment due to patient preference and appeared to have shorter median overall survival than non-Indigenous patients (17.1 vs 30.4 months; hazard ratio (HR) = 1.5, 95% confidence interval (CI) = 0.92-2.66). There was no difference in mortality between remote and urban patients (median overall survival 27.5 vs 30.2 months; HR = 1.1, 95% CI = 0.7-1.7). CONCLUSIONS: Rates of irAE in our cohort are comparable to those in the published literature. There was no significant difference in any-grade or severe irAE incidence observed between Indigenous and non-Indigenous patients.

Significance of lung nodules detected on chest CT among adult Aboriginal Australians - a retrospective descriptive study.

INTRODUCTION: There are limited data on chest computed tomography (CT) findings in the assessment of lung nodules among adult Aboriginal Australians. In this retrospective study, we assessed lung nodules among a group of adult Aboriginal Australians in the Northern Territory of Australia. METHODS: Patients who underwent at least two chest CT scans between 2012 and 2020 among those referred to undergo lung function testing (spirometry) were included. Chest CT scans were assessed for the number, location, size and morphological characteristics of lung nodules. RESULTS: Of the 402 chest CTs assessed, 75 patients (18.7%) had lung nodules, and 57 patients were included in the final analysis with at least two CT scans available for assessment over a median follow-up of 87 weeks. Most patients (68%) were women, with a median age of 58 years and smoking history in 83%. The majority recorded only a single nodule 43 (74%). Six patients (10%) were diagnosed with malignancy, five with primary lung cancer and one with metastatic thyroid cancer. Of the 51 (90%) patients assessed to be benign, 64 nodules were identified, of which 25 (39%) resolved, 38 (59%) remained stable and one (1.8%) enlarged on follow-up. Nodules among patients with malignancy were typically initially larger and enlarged over time, had spiculated margins and were solid, showing no specific lobar predilection. CONCLUSIONS: Most lung nodules in Aboriginal Australians are likely to be benign. However, a proportion could be malignant. Further prospective studies are required for prognostication and monitoring of lung nodules in this population.

The molecular characteristics of non-small cell lung cancer in the Northern Territory's Top End.

AIM: Indigenous Australians with lung cancer have poorer survival than non-Indigenous Australians. The reasons for the disparity are not fully understood and this study hypothesized that there may be a difference in the molecular profiles of tumors. The aim of this study, therefore, was to describe and compare the characteristics of non-small cell lung cancer (NSCLC) in the Northern Territory's Top End, between Indigenous and non-Indigenous patients, and describe the molecular profile of tumors in the two groups. METHODS: A retrospective review was conducted of all adults with a new diagnosis of NSCLC in the Top End from 2017 to 2019. Patient characteristics assessed were Indigenous status, age, sex, smoking status, disease stage, and performance status. Molecular characteristics assessed were epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), v-raf murine sarcoma viral oncogene homolog B (BRAF), ROS proto-oncogene 1 (ROS1), Kirsten rat sarcoma viral oncogene homolog (KRAS), mesenchymal-epithelial transition (MET), human epidermal growth factor receptor 2 (HER2), and programmed death-ligand 1 (PD-L1). Student's t-test and Fisher's Exact Test were used in the statistical analysis. RESULTS: There were 152 patients diagnosed with NSCLC in the Top End from 2017-2019. Thirty (19.7%) were Indigenous and 122 (80.3%) were non-Indigenous. Indigenous patients compared to non-Indigenous patients were younger at diagnosis (median age 60.7 years versus 67.1 years, p = 0.00036) but were otherwise similar in demographics. PD-L1 expression was similar between Indigenous and non-Indigenous patients (p = 0.91). The only mutations identified among stage IV non-squamous NSCLC patients were EGFR and KRAS but testing rates and overall numbers were too small to draw conclusions about differences in prevalence between Indigenous and non-Indigenous patients. CONCLUSION: This is the first study to investigate the molecular characteristics of NSCLC in the Top End.

Utility of prechemotherapy echocardiographical assessment of cardiac abnormalities.

BACKGROUND: Echocardiography provides both morphological and functional information offering a potential advantage over nuclear medicine gated blood pool scans which only estimate ejection fraction. This additional information may be relevant to management of patients receiving potentially cardiotoxic cancer treatment. PATIENTS AND METHODS: We retrospectively audited all prechemotherapy echocardiograms (ECHO) ordered by medical oncologists at our institution over a 36 months period. The primary objective was to determine the frequency of cardiac abnormality detection on the initial ECHO. We also looked at the frequency of clinically relevant cardiac abnormalities other than ejection fraction abnormalities including diastolic dysfunction, intracardiac shunts, moderate-severe valvular abnormalities, pulmonary hypertension, ventricular hypertrophy, pericardial effusion, wall motional abnormalities, ventricular dysfunction/dilatation, cardiac tumours and congenital anomalies. RESULTS: Baseline ECHOs were analysed in 217 consecutive patients. Female patients comprised 89% of population, and the majority had breast cancer (75.5%). The median age of the patients at the time of ECHO was 55 years (range, 16 to 87); 13.4% of patients had at least one clinically relevant abnormality on ECHO. Systolic and moderate diastolic dysfunctions were seen in 5% and 2.7%, respectively. Aortic stenosis was seen in five (2.3%) patients. Atrial septal defects were seen in two patients, moderate mitral regurgitations in two patients and left atrial tumour in one patient. A total of 7.4% of patients had abnormalities, which would not have been detected by gated blood pool scan (GBPS). The ECHO resulted in change in chemotherapy plan in 2.8% and referral to cardiology in 3.7%. CONCLUSIONS: Our retrospective analysis suggests that prechemotherapy ECHO can provide more useful clinical information than the GBPS, which may impact on clinical management of cancer patients.

Bilateral facial nerve palsy associated with amphiphysin antibody in metastatic breast cancer: a case report.

BACKGROUND: Paraneoplastic neurological syndrome is an immune-mediated phenomenon where antibodies from tumor cells are produced against neuronal proteins. Amphiphysin antibody is an onconeural antibody linked to the diagnosis of breast cancer and small-cell lung cancer. It is uncommon and typically associated with stiff-person syndrome, of which 90% of patients are eventually diagnosed with breast cancer. CASE PRESENTATION: We present a case of a 47-year-old Caucasian woman with metastatic hormone receptor-positive breast cancer who developed bilateral facial nerve palsy while on treatment with nab-paclitaxel. The patient was found to have anti-amphiphysin antibody in the serum and cerebrospinal fluid. She was treated with methylprednisolone and intravenous immunoglobulin, which resulted in partial improvement in her facial nerve palsy. CONCLUSIONS: This case highlights a rare presentation of bilateral facial nerve palsy that likely related to paraneoplastic syndrome associated with the presence of anti-amphiphysin antibody.

Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report.

BACKGROUND: Transplant patients were excluded from the pivotal phase III trials of checkpoint inhibitors in metastatic melanoma. The efficacy and toxicity profiles of checkpoint inhibitors in this cohort of patients are not well described. To the best of our knowledge, this is the first case report of a renal transplant patient with stage IV melanoma treated with a programmed cell death protein 1 checkpoint inhibitor that led to both treatment failure and renal graft rejection. CASE PRESENTATION: We present a case of a 58-year-old white man with a long-standing cadaveric renal transplant who was diagnosed with a B-Raf Proto-Oncogene, Serine/Threonine Kinase wild-type metastatic melanoma. He was treated with first-line pembrolizumab but experienced subsequent graft failure and rapid disease progression. CONCLUSIONS: This case highlights the risks associated with the administration of checkpoint inhibitors in patients with a renal transplant and on immunosuppressive therapy. More specifically, it adds to the literature indicating that, compared with the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab, anti-programmed cell death protein 1 agents are more likely to lead to renal graft failure. Additionally, these novel immunotherapeutics may be ineffective in transplant patients; therefore, clinicians should be very aware of those risks and carefully consider selection of agents and full disclosure of the risks to their patients.