Successful management of in-transit cutaneous squamous cell carcinoma with anti-PD-1 immunotherapy.

This report describes the case of a 70-year-old man with metastatic squamous cell carcinoma (SCC) of the right lower leg. Soon after definitive surgical management of the primary and nodal metastases with curative intent, he relapsed, developing aggressive in-transit metastatic disease and recurrent nodal disease. The patient was treated with systemic immunotherapy alone, which not only prompted the progressive nodal metastases to regress, but also resulted in a complete response of the in-transit disease.

Loss of STING expression is prognostic in non-small cell lung cancer.

Background: Stimulator of interferon (IFN) genes (STING) is a protein that promotes type I IFN production essential for T-cell activation. In this study, we aim to characterize STING expression comprehensively using The Cancer Genome Atlas (TCGA) database, cell lines, and patient tumor samples stained with immunohistochemistry.

Methods: Two cohorts were evaluated comprising 721 non-small cell lung cancer (NSCLC) patients and 55 NSCLC cell lines for STING and cyclic GMP-AMP synthase (cGAS) expression using immunohistochemistry.

PIVOT-12: a phase III study of adjuvant bempegaldesleukin plus nivolumab in resected stage III/IV melanoma at high risk for recurrence.

Bempegaldesleukin (BEMPEG: NKTR-214) is an immunostimulatory IL-2 cytokine prodrug engineered to deliver a controlled, sustained and preferential IL-2 pathway signal. Nivolumab (NIVO), a PD-1 inhibitor, has been shown to prolong survival in patients with advanced melanoma and recurrence-free survival in the adjuvant setting. PIVOT-02 showed that BEMPEG plus NIVO was well-tolerated and demonstrated clinical activity as first-line therapy in metastatic melanoma.

A case of hyperprolactinaemia in a patient with metastatic melanoma.

Ectopic prolactin production from a malignancy is infrequently reported. We report here a 60-year-old gentleman who presented with hyperprolactinaemia (9100 mIU/L) causing expressible galactorrhoea, decreased libido and fatigue thought to be due to ectopic prolactin secretion from a metastatic melanoma. Upon initiation of pembrolizumab, the patient's symptoms resolved and he became normoprolactinaemic.

Cardiac Troponin I and T in Checkpoint Inhibitor-associated Myositis and Myocarditis.

Checkpoint inhibitor-associated myocarditis (ir-myocarditis) and myositis (ir-myositis) may occur concurrently among patients on checkpoint inhibitor immunotherapy. While cardiac-specific troponin I (cTnI) and troponin T (cTnT) are regarded to have similar sensitivities and specificities in conditions such as acute coronary syndrome, the cardiac specificity of cTnT has been challenged following observation that patients with neuromuscular diseases, including myositis, may have elevated cTnT without apparent clinical evidence of myocardial injury. Consequently, in the context of concurrent ir-myositis, cTnI may be a more appropriate biomarker for diagnosing and monitoring ir-myocarditis.

Preliminary study highlights the potential of immune checkpoint inhibitors in sarcomatoid mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is well known as an aggressive disease with poor survival. This has sparked trials of alternate immune-based therapies in MPM. While up to a quarter of MPM patients respond to immune checkpoint inhibitors (ICIs), predicting response remains challenging and PD-L1 expression alone has been deemed insufficient.

NTRK and ALK rearrangements in malignant pleural mesothelioma, pulmonary neuroendocrine tumours and non-small cell lung cancer.

Objectives: Gene rearrangements involving NTRK1, NTRK2, NTRK3, ROS1 and ALK have been identified in many types of cancer, including non-small cell lung cancer (NSCLC). Data in malignant pleural mesothelioma (MPM), lung neuroendocrine tumors (NETs) and small-cell lung cancer (SCLC) are lacking. Given the activity of NTRK, ROS-1 and ALK inhibitors in tumors harboring gene fusions, we sought to explore such rearrangements in these less common tumors in addition to NSCLC.

Osimertinib in NSCLC: Real-World Data From New Zealand.

Introduction: EGFR tyrosine kinase inhibitors (TKIs) are more effective than chemotherapy in patients with -mutant NSCLC. Disease progression on EGFR TKI therapy occurs most often owing to acquired resistance from the gain of an T790M mutation. Osimertinib, a third-generation EGFR TKI, significantly improves outcomes in patients with T790M mutation-positive NSCLC compared with platinum-pemetrexed chemotherapy.

Standard dose osimertinib for erlotinib refractory T790M-negative -mutant non-small cell lung cancer with leptomeningeal disease.

Background: Leptomeningeal spread in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor () mutations who experience disease progression on TKIs portends a poor prognosis. Mutation profiling of tumour DNA in cerebrospinal fluid (CSF) samples can be used to determine the presence of the T790M resistance mutation, indicating that osimertinib, a CNS-penetrating 3 generation TKI may be efficacious.

Methods: Eight patients on EGFR TKIs who progressed with cytology-proven leptomeningeal disease at our institution were studied.

Mesenchyme to epithelial transition protein expression, gene copy number and clinical outcome in a large non-small cell lung cancer surgical cohort.

Background: In non-small cell lung cancer (NSCLC), mesenchyme to epithelial transition (MET) protein abundance increases with disease stage and is implicated in resistance to tyrosine kinase inhibitors. To better clarify the impact of MET overexpression on tumor behavior, we investigated a large cohort of patients who underwent curative surgical resection to determine whether MET gene amplification or protein abundance was prognostic.

Methods: Tissue microarrays (TMAs) were constructed using triplicate 1 mm cores of FFPE primary NSCLC specimens.

The immune checkpoint, HVEM may contribute to immune escape in non-small cell lung cancer lacking PD-L1 expression.

Background: Herpes Virus Entry Mediator (HVEM) is an important immune checkpoint in cancer recognition. HVEM expressed on tumor cell membranes activates immune cell signaling pathways leading to either inhibition of activity (B- and T-lymphocyte attenuator, BTLA) or activation of immune activity (LIGHT). The aim of this study is to investigate the prevalence of HVEM expression and its association with PDL1 expression in NSCLC.

Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma.

Introduction: There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1).

Standard of care in immunotherapy trials: Challenges and considerations.

The success of immunotherapeutics over the past decade has fundamentally altered the therapeutic landscape in melanoma and non-small cell lung (NSCLC) cancer care. Multiple clinical trials have confirmed significant improvements in survival with a variety of immunotherapeutic strategies. The careful and appropriate selection of standard of care (SOC) therapies is key to the successful design and interpretation of these trials.

Combination approaches in NSCLC involving immune checkpoint inhibitors.

Immune checkpoint inhibition has been proven to be highly efficacious in NSCLC and associated with durable responses in a limited number of patients. Chemotherapy and targeted therapies, which have also expanded rapidly in this field lead to high response rates and improved survival although inevitably resistance occurs and hence treatment failure. There is increasing evidence showing that chemotherapy and targeted therapy interplay with the immune system including exerting effects on tumor cells and the host immune cells.

Digital PCR of Genomic Rearrangements for Monitoring Circulating Tumour DNA.

Identifying circulating tumour DNA (ctDNA) for monitoring of cancer therapy is dependent on the development of readily designed, sensitive cancer-specific DNA markers. Genomic rearrangements that are present in the vast majority of cancers provide such markers.Tumour DNA isolated from two fresh-frozen lung tumours underwent whole genome sequencing.

Update on Mucin-1 immunotherapy in cancer: a clinical perspective.

Introduction: Mucin 1 (MUC1) is particularly well suited as a cancer immunotherapy target due to the elevated protein expression and aberrant forms associated with malignancy. A variety of therapeutic strategies have been explored, including antibodies intended to induce cancer cell destruction, and vaccinations with peptides, tumor extracts, and gene expression systems.

Areas Covered: MUC1 immunotherapeutic strategies have included vaccination with peptide sequences, glycan molecules, viruses, and dendritic cells, monoclonal antibodies and monoclonal antibody conjugates.

Cost-effectiveness analysis of docetaxel versus weekly paclitaxel in adjuvant treatment of regional breast cancer in New Zealand.

Background: There have been recent important changes to adjuvant regimens and costs of taxanes for the treatment of early breast cancer, requiring a re-evaluation of comparative cost effectiveness. In particular, weekly paclitaxel is now commonly used but has not been subjected to cost-effectiveness analysis.

Aim: Our aim was to estimate the cost effectiveness of adjuvant docetaxel and weekly paclitaxel versus each other, and compared with standard 3-weekly paclitaxel, in women aged ≥25 years diagnosed with regional breast cancer in New Zealand.

Pulmonary barotrauma and cerebral arterial gas embolism during hyperbaric oxygen therapy.

Hyperbaric oxygen therapy (HBOT) is used to treat a variety of disorders. It is a safe treatment modality, but rare catastrophic complications may occur. In this case report, we describe the occurrence of irreversible spastic quadriparesis in a patient who suffered a cerebral arterial gas embolism (CAGE) during decompression from HBOT.