A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma.

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive.

Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial.

Importance: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma.

Objective: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor.

Genetic and immune landscape evolution in MMR-deficient colorectal cancer.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve.

CD8 T-cell-mediated cerebellitis directed against Purkinje cell antigen after ipilimumab for small cell lung cancer.

We report a rapidly progressive and fatal CD8 T-cell-mediated cerebellitis after ipilimumab (cytotoxic T-lymphocyte-associated protein 4 inhibitor) for small cell lung cancer. Clinical features and histopathology were consistent with an accelerated form of paraneoplastic cerebellar degeneration. A patchy CD8 T-cell infiltrate spatially corresponded to areas of Purkinje cell loss, with occasional CD8 polarisation towards Purkinje cells.

Influences of landscape change and winter severity on invasive ungulate persistence in the Nearctic boreal forest.

Climate and landscape change are drivers of species range shifts and biodiversity loss; understanding how they facilitate and sustain invasions has been empirically challenging. Winter severity is decreasing with climate change and is a predicted mechanism of contemporary and future range shifts. For example, white-tailed deer (Odocoileus virginianus) expansion is a continental phenomenon across the Nearctic with ecological consequences for entire biotic communities.

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer.

. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed.

Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study.

Purpose: Inhibition of focal adhesion kinase has been shown to selectively kill mesothelioma cells that express low levels of moesin-ezrin-radixin-like protein (merlin). On this basis, we designed a randomized, phase II trial to investigate whether defactinib as maintenance therapy after standard first-line chemotherapy could improve progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM).

Methods: This global, double-blind, randomized, placebo-controlled trial was conducted in patients with advanced MPM and disease control after at least four cycles of first-line chemotherapy.

Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma: A Randomized Clinical Trial.

Importance: Preclinical studies show that arginine deprivation is synthetically lethal in argininosuccinate synthetase 1 (ASS1)-negative cancers, including mesothelioma. The role of the arginine-lowering agent pegylated arginine deiminase (ADI-PEG20) has not been evaluated in a randomized and biomarker-driven study among patients with cancer.

Objective: To assess the clinical impact of arginine depletion in patients with ASS1-deficient malignant pleural mesothelioma.

Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide as First-Line Therapy for Extensive-Stage SCLC.

Objectives: Our aim was to evaluate the safety and efficacy of ipilimumab combined with standard first-line chemotherapy for patients with extensive-stage SCLC.

Methods: Patients with chemotherapy-naive extensive-stage SCLC were treated with carboplatin and etoposide for up to six cycles. Ipilimumab, 10 mg/kg, was given on day 1 of cycles 3 to 6 and every 12 weeks.

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus.

Aim: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.

Methods: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1.

A phase I clinical trial of irinotecan and carboplatin in patients with extensive stage small cell lung cancer.

Background: Treatment options for small cell lung cancer (SCLC) remain inadequate. Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain. We undertook a phase I trial to optimise the dose intensity of a 3-weekly irinotecan/carboplatin combination.

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older.

Unlabelled: What's known on the subject ? and What does the study add? The treatment of younger men with testicular germ cell cancers is well documented with established intensive chemotherapy regimens for those with advanced disease. Although the majority of patients present in the third or fourth decade, men also present in later life. These patients are typically excluded from clinical trials and there are no contemporary published series describing their management.

The incidence of symptomatic thromboembolism in patients receiving adjuvant anthracycline-based chemotherapy for early stage breast cancer.

Thromboembolism is a well recognised complication of systemic chemotherapy and cancer. Its incidence is frequently not reported in clinical trials of adjuvant chemotherapy for early stage breast cancer. Our own experience suggested that thromboembolic complications were common and we undertook a retrospective review of consecutive patients receiving adjuvant chemotherapy to determine the incidence and morbidity/mortality of this complication.

Late relapse (>2 years) on surveillance in stage I non-seminomatous germ cell tumours; predominant seminoma only histology.

Objectives: Surveillance is a standard management approach following orchidectomy for stage I non-seminomatous and mixed germ cell tumours. Patients who relapse following this approach are treated with cisplatin-based chemotherapy, with retroperitoneal lymph node dissection considered for patients with post-chemotherapy residual masses.

Patients And Methods: We reviewed the clinicopathological data for all patients who relapse greater than 24 months after commencing our surveillance programme.