Evolocumab in metastatic castration-resistant prostate cancer: study protocol for a single-arm, phase II trial, and initial experience with use of a validated lipid biomarker to direct therapy.

Background: Despite advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), primary and secondary resistance to current therapies remains. Elevated circulating sphingolipids are associated with poor outcomes in patients with mCRPC, including therapeutic resistance and shorter overall survival. PCPro is a clinically accessible, regulatory compliant plasma lipid biomarker of poor prognosis in mCRPC, which incorporates prognostic sphingolipids.

Outcomes following long-term disease control with immune checkpoint inhibitors in patients with advanced melanoma.

Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI.

The status quo of global geriatric radiation oncology education: A scoping review.

Purpose: To identify potential gaps in geriatric radiation oncology (RO) education worldwide, as measured by geriatric oncology (GO) content within postgraduate RO training program (TP) curricula across 8 focus countries.

Methods And Materials: The need for improved education around GO is internationally recognized and is a key strategic priority of the International Society of Geriatric Oncology (SIOG).Two reviewers undertook a systematic scoping review from March to September 2023.

Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.

Nature and impact of symptoms at time of initial presentation for patients with glioblastoma.

Introduction: In patients diagnosed with glioblastoma (GBM), minimal data exist on the pathway to presentation and the impact of symptoms on survival outcomes. This study aims to detail the symptoms that occur at time of initial presentation, the response to subsequent intervention, and the factors that predict survival in patients managed for GBM.

Methods: A retrospective audit was performed from established prospective databases in patients managed consecutively with radiation therapy (RT) for GBM between 2016 and 2019.

Radiotherapy Improves Survival in NSCLC After Oligoprogression on Immunotherapy: A Cohort Study.

Introduction: The patterns of oligoprogression after first-line immune checkpoint inhibitors (ICIs) for metastatic NSCLC are yet to be well established. An increasing volume of data suggests that directed radiotherapy improves survival outcomes in patients with progression after ICIs.

Methods: A retrospective cohort study was performed on patients with metastatic NSCLC who had completed first-line programmed death-(ligand) 1 inhibitor therapy with or without chemotherapy at two high-volume cancer centers.

Mechanistic Insights and Knowledge Gaps in the Effects of Radiation Therapy on Cardiac Arrhythmias.

Stereotactic body radiation therapy (SBRT) is an innovative modality for the treatment of refractory ventricular arrhythmias (VAs). Phase 1/2 clinical trials have demonstrated the remarkable efficacy of SBRT at reducing VA burden (by >85%) in patients with good short-term safety. SBRT as an option for VA treatment delivered in an ambulatory nonsedated patient in a single fraction during an outpatient session of 15 to 30 minutes, without added risks of anesthetic or surgery, is clinically relevant.

Cardiac Substructure Dose and Survival in Stereotactic Radiotherapy for Lung Cancer: Results of the Multi-Centre SSBROC Trial.

Background And Purpose: Stereotactic ablative body radiotherapy (SABR) is increasingly used for early-stage lung cancer, however the impact of dose to the heart and cardiac substructures remains largely unknown. The study investigated doses received by cardiac substructures in SABR patients and impact on survival.

Materials And Methods: SSBROC is an Australian multi-centre phase II prospective study of SABR for stage I non-small cell lung cancer.

Single-cell spatial multiomics reveals tumor microenvironment vulnerabilities in cancer resistance to immunotherapy.

Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched 40-plex PhenoCycler tissue imaging, we performed longitudinal multimodal single-cell analysis of tumors from metastatic melanoma patients with innate resistance, acquired resistance, or response to immunotherapy. We established the multimodal integration toolkit to align transcriptomic features, cellular epitopes, and spatial information to provide deeper insights into the tumors.

The histopathological spectrum and molecular changes associated with KRAS G12C mutation in non-small cell lung carcinoma.

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years.

Exploiting temporal aspects of cancer immunotherapy.

Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

Nivolumab plus relatlimab in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II CheckMate 142 study.

Background: Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma.

Estimating scenarios for survival time in patients with advanced melanoma receiving immunotherapy and targeted therapy.

Background: We aim to provide survival scenario estimates for patients with advanced melanoma starting targeted therapies and immunotherapies.

Materials And Methods: We sought randomized trials of targeted therapies and immunotherapies for advanced melanoma and recorded the following percentiles (represented survival scenario) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We tested whether these scenarios can be estimated for each OS curve by multiplying its median by 4 multiples: 0.

Anti-PD-1 alone or in combination with anti-CTLA-4 for advanced melanoma patients with liver metastases.

Background: The combination of anti-PD-1 and anti-CTLA-4 has been associated with improvement in response and survival over anti-PD-1 monotherapy in unselected patients with advanced melanoma. Whether patients with liver metastases also benefit from the combination of anti-PD-1 and anti-CTLA-4 over anti-PD-1, is unclear. In this study, we sought to assess whether the combination of anti-PD-1 and anti-CTLA-4 leads to better response, progression-free survival and overall survival, compared with anti-PD-1 monotherapy for patients with liver metastases.

Radiation therapy for ventricular arrhythmias.

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA.

A study of polarity effect for various ionization chambers in kilovoltage x-ray beams.

Background: Ionization chambers play an essential role in dosimetry measurements for kilovoltage (kV) x-ray beams. Despite their widespread use, there is limited data on the absolute values for the polarity correction factors across a range of commonly employed ionization chambers.

Purpose: This study aimed to investigate the polarity effects for five different ionization chambers in kV x-ray beams.