Quantifying non-clinical outcomes of ultra-hypofractionated breast radiotherapy in Western NSW-A narrative review.

Ultra-Hypofractionated Whole Breast Radiotherapy (U-WBRT) has been proven to be a viable treatment option for breast cancer patients receiving radiation therapy, however, due to its novelty our understanding of its non-clinical benefits is still evolving. With increasing U-WBRT selection during COVID and in rural and regional settings such as the Western New South Wales Local Health District (WNSWLHD), it's important to quantify the savings when compared to other fractionation schedules (e.g.

Detection of Tn-antigen in breast and prostate cancer models by VVL-labeled red dye-doped nanoparticles.

Fluorescence detection of breast and prostate cancer cells expressing Tn-antigen, a tumor marker, with lectin (VVL)-labeled nanoparticles. Breast and prostate cancer cells engineered to express high levels of Tn-antigen and non-engineered controls were incubated with VVL-labeled or unlabeled red dye-doped silica-coated polystyrene nanoparticles. The binding to cells was studied with flow cytometry, confocal microscopy, and electron microscopy.

ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial.

Purpose: The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously.

Experimental Design: Next-generation sequencing (Guardant360) was conducted in serial plasma samples.

Experiences and Satisfaction With Telehealth During the COVID-19 Pandemic: The Perspectives of Patients With Cancer in Australia.

Purpose: There has been a significant rise in telehealth consultations across Australia since COVID-19 was declared a worldwide pandemic. We aimed to obtain patient feedback on telehealth, identify key strengths and weaknesses, and assess the feasibility of telehealth beyond the pandemic.

Methods: A survey was developed to obtain patient feedback on telehealth.

Implementation of a simulation free palliative Radiation Therapy pathway: An inter-professional collaborative project.

The Western New South Wales Local Health District (WNSWLHD) has a significant footprint within the state of New South Wales (NSW). Due to the significant size of the WNSWLHD, patients residing in the local health district face many barriers to receiving Radiation Therapy. The inter-professional collaboration behind the successful implementation and evaluation of a simulation free pathway for palliative Radiation Therapy in WNSWLHD will be explored within this narrative.

Regression fitting megavoltage depth dose curves to determine material relative electron density in radiotherapy.

The relative electron density (RED) parameter is ubiquitous throughout radiotherapy for clinical dosimetry and treatment planning purposes as it provides a more accurate description of the relevant radiological properties over mass density alone. RED is in practice determined indirectly from calibrated CT Hounsfield Units (HU). While CT images provide useful 3D information, the spectral differences between CT and clinical LINAC beams may impact the validity of the CT-ED calibration, especially in the context of novel tissue-mimicking materials where deviations from biologically typical atomic number to atomic weight ratios 〈Z/A〉 occur and/or high-Z materials are present.

CD73 regulates zoledronate-induced lymphocyte infiltration in triple-negative breast cancer tumors and lung metastases.

Introduction: Bisphosphonates (BPs) are bone-protecting osteoclast inhibitors, typically used in the treatment of osteoporosis and skeletal complications of malignancies. When given in the adjuvant setting, these drugs may also prevent relapses and prolong overall survival in early breast cancer (EBC), specifically among postmenopausal patients. Because of these findings, adjuvant nitrogen-containing BPs (N-BPs), such as zoledronate (ZOL), are now the standard of care for high-risk EBC patients, but there are no benefit-associated biomarkers, and the efficacy remains low.

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC-a systematic review and meta-analysis.

Background: The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study.

Methods: A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out.

An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma.

The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM.

A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry.

Introduction: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far.

Methods: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics.

Results: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis.

Inoperable metastatic colorectal cancer with primary tumour : Evaluating discordant responses to upfront systemic therapy of the primary tumours and metastatic sites and complications arising from primary tumours (experiences from an Irish Cancer Centre).

Systemic therapy is the mainstay of treatment for metastatic colorectal cancer (mCRC). Heterogeneity between primary tumours and metastases may lead to discordant responses to systemic therapy at these sites. The aim of the present study was to examine these discrepancies and to evaluate the rates of complications arising from the primary tumour and the strategies employed to manage these complications.

Overview of Registered Clinical Trials on Manual Therapy: Possible Implications of Genetic Testing for Personalized Treatment.

Background/aim: Manual therapy (MT) is a frequently applied intervention offering individualized treatment in the clinic. In addition to the traditional approaches of MT, measuring molecular response to MT may offer better understanding of MT outcomes in order to provide specific personalized treatment. The aim of this study was to summarize MT-related registered clinical trials, as well as to search for any evidence on MT and genetics.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance.

Patients And Methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy.

Combined, patient-level, analysis of two randomised trials evaluating the addition of denosumab to standard first-line chemotherapy in advanced NSCLC - The ETOP/EORTC SPLENDOUR and AMGEN-249 trials.

Introduction: The efficacy of adding denosumab to standard first-line chemotherapy for advanced NSCLC patients has been evaluated in two separate randomised trials (SPLENDOUR and AMGEN-249). In this pooled analysis, we will assess the combination-treatment effect in the largest available population, in order to conclude about the potential impact of denosumab in NSCLC.

Methods: Both trials included in this combined analysis, were randomised (SPLENDOUR 1:1, AMGEN-249 2:1) multi-centre trials stratified by histology, bone metastasis, geographical region and for SPLENDOUR only, ECOG PS.

The Rise of the TROP2-Targeting Agents in NSCLC: New Options on the Horizon.

Background: Lung cancer is the most common thoracic malignancy, representing the leading cause of cancer-related deaths worldwide with a 5-year survival rate of <10%.

Summary: The emergence of targeted therapy and immunotherapy has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). However, for those who are not eligible for such therapy or currently have no available standard treatment options, new precision treatment approaches are needed.

Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis.

The Notch signaling pathway is a critical player in embryogenesis but also plays various roles in tumorigenesis, with both tumor suppressor and oncogenic activities. Mutations, deletions, amplifications, or over-expression of Notch receptors, ligands, and a growing list of downstream Notch-activated genes have by now been described for most human cancer types. Yet, it often remains unclear what may be the functional impact of these changes for tumor biology, initiation, and progression, for cancer therapy, and for personalized medicine.

Genetic biomarkers to guide poly(ADP-ribose) polymerase inhibitor precision treatment of prostate cancer.

Precision therapy for a subgroup of genetically defined metastatic castration-resistant prostate cancer patients may become a reality in the near future. DNA damage repair gene mutated prostate cancer might be vulnerable to treatment with PARP inhibitors (PARPi). PARPi clinical trials for prostate cancer investigate both germline and somatic genomic alterations of 43 genes for the applicability as genomic biomarker of PARPi sensitivity.

A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial.

Introduction: Receptor activator of NF-kB ligand stimulates NF-kB-dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01).

Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas.

Long non-coding RNAs (lncRNAs) are a largely uncharacterized group of non-coding RNAs with diverse regulatory roles in various biological processes. Recent observations have elucidated the functional roles of lncRNAs in cutaneous biology, e.g.

p53-Regulated Long Noncoding RNA PRECSIT Promotes Progression of Cutaneous Squamous Cell Carcinoma via STAT3 Signaling.

Long noncoding RNAs (lncRNAs) have emerged as putative biomarkers and therapeutic targets in cancer. The role of lncRNA LINC00346 in cutaneous squamous carcinoma (cSCC) was examined. The expression of LINC00346 was up-regulated in cSCC cells compared with normal human epidermal keratinocytes.

H-Ras activation and fibroblast-induced TGF-β signaling promote laminin-332 accumulation and invasion in cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, with increasing incidence worldwide. The molecular basis of cSCC progression to invasive and metastatic disease is still incompletely understood. Here, we show that fibroblasts and transforming growth factor-β (TGF-β) signaling promote laminin-332 synthesis in cancer cells in an activated H-Ras-dependent manner, which in turn promotes cancer cell invasion.

PARP Inhibitors in Prostate Cancer—The Preclinical Rationale and Current Clinical Development.

Prostate cancer is globally the second most commonly diagnosed cancer type in men. Recent studies suggest that mutations in DNA repair genes are associated with aggressive forms of prostate cancer and castration resistance. Prostate cancer with DNA repair defects may be vulnerable to therapeutic targeting by Poly(ADP-ribose) polymerase (PARP) inhibitors.

Complement System in Cutaneous Squamous Cell Carcinoma.

Epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with high mortality rates in the advanced stage. Chronic inflammation is a recognized risk factor for cSCC progression and the complement system, as a part of innate immunity, belongs to the microenvironment of tumors. The complement system is a double-edged sword in cancer, since complement activation is involved in anti-tumor cytotoxicity and immune responses, but it also promotes cancer progression directly and indirectly.