Validated machine learning tools to distinguish immune checkpoint inhibitor, radiotherapy, COVID-19 and other infective pneumonitis.

Background: Pneumonitis is a well-described, potentially disabling, or fatal adverse effect associated with both immune checkpoint inhibitors (ICI) and thoracic radiotherapy. Accurate differentiation between checkpoint inhibitor pneumonitis (CIP) radiation pneumonitis (RP), and infective pneumonitis (IP) is crucial for swift, appropriate, and tailored management to achieve optimal patient outcomes. However, correct diagnosis is often challenging, owing to overlapping clinical presentations and radiological patterns.

Locoregional control and toxicity following high-dose hypofractionated and accelerated palliative radiotherapy regimens in breast cancer.

Aims: For patients with locally advanced primary/recurrent breast cancer, radiotherapy is an effective treatment for locoregional control. 36 Gy in 6 Gy once-weekly fractions is a commonly used schedule, but there are no data comparing local control and toxicity between 36 Gy delivered once-weekly versus accelerated schedules of multiple 6 Gy fractions per week. This retrospective study compared local control rates and acute and late toxicity in patients undergoing 30-36 Gy in 6 Gy fractions over 6 weeks versus more accelerated schedules over 2-3 weeks for an unresected breast cancer.

Regulation of TNF-Induced Osteoclast Differentiation.

Increased osteoclast (OC) differentiation and activity is the critical event that results in bone loss and joint destruction in common pathological bone conditions, such as osteoporosis and rheumatoid arthritis (RA). RANKL and its decoy receptor, osteoprotegerin (OPG), control OC differentiation and activity. However, there is a specific concern of a rebound effect of denosumab discontinuation in treating osteoporosis.

Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications.

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials.

A Comparison of Isotoxic Dose-escalated Radiotherapy in Lung Cancer with Moderate Deep Inspiration Breath Hold, Mid-ventilation and Internal Target Volume Techniques.

Aims: With interest in normal tissue sparing and dose-escalated radiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer, this study investigated the impact of motion-managed moderate deep inspiration breath hold (mDIBH) on normal tissue sparing and dose-escalation potential and compared this to planning with a four-dimensional motion-encompassing internal target volume or motion-compensating mid-ventilation approach.

Materials And Methods: Twenty-one patients underwent four-dimensional and mDIBH planning computed tomography scans. Internal and mid-ventilation target volumes were generated on the four-dimensional scan, with mDIBH target volumes generated on the mDIBH scan.

Implementation of Royal College of Radiologists Consensus Statements and National Institute for Health and Care Excellence Guidance: Breast Radiotherapy Practice in the UK.

Aims: Breast radiotherapy practice, driven by large randomised controls trials, is increasingly being risk adapted to the biology and stage of the cancer. The aim of this audit was to measure current breast radiotherapy practice in the UK against quality standards from the 2016 Royal College of Radiologists (RCR) consensus statements and the 2018 updated National Institute for Health and Care Excellence (NICE) guidelines. These guidelines include new recommendations for partial breast irradiation for women at lower risk of recurrence and internal mammary chain radiotherapy for those at higher risk.

Real-world outcomes in thoracic cancer patients with severe Acute respiratory syndrome Coronavirus 2 (COVID-19): Single UK institution experience.

Background: UK COVID-19 mortality rates are amongst the highest globally. Controversy exists on the vulnerability of thoracic cancer patients. We describe the characteristics and sequelae of patients with thoracic cancer treated at a UK cancer centre infected with COVID-19.

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial.

Purpose: Hydrogen peroxide (HO) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral HO + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action.

Methods And Materials: Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral HO with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.

Novel anti-inflammatory and chondroprotective effects of the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride and human melanocortin MC3 receptor agonist PG-990 on lipopolysaccharide activated chondrocytes.

Human melanocortin MC1 and MC3 receptors expressed on C-20/A4 chondrocytes exhibit chondroprotective and anti-inflammatory effects when activated by melanocortin peptides. Nearly 9 million people in the UK suffer from osteoarthritis, and bacterial infections play a role in its development. Here, we evaluate the effect of a panel of melanocortin peptides with different selectivity for human melanocortin MC1 (α-MSH, BMS-470539 dihydrochloride) and MC3 ([DTrp]-γ-MSH, PG-990) receptors and C-terminal peptide α-MSH(KPV), on inhibiting LPS-induced chondrocyte death, pro-inflammatory mediators and induction of anti-inflammatory proteins.

F-Fludeoxyglucose PET/CT in SCLC: Analysis of the CONVERT Randomized Controlled Trial.

Introduction: We used phase-3 CONVERT trial data to investigate the impact of fludeoxyglucose F 18 (F-FDG) positron emission tomography (PET)/computed tomography (CT) in SCLC.

Methods: CONVERT randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) chemoradiotherapy. Patients were divided into two groups in this unplanned analysis: those staged with conventional imaging (contrast-enhanced thorax and abdomen CT and brain imaging with or without bone scintigraphy) and those staged with F-FDG PET/CT in addition.

Association of Chemoradiotherapy With Outcomes Among Patients With Stage I to II vs Stage III Small Cell Lung Cancer: Secondary Analysis of a Randomized Clinical Trial.

Importance: There is limited evidence to guide stage I to II small cell lung cancer (SCLC) treatment.

Objective: To examine the characteristics and outcomes among patients with stage I to II SCLC treated with modern chemoradiotherapy.

Design, Setting, And Participants: In this post hoc secondary analysis of the Concurrent Once-Daily vs Twice-Daily Radiotherapy Trial (CONVERT), a multicenter phase 3 trial conducted in patients with limited-stage SCLC from April 7, 2008, to November 29, 2013, patients with TNM stage I to II SCLC were compared with those with stage III disease.

Chondroprotection by urocortin involves blockade of the mechanosensitive ion channel Piezo1.

Osteoarthritis (OA) is characterised by progressive destruction of articular cartilage and chondrocyte cell death. Here, we show the expression of the endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF-R2, in primary human articular chondrocytes (AC) and demonstrate its role as an autocrine/paracrine pro-survival factor. This effect could only be removed using the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1 when promoting chondrocyte survival.

Poly(3-hydroxyoctanoate), a promising new material for cardiac tissue engineering.

Cardiac tissue engineering (CTE) is currently a prime focus of research because of an enormous clinical need. In the present work, a novel functional material, poly(3-hydroxyoctanoate), P(3HO), a medium chain-length polyhydroxyalkanoate (PHA), produced using bacterial fermentation, was studied as a new potential material for CTE. Engineered constructs with improved mechanical properties, crucial for supporting the organ during new tissue regeneration, and enhanced surface topography, to allow efficient cell adhesion and proliferation, were fabricated.

Clinical impact of IMPORT HIGH trial (CRUK/06/003) on breast radiotherapy practices in the United Kingdom.

Objective: IMPORT HIGH is a multicentre randomized UK trial testing dose-escalated intensity-modulated radiotherapy (IMRT) after tumour excision in females with early breast cancer and higher than average local recurrence risk. A survey was carried out to investigate the impact of this trial on the adoption of advanced breast radiotherapy (RT) techniques in the UK.

Methods: A questionnaire was sent to all 26 IMPORT HIGH recruiting RT centres to determine whether the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification.

Poly(3-hydroxybutyrate)-ethyl cellulose based bio-composites with novel characteristics for infection free wound healing application.

A series of bio-composites including poly3-hydroxybutyrate [P(3HB)] grafted ethyl cellulose (EC) stated as P(3HB)-EC were successfully synthesised. Furthermore, natural phenols e.g.

A prospective study comparing radiographer- and clinician-based localization for patients with metastatic spinal cord compression (MSCC) to assess the feasibility of a radiographer-led service.

Objective: To investigate whether there was parity between treatment fields localized by radiographers and clinicians, by comparing geographical variations and hence determining the feasibility of a radiographer-led service.

Methods: 23 patients with metastatic spinal cord compression (MSCC) were prospectively sampled. Four radiographers not involved in the original planning performed localization on each patient.

Development of bio-composites with novel characteristics: Evaluation of phenol-induced antibacterial, biocompatible and biodegradable behaviours.

This paper describes a laccase-assisted grafting of gallic acid (GA) and thymol (T) as functional entities onto the previously developed P(3HB)-g-EC composite. GA-g-P(3HB)-g-EC and T-g-P(3HB)-g-EC bio-composites were prepared by laccase-assisted free radical-induced graft polymerisation of GA and T onto the P(3HB)-g-EC based composite using surface dipping and incorporation technique. The results of the antibacterial evaluation for the prepared composites indicated that 15GA-g-P(3HB)-g-EC, 15T-g-P(3HB)-g-EC and 20T-g-P(3HB)-g-EC composites possessed the strongest bacteriostatic and bactericidal activities against Gram-positive Bacillus subtilis NCTC 3610 and Staphylococcus aureus NCTC 6571 and Gram-negative Escherichia coli NTCT 10418 and Pseudomonas aeruginosa NCTC 10662 strains.

The UK HeartSpare Study (Stage IB): randomised comparison of a voluntary breath-hold technique and prone radiotherapy after breast conserving surgery.

Purpose: To compare mean heart and left anterior descending coronary artery (LAD) doses (NTDmean) and positional reproducibility in larger-breasted women receiving left breast radiotherapy using supine voluntary deep-inspiratory breath-hold (VBH) and free-breathing prone techniques.

Materials And Methods: Following surgery for early breast cancer, patients with estimated breast volumes >750 cm(3) underwent planning-CT scans in supine VBH and free-breathing prone positions. Radiotherapy treatment plans were prepared, and mean heart and LAD doses were calculated.