Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states.

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature.

Cancer Biology and the Perioperative Period: Opportunities for Disease Evolution and Challenges for Perioperative Care.

Efforts to deconvolve the complex interactions of cancer cells with other components of the tumor micro- and macro-environment have exposed a common tendency for cancers to subvert systems physiology and exploit endogenous programs involved in homeostatic control of metabolism, immunity, regeneration, and repair. Many such programs are engaged in the healing response to surgery which, together with other abrupt biochemical changes in the perioperative period, provide an opportunity for the macroevolution of residual disease. This review relates contemporary perspectives of cancer as a systemic disease with the overlapping biology of host responses to surgery and events within the perioperative period.

Circulating tumor DNA dynamics and clinical outcome in metastatic colorectal cancer patients undergoing front-line chemotherapy.

Purpose: we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT).

Experimental Design: 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA.

Upper Urinary Tract Stereotactic Body Radiotherapy Using a 1.5 Tesla Magnetic Resonance Imaging-Guided Linear Accelerator: Workflow and Physics Considerations.

Advancements in radiotherapy technology now enable the delivery of ablative doses to targets in the upper urinary tract, including primary renal cell carcinoma (RCC) or upper tract urothelial carcinomas (UTUC), and secondary involvement by other histologies. Magnetic resonance imaging-guided linear accelerators (MR-Linacs) have shown promise to further improve the precision and adaptability of stereotactic body radiotherapy (SBRT). This single-institution retrospective study analyzed 34 patients (31 with upper urinary tract non-metastatic primaries [RCC or UTUC] and 3 with metastases of non-genitourinary histology) who received SBRT from August 2020 through September 2024 using a 1.

Economic evaluation of an adjunctive intraocular and peri-ocular steroid vitreoretinal surgery for open globe trauma: Cost-effectiveness of the ASCOT randomised controlled trial.

Background: In the United Kingdom, it is estimated that 5,000 patients sustain eye injuries or ocular trauma requiring hospital admission annually, of which 250 patients will be permanently blinded. This study explores the cost-effectiveness of Adjunctive Steroid Combination in Ocular Trauma (ASCOT) given during surgery versus standard treatment in vitreoretinal surgery in patients with open globe trauma.

Methods: This economic evaluation was embedded alongside the ASCOT RCT (ClinicalTrials.

The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational study.

Background: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.

Transformative or transitional? Deciphering the role of NIAGARA in shaping future practice.

The phase 3 NIAGARA trial demonstrated a statistically significant improvement in event-free and overall survival in cisplatin-eligible patients with muscle-invasive bladder cancer treated with perioperative durvalumab in combination with neoadjuvant chemotherapy, compared to neoadjuvant chemotherapy alone. The combination was manageable and did not adversely impact surgery. NIAGARA positions perioperative durvalumab with chemotherapy as a potential new standard of care.

Speech and language therapist-led clinics for low-risk suspected head and neck cancer referrals: A qualitative study of ear, nose and throat surgeons' views.

Background: Over 200,000 patients are referred onto the suspected head and neck cancer (HNC) pathway annually in the UK, with around 3% receiving a cancer diagnosis. With new HNC advancements in identifying patients at low risk of a cancer diagnosis, one proposal is a speech and language therapy (SLT)-led first point of contact clinic for low-risk patients presenting with voice or swallowing symptoms.

Aims: To explore ear, nose and throat (ENT) surgeons' views regarding this model.

The role of the gut microbiome in regulating the response to immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet the proportion of patients who achieve long-term disease control remain suboptimal. Over the past decade, the gut microbiome has been shown to influence immune-mediated tumour suppression as well as responses to ICI therapies. Compositional differences in gut microbiome may account for the differences in outcomes from immune checkpoint blockade.

Delayed surgery during the Covid-19 pandemic did not affect long-term outcomes of pancreatic adenocarcinoma.

Background: During the Covid-19 pandemic cancer surgery was severely affected due to relocation of healthcare resources and the resulting restructuring of cancer pathways. Although this potentially affected rapidly progressing malignancies like pancreatic cancer the most, little is known about long-term outcomes following pancreatectomy.

Materials And Methods: Survival data from two pancreatic surgery centres in the UK was analysed with patients being compared across pre-pandemic (C19-) and intra-pandemic (C19+) groups.

Advanced epithelioid haemangioendothelioma in a child presenting as deep vein thrombosis.

Venous thromboembolism (VTE) is a rare event in children and does not usually trigger investigation for malignancy. We report the case of a previously healthy female teenager presenting with unilateral leg swelling. Colour-Doppler ultrasound confirmed deep vein thrombosis (DVT), and the thrombophilia workup was negative.

Clinical performance of a simulated abbreviated liver magnetic resonance imaging in combination with contrast-enhanced computed tomography for the baseline evaluation of the liver in patients with colorectal cancer.

Aim: To assess the diagnostic accuracy and inter-reader agreement of a simulated abbreviated gadoxetate liver magnetic resonance imaging (MRI) protocol together with contrast-enhanced computed tomography (CE-CT) against a standard gadoxetate MRI for the detection of colorectal liver metastases at baseline.

Materials And Methods: Three readers independently evaluated two sets of images per patient, recording number and location of metastases and benign lesions. Set 1 comprised T1w, T2w, DWI, multiphase CE-T1w, and hepatobiliary phase (HBP) images (standard).

Comparing epidemiological and clinical data from RPS patients documented in a German cancer registry to a cohort from TARPSWG reference centres.

Purpose: Retroperitoneal sarcomas (RPS) are rare, heterogeneous tumours. Treatment recommendations are mainly derived from cohorts treated at reference centres. The applicability of data from cancer registries (CR) is controversial.

Plasma prolactin and postmenopausal breast cancer risk: a pooled analysis of four prospective cohort studies.

Background: Prolactin, a hormone produced by the pituitary gland, regulates breast development and may contribute to breast cancer etiology. However, most epidemiologic studies of prolactin and breast cancer have been restricted to single, often small, study samples with limited exploration of effect modification.

Methods: The Biomarkers in Breast Cancer Risk Prediction consortium includes 8,279 postmenopausal women sampled from four prospective cohort studies, of whom 3,441 were diagnosed with invasive breast cancer after enrollment.

Robotic MRI/CT Guided Multiregional 'smart' Biopsy for Characterization of Tumor Heterogeneity: A Prospective Development Study.

Rationale And Objectives: Intratumoral heterogeneity means single site tumor biopsy might not be representative. Here we develop and optimize an MRI-informed robotic multiregional 'smart' biopsy technique in retroperitoneal and pelvic sarcomas (RPS). We also explore the relationship between imaging and histological biomarkers.

Neurological complications of immune checkpoint inhibitors: a practical guide.

Immune checkpoint inhibition unleashes the power of the immune system against tumour cells. Immune checkpoint inhibitors (ICIs) block the inhibitory effects of cytotoxic T-lymphocyte associated protein 4, programmed death protein 1, programmed death ligand 1 and lymphocyte activation gene 3 molecules on T-cells, and so enhance physiological cytotoxic effects. ICIs can significantly improve survival from cancers, including those previously associated with poor treatment response, such as metastatic melanoma.

Implications of Implementing Children's Oncology Group Risk Stratification to Patients With Rhabdomyosarcoma Treated on European Paediatric Soft Tissue Sarcoma Study Group Clinical Trial.

Background: Prognostic factors are crucial in tailoring treatments for patients with rhabdomyosarcoma (RMS). The European paediatric Soft tissue sarcoma Study Group (EpSSG) and the Children's Oncology Group (COG) employ similar prognostic factors, but utilize them differently resulting in diverse stratification systems. This diversity may result in dissimilar treatment approaches for comparable patients and hinder the comparison of clinical trial results.

Parameningeal Rhabdomyosarcoma: Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 Study.

Background: Parameningeal (PM) site is an unfavorable characteristic in rhabdomyosarcoma (RMS). We described the treatment and outcome for patients with PM RMS and investigated the prognostic value of risk factors. We scored PM site by originating site and by highest risk extension.