Comparative Effectiveness of Teclistamab Versus Real-World Physician's Choice of Therapy in LocoMMotion and MoMMent in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma.

Introduction: Teclistamab is the first approved B cell maturation antigen × CD3 bispecific antibody with precision dosing for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). We compared the effectiveness of teclistamab in MajesTEC-1 versus real-world physician's choice of therapy (RWPC) in patients from the prospective, non-interventional LocoMMotion and MoMMent studies.

Methods: Patients treated with teclistamab from MajesTEC-1 (N = 165) were compared with an external control arm from LocoMMotion (N = 248) or LocoMMotion + MoMMent pooled (N = 302).

Functional lung avoidance in radiotherapy using optimisation of biologically effective dose with non-coplanar beam orientations.

Background And Purpose: In external beam radiotherapy for non-small cell lung cancer, dose to functioning lung should be minimised to reduce lung morbidity. This study aimed to develop a method for avoiding beam delivery through functional lung and to quantify the possible benefit to the patients.

Materials And Methods: Twelve patients that were treated as part of a clinical trial of single photon emission computed tomography (SPECT) functional lung avoidance were retrospectively studied.

Accelerating 4D image reconstruction for magnetic resonance-guided radiotherapy.

Background And Purpose: Physiological motion impacts the dose delivered to tumours and vital organs in external beam radiotherapy and particularly in particle therapy. The excellent soft-tissue demarcation of 4D magnetic resonance imaging (4D-MRI) could inform on intra-fractional motion, but long image reconstruction times hinder its use in online treatment adaptation. Here we employ techniques from high-performance computing to reduce 4D-MRI reconstruction times below two minutes to facilitate their use in MR-guided radiotherapy.

A discrete ordinates Boltzmann solver for application to inverse planning of photons and protons.

The aim of this work is to develop a discrete ordinates Boltzmann solver that can be used for calculation of absorbed dose from both photons and protons within an inverse planning optimiser, so as to perform accurate dose calculation throughout the whole of the inverse planning process. With photons, five transport sweeps were performed to obtain scattered photon fluence, and unscattered electron fluence was then obtained and used as a fixed source for solution of the electron transport equations. With protons, continuous slowing down was treated as a fixed source, and five transport sweeps were used to calculate scattered fluence.

Unbiased differential proteomic profiling between cancer-associated fibroblasts and cancer cell lines.

Cancer-associated fibroblasts (CAFs) are a key component of tumors. We aimed to profile the proteome of cancer cell lines representing three common cancer types (lung, colorectal and pancreatic) and a representative CAF cell line from each tumor type to gain insight into CAF function and novel CAF biomarkers. We used isobaric labeling, liquid chromatography and mass spectrometry to evaluate the proteome of 9 cancer and 3 CAF cell lines.

Recommendations for improved reproducibility of ADC derivation on behalf of the Elekta MRI-linac consortium image analysis working group.

Background And Purpose: The apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of this study was to evaluate the multi-centre delineation- and calculation-related ADC variation and give recommendations to minimize it.

Materials And Methods: Nine centres received identical diffusion-weighted and anatomical magnetic resonance images of different cancerous tumours (adrenal gland, pelvic oligo metastasis, pancreas, and prostate).

Critical role of antioxidant programs in enzalutamide-resistant prostate cancer.

Therapy resistance to second-generation androgen receptor (AR) antagonists, such as enzalutamide, is common in patients with advanced prostate cancer (PCa). To understand the metabolic alterations involved in enzalutamide resistance, we performed metabolomic, transcriptomic, and cistromic analyses of enzalutamide-sensitive and -resistant PCa cells, xenografts, patient-derived organoids, patient-derived explants, and tumors. We noted dramatically higher basal and inducible levels of reactive oxygen species (ROS) in enzalutamide-resistant PCa and castration-resistant PCa (CRPC), in comparison to enzalutamide-sensitive PCa cells or primary therapy-naive tumors respectively.

Clinical trial designs for evaluating and exploiting cancer evolution.

The evolution of drug-resistant cell subpopulations causes cancer treatment failure. Current preclinical evidence shows that it is possible to model herding of clonal evolution and collateral sensitivity where an initial treatment could favourably influence the response to a subsequent one. Novel therapy strategies exploiting this understanding are being considered, and clinical trial designs for steering cancer evolution are needed.

Benchmarking Tests of Contemporary SRS Platforms: Have Technological Developments Resulted in Improved Treatment Plan Quality?

Purpose: Stereotactic radiosurgery treatment delivery can be performed with a range of devices, each of which have evolved over recent years. We sought to evaluate the differences in performance of contemporary stereotactic radiosurgery platforms and also to compare them with earlier platform iterations from a previous benchmarking study.

Methods And Materials: The following platforms were selected as "state of the art" in 2022: Gamma Knife Icon (GK), CyberKnife S7 (CK), Brainlab Elements (Elekta VersaHD and Varian TrueBeam), Varian Edge with HyperArc (HA), and Zap-X.

Joint radial trajectory correction for accelerated T mapping on an MR-Linac.

Background: T mapping can characterize tumor hypoxia, which may be associated with resistance to therapy. Acquiring T maps during MR-guided radiotherapy could inform treatment adaptation by, for example, escalating the dose to resistant sub-volumes.

Purpose: The purpose of this work is to demonstrate the feasibility of the accelerated T mapping technique using model-based image reconstruction with integrated trajectory auto-correction (TrACR) for MR-guided radiotherapy on an MR-Linear accelerator (MR-Linac).

Notch and Wnt Signaling Modulation to Enhance DPSC Stemness and Therapeutic Potential.

The Dental Pulp of permanent human teeth is home to stem cells with remarkable multilineage differentiation ability: human Dental Pulp Stem Cells (DPSCs). These cells display a very notorious expression of pluripotency core factors, and the ability to give rise to mature cell lineages belonging to the three embryonic layers. For these reasons, several researchers in the field have long considered human DPSCs as pluripotent-like cells.

External Validation of a Prognostic Model of Overall Survival in Men With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

Purpose: We have previously developed and externally validated a prognostic model of overall survival (OS) in men with metastatic, castration-resistant prostate cancer (mCRPC) treated with docetaxel. We sought to externally validate this model in a broader group of men with docetaxel-naïve mCRPC and in specific subgroups (White, Black, Asian patients, different age groups, and specific treatments) and to classify patients into validated two and three prognostic risk groupings on the basis of the model.

Methods: Data from 8,083 docetaxel-naïve mCRPC men randomly assigned on seven phase III trials were used to validate the prognostic model of OS.

Quality of Life Measurements from the Patient Perspective: Capturing the Heterogeneity of the Patient Experience in a Standardised Way.

For patients, quality of life is the confluence and interaction of multiple factors related to both the disease and to how life is lived with and beyond the disease. When tasked with completing a quality-of-life questionnaire, patients may well wonder for whose benefit this is, which really needs to be made clear. We discuss some of the issues around quality-of-life questionnaires and the challenge of the heterogeneity of the patient experience.

Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer.

Tumor cells promote the recruitment of immunosuppressive neutrophils, a subset of myeloid cells driving immune suppression, tumor proliferation, and treatment resistance. Physiologically, neutrophils are known to have a short half-life. Here, we report the identification of a subset of neutrophils that have upregulated expression of cellular senescence markers and persist in the tumor microenvironment.

Case Report: Disease progression of renal cell carcinoma containing a novel putative pathogenic fusion on Ipilimumab- Nivolumab immunotherapy. A case study and review of the literature.

Renal cell carcinoma still carries a poor prognosis despite therapeutic advancements. Detection of genetic mutations is vital in improving our understanding of this disease as well as potential role in targeted therapy. Here we present a case of a 49 year old man with an aggressive renal cell carcinoma bearing a novel pathogenic fusion.

An ESTRO-ACROP guideline on quality assurance and medical physics commissioning of online MRI guided radiotherapy systems based on a consensus expert opinion.

Objective: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system.

Materials And Methods: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected.

Incidental coronary artery calcification on non-gated CT thorax correlates with risk of cardiovascular events and death.

Objectives: To assess coronary artery calcification (CAC) on non-contrast non-ECG-gated CT thorax (NC-NECG-CTT) and to evaluate its correlation with short-term risk of cardiovascular disease (CVD) events and death.

Methods: Single-institution retrospective study including all patients 40-70 years old who underwent NC-NECG-CTT over a period of 6 months. Individuals with known CVD were excluded.

Algorithmic considerations when analysing capture Hi-C data.

Chromosome conformation capture methodologies have provided insight into the effect of 3D genomic architecture on gene regulation. Capture Hi-C (CHi-C) is a recent extension of Hi-C that improves the effective resolution of chromatin interactions by enriching for defined regions of biological relevance. The varying targeting efficiency between capture regions, however, introduces bias not present in conventional Hi-C, making analysis more complicated.

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study.

Purpose: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented.

Methods: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy.

A phase space model of a Versa HD linear accelerator for application to Monte Carlo dose calculation in a real-time adaptive workflow.

Purpose: This study aims to develop and validate a simple geometric model of the accelerator head, from which a particle phase space can be calculated for application to fast Monte Carlo dose calculation in real-time adaptive photon radiotherapy. With this objective in view, the study investigates whether the phase space model can facilitate dose calculations which are compatible with those of a commercial treatment planning system, for convenient interoperability.

Materials And Methods: A dual-source model of the head of a Versa HD accelerator (Elekta AB, Stockholm, Sweden) was created.