Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

Treatment planning for very high energy electrons: Studies that indicate the potential of the modality.

Background And Purpose: Radiotherapy using Very High Energy Electrons (VHEE) has the potential to reduce dose to organs at risk compared to photons. This article therefore reviews treatment planning for VHEE, to clarify the potential benefit of the modality.

Materials And Methods: Articles on VHEE were identified and those which focused on treatment planning were manually selected, particularly those which contained results on patient datasets.

Multivariable models of outcomes with [Lu]Lu-PSMA-617: analysis of the phase 3 VISION trial.

Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival.

A Four-dimensional Computed Tomography Generated Internal Target Volume Approach to Paediatric High Risk Neuroblastoma to Reduce Organ at Risk and Normal Tissue Irradiation.

Aims: The magnitude of upper abdominal organ motion in children may be overestimated by current planning target volumes (PTV). A four-dimensional computed tomography (4DCT) - derived internal target volume (ITV) is frequently used in adult radiotherapy to take respiratory-related organ motion into account. In this study, the dosimetric consequences for target coverage and organs at risk from the use of an ITV approach compared to standard PTV margins in children with high-risk neuroblastoma were investigated.

Quantitative Prostate MRI, From the Special Series on Quantitative Imaging.

Prostate MRI has traditionally relied on qualitative interpretation. However, quantitative components hold the potential to markedly improve performance. The ADC from DWI is probably the most widely recognized quantitative MRI biomarker and has shown strong discriminatory value for clinically significant prostate cancer (csPCa) as well as for recurrent cancer after treatment.

Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial.

Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer.

Methods: In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling).

Association of Declining Prostate-specific Antigen Levels with Clinical Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer Receiving [Lu]Lu-PSMA-617 in the Phase 3 VISION Trial.

Background And Objective: The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [Lu]Lu-PSMA-617 (Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving Lu-PSMA-617.

Methods: Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to Lu-PSMA-617 plus protocol-permitted standard of care (SoC).

Implementing Plan of the Day for Cervical Cancer: A Comparison of Target Volume Generation Methods.

Purpose: Owing to substantial interfraction motion in cervical cancer, plan-of-the-day (PotD) adaptive radiation therapy may be of benefit to patients. Implementation is limited by uncertainty over how to generate the planning target volumes (PTVs). We compared published methods on our own patients.

Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy.

Background: Androgen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and metastasize, despite ongoing treatment, and impacts negatively on patient survival.

An Atlas of Accessible Chromatin in Advanced Prostate Cancer Reveals the Epigenetic Evolution during Tumor Progression.

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that resists therapy targeting androgen signaling, the primary driver of prostate cancer. mCRPC resists androgen receptor (AR) inhibitors by amplifying AR signaling or by evolving into therapy-resistant subtypes that do not depend on AR. Elucidation of the epigenetic underpinnings of these subtypes could provide important insights into the drivers of therapy resistance.

Magnetic resonance image-guided adaptive radiotherapy enables safe CTV-to-PTV margin reduction in prostate cancer: a cine MRI motion study.

Introduction: We aimed to establish if stereotactic body radiotherapy to the prostate can be delivered safely using reduced clinical target volume (CTV) to planning target volume (PTV) margins on the 1.5T MR-Linac (MRL) (Elekta, Stockholm, Sweden), in the absence of gating.

Methods: Cine images taken in 3 orthogonal planes during the delivery of prostate SBRT with 36.

Stereotactic Body Radiotherapy (SBRT) to Localised Prostate Cancer in the Era of MRI-Guided Adaptive Radiotherapy: Doses Delivered in the HERMES Trial Comparing Two- and Five-Fraction Treatments.

HERMES is a phase II trial of MRI-guided daily-adaptive radiotherapy (MRIgART) randomising men with localised prostate cancer to either 2-fractions of SBRT with a boost to the tumour or 5-fraction SBRT. In the context of this highly innovative regime the dose delivered must be carefully considered. The first ten patients recruited to HERMES were analysed in order to establish the dose received by the targets and organs at risk (OARS) in the context of intrafraction motion.

Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol.

Background And Purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac.

Secretome of Cancer-Associated Fibroblasts (CAFs) Influences Drug Sensitivity in Cancer Cells.

Resistance is a major problem with effective cancer treatment and the stroma forms a significant portion of the tumor mass but traditional drug screens involve cancer cells alone. Cancer-associated fibroblasts (CAFs) are a major tumor stroma component and its secreted proteins may influence the function of cancer cells. The majority of secretome studies compare different cancer or CAF cell lines exclusively.

Spatial profiling of in vivo diffusion-weighted MRI parameters in the healthy human kidney.

Objective: Diffusion-weighted MRI is a technique that can infer microstructural and microcirculatory features from biological tissue, with particular application to renal tissue. There is extensive literature on diffusion tensor imaging (DTI) of anisotropy in the renal medulla, intravoxel incoherent motion (IVIM) measurements separating microstructural from microcirculation effects, and combinations of the two. However, interpretation of these features and adaptation of more specific models remains an ongoing challenge.

Longitudinal Assessment of Tumor-Infiltrating Lymphocytes in Primary Breast Cancer Following Neoadjuvant Radiation Therapy.

Purpose: Tumor-infiltrating lymphocytes (TILs) have prognostic significance in several cancers, including breast cancer. Despite interest in combining radiation therapy with immunotherapy, little is known about the effect of radiation therapy itself on the tumor-immune microenvironment, including TILs. Here, we interrogated longitudinal dynamics of TILs and systemic lymphocytes in patient samples taken before, during, and after neoadjuvant radiation therapy (NART) from PRADA and Neo-RT breast clinical trials.

Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial.

Background: Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC.

Methods: In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy.

Predicting cervical cancer target motion using a multivariate regression model to enable patient selection for adaptive external beam radiotherapy.

Background And Purpose: Interfraction motion during cervical cancer radiotherapy is substantial in some patients, minimal in others. Non-adaptive plans may miss the target and/or unnecessarily irradiate normal tissue. Adaptive radiotherapy leads to superior dose-volume metrics but is resource-intensive.

Characterisation of paediatric brain tumours by their MRS metabolite profiles.

H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.