Intrapatient 16α-[F]Fluoro-17β-Estradiol PET Heterogeneity as a Prognostic Factor for Endocrine Therapy Response and Survival in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

Intrapatient heterogeneity of estrogen receptor (ER) expression on 16α-[F]fluoro-17β-estradiol ([F]FES) PET is related to outcome in patients with ER-positive metastatic breast cancer (MBC), but a validated and practical method to support clinical decision-making is lacking. Therefore, the [F]FES PET heterogeneity score (i.e.

A minimal physiologically-based pharmacokinetic modeling platform to predict intratumor exposure and receptor occupancy of an anti-LAG-3 monoclonal antibody.

In oncology drug development, measuring drug concentrations at the tumor site and at the targeted receptor remains an ongoing challenge. Positron emission tomography (PET)-imaging is a promising noninvasive method to quantify intratumor exposure of a radiolabeled drug (biodistribution data) and target saturation by treatment doses in vivo. Here, we present the development and application of a minimal physiologically-based pharmacokinetic (mPBPK) modeling approach to integrate biodistribution data in a quantitative platform to characterize and predict intratumor exposure and receptor occupancy (RO) of BI 754111, an IgG-based anti-lymphocyte-activation gene 3 (LAG-3) monoclonal antibody (mAb).

Whole-Body HER2 Heterogeneity Identified on HER2 PET in HER2-Negative, -Low, and -Positive Metastatic Breast Cancer.

Understanding which patients with human epidermal growth factor receptor 2 (HER2)-negative or -low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included.

Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer.

Background: Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome.

Methods: In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response.

Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as measured by F-BMS986-192 PET: pooled analysis of data from four solid tumor types.

Introduction: Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using F-BMS-986192 positron emission tomography (PET)-imaging and looked for correlations with response and immune-related adverse events.

Methods: Four F-BMS-986192 PET studies in patients with melanoma, lung, pancreatic and oral cancer, receiving ICI treatment, were combined.

Correlation between Histopathological Prognostic Tumor Characteristics and [F]FDG Uptake in Corresponding Metastases in Newly Diagnosed Metastatic Breast Cancer.

Background: In metastatic breast cancer (MBC), [F]fluorodeoxyglucose positron emission tomography/computed tomography ([F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [F]FDG uptake in corresponding metastases.

Patients And Methods: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [F]FDG-PET.

Non-specific irreversible Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using Zr-immuno-PET.

Background: Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on Zr-immuno-PET data of biopsy-proven target-negative tumours.

How to obtain the image-derived blood concentration from Zr-immuno-PET scans.

Background: PET scans using zirconium-89 labelled monoclonal antibodies (Zr-mAbs), known as Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling.

Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial).

Efficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in "whole-body" assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1.

Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs.

Introduction: Zr-immuno-PET (positron emission tomography with zirconium-89-labeled monoclonal antibodies ([Zr]Zr-mAbs)) can be used to study the biodistribution of mAbs targeting the immune system. The measured uptake consists of target-specific and non-specific components, and it can be influenced by plasma availability of the tracer. To find evidence for target-specific uptake, i.

Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies.

Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting.

According to the current guidelines, watchful waiting (WW) is a feasible option for patients with good or intermediate prognosis renal-cell carcinoma (RCC). However, some patients rapidly progress during WW, requiring the initiation of treatment. Here, we explore whether we can identify those patients using circulating cell-free DNA (cfDNA) methylation.

Zr-immuno-PET using the anti-LAG-3 tracer [Zr]Zr-BI 754111: demonstrating target specific binding in NSCLC and HNSCC.

Purpose: Although lymphocyte activation gene-3 (LAG-3) directed therapies demonstrate promising clinical anti-cancer activity, only a subset of patients seems to benefit and predictive biomarkers are lacking. Here, we explored the potential use of the anti-LAG-3 antibody tracer [Zr]Zr-BI 754111 as a predictive imaging biomarker and investigated its target specific uptake as well as the correlation of its tumor uptake and the tumor immune infiltration.

Methods: Patients with head and neck (N = 2) or lung cancer (N = 4) were included in an imaging substudy of a phase 1 trial with BI 754091 (anti-PD-1) and BI 754111 (anti-LAG-3).

Validation of simplified uptake measures against dynamic Patlak K for quantification of lesional Zr-Immuno-PET antibody uptake.

Purpose: Positron emission tomography imaging of zirconium-89-labelled monoclonal antibodies (Zr-Immuno-PET) allows for visualisation and quantification of antibody uptake in tumours in vivo. Patlak linearization provides distribution volume (V) and nett influx rate (K) values, representing reversible and irreversible uptake, respectively. Standardised uptake value (SUV) and tumour-to-plasma/tumour-to-blood ratio (TPR/TBR) are often used, but their validity depends on the comparability of plasma kinetics and clearances.

[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant.

Purpose: PET with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.

Experimental Design: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES).

Systemic Therapy for Patients with HER2-Positive Breast Cancer and Brain Metastases: A Systematic Review and Meta-Analysis.

Aim: Patients with HER2-positive (HER2+) metastatic breast cancer (mBC) develop brain metastases (BM) in up to 30% of cases. Treatment of patients with BM can consist of local treatment (surgery and/or radiotherapy) and/or systemic treatment. We undertook a systematic review and meta-analysis to determine the effect of different systemic therapies in patients with HER2+ mBC and BM.

Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles.

Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLac) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM).

Changes in breast cancer treatment during the COVID-19 pandemic: a Dutch population-based study.

Purpose: We aimed to compare (1) treatments and time intervals between treatments of breast cancer patients diagnosed during and before the COVID-19 pandemic, and (2) the number of treatments started during and before the pandemic.

Methods: Women were selected from the Netherlands Cancer Registry. For aim one, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the treatment of women diagnosed within four periods of 2020: pre-COVID (weeks 1-8), transition (weeks 9-12), lockdown (weeks 13-17), and care restart (weeks 18-26), with data from 2018/2019 as reference.

Evaluating new treatments for anaplastic thyroid cancer.

Introduction: Anaplastic thyroid cancer (ATC) is one of the most lethal diseases known to humans with a median survival of 5 months. The American Thyroid Association (ATA) recently published guidelines for the treatment of this dreadful thyroid malignancy.

Areas Covered: This review presents the current therapeutic landscape of this challenging disease.