Quantitative MRI to Characterize Hypoxic Tumors in Comparison to FMISO PET/CT for Radiotherapy in Oropharynx Cancers.

Intratumoral hypoxia is associated with a poor prognosis and poor response to treatment in head and neck cancers. Its identification would allow for increasing the radiation dose to hypoxic tumor subvolumes. 18F-FMISO PET imaging is the gold standard; however, quantitative multiparametric MRI could show the presence of intratumoral hypoxia.

Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial.

Objectives: Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) has been proposed for patients with dementia. Here, we aim to assess the safety and effects of NBM-DBS in patients with Lewy body dementia (LBD), in a randomized, double-blind, crossover clinical trial.

Methods: Six patients with mild to moderate LBD (mean [SD] age, 62.

Prognostic value of sarcopenia in patients treated by Radiochemotherapy for locally advanced oesophageal cancer.

Background: Sarcopenia is defined by a loss of skeletal muscle mass with or without loss of fat mass. Sarcopenia has been associated to reduced tolerance to treatment and worse prognosis in cancer patients, including patients undergoing surgery for limited oesophageal cancer. Concomitant chemo-radiotherapy is the standard treatment for locally-advanced tumour, not accessible to surgical resection.

Comparison of Hypermetabolic and Hypoxic Volumes Delineated on [F]FDG and [F]Fluoromisonidazole PET/CT in Non-small-cell Lung Cancer Patients.

Purpose: The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small-cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. 2-Deoxy-2-[F]fluoro-D-glucose ([F]FDG) and [F]fluoromisonidazole ([F]FMISO) (hypoxia) uptake on pre-radiotherapy positron emission tomography (PET)/X-ray computed tomography (CT) have been independently reported to identify intratumor subvolumes at higher risk of relapse after radiotherapy. We have compared the [F]FDG and [F]FMISO volumes defined by PET/CT in NSCLC patients included in a prospective study.

Radiotherapy boost in patients with hypoxic lesions identified by F-FMISO PET/CT in non-small-cell lung carcinoma: can we expect a better survival outcome without toxicity? [RTEP5 long-term follow-up].

Purpose: Chemoradiotherapy is the reference curative-intent treatment for nonresectable locally advanced non-small-cell lung carcinoma (NSCLC), with unsatisfactory survival, partially due to radiation resistance in hypoxic tissues. The objective was to update survival and toxicity at 3 years following radiotherapy boost to hypoxic tumours in NSCLC patients treated with curative-intent chemoradiotherapy.

Methods: This was an open-label, nonrandomized, multicentre, phase II clinical trial.

FDG and FMISO PET-guided dose escalation with intensity-modulated radiotherapy in lung cancer.

Background: Concomitant chemo-radiotherapy is the reference treatment for non-resectable locally-advanced Non-Small Cell Lung Cancer (NSCLC). Increasing radiotherapy total dose in the whole tumour volume has been shown to be deleterious. Functional imaging with positron emission tomography (PET/CT) offers the potential to identify smaller and biologically meaningful target volumes that could be irradiated with larger doses without compromising Organs At Risk (OAR) tolerance.

Predictive Value of PET Response Combined with Baseline Metabolic Tumor Volume in Peripheral T-Cell Lymphoma Patients.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes on current therapy. We investigated whether response assessed with PET/CT combined with baseline total metabolic tumor volume (TMTV) could detect early relapse or refractory disease. From 7 European centers, 140 patients with nodal PTCL who underwent baseline PET/CT were selected.

In- and ex-vivo molecular imaging of apoptosis to assess sensitivity of non-small cell lung cancer to EGFR inhibitors using probe-based confocal laser endomicroscopy.

Background: Prediction of treatment outcome of non-small cell lung cancer (NSCLC) with EGFR inhibitors on the basis of the genetic analysis of the tumor can be incorrect in case of rare or complex mutations, bypass molecular activation pathways, or pharmacodynamic variations. The aim of this study was to develop an ex vivo and in vivo real-time quantitative imaging test for EGFR inhibitors sensitivity assessment.

Methods: Erlotinib resistant (A549, H460, H1975), insensitive (H1650) and hypersensitive (HCC827) cell lines were injected subcutaneously in Nude mice.

Donepezil-Based Central Acetylcholinesterase Inhibitors by Means of a "Bio-Oxidizable" Prodrug Strategy: Design, Synthesis, and in Vitro Biological Evaluation.

With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer's disease, we report herein a new class of donepezil-based "bio-oxidizable" prodrugs 1 designed to be converted into dual binding site AChEIs 2. While most of indanone-derived N-benzylpyridinium salts 2 revealed to be highly potent dual binding site hAChEIs (IC up to 3 nM), outperforming the standard drug donepezil (IC = 11 nM), most of the corresponding 1,4-dihydropyridines 1 were found to be inactive. Promisingly, whereas the selected prodrug 1r showed good permeability in the PAMPA-BBB model and high in vitro antioxidant activity, its conversion to AChEI 2r could be easily achieved under mild conditions when incubated in various oxidizing media.

Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by F-Misonidazole PET/CT in Patients with Non-Small Cell Lung Carcinoma (RTEP5 Study).

See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant F-misonidazole (F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy.

Baseline Total Metabolic Tumor Volume Measured with Fixed or Different Adaptive Thresholding Methods Equally Predicts Outcome in Peripheral T Cell Lymphoma.

Unlabelled: The purpose of this study was to compare in a large series of peripheral T cell lymphoma, as a model of diffuse disease, the prognostic value of baseline total metabolic tumor volume (TMTV) measured on F-FDG PET/CT with adaptive thresholding methods with TMTV measured with a fixed 41% SUV threshold method.

Methods: One hundred six patients with peripheral T cell lymphoma, staged with PET/CT, were enrolled from 5 Lymphoma Study Association centers. In this series, TMTV computed with the 41% SUV threshold is a strong predictor of outcome.

Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma.

Purpose: The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment (18)F-FDG PET/CT and its added value to molecular characteristics was investigated in patients with diffuse large B-cell lymphoma (DLBCL).

Experimental Design: For 81 newly diagnosed patients with DLBCL treated with rituximab and CHOP/CHOP-like regimen, TMTV was computed using the 41% SUVmax thresholding method. According to the gene expression profile, determined using DASL (cDNA-mediated Annealing, Selection, Ligation and extension) technology, a subset of 57 patients was classified in germinal center B (GCB) or activated B-cell (ABC) subtypes and MYC or BCL2 overexpressed.

Bevacizumab enhances efficiency of radiotherapy in a lung adenocarcinoma rodent model: Role of αvβ3 imaging in determining optimal window.

Introduction: Earlier studies indicated that bevacizumab could favorably be combined with radiation. However excessive damage to tumor vasculature can result in radioresistance and clinical data suggest that treatment sequencing may be important when combining bevacizumab with radiation. The aim of this study was to evaluate whether αvβ3 scintigraphic imaging could provide information to determine the optimal combination schedule of bevacizumab and radiotherapy on a lung adenocarcinoma model in mice.

High FDG uptake areas on pre-radiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for locally advanced oesophageal cancer.

Purpose: The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUVmax) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance.

Areas of high 18F-FDG uptake on preradiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for non-small cell lung cancer.

Unlabelled: The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. Areas of high (18)F-FDG uptake on preradiotherapy (18)F-FDG PET/CT have been reported to identify intratumor subvolumes at high risk of relapse after radiotherapy. We wanted to confirm these observations on a cohort of patients included in 3 sequential prospective studies.

Interobserver agreement of qualitative analysis and tumor delineation of 18F-fluoromisonidazole and 3'-deoxy-3'-18F-fluorothymidine PET images in lung cancer.

Unlabelled: As the preparation phase of a multicenter clinical trial using (18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), (18)F-fluoromisonidazole ((18)F-FMISO), and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in non-small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods.

Methods: Ten (18)F-FDG, ten (18)F-FMISO, and ten (18)F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts.

The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3).

Purpose: FDG PET has been suggested to have predictive value in the prognosis of oesophageal carcinoma. However, the retrospective studies reported in the literature have shown discordant results. Additionally, only four studies have evaluated FDG PET during chemoradiotherapy (CRT) in patients with different histological lesions.

Does enhanced CT influence the biological GTV measurement on FDG-PET images?

Objectives: To test the influence of media injection in PET/CT on the functional or gross tumour volume measurement.

Patients And Methods: Thirty-three patients (56 ± 19 years) with non-Hodgkin's lymphoma (n=22) or Hodgkin's disease (n=11) were prospectively studied at staging. PET/CTs were performed 60 min after injection of FDG.

Serial assessment of FDG-PET FDG uptake and functional volume during radiotherapy (RT) in patients with non-small cell lung cancer (NSCLC).

Objectives: The objectives were (i) to confirm that diagnostic FDG-PET images could be obtained during thoracic radiotherapy, (ii) to verify that significant changes in FDG uptake or volume could be measured early enough to adapt the radiotherapy plan and (iii) to determine an optimal time window during the radiotherapy course to acquire a single FDG-PET examination that would be representative of tumour response.

Methods: Ten non-small cell lung carcinoma (NSCLC) patients with significant PET/CT-FDG tumour radioactivity uptake (versus the background level), candidates for curative radiotherapy (RT, n=4; 60-70 Gy, 2 Gray per fraction, 5 fractions per week) or RT plus chemotherapy (CT-RT, n=6), were prospectively evaluated. Using a Siemens Biograph, 5 or 6 PET/CT scans (PET(n), n=0-5) were performed for each patient.

Simultaneous positron emission tomography (PET) assessment of metabolism with ¹⁸F-fluoro-2-deoxy-d-glucose (FDG), proliferation with ¹⁸F-fluoro-thymidine (FLT), and hypoxia with ¹⁸fluoro-misonidazole (F-miso) before and during radiotherapy in patients with non-small-cell lung cancer (NSCLC): a pilot study.

Objectives: To investigate the changes in tumour proliferation (using FLT), metabolism (using FDG), and hypoxia (using F-miso) during curative (chemo-) radiotherapy (RT) in patients with non-small-cell lung cancer (NSCLC).

Patients And Methods: Thirty PET scans were performed in five patients (4 males, 1 female) that had histological proof of NSCLC and were candidates for curative-intent RT. Three PET-CT (Biograph S16, Siemens) scans were performed before (t(0)) and during (around dose 46 Gy, t(46)) RT with minimal intervals of 48 h between each PET-CT scan.