Åslaug Helland | Theragnostic Imaging

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine

Wed, 01 Jan 2025 00:00:00 +0000

The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy. Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUV_peak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUV_max) and SUV_peak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response. Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUV_peak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUV_max and SUV_peak at week-5. MTV provides prognostic value in PM treated with immunotherapy. High SUV_peak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response. The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic. gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

Mapping Bone Marrow Response in the Vertebral Column by Positron Emission Tomography Following Radiotherapy and Erlotinib Therapy of Lung Cancer

Mon, 01 Apr 2019 00:00:00 +0000

To map functional bone marrow (BM) by 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography (PET) in the vertebral column of lung cancer patients prior to, during, and after treatment. Moreover, to identify radiation- and erlotinib-induced changes in the BM. Twenty-six patients with advanced non-small cell lung cancer, receiving radiotherapy (RT) alone or concomitantly with erlotinib, were examined by [¹⁸F]FDG PET before, during, and after treatment. A total of 61 [¹⁸F]FDG PET scans were analyzed. Vertebral column BM [¹⁸F]FDG standardized uptake value normalized to the liver (SUV_BMLR) was used as uptake measure. Wilcoxon signed-rank test was used to assess changes in BM uptake of [¹⁸F]FDG between sessions. Effects of erlotinib on the BM activity during and after treatment were assessed using Mann-Whitney U test. A homogeneous uptake of [¹⁸F]FDG was observed within the vertebral column prior to treatment. Mean SUV_BMLR (± S.E.M) in the body of thoracic vertebrae receiving a total RT dose of 10 Gy or higher was 0.64 ± 0.01, 0.56 ± 0.01, and 0.59 ± 0.01 at pre-, mid-, and post-therapy, respectively. A significant reduction in the mean SUV_BMLR was observed from pre- to both mid- and post-therapy (p < 0.05). Mean SUV_BMLR was significantly higher at post-therapy compared to mid-therapy for patients receiving erlotinib in addition to RT (p < 0.05). RT reduces BM [¹⁸F]FDG uptake in the vertebral column, especially in the high-dose region. Concomitant erlotinib may stimulate a recovery in BM [¹⁸F]FDG uptake from mid- to post-therapy. NCT02714530. Registered 10 September 2015.

Serum cytokine profiles and metabolic tumor burden in patients with non-small cell lung cancer undergoing palliative thoracic radiation therapy

Tue, 13 Feb 2018 00:00:00 +0000

Radiation therapy effectively kills cancer cells and elicits local effects in the irradiated tissue. The aim of this study was to investigate the kinetics of cytokines in the serum of patients with lung cancer undergoing radiation therapy and to identify associations with metabolic tumor burden as determined by 2-deoxy-2-fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET). Forty-five patients with advanced non-small cell lung cancer were included in a phase 2 clinical trial and randomized between fractionated thoracic radiation therapy alone or concurrent with an epidermal growth factor receptor inhibitor. Blood was sampled at 4 different time points: prior to treatment, midtherapy, at the end of therapy, and 6 to 8 weeks after the start of treatment. The serum concentrations of 48 cytokines and 9 matrix metalloproteinases were measured with multiplex immunoassays. A subset of patients was examined by ¹⁸F-FDG PET/computed tomography before, during, and after radiation therapy. The maximum standardized uptake values (SUV_max) of the primary lung tumor, whole-body metabolic tumor volume, and total lesion glycolysis were calculated, and correlations between the PET parameters and cytokines were investigated. The SUV_max decreased from baseline through midtherapy to posttherapy ¹⁸F-FDG PET/computed tomography (P = .018). The serum levels of C-C motif chemokine ligand (CCL) 23, CCL24, C-X3-C motif chemokine ligand 1, and interleukin-8 (C-X-C motif ligand [CXCL]8) were significantly correlated to SUV_max, metabolic tumor volume, and total lesion glycolysis before, during, and after radiation therapy. CXCL2 (P = .030) and CXCL6 (P = .010) decreased after the start of therapy and changed significantly across the sample time points. Serum concentrations of CCL15 (P = .031), CXCL2 (P = .028), and interleukin-6 (P = .007) were positively correlated to the irradiated volume during the second week of treatment. Cytokine serum levels vary and correlate with metabolic tumor burden in patients with advanced non-small cell lung cancer undergoing palliative thoracic radiation therapy.

A new method to assess pulmonary changes using 18F-fluoro-2-deoxyglucose positron emission tomography for lung cancer patients following radiotherapy

Wed, 01 Nov 2017 00:00:00 +0000

¹⁸F-fluoro-2-deoxyglucose positron emission tomography (¹⁸F-FDG-PET) may be used for assessing radiation induced alterations in the lung. However, there is a need to further develop methodologies to improve quantification. Using computed tomography (CT), a local structure method has been shown to be superior to conventional CT-based analysis. Here, we investigate whether the local structure method based on ¹⁸F-FDG-PET improves radiotherapy (RT) dose-response quantification for lung cancer patients. Sixteen patients with lung cancer undergoing fractionated RT were examined by ¹⁸F-FDG-PET/CT at three sessions (pre, mid, post) and the lung was delineated in the planning CT images. The RT dose matrix was co-registered with the PET images. For each PET image series, mean (μ) and standard deviation (σ) maps were calculated based on cubes in the lung (3 × 3 × 3 voxels), where the spread in pre-therapy μ and σ was characterized by a covariance ellipse in a sub-volume of 3 × 3 × 3 cubes. Mahalanobis distance was used to measure the distance of individual cube values to the origin of the ellipse and to further form local structure ‘S’ maps. The structural difference maps (ΔS) and mean difference maps (Δμ) were calculated by subtracting pre-therapy maps from maps at mid- and post-therapy. Corresponding maps based on CT images were also generated. ΔS identified new areas of interest in the lung compared to conventional Δμ maps. ΔS for PET and CT gave a significantly elevated lung signal compared to a control group during and post-RT (p < .05). Dose-response analyses by linear regression showed that ΔS between pre- and post-therapy for ¹⁸F-FDG-PET was the only parameter significantly associated with local lung dose (p = .04). The new method using local structures on ¹⁸F-FDG-PET provides a clearer uptake dose-response compared to conventional analysis and CT-based approaches and may be valuable in future studies addressing lung toxicity.

Assessment of pulmonary 18F-FDG-PET uptake and cytokine profiles in non-small cell lung cancer patients treated with radiotherapy and erlotinib

Thu, 15 Jun 2017 00:00:00 +0000

To investigate effects of radiotherapy (RT) and erlotinib on pulmonary glucose uptake using 2-deoxy-2-(18F)fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET) during and after treatment of non-small cell lung cancer (NSCLC) and to identify associations between serum cytokine levels and lung glucose uptake. Twenty-seven patients with advanced NSCLC, receiving RT alone or concomitant RT and erlotinib therapy, were examined by ¹⁸F-FDG PET before, during, and after treatment. A total of 57 ¹⁸F-FDG PET scans were analyzed. Pulmonary ¹⁸F-FDG uptake and radiotherapy dose mapping were used to acquire dose-response curves for each patient, where subsequent linear regression gave a glucose uptake level in the un-irradiated parts of the lungs (SUV₀) and a response slope (ΔSUV). Serum cytokine levels at corresponding time points were assessed using a multiplex bioassay. Correlations between the most robust cytokines and lung ¹⁸F-FDG dose response parameters were further investigated. From the dose response analysis, SUV₀ at post-therapy was significantly higher (P < 0.001) than at mid- and pre-therapy (45% and 58%, respectively) for the group receiving RT + erlotinib. Also, SUV₀ at post-therapy was higher for patients receiving RT + erlotinib compared to RT alone (42%; P < 0.001). No differences in ΔSUV were seen with treatments or time. SUV₀ was positively associated (r = 0.47, P = 0.01) with serum levels of the chemokine C-C motif ligand 21 (CCL21) for patients receiving RT + erlotinib. Concomitant RT and erlotinib causes an elevation in pulmonary ¹⁸F-FDG uptake post treatment compared to RT alone. Pulmonary glucose uptake is associated with an upregulation of a chemokine (CCL21) involved in inflammatory reactions.