Eirik Malinen | 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.

Risk of recurrence after chemoradiotherapy identified by multimodal MRI and 18F-FDG-PET/CT in locally advanced cervical cancer

Tue, 01 Nov 2022 00:00:00 +0000

MRI, applying dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) sequences, and 18F-fluorodeoxyglucose (18F-FDG) PET/CT provide information about tumor aggressiveness that is unexploited in treatment of locally advanced cervical cancer (LACC). We investigated the potential of a multimodal combination of imaging parameters for classifying patients according to their risk of recurrence. Eighty-two LACC patients with diagnostic MRI and FDG-PET/CT, treated with chemoradiotherapy, were collected. Thirty-eight patients with MRI only were included for validation of MRI results. Endpoints were survival (disease-free, cancer-specific, overall) and tumor control (local, locoregional, distant). K^trans, reflecting vascular function, apparent diffusion coefficient (ADC), reflecting cellularity, and standardized uptake value (SUV), reflecting glucose uptake, were extracted from DCE-MR, DW-MR and FDG-PET images, respectively. By applying an oxygen consumption and supply-based method, ADC and K^trans parametric maps were voxel-wise combined into hypoxia images that were used to determine hypoxic fraction (HF). HF showed a stronger association with outcome than the single modality parameters. This association was confirmed in the validation cohort. Low HF identified low-risk patients with 95% precision. Based on the 50th SUV-percentile (SUV₅₀), patients with high HF were divided into an intermediate- and high-risk group with high and low SUV₅₀, respectively. This defined a multimodality biomarker, HF/SUV₅₀. HF/SUV₅₀ increased the precision of detecting high-risk patients from 41% (HF alone) to 57% and showed prognostic significance in multivariable analysis for all endpoints. Multimodal combination of MR- and FDG-PET/CT-images improves classification of LACC patients compared to single modality images and clinical factors.

Mucosa-sparing dose painting of head and neck cancer

Tue, 01 Feb 2022 00:00:00 +0000

No abstract available

Deep learning-based automatic delineation of anal cancer gross tumour volume: a multimodality comparison of CT, PET and MRI

Sat, 01 Jan 2022 00:00:00 +0000

Accurate target volume delineation is a prerequisite for high-precision radiotherapy. However, manual delineation is resource-demanding and prone to interobserver variation. An automatic delineation approach could potentially save time and increase delineation consistency. In this study, the applicability of deep learning for fully automatic delineation of the gross tumour volume (GTV) in patients with anal squamous cell carcinoma (ASCC) was evaluated for the first time. An extensive comparison of the effects single modality and multimodality combinations of computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have on automatic delineation quality was conducted. 18F-fluorodeoxyglucose PET/CT and contrast-enhanced CT (ceCT) images were collected for 86 patients with ASCC. A subset of 36 patients also underwent a study-specific 3T MRI examination including T2- and diffusion-weighted imaging. The resulting two datasets were analysed separately. A two-dimensional U-Net convolutional neural network (CNN) was trained to delineate the GTV in axial image slices based on single or multimodality image input. Manual GTV delineations constituted the ground truth for CNN model training and evaluation. Models were evaluated using the Dice similarity coefficient (Dice) and surface distance metrics computed from five-fold cross-validation. CNN-generated automatic delineations demonstrated good agreement with the ground truth, resulting in mean Dice scores of 0.65-0.76 and 0.74-0.83 for the 86 and 36-patient datasets, respectively. For both datasets, the highest mean Dice scores were obtained using a multimodal combination of PET and ceCT (0.76-0.83). However, models based on single modality ceCT performed comparably well (0.74-0.81). T2W-only models performed acceptably but were somewhat inferior to the PET/ceCT and ceCT-based models. CNNs provided high-quality automatic GTV delineations for both single and multimodality image input, indicating that deep learning may prove a versatile tool for target volume delineation in future patients with ASCC.

Anal cancer chemoradiotherapy outcome prediction using 18F-fluorodeoxyglucose positron emission tomography and clinicopathological factors

Wed, 01 May 2019 00:00:00 +0000

To assess the role of [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET), obtained before and during chemoradiotherapy, in predicting locoregional failure relative to clinicopathological factors for patients with anal cancer. 93 patients with anal squamous cell carcinoma treated with chemoradiotherapy were included in a prospective observational study (NCT01937780). FDG-PET/CT was performed for all patients before treatment, and for a subgroup (n = 39) also 2 weeks into treatment. FDG-PET was evaluated with standardized uptake values (SUV_{max/peak/mean}), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and a proposed Z-normalized combination of MTV and SUV_peak (ZMP). The objective was to predict locoregional failure using FDG-PET, tumor and lymph node stage, gross tumor volume (GTV) and human papilloma virus (HPV) status in univariate and bivariate Cox regression analysis. N3 lymph node stage, HPV negative tumor, GTV, MTV, TLG and ZMP were in univariate analysis significant predictors of locoregional failure (p < 0.01), while SUV_{max/peak/mean} were not (p > 0.2). In bivariate analysis HPV status was the most independent predictor in combinations with N3 stage, ZMP, TLG, and MTV (p < 0.02). The FDG-PET parameters at 2 weeks into radiotherapy decreased by 30-40 % of the initial values, but neither absolute nor relative decrease improved the prediction models. Pre-treatment PET parameters are predictive of chemoradiotherapy outcome in anal cancer, although HPV negativity and N3 stage are the strongest single predictors. Predictions can be improved by combining HPV with PET parameters such as MTV, TLG or ZMP. PET 2 weeks into treatment does not provide added predictive value. Pre-treatment PET parameters of anal cancer showed a predictive role independent of clinicopathological factors. Although the PET parameters show substantial reduction from pre- to mid-treatment, the changes were not predictive of chemoradiotherapy outcome.

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.

Target volume delineation of anal cancer based on magnetic resonance imaging or positron emission tomography

Wed, 06 Sep 2017 00:00:00 +0000

To compare target volume delineation of anal cancer using positron emission tomography (PET) and magnetic resonance imaging (MRI) with respect to inter-observer and inter-modality variability. Nineteen patients with anal cancer undergoing chemoradiotherapy were prospectively included. Planning computed tomography (CT) images were co-registered with 18F-fluorodexocyglucose (FDG) PET/CT images and T2 and diffusion weighted (DW) MR images. Three oncologists delineated the Gross Tumor Volume (GTV) according to national guidelines and the visible tumor tissue (GTV_T). MRI and PET based delineations were evaluated by absolute volumes and Dice similarity coefficients. The median volume of the GTVs was 27 and 31 cm³ for PET and MRI, respectively, while it was 6 and 11 cm³ for GTV_T. Both GTV and GTV_T volumes were highly correlated between delineators (r = 0.90 and r = 0.96, respectively). The median Dice similarity coefficient was 0.75 when comparing the GTVs based on PET/CT (GTV_PET) with the GTVs based on MRI and CT (GTV_MRI). The median Dice coefficient was 0.56 when comparing the visible tumor volume evaluated by PET (GTV_{T_PET}) with the same volume evaluated by MRI (GTV_{T_MRI}). Margins of 1-2 mm in the axial plane and 7-8 mm in superoinferior direction were required for coverage of the individual observer’s GTVs. The rather good agreement between PET- and MRI-based GTVs indicates that either modality may be used for standard target delineation of anal cancer. However, larger deviations were found for GTV_T, which may impact future tumor boost strategies.

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.

Dynamic 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts

Sat, 01 Apr 2017 00:00:00 +0000

Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography ([¹⁸F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens. Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [¹⁸F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUV_E and SUV_L, respectively); the rate constants k ₁, k ₂, and k ₃, and the intravascular fraction v _B were estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response. Treatment responders had significantly larger perfusion-related parameters (k ₁ and k ₂) and lower metabolism-related parameter (k ₃) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k ₁ and k ₂ at day 10 and changes in k ₃ explained most of the variability in response to therapy, whereas SUV_L and particularly SUV_E were of lesser importance. Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [¹⁸F]FDG uptake such as SUV_E and SUV_L apparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.