Assessment of Waldeyer's ring in pediatric and adolescent Hodgkin lymphoma patients-Importance of multimodality imaging: Results from the EuroNet-PHL-C1 trial.

BACKGROUND: In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging. PATIENTS, MATERIALS, AND METHODS: The EuroNet-PHL-C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross-sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re-assessed by applying an imaging-based algorithm considering information from 18 F-fluorodeoxyglucose positron emission tomography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging-based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment. RESULTS: The imaging-based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging-based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient. CONCLUSIONS: The imaging-based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future.

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

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Dose painting by numbers in a standard treatment planning system using inverted dose prescription maps.

BACKGROUND: Dose painting by numbers (DPBN) is a method to deliver an inhomogeneous tumor dose voxel-by-voxel with a prescription based on biological medical images. However, planning of DPBN is not supported by commercial treatment planning systems (TPS) today. Here, a straightforward method for DPBN with a standard TPS is presented. MATERIAL AND METHODS: DPBN tumor dose prescription maps were generated from (18)F-FDG-PET images applying a linear relationship between image voxel value and dose. An inverted DPBN prescription map was created and imported into a standard TPS where it was defined as a mock pre-treated dose. Using inverse optimization for the summed dose, a planned DPBN dose distribution was created. The procedure was tested in standard TPS for three different tumor cases; cervix, lung and head and neck. The treatment plans were compared to the prescribed DPBN dose distribution by three-dimensional (3D) gamma analysis and quality factors (QFs). Delivery of the DPBN plans was assessed with portal dosimetry (PD). RESULTS: Maximum tumor doses of 149%, 140% and 151% relative to the minimum tumor dose were prescribed for the cervix, lung and head and neck case, respectively. DPBN distributions were well achieved within the tumor whilst normal tissue doses were within constraints. Generally, high gamma pass rates (> 89% at 2%/2 mm) and low QFs (< 2.6%) were found. PD showed that all DPBN plans could be successfully delivered. CONCLUSIONS: The presented methodology enables the use of currently available TPSs for DPBN planning and delivery and may therefore pave the way for clinical implementation.

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

PURPOSE: 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. PROCEDURES: 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 (SUVBMLR) 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. RESULTS: A homogeneous uptake of [18F]FDG was observed within the vertebral column prior to treatment. Mean SUVBMLR (± 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 SUVBMLR was observed from pre- to both mid- and post-therapy (p < 0.05). Mean SUVBMLR was significantly higher at post-therapy compared to mid-therapy for patients receiving erlotinib in addition to RT (p < 0.05). CONCLUSIONS: 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. TRIAL REGISTRATION: NCT02714530. Registered 10 September 2015.

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

PURPOSE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Short-course PET based simultaneous integrated boost for locally advanced cervical cancer.

BACKGROUND: Patients with large, locally advanced cervical cancers (LACC) are challenging to treat. The purpose of this work is to use 18F-FDG PET as planning basis for a short-course simultaneous integrated boost (SIB) in external beam radiotherapy of LACC in order to increase tumour shrinkage and likelihood of local control. METHODS: Ten previously treated patients with LACC were included, all with pre-treatment FDG PET/CT images available. The FDG avid tumour volume, MTV50, was dose escalated in silico by intensity modulated radiotherapy from the standard 1.8 Gy to 2.8 Gy per fraction for the 10 first fractions; a short-course SIB. For the 18 remaining external fractions, standard pelvic treatment followed to total PTV and MTV50 doses of 50.4 Gy and 60.4 Gy, respectively. Photon and proton treatment were considered using volumetric modulated arc treatment (VMAT) and intensity-modulated proton therapy (IMPT), respectively. All treatment plans were generated using the Eclipse Treatment Planning System (TPS). The impact of tumour shrinkage on doses to organs at risk (OARs) was simulated in the TPS for the SIB plans. RESULTS: Dose escalation could be implemented using both VMAT and IMPT, with a D98 ≥ 95 % for MTV50 being achieved in all cases. The sum of the 10 fraction short-course SIB and subsequent 18 standard fractions was compared to the standard non-SIB approach by dose volume histogram (DVH) analysis. Only marginal increase of dose to OARs was found for both modalities and a small further increase estimated from tumour shrinkage. Most DVH parameters showed a mean difference below 2 %. IMPT had, compared to VMAT, reduced OAR doses in the low to intermediate dose range, but showed no additional advantage in dose escalation. CONCLUSIONS: Planning of dose escalation based on a FDG avid boost volume was here demonstrated feasible. The concept may allow time for enhanced tumour shrinkage before brachytherapy. Thus, this strategy may prove clinically valuable, in particular for patients with large tumours.