Respiratory-gated (4D) contrast-enhanced FDG PET-CT for radiotherapy planning of lower oesophageal carcinoma: Feasibility and impact on planning target volume

Background: To assess the feasibility and potential impact on target delineation of respiratory-gated (4D) contrast-enhanced 18 Fluorine fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT), in the treatment planning position, for a prospective cohort of patients with lower third oesophageal cancer. Methods: Fifteen patients were recruited into the study. Imaging included 4D PET-CT, 3D PET-CT, endoscopic ultrasound and planning 4D CT. Target volume delineation was performed on 4D CT, 4D CT with co-registered 3D PET and 4D PET-CT. Planning target volumes (PTV) generated with 4D CT (PTV 4DCT), 4D CT co-registered with 3D PET-CT (PTV 3DPET4DCT) and 4D PET-CT (PTV 4DPETCT ) were compared with multiple positional metrics. Results: Mean PTV 4DCT , PTV 3DPET4DCT and PTV 4DPETCT were 582.4 ± 275.1 cm 3 , 472.5 ± 193.1 cm 3 and 480.6 ± 236.9 cm 3 respectively (no significant difference). Median DICE similarity coefficients comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.85 (range 0.65-0.9), 0.85 (range 0.69-0.9) and 0.88 (range 0.79-0.9) respectively. The median sensitivity index for overlap comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.78 (range 0.65-0.9), 0.79 (range 0.65-0.9) and 0.89 (range 0.68-0.94) respectively. Conclusions: Planning 4D PET-CT is feasible with careful patient selection. PTV generated using 4D CT, 3D PET-CT and 4D PET-CT were of similar volume, however, overlap analysis demonstrated that approximately 20% of PTV 3DPETCT and PTV 4DPETCT are not included in PTV 4DCT , leading to under-coverage of target volume and a potential geometric miss. Additionally, differences between PTV 3DPET4DCT and PTV 4DPETCT suggest a potential benefit for 4D PET-CT. Trial registration: ClinicalTrials.gov Identifier - NCT02285660(Registered 21/10/2014)

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.

Background Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC).Methods Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT.Discussion Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC.Trial registration ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017

SU‐GG‐J‐137: Application of Unsupervised Spectral Clustering in 3D for PET Tumor Segmentation: A Digital Phantom Study

Purpose: Spectral clustering refers to a class of techniques which rely on the eigenstructure of a similarity matrix to partition pixels into disjoint clusters. This study intended to investigate the feasibility of using the unsupervised spectral clustering method for PET tumor segmentation. Method and Materials: In this study a digital PET phantom was adopted as the source to generate PET images with heterogeneous and/or irregular shaped tumors. The simulation was carried out by feeding the Zubal phantom as anatomical input to the SimSET (the Simulation System for Emission Tomography) software, which employs Monte Carlo techniques to model the underlying physical processes and imaging system to produce simulated emission tomography data. There were a total of 30 lung tumors with a variety of heterogeneous activities and/or irregular shapes simulated. The unsupervised spectral clustering algorithm was then applied to segment the simulated images. Segmentation accuracy was assessed with two metrics: volume detection error (VDE) and volume overlap measure (VOM). Results: The spectral clustering technique partitions the image volume into an optimal number of clusters according to the pair‐wise similarity measure between voxels. Upon segmentation, one can then select the segmented tumor regions for subsequent processing and analysis. Applying the spectral clustering technique on all the 30 simulated PET images shows that VDE ranges from −5.5% to 6.2%, and VOM ranges from 0.94 to 1.Conclusion: This study shows the potential of the unsupervised 3D spectral clustering method for PET tumor segmentation. Segmentation performance in terms of VDE and VOM on stimulated PET images shows this method may have the potential for accurate and consistent segmentation of tumors. Compared with thresholding‐based PET tumor delineation techniques, it segments the PET image without requiring any threshold‐volume relationship. Studies to further evaluate this method on patient data are planned

Differences between planned and delivered dose for head and neck cancer, and their consequences for normal tissue complication probability and treatment adaptation

Background and purpose: Anatomical changes induce differences between planned and delivered dose. Adaptive radiotherapy (ART) may reduce these differences but the optimal implementation is insufficiently clear. The aims of this study were to quantify the difference between planned and delivered dose in HNC patients, assess the consequential difference in normal tissue complication probability (Delta NTCP) and to explore the value of Delta NTCP as an objective selection strategy for ART.Materials and methods: For 52 patients, daily doses were accumulated to estimate the delivered dose. The difference from planned dose was analyzed for CTVs and 9 organs-at-risk (OAR). Delta NTCP was calculated for xerostomia, dysphagia, parotid gland dysfunction and tube feeding dependency at 6 months. ART was deemed necessary if Delta NTCP was >5%. The positive predicted value (PPV) was calculated for identification of ART-patients by clinical judgement, and Delta NTCP at fraction 10 and 15.Results: Delta NTCP >5% was seen five times for dysphagia and twice for the other toxicities. Only 5/9 patients with any Delta NTCP >5% clinically received ART, although ART had been done for 13/52 patients (PPV: 0.38). PPV was 0.86 and 0.75 for accumulated dose at fraction 10 and 15, respectively, using a Delta NTCP cut-off for the allocation of ART of 5%. Using other Delta NTCP cut-offs did not substantially improve PPV. With this cutoff the negative predictive value was 0.93 for Delta NTCP method of fraction 10 and fraction 15, and 0.90 for clinical judgement.Conclusion: To identify patients accurately for ART, NTCP calculations based on the dose differences between planned and delivered dose at fraction 10 are superior to clinical judgement. (C) 2019 Published by Elsevier B.V.Biological, physical and clinical aspects of cancer treatment with ionising radiatio