Publications by authors named "Ulrike Schick"

93 Publications

N3 (> 6 cm) squamous cell carcinoma of the head and neck: outcomes and predictive factors in 104 patients.

Acta Otorhinolaryngol Ital 2021 Jun;41(3):221-229

Oncology Department, University Hospital, Brest, France.

Objective: To report outcome and predictive factors in patients with N3 (> 6 cm) non-metastatic locally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with a conservative approach or with initial surgery.

Methods: 104 patients were included: 69 treated with radiotherapy (RT) ± chemotherapy (CT) and 35 with nodal surgery with or without primary tumour resection, which was completed in 30 patients by adjuvant RT ± CT. Positron-emission tomography-computed tomography (PET-CT) guided surveillance after RT ± CT was standard.

Results: Two-year overall survival (OS) and locoregional control (LRC) were 39.4% and 37.5%, respectively. In univariate analysis, body mass index (BMI), performance status (PS), p16 status and haemoglobin value influenced OS and disease-free survival (DFS). In multivariate analysis, p16 positive status and BMI ≥ 25 remained independent prognostic factors for better OS (p = 0.023) and DFS (p = 0.002). Only under/normal weight remained an independent and adverse significant prognostic factor in multivariate analysis for regional control (RC). Patients treated with primary RT ± CT had slightly better 2-year OS (43.5% 33.3%, p = 0.31).

Conclusions: Patients with N3 LAHNSCC have poor prognosis, but long term LRC is achievable, especially in overweight patients and those with a good PS.
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http://dx.doi.org/10.14639/0392-100X-N1437DOI Listing
June 2021

A transfer learning approach to facilitate ComBat-based harmonization of multicentre radiomic features in new datasets.

PLoS One 2021 1;16(7):e0253653. Epub 2021 Jul 1.

INSERM, UMR 1101, LaTIM, University of Brest, Brest, France.

Purpose: To facilitate the demonstration of the prognostic value of radiomics, multicenter radiomics studies are needed. Pooling radiomic features of such data in a statistical analysis is however challenging, as they are sensitive to the variability in scanner models, acquisition protocols and reconstruction settings, which is often unavoidable in a multicentre retrospective analysis. A statistical harmonization strategy called ComBat was utilized in radiomics studies to deal with the "center-effect". The goal of the present work was to integrate a transfer learning (TL) technique within ComBat-and recently developed alternate versions of ComBat with improved flexibility (M-ComBat) and robustness (B-ComBat)-to allow the use of a previously determined harmonization transform to the radiomic feature values of new patients from an already known center.

Material And Methods: The proposed TL approach were incorporated in the four versions of ComBat (standard, B, M, and B-M ComBat). The proposed approach was evaluated using a dataset of 189 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging (MRI) and positron emission tomography (PET) images, with the clinical endpoint of predicting local failure. The impact performance of the TL approach was evaluated by comparing the harmonization achieved using only parts of the data to the reference (harmonization achieved using all the available data). It was performed through three different machine learning pipelines.

Results: The proposed TL technique was successful in harmonizing features of new patients from a known center in all versions of ComBat, leading to predictive models reaching similar performance as the ones developed using the features harmonized with all the data available.

Conclusion: The proposed TL approach enables applying a previously determined ComBat transform to new, previously unseen data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253653PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248970PMC
July 2021

The prognostic significance of PD-L1 expression on tumor and immune cells in Merkel cell carcinoma.

J Cancer Res Clin Oncol 2021 Sep 11;147(9):2569-2578. Epub 2021 Jun 11.

Radiation Oncology Department, University Hospital Morvan, 2 avenue Foch, 29200, Brest, France.

Introduction: The aim of this study was to evaluate prognostic factors in patients with non-metastatic Merkel cell carcinoma (MCC), with a particular focus on immunological markers such as TILs subtyping (CD3, CD8, CD68, FoxP3, PD-L1 and PD-1) and MCPyV.

Methods: Patients treated for a non-metastatic MCC with oncologic surgical resection followed or not by adjuvant radiotherapy between 01/2007 and 12/2018 were analyzed. Local and regional control (LC, RC), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated. Clinical variables analyzed included age, gender, performance status, comorbidity, tumor size, location and presentation type, extension, oncologic resection and adjuvant radiotherapy. Pathological variables analyzed included type of tumor-infiltrating lymphocytes, CD3, CD8, CD68, PD-L1 expression on immune cells and tumors cells, PD-1, FoxP3 and MCPyV, assessed with immunohistochemistry (IHC).

Results: 77 patients were included. After a median follow-up of 18 months (range 0.2-144), the 1-year LC, RC, DMFS and OS were 83%, 60%, 82% and 75%, respectively. In multivariate analysis, a percentage of PD-L1 expression by immune cells ≥ 1% was significantly correlated with improvement of RC (p = 0.012), DMFS (p = 0.003) and OS (p = 0.006). Adjuvant radiotherapy significantly improved DMFS (p = 0.021) and OS (0.041) rates. There was a correlation between the presence of MCPyV + and the expression of PD-L1 on IC (p = 0.05) and TC (p = 0.03).

Conclusion: PD-L1 expression by immune and tumor cells in non-metastatic MCC seems to significantly improve outcome in patients who did not received PD-1/PD-L1 inhibitors. Prospective studies are needed to confirm our hypothesis.
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http://dx.doi.org/10.1007/s00432-021-03676-6DOI Listing
September 2021

Radiomics Analysis of 3D Dose Distributions to Predict Toxicity of Radiotherapy for Cervical Cancer.

J Pers Med 2021 May 11;11(5). Epub 2021 May 11.

Radiation Oncology Department, University Hospital, CHRU Morvan, 2 avenue Foch, CEDEX, 29609 Brest, France.

Standard treatment for locally advanced cervical cancer (LACC) is chemoradiotherapy followed by brachytherapy. Despite radiation therapy advances, the toxicity rate remains significant. In this study, we compared the prediction of toxicity events after radiotherapy for locally advanced cervical cancer (LACC), based on either dose-volume histogram (DVH) parameters or the use of a radiomics approach applied to dose maps at the voxel level. Toxicity scores using the Common Terminology Criteria for Adverse Events (CTCAE v4), spatial dose distributions, and usual clinical predictors for the toxicity of 102 patients treated with chemoradiotherapy followed by brachytherapy for LACC were used in this study. In addition to usual DVH parameters, 91 radiomic features were extracted from rectum, bladder and vaginal 3D dose distributions, after discretization into a fixed bin width of 1 Gy. They were evaluated for predictive modelling of rectal, genitourinary (GU) and vaginal toxicities (grade ≥ 2). Logistic Normal Tissue Complication Probability (NTCP) models were derived using clinical parameters only or combinations of clinical, DVH and radiomics. For rectal acute/late toxicities, the area under the curve (AUC) using clinical parameters was 0.53/0.65, which increased to 0.66/0.63, and 0.76/0.87, with the addition of DVH or radiomics parameters, respectively. For GU acute/late toxicities, the AUC increased from 0.55/0.56 (clinical only) to 0.84/0.90 (+DVH) and 0.83/0.96 (clinical + DVH + radiomics). For vaginal acute/late toxicities, the AUC increased from 0.51/0.57 (clinical only) to 0.58/0.72 (+DVH) and 0.82/0.89 (clinical + DVH + radiomics). The predictive performance of NTCP models based on radiomics features was higher than the commonly used clinical and DVH parameters. Dosimetric radiomics analysis is a promising tool for NTCP modelling in radiotherapy.
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http://dx.doi.org/10.3390/jpm11050398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151048PMC
May 2021

Statistical harmonization can improve the development of a multicenter CT-based radiomic model predictive of nonresponse to induction chemotherapy in laryngeal cancers.

Med Phys 2021 Jul 5;48(7):4099-4109. Epub 2021 Jul 5.

LaTIM, INSERM, UMR 1101, Univ Brest, Brest, France.

Purpose: To develop a radiomic model predicting nonresponse to induction chemotherapy in laryngeal cancers, from multicenter pretherapeutic contrast-enhanced computed tomography (CE-CT) and evaluate the benefit of feature harmonization in such a context.

Methods: Patients (n = 104) eligible for laryngeal preservation chemotherapy were included in five centers. Primary tumor was manually delineated on the CE-CT images. The following radiomic features were extracted with an in-house software (MIRAS v1.1, LaTIM UMR 1101): intensity, shape, and textural features derived from Gray-Level Co-occurrence Matrix (GLCM), Neighborhood Gray Tone Difference Matrix (NGTDM), Gray-Level Run Length Matrix (GLRLM), and Gray-Level Size Zone Matrix (GLSZM). Harmonization was performed using ComBat after unsupervised hierarchical clustering, used to determine labels automatically, given the high heterogeneity of imaging characteristics across and within centers. Patients with similar feature distributions were grouped with unsupervised clustering into an optimal number of clusters (2) determined with "silhouette scoring." Statistical harmonization was then carried out with ComBat on these 2 identified clusters. The cohort was split into training/validation (n = 66) and testing (n = 32) sets. Area under the receiver operating characteristics curves (AUC) were used to evaluate the ability of radiomic features (before and after harmonization) to predict nonresponse to chemotherapy, and specificity (Sp) and sensitivity (Se) were used to quantify their performance in the testing set.

Results: Without harmonization, none of the features identified as predictive in the training set remained significant in the testing set. After ComBat, one textural feature identified in the training set keeps a predictive trend in the testing set-Zone Percentage, derived from the GLSZM, was predictive of nonresponse in the training set (AUC = 0.62, Se = 70%, Sp = 64%, P = 0.04) and obtained a satisfactory performance in the testing set (Se = 80%, Sp = 67%, P = 0.03), although significance was limited by the size of the testing set. These results are consistent with previously published findings in head and neck cancers.

Conclusions: Radiomic features from CE-CT could help in the selection of patients for induction chemotherapy in laryngeal cancers, with relatively good sensitivity and specificity in predicting lack of response. Statistical harmonization with ComBat and unsupervised clustering seems to improve the predictive value of features extracted in such a heterogeneous multicenter setting.
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http://dx.doi.org/10.1002/mp.14948DOI Listing
July 2021

Dosimetric Validation of a GAN-Based Pseudo-CT Generation for MRI-Only Stereotactic Brain Radiotherapy.

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Radiation Oncology Department, CHRU Brest, 2 Avenue Foch, 29200 Brest, France.

Purpose: Stereotactic radiotherapy (SRT) has become widely accepted as a treatment of choice for patients with a small number of brain metastases that are of an acceptable size, allowing for better target dose conformity, resulting in high local control rates and better sparing of organs at risk. An MRI-only workflow could reduce the risk of misalignment between magnetic resonance imaging (MRI) brain studies and computed tomography (CT) scanning for SRT planning, while shortening delays in planning. Given the absence of a calibrated electronic density in MRI, we aimed to assess the equivalence of synthetic CTs generated by a generative adversarial network (GAN) for planning in the brain SRT setting.

Methods: All patients with available MRIs and treated with intra-cranial SRT for brain metastases from 2014 to 2018 in our institution were included. After co-registration between the diagnostic MRI and the planning CT, a synthetic CT was generated using a 2D-GAN (2D U-Net). Using the initial treatment plan (Pinnacle v9.10, Philips Healthcare), dosimetric comparison was performed using main dose-volume histogram (DVH) endpoints in respect to ICRU 91 guidelines (Dmax, Dmean, D2%, D50%, D98%) as well as local and global gamma analysis with 1%/1 mm, 2%/1 mm and 2%/2 mm criteria and a 10% threshold to the maximum dose. -test analysis was used for comparison between the two cohorts (initial and synthetic dose maps).

Results: 184 patients were included, with 290 treated brain metastases. The mean number of treated lesions per patient was 1 (range 1-6) and the median planning target volume (PTV) was 6.44 cc (range 0.12-45.41). Local and global gamma passing rates (2%/2 mm) were 99.1 CI95% (98.1-99.4) and 99.7 CI95% (99.6-99.7) respectively (CI: confidence interval). DVHs were comparable, with no significant statistical differences regarding ICRU 91's endpoints.

Conclusions: Our study is the first to compare GAN-generated CT scans from diagnostic brain MRIs with initial CT scans for the planning of brain stereotactic radiotherapy. We found high similarity between the planning CT and the synthetic CT for both the organs at risk and the target volumes. Prospective validation is under investigation at our institution.
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http://dx.doi.org/10.3390/cancers13051082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959466PMC
March 2021

PD-L1 expression in recurrent head and neck squamous cell carcinoma.

Eur Arch Otorhinolaryngol 2021 Apr 1. Epub 2021 Apr 1.

Radiation Oncology Department, University Hospital Morvan, 2 avenue Foch, 29200, Brest, France.

Purpose: To evaluate the Programmed Cell Death Ligand (PD-L1) expression at diagnosis and relapse in patients with head and neck carcinoma (HNSCC) treated with radio(chemo)therapy.

Methods: PD-L1 immunohistochemistry was performed in tumor cells (TC) and immune cells (IC) in 44 patients and scored as 0 = 0%, 1 =  < 5%, 2 = 6-49% or 3 =  ≥ 50% cells.

Results: PD-L1 expression on TC before RT was scored as 0, 1, 2 and 3 in 28, 4, 8 and 4 patients, respectively. In 10 patients, IC did not show any PD-L1 expression; while in 8, 16, and 10 patients, PD-L1 expression was scored 1, 2 and 3, respectively. At relapse, 7/36 patients had a PD-L1 expression positivation in TC, while the opposite was observed in 6 patients. Overall, survival at 2 years was higher in patients with PD-L1 expression (90% versus 62.5%, p = 0.032).

Conclusion: PD-L1 expression may vary throughout the course of the disease. A re-evaluation of PD-L1 expression on biopsies at the time of recurrence should be recommended.
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http://dx.doi.org/10.1007/s00405-021-06777-7DOI Listing
April 2021

18F-FET PET/CT in Early Subventricular Zone Recurrence of Adult Glioblastoma.

Clin Nucl Med 2021 06;46(6):499-500

Abstract: Glioma stem cells (GSCs) are the source of tumor recurrence in glioblastoma and are capable of whole tumor regeneration once the treatment has concluded. Compelling evidence from the last decade suggests that GSC may arise from neural stem cells residing in the adult subventricular zone (SVZ). We report the findings of an 18F-FET PET/CT showing pathological uptake in SVZ with a tumor-background ratio of greater than 1.6, giving evidence for glioblastoma recurrence. This case highlights the particular attention to be paid to the SVZ given the possible development of GSC.
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http://dx.doi.org/10.1097/RLU.0000000000003639DOI Listing
June 2021

Convolutional neural networks for PET functional volume fully automatic segmentation: development and validation in a multi-center setting.

Eur J Nucl Med Mol Imaging 2021 Mar 27. Epub 2021 Mar 27.

LaTIM, INSERM, UMR 1101, University Brest, Brest, France.

Purpose: In this work, we addressed fully automatic determination of tumor functional uptake from positron emission tomography (PET) images without relying on other image modalities or additional prior constraints, in the context of multicenter images with heterogeneous characteristics.

Methods: In cervical cancer, an additional challenge is the location of the tumor uptake near or even stuck to the bladder. PET datasets of 232 patients from five institutions were exploited. To avoid unreliable manual delineations, the ground truth was generated with a semi-automated approach: a volume containing the tumor and excluding the bladder was first manually determined, then a well-validated, semi-automated approach relying on the Fuzzy locally Adaptive Bayesian (FLAB) algorithm was applied to generate the ground truth. Our model built on the U-Net architecture incorporates residual blocks with concurrent spatial squeeze and excitation modules, as well as learnable non-linear downsampling and upsampling blocks. Experiments relied on cross-validation (four institutions for training and validation, and the fifth for testing).

Results: The model achieved good Dice similarity coefficient (DSC) with little variability across institutions (0.80 ± 0.03), with higher recall (0.90 ± 0.05) than precision (0.75 ± 0.05) and improved results over the standard U-Net (DSC 0.77 ± 0.05, recall 0.87 ± 0.02, precision 0.74 ± 0.08). Both vastly outperformed a fixed threshold at 40% of SUVmax (DSC 0.33 ± 0.15, recall 0.52 ± 0.17, precision 0.30 ± 0.16). In all cases, the model could determine the tumor uptake without including the bladder. Neither shape priors nor anatomical information was required to achieve efficient training.

Conclusion: The proposed method could facilitate the deployment of a fully automated radiomics pipeline in such a challenging multicenter context.
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http://dx.doi.org/10.1007/s00259-021-05244-zDOI Listing
March 2021

[F]FDG PET radiomics to predict disease-free survival in cervical cancer: a multi-scanner/center study with external validation.

Eur J Nucl Med Mol Imaging 2021 Mar 26. Epub 2021 Mar 26.

GIGA-CRC in vivo Imaging, University of Liège, GIGA, Avenue de l'Hôpital 11, 4000, Liege, Belgium.

Purpose: To test the performances of native and tumour to liver ratio (TLR) radiomic features extracted from pre-treatment 2-[F] fluoro-2-deoxy-D-glucose ([F]FDG) PET/CT and combined with machine learning (ML) for predicting cancer recurrence in patients with locally advanced cervical cancer (LACC).

Methods: One hundred fifty-eight patients with LACC from multiple centers were retrospectively included in the study. Tumours were segmented using the Fuzzy Local Adaptive Bayesian (FLAB) algorithm. Radiomic features were extracted from the tumours and from regions drawn over the normal liver. Cox proportional hazard model was used to test statistical significance of clinical and radiomic features. Fivefold cross validation was used to tune the number of features. Seven different feature selection methods and four classifiers were tested. The models with the selected features were trained using bootstrapping and tested in data from each scanner independently. Reproducibility of radiomics features, clinical data added value and effect of ComBat-based harmonisation were evaluated across scanners.

Results: After a median follow-up of 23 months, 29% of the patients recurred. No individual radiomic or clinical features were significantly associated with cancer recurrence. The best model was obtained using 10 TLR features combined with clinical information. The area under the curve (AUC), F-score, precision and recall were respectively 0.78 (0.67-0.88), 0.49 (0.25-0.67), 0.42 (0.25-0.60) and 0.63 (0.20-0.80). ComBat did not improve the predictive performance of the best models. Both the TLR and the native models performance varied across scanners used in the test set.

Conclusion: [F]FDG PET radiomic features combined with ML add relevant information to the standard clinical parameters in terms of LACC patient's outcome but remain subject to variability across PET/CT devices.
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http://dx.doi.org/10.1007/s00259-021-05303-5DOI Listing
March 2021

Prospective study of dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors.

Sci Rep 2021 Mar 1;11(1):4727. Epub 2021 Mar 1.

EA GETBO 3878, University Hospital of Brest, Brest, France.

To present the feasibility of a dynamic whole-body (DWB) Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1-5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB Ga-DOTATOC-PET/CT acquisition in WD-NETs.
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http://dx.doi.org/10.1038/s41598-021-83965-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921579PMC
March 2021

Toxicity after volumetric modulated arc therapy for lung cancer: a monocentric retrospective study.

Transl Lung Cancer Res 2021 Jan;10(1):156-166

Radiation Oncology Department, CHRU Brest, Brest, France.

Background: Intensity-modulated radiotherapy (RT) is now widely implemented and has replaced classical three-dimensional (3D)-RT in many tumor sites, as it allows a better target dose conformity and a better sparing of organs a risk (OAR), at the expense, however, of increasing the volume of low dose to normal tissues. Clinical data on toxicities using volumetric modulated arc therapy (VMAT) in lung cancer remain scarce. We aimed to report both acute (APT) and late (LPT) pulmonary and acute (AET) and late (LET) oesophageal toxicities in such setting.

Methods: All patients treated for a primary lung cancer with VMAT +/- chemotherapy (ChT) in our center from 2014 to 2018 were retrospectively included. Usual clinical, treatment and dosimetric features were collected. Univariate analysis was performed using the receiver operative characteristics approach while multivariate analysis (MVA) relied on logistic regression, calculated with Medcalc 14.8.1.

Results: In total, 167 patients were included, with a median age of 66 years (39-88 years). Median radiation dose was 66 Gy (30-66 Gy); 82% patients received concomitant (32.3%), induction (25.7%) or induction followed by concomitant ChT (24%). After a median follow-up of 14.0 months, the G ≥2 APT, AET, LPT and LET rates were 22.2%, 30.0%, 16.8% and 5.4%, respectively with low grade ≥3 toxicity rates (respectively, 3%, 6.6%, 3% and 0%). On MVA, APT was significantly associated with V30 to the homolateral lung, AET with age, LPT with MEVS while no feature remained significantly correlated with LET.

Conclusions: Low rates of pulmonary and esophageal toxicity were observed in our cohort. Larger prospective studies are needed to confirm these results.
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http://dx.doi.org/10.21037/tlcr-20-406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867762PMC
January 2021

Cranial organs at risk delineation: heterogenous practices in radiotherapy planning.

Radiat Oncol 2021 Feb 4;16(1):26. Epub 2021 Feb 4.

Department of Radiation Oncology, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Sorbonne Université, Paris, France.

Background: Segmentation is a crucial step in treatment planning that directly impacts dose distribution and optimization. The aim of this study was to evaluate the inter-individual variability of common cranial organs at risk (OAR) delineation in neurooncology practice.

Methods: Anonymized simulation contrast-enhanced CT and MR scans of one patient with a solitary brain metastasis was used for delineation and analysis. Expert professionals from 16 radiotherapy centers involved in brain structures delineation were asked to segment 9 OAR on their own treatment planning system. As reference, two experts in neurooncology, produced a unique consensual contour set according to guidelines. Overlap ratio, Kappa index (KI), volumetric ratio, Commonly Contoured Volume, Supplementary Contoured Volume were evaluated using Artiview™ v 2.8.2-according to occupation, seniority and level of expertise of all participants.

Results: For the most frequently delineated and largest OAR, the mean KI are often good (0.8 for the parotid and the brainstem); however, for the smaller OAR, KI degrade (0.3 for the optic chiasm, 0.5% for the cochlea), with a significant discrimination (p < 0.01). The radiation oncologists, members of Association des Neuro-Oncologue d'Expression Française society performed better in all indicators compared to non-members (p < 0.01). Our exercise was effective in separating the different participating centers with 3 of the reported indicators (p < 0.01).

Conclusion: Our study illustrates the heterogeneity in normal structures contouring between professionals. We emphasize the need for cerebral OAR delineation harmonization-that is a major determinant of therapeutic ratio and clinical trials evaluation.
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http://dx.doi.org/10.1186/s13014-021-01756-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863275PMC
February 2021

Radiomics in PET/CT: Current Status and Future AI-Based Evolutions.

Semin Nucl Med 2021 Mar 1;51(2):126-133. Epub 2020 Nov 1.

LaTIM, INSERM, UMR 1101, University of Brest, CHRU Brest, France. Electronic address:

This short review aims at providing the readers with an update on the current status, as well as future perspectives in the quickly evolving field of radiomics applied to the field of PET/CT imaging. Numerous pitfalls have been identified in study design, data acquisition, segmentation, features calculation and modeling by the radiomics community, and these are often the same issues across all image modalities and clinical applications, however some of these are specific to PET/CT (and SPECT/CT) imaging and therefore the present paper focuses on those. In most cases, recommendations and potential methodological solutions do exist and should therefore be followed to improve the overall quality and reproducibility of published studies. In terms of future evolutions, the techniques from the larger field of artificial intelligence (AI), including those relying on deep neural networks (also known as deep learning) have already shown impressive potential to provide solutions, especially in terms of automation, but also to maybe fully replace the tools the radiomics community has been using until now in order to build the usual radiomics workflow. Some important challenges remain to be addressed before the full impact of AI may be realized but overall the field has made striking advances over the last few years and it is expected advances will continue at a rapid pace.
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http://dx.doi.org/10.1053/j.semnuclmed.2020.09.002DOI Listing
March 2021

Toxicity in patients treated with permanent prostate brachytherapy using intraoperatively built custom-linked seeds versus loose seeds.

J Contemp Brachytherapy 2020 Dec 16;12(6):547-553. Epub 2020 Dec 16.

Service de Radiothérapie, CHU Brest, Brest, France.

Purpose: Low-dose-rate brachytherapy (BT) with permanent iodine-125 radioactive seeds is a highly effective treatment option for low- and favorable intermediate-risk prostate cancer. However, optimal implantation is not always achieved due to edema or seeds loss. One way to improve seed placement is the use of stranded seeds called "intraoperatively built custom-linked seeds (IBCLS)" in an opposition to loose seeds (LS). To date, there are few data comparing toxicity rates between these two techniques. The aim of this study was to compare dosimetric parameters and toxicity rates at 2 years between both procedures in a matched-paired population.

Material And Methods: Patients were considered for BT according to European guidelines. Among 548 patients treated at our institution, 105 patients in the loose seeds cohort were individually matched to 105 patients in the IBCLS group according to age, prostate volume, pre-operative international prostate symptom score (IPSS), clinical stage, and Gleason score. Erectile function was scored using the five-item international index of erectile function (IIEF-5) score. A multivariable linear mixed-effects model was applied to examine the association between total and individual scores (repeated measures) and covariates.

Results: Overall, 61 (29%) patients presented with a favorable intermediate-risk prostate cancer. There were no significant changes in IPSS over time ( = 0.57). During follow-up, the IIEF-5 was similar in the two groups, except at one month, where it was lower in the IBCLS group (10.9 vs. 6.9, = 0.029). Also, there was no difference in grade ≥ 2 rectal toxicity. At 1 month, D, V, and V were higher in the LS group compared to the IBCLS group.

Conclusions: Low-dose-rate prostate brachytherapy using IBCLS is a safe technique, with comparable toxicity profiles at 2 years compared to LS brachytherapy.
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http://dx.doi.org/10.5114/jcb.2020.101687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787198PMC
December 2020

Breast cancer tumor heterogeneity has only little impact on the estimation of the Oncotype DX® recurrence score using Magee Equations and Magee Decision Algorithm™.

Hum Pathol 2021 02 24;108:51-59. Epub 2020 Nov 24.

CHRU Brest, Department of Pathology, Brest, F-29220, France; Univ Brest, Inserm, CHU de Brest, LBAI, UMR1227, Brest, France. Electronic address:

Oncotype DX® assay is used to guide therapeutic decisions in early-stage invasive breast carcinoma but remains expensive. Magee Equations (MEs) and Magee Decision Algorithm (MDA) predict the Oncotype DX® recurrence score (RS) on the basis of histopathological parameters. The influence of intratumor heterogeneity on MEs and MDA remains uncertain. We compared Ki-67, estrogen and progesterone receptors, and human erb-b2 receptor tyrosine kinase 2 (HER2) status on tissue microarray cores with the corresponding findings on the whole slides to calculate MEs scores and to decide if Oncotype DX® testing was required as per MDA in two sets of 175 and 59 tumors, without and with Oncotype DX® results, respectively. Agreements in the interpretation of Ki-67, estrogen and progesterone receptors, and HER2 status were very good between limited areas and whole-slide analyses. This resulted also in very good agreements about the results of MEs and MDA. For 7 of 175 (4%) and 3 of 59 (5.1%) cases, MEs and MDA results in different tumor areas would have changed the indication to perform or not perform Oncotype DX® assays. Oncotype DX® RSs were significantly correlated with MEs and MDA results, but among cases initially predicted to have an RS ≤25 using MDA, 3 of 34 cases (8.8%) had in fact an RS >25. Tumor heterogeneity appears to have little impact on the estimation of the Oncotype DX® RS using MEs and MDA and would have permitted to avoid half of Oncotype DX® assays in our series. Caution is nevertheless required in discarding Oncotype DX® assay in cases with ME scores >18 associated with low mitotic activity.
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http://dx.doi.org/10.1016/j.humpath.2020.11.006DOI Listing
February 2021

Incidental Findings of a Vestibular Schwannoma on 18F-Choline PET/CT.

Clin Nucl Med 2021 Feb;46(2):e75-e77

Radiotherapy, University Hospital of Brest.

Abstract: We report an increased uptake of 18F-choline in the right cerebellopontine angle area in a 73-year-old man with biochemical failure prostate cancer after radical prostatectomy, potentially suggestive of bone metastasis in the base of the skull. A brain MRI was also performed showing an intense gadolinium enhancement focus in the same area, concordant with a right vestibular schwannoma, subsequently histologically proven. This case underlines that schwannoma is a diagnostic pitfall in 18F-choline PET/CT, suggesting this radiolabeled tracer as a promising tool for brain tumors characterization due to its higher signal-to-background ratio than 18F-FDG.
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http://dx.doi.org/10.1097/RLU.0000000000003427DOI Listing
February 2021

Clinical Assessment of 177Lu-DOTATATE Quantification by Comparison of SUV-Based Parameters Measured on Both Post-PRRT SPECT/CT and 68Ga-DOTATOC PET/CT in Patients With Neuroendocrine Tumors: A Feasibility Study.

Clin Nucl Med 2021 Feb;46(2):111-118

Department of Oncology, University Hospital of Brest, Brest, France.

Patients And Methods: Patients with WD-GEP-NET who benefited from a pretherapeutic 68Ga-DOTATOC PET/CT and a 177Lu-DOTATATE SPECT/CT after the cycle 1 of peptide receptor radionuclide therapy were prospectively included. SPECT/CT acquisitions were performed on a system calibrated with a conversion factor of 9.48 counts/MBq per second and were reconstructed with an iterative algorithm allowing quantification using the SPECTRA Quant software (MIM Software, Cleveland, OH). For each patient, different SUV parameters were recorded on both PET/CT (Ga parameters) and SPECT/CT (Lu parameters) for comparison: physiological uptakes (liver/spleen), tumor uptake (1-10/patient; SUVmax, SUVmean, SUVpeak, MTV), tumor-to-liver and tumor-to-spleen ratios according to liver/spleen SUVmax and SUVmean (TLRmax, TLRmean, TSRmax, and TSRmean, respectively).

Results: Ten patients (8 female; 2 male) aged from 50 to 83 years presenting with a metastatic progressive WD-GEP-NET (7 small intestine, 2 pancreas, 1 rectum) were included. Median values of lesional Lu-SUV were significantly lower than the corresponding Ga-SUV (P < 0.001), whereas median values of lesional Lu-MTV, Lu-TLR, and Lu-TSR were significantly higher than the corresponding Ga-MTV, Ga-TLR, and Ga-TSR (P < 0.02). Pearson correlation coefficients were strong for both SUV and MTV parameters (0.779-0.845), weak for TLR parameters (0.365-0.394), and moderate-to-strong for TSR parameters (0.676-0.750).

Conclusions: Our results suggest the feasibility of 177Lu-DOTATATE SPECT/CT quantification in clinical practice and show a strong correlation of several SUV-based parameters with the corresponding in 68Ga-DOTATOC PET/CT.
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http://dx.doi.org/10.1097/RLU.0000000000003412DOI Listing
February 2021

Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases.

BMC Cancer 2020 Oct 13;20(1):991. Epub 2020 Oct 13.

Radiation Oncology Department, University Hospital Morvan, 2 Avenue Foch, F-29200, Brest, France.

Background: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM).

Methods: Ninety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated.

Results: After a median follow-up of 11.9 months (range 0.7-29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53% (p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03).

Conclusion: SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.
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http://dx.doi.org/10.1186/s12885-020-07491-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557085PMC
October 2020

Minimal channel GreenLight photovaporization before permanent implant prostate brachytherapy for patients with obstructive symptoms: Technically feasible and safe.

Brachytherapy 2021 Jan-Feb;20(1):50-57. Epub 2020 Sep 3.

Urology Department, CHU, Brest, France; Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale, Brest, France; LaTIM, INSERM, UMR 1101, Université de Bretagne Occidentale, Brest, France; CeRePP, Paris, France. Electronic address:

Purpose: Brachytherapy (BrT) is a standard treatment for low-risk to favorable-intermediate-risk prostate cancer but is a relative contraindication for patients with obstructive symptoms. We aimed to assess the feasibility and urinary toxicity of a minimal photovaporization (mPVP) before implantation.

Materials And Methods: Between 04/2009 and 08/2016, 50 patients candidates for BrT but with International Prostate Symptom Score (IPSS)>15, uroflowmetry <15 mL/s, obstructive prostate or large median lobe underwent a mPVP (GreenLight Laser) at least 6 weeks (median 8.5) before permanent seed implantation (loose seeds, I, 160 Gy).

Results: Two patients (4%) did not have sufficient improvement and did not undergo BrT, although it would have been possible at 3 months. For the 48 (96%) other patients, at the baseline, mean IPSS was 15.5 (±5.3), vs. 8.6 (±4.4) after mPVP (p = 1 × 10), and uroflowmetry 11.7 mL/s (±4), vs. 17.4 (±5.4) (p = 1.4 × 10). We did not experience any difficulty for BrT. Mean IPSS did not significantly increase 1, 3, or 6 months after BrT. With a median followup of 60 months [30-120], (92% assessed at last followup), only 4 patients (4/48 = 8.3%) experienced urinary retention and 5 (10.4%) needed surgery for urinary toxicity. In addition, only 2 patients (4%) needed medical treatment at last followup. Considering the 8 patients with de novo incontinence at 1 year, only 2 (4%) had persistent mild symptoms at last followup (36 months) (ICS1-2).

Conclusions: These results suggest that a two-step approach with an mPVP at least 6 weeks before BrT is feasible, with no excessive urinary toxicity, and may be a good strategy for obstructive patients seeking BrT.
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http://dx.doi.org/10.1016/j.brachy.2020.08.003DOI Listing
September 2020

Diagnostic performance of a whole-body dynamic 68GA-DOTATOC PET/CT acquisition to differentiate physiological uptake of pancreatic uncinate process from pancreatic neuroendocrine tumor.

Medicine (Baltimore) 2020 Aug;99(33):e20021

EA GETBO 3878.

To evaluate the diagnostic performance of net influx rate (Ki) values from a whole-body dynamic (WBD) Ga-DOTATOC-PET/CT acquisition to differentiate pancreatic neuroendocrine tumors (pNETs) from physiological uptake of pancreatic uncinate process (UP).Patients who were benefited from a WBD acquisition for the assessment of a known well-differentiated neuroendocrine tumor (NET)/suspicion of disease in the prospective GAPET-NET cohort were screened. Only patients with a confirmed pNET/UP as our gold standard were included. The positron emission tomography (PET) procedure consisted in a single-bed dynamic acquisition centered on the heart, followed by a whole-body dynamic acquisition and then a static acquisition. Dynamic (Ki calculated according to Patlak method), static (SUVmax, SUVmean, SUVpeak) parameters, and tumor-to-liver and tumor-to-spleen ratio (TLRKi and TSRKi (according to hepatic/splenic Ki)), tumor SUVmax to liver SUVmax (TM/LM), tumor SUVmax to liver SUVmean (TM/Lm), tumor SUVmax to spleen SUVmax (TM/SM), and tumor SUVmax to spleen SUVmean (TM/Sm) (according to hepatic/splenic SUVmax and SUVmean respectively) were calculated. A Receiver Operating Characteristic (ROC) analysis was performed to evaluate their diagnostic performance to distinguish UP from pNET.One hundred five patients benefited from a WBD between July 2018 and July 2019. Eighteen (17.1%) had an UP and 26 (24.8%) a pNET. For parameters alone, the Ki and SUVpeak had the best sensitivity (88.5%) while the Ki, SUVmax, and SUVmean had the best specificity (94.4%). The best diagnostic accuracy was obtained with Ki (90.9%). For ratios, the TLRKi and the TSRKi had the best sensitivity (95.7%) while the TM/SM and TM/Sm the best specificity (100%). TLRKi had the best diagnostic accuracy (95.1%) and the best area under the curve (AUC) (0.990).Our study is the first one to evaluate the interest of a WBD acquisition to differentiate UP from pNETs and shows excellent diagnostic performances of the Ki approach.
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http://dx.doi.org/10.1097/MD.0000000000020021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437793PMC
August 2020

Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study.

Clin Otolaryngol 2020 Nov 16;45(6):877-884. Epub 2020 Sep 16.

Radiation oncology, Centre François Baclesse / ARCHADE, Caen, France.

Objectives: In patients with N3 head and neck squamous cell carcinoma (HNSCC), N3 disease is associated with high regional relapse and metastatic risks. Patients with resectable N3 disease have better prognosis although their metastatic risk may be similar as in patients with unresectable disease. Neoadjuvant chemotherapy has been associated with lower metastatic rates, but N3 patients may die of rapid locoregional progression. We assessed outcomes with the three modalities in patients with low primary burden to better assess the specific prognosis of N3 disease.

Methods: This retrospective multicentric study included T0-2 N3 HNSCC patients. Outcomes and morbidity in upfront neck dissection (uND) vs non-surgical groups were analysed and oncological outcomes and morbidity compared between patients undergoing chemoradiation or neoadjuvant chemotherapy in patients with initially unresectable N3 nodes.

Results: Of 301 patients, 142 (47%) underwent uND, 68 (23%) neoadjuvant chemotherapy and 91 (30%) chemoradiation. The 24- and 60-month incidence of locoregional relapse was 23.2% [18.3%; 28.4%] and 27.4% [21.8%; 33.3%]; it was lower in patients undergoing uND (P = .006). In patients with non-surgical treatments, success rates were 57.8% [49.4%; 66.3%] after chemoradiation and 38.1% [29.6%; 46.7%] after neoadjuvant chemotherapy (P = .001). Overall morbidity was more frequent in patients undergoing uND (68.8%) (P < .001).

Conclusion: uND improved locoregional control but increased morbidity and showed no survival benefit. Success rates were better after chemoradiation versus neoadjuvant chemotherapy. Neoadjuvant chemotherapy did not reduce metastatic rates but non-responders to chemoradiation had poor PFS and survival rate, suggesting that predictive criteria are warranted.
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http://dx.doi.org/10.1111/coa.13615DOI Listing
November 2020

Integration of 18-FDG PET/CT in the Initial Work-Up to Stage Head and Neck Cancer: Prognostic Significance and Impact on Therapeutic Decision Making.

Front Med (Lausanne) 2020 26;7:273. Epub 2020 Jun 26.

Department of Nuclear Medicine, Brest University Hospital, Brest, France.

The objective of this study was to assess the therapeutic and prognostic impact of integrating18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET)/computed tomography (CT) into work-up (WU) at initial staging of patients with head and neck squamous cell carcinoma (HNSCC). 477 consecutive patients (414M/63F, mean age 62.3 ± 9.7 years) with newly diagnosed HNSCC who underwent pre-treatment 18-FDG PET/CT were retrospectively included. The 18-FDG PET/CT stage (sPET) was compared to the conventional work-up stage (sCWU). A group of cancer specialists determined whether integrating PET/CT into WU at initial staging had an impact on the therapeutic decision, classifying the clinical impact as high (change in therapeutic modality), medium (change in the radiotherapy or surgical procedure), or low (modification of TNM staging and/or detection of synchronous cancer without high or medium impact). Three-year overall survival (OS) was considered as primary endpoint of the prognostic analysis. 18-FDG PET/CT had a clinical impact in 221 patients (46.3%) with a medium or high impact on management in 94 (19.5%) patients. Medium and high impact of 18-FDG PET/CT was statistically equivalent between sCWU-stage I/II and III/IV subgroups ( = 0.02). 42 patients were PET/CT-upstaged from early stage I/II to advanced stage III/IV and had a significantly lower 3-year OS than those with concordant CWU and 18-FDG PET/CT early stage (54.8 vs. 82.6%, = 0.001). This study demonstrated that implementing 18-FDG PET/CT in the initial WU of HNSCC provides valuable staging information with a better prognostic stratification. Patient management was modified for any disease stage, even for early stage I-II, with consequences on survival.
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http://dx.doi.org/10.3389/fmed.2020.00273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344296PMC
June 2020

Complete Metabolic Response Assessed by FDG PET/CT to FOLFOXIRI-Bevacizumab in First-Line Treatment of BRAFV600E Mutated Metastatic Colorectal Cancer.

Clin Nucl Med 2020 Sep;45(9):707-708

From the Departments of Oncology.

Triplet chemotherapy (FOLFOXIRI) + bevacizumab regimen is indicated as first-line treatment of BRAF-mutated metastatic colorectal cancer (mCRC). Nevertheless, its proven therapeutic efficacy in clinical trials was solely based on partial morphologic responses assessed by CT. To date, only 1 case of complete response assessed by FDG PET/CT was reported in literature in BRAF-mutated mCRC, but treated with doublet chemotherapy (FOLFIRI) + cetuximab regimen. We report a complete metabolic response assessed by FDG PET/CT, maintained over time (13 months) in a 60-year-old woman with BRAF-mutated mCRC treated by FOLFOXIRI-bevacizumab. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.
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http://dx.doi.org/10.1097/RLU.0000000000003190DOI Listing
September 2020

Correlation Between FDG Hotspots on Pre-radiotherapy PET/CT and Areas of HNSCC Local Relapse: Impact of Treatment Position and Images Registration Method.

Front Med (Lausanne) 2020 4;7:218. Epub 2020 Jun 4.

Department of Nuclear Medicine, Brest University Hospital, Brest, France.

Several series have already demonstrated that intratumoral subvolumes with high tracer avidity (hotspots) in 18F-flurodesoxyglucose positron-emission tomography (FDG-PET/CT) are preferential sites of local recurrence (LR) in various solid cancers after radiotherapy (RT), becoming potential targets for dose escalation. However, studies conducted on head and neck squamous cell carcinoma (HNSCC) found only a moderate overlap between pre- and post-treatment subvolumes. A limitation of these studies was that scans were not performed in RT treatment position (TP) and were coregistred using a rigid registration (RR) method. We sought to study (i) the influence of FDG-PET/CT acquisition in TP and (ii) the impact of using an elastic registration (ER) method to improve the localization of hotpots in HNSCC. Consecutive patients with HNSCC treated by RT between March 2015 and September 2017 who underwent FDG-PET/CT in TP at initial staging (PET) and during follow-up (PET) were prospectively included. We utilized a control group scanned in non treatment position (NTP) from our previous retrospective study. Scans were registered with both RR and ER methods. Various sub-volumes (A; x = 30, 40, 50, 60, 70, 80, and 90%SUVmax) within the initial tumor and in the subsequent LR (R; x = 40 and 70%SUVmax) were overlaid on the initial PET/CT for comparison [Dice, Jaccard, overlap fraction = OF, common volume/baseline volume = AnR/A, common volume/recurrent volume = AnR/R]. Of 199 patients included, 43 (21.6%) had LR (TP = 15; NTP = 28). The overlap between A, A, and A sub-volumes on PET and the whole metabolic volume of recurrence R and R on PET showed moderate to good agreements (0.41-0.64) with OF and AnR/R index, regardless of registration method or patient position. Comparison of registration method demonstrated OF and AnR/R indices (x = 30% to 50%SUVmax) were significantly higher with ER vs. RR in NTP ( < 0.03), but not in TP. For patient position, the OF and AnR/R indices were higher in TP than in NTP when RR was used with a trend toward significance, particularly for x=40%SUVmax (0.50±0.22 vs. 0.31 ± 0.13, = 0.094). Our study suggested that PET/CT acquired in TP improves results in the localization of FDG hotspots in HNSCC. If TP is not possible, using an ER method is significantly more accurate than RR for overlap estimation.
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http://dx.doi.org/10.3389/fmed.2020.00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287148PMC
June 2020

Radiotherapy target volume definition in newly diagnosed high grade glioma using F-FET PET imaging and multiparametric perfusion MRI: A prospective study (IMAGG).

Radiother Oncol 2020 09 21;150:164-171. Epub 2020 Jun 21.

Radiation Oncology Department, University Hospital, Brest, France; Université de Bretagne Occidentale, Brest, France; LaTIM, INSERM 1101, Brest, France.

Purpose: The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG).

Materials And Methods: Thirty patients with histologically confirmed HGG underwent O-(2-[F]-fluoroethyl)-l-tyrosine (F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented. The percentage overlap volumes, Dice and Jaccard spatial similarity coefficients (OV, DSC, JSC) were calculated.

Results: The F-FET tumor volume was significantly larger than the CE volume (median 43.5 mL (2.5-124.9) vs. 23.8 mL (1.4-80.3), p = 0.005). The OV between F-FET uptake and CE volume was low (median OV 0.59 (0.10-1)), as well as spatial similarity (median DSC 0.52 (0.07-0.78); median JSC 0.35 (0.03-0.64)). Twenty-five patients demonstrated both rCBV and CE on MRI: The median rCBV tumor volume was significantly smaller than the median CE volume (p < 0.001). The OV was high (median 0.83 (0.54-1)), but the spatial similarity was low (median DSC 0.45 (0.04-0.83); median JSC 0.29 (0.07-0.71)). Twenty-eight patients demonstrated both K2 and CE on MRI. The median K2 tumor volume was not significantly larger than the median CE volume. The OV was high (median OV 0.90 (0.61-1)), and the spatial similarity was moderate (median DSC 0.75 (0.01-0.83); median JSC 0.60 (0.11-0.89)).

Conclusion: We demonstrated that multiparametric perfusion MRI volumes (rCBV, K2) were highly correlated with CE T1 gadolinium volumes whereas F-FET PET provided complementary information, suggesting that the metabolically active tumor volume in patients with newly diagnosed untreated HGG is critically underestimated by contrast enhanced MRI. F-FET PET imaging may help to improve target volume delineation accuracy for radiotherapy planning.
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http://dx.doi.org/10.1016/j.radonc.2020.06.025DOI Listing
September 2020

Use of Baseline F-FDG PET/CT to Identify Initial Sub-Volumes Associated With Local Failure After Concomitant Chemoradiotherapy in Locally Advanced Cervical Cancer.

Front Oncol 2020 7;10:678. Epub 2020 May 7.

Radiation Oncology Department, University Hospital, Brest, France.

Locally advanced cervical cancer (CC) patients treated by chemoradiotherapy (CRT) have a significant local recurrence rate. The objective of this work was to assess the overlap between the initial high-uptake sub-volume (V1) on baseline F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scans and the metabolic relapse (V2) sites after CRT in locally advanced CC. PET/CT performed before treatment and at relapse in 21 patients diagnosed with LACC and treated with CRT were retrospectively analyzed. CT images at the time of recurrence were registered to baseline CT using the 3D Slicer TM Expert Automated Registration module. The corresponding PET images were then registered using the corresponding transform. The fuzzy locally adaptive Bayesian (FLAB) algorithm was implemented using 3 classes (one for the background and the other two for tumor) in PET1 to simultaneously define an overall tumor volume and the sub-volume V1. In PET2, FLAB was implemented using 2 classes (one for background, one for tumor), in order to define V2. Four indices were used to determine the overlap between V1 and V2 (Dice coefficients, overlap fraction, X = (V1nV2)/V1 and Y = (V1nV2)/V2). The mean (±standard deviation) follow-up was 26 ± 11 months. The measured overlaps between V1 and V2 were moderate to good according to the four metrics, with 0.62-0.81 (0.72 ± 0.05), 0.72-1.00 (0.85 ± 0.10), 0.55-1.00 (0.73 ± 0.16) and 0.50-1.00 (0.76 ± 0.12) for Dice, overlap fraction, X and Y, respectively. In our study, the overlaps between the initial high-uptake sub-volume and the recurrent metabolic volume showed moderate to good concordance. These results now need to be confirmed in a larger cohort using a more standardized patient repositioning procedure for sequential PET/CT imaging, as there is potential for RT dose escalation exploiting the pre-treatment PET high-uptake sub-volume.
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http://dx.doi.org/10.3389/fonc.2020.00678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221149PMC
May 2020

Impact of suboptimal dosimetric coverage of pretherapeutic 18F-FDG PET/CT hotspots on outcome in patients with locally advanced cervical cancer treated with chemoradiotherapy followed by brachytherapy.

Clin Transl Radiat Oncol 2020 Jul 11;23:50-59. Epub 2020 May 11.

Radiation Oncology Department, University Hospital, Brest, France.

Introduction: Areas of high uptake on pre-treatment F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT), denoted as "hotspots", have been identified as preferential sites of local relapse in locally advanced cervical cancer (LACC). The purpose of this study was to analyze the dosimetric coverage of these hotspots with high dose-rate brachytherapy (BT).

Methods: For each patient, a rigid registration of the CT from the pre-treatment PET/CT with the radiotherapy planning CT was performed using 3D Slicer, followed by a manual volume correction by translation and deformation if necessary. The fuzzy locally adaptive Bayesian (FLAB) algorithm was applied to PET images to simultaneously define an overall tumour volume and the high-uptake sub-volume V1. The inclusion of V1 in the high-risk clinical target volume (CTV HR) and its dosimetric coverage were evaluated using 3D Slicer. The average of the 3-4 BT sessions was reported.

Results: Forty-two patients with recurrence after chemoradiotherapy (CRT) for LACC were matched to 42 patients without recurrence. Mean ± standard deviation follow-up was 26 ± 11 months. In the recurrence group, V1 was not included in the CTV HR and not covered by the 85 Gy isodose in 17/42 patients (41%) (1/20 with pelvic recurrence and 16/22 with distant recurrence) and not by the 80 Gy isodose in 7/42 patients (17%) (all with distant recurrence). In the non-recurrence group, V1 was not included in CTV HR and not covered by the 85 Gy isodose in 3 patients only (7%). The hotspots coverage by the 85 Gy isodose was significantly better in patients who did not recur, but only when compared to patients with distant relapse (p < 0.0001).

Conclusion: Suboptimal dosimetric coverage of high FDG uptakes on pretherapeutic PET could be associated with an increased risk of recurrence.
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http://dx.doi.org/10.1016/j.ctro.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229342PMC
July 2020

External Validation of an MRI-Derived Radiomics Model to Predict Biochemical Recurrence after Surgery for High-Risk Prostate Cancer.

Cancers (Basel) 2020 Mar 28;12(4). Epub 2020 Mar 28.

Department of Radiation Oncology, CHRU Brest, 29200 Brest, France.

Adjuvant radiotherapy after prostatectomy was recently challenged by early salvage radiotherapy, which highlighted the need for biomarkers to improve risk stratification. Therefore, we developed an MRI ADC map-derived radiomics model to predict biochemical recurrence (BCR) and BCR-free survival (bRFS) after surgery. Our goal in this work was to externally validate this radiomics-based prediction model.

Experimental Design: A total of 195 patients with a high recurrence risk of prostate cancer (pT3-4 and/or R1 and/or Gleason's score > 7) were retrospectively included in two institutions. Patients with postoperative PSA (Prostate Specific Antigen) > 0.04 ng/mL or lymph node involvement were excluded. Radiomics features were extracted from T2 and ADC delineated tumors. A total of 107 patients from Institution 1 were used to retrain the previously published model. The retrained model was then applied to 88 patients from Institution 2 for external validation. BCR predictions were evaluated using AUC (Area Under the Curve), accuracy, and bRFS using Kaplan-Meier curves.

Results: With a median follow-up of 46.3 months, 52/195 patients experienced BCR. In the retraining cohort, the clinical prediction model (combining the number of risk factors and postoperative PSA) demonstrated moderate predictive power (accuracy of 63%). The radiomics model (ADC-based SZE predicted BCR with an accuracy of 78% and allowed for significant stratification of patients for bRFS ( < 0.0001). In Institution 2, this radiomics model remained predictive of BCR (accuracy of 0.76%) contrary to the clinical model (accuracy of 0.56%).

Conclusions: The recently developed MRI ADC map-based radiomics model was validated in terms of its predictive accuracy of BCR and bRFS after prostatectomy in an external cohort.
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http://dx.doi.org/10.3390/cancers12040814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226108PMC
March 2020
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