Publications by authors named "Olivier Pradier"

97 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283407PMC
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

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

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

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

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

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

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

Transcriptomics in cancer revealed by Positron Emission Tomography radiomics.

Sci Rep 2020 03 27;10(1):5660. Epub 2020 Mar 27.

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

Metabolic images from Positron Emission Tomography (PET) are used routinely for diagnosis, follow-up or treatment planning purposes of cancer patients. In this study we aimed at determining if radiomic features extracted from F-Fluoro Deoxy Glucose (FDG) PET images could mirror tumor transcriptomics. In this study we analyzed 45 patients with locally advanced head and neck cancer (H&N) that underwent FDG-PET scans at the time of diagnosis and transcriptome analysis using RNAs from both cancer and healthy tissues on microarrays. Association between PET radiomics and transcriptomics was carried out with the Genomica software and a functional annotation was used to associate PET radiomics, gene expression and altered biological pathways. We identified relationships between PET radiomics and genes involved in cell-cycle, disease, DNA repair, extracellular matrix organization, immune system, metabolism or signal transduction pathways, according to the Reactome classification. Our results suggest that these FDG PET radiomic features could be used to infer tissue gene expression and cellular pathway activity in H&N cancers. These observations strengthen the value of radiomics as a promising approach to personalize treatments through targeting tumor-specific molecular processes.
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http://dx.doi.org/10.1038/s41598-020-62414-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101432PMC
March 2020

Pretreatment F-FDG PET/CT Radiomics Predict Local Recurrence in Patients Treated with Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: A Multicentric Study.

J Nucl Med 2020 06 15;61(6):814-820. Epub 2019 Nov 15.

Radiation Oncology Department, University Hospital, Brest, France.

The aim of this retrospective multicentric study was to develop and evaluate a prognostic F-FDG PET/CT radiomic signature in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy (SBRT). Patients from 3 different centers ( = 27, 29, and 8) were pooled to constitute the training set, whereas the patients from a fourth center ( = 23) were used as the testing set. The primary endpoint was local control. The primary tumor was semiautomatically delineated in the PET images using the fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. In total, 184 Image Biomarkers Standardization Initiative-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the 4 institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model, and models were built by combining independent prognostic factors. Median follow-up was 21.1 mo (range, 1.7-63.4 mo) and 25.5 mo (range, 7.7-57.8 mo) in training and testing sets, respectively. In univariate analysis, none of the clinical variables, 2 PET features, and 2 CT features were significantly predictive of local control. The best predictive models in the training set were obtained by combining one feature from PET (Information Correlation 2) and one feature from CT (flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (Information Correlation 2 and strength) reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio ( < 0.001). The latter model obtained an accuracy of 0.91 (sensitivity, 100%; specificity, 81%), with a hazard ratio undefined ( = 0.023) in the testing set; however, other models relying on CT radiomic features only or the combination of PET and CT features failed to validate in the testing set. We showed that 2 radiomic features derived from F-FDG PET were independently associated with local control in patients with non-small cell lung cancer undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision making.
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http://dx.doi.org/10.2967/jnumed.119.228106DOI Listing
June 2020

MRI-derived radiomics: methodology and clinical applications in the field of pelvic oncology.

Br J Radiol 2019 Dec 10;92(1104):20190105. Epub 2019 Oct 10.

LaTIM, INSERM, UMR 1101, University of Brest, ISBAM, UBO, UBL, Brest, France.

Personalized medicine aims at offering optimized treatment options and improved survival for cancer patients based on individual variability. The success of precision medicine depends on robust biomarkers. Recently, the requirement for improved non-biologic biomarkers that reflect tumor biology has emerged and there has been a growing interest in the automatic extraction of quantitative features from medical images, denoted as radiomics. Radiomics as a methodological approach can be applied to any image and most studies have focused on PET, CT, ultrasound, and MRI. Here, we aim to present an overview of the radiomics workflow as well as the major challenges with special emphasis on the use of multiparametric MRI datasets. We then reviewed recent studies on radiomics in the field of pelvic oncology including prostate, cervical, and colorectal cancer.
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http://dx.doi.org/10.1259/bjr.20190105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913356PMC
December 2019

Radiotherapy mucositis in head and neck cancer: prevention by low-energy surface laser.

BMJ Support Palliat Care 2019 Sep 16. Epub 2019 Sep 16.

Radiation Oncology Department, CHU Brest, Brest, France.

Background: Modern radiotherapy (RT) planning techniques and the use of oral supportive care have reduced the occurrence of acute radiation-induced toxicities. Oral mucositis remains a major concern in patients with head and neck cancer as it can compromise treatment compliance and outcome.

Objective: To report the rate of mucositis with the preventive use of surface low-level laser therapy in patients with head and neck cancer.

Methods: Forty patients treated with definitive (n=27) or adjuvant (n=13) RT using volumetric arc therapy between August 2014 and October 2015 for squamous cell carcinoma of the head and neck were included. All patients were treated using photobiomodulation using surface low-level laser therapy (Heltschl kind FL 3500, 350 mW), 3 times a week during the whole treatment course. The grade of mucositis was obtained from week 1 to week 7 and at 1 month.

Results: The median RT dose was 70 Gy (64-70). Concomitant chemotherapy was administered in 29 patients. According to the Common Terminology Criteria for Adverse Events (CTCAE) v. 3, grade 0, 1, 2 and 3 mucositis was observed in 9 (22.5%), 9 (22.5%), 16 (40%) and 6 (15%) patients at week 7, and 32 (80%), 2 (5%), 3 (7.5%) and 3 (7.5%) patients at 1 month following treatment. No grade 4 occurred. Median average and maximum dose to the oral mucosa was 42 Gy (12.9-66.3) and 66.6 Gy (39-76), respectively.

Conclusion: Despite a substantial dose to the oral mucosa, the rate of acute radiation-induced mucositis of grade ≥3 remains low in patients receiving extraoral low-energy laser during RT.
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http://dx.doi.org/10.1136/bmjspcare-2019-001851DOI Listing
September 2019

MRI-Derived Radiomics to Guide Post-operative Management for High-Risk Prostate Cancer.

Front Oncol 2019 27;9:807. Epub 2019 Aug 27.

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

Prostatectomy is one of the main therapeutic options for prostate cancer (PCa). Studies proved the benefit of adjuvant radiotherapy (aRT) on clinical outcomes, with more toxicities when compared to salvage radiotherapy. A better assessment of the likelihood of biochemical recurrence (BCR) would rationalize performing aRT. Our goal was to assess the prognostic value of MRI-derived radiomics on BCR for PCa with high recurrence risk. We retrospectively selected patients with a high recurrence risk (T3a/b or T4 and/or R1 and/or Gleason score>7) and excluded patients with a post-operative PSA > 0.04 ng/mL or a lymph-node involvement. We extracted IBSI-compliant radiomic features (shape and first order intensity metrics, as well as second and third order textural features) from tumors delineated in T2 and ADC sequences. After random division (training and testing sets) and machine learning based feature reduction, a univariate and multivariate Cox regression analysis was performed to identify independent factors. The correlation with BCR was assessed using AUC and prediction of biochemical relapse free survival (bRFS) with a Kaplan-Meier analysis. One hundred seven patients were included. With a median follow-up of 52.0 months, 17 experienced BCR. In the training set, no clinical feature was correlated with BCR. One feature from ADC (SZE) outperformed with an AUC of 0.79 and a HR 17.9 ( = 0.0001). Lower values of SZE are associated with more heterogeneous tumors. In the testing set, this feature remained predictive of BCR and bRFS (AUC 0.76, = 0.0236). One radiomic feature was predictive of BCR and bRFS after prostatectomy helping to guide post-operative management.
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http://dx.doi.org/10.3389/fonc.2019.00807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719613PMC
August 2019

Prospective four years of evaluation of erectile function after low-dose-rate prostate brachytherapy using baseline IIEF-5 > 16.

J Contemp Brachytherapy 2019 Jun 28;11(3):195-200. Epub 2019 Jun 28.

CHU Brest, Service Urologie, Brest, France.

Purpose: Prostate brachytherapy (BT) is a validated treatment for localized prostate cancer (CaP) and an attractive therapy option for patients seeking to preserve erectile function (EF). The aim of this paper is to prospectively assess EF evolution during 4 years after BT.

Material And Methods: Between February 2007 and July 2012, 179 patients underwent an exclusive Iodine-125 BT, for low-intermediate favorable risk CaP of whom, 102 had an initial international index of erectile function 5 score (IIEF-5) > 16 and were included in the study. Of those, 12.7% received neo-adjuvant hormonotherapy (HT) to decrease the prostate volume. Post-BT intake of phosphodiesterase inhibitors (PDE5i) was not an exclusion criterion. Erectile function was prospectively assessed using a validated questionnaire IIEF-5 before treatment and annually for 4 years.

Results: At 1-year follow-up, 54% of patients preserved an IIEF-5 > 16 and only 8% suffered from severe ED. During the next 3 years, the results were not statistically different. The mean IIEF-5 lost 4 points during the first year, 17 vs. 21, and remained stable during the following 3 years. We did not find any significant differences in the proportion of patients treated by PDE5i (18-20%). As for patients with a normal preoperative IIEF-5 (> 21) ( = 52), 35-42% preserved a normal EF and 71-77% maintained an IIEF-5 > 16, including 13-19% of patients who needed PDE5i. Those results were stable for over 4 years.

Conclusions: During the first 4 years after BT, more than half of patients maintained an IIEF-5 > 16, and EF results remained stable. Severe erectile dysfunction (ED) was very rare.
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http://dx.doi.org/10.5114/jcb.2019.85793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701385PMC
June 2019

Dose to the penile bulb and individual patient anatomy are predictive of erectile dysfunction in men treated with I low dose rate brachytherapy for localized prostate cancer.

Acta Oncol 2019 Jul 14;58(7):1029-1035. Epub 2019 Feb 14.

a Radiation Oncology Department , CHU , Brest , France.

To evaluate the occurrence of erectile dysfunction at 3 years (3yED) after prostate brachytherapy (BT) and to predict 3yED after treatment based on patients and treatments characteristics. From September 2007 to July 2015, 117 men with mild or no ED [International Index of Erectile Function (IIEF-5) > 16] underwent Iodine real-time ultrasound-guided low-dose rate BT to a total dose of 160 Gy for low-risk or favorable intermediate-risk prostate adenocarcinoma, and were followed prospectively during 3 years. Median age was 63 years (51-79). The post-implant dosimetric parameters on the postoperative computer tomography were derived from the dose-volume histogram of the prostate and the penile bulb (PB), crura, neurovascular bundles (NVBs) and internal pudendal arteries (IPAs). Potential clinical confounding factors were collected. Additionally, anatomical indexes reflecting the prostate anatomical location within the pelvis were studied. These variables were compared between patients with and without 3yED. 3yED was defined as an IIEF-5 score change to the lower category between baseline, with or without medication. The 3yED rate was 59% (62% maintained an IIEF-5 > 16). On multivariate analysis, prostate D90% ( > .5) and pretreatment characteristics including age ( > .5), pre-implant potency ( > .5), diabetes ( = .08) and high cardiovascular risk rates ( = .1) did not influence the occurrence of 3yED. Only the PB dose especially the D10% > 51 Gy was associated with 3yED ( = .005). Conversely, dose to the crura, IPAs or NVBs did not seem to impact the erectile function. The prostate position, especially the apex location varied significantly between potent and impotent patients and 3yED was significantly associated with close position of the prostate apex to PB ( = .008). The most predictive factor of 3yED was the dose to the PB. This may be explained by variation in individual patients' anatomy and this could allow for the development of better strategies to prevent ED.
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http://dx.doi.org/10.1080/0284186X.2019.1574981DOI Listing
July 2019

External validation of a combined PET and MRI radiomics model for prediction of recurrence in cervical cancer patients treated with chemoradiotherapy.

Eur J Nucl Med Mol Imaging 2019 Apr 7;46(4):864-877. Epub 2018 Dec 7.

Radiation Oncology Department, University Hospital, Brest, France.

Purpose: The aim of this study was to validate previously developed radiomics models relying on just two radiomics features from F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) images for prediction of disease free survival (DFS) and locoregional control (LRC) in locally advanced cervical cancer (LACC).

Methods: Patients with LACC receiving chemoradiotherapy were enrolled in two French and one Canadian center. Pre-treatment imaging was performed for each patient. Multicentric harmonization of the two radiomics features was performed with the ComBat method. The models for DFS (using the feature from apparent diffusion coefficient (ADC) MRI) and LRC (adding one PET feature to the DFS model) were tuned using one of the French cohorts (n = 112) and applied to the other French (n = 50) and the Canadian (n = 28) external validation cohorts.

Results: The DFS model reached an accuracy of 90% (95% CI [79-98%]) (sensitivity 92-93%, specificity 87-89%) in both the French and the Canadian cohorts. The LRC model reached an accuracy of 98% (95% CI [90-99%]) (sensitivity 86%, specificity 100%) in the French cohort and 96% (95% CI [80-99%]) (sensitivity 83%, specificity 100%) in the Canadian cohort. Accuracy was significantly lower without ComBat harmonization (82-85% and 71-86% for DFS and LRC, respectively). The best prediction using standard clinical variables was 56-60% only.

Conclusions: The previously developed PET/MRI radiomics predictive models were successfully validated in two independent external cohorts. A proposed flowchart for improved management of patients based on these models should now be confirmed in future larger prospective studies.
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http://dx.doi.org/10.1007/s00259-018-4231-9DOI Listing
April 2019

Prostate Volume Segmentation in TRUS Using Hybrid Edge-Bhattacharyya Active Surfaces.

IEEE Trans Biomed Eng 2019 04 14;66(4):920-933. Epub 2018 Aug 14.

Objective: We present a new hybrid edge and region-based parametric deformable model, or active surface, for prostate volume segmentation in transrectal ultrasound (TRUS) images.

Methods: Our contribution is threefold. First, we develop a new edge detector derived from the radial bas-relief approach, allowing for better scalar prostate edge detection in low contrast configurations. Second, we combine an edge-based force derived from the proposed edge detector with a new region-based force driven by the Bhattacharyya gradient flow and adapted to the case of parametric active surfaces. Finally, we develop a quasi-automatic initialization technique for deformable models by analyzing the profiles of the proposed edge detector response radially to obtain initial landmark points toward which an initial surface model is warped.

Results: We validate our method on a set of 36 TRUS images for which manual delineations were performed by two expert radiation oncologists, using a wide variety of quantitative metrics. The proposed hybrid model achieved state-of-the-art segmentation accuracy.

Conclusion: Results demonstrate the interest of the proposed hybrid framework for accurate prostate volume segmentation.

Significance: This paper presents a modular framework for accurate prostate volume segmentation in TRUS, broadening the range of available strategies to tackle this open problem.
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http://dx.doi.org/10.1109/TBME.2018.2865428DOI Listing
April 2019

Inhomogeneous tumor dose distribution provides better local control than homogeneous distribution in stereotactic radiotherapy for brain metastases.

Radiother Oncol 2019 01 17;130:132-138. Epub 2018 Jul 17.

Radiation Oncology Department, University Hospital, Brest, France; LaTIM, INSERM, UMR 1101, University of Brest, ISBAM, UBO, UBL, Brest, France.

Introduction: The aim of this study was to analyze the impact of inhomogeneous versus homogeneous dose distribution on local control (LC) and radionecrosis (RN) in patients treated with fractionated stereotactic radiotherapy (SRT) for newly-diagnosed brain metastases (BM).

Patients And Methods: From 2014 to 2017, 134 patients (median age 61 years) underwent SRT for BM (n = 114 with ≤2, n = 20 with 3-6 BM) at our institution. Treatment was delivered using volumetric modulated arc therapy on a linear accelerator. Ninety-one consecutive patients (BM = 136) were irradiated at a dose of 21-23.1 Gy in 3 fractions delivered homogeneously (99% of the dose had to cover 99% of the planning target volume (PTV)) (group 1) whereas the following 43 patients (BM = 72) received an inhomogeneous dose of 10 or 11 Gy prescribed to the isocenter with the 70% isodose line covering the PTV (group 2). Variables analyzed included dose distribution, age, gender, histology, diagnosis-specific Graded Prognostic Assessment score, number of brain metastases, presence of extracranial metastases, and tumor volumes.

Results: After a median follow-up of 12.4 months (range, 1.4-33.1), the 1-year LC and RN rate were 78% and 7.5% in group 1 and 93% and 0% in group 2, respectively (p = 0.005). In multivariate analysis, improved LC was significantly correlated with SRT dose distribution (p = 0.009) and tumor volume (p = 0.03). The number of metastases (p = 0.03) and SRT dose distribution (p = 0.04) were both associated with increased risk of RN.

Conclusion: SRT delivered with inhomogeneous dose distribution resulted in better LC and a lower risk of RN compared to homogeneous distribution.
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http://dx.doi.org/10.1016/j.radonc.2018.06.039DOI Listing
January 2019

Evaluation of the "Quadrella" at 3 years: New index to assess functional and oncological performance specific to prostate brachytherapy.

Brachytherapy 2018 Sep - Oct;17(5):782-787. Epub 2018 Jun 21.

CHU Brest, Service Urologie, Brest, France; Université de Brest, Faculté de Médecine et des Sciences de la Santé, Brest, France; Université de Bretagne Occidentale, Bretagne, France; CeRePP, Paris, France.

Purpose: "Quadrella" index has been recently developed to assess oncological and functional outcomes after prostate brachytherapy (PB). We aimed to evaluate this index at 1, 2, and 3 years, using validated questionnaires, assessed prospectively.

Methods And Materials: From 08/2007 to 01/2013, 193 patients underwent Iodine PB for low-risk or favorable intermediate-risk prostate adenocarcinoma. Inclusion criteria were as follows: no incontinence (International Continence Society Index initial score = 0) and good erectile function (International Index of Erectile Function-5 items: >16). One hundred patients were included (mean age: 64 y). Postimplantation intake of phosphodiesterase inhibitors was not considered as failure. The "Quadrella" index was defined by the absence of biochemical recurrence (Phoenix criteria), significant erectile dysfunction (ED) (Index of Erectile Function-5 items: >16), urinary toxicity (UT) (International Prostate Score Symptom [IPSS] <15 or IPSS> 15 with ΔIPSS <5), and rectal toxicity (RT) (Radiation Therapy Oncology Group = 0).

Results: At 12 months, 90 patients were evaluable: 42/90 (46.7%) achieved Quadrella. The main criteria for failure were as follows: ED in 77.1% (37/48) of cases, RT in 20.8% (10/48) of cases, and UT in 12.5% (9/57) of cases. At 24 and 36 months, 59.3% (48/81) and 61.1% (44/72) of patients achieved Quadrella, respectively. The main cause of failure was ED in 69.7% (23/33) and 85.7% (24/28) of cases, while RT was involved in 21.2% (7/33) and in 3.6% (1/28) of cases, and UT in 9.1% (3/33) and 3.6% (1/28) of cases. Only one case of biochemical recurrence was observed (i.e., 1/28 = 3.6% at 3 y).

Conclusions: The Quadrella can be used at 1, 2, and 3 years after PB. It allows to take into account the urinary and RT specific to PB. ED was the main cause of failure. This index will be useful to assess midterm and long-term results.
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http://dx.doi.org/10.1016/j.brachy.2018.05.007DOI Listing
March 2019

Prediction of outcome using pretreatment F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy.

Eur J Nucl Med Mol Imaging 2018 05 9;45(5):768-786. Epub 2017 Dec 9.

Radiation Oncology Department, University Hospital, Brest, France.

Purpose: The aim of this study is to determine if radiomics features from fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) images could contribute to prognoses in cervical cancer.

Methods: One hundred and two patients (69 for training and 33 for testing) with locally advanced cervical cancer (LACC) receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this study. F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET images and with 3D Slicer™ in the MRI images. Radiomics features (intensity, shape, and texture) were extracted and their prognostic value was compared with clinical parameters for recurrence-free and locoregional control.

Results: In the training cohort, median follow-up was 3.0 years (range, 0.43-6.56 years) and relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I-II vs. III-IV) and metabolic response (complete vs. non-complete) were probably associated with outcome without reaching statistical significance, contrary to several radiomics features from both PET and MRI sequences. Multivariate analysis in training test identified Grey Level Non Uniformity in PET and Entropy in ADC maps from DWI MRI as independent prognostic factors. These had significantly higher prognostic power than clinical parameters, as evaluated in the testing cohort with accuracy of 94% for predicting recurrence and 100% for predicting lack of loco-regional control (versus ~50-60% for clinical parameters).

Conclusions: In LACC treated with CRT, radiomics features such as EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively, are independent predictors of recurrence and loco-regional control with significantly higher prognostic power than usual clinical parameters. Further research is warranted for their validation, which may justify more aggressive treatment in patients identified with high probability of recurrence.
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http://dx.doi.org/10.1007/s00259-017-3898-7DOI Listing
May 2018

Target definition in salvage postoperative radiotherapy for prostate cancer: 18F-fluorocholine PET/CT assessment of local recurrence.

Acta Oncol 2018 Mar 6;57(3):375-381. Epub 2017 Oct 6.

a Radiation Oncology Department , University Hospital Morvan , Brest , France.

Purpose: Inadequate clinical target volume (CTV) definition is likely to be a major contributing factor to local recurrence (LR) rate after radiotherapy. Our aims were to identify sites of prostate cancer LR in biochemical recurrence post-prostatectomy using F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) and to compare different CTV-delineation guidelines in a cohort of postoperative patients.

Material And Methods: Thirty-six patients presenting with LR within the prostatic bed on 18F-FCH PET/CT between 10/2011 and 06/2016 were included in this retrospective study. Median PSA at the time of 18F-FCH PET/CT was 2.7 ng/mL (0.8-9.4) and median PSA doubling time was 11 months (3-28). For each patient, the CTV, CTV and CTV following the corresponding guidelines were outlined and compared. Forty-one LR were delineated using a gradient-based method and the percentage of FCH uptake included in each CTV was evaluated.

Results: The anastomosis was the most common recurrence site (52.8%), followed by the retrovesical region (31.7%) and the bladder neck (7%). The median SUV max value was 4.8 (2.3-16.1). The percentage of LR entirely included in the CTV was not significantly different from that included in the CTV (84% versus 83%, p = .5). Significantly more recurrences were included in the CTV volume compared to the CTV (84% versus 68%, p=.006), due to a better coverage of the bladder neck and retrovesical regions. Six out of 10 relapses occurring in the posterior region of the anastomosis were not covered by any of the CTVs.

Conclusions: In our study, the CTV and CTV ensured the best coverage of LR seen on 18F-FCH PET/CT. When outlining the prostatic fossa, greater coverage of the posterior vesico-urethral region may allow better coverage of potential microscopic disease.
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http://dx.doi.org/10.1080/0284186X.2017.1385843DOI Listing
March 2018

Cosmetic Outcome and Chronic Breast Toxicity After Intraoperative Radiation Therapy (IORT) as a Single Modality or as a Boost Using the Intrabeam Device: A Prospective Study.

Ann Surg Oncol 2017 Sep 12;24(9):2547-2555. Epub 2017 Jun 12.

Radiation Oncology Department, University Hospital, Brest, France.

Purpose: We aim to report our results in terms of chronic toxicities and cosmetic outcomes after intraoperative radiotherapy (IORT) using kV X-rays in women treated for early breast cancer at our institution.

Methods: Patients with early breast carcinoma were recruited between April 2011 and November 2014. After breast-conserving surgery, patients were treated with IORT using the Intrabeam device. IORT was completed by whole-breast radiotherapy (WBRT) at a dose of 46-50.4 Gy in 23-28 fractions in case of adverse pathologic criteria on the final specimen examination. Skin toxicity was graded using the Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic (LENT-SOMA) scale every 6 months, and cosmetic outcomes were evaluated at 36 months by patient self-evaluation and by two radiation oncologists, on a 1-10 scale.

Results: Forty-one women received IORT only and 30 patients received IORT followed by WBRT (IORT + WBRT group). After a median follow-up of 38.9 months, no locoregional or distant recurrence occurred. After IORT only, 2.4% of grade 2 or higher breast fibrosis, and no other grade 2 or higher disease, was observed. In the IORT + WBRT group, grade 2 or higher fibrosis and grade 2 or higher breast retraction were observed in 43.3 and 23.3% of patients, respectively. Objective cosmetic outcomes were very good and significantly better in the IORT-only group compared with the IORT + WBRT group (8.87 vs. 6.96) (p < 0.001).

Conclusion: IORT using the Intrabeam is well-tolerated, with very little chronic toxicity and good cosmetic outcome. However, a high rate of grade 2 or higher chronic breast toxicity was observed when IORT had to be completed by WBRT.
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http://dx.doi.org/10.1245/s10434-017-5920-5DOI Listing
September 2017

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab.

Target Oncol 2017 08;12(4):505-512

Radiation Oncology Department, University Hospital, CHRU, Brest, France.

Background: Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity.

Objective: We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck.

Patients And Methods: Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%).

Results: Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47-75) compared to 51 days (47-65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3-107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively).

Conclusions: Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.
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http://dx.doi.org/10.1007/s11523-017-0499-0DOI Listing
August 2017
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