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Purpose Interstitial brachytherapy is indicated as part of a conservative strategy for children with bladder and/or prostate rhabdomyosarcoma (RMS), providing high local control probability with acceptable functional results. Vaginal and/or rectal complications were however reported, due to the close proximity to the implanted volume. We investigated the dosimetric impact of a vaginal spacer in terms of rectal and vaginal doses. Methods and patients Medical records of 12 consecutive female patients with bladder neck RMS, median age 32 months (range: 1.3–6 years), were reviewed. Five patients were treated prior to 2017 without a vaginal spacer and seven patients treated after 2017 had their brachytherapy delivered with a vaginal spacer placed at time of implant. Results Minimal doses delivered to the most exposed 2 cm3, 1 cm3, and 0.5 cm3 of the rectum were all statistically significantly lower among patients treated with a vaginal spacer, as compared to those treated without a spacer. Median rectal D2cm3 was 22 GyEQD2 versus 38 GyEQD2 (P = 0.02), D1cm3 was 29 GyEQD2 versus 51 GyEQD2 (P = 0.013), and D0.5cm3 was 32 GyEQD2 versus 61 GyEQD2 (P = 0.017), with and without the vaginal spacer, respectively. The posterior vaginal wall D0.5cm3 dose was also significantly decreased, with median D0.5cm3 of 92 GyEQD2 versus 54 GyEQD2 (P Conclusions The use of vaginal spacers in brachytherapy of female pediatric patients with bladder neck RMS resulted in significantly decreased doses to the rectum and the posterior vaginal wall. Though the clinical impact of such dose reduction remains undemonstrated, routine utilization of a vaginal spacer could be a method to decrease long-term morbidity in these patients.

Objective: To compare the performance of conventional and machinelearning approaches for the diagnosis of tumor recurrence after radiation therapy of brain metastases. Methods: 184 symptomatic patients with solitary metastatic brain lesions treated with radiation therapy were enrolled in a monocentric retrospective study from June 2013 to May 2018. The diagnosis was tumor recurrence (n=71) and radiation necrosis (n=113) using as reference standard expert-consensus derived from pathology and long-term follow-up. 37 potential predictors were recorded at the time of radiological progression (7-15 months after therapy): 6 clinical features and 31 imaging features including 20 radiomics features derived from standard of care 3D T1-gadolinium sequences. We compared four approaches (A, B, C, D): expert report using MRI sequences without (A) and with delayedcontrast MRI (TRAM) sequences (B), 11 non-Radiomics imaging features alone (C) and a signature combining variables selected using unsupervised machinelearning algorithms (D), training:validation sets: n=144:40 pts). Results: Overall (n=184), approaches B and C (using TRAM sequence alone) reached comparable performances with respective AUCs [95% CI] of 78.7% [72.3%-85.1%] and 76.8% [70.3%-83.3%]. Both significantly outperformed approach A with AUC [95% CI] of 57.4% [50.7%-64.1%] (DeLong’s test, p-value=10-7). In the validation set (n=40), the signature reached an AUC [95% CI] of 92% [87%-97%]. Conclusion: A quantitative analysis of TRAM sequence seems the best approach for the diagnosis of recurrent tumor after radiation therapy. It is parsimonious, objective and less time-consuming than interpreting all sequences. A signature derived from the analysis of standard of care 3D T1- gadolinium sequence showed promising results that warrant prospective validation.

Resume En permettant de delivrer des doses elevees de facon tres conformationnelle, la curietherapie demeure l’une des techniques de radiotherapie offrant l’index therapeutique le plus interessant. Pourtant, un declin de son utilisation est decrit. Seulement 55 a 88 % des patientes presentant un cancer localement avance du col de l’uterus beneficieraient d’une curietherapie utero-vaginale, bien qu’elle apporte un benefice en termes de survie sans progression et de survie globale. Un declin de l’usage de la curietherapie exclusive a bas debit de dose est egalement decrit dans le cadre des cancers de la prostate de faible risque ou de risque intermediaire favorable. Plusieurs facteurs pourraient expliquer ce defaut d’usage. Le nombre d’oncologues-radiotherapeutes maitrisant les techniques de curietherapie semble insuffisant, au regard des besoins. L’expertise des praticiens necessite un nombre important d’applications, pouvant etre superieur au recrutement de certains centres. Ainsi, la formation initiale, puis la formation continue des praticiens a cette technique ne peuvent etre garanties dans l’ensemble des etablissements. Le developpement de techniques modernes de radiotherapie externe semblerait avoir accelere ce desinteret pour la curietherapie, en offrant un substitut dont la mise en place est plus simple, et les retombees plus lucratives. Pourtant, l’incidence croissante des indications de curietherapie, leurs niveaux de preuve et leurs rapports benefice-risque grandissants, imposent d’affronter les defis de formation aux techniques de curietherapie et d’organisation de son offre sur le territoire.

Radiomics extracts high-throughput quantitative data from medical images to contribute to precision medicine. Radiomic shape features have been shown to correlate with patient outcomes. However, how radiomic shape features vary in function of tumor complexity and tumor volume, as well as with method used for meshing and voxel resampling, remains unknown. The aims of this study are to create tumor models with varying degrees of complexity, or spiculatedness, and evaluate their relationship with quantitatively extracted shape features. Twenty-eight tumor models were mathematically created using spherical harmonics with the spiculatedness degree d being increased by increments of 3 (d = 11 to d = 92). Models were 3D printed with identical bases of 5 cm, imaged with a CT scanner with two different slice thicknesses, and semi-automatically delineated. Resampling of the resulting masks on a 1 × 1 × 1 mm3 grid was performed, and the voxel size of each model was then calculated to eliminate volume differences. Four MATLAB-based algorithms (isosurface (M1), isosurface filter (M2), isosurface remeshing (M3), and boundary (M4)) were used to extract nine 3D features (Volume, Surface area, Surface-to-volume, Compactness1, Compactness2, Compactness3, Spherical Disproportion, Sphericity and Fractional Concavity). To quantify the impact of 3D printing, acquisition, segmentation and meshing, features were computed directly from the stereolithography (STL) file format that was used for 3D printing, and compared to those computed. Changes in feature values between 0.6 and 2 mm slice acquisitions were also compared. Spearman’s rank-order correlation coefficients were computed to determine the relationship of each shape feature with spiculatedness for each of the four meshing algorithms. Percent changes were calculated between shape features extracted from the original and resampled contoured images to evaluate the influence of spatial resampling. Finally, the percent change in shape features when the volume was changed from 25% to 150% of their original volume was quantified for three distinct tumor models and compared to the percent change observed when modifying the spiculatedness of the model from d = 11 to d = 92. Values extracted using isosurface remeshing method are the closest to the STL reference ones, with mean differences less than 10.8% (Compactness2) for all features. Seven of the eight features had strong significant correlations with tumor model complexity irrespective of the meshing algorithm (r > 0.98, p < 10-4), with fractional concavity having the lowest correlation coefficient (r = 0.83, p < 10-4, M2). Comparisons of features extracted from the 0.6 and 2 mm slice thicknesses showed that mean differences were from 2.1% (Compactness3) to 12.7% (Compactness2) for the isosurface remeshing method. Resampling on a 1 × 1 × 1 mm3 grid resulted in between 1.3% (Compactness3) to 9.5% (Fractional Concavity) mean changes in feature values. Compactness2, Compactness3, Spherical Disproportion, Sphericity and Fractional Concavity were the features least affected by volume changes. Compactness1 had a 90.4% change with volume, which was greater than the change between the least and most spiculated models. This is the first methodological study that directly demonstrates the relationship of tumor spiculatedness with radiomic shape features, that also produced 3D tumor models, which may serve as reference phantoms for future radiomic studies. Surface Area, Surface-to-volume, and Spherical Disproportion had direct relationships with spiculatedness while the three formulas for Compactness, Sphericity and Fractional Concavity had inverse relationships. The features Compactness2, Compactness3, Spherical Disproportion, and Sphericity should be prioritized as these have minimal variations with volume changes, slice thickness and resampling.

International audience; Anti-angiogenic therapy with bevacizumab is a widely used therapeutic option for recurrent glioblastoma (GBM). Nevertheless, the therapeutic response remains highly heterogeneous among GBM patients with discordant outcomes. Recent data have shown that radiomics, an advanced recent imaging analysis method, can help to predict both prognosis and therapy in a multitude of solid tumours. The objective of this study was to identify novel biomarkers, extracted from MRI and clinical data, which could predict overall survival (OS) and progression-free survival (PFS) in GBM patients treated with bevacizumab using machine-learning algorithms. In a cohort of 194 recurrent GBM patients (age range 18–80), radiomics data from pre-treatment T2 FLAIR and gadolinium-injected MRI images along with clinical features were analysed. Binary classification models for OS at 9, 12, and 15 months were evaluated. Our classification models successfully stratified the OS. The AUCs were equal to 0.78, 0.85, and 0.76 on the test sets (0.79, 0.82, and 0.87 on the training sets) for the 9-, 12-, and 15-month endpoints, respectively. Regressions yielded a C-index of 0.64 (0.74) for OS and 0.57 (0.69) for PFS. These results suggest that radiomics could assist in the elaboration of a predictive model for treatment selection in recurrent GBM patients.

Objective This study assessed outcomes of inoperable endometrial cancer (IEC) patients treated with definitive external beam radiation therapy (EBRT) followed by a 3D image-guided brachytherapy boost. Methods All consecutive patients treated with EBRT followed by 3D image-guided brachytherapy for IEC were retrospectively included. EBRT delivered a dose of 45Gy. Then, patients had an uterovaginal brachytherapy guided by 3D imaging. Clinical target volume (CTVBT) included the whole uterus and the initial disease extent. Gross tumour volume (GTVres) included the residual disease at time of brachytherapy. Results Twenty-seven patients were identified. Causes of inoperability were comorbidities (37%) or tumour loco regional extent (63%). Including EBRT and brachytherapy, the median D90 (minimal dose delivered to 90% of the volume) was 60.7 GyEQD2 (IQR = 56.4–64.2) for the CTVBT, and was 73.6 GyEQD2 (IQR = 64.1–83.7) for the GTVres. The median overall treatment time was 50 days (IQR = 46–54). The mean follow-up was 36.5 months (SD = 30.2). The cumulative incidence of local, pelvic and distant failures was 19% (n = 5), 7% (n = 2) and 26% (n = 7), respectively. Five-year overall survival was 63% (95% CI = 43–91). Late urinary and gastro intestinal toxicities ≥ grade 2 were reported in four (15%) and two patients (7%) respectively. No vaginal toxicity ≥ grade 2 was reported. Conclusions EBRT followed by intracavitary brachytherapy seems to be an effective option for IEC. The implementation of 3D concepts at time of brachytherapy may contribute to high local control probability and low toxicity profile. Large scale retrospective or prospective data are needed to confirm these early data.

// Roger Sun 1, 2 , Ines Koubaa 3 , Elaine Johanna Limkin 1, 2 , Isabelle Dumas 4 , Enrica Bentivegna 5 , Eduardo Castanon 6 , Sebastien Gouy 5 , Cynthia Baratiny 1 , Fyo Monnot 1 , Pierre Maroun 1 , Samy Ammari 3 , Elise Zareski 3 , Corinne Balleyguier 3 , Eric Deutsch 1, 2, 7 , Philippe Morice 5, 7 , Christine Haie-Meder 1 and Cyrus Chargari 1, 2, 8, 9 1 Department of Radiotherapy, Gustave Roussy Cancer Campus, Villejuif, France 2 INSERM U1030 Molecular Radiotherapy, Gustave Roussy Cancer Campus, Villejuif, France 3 Department of Radiology, Gustave Roussy Cancer Campus, Villejuif, France 4 Department of Medical Physics, Gustave Roussy Cancer Campus, Villejuif, France 5 Department of Surgery, Gustave Roussy Cancer Campus, Villejuif, France 6 Department of Drug development, Gustave Roussy Cancer Campus, Villejuif, France 7 Universite Paris Sud, Universite Paris-Saclay, Le Kremlin-Bicetre, France 8 Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France 9 French Military Health Service Academy, Ecole du Val-de-Grace, Paris, France Correspondence to: Cyrus Chargari, email: cyrus.chargari@gustaveroussy.fr Keywords: cervical cancer; locally advanced; brachytherapy; bladder invasion; vesicovaginal fistula Received: August 29, 2017 Accepted: January 01, 2018 Published: January 18, 2018 ABSTRACT Objective: We report outcomes of cervical cancer patients with bladder invasion (CCBI) at diagnosis, with focus on the incidence and predictive factors of vesicovaginal fistula (VVF). Results: Seventy-one patients were identified. Twenty-one (30%) had para-aortic nodal involvement. Eight had VVF at diagnosis. With a mean follow-up time of 34.2 months (range: 1.9 months–14.8 years), among 63 patients without VVF at diagnosis, 15 (24%) developed VVF. A VVF occurred in 19% of patients without local relapses (9/48) and 40% of patients with local relapse (6/15). Two-year overall survival (OS), disease-free survival (DFS) and local control rates were 56.4% (95% CI: 44.1–67.9%), 39.1% (95% CI: 28.1–51.4%) and 63.8% (95% CI: 50.4–75.4%), respectively. Para-aortic nodes were associated with poorer OS (adjusted HR = 3.78, P -value = 0.001). In multivariate analysis, anterior tumor necrosis on baseline MRI was associated with VVF formation (63% vs 0% at 1 year, adjusted-HR = 34.13, 95% CI: 4.07–286, P -value = 0.001), as well as the height of the bladder wall involvement of >26 mm (adjusted-HR = 5.08, 95% CI: 1.38–18.64, P -value = 0.014). Conclusions: A curative intent strategy including brachytherapy is feasible in patients with CCBI, with VVF occurrence in 24% of the patients. MRI patterns help predicting VVF occurrence. Methods: Patients with locally advanced CCBI treated with (chemo)radiation ± brachytherapy in our institute from 1989 to 2015 were analyzed. Reviews of baseline magnetic resonance imaging (MRI) scans were carried out blind to clinical data, retrieving potential parameters correlated to VVF formation (including necrosis and tumor volume).

The arrival of immunotherapy has profoundly changed the management of multiple cancers, obtaining unexpected tumour responses. However, until now, the majority of patients do not respond to these new treatments. The identification of biomarkers to determine precociously responding patients is a major challenge. Computational medical imaging (also known as radiomics) is a promising and rapidly growing discipline. This new approach consists in the analysis of high-dimensional data extracted from medical imaging, to further describe tumour phenotypes. This approach has the advantages of being non-invasive, capable of evaluating the tumour and its microenvironment in their entirety, thus characterising spatial heterogeneity, and being easily repeatable over time. The end goal of radiomics is to determine imaging biomarkers as decision support tools for clinical practice and to facilitate better understanding of cancer biology, allowing the assessment of the changes throughout the evolution of the disease and the therapeutic sequence. This review will develop the process of computational imaging analysis and present its potential in immuno-oncology.

INTRODUCTION: A number of phase I immunotherapy trials for cancer patients incorporate the absolute lymphocyte count (ALC) as an inclusion criteria. This study aims to assess whether ALC is associated with a lack of response to anti-PD-1/PD-L1 in early clinical trials. METHODS: All consecutive patients treated with anti-PD-1/PD-L1 monotherapy in phase I trials in our institution between December 2011 and January 2014 were reviewed. Baseline ALC, neutrophil-to-lymphocyte ratio (NLR), Royal-Marsden Hospital (RMH) prognostic score, objective response rate (ORR) and disease control rate (DCR = SD + PR + CR, stable disease (SD), partial response (PR), complete response (CR)) defined by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 were retrieved. RESULTS: Out of a total of 167 patients, 48 (28.7%) and 8 patients (4.8%) had baseline ALCs of 1 G/l. When using 0.5 G/l as ALC threshold, we did not find any difference either in ORR or in DCR. In a multivariate Cox regression analysis, baseline ALC was not associated with overall survival, whereas the RMH and the number of previous lines of treatment remained independent prognostic factors. CONCLUSIONS: Baseline ALC was not associated with response to anti-PD-1/PD-L1 in cancer patients enrolled in phase I trials. Patients should not be excluded from early phase clinical trials testing immune checkpoints blockers because of ALC.

We investigated whether a score combining baseline neutrophilia and a PET biomarker could predict outcome in patients with locally advanced cervical cancer (LACC). Patients homogeneously treated with definitive chemoradiation plus image-guided adaptive brachytherapy (IGABT) between 2006 and 2013 were analyzed retrospectively. We divided patients into two groups depending on the PET device used: a training set (TS) and a validation set (VS). Primary tumors were semi-automatically delineated on PET images, and 11 radiomics features were calculated (LIFEx software). A PET radiomic index was selected using the time-dependent area under the curve (td-AUC) for 3-year local control (LC). We defined the neutrophil SUV grade (NSG = 0, 1 or 2) score as the number of risk factors among (i) neutrophilia (neutrophil count >7 G/L) and (ii) high risk defined from the PET radiomic index. The NSG prognostic value was evaluated for LC and overall survival (OS). Data from 108 patients were analyzed. Estimated 3-year LC was 72% in the TS (n = 69) and 65% in the VS (n = 39). In the TS, SUVpeak was selected as the most LC-predictive biomarker (td-AUC = 0.75), and was independent from neutrophilia (p = 0.119). Neutrophilia (HR = 2.6), high-risk SUVpeak (SUVpeak > 10, HR = 4.4) and NSG = 2 (HR = 9.2) were associated with low probability of LC in TS. In multivariate analysis, NSG = 2 was independently associated with low probability of LC (HR = 7.5, p

Aims In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. Materials and methods The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR-CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm 3 , respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. Results A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 ± 8.0 versus 82.4 ± 8.0, P 3 of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two cases. Those cases were unpredictable and due to unfavourable organs at risk topography and poor response to external beam radiotherapy. Conclusion The delivery of 45 Gy in 25 fractions to the pelvis before brachytherapy warrants a higher probability to reach brachytherapy planning aims, in comparison with 50.4 Gy in 28 fractions.

Purpose Although dose–volume parameters in image-guided brachytherapy have become a standard, the use of posterior–inferior border of the pubic symphysis (PIBS) points has been recently proposed in the reporting of vaginal doses. The aim was to evaluate their pertinence. Methods and Materials Nineteen patients who received image-guided brachytherapy after concurrent radiochemotherapy were included. Per treatment, CT scans were performed at Days 2 and 3, with reporting of the initial dwell positions and times. Doses delivered to the PIBS points were evaluated on each plan, considering that they were representative of one-third of the treatment. The movements of the applicator according to the PIBS point were analysed. Results Mean prescribed doses at PIBS −2, PIBS, PIBS +2 were, respectively, 2.23 ± 1.4, 6.39 ± 6.6, and 31.85 ± 36.06 Gy. Significant differences were observed between the 5 patients with vaginal involvement and the remaining 14 at the level of PIBS +2 and PIBS: +47.60 Gy and +7.46 Gy, respectively (p = 0.023 and 0.03). The variations between delivered and prescribed doses at PIBS points were not significant. However, at International commission on radiation units and measurements rectovaginal point, the delivered dose was decreased by 1.43 ± 2.49 Gy from the planned dose (p = 0.019). The delivered doses at the four points were strongly correlated with the prescribed doses with R2 ranging from 0.93 to 0.95. The movements of the applicator in regard of the PIBS point assessed with the Digital Imaging and Communications in Medicine coordinates were insignificant. Conclusion The doses evaluated at PIBS points are not impacted by intrafractional movements. PIBS and PIBS +2 dose points allow distinguishing the plans of patients with vaginal infiltration. Further studies are needed to correlate these parameters with vaginal morbidity.

Nasopharyngeal cancer (NPC) is notable for its wide geographic variation, with incidences as high as 30 in 100,000 in endemic regions but < 1 in 100,000 worldwide. This review aims to identify areas where there could be differences in prognosis, management or outcomes among countries with high or low incidence of NPC. The incidence has generally declined both in endemic and non-endemic regions throughout the years, which may be attributed to the decrease in exposure to risk factors such as early exposure to salted fish and smoking. Ethnicity has an impact both on incidence and prognosis, with Southeast Asians having the highest incidence but also better survival. Concurrent chemoradiotherapy, with or without adjuvant and/or induction chemotherapy, is the standard of care for locoregionally advanced disease, as reflected in clinical practice guidelines. Despite improvements in management, a proportion of patients relapse. Salvage treatment is associated with significant morbidity due to the critical location of the nasopharynx and the toxicities of initial therapy. Clinical expertise is paramount, but is easier to attain in endemic regions and high volume centers where enrollment of patients in clinical trials is more feasible. Collaboration between low and high incidence countries and between low and high volume facilities is key to improving NPC prognosis worldwide.

Because responses of patients with cancer to immunotherapy can vary in success, innovative predictors of response to treatment are urgently needed to improve treatment outcomes. We aimed to develop and independently validate a radiomics-based biomarker of tumour-infiltrating CD8 cells in patients included in phase 1 trials of anti-programmed cell death protein (PD)-1 or anti-programmed cell death ligand 1 (PD-L1) monotherapy. We also aimed to evaluate the association between the biomarker, and tumour immune phenotype and clinical outcomes of these patients.In this retrospective multicohort study, we used four independent cohorts of patients with advanced solid tumours to develop and validate a radiomic signature predictive of immunotherapy response by combining contrast-enhanced CT images and RNA-seq genomic data from tumour biopsies to assess CD8 cell tumour infiltration. To develop the radiomic signature of CD8 cells, we used the CT images and RNA sequencing data of 135 patients with advanced solid malignant tumours who had been enrolled into the MOSCATO trial between May 1, 2012, and March 31, 2016, in France (training set). The genomic data, which are based on the CD8B gene, were used to estimate the abundance of CD8 cells in the samples and data were then aligned with the images to generate the radiomic signatures. The concordance of the radiomic signature (primary endpoint) was validated in a Cancer Genome Atlas [TGCA] database dataset including 119 patients who had available baseline preoperative imaging data and corresponding transcriptomic data on June 30, 2017. From 84 input variables used for the machine-learning method (78 radiomic features, five location variables, and one technical variable), a radiomics-based predictor of the CD8 cell expression signature was built by use of machine learning (elastic-net regularised regression method). Two other independent cohorts of patients with advanced solid tumours were used to evaluate this predictor. The immune phenotype internal cohort (n=100), were randomly selected from the Gustave Roussy Cancer Campus database of patient medical records based on previously described, extreme tumour-immune phenotypes: immune-inflamed (with dense CD8 cell infiltration) or immune-desert (with low CD8 cell infiltration), irrespective of treatment delivered; these data were used to analyse the correlation of the immune phenotype with this biomarker. Finally, the immunotherapy-treated dataset (n=137) of patients recruited from Dec 1, 2011, to Jan 31, 2014, at the Gustave Roussy Cancer Campus, who had been treated with anti-PD-1 and anti-PD-L1 monotherapy in phase 1 trials, was used to assess the predictive value of this biomarker in terms of clinical outcome.We developed a radiomic signature for CD8 cells that included eight variables, which was validated with the gene expression signature of CD8 cells in the TCGA dataset (area under the curve [AUC]=0·67; 95% CI 0·57-0·77; p=0·0019). In the cohort with assumed immune phenotypes, the signature was also able to discriminate inflamed tumours from immune-desert tumours (0·76; 0·66-0·86; p0·0001). In patients treated with anti-PD-1 and PD-L1, a high baseline radiomic score (relative to the median) was associated with a higher proportion of patients who achieved an objective response at 3 months (vs those with progressive disease or stable disease; p=0·049) and a higher proportion of patients who had an objective response (vs those with progressive disease or stable disease; p=0·025) or stable disease (vs those with progressive disease; p=0·013) at 6 months. A high baseline radiomic score was also associated with improved overall survival in univariate (median overall survival 24·3 months in the high radiomic score group, 95% CI 18·63-42·1; vs 11·5 months in the low radiomic score group, 7·98-15·6; hazard ratio 0·58, 95% CI 0·39-0·87; p=0·0081) and multivariate analyses (0·52, 0·35-0·79; p=0·0022).The radiomic signature of CD8 cells was validated in three independent cohorts. This imaging predictor provided a promising way to predict the immune phenotype of tumours and to infer clinical outcomes for patients with cancer who had been treated with anti-PD-1 and PD-L1. Our imaging biomarker could be useful in estimating CD8 cell count and predicting clinical outcomes of patients treated with immunotherapy, when validated by further prospective randomised trials.Fondation pour la Recherche Médicale, and SIRIC-SOCRATE 2.0, French Society of Radiation Oncology.

// Sylvain Reuze 1, 2, 3, 4 , Fanny Orlhac 1, 5 , Cyrus Chargari 1, 2, 3, 6, 7 , Christophe Nioche 5 , Elaine Limkin 1 , Francois Riet 3 , Alexandre Escande 3 , Christine Haie-Meder 3 , Laurent Dercle 8, 9 , Sebastien Gouy 10 , Irene Buvat 5 , Eric Deutsch 1, 2, 3 and Charlotte Robert 1, 2, 3, 4 1 INSERM, U1030, F-94805, Villejuif, France 2 Universite Paris-Sud, Universite Paris-Saclay, F-94270, Le Kremlin-Bicetre, France 3 Gustave Roussy, Universite Paris-Saclay, Department of Radiotherapy, F-94805, Villejuif, France 4 Gustave Roussy, Universite Paris-Saclay, Department of Medical Physics, F-94805, Villejuif, France 5 IMIV, CEA, INSERM, CNRS, Universite Paris-Sud, Universite Paris-Saclay, CEA-SHFJ, Orsay, France 6 French Military Health Services Academy, Ecole du Val-de-Grâce, Paris, France 7 Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France 8 INSERM, U1015, F-94805, Villejuif, France 9 Gustave Roussy, Universite Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, F-94805, Villejuif, France 10 Gustave Roussy, Universite Paris-Saclay, Department of Gynecologic Surgery, F-94805, Villejuif, France Correspondence to: Charlotte Robert, email: ch.robert@gustaveroussy.fr Keywords: radiomics, cervical cancer, texture, PET imaging Received: February 24, 2017 Accepted: April 11, 2017 Published: May 15, 2017 ABSTRACT Objectives: To identify an imaging signature predicting local recurrence for locally advanced cervical cancer (LACC) treated by chemoradiation and brachytherapy from baseline 18 F-FDG PET images, and to evaluate the possibility of gathering images from two different PET scanners in a radiomic study. Methods: 118 patients were included retrospectively. Two groups (G1, G2) were defined according to the PET scanner used for image acquisition. Eleven radiomic features were extracted from delineated cervical tumors to evaluate: (i) the predictive value of features for local recurrence of LACC, (ii) their reproducibility as a function of the scanner within a hepatic reference volume, (iii) the impact of voxel size on feature values. Results: Eight features were statistically significant predictors of local recurrence in G1 (p < 0.05). The multivariate signature trained in G2 was validated in G1 (AUC=0.76, p

3016Background: The aim was to develop a radiomic estimator of tumor infiltrating CD8 T-cells, to assess its association with tumor immune phenotype, and to evaluate outcomes of cancer patients enr...

Background: The discovery of biomarkers identifying responders to immunotherapy is a major challenge. Tumor and peritumoral immune infiltration has been shown to be associated with response to anti-PD-1/PD-L1. The aim of this study was to develop a radiomics-based imaging tool of tumor immune infiltrate and to assess whether such a tool could predict clinical outcomes of patients treated with anti-PD1/PDL1. Methods: A predictive radiomics-based model of tumor-infiltrating CD8+ T cells was trained using data from the head and neck cohort of The Cancer Imaging Archive (HNSC-TCIA). Two cohorts from our institute were used for validation. Contrast-enhanced CTs of 57 patients from the HNSC-TCIA were manually segmented (tumor and surrounding tissue) and 76 radiomics features extracted. A radiomics-based score was build using radiomics features to predict tumor-infiltrating CD8+ T-cells' abundance, which was estimated using RNA-sequencing data from The Cancer Genome Atlas, and the Microenvironment Cell Populations-counter signature. As a first validation, this signature was applied to an independent cohort of 100 patients for whom the pathologic tumor immune infiltrate was postulated as either favorable (lymphoma, melanoma, lung, bladder, renal, MSI+ cancers, and adenopathy; 70 patients) or unfavorable (adenoid cystic carcinoma, low-grade neuroendocrine tumors, uterine leiomyoma; 30 patients). The signature was then applied on baseline-CTs of a second external cohort of 139 patients prospectively enrolled in anti PD-1/PD-L1 phase 1 trials. The median of the radiomics-based CD8+ score was used to separate patients into two groups (high and low score). Survival was estimated using Cox-proportional hazards model. Results: We developed a radiomics-based CD8+ signature using the six radiomics features that had highest performance on random forest. In the first external cohort, the radiomics-based CD8 T-cells score was associated with the postulated tumor immune infiltrate (Wilcoxon test, P < 0.001). In the second external cohort of patients treated with anti-PD-1/anti-PD-L1, median (±SD) radiomics score was 109.6±61.3. Patients with high-predicted score had significantly better OS (HR= 0.55, 95%CI=0.36-0.86, P= 0.009). The radiomics-based CD8+ predicted score remained significant in a multivariate Cox regression analysis including RMH score (HR= 0.50, 95%CI=0.32-0.78, P= 0.003). Conclusions: The radiomics-based signature of CD8+ T cells appears as a promising tool to estimate tumor immune infiltrate and to infer the outcome of patients treated with anti-PD-1/PD-L1. Citation Format: Roger Sun, Elaine Johanna Limkin, Laurent Dercle, Sylvain Reuzé, Stéphane Champiat, David Brandao, Loic Verlingue, Samy Ammari, Sandrine Aspeslagh, Antoine Hollebecque, Christophe Massard, Aurélien Marabelle, Jean-Yves Scoazec, Charlotte Robert, Jean-Charles Soria, Eric Deutsch, Charles Ferté. Prediction of clinical outcomes of cancer patients treated with anti-PD-1/PD-L1 using a radiomics-based imaging score of immune infiltrate [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A051.

11571Background: Tumor invasion patterns are known to be associated with HNSCC pts outcome. Radiomics is a rapidly-emerging field involving the extraction of quantitative imaging features from stan...