BACKGROUND:Patient recruitment for clinical trials remains a major challenge, with 86% of trials failing to meet enrollment targets on time. In over 77% of cases, recruitment difficulties stem from matching problems between trials and patients. Case-Based Reasoning (CBR) offers a distinct patient-to-patient approach by determining eligibility through comparison with previously enrolled patients, yet this methodology remains underexplored in contemporary oncology trial matching despite its potential advantages. OBJECTIVE:To compare the performance of two CBR approaches-random forest (RF) and target patient similarity (TPS)-in predicting patient eligibility for recent oncology clinical trials using real-world electronic health record data. METHODS:We selected three breast cancer clinical trials (2019-2022) from our institutional registry. Patient data were extracted from our clinical data warehouse, including structured data (laboratory results, diagnosis codes, procedures, treatments) and unstructured clinical narratives processed using natural language processing. For each trial, we trained RF classifiers and TPS models using repeated hold-out validation (25 splits, 70/30 train-test). Performance was evaluated using discriminative metrics (AUC, positive precision, recall, F1-score) and ranking metrics (P@5, P@10, MAP, MRR, NDCG@5, NDCG@10). We analyzed model performance across varying numbers of eligible patients in training datasets (2 to 70% of the total number of eligible patients). RESULTS:Both approaches demonstrated strong discriminative performance across three trials, with average AUCs of 84.1 % for RF and 76.4 % for TPS, driven primarily by high recall (82.3 % and 77.7 %, respectively). However, positive precision remained low (13.3 % and 9.9 %), reflecting high false-positive rates due to class imbalance. RF showed superior ranking performance, particularly for the trial with the largest eligible cohort (n = 542; P@5 = 78.6 %, MRR = 88.0 %), compared to TPS (P@5 = 47.9 %, MRR = 69.2 %). Both approaches reached performance plateaus with only around 10 eligible patients in training datasets. Variable importance analysis revealed that treatment-related features, diagnostic codes, and procedures were consistently the most important predictors, with relevant patterns identified even with minimal training data. CONCLUSIONS:CBR approaches can effectively support patient pre-screening for oncology clinical trials, with RF demonstrating moderately superior performance over TPS. Both methods show robust discriminative performance with small training datasets, though ranking performance varies substantially across trials. Our findings suggest that CBR approaches may benefit from integration with query-based or prompt-based methods during early recruitment phases when training data is scarce.

PURPOSE:Xerostomia is a common and debilitating toxicity following head and neck cancer radiation therapy (RT). Although adaptive RT (ART) strategies can reduce mean parotid gland (PG) dose, clinical trials have shown limited benefit in reducing xerostomia, suggesting global dose metrics may be insufficient. Voxel-based analysis (VBA) enables assessing local dose-toxicity relationships and may identify symptom-related subregions (SRS) more predictive of toxicity. This study aimed to identify xerostomia-associated SRS using VBA and assess their relevance using a functional salivary atlas. METHODS AND MATERIALS:Sixty patients with locally advanced oropharyngeal cancer treated with chemoradiation therapy were randomized to receive standard RT or weekly ART. Xerostomia was assessed at 12 months posttreatment using stimulated salivary flow, with values ≤500 mg/min indicating xerostomia. A customized VBA was applied to identify subregions from voxelwise dose differences between patients with and without xerostomia using a permutation test (planned dose in the standard arm and accumulated dose in the ART arm). To assess clinical relevance, a functional salivary atlas was generated from prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) scans of 13 patients with prostate cancer and compared with the subregions. A dosimetric analysis evaluated the predictive value of dose in overlapping regions. RESULTS:VBA identified a subregion (300.2 cc) with significantly higher doses in patients with xerostomia, located contralaterally near the nasopharynx. Overlap with the functional PSMA-PET atlas revealed 2 clinically relevant subregions in the contralateral PG (SRSPG, 6.8 cc) and tubarial gland (SRStubarial, 12.7 cc), with doses >11.5 Gy higher in patients with xerostomia. Logistic regression models yielded high predictive performance, with maximum areas under the curve of 0.88 for SRSPG and 0.88 for SRStubarial. CONCLUSIONS:VBA revealed 2 predictive subregions-within the contralateral PG and tubarial glands-strongly associated with xerostomia at 12 months post-RT. Our findings offer a plausible explanation for the persistence of xerostomia despite PG sparing and support incorporating subregional dose metrics and tubarial gland sparing into RT planning.

BACKGROUND:Hepatocellular carcinoma (HCC) frequently develops in underlying cirrhosis. Liver dysfunction impacts survival and may influence treatment results. About a quarter of patients with advanced HCC present with Child-Pugh B liver functions. All recent phase 3 trials validating standard of care limited inclusion to patients with Child-Pugh A liver function. Results of immunotherapy is less described in patients with altered liver function. We previously showed that the ALBI grade might be able to better select patients with Child-Pugh B liver functions who could benefit from sorafenib. Single-agent anti-PD-(L)1 antibodies might have a more favorable safety profile than standard of care combinations. METHODS:We thus launched a study, the HESTIA trial, testing tislelizumab, an anti-PD-1 antibody that was demonstrated as non-inferior to sorafenib as first-line treatment, in the population of patients with advanced HCC, Child-Pugh B and ALBI grade 1 or 2 liver function. RESULTS:In this article, we present the design of the study and first safety results. This is a single-arm phase 2 study. Fifty patients will be included. The primary endpoint is objective response rate. The first safety analysis showed no signal of increased toxicity of the drugs. However, this population is at high risk for liver-related adverse events. CONCLUSION:The study is currently pursuing accrual.

BACKGROUND:Acute respiratory distress syndrome (ARDS), a common condition among intensive care patients, is characterized by severe hypoxemia that may lead to acute brain injury. Although prone positioning has emerged as a lifesaving strategy in the management of ARDS, its effects on cerebral oxygenation remain insufficiently explored. OBJECTIVE:To evaluate the evolution of cerebral oxygenation during prone positioning in patients with ARDS. METHODS:This prospective, single-center study was done in the intensive care unit of a community hospital. Consecutive patients with moderate or severe ARDS were prospectively enrolled during a 12-month period. Cerebral oxygenation was assessed by near-infrared spectroscopy before and during an 18-hour period of prone positioning. Continuous variables were compared before and during prone positioning using the Wilcoxon signed rank test. Correlations were assessed using the Spearman rank test. RESULTS:Ten patients were included in the study, with 2 patients exiting at hours 6 and 12 after the start of prone positioning because of hemodynamic instability. Evidence of oxygenation improvement during prone positioning was indicated by an increase in regional cerebral oxygen saturation (rSo2) and the ratio of Pao2 to fraction of inspired oxygen (Fio2). The rSo2/Fio2 ratio was significantly increased from hour 3 to 12 (P = .049 at hour 3, P = .02 at hour 8, and P = .02 at hour 12). Also, rSo2 was significantly correlated with oxygen delivery (ρ = 0.811, P < .001) and cardiac index (ρ = 0.463, P < .001). CONCLUSION:Prone positioning in patients with ARDS seems to be associated with improved cerebral oxygenation based on rSo2/Fio2 ratio.

Interim analysis of the DOSISPHERE-01 study demonstrated a strongimprovement in response and overall survival (OS) on using90Y-loaded glass microspheres with personalized dosimetry comparedwith standard dosimetry in patients with nonoperable locally advancedhepatocellular carcinoma. This report sought to provide a long-termanalysis of OS.Methods:In this phase II study (ClinicalTrials.goviden-tifier NCT02582034), treatment was randomly assigned (1:1) with thegoal to deliver either at least 205Gy (if possible.250-300Gy) to theindex lesion in the personalized dosimetry approach (PDA) or120620Gy to the treated volume in the standard dosimetry approach(SDA). The 3-mo response of the index lesion was the primary end-point, with OS being one of the secondary endpoints. This report is apost hoc long-term analysis of OS.Results:Overall, 60 hepatocellularcarcinoma patients with at least 1 lesion larger than 7cm and morethan 30% of hepatic reserve were randomized (intent-to-treat popula-tion: PDA,n531; SDA,n529), with 56 actually treated (modifiedintent-to-treat population:n528 in each arm). The median follow-upfor long-term analysis was 65.8mo (range, 2.1-73.1mo). Median OSwas 24.8mo and 10.7mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9;P50.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9mo for patients with a tumordose of at least 205Gy, versus 10.3mo for those with a tumor dose ofless than 205Gy (HR, 0.42; 95% CI, 0.22-0.81;P50.0095), and was22.9mo for patients with a perfused liver dose of 150Gy or higher, ver-sus 10.3mo for those with a perfused liver dose of less than 150Gy(HR, 0.42; 95% CI, 0.23-0.75;P50.0033). Lastly, median OS was notreached in patients who were secondarily resected (n511, 10 in thePDA group and 1 in the SDA group), versus 10.8mo in those withoutsecondary resection (n545) (HR, 0.17; 95% CI, 0.065-0.43;P50.0002). Only resected patients displayed favorable long-term OSrates, meaning an OS of more than 50% at 5 y.Conclusion:After longer follow-up, personalized dosimetry sustained a meaningful im-provement in OS, which was dramatically improved for patients whowere accurately downstaged toward resection, including most portalvein thrombosis patients

Background and purposeWe performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT.Materials and methodsWe conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed.ResultsOf the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT.ConclusionThe ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

Introduction L'inclusion de patients dans les essais cliniques (EC) en oncologie est insuffisante. L'objectif de cette étude était de comprendre les modalités d'identification des patients éligibles à l'inclusion dans les EC, et les perspectives possibles de support informatique fondé sur les bases de données de santé. Méthodes Etude qualitative par entretiens semi-structurés d'acteurs impliquées dans la recherche clinique en oncologie depuis au moins cinq ans. Recrutement par échantillonnage délibéré pour intégrer divers profils (investigateurs, attachés de recherche clinique (ARC), support IT, promoteurs, patient) et institutions (public/privé, entreprises, tutelles). Entretiens enregistrés et retranscrits. Analyse qualitative par codage inductif des transcrits. Résultats Nous avons interrogé 24 participants, dont 10 oncologues et 5 ARCs. Nous mettons en évidence de grandes étapes stables entre institutions, avec une étape de préscreening très dépendante de l'oncologue référent du patient et de l'ARC, puis une étape de vérification manuelle chronophage. Le processus est très dépendant de la qualité des relations entre acteurs, et de la possibilité d'envisager l'inclusion dans un EC à chaque étape de soin du patient. La performance de ce processus est modérée par la culture de recherche clinique des centres : représentation des EC comme option de soin, satisfaction quant aux taux d'inclusion actuels, incitation à inclure pour les médecins. Par ailleurs, le préscreening est affecté par l'infrastructure en données mise à disposition des investigateurs. D'abord, l'absence de registre en temps réel des ECs ouverts est préjudiciable. Ensuite, l'automatisation même partielle du préscreening, pour aligner les critères d'inclusion aux caractéristiques des patients, supposerait à la fois une structuration standardisée de ces informations suivant une norme interopérable, et la compatibilité avec le dossier patient. Automatiser demanderait de redistribuer les rôles dans le processus, avec implication des spécialistes des données, et réflexion sur l'utilisateur principal d'une solution. La RCP apparaît comme un temps stratégique pour renforcer l'inclusion des patients dans les ECs. Conclusion L'inclusion dans les essais reste un processus manuel. Un support informatique serait utile mais les prérequis techniques et organisationnels ne sont pas encore remplis.

BACKGOUND AND AIMS:In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT. APPROACH AND RESULTS:We collected individual patients' data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses. CONCLUSIONS:This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings.

BACKGROUND:Recruitment of cancer patients into clinical trials (CTs) is a challenge. We aimed to explore how patient eligibility assessment is conducted in practice, what factors support or hinder this process, and to assess the potential usefulness of Clinical Trial Recruitment Support Systems (CTRSS) for patient-to-trial matching. METHODS:We conducted semi-structured interviews in France with healthcare professionals involved in cancer CTs and experts on trial recruitment. We focused on the stages in-between trial feasibility, and patient information and consent. Interviews were recorded, and the transcripts were analyzed thematically. We used the Systems Engineering Initiative for Patient Safety (SEIPS) 2.0 framework to organize our results. RESULTS:We interviewed 25 participants. We identified common steps for cancer patient eligibility assessment: prescreening under medical supervision, followed by the validation of patient-trial matching based on manual chart review. This process built on rich interactions between clinicians, other professionals (clinical research assistants, data scientists, medical coding experts), and patients. Technological factors, mainly related to data infrastructure (both for patient data and trial data), and organizational factors (research culture, incentives, formal and informal research networks) mediated the performance of the recruitment process. Participants had mixed feelings towards CTRSSs; they welcomed automated pre-screening but insisted on manual verification. Given the necessary collaborative nature of multisite trials, coordinated efforts to support a common data infrastructure could be helpful. CONCLUSIONS:Material, organizational, and human factors affect cancer patient eligibility assessment for CTs. Patient-to-trial matching tools bear potential, but good understanding of the ecosystem, including stakeholders' motivations, is a prerequisite.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.2515/therapie/2015055. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Purpose Triple-negative breast cancers (TNBC) account for 15% of all breast cancers but carry the worst prognosis. Because of their heterogenicity, these tumors are not all prone to targeted therapies. However, due to their high immune infiltration, targeting their immune microenvironment is of tremendous interest and is becoming the standard of care for high-risk early-stage TNBC. Nevertheless, the characterization of this immune infiltrate is often limited to general tumor-infiltrating lymphocytes (TILs) counting, without characterization of lymphocytes subtypes. Thus, we aimed at precisely characterizing these sub-populations and evaluating their prognostic significance.Methods We selected 91 TNBC tumors for which we had both the TILs count on hematoxylin and eosin (H&E) slides determined by an expert pathologist and the immune microenvironment cell subtypes characterization using flow cytometry (FC). We then compared the prognostic value of immune microenvironment subpopulations vs total TILs count.Results TNBCs contained a mean of 22.8±25.9% TILs in the tumor surface area, including mainly CD4+ helper T lymphocytes (14.1%), mostly Th2 (11.7%), CD8+ cytotoxic T lymphocytes (11.1%), and myeloid cells (8.4%) including antigen presenting cells (APC). The TILs count was correlated with the abundance of these cellular subpopulations (p≤0.004). TILs percentage was predictive of overall survival (OS) in univariate analysis (p=0.044), high APC infiltration was predictive of relapse-free survival (RFS) in univariate analysis (p≤0.030), and Th2 infiltration was predictive of both RFS and OS in univariate (p=0.009, 0.008 respectively) and multivariate analyses (p=0.002, 0.010 respectively).Conclusion The characterization of TILs composition is essential to better understand the potential antitumoral functions of these cells, and to strongly improve the associated prognostic and predictive values. We here demonstrate that Th2 subpopulation is associated with a better overall survival in TNBC and could be of use to predict response to the newly used immunotherapies.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study was funded by grants from Rennes University Hospital (CORECT 2021-UF 8946-03) and association La Vannetaise### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Ethics Committee Review Board of Centre de lutte contre le Cancer Eugene Marquis gave ethical approval for this workI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors* BC : Breast Cancer BCSC : Breast Cancer Stem Cell CD : Cluster of Differentiation DBCC : Differentiated Breast Cancer Cell DC : Dendritic cells DCIS : Ductal Carcinoma In Situ FC : Flow Cytometry FFPE : Formalin-Fixed Paraffin-Embedded H&E : Hematoxylin and Eosin LN : Lymph Node NAC : Neoadjuvant chemotherapy OS : Overall Survival pCR : pathological Complete Response pTNM : pathological classification of Tumor size (T), Node involvement (N), and Metastasis (M) according to international guidelines RFS : Relapse-Free Survival TC : T Cells (Lymphocytes) Th response : T helper response TILs : Tumor-Infiltrating Lymphocytes TNBC : Triple-Negative Breast Cancer

Importance:Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers.Objective:To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer.Design, Setting, and Participants:This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022.Interventions:The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning).Main Outcomes and Measures:The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival.Results:A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms.Conclusions and Relevance:This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates.Trial Registration:ClinicalTrials.gov Identifier: NCT01874587.

Purpose. Triple-negative breast cancers (TNBC) are defined as negative for hormonal receptors and human epidermal growth factor receptors 2 and account for 15% of breast cancers. TNBC carry the worst prognosis mainly because of their high proliferation index and the absence of efficient targeted therapies due to their molecular heterogeneity, even though some promising options are emerging. Besides, they do share a very high and distinct tumor-infiltrating lymphocytes (TILs) infiltration. Amongst TILs, CD8+ cytotoxic and CD4+ helper T-cells (TC) proved to be markers of a good outcome. However, pathologists routinely quantify overall TILs density only. Anti-PD-1/PD-L1 immunotherapies recently became available for immunosuppressive TNBC. Unfortunately, neither PD-1/PD-L1 expression nor TILs quantification is able to predict patients’ responses accurately. Thus, we aimed at precisely characterizing TILs sub-populations and evaluating their prognostic significance before their predictive one. Methods. We selected 91 patients at the time of surgery before any adjuvant therapy from January 2013 to December 2018 in Rennes, France. TNBC tumors went through TILs quantification on hematoxylin and eosin slides by a trained pathologist and immune microenvironment characterization using flow cytometry. We then compared the prognostic value of immune microenvironment subpopulations vs total TILs count. Results. TNBCs contained a mean of 22.8±25.9% TILs, including CD4+ TC (14.1%) mainly made of Th2 (11.7%), CD8+ TC (11.1%), and myeloid cells (8.4%) such as antigen presenting cells (APC). TILs groups and percentages were correlated with the abundance of these cellular subpopulations (p≤0.004). TILs percentage was predictive of overall survival (OS), while high APC infiltration was of relapse-free survival (RFS) in univariate analyses (p=0.044 & p≤0.030 respectively). Only Th2 infiltration was predictive of both RFS and OS in univariate (p=0.009 & p=0.008 respectively) and multivariate analyses (p=0.002 & p=0.010 respectively). When considering the different Th populations, only Th2 was a better predictive factor of survival than total leukocytes. Discussion. The development of immune therapies aiming at unlocking the anti-tumor immune response has revealed the desperate need to better characterize the tumor immune infiltrate. TILs quantification by pathologists is the only parameter routinely measured so far but it must be standardized since variability can affect their correlation with pCR. In our study, and contrary to most previous ones, stromal TILs were not significantly associated with RFS and OS. Thus, the characterization of TILs subtypes is critical since they can have either a pro- or an anti-tumorigenic function. Thus, we counteracted the limitations of TILs pathological quantification by finely characterizing the immune infiltrate using flow cytometry. Th2 infiltrate was the most frequent, as previously reported, and counterintuitively, was associated with a favorable prognostic value. This is rarely shown as Th2 infiltration is frequently reported to favor pro-tumorigenic immune tolerance. This proves that a more refined characterization of the intra-tumoral immune landscape is essential to derive interesting therapeutic perspectives, either by recapacitating Th2 response or by targeting their interaction with other immune subsets, like fibroblasts, macrophages, dendritic cells, or eosinophils and IgE. Finally, immunotherapies modulating Th2 response could also be used around the time of surgery that has been proved to induce immunomodulation. Conclusion. The characterization of TILs composition is essential to better understand the potential antitumoral functions of these cells and to substantially improve the associated prognostic and predictive values. Citation Format: Susie Brousse, Florence Godey, Elodie Laffont, Patrick Tas, Boris Campillo-Gimenez, Vincent Lavoué, Matthieu Le Gallo. Evaluation of T-cell infiltrating lymphocytes vs. Th2 in triple negative breast cancers (TNBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-23.

Aim. - To evaluate the performance of the collection of cases of anaphylactic shock during anesthesia in the Regional Pharmacovigilance Center of Rennes and the contribution of a query in the biomedical data warehouse of the French University Hospital of Rennes in 2009. Methods. - Different sources were evaluated: the French pharmacovigilance database (including spontaneous reports and reports from a query in the database of the programme de medicalisation des systemes d'information [PMSI]), records of patients seen in allergo-anesthesia (source considered as comprehensive as possible) and a query in the data warehouse. Results. - Analysis of allergo-anesthesia records detected all cases identified by other methods, as well as two other cases (nine cases in total). The query in the data warehouse enabled detection of seven cases out of the nine. Conclusion. - Querying full-text reports and structured data extracted from the hospital information system improves the detection of anaphylaxis during anesthesia and facilitates access to data. (C) 2016 Societe francaise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.

BACKGROUND:Despite the wide development of 90Y-loaded microspheres, 188Re-labeled lipiodol is still being used for radioembolization of hepatocellular carcinoma (HCC). However, the use of this latter compound is limited by in vivo instability. This study sought to evaluate the safety, bio-distribution, and response to 188Re-SSS lipiodol, a new and more stable compound.METHOD:Lip-Re-01 was an activity-escalation Phase 1 study involving HCC patients progressing after sorafenib. The primary endpoint was safety based on Common Terminology Criteria for Adverse Events (AEs) of Grade ≥3 within 2 months. Secondary endpoints included bio-distribution assessed by scintigraphy quantification from 1 to 72 h, tumor to non-tumor uptake ratio (T/NT), as well as blood, urine and feces collection over 72 h, dosimetry, and response evaluation (mRECIST).RESULTS:Overall, 14 heavily pre-treated HCC patients were treated using a whole liver approach. The mean injected activity was 1.5 ± 0.4 GBq for activity Level 1 (n = 6), 3.6 ± 0.3 GBq for Level 2 (n = 6), and 5.0 ± 0.4 GBq for Level 3 (n = 2). Safety was acceptable with only 1/6 of Level 1 and 1/6 of Level 2 patients experiencing limiting toxicity (one liver failure; one lung disease). The study was prematurely discontinued unrelated to clinical outcomes. Uptake occurred in the tumor, liver, and lungs, and only sometimes in the bladder. The T/NT ratio was high with a mean of 24.9 ± 23.4. Cumulative urinary elimination and fecal eliminations at 72 h were very low, 4.8 ± 3.2% and 0.7 ± 0.8%, respectively. Partial response occurred in 21% of patients (0% in the first activity level; 37.5% in the others).CONCLUSION:The high in vivo stability of 188Re-SSS lipiodol was confirmed, resulting in encouraging responses for a Phase 1 study. As the 3.6 GBq activity proved to be safe, it will be used in a future Phase 2 study.

Xerostomia is major toxicity associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. By performing several replanning sessions, adaptive radiotherapy (ART) aims to correct the parotid gland overdose during treatment and decrease xerostomia when compared to standard IMRT. We undertook a cost-effectiveness analysis (CEA) to compare replanning strategy to standard IMRT. The CEA was designed as part of the ARTIX trial, a randomised, parallel-group, multicentre study comparing systematic weekly replanning ART with standard IMRT (where a single replanning was left to the physician's appreciation) for patients with locally advanced oropharyngeal cancer. The French national insurance perspective was retained. For each patient included in the study, healthcare consumptions and costs (in Euros, 2020) were provided by the French national health insurance database (SNDS). More precisely, the trial was link to a dataset extracted from the SNDS comprising 22,426 adults selected on the basis of having cancer cared for in one of the participating clinical centers. The two databases to be linked shared many common timestamps, so the record linkage was expected to provide good results. Effectiveness criteria were based on the primary endpoint of the ARTIX trial, i.e. the frequency of xerostomia, measured by stimulating salivary flow with paraffin at 12-months, but also on progression-free and overall survival at 24-months. Uncertainty around the incremental cost-effectiveness ratios (ICERs) was captured by a probabilistic analysis using a non-parametric bootstrap method. Only 2 records among the 129 records were not linked due to a lack of information in the trial, which provides a linkage proportion of 98.4%. All the other 127 records were linked with good (R=2) to very good (R=7) robustness. A minimum robustness of 2 indicates that the linked pairs are very reliable. The linkage robustness was 4.18. Since five patients did not consent, two patients did not match with the SNDS, and seven patients followed major protocol violations, the analysis was based on 121 patients ultimately enrolled in the study on the per-protocol population between 2013 and 2018. Sixty patients entered the ART arm and Sixty-one patients in the standard IMRT arm. At 12-months, total mean costs per patient were €40,875 (SD 24,109) and €33,390 (SD 16,390) for ART and standard IMRT arms respectively (p = 0.009). At 24-months, costs were €49,301 (SD 30,218) and €41,840 (SD 23,671) respectively (p = 0.229). The largest portion of the total cost was represented by the costs of hospitalization. ICERs were €271,252 per percentage point of xerostomia avoided, and €168,919 per progression-free life year (PF-LY) gained. The probability of the ART strategy being cost-effective never exceeded 60% at high level of willingness to pay. ART strategy was dominated regarding the overall survival criteria. The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer. To the best of our knowledge, this is the first study evaluating the cost-effectiveness of replanning ART and the first CEA based on a Randomized Clinical Trial matched to the SNDS. The feasibility on real datasets with high record linkage and good robustness was also shown representative of record linkages involving the SNDS. Adaptive, Radiotherapy, Cost-effectiveness, Cancer, SNDS Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.

DOSISPHER-01 study (1) demonstrated at interim analysis a strong improvement of response and overall survival (OS) using 90Y loaded glass microsphere with personalized dosimetry compared with standard dosimetry in non-operable locally advanced hepatocellular carcinoma patients. The aim of this report is to provide long-term analysis of OS. In this phase II study, treatment arm was randomly assigned (1:1) to personalized dosimetry arm (PDA) with the goal to deliver at least 205 Gy (if possible, more than 250-300 Gy) to the index lesion or to the standard dosimetry arm (SDA), with the goal to deliver 120 ± 20 Gy to the treated volume. Response rate was the primary endpoint and OS was one the secondary endpoints. This report is a post hoc long-term analysis of OS. 60 HCC patients, with a least one lesion >7 cm and at least > 30% of hepatic reserve, were randomized (ITT population, PDA 31, SDA 29), and 56 treated (modified ITT population, 28 in each arm). Portal vein thrombosis (PVT) was present in 68% and of the patients (ITT and modified ITT population). The median follow-up for long-term analysis was 65.8 months (2.1-73.1). Median OS was 22.9 months in the PDA versus 10.8 months in the SDA, HR 0.52 (95% CI: 0.3-0.91), P = 0.023 in the ITT population, and respectively 24.8 months versus 10.7 months, HR 0.51 (95% CI: 0.29-0.9), P = 0.02 in the modified ITT population. According to dosimetry results, median OS was 22.9 months for patients with a Tumor Absorbed Dose (TAD) ≥ 205 Gy versus 10.3 months for those with a TAD < 205 Gy, HR 0.42 (95% CI: 0.22-0.81), P = 0.0095 and median OS was 22.9 months for patients with a Perfused Liver Dose (PLD) ≥ 150 Gy versus 10.3 months for those with a TAD < 205 Gy, HR 0.42 (95% CI: 0.23-0.75), P = 0.0033.Finally, median OS was not reached in the patients secondarily resected (n = 11, 10 in the PDA and 1 in the SDA) versus 10.8 months for the patients without secondary resection (n = 45), HR 0.17 (95% CI: 0.065-0.43), P = 0.0002. OS rates at 1, 2, 3, and 5 years are presented in the table. After longer follow-up, personalized dosimetry maintained a meaningful improvement of OS. OS was dramatically improved for patients accurately down staged toward resection.

Clinical image data analysis is an active area of research. Integrating such data in a Clinical Data Warehouse (CDW) implies to unlock the PACS and RIS and to address interoperability and semantics issues. Based on specific functional and technical requirements, our goal was to propose a web service (I4DW) that allows users to query and access pixel data from a CDW by fully integrating and indexing imaging metadata. Here, we present the technical implementation of this workflow as well as the evaluation we carried out using a prostate cancer cohort use case. The query mechanism relies on a Dicom metadata hierarchy dynamically generated during the ETL Process. We evaluated the Dicom data transfer performance of I4DW, and found mean retrieval times of 5.94 seconds and 0.9 seconds to retrieve a complete DICOM series from the PACS and all metadata of a series. We could retrieve all patients and imaging tests of the prostate cancer cohort with a precision of 0.95 and a recall of 1. By leveraging the CMOVE method, our approach based on the Dicom protocol is scalable and domain-neutral. Future improvement will focus on performance optimization and de identification.