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In therapeutic research, the safety and efficacy of pharmaceutical products are necessarily tested on humans via clinical trials after an extensive and expensive preclinical development period. Methodologies such as computer modeling and clinical trial simulation (CTS) might represent a valuable option to reduce animal and human assays. The relevance of these methods is well recognized in pharmacokinetics and pharmacodynamics from the preclinical phase to postmarketing. However, they are barely used and are poorly regarded for drug approval, despite Food and Drug Administration and European Medicines Agency recommendations. The generalization of CTS could be greatly facilitated by the availability of software for modeling biological systems, by clinical trial studies and hospital databases. Data sharing and data merging raise legal, policy and technical issues that will need to be addressed. Development of future molecules will have to use CTS for faster development and thus enable better patient management. Drug activity modeling coupled with disease modeling, optimal use of medical data and increased computing speed should allow this leap forward. The realization of CTS requires not only bioinformatics tools to allow interconnection and global integration of all clinical data but also a universal legal framework to protect the privacy of every patient. While recognizing that CTS can never replace 'real-life' trials, they should be implemented in future drug development schemes to provide quantitative support for decision-making. This in silico medicine opens the way to the P4 medicine: predictive, preventive, personalized and participatory. [ABSTRACT FROM AUTHOR]

Purpose: To analyze long-term oncological outcome after 2nd conservative treatment (2 nd CT) for patients with ipsilateral 2nd ipsilateral breast tumor event (2 nd IBTE)., Materials/methods: In this retrospective observational study (N°F20210402152843), patients with 2 nd IBTE underwent 2 nd CT (lumpectomy + tumor bed re-irradiation). 3 rd IBTE (3 rd IBTE-FS), regional relapse- (RRFS) and metastatic disease- (MD-FS) free survivals as well as disease-free (DFS), specific (SS) and overall (OS) survival were analyzed. Late toxicity was reported., Results: Between 09/2000 and 04/2022, 244 patients presented a 2 nd IBTE and underwent a 2 nd CT. Among them, 113 pts with a minimum follow-up of 60 months were analyzed. Median time interval between 1st and 2 nd IBTE was 13.5 years [2-35]. Median 2 nd IBTE age was 66.2 years [31-85]. 2 nd IBTE were adenocarcinomas (77 %). Tumor size was < 20 mm (86.7 %). 2 nd IBTE were grade 1/2 (75 %), with positive hormonal receptor (85 %) and clear surgical margins (no ink on tumor, 90.3 %). In the APBI classification, 21 pts were high-risk (18.6 %), while 77 % were Luminal A/BHer2-. With a MFU of 121.5 months [CI95% 111.7-129.6], 10-year 3 rd IBTE-FS was 89 % [83-96]. Then-year RRFS, MDFS, DFS, SS and OS were 94 % [89-100], 89 % [83-96], 78 % [70-87], 95 % [91-100] and 94 % [90 -99] respectively. In multivariate analysis, APBI classification (high-risk; HR2.66 [1.01-7.1], p = 0.049) and tumor size (≥20 mm; HR2.64 [1.02-6.8], p = 0.045) were considered independent prognostic factors for DFS.Ninety-seven late complications were observed (fibrosis 64 %) with 6.2 % G ≥ 3 late toxicity. Cosmetic outcome was excellent/good in 91.2 %., Conclusions: With long follow-up, 2 nd IBTE managed with 2 nd CT allows second breast preservation without oncological outcome compromise and acceptable G ≥ 3 toxicity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Purpose: Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT., Patients and Methods: This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported., Results: From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45-132] and median EQD2 10 D 90 CTV HR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81-90], 83% [79-86], 70% [67-73], 61% [57-64] and 75% [69-78] respectively, with no significant difference between the groups. EQD2 10 D 90 CTV HR  < 85 Gy was a prognostic factor for local recurrence in univariate analysis (p = 0.045). The rates of acute/late grade ≥ 2 urinary, digestive and gynecological toxicities were 9%/15%, 3%/15% and 9%/25% respectively., Conclusion: Bi-fractionated HDR-BT boost seems feasible with good oncological outcome and slightly more toxicity after dose escalation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Introduction: The aim of this study was to translate into French the 24 items of the THYCA-QoL questionnaire used in thyroid cancers and then to study its psychometric properties., Materials and Methods: The THYCA-QoL is a specific questionnaire for evaluating the quality of life of patients undergoing thyroid cancer surgery. It consists of 24 items and is divided into seven dimensions and six isolated questions. The translation has been carried out according to the recommendations of the EORTC. Validation of the translated version was obtained by finding a consensus of experts for each of the items., Results: All the original questions of the questionnaire have been adapted into French. The translated questionnaire, named THYCA-CoL-fr, was tested on 60 patients (65 % female), mean age 54.5 years. All questions were well accepted and understood and no missing data were reported. Eight patients (13 %) proposed an item correction to the questionnaire. No attenuation effects (floor or ceiling) were detected. The internal structure was comparable to the original questionnaire: Cronbach α coefficients varied from 0.53 for the oropharyngeal dimension to 0.88 for the voice dimension. The scree-plot highlighted the seven dimensions of the English version., Conclusion: THYCA-QoL-fr is the first specific French language questionnaire to evaluate the quality of life in thyroid cancer patients undergoing surgery. These first exploratory psychometric results confirmed the conceptual similarity of the French translation and the English version., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the impact of systematic radiological review by breast specialist radiologist of malignant breast lesion imaging on the therapeutic management of patients., Materials and Methods: Data collection was performed for patients with histopathologically proved breast cancer or suspicious breast lesion on imaging realized out of our institution. Patients underwent systematic mammary and axillary ultrasound, imaging review and if necessary complementary mammographic images. We analyzed the number of additional breast biopsies and axillary lymph node fine needle aspiration (FNA) with their histopathological results. We assessed their impact by comparing the final surgical treatment to the one planned before review., Results: Two hundred and seventeen patients were included, with a total of 230 BIRADS 0, 4, 5 or 6 breast lesions. Seventy-six additional breast core biopsies were realized, leading to diagnose 43 additional BIRADS 6 lesions (24 infiltrative carcinomas, 9 DCIS and 10 atypical lesions) in 30 patients (13.82%). Thirty-five additional lymph node FNA were realized with 12 metastatic nodes and 3 false negative samples. Imaging review lead to change surgical treatment in 59 patients (27.19%, P<0.01) with modification in breast surgery in 37 patients, axillary surgery in 8 patients and both sites surgery in 12 patients., Conclusion: This study shows an impact of systematic radiological review by breast specialist radiologist in therapeutic management of patients treated for malignant breast lesion., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The objective of the study was to use CD146 mRNA to predict the evolution of patients with non-metastatic clear cell renal cell carcinoma (M0 ccRCC) towards metastatic disease, and to use soluble CD146 (sCD146) to anticipate relapses on reference treatments by sunitinib or bevacizumab in patients with metastatic ccRCC (M1). Methods : A retrospective cohort of M0 patients was used to determine the prognostic role of intra-tumor CD146 mRNA. Prospective multi-center trials were used to define plasmatic sCD146 as a predictive marker of sunitinib or bevacizumab efficacy for M1 patients. Results : High tumor levels of CD146 mRNA were linked to shorter disease-free survival (DFS) and overall survival (OS). ccRCC patients from prospective cohorts with plasmatic sCD146 variation <120% following the first cycle of sunitinib treatment had a longer progression-free survival (PFS) and OS. The plasmatic sCD146 variation did not correlate with PFS or OS for the bevacizumab-based treatment. In vitro, resistant cells to sunitinib expressed high levels of CD146 mRNA and protein in comparison to sensitive cells. Moreover, recombinant CD146 protected cells from the sunitinib-dependent decrease of cell viability. Conclusion : CD146/sCD146 produced by tumor cells is a relevant biological marker of ccRCC aggressiveness and relapse on sunitinib treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Depression is a sustainable state of deep sadness and abatement. It is frequently identified in patients with cancer and often undervalued by oncologists. The reduced PRIME-MD questionnaire is a questionnaire of 2 items validated in French. However, it has been neither translated nor validated in French. The objective of our study is to translate the PRIME-MD and validate it into French., Method: The PRIME-MD questionnaire was translated into French by using the recommendations of the EORTC and compared to the French gold standard questionnaire Mini-International Neuropsychiatric Interview (MINI)., Results: Two hundred and ninety-nine patients were included in our study. With a 98% filling rate, the Q2i questionnaire has been well accepted. The prevalence of depression in our population was measured at 7.4%. With a sensitivity of 89.47%, a specificity of 58.85%, found percentages are equal to those of the questionnaire in English. The negative predictive value was measured at 98.52%., Conclusion: This study demonstrates that the Q2i questionnaire is a quick and easy screening tool, requiring less than 2minutes to target patients likely to benefit from psychological support., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)