The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer.

BACKGROUND: Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient's tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients. METHOD: The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model. DISCUSSION: This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation. TRIAL REGISTRATION: The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.

General practitioners' views on genomics, practice and education: A qualitative interview study.

BACKGROUND AND OBJECTIVES: Genomics is moving rapidly into mainstream medicine through clinical genomic testing and consumer-initiated online DNA testing. The aim of this study was to identify Australian general practitioners' (GPs') views on genomics, impact on practice and educational needs to inform continuing education. METHOD: Semi-structured interviews were conducted, with constant comparative inductive analysis and governance from a national taskforce. RESULTS: Twenty-eight GPs (43% female) were interviewed; 71% worked in a metropolitan workplace. Most initially reported little experience with genetic/genomic tests but, when prompted, recognised encountering genomics, mainly non-invasive prenatal and single-gene tests. Many GPs referred patients for cancer screening to genetic services or specialists. GPs reported needing continuing education and resources, with preferences underpinned by relevance to practice. DISCUSSION: GPs are integrating genomic testing into care, mainly through prenatal screening, and anticipate further impact. They want diverse and context-dependent education but are unaware of some available resources, such as The Royal Australian College of General Practitioners' Genomics in general practice guideline.

[Adherence to rabies vaccine treatment for people exposed to rabies in Abidjan (Côte d' Ivoire)]. / Observance du traitement vaccinal antirabique chez les sujets exposés à la rage à Abidjan (Côte d'Ivoire).

This descriptive retrospective study ran from August 2003 to December 2003 at the Rabies Center of the National Institute of Public Health in Abidjan. It covers subjects at risk of rabies transmission during 2004. Identification of participants in the study was made via a census of patients consulting the rabies clinic: a total of 533 subjects were included, predominantly male (54.6%), without gainful employment (57%), with an average age of 26.7 years. Those who lived outside the city of Abidjan accounted for 21.6%. In 88.2% of cases, they were exposed due to a bite. Dogs (90.8%) represented the main species responsible for this kind of exposure. Only 3.2% of these animals had a current valid rabies vaccine. The owner of the animal was not known in 71% of cases. The observance of the recommended immunization schedule for 4 doses was 53.1%. Of the 533 patients registered in the study, 46.9% had stopped treatment vaccine. Some factors have been identified as adversely affecting adherence, such as the vaccination treatment plan of 5 doses, exposure outside the city of Abidjan, unemployment, incurrence of superficial injuries, exposure from an animal bite and lack of immunization of the animal. The results show that the strategies against rabies must focus increasingly on the importance of adherence to treatment and education of the population vis-à-vis the risk of rabies.

Low participation in organized colorectal cancer screening in France: underlying ethical issues.

International studies have shown a significant reduction in colorectal cancer (CRC) mortality following the implementation of organized screening programs, given a sufficient participation rate and adequate follow-up. The French national CRC screening program has been generalized since 2008 and targets 18 million men and women aged 50-74 years. Despite broad recommendations, the participation rate remains low (29.8%), questioning the efficiency of the program. A panel of experts was appointed by the French National Cancer Institute to critically examine the place of autonomy and efficiency in CRC screening and propose recommendations. In this paper, we explore the ethical significance of a public health intervention that falls short of its objectives owing to low take-up by the population targeted. First, we analyze the reasons for the low CRC screening participation. Second, we examine the models that can be proposed for public health actions, reconciling respect for the individual and the collective good. Our expert panel explored possible ways to enhance take-up of CRC screening within the bounds of individual autonomy, adapting awareness campaigns, and new educational approaches that take into account knowledge and analysis of sociocultural hurdles. Although public health actions must be universal, target actions should nonetheless be developed for nonparticipating population subgroups.

Radiosurgery or hypofractionated stereotactic radiotherapy for brain metastases from radioresistant primaries (melanoma and renal cancer).

BACKGROUND: Until 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS). METHODS: Between 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data. RESULTS: After a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65-2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively. CONCLUSION: Fractionation does not decrease LPFS. Even for small radioresistant brain metastases (< 3 cm), HFSRT, with 3 or 6 fractions, leads to an excellent local control rate of 72% at 1 year with a rate of 7.1% of radionecrosis. HFSRT is a safe and efficient alternative treatment to SRS.

Are the criteria of Tabar and Dean still relevant to radial scar?

OBJECTIVE: Aschoff's center of proliferation (ACP), poses significant problems of differential diagnosis both in imagery and histology with infiltrating carcinoma. Up to now the criteria of Tabar and Dean (classical criteria) are considered as diagnostically relevant. MATERIAL: A retrospective study of 113 cases, enabled us to study their clinical, radiological and histological aspects. RESULTS: The ACP is a subclinical and seldom palpable entity (12%). The radiological signs of ACP are quite variable. The classical criteria lack specificity and are observed only in 48% of our stellate images. Whereas the frequency of microcalcifications is high (58.5% of the cases), their presence and their type are not predictive of an associated malignancy. The echographic diagnosis of ACP could be made in 55% of the cases but the echographic semiology lacked specificity. We noticed an associated atypical epithelial hyperplasia in 28.5% of the cases, intraductal or lobular in situ carcinoma in 9% and/or a ductal invasive carcinoma in 2% of the cases. Neither tumor size, age of the patients, nor any radiological signs were predictive of such an association. CONCLUSIONS: The classical criteria are not completely reliable and are observed only in half of our stellate images, whereas microcalcifications are often present but are not predictive of an associated malignancy.

[Multidisciplinary meetings in oncology do not impact the physician-patient relationship]. / La réunion de concertation pluridisciplinaire en cancérologie ne modifie pas la relation entre le médecin et son patient.

CONTEXT: The setting of multidisciplinary meeting (MDM) by the French Cancer Plan has introduced new decisional elements in the patient-physician relationship in oncology. METHODS: To assess the potential impact of MDM on this relationship, a study was conducted at the Tours Hospital: 145 questionnaires were collected from patients whose files have been discussed in MDM, 40 questionnaires were collected from physicians attending these meetings and an analysis of 324 files was performed. RESULTS: Patients recognize the decisional process of MDM as reassuring for 80% of them. However, a majority (73%) expressed that the most important for them is the relationship with the referring physician, almost all (96%) having a total or great confidence in him. The results emphasize that trust appears to be related to the quality of communication, open dialogue and the competence of the doctor in particular in the choice of treatment. A review of files shows that in 91% of cases, the opinion of the RCP is applied and that, in 69% of cases, the referring doctor delivers the information to the patient after MDM. From the physicians' perspective, 33/40 report that the MDM do not alter their relationship with the patient. We note that 35/40 express that the consultation after MDM facilitates the presentation of the decision and 37/40 that the decision is always or often applied in accordance with the opinion of the MDM. CONCLUSION: MDM appears in most cases in this study not to modify the patient-physician relationship. Due to the patient confidence into the referring physician, the role of this one is essential in integrating the decisional multidisciplinary opinion of MDM and it is important to ensure from his/her disengagement in the decisional process.