Refining patient selection for breast cancer immunotherapy: beyond PD-L1.

Therapies that modulate immune response to cancer, such as immune checkpoint inhibitors, began an intense development a few years ago; however, in breast cancer (BC), the results have been relatively disappointing so far. Finding biomarkers for better selection of BC patients for various immunotherapies remains a significant unmet medical need. At present, only tumour tissue programmed death-ligand 1 (PD-L1) and mismatch repair deficiency status are approved as theranostic biomarkers for programmed cell death-1 (PD-1)/PD-L1 inhibitors in BC. However, due to the complexity of tumour microenvironment (TME) and cancer response to immunomodulators, none of them is a perfect selector. Therefore, an intense quest is ongoing for complementary tumour- or host-related predictive biomarkers in breast immuno-oncology. Among the upcoming biomarkers, quantity, immunophenotype and spatial distribution of tumour-infiltrating lymphocytes and other TME cells as well as immune gene signatures emerge as most promising and are being increasingly tested in clinical trials. Biomarkers or strategies allowing dynamic assessment of BC response to immunotherapy, such as circulating/exosomal PD-L1, quantity of white/immune blood cell subpopulations and molecular imaging are particularly suitable for immunotreatment monitoring. Finally, host-related factors, such as microbiome and lifestyle, should also be taken into account when planning integration of immunomodulating therapies into BC management. As none of the biomarkers taken separately is accurate enough, the solution could come from composite biomarkers, which would combine clinical, molecular and immunological features of the disease, possibly powered by artificial intelligence.

Benign Brenner tumour of the ovary: CT and MRI features.

AIM: To evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) features of benign Brenner tumours (BBT) of the ovary. MATERIAL AND METHODS: This was a retrospective two-centre study comprising 35 female patients with a definitive diagnosis of BBT at histology in whom CT and/or MRI examinations had been performed. Two experienced radiologists reviewed the CT and MRI features of 39 ovarian BBT retrospectively with consensus reading. The morphological appearance and size of each tumour were recorded. The presence or absence of calcifications within the solid portion was noted at CT. The reviewed characteristics at MRI included qualitative assessment of the signal intensity of the solid portion on diffusion sequence and contrast enhancement, compared to that of the myometrium. RESULTS: CT and MRI images were available for 27 and 28 lesions, respectively. Sixteen patients had both CT and MRI examinations. BBT were unilateral in 89% of patients, and 49% of lesions were solid and 51% were mixed. Calcifications were depicted at CT in 70.4% of lesions. When present, the cystic portion was multilocular in 85% of cases and corresponded to a mucinous lesion in 74% of cases. Enhancement of the solid portion at MRI was inferior or equal to that of the myometrium in 89% of cases and signal on high b-values diffusion images was deemed low or moderate in 93% of cases. CONCLUSION: The combined CT and MRI findings of a unilateral fibrous ovarian mass containing punctate calcifications often associated with a multilocular cyst suggest the diagnosis of ovarian BBT.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

Antitumor activity in advanced cancer patients with thymic malignancies enrolled in early clinical drug development programs (Phase I trials) at Gustave Roussy.

OBJECTIVES: Thymic epithelial neoplasms (TENs) represent a rare entity with poor prognosis and limited systemic treatment options. The aim of this study was to assess the clinical benefit, the efficacy and toxicities of agents for patients with TEN enrolled in Phase I trials. MATERIALS AND METHODS: We reviewed retrospectively patients with advanced TEN enrolled in Phase I trials at Gustave Roussy (DITEP) between 1994 and 2012. Efficacy was assessed using RECIST version 1.1. RESULTS: Twenty-two treated patients were enrolled (15 with thymic carcinoma, 7 with thymoma). The median number of prior systemic therapies was 2 (0-8). The median age was 50 years (range 23-72), and 4 females were treated. Treatments received encompassed mTOR inhibitor (mTORi) in 4 of patients, antiangiogenic agents (AA) in 11 patients, and other targeted therapies in 7 patients. 18% had grade 3-4 toxicity, 85% all grade toxicity and no toxic death was reported. One patient experienced a complete response (CR) and 3 a partial response (PR); 16 patients had stable disease (median 6.6 months; range 1.0-30.7) and 2 had a progressive disease. The median overall survival was 54.5 months (95% CI 25-75.50). The median progression free survival (PFS) was 6.6 months (95% CI 1.35-11.59). Median PFS was 11.6 months for mTORi, 6.9 for AA, and 6.6 for other targeted therapies. CONCLUSION: Phase I trials appear as a sound therapeutic option in TENs pts progressing after standard treatments. Use of AA and mTORi seem to yield a good clinical response and warrant further investigation.