Place of radiotherapy for treatment of metastatic cervical, vaginal and endometrial uterine cancer.

Beyond classical palliative-intent irradiation schemes, there are increasing data suggesting a benefit for intensive locoregional treatments in metastatic gynecological cancers. Such approach aims at avoiding local symptoms related to tumor progression, but may also improve survival outcome by shrinking tumor burden to a microscopic state. This strategy is rarely considered upfront (in highly selected patients with very limited oligometastatic disease), but rather after systemic treatment.

Clinical, pathological, and comprehensive molecular analysis of the uterine clear cell carcinoma: a retrospective national study from TMRG and GINECO network.

Background: Uterine clear cell carcinomas (CCC) represent less than 5% of uterine cancers. Their biological characteristics and clinical management remain uncertain. A multicenter study to explore both clinical and molecular features of these rare tumors was conducted.

Mesenchymal-like Tumor Cells and Myofibroblastic Cancer-Associated Fibroblasts Are Associated with Progression and Immunotherapy Response of Clear Cell Renal Cell Carcinoma.

Unlabelled: Immune checkpoint inhibitors (ICI) represent the cornerstone for the treatment of patients with metastatic clear cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease, highlighting the need to precisely understand the plasticity of cancer cells and their cross-talk with the microenvironment to better predict therapeutic response and personalize treatment. Single-cell RNA sequencing of ccRCC at different disease stages and normal adjacent tissue (NAT) from patients identified 46 cell populations, including 5 tumor subpopulations, characterized by distinct transcriptional signatures representing an epithelial-to-mesenchymal transition gradient and a novel inflamed state.

3D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System.

Routine clinical assays, such as conventional immunohistochemistry, often fail to resolve the regional heterogeneity of complex inflammatory skin conditions. We introduce MANTIS (Multiplex Annotated Tissue Imaging System), a flexible analytic pipeline compatible with routine practice, specifically designed for spatially resolved immune phenotyping of the skin in experimental or clinical samples. On the basis of phenotype attribution matrices coupled to α-shape algorithms, MANTIS projects a representative digital immune landscape while enabling automated detection of major inflammatory clusters and concomitant single-cell data quantification of biomarkers.

Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results.

Background: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB.

Methods: Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months.

Contextualizing Olaparib and Abiraterone in the Current Treatment Landscape for Metastatic Castration-resistant Prostate Cancer.

Unlabelled: The PROpel trial assessed the combination of olaparib + abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms.

[Rare cancers of the head and neck on behalf of the REFCOR, part 1].

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology, which determines their local invasiveness, and their hematogenous/nodal spread.

[Rare cancers of the head and neck on behalf of the REFCOR, part 2].

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology as well as their anatomical location when arising from the paranasal sinuses, salivary glands and ear.

Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a refined classification from the European society for blood and marrow transplantation (EBMT).

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). A new definition for diagnosis, and a severity grading system for SOS/VOD in adult patients, was reported a few years ago on behalf of the European Society for Blood and Marrow Transplantation (EBMT). The aim of this work is to update knowledge regarding diagnosis and severity assessment of SOS/VOD in adult patients, and also its pathophysiology and treatment.

Inhibition of MYC translation through targeting of the newly identified PHB-eIF4F complex as a therapeutic strategy in CLL.

Dysregulation of messenger RNA (mRNA) translation, including preferential translation of mRNA with complex 5' untranslated regions such as the MYC oncogene, is recognized as an important mechanism in cancer. Here, we show that both human and murine chronic lymphocytic leukemia (CLL) cells display a high translation rate, which is inhibited by the synthetic flavagline FL3, a prohibitin (PHB)-binding drug. A multiomics analysis performed in samples from patients with CLL and cell lines treated with FL3 revealed the decreased translation of the MYC oncogene and of proteins involved in cell cycle and metabolism.

A fixed-duration immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial.

In previously untreated, medically fit patients with chronic lymphocytic leukemia (CLL), research is focused on developing fixed-duration strategies to improve long-term outcomes while sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach in which after obinutuzumab-ibrutinib induction for 9 months, patients (n = 10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) <0.01% continued only ibrutinib 420 mg/day for 6 additional months (I arm), whereas the majority (n = 115) received up to 4 cycles of fludarabine/cyclophosphamide-obinutuzumab 1000 mg alongside the ibrutinib (I-FCG arm).

Targeting Tumor Angiogenesis with the Selective VEGFR-3 Inhibitor EVT801 in Combination with Cancer Immunotherapy.

Unlabelled: The receptor tyrosine kinase VEGFR-3 plays a crucial role in cancer-induced angiogenesis and lymphangiogenesis, promoting tumor development and metastasis. Here, we report the novel VEGFR-3 inhibitor EVT801 that presents a more selective and less toxic profile than two major inhibitors of VEGFRs (i.e.

Oral mucosal toxicities induced by immune checkpoint inhibitors: Clinical features and algorithm management.

Immune checkpoint inhibitors (ICIs) have emerged as standard therapies for an increasing number of advanced cancers. Nonspecific immune activation may lead to immune-related adverse events among which dermatological reactions are one of the most prevalent (all-grade incidence ranging from 30 to 60%). Oral mucosal adverse reactions to ICIs are far less common than cutaneous adverse events.

[Women with a very high risk of breast cancer: Contraceptives, hormonal replacement therapy use and personalized screening].

Women with a high family risk of breast cancer are those with an identified genetic predisposition or those who have a suggestive family history without an identified germinal mutation, particularly for BRCA1 and BRCA2. Among these women with a very high risk of breast cancer, the fear of a potentially increased risk of breast cancer linked to some hormonal contraceptives and to the use of hormone replacement therapy, in connection with the general population data collected in literature, has led to certain reluctance to prescribe them to these women. Moreover, confusion often sets due to poor knowledge of the literature.

TRANSLACOL project: Nodal human papillomavirus tumoral DNA detection by ddPCR for survival prediction in early cervical cancer patients without pelvic lymph node invasion.

Introduction: In early cervical cancer (EEC), 10 to 15% of patients without nodal metastasis (N-) will suffer from recurrences with further similar survival as N+ patients. However, no clinical, imaging or pathological risk-factor is today available to identify them. In the present study, we hypothesized that the N- histologically characterized patients who present a poor prognosis could be patients for whom metastasis are missed by classical procedure.

[Serous fluid cytopathology: International system].

The International System for Serous Fluid Cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. Five diagnostic categories are proposed associated to an increased rate of malignancy and specific cytological criteria. The categories are reported as: (I) Non-diagnostic (ND), the cells are insufficient for interpretation; (II) Negative for malignancy (NFM), only benign cells are present; (III) Atypia of undetermined significance (AUS), the cells present mild atypia more likely to be benign, but a malignant process cannot be definitively excluded; (IV) Suspicious for malignancy (SFM), the cells are present with atypia or in a number suspect of malignancy but with insufficient ancillary studies to give a positive malignant diagnosis; (V) Malignant (MAL), the cytological criteria are absolutely and definitively malignant.

Do perioperative blood transfusions impact oncological outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion? Results from a large multi-institutional registry.

Background: Blood transfusions (BT) have been associated with adverse oncologic outcomes in multiple malignancies including open radical cystectomy (ORC) for urothelial carcinoma of the bladder (UCB). Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) delivers similar oncologic outcomes compared to ORC, yet with lower blood loss and reduced transfusions. However, the impact of BT after robotic cystectomy is still unknown.

Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study.

Introduction: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies evaluating antiangiogenic agents. Few data are available regarding immune checkpoint inhibitors (ICI) in patients with bone metastatic RCC. NIVOREN is a multicentre prospective study in which patients were treated with nivolumab after the failure of antiangiogenic agents.