Imaging Mass Cytometry in Psoriatic Disease Reveals Immune Profile Heterogeneity in Skin and Synovial Tissue.

Imaging mass cytometry is a technology that enables comprehensive analysis of cellular phenotypes at the tissue level. We performed a multiparameter characterization of structural and immune cell populations in psoriatic skin and synovial tissue samples aimed at characterizing immune cell differences in patients with psoriasis and psoriatic arthritis. A panel of 33 antibodies was used to stain selected immune and structural cell populations.

Incidence, mortality and survival of Merkel cell carcinoma: a systematic review of population-based studies.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that most commonly occurs in ultraviolet-exposed body sites. The epidemiology of MCC in different geographies and populations is not well characterized.

Objectives: The objective of this systematic review is to summarize evidence on the incidence, mortality and survival rates of MCC from population-based studies.

Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers.

Purpose: To evaluate tipapkinogene sovacivec (TG4001), a viral immunotherapeutic vaccine expressing human papillomavirus (HPV)16 E6/E7 non-oncogenic proteins and IL-2, in combination with avelumab in HPV16+ cancer patients.

Patients And Methods: In this open-label, phase Ib/II, multicenter study, HPV16+ advanced cancer patients received subcutaneous TG4001 at two dose levels (DL) in phase Ib and at the recommended phase II dose (RP2D) in phase II weekly for 6 weeks, then every 2 weeks (q2Wk) until 6 months, thereafter every 12 weeks, in combination with avelumab q2Wk starting from day 8. Exploratory end-points included immunomonitoring from sequential tumour and blood samples.

Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease.

Background: Three partially overlapping breast cancer polygenic risk scores (PRS) comprising 77, 179 and 313 SNPs have been proposed for European-ancestry women by the Breast Cancer Association Consortium (BCAC) for improving risk prediction in the general population. However, the effect of these SNPs may vary from one country to another and within a country because of other factors.

Objective: To assess their associated risk and predictive performance in French women from (1) the CECILE population-based case-control study, (2) BRCA1 or BRCA2 (BRCA1/2) pathogenic variant (PV) carriers from the GEMO study, and (3) familial breast cancer cases with no BRCA1/2 PV and unrelated controls from the GENESIS study.

Consequences of Discontinuing a 4/6 Cyclin D-Dependent Kinase Inhibitor During Endocrine Treatment in Hormone-Sensitive Metastatic Breast Cancer Patients in the Context of the COVID-19 Outbreak.

Background: The impact of some hasty medical decision made during the first wave of the Coronavirus Disease 2019 (COVID-19) remains unknown. We have evaluated the consequences of one of these precautionary measures: the withdrawal of the cyclin D-dependent kinases 4/6 inhibitor (CDK4/6i) in patients whose metastatic disease was controlled by a combination of endocrine treatment and CDK 4/6i.

Method: This study was noninterventional, retrospective, multicentric, and included 60 patients with HR+ HER2- metastatic disease.

Pain Levels of Women Diagnosed with Endometriosis: Is There a Difference in Younger Women?

Study Objective: Early diagnosis and treatment of endometriosis affecting adolescent women are important in preventing chronic pain. Our aim was to analyze the clinical characteristics and severity of symptoms in adolescent patients with endometriosis compared with older patients.

Methods: This single-center retrospective cohort study in a tertiary referral hospital analyzed women whose first consultation at the certified endometriosis center of Bern University Hospital between January 2017 and December 2020 resulted in the clinical diagnosis of endometriosis.

The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients.

Germline DNA alterations affecting homologous recombination pathway genes have been associated with pancreatic cancer (PC) risk. BRCA2 is the most studied gene and affects the management of PC patients and their families. Even though recent reports have suggested a similar role of germline ATM pathogenic variants (PV) in familial PC, there is still a disagreement between experts on how it could affect patient management given the lack of proper PC risk estimates.

Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I.

Hereditary papillary renal cell carcinoma (HPRC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of the MET gene were identified in HPRC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants.

Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach.

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs.

Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation.

Background: Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation.

COVID-19 in Patients with Cancer: A Retrospective Study of 212 Cases from a French SARS-CoV-2 Cluster During the First Wave of the COVID-19 Pandemic.

We describe a large series of patients with solid tumors in an early COVID-19 cluster in the eastern part of France. From February to May 2020, this multicenter retrospective study enrolled 212 patients with cancer under treatment or on follow-up for any type of malignant solid tumor and positive for SARS-CoV-2. The mortality rate was 30%.

Superficial Granulomatous Pyoderma Gangrenosum Involving the Face: A Case Series of Five Patients and a Review of the Literature [Formula: see text].

Background: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful and ulcerating lesions on the skin. It rarely involves the face and is often difficult to diagnose. There are few cases reported in the literature of PG involving the face.

Multidisciplinary management of locally advanced and metastatic cutaneous squamous cell carcinoma.

Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cscc) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cscc face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist.

Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE).

Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE).

The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up.

Background: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types.

Methods: Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo).

Angiosarcoma complicating lower leg elephantiasis in a male patient: An unusual clinical complication, case report and literature review.

Chronic lymphedema is rarely complicated by an angiosarcoma. Angiosarcoma superimposed on chronic lymphedema (Stewart-Treves syndrome) is usually seen post breast cancer surgery accompanied by lymph node resection of the axilla. This is a case report of a 59-year-old male patient with elephantiasis that developed an angiosarcoma of the lower leg.

Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.

Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost-effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious-predicted variants in DNA repair genes in familial breast cancer (BC) in a well-characterized and homogeneous population.

Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC.

Background: Advanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine.

Method: The TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC.

Prognostic impact of the expression of NCR1 and NCR3 NK cell receptors and PD-L1 on advanced non-small cell lung cancer.

The putative contribution of natural killer (NK) cells to immunosurveillance in non-small cell lung cancer (NSCLC) has been an ongoing conundrum. Here, we used a readily standardizable quantitative real time polymerase chain reaction (qRT-PCR) to measure the expression of NK cell receptors in total peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV), patients with gastrointestinal stromal tumors (GIST), neuroblastoma (NB), melanoma or NSCLC. We quantified (which codes for NKp46) and (which codes for NKp30), as well as that of three splice variants (which give rise to immunostimulatory NKp30A and NKp30B, as well as to immunosuppressive NKp30C).

Vectorized gene therapy of liver tumors: proof-of-concept of TG4023 (MVA-FCU1) in combination with flucytosine.

Background: TG4023 is a modified vaccinia virus Ankara (MVA) containing the yeast-originated transgene FCU1, expressing cytosine deaminase and uracil phosphoribosyltransferase enzymes that transform the prodrug flucytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluorouridine-5′-monophosphate, respectively. This first-in-human study aimed to assess the maximum tolerated dose (MTD) of intratumoral (IT) TG4023 and the safety, feasibility, and proof-of-concept (PoC) of TG4023/5-FC combination to deliver high 5-FU concentrations in tumors.

Patients And Methods: Cancer patients without further therapeutic option and with at least one injectable primary or metastatic liver tumor underwent on day 1 a percutaneous IT injection of TG4023 at doses of 107, 108, or 4.

Trial Watch-Oncolytic viruses and cancer therapy.

Oncolytic virotherapy relies on the administration of non-pathogenic viral strains that selectively infect and kill malignant cells while favoring the elicitation of a therapeutically relevant tumor-targeting immune response. During the past few years, great efforts have been dedicated to the development of oncolytic viruses with improved specificity and potency. Such an intense wave of investigation has culminated this year in the regulatory approval by the US Food and Drug Administration (FDA) of a genetically engineered oncolytic viral strain for use in melanoma patients.

GENESIS: a French national resource to study the missing heritability of breast cancer.

Background: Less than 20% of familial breast cancer patients who undergo genetic testing for BRCA1 and BRCA2 carry a pathogenic mutation in one of these two genes. The GENESIS (GENE SISter) study was designed to identify new breast cancer susceptibility genes in women attending cancer genetics clinics and with no BRCA1/2 mutation.

Methods: The study involved the French national network of family cancer clinics.