The disruption of the CCDC6 - PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma

Treatment with PARP inhibitors (PARPi) is primarily effective against high-grade serous ovarian cancers (HGSOC) with BRCA1/2 mutations or other deficiencies in homologous recombination (HR) repair mechanisms. However, resistance to PARPi frequently develops, mostly as a result of BRCA1/2 reversion mutations. The tumour suppressor CCDC6 is involved in HR repair by regulating the PP4c phosphatase activity on γH2AX. In this work, we reported that in ovarian cancer cells, a physical or functional loss of CCDC6 results synthetic lethal with the PARP-inhibitors drugs, by affecting the HR repair. We also unravelled a role for CCDC6 as predictive marker of PARPi sensitivity in ovarian cancer, and the impact of CCDC6 downregulation in overcoming PARPi resistance in these tumours

Costs of clinical trials with anticancer biological agents in an Oncologic Italian Cancer Center using the activity-based costing methodology

The aim of the present study was to assess the estimated "per patient" total cost for a single Oncologic Italian Cancer Center participating in a multicenter clinical trial with new anticancer biological agents using the activity-based costing (ABC) methodology

Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22)

BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine (R)).RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found.CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics

A case of Vaccine-Induced Thrombotic Thrombocytopenia (VITT) with thrombosis of the superior mesenteric artery after ChAdOx1 nCov-19 COVID-19 Vaccine

We describe the case of a 64 years-old woman admitted to the Emergency Department of the ASST-Spedali Civili of Brescia with fever and gastrointestinal symptoms 10 days after the first dose of ChAdOx1 nCov-19 vaccine. Laboratory investigations showed severe thrombocytopenia and high D-dimer, while an abdominal CT scan reported a partially occluding thrombosis of the superior mesenteric artery. Following treatment with fondaparinux, immunoglobulins and high dosage steroid therapy, we observed a rapid improvement of patient’s conditions. An ELISA assay showed the presence of antibodies against heparin PF4-complex. Subsequent abdominal CT-scan showed the superior mesenteric artery thrombosis resolution, and the patient was finally discharged after 12 days of hospitalization. Several reports pointed to the venous system as the main district affected by Vaccine-Induced Thrombotic Thrombocytopenia (VITT), while a peculiar feature of this report is the involvement of the mesenteric arterial system. Further investigation of VITT’s pathophysiological mechanisms is mandatory to develop preventive strategies and effective treatments

The Public Health Impact of the So-Called "Fluad Effect" on the 2014/2015 Influenza Vaccination Campaign in Italy: Ethical Implications for Health-Care Workers and Health Communication Practitioners

Seasonal influenza, causing complications, hospitalizations and deaths, generates a serious socio-economic burden, especially among elderly and high-risk subjects, as well as among adult individuals. Despite the availability and active free-of charge offer of influenza vaccines, vaccine coverage rates remain low and far from the target established by the Ministry of Health. Notwithstanding their effectiveness, vaccines are victims of prejudices and false myths, that contribute to the increasing phenomenon of vaccine hesitancy and loss of confidence. Media and, in particular, new media and information and communication technologies (ICTs) play a major role in disseminating health-related information. They are extremely promising devices for delivering health education and promoting disease prevention, including immunization. However, they can also have a negative impact on population\ue2\u80\u99s health attitudes and behaviors when channeling wrong, misleading information. During the 2014/2015 influenza vaccination campaign, the report of four deaths allegedly caused by administration of an adjuvanted influenza vaccine, Fluad the so-called \ue2\u80\u9cFluad case\ue2\u80\u9d received an important media coverage, which contributed to the failure of the vaccination campaign, dramatically reducing the influenza vaccine uptake. In the extant literature, there is a dearth of information concerning the effect of the \ue2\u80\u9cFluad case\ue2\u80\u9d. The current study aims at quantifying the impact of the \ue2\u80\u9cFluad effect\ue2\u80\u9d at the level of the Local Health Unit 3 (LHU3) ASL3 Genovese, Genoa, Italy. Ethical implications for health-care workers and health communication practitioners are also envisaged

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy.

ABSTRACT Background Chemotherapy with carboplatin, paclitaxel, and bevacizumab is the standard therapy for patients with advanced stage ovarian cancer wild-type BRCA after primary surgery. The most frequent side effects of bevacizumab in this setting are hypertension, thrombosis, hemorrhage, and proteinuria, while arthralgia has been poorly described. Objective To examine the incidence, duration, and reversibility of arthralgia. Patients and methods A retrospective analysis was performed to describe the occurrence and outcome of arthralgia in 114 patients with advanced ovarian cancer, given first-line treatment with a combination of carboplatin, paclitaxel, and bevacizumab. Statistical analysis was performed to investigate a possible prognostic role of arthralgia, with progression-free survival as endpoint. Results 47 of 114 patients (41%) developed arthralgia during therapy. All patients had grade 1 or grade 2 arthralgia. Toxicity persisted after the end of bevacizumab in 17/47 patients (36%). Median progression-free survival for patients without arthralgia was 18 months (95% CI 14 to 24) compared with 29 months (95% CI 21 to not reached) for patients experiencing arthralgia (p=0.03). In order to avoid possible biases related to treatment duration, a multivariable Cox proportional hazards model including toxicity as a time dependent variable and age, stage, and residual disease after primary surgery was performed. In this model no variable showed a statistically significant association with progression-free survival. Conclusion A high incidence of arthralgia (41%) was found and although rogression-free survival was worse for those patients who developed arthralgia, this was not maintained on multivariate analysis. Guidelines for treatment of this adverse event are needed

A qualitative analysis and development of a conceptual model assessing financial toxicity in cancer patients accessing the universal healthcare system

Purpose This paper illustrates a conceptual model for a new patient-reported outcome measure (PROM) aimed at measuring financial toxicity (FT) in oncological setting in Italy, where citizens are provided universal healthcare coverage. Methods Focus groups with overall 34 patients/caregivers in three different Italian centers (from Northern, Centre, and Southern Italy) and an open-ended survey with 97 medical oncologists were undertaken. Transcripts from focus groups and the open-ended survey were analyzed to identify themes and links between themes. Themes from the qualitative research were supplemented with those reported in the literature; concepts identified formed the basis for item development that were then tested through the importance analysis (with 45 patients) and the cognitive debriefing (with other 45 patients) to test relevance and comprehension of the first draft PRO instrument. Results Ten domains were extracted by analyzing 156 concepts generated from focus groups and the open-ended survey. After controlling for redundancy, 55 items were generated and tested through the importance analysis. After controlling comprehension and feasibility through cognitive debriefing interviews, a first version of the questionnaire consisting of 30 items was devised. Conclusions This qualitative study represents the first part of a study conducted to develop a new PROM to assess FT in Italy, by using a bottom-up approach that makes the most of patients’ experiences and the health system analysis. Trial registration clinicaltrials.gov NCT03473379 first posted on March 22, 2018