Safety and dose modification for patients receiving niraparib.

Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.

Tumor progression and metastatic dissemination in ovarian cancer after dose-dense or conventional paclitaxel and cisplatin plus bevacizumab.

The efficacy of therapeutic regimens incorporating weekly or every-3-weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose-dense-equi (every other day to the conventional cumulative dose), or dose-dense-high (total dose 1.

Radiomics of high-grade serous ovarian cancer: association between quantitative CT features, residual tumour and disease progression within 12 months.

Objectives: To determine if radiomic features, alone or combined with clinical data, are associated with residual tumour (RT) at surgery, and predict the risk of disease progression within 12 months (PD12) in ovarian cancer (OC) patients.

Methods: This retrospective study enrolled 101 patients according to the following inclusion parameters: cytoreductive surgery performed at our institution (9 May 2007-23 February 2016), assessment of BRCA mutational status, preoperative CT available. Radiomic features of the ovarian masses were extracted from 3D structures drawn on CT images.

Radiotherapy in patients with cardiac implantable electronic devices: clinical and dosimetric aspects.

As a result of aging, the number of patients with cardiac implantable electronic device (CIED) requiring radiotherapy (RT) continues to rise. The aim of this work was to evaluate RT-related malfunctions of CIED in a cohort of patients who underwent RT in our clinic from June 2010 to December 2016. We retrospectively analyzed 93 RT treatments in 63 patients with CIEDs.

Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer.

Purpose There is a growing demand for BRCA1/ 2 mutation ( BRCAm) testing in patients with ovarian cancer; however, the limited number of genetic counselors presents a potential barrier. To facilitate more widespread BRCAm testing in ovarian cancer, pretest counseling by the oncology team could shorten testing turnaround times and ease the pressure on genetic counselors. Patients and Methods The prospective, observational Evaluating a Streamlined Onco-genetic BRCA Testing and Counseling Model Among Patients With Ovarian Cancer (ENGAGE) study evaluated a streamlined, oncologist-led BRCAm testing pathway.

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells.

Cancer-initiating cells (CICs) have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC), CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs) remain elusive.

Safety and Efficacy of Extended Bevacizumab Therapy in Elderly (≥70 Years) Versus Younger Patients Treated for Newly Diagnosed Ovarian Cancer in the International ROSiA Study.

Objective: The single-arm ROSiA study explored an extended duration of frontline bevacizumab-containing therapy for ovarian cancer. Post hoc analyses explored safety and efficacy according to age.

Patients And Methods: After primary debulking surgery, patients with stage IIB-IV or grade 3 stage I-IIA ovarian cancer received 4-8 cycles of paclitaxel [weekly or every 3 weeks (q3w)], carboplatin AUC 5-6 q3w, and bevacizumab 15 (or 7.

Epigenome-based cancer risk prediction: rationale, opportunities and challenges.

The incidence of cancer is continuing to rise and risk-tailored early diagnostic and/or primary prevention strategies are urgently required. The ideal risk-predictive test should: integrate the effects of both genetic and nongenetic factors and aim to capture these effects using an approach that is both biologically stable and technically reproducible; derive a score from easily accessible biological samples that acts as a surrogate for the organ in question; and enable the effectiveness of risk-reducing measures to be monitored. Substantial evidence has accumulated suggesting that the epigenome and, in particular, DNA methylation-based tests meet all of these requirements.

Fibroblastic Malignant Peripheral Nerve Sheath Tumour of the Uterine Cervix: Report of a Case and Literature Review With Emphasis on Possible Differential Diagnosis.

Cervical sarcomas are rare neoplasms, accounting for <1% of all cervical malignancies and characterized by an aggressive course despite radical excision. We report the clinical and microscopic features of a spindle cell sarcoma arising as a polypoid endocervical mass in a 45-yr-old woman. The neoplasm was characterized by a monotonous, mildly atypical proliferation of spindle cells, displaying a fibrosarcoma-like parallel pattern of highly dense fascicles, growing under the cervical epithelium.

Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer.

Background: Linsitinib, an oral, dual inhibitor of insulin-like growth factor-1 receptor and insulin receptor, in combination with weekly paclitaxel, may improve clinical outcomes compared with paclitaxel alone in patients with refractory or platinum-resistant ovarian cancer.

Patients And Methods: This open-label phase 1/2 clinical trial (NCT00889382) randomized patients with refractory or platinum-resistant ovarian cancer (1:1:1) to receive either oral intermittent linsitinib (600mg once daily on Days 1-3 per week) combined with paclitaxel (80mg/m on Days 1, 8, and 15; Arm A) or continuous linsitinib (150mg twice daily) in combination with paclitaxel (Arm B), or paclitaxel alone (Arm C). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety/tolerability.

Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells' vulnerability to DNA-damaging agents.

Genomic instability plays a pathological role in various malignancies, including acute myeloid leukemia (AML), and thus represents a potential therapeutic target. Recent studies demonstrate that SIRT6, a NAD-dependent nuclear deacetylase, functions as genome-guardian by preserving DNA integrity in different tumor cells. Here, we demonstrate that also CD34 blasts from AML patients show ongoing DNA damage and SIRT6 overexpression.

When nonplatinum is the answer: the role of trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer.

Trabectedin + pegylated liposomal doxorubicin (PLD) offers a well tolerated and effective nonplatinum, nontaxane alternative for treatment of ovarian cancer patients with a treatment-free interval after platinum beyond 6 months, especially for those relapsing between 6 and 12 months and those who are not candidates to receive platinum-based therapy. Using the nonplatinum trabectedin + PLD combination gives patients time to recover from platinum-related toxicities and may restore platinum sensitivity in tumor cells. The sequence effect, by which intercalation of trabectedin + PLD between platinum regimens may enhance the activity of next platinum and improve survival, is currently under investigation in the Phase III prospective INternational OVArian cancer patients Trial with YONdelis.

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.

Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries.

Risk-reducing Salpingo-Oophorectomy in Women at Higher Risk of Ovarian and Breast Cancer: A Single Institution Prospective Series.

Background/aim: Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center.

Patients And Methods: A series of RRSO specimens (including endometrial biopsy) from women carrying a BRCA mutation, BRCA-unknown and BRCA-negative were collected between January 1998 and April 2016 at the Division of Gynecology at the European Institute of Oncology.

Quantitative assessment of salivary oral bacteria according to the severity of dental caries in childhood.

This study aimed to assess differences in selected oral bacteria in children according to the severity of dental caries. One hundred and thirty-six children, 36-60 months old were divided into three groups according to caries status: caries-free (CF) (n=47), early childhood caries (ECC) (n=40) and severe-early childhood caries (S-ECC) (n=49). Saliva was collected for detection and quantification of selected oral streptococci, Actinomyces naeslundii, Lactobacillus spp.

Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.

Background: Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib.

Methods: This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy.

Genotypic diversity and phenotypic traits of Streptococcus mutans isolates and their relation to severity of early childhood caries.

Background: Early childhood caries (ECC) is an aggressive condition that can affect teeth of young children. This study aimed to evaluate genotypic diversity and phenotypic traits of S. mutans isolated from dental biofilms of children with different caries status in comparison with caries free (CF) children.

Clinical benefit and risk of death with endocrine therapy in ovarian cancer: A comprehensive review and meta-analysis.

Background: Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown.

Methods: Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed.