Effects of a combined exercise and dietary intervention on clinical outcomes in patients with ovarian cancer: the Physical Activity and Dietary intervention in OVArian cancer (PADOVA) randomized controlled trial.

Objective: Chemotherapy treatment modifications can impact survival in patients with ovarian cancer, particularly when the relative dose intensity falls below 85%. Exercise and dietary interventions may benefit treatment tolerability. This study aimed to explore the effects of a combined exercise and dietary intervention on secondary outcomes of the Physical Activity and Dietary intervention in OVArian cancer (PADOVA) trial, specifically relative dose intensity and progression-free survival.

Dendritic cell vaccination combined with carboplatin/paclitaxel for metastatic endometrial cancer patients: results of a phase I/II trial.

Background: Metastatic endometrial cancer (mEC) continues to have a poor prognosis despite the introduction of several novel therapies including immune checkpoints inhibitors. Dendritic cell (DC) vaccination is known to be a safe immunotherapeutic modality that can induce immunological and clinical responses in patients with solid tumors. Platinum-based chemotherapy is known to act synergistically with immunotherapy by selectively depleting suppressive immune cells.

Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol.

Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors.

PAZEC: a Dutch Gynaecological Oncology Group open-label, multicenter, phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer.

Objective: There is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer.

Methods: In this phase II, open-label study, eligible patients had histologically or cytologically confirmed endometrial cancer, documented progressive disease, and a WHO performance status of ≤2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity, or patient refusal.

Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100.

Objective: This prespecified exploratory analysis evaluated the association of gene expression signatures, tumor mutational burden (TMB), and multiplex immunohistochemistry (mIHC) tumor microenvironment-associated cell phenotypes with clinical outcomes of pembrolizumab in advanced recurrent ovarian cancer (ROC) from the phase II KEYNOTE-100 study.

Methods: Pembrolizumab-treated patients with evaluable RNA-sequencing (n = 317), whole exome sequencing (n = 293), or select mIHC (n = 125) data were evaluated. The association between outcomes (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) and gene expression signatures (T-cell-inflamed gene expression profile [TcellGEP] and 10 non-TcellGEP signatures), TMB, and prespecified mIHC cell phenotype densities as continuous variables was evaluated using logistic (ORR) and Cox proportional hazards regression (PFS; OS).

Pharmacokinetic boosting of olaparib: A randomised, cross-over study (PROACTIVE-study).

Background: Pharmacokinetic (PK) boosting is the intentional use of a drug-drug interaction to enhance systemic drug exposure. PK boosting of olaparib, a CYP3A-substrate, has the potential to reduce PK variability and financial burden. The aim of this study was to investigate equivalence of a boosted, reduced dose of olaparib compared to the non-boosted standard dose.

Psychological impact over time of women with pregnancy loss due to gestational trophoblastic disease compared with miscarriage.

Objectives: Pregnancy loss, occurring after miscarriage or after gestational trophoblastic disease, has a psychological impact. Besides pregnancy loss, women diagnosed with gestational trophoblastic disease have to deal with a prolonged period of follow-up and potential advice to postpone a future pregnancy. We studied the severity and course of the psychological impact after gestational trophoblastic disease and miscarriage, to identify whether women with gestational trophoblastic disease need different psychological care.

Patient decision aids for patients with differentiated thyroid carcinoma: development process and alpha and beta testing.

Background: Patient decision aids (PtDAs) are structured clinical tools that facilitate shared decision-making. Two important treatment decisions for patients with differentiated thyroid cancer (DTC), which could benefit from PtDAs, are as follows (1): the extent of surgery decision in patients with low-risk DTC and (2) the decision to start or delay starting the treatment with tyrosine kinase inhibitors (TKIs) in patients with advanced tumors.

Material And Methods: PtDAs for these two decisions were developed using the International Patient Decision Aids Standards (IPDAS) quality criteria in an iterative process of prototype development alpha and beta testing by patients and physicians.

CINOVA: a phase II study of CPC634 (nanoparticulate docetaxel) in patients with platinum resistant recurrent ovarian cancer.

Objective: Recurrent platinum-resistant ovarian cancer has a poor prognosis with limited therapeutic options. Sub-therapeutic intra-tumoral drug concentrations may add to therapy resistance. CPC634 (docetaxel entrapped in CriPec nanoparticles) was designed to enhance tumor accumulation of drug with localized drug release at the target site to increase therapeutic efficacy.

Systemic exposure to cisplatin and paclitaxel after intraperitoneal chemotherapy in ovarian cancer.

Purpose: To determine the systemic exposure to cisplatin and paclitaxel after adjuvant intraperitoneal administration in patients with advanced ovarian cancer who underwent primary debulking surgery. This could provide an explanation for the high incidence of systemic adverse events associated with this treatment regimen.

Methods: This is a prospective pharmacokinetic study in patients with newly diagnosed advanced ovarian cancer who were treated with intraperitoneal administered cisplatin and paclitaxel.

The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis.

Background: The RAS/RAF/MEK/ERK (MAPK) pathway plays a role in ovarian carcinogenesis. Low-grade serous ovarian carcinoma (LGSOC) frequently harbors activating MAPK mutations. MAPK inhibitors have been used in small subsets of ovarian carcinoma (OC) patients to control tumor growth.

Attitudes Toward Striving for Quality and Length of Life Among Patients With Advanced Cancer and a Poor Prognosis.

Purpose: When deliberating palliative cancer treatment, insight into patients' attitudes toward striving for quality of life (QL) and length of life (LL) may facilitate goal-concordant care. We investigated the (1) attitudes of patients with advanced cancer toward striving for QL and/or LL and whether these change over time, and (2) characteristics associated with these attitudes (over time).

Methods: We performed a secondary analysis of a randomized controlled trial on improving shared decision making (SDM), without differentiation between intervention arms.

The progression-free survival ratio as outcome measure in recurrent ovarian carcinoma patients: Current and future perspectives.

Objective: Clinical efficacy of cytostatic anticancer agents can be determined with the progression-free survival (PFS) ratio. This outcome measure compares PFS achieved by a new treatment (PFS2) to the PFS of the most recent treatment on which the patient has experienced progression (PFS1). Clinical benefit has been defined as a PFS-ratio (PFS2/PFS1) > 1.

Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial).

Background: This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC).

Methods: This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months.

PD-L1 in gestational trophoblastic disease: an antibody evaluation.

Introduction: Treatment with antibodies directed against programed-cell death ligand 1 (PD-L1) is a novel therapy for patients with gestational trophoblastic disease. Assessment of PD-L1 expression in tumor tissue is commonly used to identify patients who might benefit from anti-PD-L1 treatment. Multiple antibodies are available to detect PD-L1-expressing cells, and percentages of PD-L1-expressing cells in samples of patients with gestational trophoblastic disease indicated by these antibodies differ substantially.

Distinct Genomic Profiles Are Associated with Treatment Response and Survival in Ovarian Cancer.

The majority of patients with ovarian cancer ultimately develop recurrent chemotherapy-resistant disease. Treatment stratification is mainly based on histological subtype and stage, prior response to platinum-based chemotherapy, and time to recurrent disease. Here, we integrated clinical treatment, treatment response, and survival data with whole-genome sequencing profiles of 132 solid tumor biopsies of metastatic epithelial ovarian cancer to explore genome-informed stratification opportunities.

Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial).

Background: Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer.

Patients And Methods: Patients with metastatic or recurrent endometrial cancer were enrolled.

Assessing the safety, tolerability and efficacy of PLGA-based immunomodulatory nanoparticles in patients with advanced NY-ESO-1-positive cancers: a first-in-human phase I open-label dose-escalation study protocol.

Introduction: The undiminished need for more effective cancer treatments stimulates the development of novel cancer immunotherapy candidates. The archetypical cancer immunotherapy would induce robust, targeted and long-lasting immune responses while simultaneously circumventing immunosuppression in the tumour microenvironment. For this purpose, we developed a novel immunomodulatory nanomedicine: PRECIOUS-01.

CD34 progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rg mice.

Combining natural killer (NK) cell adoptive transfer with tumor-sensitizing chemotherapy is an attractive approach against recurrent ovarian cancer (OC), as OC is sensitive to NK cell-mediated immunity. Previously, we showed that CD34 hematopoietic progenitor cell (HPC)-derived NK cells can kill OC cells and inhibit OC tumor growth in mice. Here, we investigated the potential of HPC-NK cell therapy combined with chemotherapeutic gemcitabine (used in recurrent OC patients) against OC.

Early prediction of post-molar gestational trophoblastic neoplasia and resistance to methotrexate, based on a single serum human chorionic gonadotropin measurement.

Background: Clinicians are unable to provide individualized counseling regarding risk of progression for patients with a complete hydatidiform mole (CHM). We developed nomograms enabling early prediction of post-molar gestational trophoblastic neoplasia (GTN) and resistance to methotrexate (MTX) based on a single serum human chorion gonadotropin (hCG) measurement.

Methods: We generated two nomograms with logistic regression: to predict post-molar GTN, and MTX resistance.

Evaluation of two strategies to implement physical cancer rehabilitation guidelines for survivors of abdominopelvic cavity tumors: a controlled before-and-after study.

Purpose: This study evaluates the effectiveness and feasibility of two strategies to implement physical cancer rehabilitation (PCR) guidelines for patients who have survived abdominopelvic cavity malignancies.

Methods: We tested and compared two tailored strategies to implement PCR guidelines for survivors of gastrointestinal, female organ and urogenital organ malignancies, in a clustered controlled before-and-after study. A patient-directed (PD) strategy was tested in five cancer centers, aiming to empower survivors.