Response to systemic therapies in patient-derived cell lines from primary and recurrent adult granulosa cell tumors.

In patients with the rare adult-type granulosa cell tumors (aGCT), surgery is the primary treatment for both primary and recurrent disease. In cases of inoperable disease, systematic therapy is administered, but variable response rates and drug resistance complicate predicting the most effective therapy. Drug screen testing on patient-derived cell lines may offer a solution.

Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma.

Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC.

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.

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study.

Objective: In the first part of this phase II study (NCT01164995), the combination of carboplatin and adavosertib (AZD1775) was shown to be safe and effective in patients with TP53 mutated platinum-resistant ovarian cancer (PROC). Here, we present the results of an additional safety and efficacy cohort and explore predictive biomarkers for resistance and response to this combination treatment.

Methods: This is a phase II, open-label, non-randomized study.

Response to Systemic Therapies in Ovarian Adult Granulosa Cell Tumors: A Literature Review.

For adult granulosa cell tumors (aGCTs), the preferred treatment modality is surgery. Chemotherapy and anti-hormonal therapy are also frequently used in patients with recurrent aGCT. We aimed to review the existing literature on the response to chemotherapy and anti-hormonal therapy in patients with aGCT.

Frailty and checkpoint inhibitor toxicity in older patients with melanoma.

Background: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) that range from mild to life-threatening. Age itself does not seem to be a predictor for the occurrence of irAEs. It is unknown whether frailty plays a role in the occurrence of irAEs.

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.

Patient-Reported Outcomes During Checkpoint Inhibition: Insight into Symptom Burden in Daily Clinical Practice.

Context: While praised for inducing durable anti-tumour responses, immune checkpoint inhibitors (ICI) also cause immune-related adverse events (irAEs) that can vary in severity and affect health-related quality of life (HRQL).

Objectives: This study was performed to provide insight into the course of symptoms and the influence of irAEs on HRQL measured with the treatment-specific Utrecht Symptom Diary Immunotherapy (USD-I).

Methods: In this observational cohort study, melanoma or non-small lung cancer (NSCLC) patients treated with PD(L)1-inhibitors between February 2016 and December 2018 were included.

The association between patient satisfaction with information and adherence to oral anticancer agents.

Introduction: Adherence to anticancer agents is a critical factor in achieving adequate clinical response, and became a major challenge for patients and caregivers since the increased substitution of parenteral cytostatic by oral drugs. One of the factors that influences adherence is how well informed patients are about their therapy. This study assesses the association between patient satisfaction with information about oral anticancer agents and adherence.

Functional decline after surgery in older patients with head and neck cancer.

Introduction: In addition to classical endpoints such as survival and complication rates, other outcomes such as quality of life and functional status are increasingly recognized as important endpoints, especially for elderly patients. However, little is known about the long-term effect of surgery with regard to these other outcomes. Our aim is to investigate the functional status and self-reported health status of patients ≥ 70 years one year after surgery for head and neck cancer.

Phase II study of definitive chemoradiation for locally advanced squamous cell cancer of the vulva: An efficacy study.

Objective: To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival.

Methods: In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated.

Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer.

Background: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy.

[F]FDG and [F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary.

Purpose: Adult granulosa cell tumors (AGCTs) of the ovary represent a rare malignancy in which timing and choice of treatment is a clinical challenge. This study investigates the value of FDG-PET/CT and FES-PET/CT in monitoring recurrent AGCTs and assessing eligibility for anti-hormonal treatment.

Materials And Methods: We evaluated 22 PET/CTs from recurrent AGCT patients to determine tumor FDG ( = 16) and FES ( = 6) uptake by qualitative and quantitative analysis.

The attributive value of comprehensive surgical staging in clinically early-stage epithelial ovarian carcinoma: A systematic review and meta-analysis.

Background: Tumor positivity and upstaging rates from various surgical staging steps performed in clinically early-stage epithelial ovarian carcinoma (EOC) vary widely in literature.

Aim: To quantify tumor positivity and upstaging rates for all staging surgery steps in EOC patients. Differences between subgroups based on their clinical and histological characteristics are explored.

Development and testing of a tailored online fertility preservation decision aid for female cancer patients.

Background: Decision making regarding future fertility can be very difficult for female cancer patients. To support patients in decision making, fertility preservation decision aids (DAs) are being developed. However, to make a well-informed decision, patients need personalized information tailored to their cancer type and treatment.

Population Pharmacokinetics of Docetaxel, Paclitaxel, Doxorubicin and Epirubicin in Pregnant Women with Cancer: A Study from the International Network of Cancer, Infertility and Pregnancy (INCIP).

Background: Based on reassuring short-term foetal and maternal safety data, there is an increasing trend to administer chemotherapy during the second and third trimesters of pregnancy. The pharmacokinetics (PK) of drugs might change as a result of several physiological changes that occur during pregnancy, potentially affecting the efficacy and safety of chemotherapy.

Objective: With this analysis, we aimed to quantitatively describe the changes in the PK of docetaxel, paclitaxel, doxorubicin and epirubicin in pregnant women compared with non-pregnant women.

In Vitro Systematic Drug Testing Reveals Carboplatin, Paclitaxel, and Alpelisib as a Potential Novel Combination Treatment for Adult Granulosa Cell Tumors.

Adult granulosa cell tumors (AGCTs) arise from the estrogen-producing granulosa cells. Treatment of recurrence remains a clinical challenge, as systemic anti-hormonal treatment or chemotherapy is only effective in selected patients. We established a method to rapidly screen for drug responses in vitro using direct patient-derived cell lines in order to optimize treatment selection.

Intraperitoneal treatment for advanced ovarian cancer, the Dutch experience. What did we learn?

Background: Combined administration of intravenous (iv) and intraperitoneal (ip) (iv/ip) chemotherapy is an effective adjuvant treatment option after primary debulking surgery (PDS) for advanced ovarian cancer (OC). Increased toxicityand patient burden limit its use in daily practice.

Objective: To assess toxicity and survival outcomes of iv/ip chemotherapy in daily practice in the Netherlands.

Validation of the G8 screening tool in older patients with cancer considered for surgical treatment.

Background: The Geriatric 8 (G8) has proven to be one of the most sensitive frailty-screening tools for older patients with cancer undergoing systemic treatment. In this study we validated whether the G8 is also suitable for identifying impairments in their comprehensive geriatric assessment (CGA) in older patients with cancer undergoing surgery. Thereby, we investigated the differences in postoperative outcomes between the fit and frail patients classified by the G8.

Prospective practice survey of management of cetuximab-related skin reactions.

Purpose: Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab.

Methods: An open-label, prospective observational study conducted in the Netherlands.

Validation of the Dutch version of the Edmonton Symptom Assessment System.

Background: The Utrecht Symptom Diary (USD) is a Dutch and adapted version of the Edmonton Symptom Assessment System, a patient-reported outcome measurement (PROM) tool to asses and monitor symptoms in cancer patients. This study analyses the validity and responsiveness of the USD and the cutoff points to determine the clinical significance of a symptom score.

Methods: Observational longitudinal cohort study including adult in- and outpatients treated in an academic hospital in the Netherlands who completed at least one USD as part of routine care (2012-2019).

Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses.

There remains an unmet need for preclinical models to enable personalized therapy for ovarian cancer (OC) patients. Here we evaluate the capacity of patient-derived organoids (PDOs) to predict clinical drug response and functional consequences of tumor heterogeneity. We included 36 whole-genome-characterized PDOs from 23 OC patients with known clinical histories.

Whole Genome Analysis of Ovarian Granulosa Cell Tumors Reveals Tumor Heterogeneity and a High-Grade TP53-Specific Subgroup.

Adult granulosa cell tumors (AGCTs) harbor a somatic c.402C>G mutation in ~95% of cases and are mainly surgically removed due to limited systemic treatment effect. In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA.