Influence of pregnancy on glioma patients.

Background: Data about the influence of pregnancy on progression-free survival and overall survival of glioma patients are sparse and controversial. We aimed at providing further evidence on this relation.

Methods: The course of 18 glioma patients giving birth to 23 children after tumor surgery was reviewed and compared to the course of 18 nulliparous female patients matched for tumor diagnosis including molecular markers, extent of resection, and tumor location.

Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial.

Objective: To analyze the safety and efficacy of niraparib in patients aged ≥70 years with recurrent ovarian cancer in the ENGOT-OV16/NOVA trial.

Methods: The trial enrolled 2 independent cohorts with histologically diagnosed recurrent ovarian, fallopian tube, or peritoneal cancer who responded to platinum rechallenge, on the basis of germline breast cancer susceptibility gene mutation (gBRCAmut) status. Patients were randomized 2:1 to receive niraparib (300 mg) or placebo once daily until disease progression.

Disruption of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α reverts key features of the neoplastic phenotype of glioma cells.

The peroxisome proliferator-activated receptor γ coactivator (PGC)-1α is a master regulator of mitochondrial biogenesis and controls metabolism by coordinating transcriptional events. Here, we interrogated whether PGC-1α is involved in tumor growth and the metabolic flexibility of glioblastoma cells. PGC-1α was expressed in a subset of established glioma cell lines and primary glioblastoma cell cultures.

Distribution and prognostic impact of microglia/macrophage subpopulations in gliomas.

While the central nervous system is considered an immunoprivileged site and brain tumors display immunosuppressive features, both innate and adaptive immune responses affect glioblastoma (GBM) growth and treatment resistance. However, the impact of the major immune cell population in gliomas, represented by glioma-associated microglia/macrophages (GAMs), on patients' clinical course is still unclear. Thus, we aimed at assessing the immunohistochemical expression of selected microglia and macrophage markers in 344 gliomas (including gliomas from WHO grade I-IV).

Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12.

Objective: Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings.

Methods: Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle.

Pattern and impact of metastatic cardiophrenic lymph nodes in advanced epithelial ovarian cancer.

Background: Cardiophrenic lymph nodes (CPLN) define FIGO stage IVB disease. We evaluate the pattern of CPLN metastases, their prognostic impact and the potential role of CPLN resection in patients with epithelial ovarian cancer (EOC).

Methods: Analysis of 595 consecutive patients with EOC treated in the period 01/2011-05/2016.

Podoplanin expression is a prognostic biomarker but may be dispensable for the malignancy of glioblastoma.

Background: Treatment options of glioblastoma, the most aggressive primary brain tumor with frequent relapses and high mortality, are still very limited, urgently calling for novel therapeutic targets. Expression of the glycoprotein podoplanin correlates with poor prognosis in various cancer entities, including glioblastoma. Furthermore, podoplanin has been associated with tumor cell migration and proliferation in vitro; however, experimental data on its function in gliomagenesis in vivo are still missing.

Uterine and Tubal Lavage for Earlier Cancer Detection Using an Innovative Catheter: A Feasibility and Safety Study.

Objectives: Poor survival of high-grade serous pelvic cancer is caused by a lack of effective screening measures. The detection of exfoliated cells from high-grade serous pelvic cancer, or precursor lesions, is a promising concept for earlier diagnosis. However, collecting those cells in the most efficient way while fulfilling all requirements for a screening approach is a challenge.

Low-grade Serous Ovarian Carcinoma.

In the early 2000s a two-tier grading system was introduced for serous ovarian cancer. Since then, we have increasingly come to accept that low-grade serous ovarian carcinoma (LGSOC) is a separate entity with a unique mutational landscape and clinical behaviour. As less than 10% of serous carcinomas of the ovary are low-grade, they are present in only a small number of patients in clinical trials for ovarian cancer.

Is there a role for HIPEC in ovarian cancer?

Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer (EOC) and other tumor entities, despite lack of robust data supporting this. Publicly available evidence addressing the value of HIPEC in EOC is rather inconclusive, revealing contradictory and inconsistent results while some studies even report harm to the patients from a higher morbidity. On this ground, we cannot recommend the implementation and use of HIPEC outside of a randomized clinical trial setting.

Diagnosis of Li-Fraumeni Syndrome: Differentiating TP53 germline mutations from clonal hematopoiesis: Results of the observational AGO-TR1 trial.

The Li-Fraumeni cancer predisposition syndrome (LFS1) presents with a variety of tumor types and the TP53 gene is covered by most diagnostic cancer gene panels. We demonstrate that deleterious TP53 variants identified in blood-derived DNA of 523 patients with ovarian cancer (AGO-TR1 trial) were not causal for the patients' ovarian cancer in three out of six TP53-positive cases. In three out of six patients, deleterious TP53 mutations were identified with low variant fractions in blood-derived DNA but not in the tumor of the patient seeking advice.

Akt and mTORC1 signaling as predictive biomarkers for the EGFR antibody nimotuzumab in glioblastoma.

Glioblastoma (GB) is the most frequent primary brain tumor in adults with a dismal prognosis despite aggressive treatment including surgical resection, radiotherapy and chemotherapy with the alkylating agent temozolomide. Thus far, the successful implementation of the concept of targeted therapy where a drug targets a selective alteration in cancer cells was mainly limited to model diseases with identified genetic drivers. One of the most commonly altered oncogenic drivers of GB and therefore plausible therapeutic target is the epidermal growth factor receptor (EGFR).

Ventriculoperitoneal Shunts Equipped with On-Off Valves for Intraventricular Therapies in Patients with Communicating Hydrocephalus due to Leptomeningeal Metastases.

Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually switch off the shunt function can be used for intraventricular injections of therapeutics in patients suffering from a communicating hydrocephalus caused by leptomeningeal metastases. These shunt devices avoid the risk of injecting therapeutics through the distal leg of the shunt system into the intraperitoneal space, which may cause toxicity. Furthermore, regular intraventricular injections of chemotherapeutics help to maintain sufficient concentrations in the ventricular space.

Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Antiangiogenic therapy has known activity in ovarian cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for platinum-resistant or platinum-refractory ovarian cancer.

Methods: We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany.

Skeletal Muscle Attenuation (Sarcopenia) Predicts Reduced Overall Survival in Patients with Advanced Epithelial Ovarian Cancer Undergoing Primary Debulking Surgery.

Background: Sarcopenia was reported as a prognostic factor in cancer patients. Using computed tomography (CT), we analyzed the impact of sarcopenia on overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS).

Methods: Preoperative CT scans of consecutive EOC patients (n = 323) were retrospectively assessed for skeletal muscle index (SMI) and muscle attenuation (MA; Hounsfield units [HU]).

EGFL7 enhances surface expression of integrin αβ to promote angiogenesis in malignant brain tumors.

Glioblastoma (GBM) is a typically lethal type of brain tumor with a median survival of 15 months postdiagnosis. This negative prognosis prompted the exploration of alternative treatment options. In particular, the reliance of GBM on angiogenesis triggered the development of anti-VEGF (vascular endothelial growth factor) blocking antibodies such as bevacizumab.

The Impact of Early Corticosteroid Pretreatment Before Initiation of Chemotherapy in Patients With Primary Central Nervous System Lymphoma.

Background: The optimal timing of corticosteroid (CS) treatment in patients with primary central nervous system (CNS) lymphoma (PCNSL) remains controversial. While poor clinical presentation may justify early treatment with CS, this may ultimately result in reduced concentrations of chemotherapeutic agents via perturbations in the permeability of the blood-brain barrier.

Objective: To investigate whether early CS exposure is associated with beneficial outcomes and/or reduced occurrence of adverse events as opposed to delayed/concomitant administration.

Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate.

The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. Here, we identify an additional activity of R-2-HG: tumor cell-derived R-2-HG is taken up by T cells where it induces a perturbation of nuclear factor of activated T cells transcriptional activity and polyamine biosynthesis, resulting in suppression of T cell activity. IDH1-mutant gliomas display reduced T cell abundance and altered calcium signaling.

Increased tumor vascularization is associated with the amount of immune competent PD-1 positive cells in testicular germ cell tumors.

Testicular germ cell cancer in a metastatic state is curable with a cisplatin-based first line chemotherapy. However, 10-15% of these patients are resistant to first line chemotherapy and are thus left with only palliative options. Immunotherapies and inhibition of angiogenesis used in multiple types of cancer; however, the molecular context of angiogenesis and immune checkpoints in the development and progression of testicular cancers is still unknown.