The brave new world of endometrial cancer : Future implications for adjuvant treatment decisions.

PURPOSE: For many decades, endometrial cancer (EC) has been considered as a homogenous tumor entity with good prognosis. The currently valid risk stratification considers clinical and pathological factors. Treatment recommendations differ considerably from country to country. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) Research Network has shown that ECs should be reclassified into four novel molecular prognostic groups, with the potential of changing adjuvant management of EC patients: ultra-mutated, hyper-mutated, copy-number low, and copy-number high. Clinical examples are shown, and the available literature has been highlighted. The European Society of Gynaecological Oncology (ESGO) guideline for endometrial cancer takes the new classification system into consideration for adjuvant treatment decisions and will be published this year. RESULTS: In the near future, we expect new treatment recommendations that may differ considerably from the clinicopathologically driven recommendations on the basis of our deeper insight and better understanding of molecular markers in endometrial cancer. The PORTEC 4a study is the only recruiting study which randomizes patients to adjuvant or no adjuvant treatment on the basis of the aforementioned new classification system. CONCLUSION: The aim of the new classification is a more personalized adjuvant radio(chemo)therapy decision and better oncologic outcomes or avoidance of overtreatment.

[BRCA diagnostics of ovarian cancer : Molecular tumor testing since the introduction of PARP inhibitor therapy]. / BRCA-Diagnostik an Ovarialkarzinomen : Molekulare Tumortestung seit Einführung der PARP-Inhibitortherapie.

Approximately 9000 women are diagnosed with ovarian cancer in Germany each year. The most common subtype is high-grade serous ovarian cancer. A relevant proportion of these tumors are associated with mutations in the breast and ovarian cancer susceptibility genes (BRCA1 and BRCA2) representing highly penetrant tumor suppressor genes with autosomal inheritance and play a crucial role in DNA repair mechanisms. These patients have predominantly germline mutations and less frequently have somatic BRCA mutations. Tumors harboring BRCA mutations show a significant improvement in progression-free survival under therapy with poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors. In 2015 the first PARP inhibitor was approved for the therapy of high-grade serous ovarian cancer with BRCA mutations. Mutation analysis can be performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue within a few days.

Our 2015 approach to invasive pulmonary aspergillosis.

At the University Hospital of Cologne, in general two patient groups at high risk for invasive aspergillosis receive posaconazole prophylaxis: Acute myelogenous leukaemia patients during remission induction chemotherapy and allogeneic haematopoietic stem cell transplant recipients. Other patients at risk undergo serum galactomannan testing three times weekly. At 72-96 h of persisting fever despite broad-spectrum antibiotics, or at onset of lower respiratory tract symptoms a thoracic computed tomography (CT) scan is performed. Without lung infiltrates on CT, IPA is ruled out. In lung infiltrates not suggestive for IPA mycological confirmation is pursued. In patients without posaconazole prophylaxis empiric caspofungin will be considered. CT findings typical for IPA prompt targeted treatment, and mycological confirmation. Bronchoalveolar lavage (BAL) is most important for cultural identification and susceptibility testing, and facilitates diagnosing other pathogens. BAL performance is virtually independent of platelet counts. If despite suggestive infiltrates BAL does not yield the diagnosis, CT-guided biopsy follows as soon as platelet counts allow. Surgery can also be beneficial in diagnosis and treatment of IPA. If the diagnosis of IPA is not established, mucormycosis is a valid concern. In patients with breakthrough IPA during posaconazole prophylaxis liposomal amphotericin B is the drug of choice. If no posaconazole prophylaxis was given, voriconazole is the treatment of choice for IPA.