Dysregulated apoptotic pathways are regarded as major reasons for chemoresistance development as a particular challenge in ovarian cancer therapy. In search of molecular factors affecting human ovarian cancer cell apoptosis and, consequently, patient survival, we examined tumors of 103 platinum-/taxane-treated ovarian cancer patients by mRNA-array hybridization, qPCR, and immunohistochemistry. We identified high expression of crystallin aB (CRYAB), a proposed negative regulator of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. By Kaplan Meier analysis, this factor turned out to be significantly associated with poor patient outcome [overall survival (OS) p 5 0.001, recurrence-free survival (RFS) p 5 0.003]. Elevated hazard ratios (HR) were estimated with regard to OS (HR 5 2.11, 95% CI 1.10-4.06) and RFS (HR 5 1.92, 95% CI 1.07-3.47) in multivariable analyses. These associations were confirmed in independent, publicly available mRNA data comprising 431 patients for OS (p < 0.001) and 413 for RFS (p < 0.001) . Our findings were validated by studying apoptotic events in cultured human ovarian cancer cells which were stably transfected to express elevated CRYAB levels. These data emphasized the crucial role of CRYAB in human ovarian cancer biology since TRAIL-as well as cisplatin-induced apoptosis was significantly impaired as a function of enhanced CRYAB expression. Taken together, we identified CRYAB as an independent biomarker for unfavourable outcome of human ovarian cancer patients. Since TRAIL is currently tested as anticancer drug and large proportions of the present patient cohort displayed low CRYAB levels in their tumors, CRYAB may enable the selection of patient subgroups benefiting most from TRAIL-containing therapy.Epithelial ovarian cancer is the fifth most common cause for cancer-related death in women in Western societies and has the highest relative mortality among gynecological cancers. 1,2Approximately 75% of patients are diagnosed at an advanced FIGO stage (III or IV). These patients display a 5-year survival rate of less than 40%.1,3 The currently recommended standard postoperative chemotherapy is platinum-taxanebased. Although initial response rates are often high, most of the patients relapse and develop chemoresistance with fatal outcome. 4 Besides decreased response to DNA damage, increased tumor cell survival largely mediated through dysregulation of apoptotic pathways is regarded as one major reason for chemoresistance. 5,6 This prompted us to search for molecular factors affecting apoptotic pathways in human ovarian cancer, and consequently, patient survival.Differential mRNA expression analysis in tumor specimens of a clinically homogenous cohort of 103 human ovarian cancer patients disclosed CRYAB, a member of the highly

Objectives: Small-cell lung cancer (SCLC) is a lung malignancy with high relapse rates and poor survival outcomes. Treatment-resistant disease relapse occurs frequently and effective salvage therapies are urgently needed. Materials and Methods: We aimed to define efficacy and safety of checkpoint inhibitors (CPIs) in a heterogeneous population of relapsed and refractory SCLC patients in a large retrospective multicentric real-world cohort across German tertiary care centers. Results: A total of 111 patients from 11 treatment centers were included. Median age of all patients was 64 years, and 63% were male. Approximately one-third of all patients had poor performance status [Eastern Cooperative Oncology Group (ECOG) ⩾ 2], and 37% had known brain metastases. Patients were heavily pretreated with a median number of prior therapy lines of 2 (range, 1–8). Median follow-up of the entire cohort was 21.7 months. Nivolumab and Nivolumab/Ipilimumab were the most common regimens. Overall disease control rate was 27.2% in all patients and was numerically higher in CPI combination regimens compared with single-agent CPI (31.8% versus 23.8%; p = 0.16). Median overall survival (OS) was 5.8 months [95% confidence interval (CI), 1.7–9.9 months]. The 12- and 24-month survival rates were 31.8% and 12.7%, respectively. The 12-week death rate was 27.9%. Disease control and response rate were significantly lower in patients with liver metastases. Platinum sensitivity (to first-line treatment), metastatic burden, and lactate dehydrogenase (LDH) showed prognostic impact on survival in univariate analysis. Neutrophil-to-lymphocyte ratio (NLR) was a significant and independent predictor of survival in univariate ( p = 0.01) and multivariate analyses [hazard ratio (HR), 2.1; 95% CI = 1.1–4.1; p = 0.03]. Conclusion: CPI in patients with relapsed or refractory (R/R) SCLC is of limited value in an overall patient cohort; however, long-term survival, in particular with CPI combination strategies, is possible. Clinical characteristics allow a more differentiated subgroup selection, in particular patients with low NLR showed less benefit from CPI in R/R SCLC.

Zusammenfassung Hintergrund Seit Ende März wurde deutschlandweit das Gesundheitswesen auf einen Notbetrieb umgestellt, um Ressourcen für die sich ausbreitende Coronavirus-disease-2019-Pandemie (COVID-19-Pandemie) zu schaffen. Ziel der Arbeit ist es, das Aufkommen von Notfallpatienten zur Zeit der Pandemie zu untersuchen, um Rückschlüsse auf den Einfluss der COVID-19-Pandemie auf das Patientenaufkommen in einer Notaufnahme ziehen zu können. Material und Methoden Im Rahmen einer deskriptiven epidemiologischen Studie wurden in dem Zeitraum vom 01.02. bis zum 30.04.2019 sowie vom 01.02. bis zum 30.04.2020 patientenbezogene Daten von insgesamt 19.357 Fällen in der zentralen Notaufnahme des Klinikums rechts der Isar erhoben und anonymisiert ausgewertet. Ergebnisse Trotz steigender Patientenzahlen von 2019 auf 2020 kam es von Februar auf März 2020 zu einem deutlichen Abfall der Notfälle bis auf ein Niveau unter das von 2019, der im April weiter anhielt. Dies betraf insbesondere den Fachbereich Unfallchirurgie mit einem Rückgang des mittleren Patientenaufkommens um etwa 40 %. Im Hinblick auf die Beschwerdebilder im März 2020 zeigte sich, dass ein vermehrtes Aufkommen von Unwohlsein (+47 %) und Atemproblemen (+36 %) zu verzeichnen war, wohingegen Rückenschmerzen (−41 %), Wunden (−29 %), thorakale (−24 %) sowie abdominelle Schmerzen (−23 %) deutlich seltener vertreten waren als im Vorjahr. Bezogen auf den Schweregrad der Beschwerden wirkte sich der Rückgang vor allem auf Beschwerdebilder mit niedriger Dringlichkeitsstufe aus. Schlussfolgerung Im Rahmen der COVID-19-Pandemie kam es zu einem deutlichen Rückgang des Patientenaufkommens in einer der größten Notaufnahmen in München. Dies sollte bei bestehenden Krankenhauskapazitäten vermieden werden, um potenziell gesundheitlichen Schäden durch eine aufgeschobene oder ausbleibende notfallmäßige Vorstellung vorzubeugen.

Background Pre-operative treatment planning in head and neck squamous cell carcinoma (HNSCC) is mainly dictated by clinical staging, which has major shortcomings. Histologic grading is irrelevant due to its lack of prognostic impact. Recently, a novel grading termed Cellular Dissociation Grade (CDG) based on Tumour Budding and Cell Nest Size was shown to be highly prognostic for resected HNSCC. We aimed to probe the predictive and prognostic impact of CDG in the pre-operative biopsies of HNSCC. Methods We evaluated CDG in n = 160 pre-therapeutic biopsies from patients who received standardised treatment following German guidelines, and correlated the results with pre- and post-therapeutic staging data and clinical outcome. Results Pre-operative CDG was highly predictive of post-operative tumour stage, including the prediction of occult lymph node metastasis. Uni- and multivariate analysis revealed CDG to be an independent prognosticator of overall, disease-specific and disease-free survival (p < 0.001). Hazard ratio for disease-specific survival was 6.1 (11.1) for nG2 (nG3) compared with nG1 tumours. Conclusions CDG is a strong outcome predictor in the pre-treatment scenario of HNSCC and identifies patients with nodal-negative disease. CDG is a purely histology-based prognosticator in the pre-therapeutic setting that supplements clinical staging and may aide therapeutic stratification of HNSCC patients.