Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

Search for Electronic Recoil Event Rate Modulation with 4 Years of XENON100 Data.

We report on a search for electronic recoil event rate modulation signatures in the XENON100 data accumulated over a period of 4 yr, from January 2010 to January 2014. A profile likelihood method, which incorporates the stability of the XENON100 detector and the known electronic recoil background model, is used to quantify the significance of periodicity in the time distribution of events. There is a weak modulation signature at a period of 431_{-14}^{+16} day in the low energy region of (2.0-5.8) keV in the single scatter event sample, with a global significance of 1.9σ; however, no other more significant modulation is observed. The significance of an annual modulation signature drops from 2.8σ, from a previous analysis of a subset of this data, to 1.8σ with all data combined. Single scatter events in the low energy region are thus used to exclude the DAMA/LIBRA annual modulation as being due to dark matter electron interactions via axial vector coupling at 5.7σ.

Search for Event Rate Modulation in XENON100 Electronic Recoil Data.

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an unbinned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1σ for all periods, suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8σ, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of weakly interacting massive particles to electrons is excluded at 4.8σ.

Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib.

A 55-year-old Caucasian woman with lung adenocarcinoma stage IV presented with repeated relapse after treatment with cytotoxic chemotherapy (carboplatin, gemcitabine, docetaxel, pemetrexed) and targeted agents (erlotinib, cetuximab, sunitinib). Comprehensive molecular diagnostics (EGFR-, ALK-, RAS-, BRAF-, PIK3CA-, HER2- and DDR2-aberrations) were performed and failed initially to detect any driver mutation. While the patient suffered from rapid deterioration of her general condition, in particular from progressive dyspnea due to lung metastases, we implemented screening for RET- and ROS1 translocations into our molecular diagnostic program based on recent reports of these new molecular subgroups in lung adenocarcinoma. On retesting the patient's tumor sample was found to harbor a ROS1-translocation. The patient was subsequently treated with crizotinib and experienced a pronounced clinical improvement corresponding to a complete metabolic response in (18)F-FDG-PET and a good and confirmed partial response in CT (RECIST 1.1). Our case exemplifies the need for rapid implementation of newly discovered rare genetic lung cancer subtypes in routine molecular diagnostics.

Object detection with a field-portable spectropolarimetric imager.

A relatively compact, lightweight, and programmable spectropolarimetric imager was used to collect spectral and polarization data from various objects and backgrounds, both in the laboratory and in field tests. This imager uses a tellurium dioxide (TeO2) acousto-optic tunable filter and a liquid-crystal retardation plate with a CCD camera. The spectral images were collected 450-1000 nm at 10- or 20-nm intervals at two or four polarization settings for each spectral interval. We analyzed a portion of these data to assess the effectiveness of this system for object detection. We present our measurements and discuss the analysis results.

[Practicability and clinical relevance of routine psychological screening of patients in general internal medicine units]. / Praktikabilität und klinische Relevanz eines routinemässigen psychologischen Screenings von Patienten internistischer Allgemeinstationen.

In medical patients, anxiety and depression are frequent but often undiagnosed problems. The aim of the present study was to test and evaluate a psychological screening in medical in-patients. Using the Hospital Anxiety and Depression Scale (HADS), we screened 454 out of 743 consecutive medical in-patients. Physical symptoms and diagnoses were also recorded. Elevated scores for anxiety and depression were found in 20.8% and 23.9%, respectively. They were relatively independent of physical findings but correlated with subjective symptoms. In a subgroup who completed the questionnaire twice, HADS scores remained constant until discharge. Cardiological patients with abnormal baseline anxiety stayed significantly longer in hospital than those who were not anxious. Over a one-year follow-up, initially depressed patients had a risk of in-hospital death that was 2.5 times higher. This effect remained stable after controlling for baseline diagnoses and indices of severity of the disease.

Diagnostic groups and depressed mood as predictors of 22-month mortality in medical inpatients.

OBJECTIVE: While depression has been found to predict mortality in acute myocardial infarction, results from many other groups of medical patients are inconclusive. It is, therefore, unclear whether depression also predicts mortality in the typical mixed patient populations treated on medical hospital wards and whether an increased risk can be identified by means of patients' self ratings of depression. METHOD: The Hospital Anxiety and Depression scale was used as a routine screening tool in consecutive admissions to the general medical wards of a university hospital. The official survival data were obtained 22 months later. For all 454 patients who completed the screening questionnaire, complete survival data were available. RESULTS: High depression scores significantly predicted mortality in univariate comparisons (odds ratio 3.2; 95% CI 1.9-5.5) and in multivariate Cox regression analyses controlling for demographic and medical baseline variables (multivariate odds ratio 1.9; 95% CI 1.2-3.1; p < .01). Other significant predictors in the multivariate model were having a principal diagnosis of hematological disease or cancer, and older age. Disability, as assessed by nurses' ratings, and gender were not related to mortality. Subgroup analyses showed that the effect of depression scores was greatest in cardiopulmonary patients, but there was also a uniform trend toward higher mortality in depressed patients with other diagnoses. CONCLUSION: Depressed mood is an independent risk factor for all-cause mortality in medical inpatients. Identifying patients at risk does not require formal psychiatric diagnoses, but can be achieved by means of a short, routinely administered self-rating questionnaire.

Abortion counseling in a general hospital.

Given the increase in the number of abortions being performed in hospitals throughout the United States and Canada, there is an obvious need for counseling programs for these patients. The authors describe one such program, and emphasize the importance of close working relationships between the counselors and their supervising staff.