Interference of tumour mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group.

BACKGROUND: Tumour mutational burden (TMB) estimated from whole exome sequencing or comprehensive gene panels has previously been established as predictive factor of response to immune checkpoint inhibitors (ICIs). Its predictive value for the efficacy of concurrent chemoradiation (cCRTX), a potential combination partner of ICI, remains unknown. METHODS: The accuracy of TMB estimation by an in-house 327-gene panel was established in the Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) data set. Interference of TMB with outcome after cCRTX was determined in a multicentre cohort of patients with locally advanced HNSCC uniformly treated with cCRTX. Targeted next-generation sequencing was successfully applied in 101 formalin-fixed, paraffin-embedded pretreatment tumour samples. In a subset of cases (n = 40), tumour RNA was used for immune-related gene expression profiling by the nanoString platform. TMB was correlated with TP53 genotype, human papilloma virus (HPV) status, immune expression signatures and survival parameters. Results were validated in the TCGA HNSCC cohort. RESULTS: A high accuracy of TMB estimation by the 327-gene panel was established. High TMB was significantly associated with an increased prevalence of TP53 mutations and immune gene expression patterns unrelated to T cell-inflamed gene expression profiles. Kaplan-Meier analysis revealed significantly reduced overall survival in the patient group with high TMB (hazard ratio for death: 1.79, 95% confidence interval: 1.02-3.14; P = 0.042) which remained significant after correcting for confounding factors in the multivariate model. The prognostic value of TMB was confirmed in the TCGA HNSCC cohort. CONCLUSION: High TMB identifies HNSCC patients with poor outcome after cCRTX who might preferentially benefit from CRTX-ICI combinations.

[The role of microRNAs in head and neck squamous cell carcinoma : Biomarkers for prognosis, therapy selection, and novel therapeutics]. / Die Bedeutung von MiRNA für das Kopf-Hals-Karzinom : Biomarker für Prognose, Therapieselektion und neue Therapeutika.

Despite recent advances in radiochemotherapy, treatment of locally advanced head and neck squamous cell carcinoma is still challenging, and survival rates have improved only slightly. This is due to the high frequency of metastases and local and/or regional tumor recurrences that have acquired radio- or chemoresistance. MiRNAs regulate diverse processes in tumorigenesis, metastasis, and therapy resistance in head and neck squamous cell carcinoma. Hence, miRNAs are highly valued in biomarker studies. Establishment of the miRNA profiles of oropharyngeal tumors enables personalized treatment selection, since expression of distinct miRNAs can predict the response to two different radiochemotherapy regimens. Development of novel miRNA therapeutics has a high clinical potential for further improving treatment of cancerous disease. The use of nanoparticles with distinct surface modifications as miRNA vectors permits prolonged bioavailability, high efficacy in tumor targeting, and low toxicity. Nevertheless, the efficacy of miRNA therapy has only been shown in animal models to date.

The effects of violent media on adolescent inkblot responses: implications for clinical and forensic assessments.

Two experiments were conducted to assess the degree to which violent media stimulate violent fantasy as depicted on inkblot responses. In Experiment I, 41 gifted high school students were exposed to a bucolic or violent film clip and then were asked to produce inkblot responses. In Experiment II, a second sample of 43 additional students were exposed to a verbal description of the bucolic or violent scene to assess whether the "hot" or "cooler" media (McLuhan, 1964) had different effects on the inkblot responses. In both experiments, the media exposure led to increased levels of violent responses, and in both cases males produced more violent responses. There was no sex by media interaction effect. Implications for clinical and forensic assessments are presented.

Aggressive response sets and subtle-obvious MMPI scale distinctions in male offenders.

The effects of aggressive and nonaggressive response sets on the MMPI subtle and obvious clinical subscales were investigated. Fifty-eight male prison inmates answered the MMPI as if they were either highly aggressive or highly nonaggressive. The clinical scales with sufficient items in each category were scored for subtle, neutral, and obvious subscales. Inmates successfully feigned aggressiveness on several of the obvious subscales (p = .0056) and one neutral scale; the subtle subscales were not significantly different across groups, consistent with previous research on this population in terms of the resistance of subtle items to these response sets.

The fakability of subtle and obvious measures of aggression by male prisoners.

Fifty-eight adult male felons were given the Minnesota Multiphasic Personality Inventory (MMPI), the Buss - Durkee Hostility Inventory ( BDHI ), and the Draw-a-Person Test (DAP) to test the relative sensitivity of subtlety or obviousness of items to response sets. The inmates were randomly assigned to three response set groups: a fake-aggressive group, a fake-nonaggressive group, and a standard-instruction control group. The MMPIs were scored for five obvious and five subtle aggression or hostility research scales. The BDHI is a totally obvious test, whereas the DAP is a very subtle measure. A paradoxical relationship between response set and subtlety of the scales was hypothesized, such that the obvious scales could be successfully faked , but the subtle scales would show scores in the opposite from the intended direction. It was found that the inmates did correctly manipulate the obvious scales, but the subtle scales did not consistently show the hypothesized trend. Possible reasons for this are discussed, including the nature of the scales used and characteristics of the population.

The WISC-R and WRAT as indicators of arithmetic achievement in juvenile delinquents.

The relationship of the WISC-R Arithmetic and WRAT Arithmetic scales to grades was determined for a sample of 8 female and 14 male juvenile delinquents. The WISC-R correlated .538 with grades and .302 with the WRAT, while the WRAT correlated .289 with grades. The WISC-R also correlated .508 with sex (females scoring higher). While WRAT Arithmetic is questioned as an indicator of academic achievement, WISC-R accounts for 29% of grades variance and may be a useful correlate.

Intellective characteristics of mothers of failure-to-thrive syndrome children.

The intelligence levels of three groups of mothers were ascertained by the vocabulary test of the Stanford-Binet Intelligence Scale. Eight mothers having children diagnosed as failure-to-thrive due to non-organic reasons (FTT-E), eight mothers with children diagnosed as failure-to-thrive due to physically traceable reasons (FTT-O), and eight mothers with children hospitalized due to reasons other than failure-to-thrive (C), were contrasted on intelligence, age, education and the presence or absence of the father in the home. Hypotheses regarding a disadvantage of FTT-E mothers on the four variables were supported. Implications of the results were discussed regarding programmes dealing with failure-to-thrive children and mothers. Further investigation in this area was proposed.

Testwiseness: some evidence for the effect of personality testing on subsequent test results.

The assumption is presented of the test-taker as a hypothesis-generating organism who can become "testwise." Testwiseness is defined as a stable skill, acquired by test-taking experiences, by which an individual can make test responses conform to a desired response pattern. Forty-three college students completed two forms of The Personality Research Form (PRF) and a rank ordering of their predicted personality need pattern. Results show significantly higher correlations of PRF predictions in the second administration. Analyses show PRF profiles, not predictions, to have been modified. Furthermore, high testwise subjects had higher needs for Understanding and Nurturance, and lower needs for Aggression and Defendence than low testwise persons. The importance of considering testwiseness, given trends in society encouraging access to psychological records, is discussed.