Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Focusing on cancer patients' intentions to use psychooncological support: A longitudinal, mixed-methods study.

OBJECTIVE: Distress screening programs aim to ensure appropriate psychooncological support for cancer patients, but many eligible patients do not use these services. To improve distress management, we need to better understand patients' supportive care needs. In this paper, we report the first key finding from a longitudinal study that focused on patients' intentions to use psychooncological support and its association with distress and uptake of the psychooncology service. METHODS: We conducted a prospective, observational study in an Oncology Outpatient Clinic and assessed distress, intention to use psychooncological support, and uptake of the psychooncology service by using the Distress Thermometer, a semistructured interview, and hospital records. We analyzed data with a mixed-methods approach. RESULTS: Of 333 patients (mean age 61 years; 55% male; 54% Distress Thermometer ≥ 5), 25% intended to use the psychooncology service (yes), 33% were ambivalent (maybe), and 42% reported no intention (no). Overall, 23% had attended the psychooncology service 4 months later. Ambivalent patients reported higher distress than patients with no intention (odds ratio = 1.18, 95% confidence interval [1.06-1.32]) but showed significantly lower uptake behavior than patients with an intention (odds ratio = 14.04, 95% confidence interval [6.74-29.24]). Qualitative analyses revealed that ambivalent patients (maybe) emphasized fears and uncertainties, while patients with clear intentions (yes/no) emphasized knowledge, attitudes, and coping concepts. CONCLUSIONS: We identified a vulnerable group of ambivalent patients with high distress levels and low uptake behavior. To optimize distress screening programs, we suggest addressing and discussing patients' supportive care needs in routine clinical practice.

Characterization of social cognition impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) has been associated with deficits in social cognition. However, little is known about which domains of social cognition are predominantly affected and what other factors are associated with it. The aim was (i) to characterize social cognition deficit in a group of MS outpatients and (ii) to relate impairment in social cognition to overall cognitive status, depression and fatigue. METHODS: Thirty-five MS patients (mean disease duration 12.9 years, median Expanded Disability Status Scale (EDSS) 3 and 34 healthy controls (HCs) were examined using the German version of the Geneva Social Cognition Scale to measure different domains of social cognition. Standard neuropsychological testing was applied to all patients and to 20 HCs. Patient-reported outcomes included questionnaires for fatigue, depression, anxiety and executive-behavioural disturbances. RESULTS: The mean social cognition raw score was lower in the MS patients compared to the HCs (86.5 ± 8.7 vs. 91.2 ± 5.9, P = 0.005; d = 0.6) and did not correlate with EDSS or disease duration. The difference was driven by facial affect recognition and the understanding of complex social situations (14% and 23% of patients respectively under the cut-off). The impairment in these two tasks did not correlate with general cognitive performance or depression but with fatigue. CONCLUSIONS: The impairment in our group was restricted to high order and affective social cognition tasks and independent of general cognitive performance, EDSS, disease duration and depression. Fatigue correlated with social cognition performance, which might be due to common underlying neuronal networks.

Validation and discussion of clinical practicability of the 2022 graded prognostic assessment for NSCLC adenocarcinoma patients with brain metastases in a routine clinical cohort.

Introduction: The goal of this analysis is to validate the 2022 graded prognostic assessment (GPA) for patients with brain metastases from adenocarcinoma of the lung and to discuss its clinical practicability. Methods/material: 137 patients with adenocarcinoma of the lung were included in this analysis. The disease specific GPA for NSCLC, Lung-molGPA and the GPA for NSCLC adenocarcinoma were calculated. Overall survival was calculated for each GPA group. Additionally, expected and actual OS in the prognostic groups of the GPA available at the time of the patients' diagnosis was compared. Results: Median overall survival (OS) from diagnosis of brain metastases was 15 months (95% confidence interval (CI) 9.7-20.3 months). The median OS in the three individual prognostic groups was 7 months for GPA 0-1, 16 months for GPA 1.5-2, 33 months for GPA 2.5-3 and not reached for GPA 3.5-4 (p<0.001). Median survival times for the individual groups were similar to those published in the original GPA publication. Regarding the expected and actual OS when using the available GPA at the time of diagnosis there was an underestimation of survival of more than 3 months for all except the worst prognosis group. Conclusion: We were able to validate the 2022 GPA for NSCLC adenocarcinoma patients with brain metastases in a similar cohort from a non-academic center. However, the practical applicability regarding the expected median OS might be limited due to the constantly evolving treatment landscape and the consecutive improvement in overall survival.

Quality of life and dyadic adjustment in oral cancer patients and their female partners.

The diagnosis of cancer affects not only the lives of patients, but also the lives of their family members. The purpose of this study was to examine the impact of oral cancer on quality of life (QoL), psychological distress and marital satisfaction in a sample of patients and their wives. Thirty-one men treated for oral cancer (mean time since diagnosis 3.7 years) and their female partners (n = 31) were assessed by questionnaires with regard to QoL (WHOQOL-BREF), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), quality of relationship (Dyadic Adjustment Scale, DAS) and physical complaints (EORTC QOL-H&N35). Quality of life was remarkably high in patients and their partners. In patients, lower QoL was associated with more physical complaints and higher levels of psychological distress (HADS), whereas in wives, QoL was found to be related to marital quality (DAS) and levels of distress. In couples with highly discrepant ratings of marital satisfaction, wives reported more psychological distress. The findings indicate that overall QoL is considerably high in patients treated for oral cancer and their partners living in stable relationships. Quality of life correlates stronger with the quality of relationship in spouses than in patients. Generally, marital satisfaction appears to be an important moderating factor regarding QoL and psychological distress.

Ovarian cancer. an institutional review of patterns of care, health insurance and prognosis.

The purpose of this study was to investigate the prognostic importance of the health insurance status in 145 consecutive patients with ovarian cancer diagnosed between 1984 and 1996. All patients had basic (Type III) insurance to cover outpatient treatment and hospital expenses for a per diem flat fee; some patients had one of two types of supplemental private insurance (Type I and Type II) to cover the treatment by physicians of their choice and fee-for-service hospital treatment. The prognostic impact of health insurance was evaluated by multivariate statistical methods. The median follow-up was 81.9 months (range: 21-181); the 5-year probability of survival was 72% (standard error of the mean (SEM) 9.8%) for stage I, 53% (SEM 16.2%) for stage II, 17% (SEM 5. 9%) for stage III and 11% (SEM 5.5%) for stage IV cancer. Age, stage, histological grade and debulking surgery were independent predictors of survival in multivariate proportional hazards regression analysis. Patients with private insurance were younger and received more chemotherapy than patients with basic insurance. In multivariate analysis, insurance was an independent predictor of survival: patients with Type II insurance had a hazard ratio of 2.31 (95% confidence interval (CI): 1.05-5.04), and patients with Type III insurance had a hazard ratio of 3.30 (95% CI 1.52-7.17) compared with the reference group of Type I insured patients. Health insurance status was an independent predictor of survival in ovarian cancer. Research is needed to devise strategies to improve the medical care of patients with basic insurance.

[Supportive needs and satisfaction in cancer outpatients and their spouses]. / Therapiewünsche und Behandlungszufriedenheit bei ambulanten Krebspatienten und deren Ehepartnern.

OBJECTIVE: To assess the satisfaction of outpatients treated for cancer and their spouses as regards to medical and psychosocial care. A second focus of interest included the understanding the extend of support needs not yet covered by the existing system. METHOD: 224 outpatients with different cancer types and different stages as well and their 224 spouses were assessed by questionnaires. RESULTS: The needs of the patients were significantly better covered in all areas investigated than those of their spouses. A high level of satisfaction was revealed in the aspect of understanding and confidence with doctors and other medical stuff as well as the information on the disease. Also regarding on the various ways of treatment and how a patient could keep his own mental balance were considered satisfactory. By patients, spouses and doctors were considered by far as the most important support. A significant number of patients and spouses reported a lack of assistance or advice in relevant social support aspects. CONCLUSION: The wishes and needs of the spouses are considerably less taken into account within the exististing outpatient oncological medical treatment than those of the patients. As the spouses are heavily impacted by a psychological stress due their partners disease and the support duties, we require to ameliorate the assessment of the needs of relatives and to communicate better existing support programmes.

[Prevalence of anxiety and depression in cancer outpatients and their spouses]. / Prävalenz von Angst und Depression bei ambulanten Krebspatienten und deren Angehörigen.

OBJECTIVE: To assess prevalence rates of anxiety disorder and depression in patients and their spouses treated in a cancer outpatient clinic of a university hospital. Also the distress-thermometer (DT) was tested as a screening instrument for anxiety disorders and depression. METHOD: 109 patients with different cancer types of different stages as well as their 109 spouses were assessed by questionnaires. RESULTS: In the patient sample anxiety levels were increased in 24.7% and in 20.2% for depression. In spouses anxiety levels were increased in 41.0% and in 21.6% for depression. Female spouses had higher anxiety levels than male spouses (p < 0.01); increased anxiety levels were found in 48% of the female spouses. In the patients sample the distress-thermometer has good values for sensitivity [0.93 (anxiety); 0.82 (depression)] and satisfying measures of specifity [0.68 (anxiety); 0.62 (depression)]. CONCLUSION: Female spouses of cancer patients are at increased risk for psychiatric morbidity, a fact that should be considered in future oncological care. The distress-thermometer is a simple, time saving and sensitive screening instrument to assess psychiatric morbidity in cancer patients, which can be recommended for clinical use.

The Notch pathway in ovarian carcinomas and adenomas.

Elements of the Notch pathway regulate differentiation; we investigated the expression of such elements in epithelial ovarian tumours. A total of 32 ovarian tumour samples (17 adenocarcinomas, three borderline tumours, 12 adenomas), two human ovarian cancer (A2780, OVCAR3), and one ovarian surface (IOSE 144) cell lines were analysed. The expression of Notch pathway elements was assessed by RT-PCR, real-time PCR (Notch 1), and by immunoblots (Notch 1 extracellular domain (EC), HES1). The proliferation and colony formation of A2780 cells were measured after stable transfection with activated Notch 1 (intracellular domain). Jagged 2, Delta-like-1, Manic Fringe, and TSL1 were expressed more frequently in adenocarcinomas whereas Deltex, Mastermind, and Radical Fringe were more frequent in adenomas. Quantitative PCR revealed decreased Notch 1 mRNA in ovarian adenocarcinomas compared with adenomas. The expression of Notch 1-EC protein was similar in benign and malignant tumours. HES1 protein was strongly expressed in 18/19 ovarian cancers and borderline tumours but not in adenomas. Transfecting A2780 cells with active Notch 1-IC resulted in a proliferative and colony formation advantage compared to mock transfected cells. Thus, Notch pathway elements are expressed in ovarian epithelial tumours and some of them are differentially expressed between adenomas and carcinomas. The Notch pathway could be a target for the development of therapies for ovarian cancer.

Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia.

The p73 protein shares structural and functional similarities with the tumour-suppressor p53, but its role in neoplastic transformation is unknown. Alternative splicing leads to the expression of at least nine p73 C-terminal mRNA splice variants (alpha, beta, gamma, delta, epsilon, zeta, eta, eta1, theta). In this survey, we analyse the expression of p73 by real-time quantitative RT-PCR, its known C-terminal variants with an RT-PCR-Southern technique and by Western blot in samples of 51 patients with B-CLL, normal B lymphocytes from eight individuals, and five haematopoetic cell lines. p73alpha protein expression positively correlated with higher risk B-CLL stages (P = 0.046). Total p73 mRNA expression was higher (P = 0.01) and p73alpha protein more frequently detected (P = 0.008) in B-CLL compared with normal CD19+-B-lymphocytes. p73 C-terminal mRNA variants were expressed both in B-CLL and in normal B-lymphocytes, but their expression was biased since the gamma (P = 0.041), the theta (P < 0.001), and the eta variant (P = 0.033) prevailed in normal B-lymphocytes. In summary, we conclude that the accumulation of p73, the expression pattern of particular p73 variants and its link to progression may play a distinct role in the molecular pathology B-CLL.

Differential expression of p73 splice variants and protein in benign and malignant ovarian tumours.

The p73 gene encodes a protein with substantial structural and functional similarities to the tumour-suppressor p53. Alternative splicing of p73 mRNA leads to expression of 6 known RNA species and proteins (alpha, beta, gamma, delta, epsilon, zeta). We analysed the expression of these splice variants in ovarian adenocarcinoma by RT-PCR followed by detection of amplicons with the Southern technique and by immunoblot in 32 malignant and benign epithelial ovarian tumour specimens and 3 ovarian adenocarcinoma cell lines (A2780, 2008, OVCAR-3). p73alpha mRNA was expressed in all 17 ovarian cancer specimens, and 14 of 17 expressed at least 3 splice variants. In contrast, a different expression pattern was present in the ovarian adenomas: p73alpha was detected in 6 of 12 benign tumours, and only 1 adenoma expressed 3 splice variants. p73 protein was expressed in 9 of 16 ovarian cancer specimens, in all cell lines and in 1 of 3 borderline tumours. In contrast, none of 9 ovarian adenomas expressed detectable amounts of p73 protein. Expression of p73 mRNA and protein was not correlated with FIGO stage and histological grade, but we observed a significant correlation with over-expression of p53 protein. In summary, epithelial ovarian cancers express a more complex p73 isoform pattern and higher levels of p73 mRNA and protein than ovarian adenomas.