Cancer patient preferences for communication of prognosis in the metastatic setting

PURPOSE: To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. PATIENTS AND METHODS: One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. RESULTS: More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P = .047) and average survival (P = .049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P = .03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P = .02). CONCLUSION: Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.

Breast cancer prognosis risk estimation using integrated gene expression and clinical data

Novel prognostic markers are needed so newly diagnosed breast cancer patients do not undergo any unnecessary therapy. Various microarray gene expression datasets based studies have generated gene signatures to predict the prognosis outcomes, while ignoring the large amount of information contained in established clinical markers. Nevertheless, small sample sizes in individual microarray datasets remain a bottleneck in generating robust gene signatures that show limited predictive power. The aim of this study is to achieve high classification accuracy for the good prognosis group and then achieve high classification accuracy for the poor prognosis group.

The study protocol of: 'initiating end of life care in stroke: clinical decision- making around prognosis'

 Background: The initiation of end of life care in an acute stroke context should be focused on those patients and families with greatest need. This requires clinicians to synthesise information on prognosis, patterns (trajectories) of dying and patient and family preferences. Within acute stroke, prognostic models are available to identify risks of dying, but variability in dying trajectories makes it difficult for clinicians to know when to commence palliative interventions. This study aims to investigate clinicians’ use of different types of evidence in decisions to initiate end of life care within trajectories typical of the acute stroke population.
Methods/design: This two-phase, mixed methods study comprises investigation of dying trajectories in acute stroke (Phase 1), and the use of clinical scenarios to investigate clinical decision-making in the initiation of palliative care (Phase 2). It will be conducted in four acute stroke services in North Wales and North West England. Patient and public involvement is integral to this research, with service users involved at each stage.
Discussion: This study will be the first to examine whether patterns of dying reported in other diagnostic groups are transferable to acute stroke care. The strengths and limitations of the study will be considered. This research will produce comprehensive understanding of the nature of clinical decision-making around end of life care in an acute stroke context, which in turn will inform the development of interventions to further build staff knowledge, skills and confidence in this challenging aspect of acute stroke care.

Differences in parent-provider concordance regarding prognosis and goals of care among children with advanced cancer

Purpose Concordance between parents of children with advanced cancer and health care providers has not been described. We aimed to describe parent-provider concordance regarding prognosis and goals of care, including differences by cancer type.

MicroRNAs: biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis

MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.

Computational methods for breast cancer diagnosis, prognosis, and treatment prediction

The research presented here develops a robust reliability algorithm for the identification of reliable protein interactions that can be incorporated with a gene expression dataset to improve the algorithm performance, and novel breast cancer based diagnostic, prognostic and treatment prediction algorithms, respectively, which take into account the existing issues in order to provide a fair estimation of their performance.

The development of a screening questionnaire for childhood cruelty to animals

Childhood cruelty to animals may be a marker of poor prognosis amongst conduct disordered children. However, other than semistructured interviews with parents or children, there are no screening instruments for this behavior. The aim of this study was to develop such an instrument. In the first phase of the study, a parent-report questionnaire, Children's Attitudes and Behaviors Towards Animals (CABTA) was designed and piloted on 360 elementary school children, enabling community norms and a factor structure for the instrument to be derived. In the second phase, the questionnaire was completed by the parents of a small sample of children (N= 17) to establish its test-retest reliability. In the third phase of the study, the CABTA was completed by the parents of 19 children who had been diagnosed with either a Disruptive Behavioral Disorder or Attention Deficit Hyperactivity Disorder, and the results were compared with the outcome of a semistructured interview with parents regarding their child's behavior toward animals. The results of the various phases of the study indicated that the CABTA consists of two factors, Typical and Malicious Cruelty to animals, and is a reliable and valid tool for detecting childhood cruelty to animals. Possible use and adaptations of the CABTA as a screening instrument in clinical and community samples are discussed.

The VISA-A questionnaire: a valid and reliable index of the clinical severity of Achilles tendinoplasty

Background: There is no disease specific, reliable, and valid clinical measure of Achilles tendinopathy. Objective: To develop and test a questionnaire based instrument that would serve as an index of severity of Achilles tendinopathy. Methods: Item generation, item reduction, item scaling, and pretesting were used to develop a questionnaire to assess the severity of Achilles tendinopathy. The final version consisted of eight  questions that measured the domains of pain, function in daily living, and sporting activity. Results range from 0 to 100, where 100 represents the perfect score. Its validity and reliability were then tested in a population of non-surgical patients with Achilles tendinopathy (n = 45), presurgical patients with Achilles tendinopathy (n = 14), and two normal control populations (total n = 87). Results: The VISA-A questionnaire had good test-retest (r = 0.93), intrarater (three tests, r = 0.90), and interrater (r = 0.90) reliability as well as good stability when compared one week apart (r = 0.81). The mean (95% confidence interval) VISA-A score in the non-surgical patients was 64 (59–69), in presurgical patients 44 (28–60), and in control subjects it exceeded 96 (94–99). Thus the VISA-A score was higher in non-surgical than presurgical patients (p = 0.02) and higher in control subjects than in both patient populations (p<0.001). Conclusions: The VISA-A questionnaire is reliable and displayed construct validity when means were compared in patients with a range of severity of Achilles tendinopathy and control subjects. The continuous numerical result of the VISA-A questionnaire has the potential to provide utility in both the clinical setting and research. The test is not designed to be diagnostic. Further studies are needed to determine whether the VISA-A score predicts prognosis.

α2β1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis

Background: Ovarian cancer is characterized by a wide-spread intra-abdominal metastases which represents a major clinical hurdle in the prognosis and management of the disease. A significant proportion of ovarian cancer cells in peritoneal ascites exist as multicellular aggregates or spheroids. We hypothesize that these cellular aggregates or spheroids are invasive with the capacity to survive and implant on the peritoneal surface. This study was designed to elucidate early inherent mechanism(s) of spheroid survival, growth and disaggregation required for peritoneal metastases.

Methods: In this study, we determined the growth pattern and adhesive capacity of ovarian cancer cell lines (HEY and OVHS1) grown as spheroids, using the well established liquid overlay technique, and compared them to a normal ovarian cell line (IOSE29) and cancer cells grown as a monolayer. The proteolytic capacity of these spheroids was compared with cells grown as a monolayer using a gelatin zymography assay to analyze secreted MMP-2/9 in conditioned serum-free medium. The disaggregation of cancer cell line spheroids was determined on extracellular matrices (ECM) such as laminin (LM), fibronectin (FN) and collagen (CI) and the expression of α2, α3, αv, α6 and β1 interin was determined by flow cytometric analysis. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin was used to inhibit disaggregation as well as activation of MMPs in spheroids.

Results: We demonstrate that ovarian cancer cell lines grown as spheroids can sustain growth for 10 days while the normal ovarian cell line failed to grow beyond 2 days. Compared to cells grown as a monolayer, cancer cells grown as spheroids demonstrated no change in adhesion for up to 4 days, while IOSE29 cells had a 2–4-fold loss of adhesion within 2 days. Cancer cell spheroids disaggregated on extracellular matrices (ECM) and demonstrated enhanced expression of secreted pro-MMP2 as well as activated MMP2/MMP9 with no such activation of MMP's observed in monolayer cells. Flow cytometric analysis demonstrated enhanced expression of α2 and diminution of α6 integrin subunits in spheroids
versus monolayer cells. No change in the expression of α3, αv and β1 subunits was evident. Conversely, except for αv integrin, a 1.5–7.5-fold decrease in α2, α3, α6 and β1 integrin subunit expression was observed in IOSE29 cells within 2 days. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin inhibited disaggregation as well as activation of
MMPs in spheroids.

Conclusion: Our results suggest that enhanced expression of α2β1 integrin may influence spheroid disaggregation and
proteolysis responsible for the peritoneal dissemination of ovarian carcinoma. This may indicate a new therapeutic target
for the suppression of the peritoneal metastasis associated with advanced ovarian carcinomas.

Interobserver reproducibility of histopathologic prognostic variables in primary cutaneous melanomas

Background: The prognosis for patients with localized primary cutaneous melanoma is known to depend principally on tumor thickness, and to a lesser extent on ulcerative state and Clark level. We have recently found in an analysis of 3661 patients that tumor mitotic rate (TMR) is also an important prognostic parameter, ranking second only to tumor thickness. However, few studies have assessed the accuracy and reproducibility with which these features of a melanoma are recorded by histopathologists.
Aim: To assess interobserver reproducibility of major pathologic prognostic parameters in cutaneous melanoma.
Methods: Single hematoxylin and eosin-stained slides of 69 dermally invasive primary cutaneous melanomas were circulated among six pathologists with differing experience in the assessment of melanocytic tumors. The observers independently determined the tumor thickness, Clark level of invasion, ulcerative state, and TMR for each lesion. Intraclass correlation coefficients and kappa scores for multiple ratings per subject were calculated.
Results: The intraclass correlation coefficients were 0.96 for tumor thickness and 0.76 for TMR. The kappa scores were 0.83 for ulcerative state and 0.60 for Clark level. These results indicated excellent agreement among the pathologists for measurements of tumor thickness, ulcerative state, and TMR and fair to good agreement for Clark level.
Conclusions: Appropriately trained and experienced histopathologists can assess prognostically important features of melanomas accurately and reproducibly. Given our recent finding of the significance of TMR in determining prognosis, it is important that this feature be assessed by a standardized method and documented for all primary cutaneous melanomas.

Shake rattle and roll: a journey with Parkinson's

This is the journey of a man suffering from Parkinson's disease. Ross Collins tells of his past twelve years' experiences of living with Parkinson's. Before, he had a steady job with Victoria Police, with promising future prospects; and was happily married with two young children. The disease struck him at an early age, changing his life and setting him on a different course. His outlook on life has changed, and his decision-making influenced; as well, his relationships with his family affected. He feels normal only when he is shaking, rattling and rolling along on his Harley. His wish for a cure leads him to pin his hopes on faith healing by the 'miracle man', in Brazil. The first two visits did not seem to have done anything to improve his physical condition. Ross is returning to Brazil for the third time, hoping against hope that his condition could be improved by a miracle healing. This documentary gives an intimate look into the life of a Parkinson's disease sufferer and that of his family. Includes al.

Importance of assessing family dysfunction in conjunction with standardised measures when treating substance abuse

In this thesis, the link between substance abuse and family dysfunction is examined, and an argument is made for the assessment of family dysfunction when treating clients with substance abuse issues. Family dysfunction has been associated with a broad range of problems in children (e.g., low self esteem, increased risk of child abuse) through to adolescence and adulthood (e.g., increased risk of mental disorders such as depressive disorders, substance abuse disorders, and personality disorders) (Kaplan & Sadock, 1998). It is not the purpose of this thesis to suggest that family dysfunction causes substance abuse but rather to highlight that family dysfunction can in some cases place the individual at greater risk of substance abuse. Therefore, in order to understand the reasons why substance abuse developed and how it is maintained in the present requires the assessment of family dysfunction. Further, the importance of assessing the role and impact that family dysfunction may have had on the client, may help to better understand the nature and extent of substance abuse so that relevant and appropriate treatment goals for change may be set, progress monitored, and risk of relapse reduced. Chapter 1 provides a brief introduction to this thesis, and Chapter 2 is a review of the literature on the impact of family dysfunction including poor parental attachment and supervision, neglect, physical and sexual abuse, in adolescence and adulthood. Four case studies are presented to illustrate how family dysfunction and substance abuse may be related, thus highlighting the importance of assessing family dysfunction when treating substance abuse clients. All of the case studies include an individual with a substance abuse disorder (namely heroin) but they are diverse in terms of the types and extent of family dysfunction. The final chapter discusses the case studies in relation to the literature reviewed. Lastly, it gives consideration to the implication of a history of family dysfunction, and how it may impact negatively on treatment and therefore prognosis.