Social Support Networks and Self-Efficacy of Peruvian Women Diagnosed with Cancer: A Biocultural Analysis of Health Behavior Constructs

Thesis (Ph.D.)--University of Washington, 2016-06

Hypertension and diabetes treatments and risk of adverse outcomes among breast cancer patients

Thesis (Ph.D.)--University of Washington, 2016-06

Reliability of a measure of prediagnosis physical activity for cancer survivors

Purpose: This study was conducted to examine the test-retest reliability of a measure of prediagnosis physical activity participation administered to colorecial cancer survivors recruited from a population-based state cancer registry. Methods: A total of 112 participants completed two telephone interviews. I month apart, reporting usual weekly physical activity in the year before their cancer diagnosis. Intraclass correlation coefficients (ICC) and standard en-or of measurement (SEM) were used to describe the test-retest reliability of the measure across the sample: the Bland-Altman approach was used to describe reliability at the individual level. The test-retest reliability for categorized total physical activity (active, insufficiently active, sedentary) was assessed using the kappa statistic. Results: When the complete sample was considered, the ICC ranged from 0.40 (95% Cl: 0.24, 0.55) for vigorous gardening to 0.77 (95% Cl: 0.68, 0.84) for moderate physical activity. The SEM, however, were large. indicating high measurement error. The Bland-Altman plots indicated that the reproducibility of data decreases as the aniount of physical activity reported each week increases The kappa coefficient for the categorized data was 0.62 (95% Cl: 0.48, 0.76). Conclusion: Overall. the results indicated low levels of repeatability for this measure of historical physical activity. Categorizing participants as active, insufficiently active, or sedentary provides a higher level of test-retest reliability.

Chromogenic in situ hybridisation testing for HER2 gene amplification in breast cancer produces highly reproducible results concordant with fluorescence in situ hybridisation and immunohistochemistry

Aims: The objective of this study was to evaluate the accuracy, ease of use and reproducibility of chromogenic in situ hybridisation (CISH) for HER2 testing by studying its inter-laboratory concordance in five Australian pathology laboratories. Methods: The HER2 status of 49 breast cancers was determined by CISH twice in two different laboratories. Each sample had previously been tested by immunohistochemistry (IHC; 2+ and 3+ cases selected) and fluorescence in situ hybridisation ( FISH). Participating laboratories were blinded to these test results. Oestrogen receptor ( ER) status was also evaluated for each cancer. Results: High correlation was observed between FISH and CISH results. No cases showing high gene amplification by FISH were scored as non-amplified by CISH ( kappa coefficient=1). High correlation was observed between IHC and CISH, all IHC 3+ samples showing amplification by CISH. Inter-laboratory CISH concordance was also good ( kappa coefficient=0.67). Fifty-six per cent of HER2-amplified samples tested ER positive, while 42% of ER-positive cases showed HER2 gene amplification, confirming that HER2 testing should not be confined to ER-negative breast cancers. Conclusions: These findings demonstrate that CISH is a robust test to assess HER2 status in breast cancer and therefore is an important addition to the HER2 testing algorithm.

Renegotiating sexual intimacy in the context of altered embodiment:the experiences of women with breast cancer and their male partners following mastectomy and reconstruction

OBJECTIVE: Breast cancer diagnosis and treatments can have a profound impact upon women's well-being, body image, and sexual functioning, but less is known about the relational context of their coping and the impact upon their intimate partners. Our study focuses upon couples' experiences of breast cancer surgery, and its impact on body image and sexual intimacy. METHOD: Utilizing a dyadic design, we conducted 8 semistructured individual interviews, with 4 long-term heterosexual couples, after the women had undergone mastectomy with reconstruction. Interviews explored both partners' experiences of diagnosis, decision-making, and experiences of body image and sexual intimacy. Interpretative phenomenological analysis (IPA) was adopted; this is a qualitative research approach characterized by in-depth analysis of the personal meaning of experiences. RESULTS: Findings illustrate the positive acceptance that partners may express toward their wives' postsurgical bodies. They illuminate ways in which gendered coping styles and normative sexual scripts may shape couples' negotiations of intimacy around "altered embodiment." Reciprocal communication styles were important for couples' coping. The management of expectations regarding breast reconstruction may also be helpful. CONCLUSIONS: The insights from the dyadic, multiple perspective design suggest that psychologists must situate the meaning of supportive relationships and other protective factors in the context of complex life events and histories, in order to understand and support people's developing responses to distress. (PsycINFO Database Record

Fractal Analysis for Cancer Research: Case Study and Simulation of Fractals

2010 Mathematics Subject Classification: 65D18.

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93-1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93-1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82-1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76-1.10]). Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).

Acceptance of relapse fears in breast cancer patients: effects of an act-based abridged intervention

Objective: Relapse fear is a common psychological scar in cancer survivors. The aim of this study is to assess the effects of an abridged version of Acceptance and Commitment Therapy (ACT) in breast cancer patients.Method: An open trial was developed with 12 non-metastatic breast cancer patients assigned to 2 conditions, ACT and waiting list. Interventions were applied in just one session and focused on the acceptance of relapse fears through a ‘defusion’ exercise. Interference and intensity of fear measured through subjective scales were collected after each intervention and again 3 months later. Distress, hypochondria and ‘anxious preocupation’ were also evaluated through standardized questionnaires.Results: The analysis revealed that ‘defusion’ contributed to decrease the interference of the fear of recurrence, and these changes were maintained three months after intervention in most subjects. 87% of participants showed clinically significant decreases in interference at follow-up sessions whereas no patient in the waiting list showed such changes. Statistical analysis revealed that the changes in interference were significant when comparing pre, post and follow-up treatment, and also when comparing ACT and waiting list groups. Changes in intensity of fear, distress, anxious preoccupation and hypochondria were also observed.Conclusions: Exposure through ‘defusion’ techniques might be considered a useful option for treatment of persistent fears in cancer patients. This study provides evidence for therapies focusing on psychological acceptance in cancer patients through short, simple and feasible therapeutic methods.

Preclincial evaluation of Gold-DTDTPA Nanoparticles As Theranostic Agents In Prostate Cancer Radiotherapy

AIM: Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and radiosensitization in prostate cancer.

MATERIALS & METHODS: In vitro assays determined Au@DTDTPA uptake, cytotoxicity, radiosensitizing potential and DNA damage profiles. Human PC3 xenograft tumor models were used to determine CT enhancement and radiation modulating effects in vivo.

RESULTS: Cells exposed to nanoparticles and radiation observed significant additional reduction in survival compared with radiation only. Au@DTDTPA produced a CT enhancement of 10% and a significant extension in tumor growth delay from 16.9 days to 38.3 compared with radiation only.

CONCLUSION: This study demonstrates the potential of Au@DTDTPA to enhance CT-image contrast and simultaneously increases the radiosensitivity of prostate tumors.

Breast cancer outcomes following predictive BRCA testing in Northern Ireland

Objectives: Since 1995, BRCA testing has identified 445 women in Northern Ireland who carry a pathogenic BRCA1/2 mutation, without breast cancer (bca) at testing. This study examined outcomes with reference to management, bca risk, and incidence following positive predictive testing. Methods: Patients were identified from the regional genetics database. Electronic clinical records were used to obtain management and outcome details. Median follow-up was to bca diagnosis, risk-reducing mastectomy (rrm), death, or last follow-up. Results: 169 women had a BRCA1 mutation, and 276 BRCA2. ■ BRCA1 cohort: Median follow-up post-testing was 3 years. 56 Women (33%) had rrm, and 12 are awaiting rrm (total 68, 40%) at a median age of 36 years. 12 Women (7%) developed bca, at a median of 2 years following testing. 4 Women were diagnosed with bcas incidentally at rrm. 7 Patients had bilateral mastectomies following a cancer diagnosis. 1 Woman developed bca following rrm (1.7%). Three deaths were reported: 1 breast cancer (1.7%), 1 ovarian cancer (1.7%), and 1 with no recorded breast/ovarian cancer diagnosis. ■ BRCA2 cohort: Median follow-up post-testing was 6 years. rrm was carried out in 75 women (27%), with 20 awaiting rrm (total 95, 35%); median age: 39 years. 16 Women developed bca (5.8%), at a median of 5 years from testing. 6 Women were diagnosed with cancer incidentally at rrm; 9 women had bilateral mastectomy following diagnosis, and 1 developed bca following rrm (1.3%). Five deaths were reported: 1 bca, 1 ovarian cancer, and 3 with no recorded breast/ovarian cancer diagnosis. Conclusions: The uptake of rrm following predictive BRCA testing in Northern Ireland is comparable with that reported elsewhere. The incidence of bca following rrm is low (<2%) in our cohort, with low breast and ovarian cancer–specific mortality following positive predictive testing.

An exploration of men’s experiences of undergoing active surveillance for favourable-risk prostate cancer: A mixed methods study protocol

Background
Prostate cancer is one of the most common male cancers worldwide. Active Surveillance (AS) has been developed to allow men with lower risk disease to postpone or avoid the adverse side effects associated with curative treatments until the disease progresses. Despite the medical benefits of AS, it is reported that living with untreated cancer can create a significant emotional burden for patients.

Methods/design
The aim of this study is to gain insight into the experiences of men eligible to undergo AS for favourable-risk PCa.

This study has a mixed-methods sequential explanatory design consisting of two phases: quantitative followed by qualitative. Phase 1 has a multiple point, prospective, longitudinal exploratory design. Ninety men diagnosed with favourable-risk prostate cancer will be assessed immediately post-diagnosis (baseline) and followed over a period of 12 months, in intervals of 3 month. Ninety age-matched men with no cancer diagnosis will also be recruited using peer nomination and followed up in the same 3 month intervals. Following completion of Phase 1, 10–15 AS participants who have reported both the best and worst psychological functioning will be invited to participate in semi-structured qualitative interviews. Phase 2 will facilitate further exploration of the quantitative results and obtain a richer understanding of participants’ personal interpretations of their illness and psychological wellbeing.

Discussion
To our knowledge, this is the first study to utilise early baseline measures; include a healthy comparison group; calculate sample size through power calculations; and use a mixed methods approach to gain a deeper more holistic insight into the experiences of men diagnosed with favourable-risk prostate cancer.

Prostate cancer markers and uses thereof

The present invention relates to composition and methods of cancer diagnosis, research and therapy including, but not limited to, cancer markers. In particular, the present invention relates to LRG1 protein markers for use in the diagnosis, prognosis and determination of treatment of prostate cancer.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment (Review)

Background

It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
Objectives

To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
Search methods

We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
Selection criteria

Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
Data collection and analysis

Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
Main results

Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
Authors' conclusions

Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

A systematic review on the factors associated with positive experiences in carers of someone with cancer.

The aim of this review was to identify the factors associated with positive experiences in non-professional carers of someone with a cancer diagnosis. A systematic search of the following electronic databases was undertaken: Cochrane Library, CINAHL, PsycINFO, SocINDEX and Medline. Literature was searched using terms relating to cancer, caring and positive experiences. Additional records were identified through a manual search of relevant reference lists. The search included studies published in English from 1990- June 2015. Two raters were involved in data extraction, quality appraisal, coding, synthesis, and analysis. Evolutionary concept analysis was used as a guiding framework in order to focus on attributes associated with positive experiences. Fifty two articles were included in this review. Analysis identified four overarching attributes: ‘gender’, ‘personal resources’, ‘finding meaning’ and ‘social context’. Despite the challenges associated with caring this combination of internal and external factors enabled some carers to report positive experiences related to caring. This knowledge may be clinically helpful when designing supportive interventions. Strengths and limitations of these claims are discussed.

Heart failure following cancer therapy in patients with hematological malignancies aged 18 years and under : a linked health data analysis (1996-2009)

Introduction: The causal link between chemotherapy treatments and subsequent cardiotoxicity is well established, particularly for children with hematological malignancies. Little information exists on the characteristics and outcomes for patients with heart failure (HF) after chemotherapy. This study aimed to describe the characteristics, survival and mortality of patients who received chemotherapy for hematological cancer (leukemias, lymphomas and related disorders) before 18 years old and subsequently developed HF compared to those who did not.

Methods: Linked health data (1996-2009) from the Queensland Cancer Registry, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. From all breast and hematological cancers patients (n=73,158), 15,987 received chemotherapy, including 819 patients aged ≤18 years at time of cancer diagnosis. Patients were categorized as those with an index HF admission (occurred after cancer diagnosis) and those without an index HF admission (non HF).

Results: Of the 819 patients, 3.7% (n=30) had an index HF admission. Median age of HF patients at time of cancer diagnosis was 5 years (IQR 3-12) compared to 7 years (IQR 3-14) in the non HF group (p=0.503). Median follow up from cancer diagnosis was 2.5 years in the HF group compared to 5.42 years in the non HF group (p<0.01). Of those who developed HF, 70% (n=21) had the index admission within 12 months of their cancer diagnosis. Of those with HF, 53.3% (n=16) died (all cause) compared to 14.6% (n=115) with no HF. On adjustment for age, sex and chemotherapy admissions, HF patients had an almost 5 fold increased mortality risk compared to non HF patients (HR 4.91 [95% CI, 2.88-8.36]) (Figure 1).

Conclusions: This study demonstrated that in children with hematological cancers the onset of HF occurred soon after chemotherapy and mortality risk is almost 5 times that of children who do not develop HF. Innovative strategies are still needed for the prevention and management of cardiotoxicity in this population.