Description:
Literature attests to the fact that psychosocial needs for cancer patients are not being adequately addressed. The tools, frameworks and guidelines developed, reflect differing professional perspectives and models of disease. Most studies have usually looked at what is happening from the patient and family's viewpoint in terms of medical and other needs. New national initiatives in psychosocial care include the organisation of nationwide practitioner workshops to encourage the implementation of the Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer. These guidelines focus mainly on the emotional and existential areas of need. The aim of this study was to: understand how a diversity of approaches and professional perspectives play out in everyday practice within a rural context; see how issues of distance and access affect this process; and highlight the deficiencies in the delivery of psychosocial services for cancer patients in rural Victoria. The study involved 59 questionnaire respondents (a 71% response rate), from which two interviews and six focus group discussions were drawn. Key findings were: regional and metropolitan hospitals and specialists not referring for support services; private patients missing out; general practitioners not referring to support services; late referrals to palliative care and district nursing; haphazard continuity of care for support needs of patients; and disputed responsibility for initial assessment.
Description:
Literature attests to the fact that psychosocial needs for cancer patients are not being adequately addressed. The tools, frameworks and guidelines developed, reflect differing professional perspectives and models of disease. Most studies have usually looked at what is happening from the patient and family's viewpoint in terms of medical and other needs. New national initiatives in psychosocial care include the organisation of nationwide practitioner workshops to encourage the implementation of the Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer. These guidelines focus mainly on the emotional and existential areas of need. The aim of this study was to: understand how a diversity of approaches and professional perspectives play out in everyday practice within a rural context; see how issues of distance and access affect this process; and highlight the deficiencies in the delivery of psychosocial services for cancer patients in rural Victoria. The study involved 59 questionnaire respondents (a 71% response rate), from which two interviews and six focus group discussions were drawn. Key findings were: regional and metropolitan hospitals and specialists not referring for support services; private patients missing out; general practitioners not referring to support services; late referrals to palliative care and district nursing; haphazard continuity of care for support needs of patients; and disputed responsibility for initial assessment.
Description:
The objective was to explore the psychosocial adaptation of female partners living with men with a diagnosis of either localized or metastatic prostate cancer. Semi-structured qualitative interviews were conducted with 50 women at two time points (baseline and 6 months later). The interviews examined emotions, experiences, attitudes to sexual and continence issues and treatment decision making. As part of a larger prospective observational study, demographic data and scores for depression and anxiety were collected. Initial analysis demonstrated that the group of 11 women assessed as distressed on the anxiety and depression measures described reduced coping skills and poorer adaptation after 6 months. In contrast, the 39 women in the non-distressed group reported emotional adaptation that fitted the Lazarus and Folkman pattern of coping through appraisal of the impact of the diagnosis on their partner and themselves, appraisal of coping strategies and reappraisal of the situation. A surprise finding was the high level of resilience displayed by majority of these women. Results suggest that a psychosocial intervention could strengthen healthy adaptation and provide better coping skills for distressed couples.
Description:
BACKGROUND: Prostate cancer treatment often results in significant psycho-sexual challenges for men following treatment; however, many men report difficulty in accessing appropriate care. METHODS: A randomized controlled trial was undertaken to assess the efficacy of a 10-week self-guided online psychological intervention called My Road Ahead (MRA) for men with localized prostate cancer in improving sexual satisfaction. Participants were randomized to 1 of 3 conditions MRA alone or MRA plus online forum, or forum access alone. Pre, post, and follow-up assessments of overall sexual satisfaction were conducted. Mixed models and structural equation modeling were used to analyze the data. RESULTS: One hundred forty-two men (mean age 61 y; SD = 7) participated. The majority of participants had undergone radical prostatectomy (88%) and all men had received treatment for localized prostate cancer. Significant differences were obtained for the 3 groups (P = .026) and a significant improvement in total sexual satisfaction was observed only for participants who were allocated to MRA + forum with a large effect size (P = .004, partial eta2 = 0.256). Structural equation modeling indicated that increases in sexual function, masculine self-esteem, and sexual confidence contributed significantly to overall sexual satisfaction for the MRA + forum plus forum condition. CONCLUSIONS: This study is the first, to our knowledge, that has evaluated a self-guided online psychological intervention tailored to the specific needs of men with prostate cancer. The findings indicate the potential for MRA to deliver support that men may not otherwise receive and also highlight the importance of psychological intervention to facilitate improved sexual outcomes.
My Road Ahead study protocol: A randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer
Description:
Background: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results: We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received >= 22 weeks of alternating therapy; 78% received >= 22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.
Description:
Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
Description:
Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
Description:
Recurrent deletions of 5q in myeloid malignancies encompass two separate regions: deletion of 5q33, which is associated with the 5q− syndrome and haploinsufficiency of RPS14, and deletion of a more proximal locus at 5q31. We present a case with a cryptic 1.3 Mb deletion in 5q31.2 identified by array comparative genomic hybridization that places the proximal boundary of the deletion proximal and close to the candidate EGR1 gene. The patient was diagnosed initially with a myelodysplastic syndrome, with a del(20)(q11.2q13.3) as the sole abnormality identified by karyotyping. The patient progressed to acute myeloid leukemia with no change to the G-banded karyotype. The 1.3 Mb deletion on the long arm of one chromosome 5 was confirmed to have been present both at presentation with myelodysplastic syndrome and at transformation. This is an interesting case because there are few array studies identifying cryptic 5q deletions, and the study of these small deletions helps to refine the common deleted region. This case, together with previously published studies, suggests that the proximal boundary of the common deleted region may lie within the KDM3B gene.
Tumour microenvironment and metabolic plasticity in cancer and cancer stem cells : Perspectives on metabolic and immune regulatory signatures in chemoresistant ovarian cancer stem cells
Description:
Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.
Description:
Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.
Description:
PURPOSE: Cognitive-existential group therapy (CEGT) was developed to improve mood and mental attitude toward cancer in women with early-stage breast cancer receiving adjuvant chemotherapy. Given the debate about group therapy's association with increased survival in women with metastatic breast cancer, we were curious to check its effect at a much earlier stage in the cancer journey. PATIENTS AND METHODS: We randomly assigned 303 women with early-stage breast cancer who were receiving adjuvant chemotherapy to either 20 sessions of weekly group therapy plus three relaxation classes (n = 154) or to a control condition of three relaxation classes alone (n = 149). The primary outcome was survival. RESULTS: CEGT did not extend survival; the median survival time was 81.9 months (95% CI, 64.8 to 99.0 months) in the group-therapy women and 85.5 months (95% CI, 67.5 to 103.6 months) in the control arm. The hazard ratio for death was 1.35 (95% CI, 0.76 to 2.39; P = .31). In contrast, histology and axillary lymph node status were significant predictors of survival. Low-grade histology yielded a hazard ratio of 0.342 (95% CI, 0.17 to 0.69), and axillary lymph node-negative status yielded a hazard ratio of 0.397 (95% CI, 0.20 to 0.78). CONCLUSION: CEGT does not prolong survival in women with early-stage breast cancer.
Description:
Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function.