Feasibility of brief psychological distress screening by a community-based telephone helpline for cancer patients and carers

Background Up to one-third of people affected by cancer experience ongoing psychological distress and would benefit from screening followed by an appropriate level of psychological intervention. This rarely occurs in routine clinical practice due to barriers such as lack of time and experience. This study investigated the feasibility of community-based telephone helpline operators screening callers affected by cancer for their level of distress using a brief screening tool (Distress Thermometer), and triaging to the appropriate level of care using a tiered model. Methods Consecutive cancer patients and carers who contacted the helpline from September-December 2006 (n = 341) were invited to participate. Routine screening and triage was conducted by helpline operators at this time. Additional socio-demographic and psychosocial adjustment data were collected by telephone interview by research staff following the initial call. Results The Distress Thermometer had good overall accuracy in detecting general psychosocial morbidity (Hospital Anxiety and Depression Scale cut-off score ≥ 15) for cancer patients (AUC = 0.73) and carers (AUC = 0.70). We found 73% of participants met the Distress Thermometer cut-off for distress caseness according to the Hospital Anxiety and Depression Scale (a score ≥ 4), and optimal sensitivity (83%, 77%) and specificity (51%, 48%) were obtained with cut-offs of ≥ 4 and ≥ 6 in the patient and carer groups respectively. Distress was significantly associated with the Hospital Anxiety and Depression Scale scores (total, as well as anxiety and depression subscales) and level of care in cancer patients, as well as with the Hospital Anxiety and Depression Scale anxiety subscale for carers. There was a trend for more highly distressed callers to be triaged to more intensive care, with patients with distress scores ≥ 4 more likely to receive extended or specialist care. Conclusions Our data suggest that it was feasible for community-based cancer helpline operators to screen callers for distress using a brief screening tool, the Distress Thermometer, and to triage callers to an appropriate level of care using a tiered model. The Distress Thermometer is a rapid and non-invasive alternative to longer psychometric instruments, and may provide part of the solution in ensuring distressed patients and carers affected by cancer are identified and supported appropriately.

An exercise intervention for women undergoing chemotherapy for ovarian cancer : feasibility and preliminary outcomes

Exercise interventions during adjuvant cancer treatment have been shown to increase functional capacity, relieve fatigue and distress and in one recent study, assist chemotherapy completion. These studies have been limited to breast, prostate or mixed cancer groups and it is not yet known if a similar intervention is even feasible among women diagnosed with ovarian cancer. Women undergoing treatment for ovarian cancer commonly have extensive pelvic surgery followed by high intensity chemotherapy. It is hypothesized that women with ovarian cancer may benefit most from a customised exercise intervention during chemotherapy treatment. This could reduce the number and severity of chemotherapy-related side-effects and optimize treatment adherence. Hence, the aim of the research was to assess feasibility and acceptability of a walking intervention in women with ovarian cancer whilst undergoing chemotherapy, as well as pre-post intervention changes in a range of physical and psychological outcomes. Newly diagnosed women with ovarian cancer were recruited from the Royal Brisbane and Women’s Hospital (RBWH), to participate in a walking program throughout chemotherapy. The study used a one group pre- post-intervention test design. Baseline (conducted following surgery but prior to the first or second chemotherapy cycles) and follow-up (conducted three weeks after the last chemotherapy dose was received) assessments were performed. To accommodate changes in side-effects associated with treatment, specific weekly walking targets with respect to frequency, intensity and duration, were individualised for each participant. To assess feasibility, adherence and compliance with prescribed walking sessions, withdrawals and adverse events were recorded. Physical and psychological outcomes assessed included functional capacity, body composition, anxiety and depression, symptoms experienced during treatment and quality of life. Chemotherapy completion data was also documented and self-reported program helpfulness was assessed using a questionnaire post intervention. Forty-two women were invited to participate. Nine women were recruited, all of whom completed the program. There were no adverse events associated with participating in the intervention and all women reported that the walking program was helpful during their neo-adjuvant or adjuvant chemotherapy treatment. Adherence and compliance to the walking prescription was high. On average, women achieved at least two of their three individual weekly prescription targets 83% of the time (range 42% to 94%). Positive changes were found in functional capacity and quality of life, in addition to reductions in the number and intensity of treatment-associated symptoms over the course of the intervention period. Functional capacity increased for all nine women from baseline to follow-up assessment, with improvements ranging from 10% to 51%. Quality of life improvements were also noted, especially in the physical well-being scale (baseline: median 18; follow-up: median 23). Treatment symptoms reduced in presence and severity, specifically, in constipation, pain and fatigue, post intervention. These positive yet preliminary results suggest that a walking intervention for women receiving chemotherapy for ovarian cancer is safe, feasible and acceptable. Importantly, women perceived the program to be helpful and rewarding, despite being conducted during a time typically associated with elevated distress and treatment symptoms that are often severe enough to alter or cease chemotherapy prescription.

A systematic review : the effects of orientation programs for cancer patients and their family/carers

Objectives To assess the effects of information interventions which orient patients and their carers/family to a cancer care facility and the services available within the facility. Design Systematic review of randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs. Data sources MEDLINE, CINAHL, PsycINFO, EMBASE and the Cochrane Central Register of Controlled Trials. Methods We included studies evaluating the effect of an orientation intervention, compared with a control group which received usual care, or with trials comparing one orientation intervention with another orientation intervention. Results Four RCTs of 610 participants met the criteria for inclusion. Findings from two RCTs demonstrated significant benefits of the orientation intervention in relation to reduced levels of distress (mean difference (MD): −8.96, 95% confidence interval (95%CI): −11.79 to −6.13), but non-significant benefits in relation to the levels state anxiety levels (MD −9.77) (95%CI: −24.96 to 5.41). There are insufficient data on the other outcomes of interest. Conclusions This review has demonstrated the feasibility and some potential benefits of orientation interventions. There was a low level of evidence to suggest that orientation interventions can reduce distress in patients. However, other outcomes, including patient knowledge recall/satisfaction, remain inconclusive. The majority of trials were subjected to high risk of bias and were likely to be insufficiently powered. Further well conducted and powered RCTs are required to provide evidence for determining the most appropriate intensity, nature, mode and resources for such interventions. Patient and carer-focused outcomes should be included.

Acceptability of the distress thermometer and problem list to community-based telephone cancer helpline operators, and to cancer patients and carers

Background Cancer can be a distressing experience for cancer patients and carers, impacting on psychological, social, physical and spiritual functioning. However, health professionals often fail to detect distress in their patients due to time constraints and a lack of experience. Also, with the focus on the patient, carer needs are often overlooked. This study investigated the acceptability of brief distress screening with the Distress Thermometer (DT) and Problem List (PL) to operators of a community-based telephone helpline, as well as to cancer patients and carers calling the service. Methods Operators (n = 18) monitored usage of the DT and PL with callers (cancer patients/carers, >18 years, and English-speaking) from September-December 2006 (n = 666). The DT is a single item, 11-point scale to rate level of distress. The associated PL identifies the cause of distress. Results The DT and PL were used on 90% of eligible callers, most providing valid responses. Benefits included having an objective, structured and consistent means for distress screening and triage to supportive care services. Reported challenges included apparent inappropriateness of the tools due to the nature of the call or level of caller distress, the DT numeric scale, and the level of operator training. Conclusions We observed positive outcomes to using the DT and PL, although operators reported some challenges. Overcoming these challenges may improve distress screening particularly by less experienced clinicians, and further development of the PL items and DT scale may assist with administration. The DT and PL allow clinicians to direct/prioritise interventions or referrals, although ongoing training and support is critical in distress screening.

Prostate cancer biomarkers and the emerging proteomic techniques used in biomarker research

Prostate cancer (CaP) is the second leading cause of cancer-related deaths in North American males and the most common newly diagnosed cancer in men world wide. Biomarkers are widely used for both early detection and prognostic tests for cancer. The current, commonly used biomarker for CaP is serum prostate specific antigen (PSA). However, the specificity of this biomarker is low as its serum level is not only increased in CaP but also in various other diseases, with age and even body mass index. Human body fluids provide an excellent resource for the discovery of biomarkers, with the advantage over tissue/biopsy samples of their ease of access, due to the less invasive nature of collection. However, their analysis presents challenges in terms of variability and validation. Blood and urine are two human body fluids commonly used for CaP research, but their proteomic analyses are limited both by the large dynamic range of protein abundance making detection of low abundance proteins difficult and in the case of urine, by the high salt concentration. To overcome these challenges, different techniques for removal of high abundance proteins and enrichment of low abundance proteins are used. Their applications and limitations are discussed in this review. A number of innovative proteomic techniques have improved detection of biomarkers. They include two dimensional differential gel electrophoresis (2D-DIGE), quantitative mass spectrometry (MS) and functional proteomic studies, i.e., investigating the association of post translational modifications (PTMs) such as phosphorylation, glycosylation and protein degradation. The recent development of quantitative MS techniques such as stable isotope labeling with amino acids in cell culture (SILAC), isobaric tags for relative and absolute quantitation (iTRAQ) and multiple reaction monitoring (MRM) have allowed proteomic researchers to quantitatively compare data from different samples. 2D-DIGE has greatly improved the statistical power of classical 2D gel analysis by introducing an internal control. This chapter aims to review novel CaP biomarkers as well as to discuss current trends in biomarker research from two angles: the source of biomarkers (particularly human body fluids such as blood and urine), and emerging proteomic approaches for biomarker research.

The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

Re: Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin

Human papillomaviruses (HPVs) cause cervical cancer and some other types of epithelial cancers. HPV types from the phylogenic beta genus (beta-PVs), formerly known as epidermodysplasia verruciformis–associated HPV types, are frequently detected in nonmelanoma skin cancers, especially in squamous cell carcinomas (SCCs). An etiologic relationship with beta-PV infection is suspected...

Enhanced skin self-examination : a novel approach to skin cancer monitoring and follow-up

Advances in mobile telephone technology and available dermoscopic attachments for mobile telephones have created a unique opportunity for consumer-initiated mobile teledermoscopy. At least 2 companies market a dermoscope attachment for an iPhone (Apple), forming a mobile teledermoscope. These devices and the corresponding software applications (apps) enable (1) lesion magnification (at least ×20) and visualization with polarized light; (2) photographic documentation using the telephone camera; (3) lesion measurement (ruler); (4) adding of image and lesion details; and (5) e-mail data to a teledermatologist for review. For lesion assessment, the asymmetry-color (AC) rule has 94% sensitivity and 62 specificity for melanoma identification by consumers [1]. Thus, consumers can be educated to recognize asymmetry and color patterns in suspect lesions. However, we know little about consumers' use of mobile teledermoscopy for lesion assessment.

COX-derived prostanoid pathways in gastrointestinal cancer development and progression : novel targets for prevention and intervention

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE 2, which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2. Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. © 2011 Elsevier B.V.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

Background Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. Methods We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. Results We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. Conclusions This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function.

The role of the Eph and ephrin proteins in prostate cancer

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer related deaths in Australian men. Treatment in the early stages of the disease involves surgery, radiation and/or hormone therapy. However, in late stages of the disease these treatments are no longer effective and only palliative care is available. Therefore, there is a focus on exploration of novel therapies to increase survival and treatment efficacy. Advanced prostate cancer is characterised by bone or other distant metastasis. Spreading of the primary tumour to a secondary location is a complex process requiring an initial loss in cell-cell adhesion followed by increased cell migration and invasion. One gene family that has been known to affect cell-to-cell contact in other model systems are the Eph receptor tyrosine kinases. They are the largest family of receptor tyrosine kinases made up of 14 vertebrate Eph receptors that bind to nine cell membrane bound ephrin ligands. Eph-ephrin interaction is crucial in regulating cell behaviour in developmental processes and it is now thought that the underlying mechanisms involved in development may also be involved in cancer. Aberrant expression has been reported in many human malignancies including prostate cancer. Furthermore, expression has been linked with metastasis and poor prognosis in other tumour models. This study explores the potential role of the Eph receptor family in prostate cancer, in particular the roles of EphA2, EphA3 and ephrin-A5. Gene expression profiles were established for the Eph family in a series of prostate cancer cell lines using quantitative real time RT-PCR. A smaller subset of the most prominently expressed genes was chosen to screen a cohort of clinical samples. Elevated levels of EphA2, EphA3 and their ligands, ephrin-A1 and ephrin-A5 were observed in individual cell lines. Interestingly high EphA3 expression was observed in the androgen responsive cell lines while EphA2 was more prominent in the androgen independent cell lines. However, studies using 5-dihydrotestosterone suggest that EphA3 expression in not regulated by androgen. Cells expressing EphA2 showed a greater ability for migration and invasion while cells expressing EphA3 showed poor migration and invasion. Forced expression of EphA2 in the LNCaP cell line resulted in a more invasive phenotype while forced expression of EphA3 in the PC-3 cell line suggests a possible negative effect for EphA3 on cell migration and invasion. Cell signalling studies show activation of EphA2 decreases activity of proteins thought to be involved in pathways regulating cell movement including Akt, Src and FAK. Changes to the activation status of Rho family members, including RhoA and Rac1, associated with reorganisation of the actin cytoskeleton, an important part of cell migration was also observed. As a result, activation of EphA2 in PC-3 cells resulted in a less invasive phenotype. A novel finding in this study was the discovery of a combination of two EphA2 Mabs able to activate EphA2. Preliminary results show a potential for this antibody combination to reduce prostate cancer invasion in vitro. A unique aspect of Eph-ephrin interaction is the resulting bi-directional signalling that occurs through both the receptor and ligand. In this study a potential role for ephrin-A5 mediated signalling in prostate cancer was observed. LNCaP cells express high levels of EphA3 and its high affinity ligand ephrin-A5. In stripe assays, used to study guidance cues, LNCaP cells show strong attraction/migration to EphA3-Fc stripes but not ephrin-A5-Fc stripes suggesting ephrin-A5 mediated reverse cell signalling is involved. Knockdown of ephrin-A5 using shRNA resulted in a decrease in attraction/migration to EphA3-Fc stripes. Furthermore a reduction in proliferation was also observed in vitro. A subcutaneous xenograft model using ephrin-A5 shRNA cells versus controls showed a decrease in tumour formation. This study demonstrates a difference in EphA2 and EphA3 function in prostate cancer migration/invasion and a potential role for ephrin-A5 in prostate cancer cell adhesion and growth.

Classification of cancer-related death certificates using machine learning

Background Cancer monitoring and prevention relies on the critical aspect of timely notification of cancer cases. However, the abstraction and classification of cancer from the free-text of pathology reports and other relevant documents, such as death certificates, exist as complex and time-consuming activities. Aims In this paper, approaches for the automatic detection of notifiable cancer cases as the cause of death from free-text death certificates supplied to Cancer Registries are investigated. Method A number of machine learning classifiers were studied. Features were extracted using natural language techniques and the Medtex toolkit. The numerous features encompassed stemmed words, bi-grams, and concepts from the SNOMED CT medical terminology. The baseline consisted of a keyword spotter using keywords extracted from the long description of ICD-10 cancer related codes. Results Death certificates with notifiable cancer listed as the cause of death can be effectively identified with the methods studied in this paper. A Support Vector Machine (SVM) classifier achieved best performance with an overall F-measure of 0.9866 when evaluated on a set of 5,000 free-text death certificates using the token stem feature set. The SNOMED CT concept plus token stem feature set reached the lowest variance (0.0032) and false negative rate (0.0297) while achieving an F-measure of 0.9864. The SVM classifier accounts for the first 18 of the top 40 evaluated runs, and entails the most robust classifier with a variance of 0.001141, half the variance of the other classifiers. Conclusion The selection of features significantly produced the most influences on the performance of the classifiers, although the type of classifier employed also affects performance. In contrast, the feature weighting schema created a negligible effect on performance. Specifically, it is found that stemmed tokens with or without SNOMED CT concepts create the most effective feature when combined with an SVM classifier.