Current Issue : October - December Volume : 2013 Issue Number : 4 Articles : 6 Articles
Background: Up to 70% of cancer survivors report clinically significant levels of fear of cancer recurrence (FCR).\r\nDespite the known negative impact of FCR on psychological wellbeing and quality of life, little research has\r\ninvestigated interventions for high FCR. Our team has developed and piloted a novel intervention (Conquer Fear)\r\nbased on the Self-Regulatory Executive Function Model and Relational Frame Theory and is evaluating Conquer\r\nFear in a randomised controlled trial (RCT). We aim to compare the efficacy and cost-efficacy of the Conquer Fear\r\nIntervention and relaxation training in reducing the impact of FCR.\r\nMethods/design: This study is a multi-centre RCT with 260 participants randomised either to the Conquer Fear\r\nIntervention or relaxation training. Both interventions will be delivered in five sessions over 10 weeks by trained\r\npsychologists, psychiatrists and social workers with five or more years experience in oncology. Conquer Fear\r\nsessions use attentional training, detached mindfulness, meta-cognitive therapy, values clarification and\r\npsycho-education to help patients change the way they regulate and respond to thoughts about cancer\r\nrecurrence. Relaxation training includes training in progressive and passive muscle relaxation, meditative relaxation,\r\nvisualisation and ââ?¬Å?quick relaxationââ?¬Â techniques. Relaxation was chosen to control for therapist time and attention\r\nand has good face-validity as an intervention. The primary outcome is fear of cancer recurrence. Secondary\r\noutcomes include distress, quality of life, unmet needs, and health care utilisation. Participants complete\r\nquestionnaires prior to starting the intervention, immediately after completing the intervention, 3 and 6 months\r\nlater. Eligible participants are early-stage breast or colorectal cancer survivors who have completed hospital-based\r\ntreatment between 2 months and 5 years prior to study entry and report a score in the clinical range on the Fear\r\nof Cancer Recurrence Inventory. The biostatistician is blinded to group allocation and participants are blinded to\r\nwhich intervention is being evaluated. Randomisation is computer generated, stratified by therapist, and uses\r\nsequentially numbered sealed envelopes.\r\nDiscussion: If successful, the study will provide an evidence-based intervention to reduce psychological morbidity\r\nin cancer survivors, and reduce overall health care costs due to more appropriate use of follow-up care and other\r\nhealth services in this very large population....
Background: Faced with a life-threatening illness, such as cancer, many patients develop stress symptoms, i.e.\r\navoidance behaviour, intrusive thoughts and worry. Stress management interventions have proven to be effective;\r\nhowever, they are mostly performed in group settings and it is commonly breast cancer patients who are studied.\r\nWe hereby present the design of a randomized controlled trial (RCT) evaluating the effectiveness and\r\ncost-effectiveness of an individual stress-management intervention with a stepped-care approach in several cancer\r\ndiagnoses.\r\nMethod: Patients (= 18 years) with a recent diagnosis of breast cancer, colorectal cancer, lymphoma, prostate\r\ncancer or testicle cancer and scheduled for adjuvant/curative oncology treatment, will consecutively be included in\r\nthe study. In this prospective longitudinal intervention study with a stepped-care approach, patients will be\r\nrandomized to control, treatment as usual, or an individual stress-management intervention in two steps. The first\r\nstep is a low-intensity stress-management intervention, given to all patients randomized to intervention. Patients\r\nwho continue to report stress symptoms after the first step will thereafter be given more intensive treatment at the\r\nsecond step of the programme. In the intervention patients will also be motivated to be physically active.\r\nAvoidance and intrusion are the primary outcomes. According to the power analyses, 300 patients are planned to\r\nbe included in the study and will be followed for two years. Other outcomes are physical activity level, sleep\r\nduration and quality recorded objectively, and anxiety, depression, quality of life, fatigue, stress in daily living, and\r\npatient satisfaction assessed using valid and standardized psychometric tested questionnaires. Utilization of hospital\r\nservices will be derived from the computerized patient administration systems used by the hospital. The\r\ncost-effectiveness of the intervention will be evaluated through a cost-utility analysis.\r\nDiscussion: This RCT will provide empirical evidence of whether an individually administered stress-management\r\nprogramme in two steps can decrease stress as well as maintain or enhance patients� physical activity level, quality\r\nof life and psychological well-being. Further, this RCT, with a stepped-care approach, will provide knowledge\r\nregarding the cost-effectiveness of an individually administered stress-management programme whose aim is to\r\nhelp and support individual patients at the right level of care....
Background: HPV is related to a number of cancer types, causing a considerable burden in both genders in\r\nEurope. Female vaccination programs can substantially reduce the incidence of HPV-related diseases in women\r\nand, to some extent, men through herd immunity. The objective was to estimate the incremental benefit of\r\nvaccinating boys and girls using the quadrivalent HPV vaccine in Europe versus girls-only vaccination. Incremental\r\nbenefits in terms of reduction in the incidence of HPV 6, 11, 16 and 18-related diseases (including cervical, vaginal,\r\nvulvar, anal, penile, and head and neck carcinomas and genital warts) were assessed.\r\nMethods: The analysis was performed using a model constructed in MicrosoftWExcel, based on a\r\npreviously-published dynamic transmission model of HPV vaccination and published European epidemiological data\r\non incidence of HPV-related diseases. The incremental benefits of vaccinating 12-year old girls and boys versus\r\ngirls-only vaccination was assessed (70% vaccine coverage were assumed for both). Sensitivity analyses around\r\nvaccine coverage and duration of protection were performed.\r\nResults: Compared with screening alone, girls-only vaccination led to 84% reduction in HPV 16/18-related\r\ncarcinomas in females and a 61% reduction in males. Vaccination of girls and boys led to a 90% reduction in HPV\r\n16/18-related carcinomas in females and 86% reduction in males versus screening alone. Relative to a girls-only\r\nprogram, vaccination of girls and boys led to a reduction in female and male HPV-related carcinomas of 40% and\r\n65%, respectively and a reduction in the incidence of HPV 6/11-related genital warts of 58% for females and 71%\r\nfor males versus girls-only vaccination.\r\nConclusions: In Europe, the vaccination of 12-year old boys and girls against HPV 6, 11, 16 and 18 would be\r\nassociated with substantial additional clinical benefits in terms of reduced incidence of HPV-related genital warts\r\nand carcinomas versus girls-only vaccination. The incremental benefits of adding boys vaccination are highly\r\ndependent on coverage in girls. Therefore, further analyses should be performed taking into account the\r\ncountry-specific situation. In addition to clinical benefits, substantial economic benefits are also anticipated and\r\nwarrant further investigation as do the social and ethical implications of including boys in vaccination programs....
Background: New pharmacologic targets are urgently needed to treat or prevent lung cancer, the most common\r\ncause of cancer death for men and women. This study identified one such target. This is the canonical Wnt\r\nsignaling pathway, which is deregulated in cancers, including those lacking adenomatous polyposis coli or �Ÿ-catenin\r\nmutations. Two poly-ADP-ribose polymerase (PARP) enzymes regulate canonical Wnt activity: tankyrase (TNKS) 1\r\nand TNKS2. These enzymes poly-ADP-ribosylate (PARsylate) and destabilize axin, a key component of the �Ÿ-catenin\r\nphosphorylation complex.\r\nMethods: This study used comprehensive gene profiles to uncover deregulation of the Wnt pathway in murine\r\ntransgenic and human lung cancers, relative to normal lung. Antineoplastic consequences of genetic and\r\npharmacologic targeting of TNKS in murine and human lung cancer cell lines were explored, and validated in vivo\r\nin mice by implantation of murine transgenic lung cancer cells engineered with reduced TNKS expression relative\r\nto controls.\r\nResults: Microarray analyses comparing Wnt pathway members in malignant versus normal tissues of a murine\r\ntransgenic cyclin E lung cancer model revealed deregulation of Wnt pathway components, including TNKS1 and\r\nTNKS2. Real-time PCR assays independently confirmed these results in paired normal-malignant murine and human\r\nlung tissues. Individual treatments of a panel of human and murine lung cancer cell lines with the TNKS inhibitors\r\nXAV939 and IWR-1 dose-dependently repressed cell growth and increased cellular axin 1 and tankyrase levels. These\r\ninhibitors also repressed expression of a Wnt-responsive luciferase construct, implicating the Wnt pathway in\r\nconferring these antineoplastic effects. Individual or combined knockdown of TNKS1 and TNKS2 with siRNAs or\r\nshRNAs reduced lung cancer cell growth, stabilized axin, and repressed tumor formation in murine xenograft and\r\nsyngeneic lung cancer models.\r\nConclusions: Findings reported here uncovered deregulation of specific components of the Wnt pathway in both\r\nhuman and murine lung cancer models. Repressing TNKS activity through either genetic or pharmacological\r\napproaches antagonized canonical Wnt signaling, reduced murine and human lung cancer cell line growth, and\r\ndecreased tumor formation in mouse models. Taken together, these findings implicate the use of TNKS inhibitors to\r\ntarget the Wnt pathway to combat lung cancer....
Background: Interleukin (IL)-11, a cytokine produced by breast cancer, has been implicated in breast\r\ncancer-induced osteolysis (bone destruction) but the mechanism(s) of action remain controversial. Some studies\r\nshow that IL-11 is able to promote osteoclast formation independent of the receptor activator of NF-?B ligand\r\n(RANKL), while others demonstrate IL-11 can induce osteoclast formation by inducing osteoblasts to secrete RANKL.\r\nThis work aims to further investigate the role of IL-11 in metastasis-induced osteolysis by addressing a new\r\nhypothesis that IL-11 exerts effects on osteoclast progenitor cells.\r\nMethods: To address the precise role of breast cancer-derived IL-11 in osteoclastogenesis, we determined the\r\neffect of breast cancer conditioned media on osteoclast progenitor cells with or without an IL-11 neutralizing\r\nantibody. We next investigated whether recombinant IL-11 exerts effects on osteoclast progenitor cells and survival\r\nof mature osteoclasts. Finally, we examined the ability of IL-11 to mediate osteoclast formation in tissue culture\r\ndishes and on bone slices in the absence of RANKL, with suboptimal levels of RANKL, or from RANKL-pretreated\r\nmurine bone marrow macrophages (BMMs).\r\nResults: We found that freshly isolated murine bone marrow cells cultured in the presence of breast cancer\r\nconditioned media for 6 days gave rise to a population of cells which were able to form osteoclasts upon\r\ntreatment with RANKL and M-CSF. Moreover, a neutralizing anti-IL-11 antibody significantly inhibited the ability of\r\nbreast cancer conditioned media to promote the development and/or survival of osteoclast progenitor cells.\r\nSimilarly, recombinant IL-11 was able to sustain a population of osteoclast progenitor cells. However, IL-11 was\r\nunable to exert any effect on osteoclast survival, induce osteoclastogenesis independent of RANKL, or promote\r\nosteoclastogenesis in suboptimal RANKL conditions.\r\nConclusions: Our data indicate that a) IL-11 plays an important role in osteoclastogenesis by stimulating the\r\ndevelopment and/or survival of osteoclast progenitor cells and b) breast cancer may promote osteolysis in part by\r\nincreasing the pool of osteoclast progenitor cells via tumor cell-derived IL-11. However, given the heterogeneous\r\nnature of the bone marrow cells, the precise mechanism by which IL-11 treatment gives rise to a population of\r\nosteoclast progenitor cells warrants further investigation...
Background: This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC)\r\nenumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive\r\nmetastatic breast cancer (MBC) patients.\r\nMethods: Sixty HER2-positive MBC patients were enrolled in the present study. Before the initiation of systemic\r\ntreatment, CTCs from 7.5 ml of blood were analyzed using the CellSearch system. The progression-free survival (PFS)\r\nof the patients was estimated using Kaplan-Meier survival curves.\r\nResults: CTCs were detected in 45% (27/60) of the patients, who had shorter median PFS than those without CTCs\r\n(2.5 vs. 7.5 months, P = 0.0125). Furthermore, referring to the standard HER2 testing that uses immunohistochemistry\r\n(IHC), we proposed a CTC HER2-positive criterion, defined as >30% of CTCs over-expressing HER2. Among patients\r\nundergoing anti-HER2 therapy, those with HER2-positive CTCs had longer PFS (8.8 vs. 2.5 months, P = 0.002). Among\r\npatients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer\r\nthan those who were not (8.8 vs. 1.5 months, P = 0.001). Notably, up to 52% (14/27) of the HER2-positive patients\r\nwere CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients\r\n(2.5 vs. 0.9 months, P = 0.499).\r\nConclusions: Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable\r\nprognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients.\r\nTo test this idea, additional large cohort, multi-center and prospective clinical trials are needed....
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