Cancer detective

The artile describes development of an automated system for detection of lung nodules in CT images.

New system to help detect lung cancer

The article tells about the development of an intelligent system that can improve early detection of lung tissue abnormalities.

Beating the blues after cancer : randomised control trial of a tele-based psychological intervention for high distress patients and carers

Background : The diagnosis and treatment of cancer is a major life stress such that approximately 35% of patients experience persistent clinically significant distress and carers often experience even higher distress than patients. This paper presents the design of a two arm randomised controlled trial with patients and carers who have elevated psychological distress comparing minimal contact self management vs. an individualised tele-based cognitive behavioural intervention.

Methods/design : 140 patients and 140 carers per condition (560 participants in total) will been recruited after being identified as high distress through caller screening at two community-based cancer helplines and randomised to 1) a single 30-minute telephone support and education session with a nurse counsellor with self management materials 2) a tele-based psychologist delivered five session individualised cognitive behavioural intervention. Session components will include stress reduction, problem-solving, cognitive challenging and enhancing relationship support and will be delivered weekly. Participants will be assessed at baseline and 3, 6 and 12 months after recruitment. Outcome measures include: anxiety and depression, cancer specific distress, unmet psychological supportive care needs, positive adjustment, overall Quality of life.

Discussion : The study will provide recommendations about the efficacy and potential economic value of minimal contact self management vs. tele-based psychologist delivered cognitive behavioural intervention to facilitate better psychosocial adjustment and mental health for people with cancer and their carers.

Saw palmetto supplement use and prostate cancer risk

Saw palmetto is an herb used to treat the symptoms of benign prostatic hyperplasia. In vitro studies have found that saw palmetto inhibits growth of prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto supplements are associated with a reduced risk of prostate cancer, we conducted a prospective cohort study of 35,171 men aged 50-76 yr in western Washington state. Subjects completed questionnaires between 2000 and 2002 on frequency of use of saw palmetto supplements and saw palmetto-containing multivitamins over the previous 10 yr in addition to other information on supplement intake, medical history, and demographics. Men were followed through December 2003 (mean of 2.3 yr of follow-up) via the western Washington Surveillance, Epidemiology, and End Results cancer registry, during which time 580 developed prostate cancer. Ten percent of the cohort used saw palmetto at least once per week for a year in the 10 yr before baseline. No association was found between this level of use of saw palmetto and risk of prostate cancer development [hazard ratio (HR) = 0.95; 95% confidence interval = 0.74-1.23] or with increasing frequency or duration of use. In this free-living population, use of commercial saw palmetto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk.

Prostate cancer : Anglo-Australian heterosexual perspectives

Prostate cancer is one of the most prominent diseases in men’s health. It is inherently 'male', given the exclusivity of the prostate gland to men’s bodies and its physiological connection to testosterone and male sexuality. The biomedical complexities of prostate cancer continue to be unravelled and researched and are often connected to identifying causes, the virtues of screening and treatment modalities. However, despite the biological male 'sex' link, most of the prostate cancer research is not connected with research on gender relations, men and masculinities. The net outcome is that men’s lives and illness experiences are absent in much of the prostate cancer research. This PhD thesis Prostate cancer: Anglo-Australian heterosexual perspectives, is an ethnographic study of thirty-five Anglo-Australian men diagnosed with prostate cancer. Participants shared their experiences of living with prostate cancer in the context of health promotion, health services and in relation to their sexuality and intimate relationships. Through participant photographic novella and in-depth semi-structured interviews, rich cultural insights are provided. A social constructionist gender analysis is used in this research that shows how the social constructions of masculinity interconnect and occasionally collide with prostate cancer throughout the illness trajectory.

Living with cancer : an ethnographic study of Thai cancer patients

This thesis is an ethnographic investigation aimed at describing the lived experiences of Thai cancer patients residing in Cancer Hostel, a shelter provided for the needy whilst undergoing radiation treatment at Siam Hospital. All names, including the hospital, the shelter, and all respondents have been altered to preserve anonymity. The practice of withholding the true diagnosis from Thai patients meant that very little was known about their own feelings on cancer and its treatment. That, coupled with entrenched medical practice beliefs, presented an unusual challenge, for which an ethnographic research method was advocated as being most appropriate in helping toward a better understanding of the problem and resolving the existing dilemma. To understand the real experiences of Thai cancer patients, it was extremely important that the researcher get as near as possible to becoming one of them. Therefore, by physically 'being with’, establishing rapport, and gaining patients trust, the researcher was assured of acceptance as an insider, and was thus allowed to share the experiences of their life encounters. Research findings graphically illustrated the flaws in the practice of protecting patients from their diagnosis, who almost universally, wanted to know more about their diagnosis in order to seek help from the medical care system. Towards this, patients created meaning by linking folk beliefs, culturally inherited knowledge and a common sense, albeit naive approach in trying to make sense of their illness and treatment. Although patients saw cancer illness and its treatment, especially radiotherapy, as life threatening, it was the fear of radiation treatment, not cancer illness which turned patients away from medical treatment. As well, uncertainty, fear and frustration through the lack of information and involvement in their treatment saw patients employ strategies of both reciprocal and fatalistic acceptance; stoic resistance; and thinking positively in their efforts at coping with those life threatening situations.

Economic evaluation of skin cancer prevention in Australia

Objectives
Australia has the highest incidence of skin cancer in the world, despite prevention campaigns being implemented since the early 1980s. This study assesses the cost-effectiveness of a skin cancer prevention program (named SunSmart) since it was introduced, together with its potential cost-effectiveness as an upgraded and ongoing national program.

Methods
The reduction in melanoma incidence attributable to SunSmart was modelled as the primary end-point. Historical expenditures on SunSmart were obtained from representative Australian states in three latitude zones. Melanoma incidence rates from these states were used to model key health outcomes. Non-melanoma skin cancer was modelled separately based on national survey results.

Results
We estimate that SunSmart has averted 28,000 disability-adjusted life-years (DALYs), equivalent to 22,000 life-years saved, in the state of Victoria since its introduction in 1988, as well as saving money from cost offset in skin cancer management (dominant). An upgraded national program for the next 20 years is estimated to avert 120,000 DALYs, with associated reductions in the use of health care resources. It remains a dominant intervention in which every dollar invested in SunSmart will return an estimated AU$2.30.

Conclusions
This study demonstrates that a sustained modest investment in skin cancer control is likely to be an excellent value for money.

Economic evaluation of a skin cancer prevention program in Australia : past achievements and future prospects

Objectives
Australia has the highest incidence of skin cancer in the world. Skin cancer prevention campaigns have been implemented in Australia for over two decades. The most notable is under the brand name, SunSmart. The aim of the current study is to assess the cost-effectiveness of SunSmart in the past and the potential cost-effectiveness of an ongoing national SunSmart program with optimal investment in the future.

Methods
An economic evaluation from a health sector perspective was conducted using the reduction in skin cancer incidence attributable to the SunSmart program modelled as the primary end-point. Historical SunSmart program expenditures were obtained from three representative states in three latitude zones, covering different levels of UVR exposure. Melanoma incidence rates from the three representative state cancer registers were used to model the health outcomes. Program effectiveness was assessed by the comparison between the well-resourced SunSmart state (Victoria) and the under-invested states (New South Wales and Queensland). Non-Melanoma Skin Cancer (NMSC) was modelled based on national survey results. 2003 was chosen as the reference year and future costs/outcomes over a 20 year time horizon were discounted at 3%.
The future level of investment in a national SunSmart was chosen to strengthen current practice by increasing current investment to a realistic and achievable level. This conservative increase in investment (expressed as ‘$ per capita’) reflected the investment level that has been achieved in Victoria over sustained periods. To model the potential cost-effectiveness of an upgraded national SunSmart program, a conservative approach was taken, whereby the same magnitude of effectiveness from 1988 to 2003 was applied to future skin cancer incidence.

Results
SunSmart in Victoria has saved 22,300 life-years, averted 27,900 disability-adjusted life-years(DALYs)(discounted) since its introduction in 1988 and achieved an incremental cost-effectiveness ratio (ICER) of $AUD 680 per life-year saved (LYS) and $AUD 540 per DALY averted. When the cost-offset from the estimated reduction in skin cancer treatment costs were taken into account, SunSmart achieved ‘dominance’. The net cost of SunSmart in the past was an estimated saving of $AUD 93 million. An upgraded national SunSmart for the next 20 years would save 91,000 life-years and avert 122,000 DALYs (discounted), involving an increased investment level from the current $AUD 0.07 per capita to the historical average of $AUD 0.28 per capita. The ICER for the upgraded SunSmart program was estimated at $AUD 940 per LYS and $AUD 700 per DALY averted. When the cost-offset is included, the program achieves dominance with a cost saving of $AUD 115 million – an estimated $AUD 2.32 return for every dollar invested between 2003 and 2022.

Conclusions
This study demonstrates that a sustained modest investment in skin cancer control is likely to be excellent value-for-money. While the available data base is certainly not prefect, key parameters would have to change dramatically for this conclusion to be challenged.

Options for change in the Australian cervical cancer screening program in context of HPV detection and vaccination

Introduction:
Cervical cancer screening has been implemented for over a decade in Australia and has significantly reduced the mortality and morbidity of the disease. The emergence of new technologies for cervical cancer, such as the Human Papillomavirus (HPV) vaccine and DNA testing has encouraged debate regarding the effective use of resources in cervical cancer prevention. The present study evaluates the cost-effectiveness, from a health sector perspective, of various screening strategies in the era of these new technologies.

Methods:
A stochastic epidemiological model using a discrete event and continuous algorithm was developed to describe the natural history of cervical cancer. By allowing one member of the cohort into the model at a time, this micro-simulation model encompasses the characteristics of heterogeneity and can track individual life histories. To evaluate the cost-effectiveness of the HPV vaccine a Markov model was built to simulate the effect on the incidence of HPV and subsequent cervical cancer. A number of proposed screening strategies were evaluated with the stochastic model for the application of HPV DNA testing, with changes in the screening interval and target population. Health outcomes were measured by Disability-Adjusted Life-Years (DALYs), adjusted for application within an evaluation setting (i.e. the mortality component of the DALY was adjusted by a disability weight when early mortality due to cervical cancer is avoided). Costs in complying with the Australian updated guidelines were assessed by pathway analysis to estimate the resources associated with cervical cancer and its pre-cancerous lesion treatment. Sensitivity analyses were performed to investigate the key parameters that influenced the cost-effectiveness results.

Results:
Current practice has already brought huge health gain by preventing more than 4,000 deaths and saving more than 86,000 life-years in a cohort of a million women. Any of the alternative screening strategies alter the total amount of health gain by a small margin compared to current practice. The results of incremental analyses of the alternative screening strategies compared to current practice suggest the adoption of the HPV DNA test as a primary screening tool every 3 years commencing at age 18, or the combined pap smear/HPV test every 3 years commencing at age 25, are more costly than current practice but with reasonable ICERs (AUD$1,810 per DALY and AUD$18,600 per DALY respectively). Delaying commencement of Pap test screening to age 25 is less costly than current practice, but involves considerable health loss. The sensitivity analysis shows, however, that the screening test accuracy has a significant impact on these conclusions. Threshold analysis indicates that a sensitivity ranging from 0.80 to 0.86 for the combined test in women younger than 30 is required to produce an acceptable incremental cost-effectiveness ratio.

Conclusions:
The adoption of HPV and combined test with an extended screening interval is more costly but affordable, resulting in reasonable ICERs. They appear good value for money for the Australian health care system, but need more information on test accuracy to make an informed decision. Potential screening policy change under current Australian HPV Vaccination Program is current work in progress. A Markov model is built to simulate the effect on the incidence of HPV and subsequent cervical cancer. Adoption of HPV DNA test as a primary screening tool in the context of HPV vaccination is under evaluation.

Analytical relationship between family history and genetic and environmental risks, with application to female breast cancer

It is well established in genetic epidemiology that family history is an important indicator of familial aggregation of disease in a family. A strong genetic risk factor or an environmental risk factor with high familial correlation can result in a strong family history. In this paper, family history refers to the number of first-degree relatives affected with the disease. Cui and Hopper (Journal of Epidemiology and Biostatistics 2001; 6: 331-342) proposed an analytical relationship between family history and relevant genetic parameters. In this paper we expand the relationship to both genetic and environmental risk factors. We established a closed-form formula for family history as a function of genetic and environmental parameters which include genetic and environmental relative risks, genotype frequency, prevalence and familial correlation of the environmental risk factor. The relationship is illustrated by an example of female breast cancer in Australia. For genetic and environmental relative risks less than 10, most of the female breast cancer cases occur between the age of 40 and 60 years. A higher genetic or environmental relative risk will move the peak of the distribution to a younger age. A more common disease allele or more prevalent environmental risk factor will move the peak to an older age. For a proband with breast cancer, it is most likely (with probability ge80%) that none of her first-degree relatives is affected with the disease. To enable the probability of having a positive family history to reach 50%, the environmental relative risks must be extremely as high as 100, the familial correlation as high as 0.8 and the prevalence as low as 0.1. For genetic risk alone, even the relative risk is as high as 100, the probability of having a positive family history can only reach about 30%. This suggests that the environmental risk factor seems to play a more important role in determining a strong family history than the genetic risk factor.

Regressive logistic and proportional hazards disease models for within-family analyses of measured genotypes, with application to a CYP17 polymorphism and breast cancer

Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population-based case families in which a mutation is known to be segregating. Here we extend the method to a common polymorphism, and use a regressive logistic approach to model familial aggregation by conditioning each individual on their mother's breast cancer history. We considered three models: 1) class A regressive logistic model; 2) age-of-onset regressive logistic model; and 3) proportional hazards familial model. Maximum likelihood estimates were calculated using the software MENDEL. We applied these methods to data from the Australian Breast Cancer Family Study on the CYP17 5UTR TC MspA1 polymorphism measured for 1,447 case probands, 787 controls, and 213 relatives of case probands found to have the CC genotype. Breast cancer data for first- and second-degree relatives of case probands were used. The three methods gave consistent estimates. The best-fitting model involved a recessive inheritance, with homozygotes being at an increased risk of 47% (95% CI, 28-68%). The cumulative risk of the disease up to age 70 years was estimated to be 10% or 22% for a CYP17 homozygote whose mother was unaffected or affected, respectively. This analytical approach is well-suited to the data that arise from population-based case-control-family studies, in which cases, controls and relatives are studied, and genotype is measured for some but not all subjects.

Genome - wide association study identifies novel breast cancer susceptibility loci

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r² > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10^-7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia)

OBJECTIVE: We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. METHODS: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. RESULTS: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. CONCLUSIONS: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.