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The article presents summaries of several papers which were presented at the 2010 World Health Organization International Consultation on Prostate Cancer. The papers centered on advances in screening, prevention and therapy for prostate cancer and discussed the future challenges of prostate cancer and its prevention and treatment.

Background. Radical prostatectomy (RP) is worldwide probably the most common procedure to treat localized prostate cancer (PC). Due to a more widespread use of Prostate-Specific Antigen (PSA) testing, patients operated today are often younger and have organ confined disease justifying a more preservative surgery. At the same time, surgical technique has improved resulting in lower risk of permanent side-effects. This paper aims to give an overview of results from modern surgery regarding cancer control and side-effects. A brief overview of the history is given. Material and Methods. A literature research identified recently published papers focusing on outcome and side-effects after RP. Results. One large randomized study (SPCG-4) compared RP and watchful waiting (WW). The study showed that RP was superior to WW in preventing local progression (RR 0.36), distant metastasis (RR 0.65) and death from PC (RR 0.65). Observational studies also show a better outcome for men treated with RP compared to WW. Peri-operative mortality after RP is low in most material around 0.1%. The risk of stricture of the vesico-urethral anastomosis has decreased with improved technique from historically 10-20% to a low incidence of around 2-9% today. Also the risk of incontinence has declined with improved technique. However, while the rates of severe incontinence is usually very low, as many as 30% still report light incontinence after long-term follow-up. Erectile dysfunction (ED) is still a frequent side-effect after RP. This risk is dependent on age, pre-operative sexual function, surgical technique and other risk factors for ED such as smoking, diabetes, etc. In selected subgroups the risk of ED is low. Inguinal hernia is a more recently described complication after open retropubic RP with a post-operative incidence of 15-20% within three years of surgery. Conclusion. RP is an effective method to achieve cancer control in selected patients. With modern technique it is a safe procedure with a low risk of permanent side-effects except for ED. [ABSTRACT FROM AUTHOR]

Background In the 1990s outcomes in Danish lung cancer patients were poor compared with the other Nordic countries. The five-year survival was only about 5%, only 10% of patients were operated on and less than 60% received active surgical or oncologic treatment. This paper describes trends in mortality and survival of lung cancer in Denmark from 2000 to 2012. Methods The study population comprised 52 435 patients with a diagnosis of cancer of the trachea and the lung, primarily ascertained from the Danish Lung Cancer Register and grouped into three cohorts by year of diagnosis. The outcome measures covered the first year as well as the first full five-year period after diagnosis and comprised absolute mortality rate (per 100 patient years), absolute survival, and the relative survival. All outcomes were estimated for the overall patient population as well as after stratification by covariates. Results Overall, the mortality rates have declined significantly over time from 117 per 100 patient years to 88 for the one-year mortality and from 75 to 65 for the five-year mortality rates, respectively. With the exception of patients with advanced stage, declining mortality was observed for all strata by gender, comorbidity, stage and surgery status and was accompanied by corresponding improvements in both absolute and relative survival. Conclusions The mortality has been significantly declining and the prognosis correspondingly improving in lung cancer in Denmark since the turn of the millennium. As of today, survival after lung cancer in Denmark is probably in line with the international standard. Based on our results we recommend introducing mortality indicators based on all-cause mortality within the patient population in international benchmarking studies as comparisons based on cancer-specific mortality relative to the total general population may be misleading when interpreted in the context of outcomes and quality of care. [ABSTRACT FROM AUTHOR]

BackgroundColorectal cancer (CRC) is a disease of the older population. The current demographic ageing leads to more elderly patients and is expected to further increase the number of patients with CRC. The objective of the present paper is to outline incidence, mortality and prevalence from 1980 to 2012 and survival data from 1968 to 2012 in Danish CRC patients focusing on the impact of ageing. Material and methodsData were derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data are delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. This study focuses on the elderly population categorized in six age groups. ResultsThe incidence of CRC has increased over the past three decades. Incidence rate has increased in patients with colon cancer, but showed a decreasing trend in the oldest patients with rectal and anal cancer. Mortality has diminished in younger patients with colon cancer, but increased with increasing age. However, mortality did not increase proportionally to incidence. In rectal and anal cancer mortality has decreased, except among the oldest patients. This correlates to a decreasing incidence rate. Prevalence is widely increasing mainly because of increased incidence and longer survival, which is reflected in the increasing one- and five-year age-specific relative survival after a diagnosis of colon, rectal and anal cancer. ConclusionThe incidence of CRC is increasing, especially in older citizens, and mortality increases with older age. There is limited knowledge on how to optimize treatment in older CRC patients and future focus must be how to select and tailor the treatment for older CRC patients. [ABSTRACT FROM PUBLISHER]

BackgroundThe incidence of melanoma is rising in Denmark. In the present paper we describe incidence, mortality and survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years. Material and methodsMelanoma was defined as ICD-10 code C43. Data derived from the NORDCAN database with comparable data on incidence, mortality, survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up until the end of 2013. ResultsIn 1980, 21.4% of the patients diagnosed with melanoma were older than 70 years compared to 28.4% in 2012. In persons aged less than 70 years, the incidence rate was higher among women than in men, but men aged 70–89 years had an incidence rate almost twice that of women. Incidence rates were increasing, particularly among the elderly. In 1980, 32.6% of the patients who died from melanoma were older than 69 years compared to 56.2% in 2012. In 1980, the mortality rate was 121.4 per 100 000 person years, increasing to 353.1 in 2012. For the younger patients, the mortality rates are only slight increasing, but for the elder patients the mortality rates are increasing dramatically. In general the survival has increased for all age groups over the years. ConclusionThe incidence rates for all age groups are rising. The increase was mainly caused by a rising incidence among the elderly. Mortality among Danish patients with melanoma is increasing and especially the mortality in the elderly. This important knowledge must be kept in mind when future treatment strategies are planned. [ABSTRACT FROM PUBLISHER]

Radiotherapy (RT) always requires a compromise between tumor control and normal tissue side-effects. Technical innova- tion in radiation therapy (RT), such as three dimensional RT, is now established. Concerning prostate cancer (PC), it is reasonable to assume that RT of PC will increase in the future. The combination of small margins, a movable target (prostate), few fractions and high doses will probably demand dynamically positioning systems and in real time. This is called four dimensional radiotherapy (4DRT). Moreover, biological factors must be included in new treatments such as hypofractionation schedules. This new era is called five dimensional radiotherapy, 5DRT. In this paper we discuss new concepts in RT in respect to PC. [ABSTRACT FROM AUTHOR]

Background. In 2009, the European Randomized Study of Screening for Prostate Cancer (ERSPC) was one of two studies to report interim data on the effect of screening for prostate cancer (PC) on the disease specific mortality. Contradictory results caused considerable discussion and misunderstanding in secondary literature. Methods. This document is based on a non systematic review of recent evidence for and against screening for PC, specifically considering three recently published randomized screening trials [1 - 3]. Results. The ERSPC data are based on a core age group of 162 387 men, aged 55-69 years, who were identified through population registries in seven European countries. Men were randomized between a screening group that received screening at an average of once every four years and a control group. After a median follow-up of nine years, a reduction in the rate of death from PC by 20% was shown which increased to 31% after adjusting for non-compliance and contamination. Overdetection and subsequent overtreatment (with a number needed to treat (NNT) of 48) are considered to be the major down sides of screening. The recently published 14-year results have shown that these down sides strongly depend on the duration of follow-up. In response to the outcomes of the ERSPC, several points of discussion have been brought up by various authors concerning the usefulness of screening considering benefits, harms and costs, the methodology of the ERSPC and the interpretation of its outcomes. Important issues to address regarding PC screening are addressed. Conclusions . This paper sheds a light on the controversial points of the ERSPC as well as on the priority issues of PC screening. On July 2, 2010 the Swedish section of ERSPC (Göteborg screening trial) published their results with a median follow-up of 14 years. With longer follow-up the data confirm the trend seen in improvement of PC mortality and suggest much more favorable future outcomes also with respect to the NNT to prevent one PC death. [ABSTRACT FROM AUTHOR]

Background. There are no established treatments for cachexia. Recently it has been suggested that the evidence for non-steroidal anti-inflammatory (NSAID) treatment is sufficient to support its regular clinical use. Primary objective in this systematic review was to assess efficacy and safety of NSAID treatment in improving body weight and muscle mass in patients with cancer cachexia. Secondary objectives were to assess whether this treatment could improve other cachexia domains such as anorexia and food intake, catabolic drive and function. Material and methods. A systematic literature review of PubMed, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms. Results. Thirteen studies were included; all but two trials showed either improvement or stabilization in weight or lean body mass. Seven studies were without a comparator. Studies are generally small and a few are methodologically flawed, often due to multiple outcomes with excess risk of false positives. Conclusion. NSAIDs may improve weight in cancer patients with cachexia, and there is some evidence on effect on physical performance, self-reported quality of life and inflammatory parameters. Evidence is too frail to recommend NSAID for cachexia outside clinical trials. This is supported by the known side effects of NSAIDs, even though the reviewed literature report almost negligible toxicity. [ABSTRACT FROM AUTHOR]

Profiles Sakari Mustakallio, a cancer doctor and head of the Radiotherapy Department in Helsinki, Finland. Educational background of Mustakallio; Work achievements; Contributions to cancer treatment.

Background Breast cancer mortality has declined from 1995 through 2012 which may be attributed to earlier diagnosis, changes in lifestyle risk factors, and improved treatments. To a large extent the relative contribution of these modalities are unknown. Mammography screening was introduced late in Denmark; in 1995 around 20% of the Danish female population aged 50-69 was covered by population-based screening, and this was in 2008 extended to the entire population. Breast conserving surgery gradually replaced mastectomy, and sentinel node biopsy was introduced. In the same period adjuvant treatment was extended considerable. Methods A population-based study of 68842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were used to evaluate improvements in mortality and standardized mortality rate in successive time periods. Results The results from this study demonstrated a significant improvement in prognosis in successive time periods covering 1995-2012. Apart from patients with a high Charlson Comorbidity Index (CCI) improvements were seen in all subgroups of patients. Prognostic factors were more favorable in the latest time period accordingly to the introduction of nationwide screening. In the study period adjuvant treatment was extended considerable. Conclusion The impact of screening was by nature of limited magnitude. The modified treatment strategies implemented by the use of nationwide guidelines seemed to have a major impact on the substantial survival improvements. [ABSTRACT FROM AUTHOR]

BackgroundThe purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark. Material and methodsCancer of the kidney was defined as ICD-10 code DC 64. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. ResultsThe proportion of patients diagnosed with kidney cancer over the age of 70 years has decreased from 43% in 1980 to 32% in 2012 in men and remained almost constant in women, around 50%. Incidence rates were at least five times higher in men aged 70 years more but there was no particular trend with time. In men aged less than 70 years, the incidence rates started increasing around 2000. The incidence rates were lower in women but with a similar pattern as in men. Mortality rates remained stable over time in persons aged 70 years or more while they decreased with time in younger women. Both the one- and the five-year relative survival increased steadily over time for all age groups but the survival was lower for patients aged 70 years or more than for younger patients. The prevalence increased three times from 1559 patients being alive after kidney cancer in1980 to 4713 in 2012. ConclusionA challenge in managing kidney cancer in the elderly is to establish interdisciplinary collaborations between different specialties, such as surgeons, clinical oncologists, and geriatricians to be able to deliver the best possible care in the future. [ABSTRACT FROM PUBLISHER]

BackgroundBreast cancer is the most frequent malignancy among women worldwide and the second most common cause of cancer-related death in developed countries. The aim of the present analysis is to describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years. Material and methodsCancer of the breast was defined as ICD-10 code C50. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. ResultsThe proportion of patients diagnosed with breast cancer over the age of 70 years increased with time to 29% of women and 44% of men in 2012. Incidence rates increased with time and peaked around 2010 in all age groups except for those aged 90 years or more. Mortality rates were clearly separated by age with increasing mortality rates by increasing age group for both women and men. Relative survival increased over time in all age groups, but patients aged 70 years or more had a poorer relative survival than those aged less than 70 years. In 2012, 58 521 persons (all ages) were alive in Denmark after a diagnosis of breast cancer. ConclusionPoorer survival of Danish breast cancer patients over the age of 70 years is likely to be due to inferior treatment and non-adherence to treatment guidelines. There is a need for clinical trials focusing on patients over the age of 70 years. [ABSTRACT FROM PUBLISHER]

BackgoundThe purpose of the study is to elucidate the epidemiology of elderly patients with prostate cancer in Denmark and identify the differences between younger (<70 years) and elderly (≥70 years) patients. Material and methodsProstate cancer was defined as ICD-10 code C61. Data were derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data are delivered from the Danish Cancer Registry and the Danish Cause of Death Registry. ResultsThe average annual number of newly diagnosed prostate cancers in Denmark has risen from 1297 patients in 1980 to 4315 patients in 2012. The prevalence increased consistently in all age groups more than seven-fold in the period, from 3987 patients in 1980 to 28 951 patients in 2012. The cancer-specific mortality in Denmark has slightly increased over the observed period, in coherence with the growth of the population, resulting in unchanged mortality rates, with the exception of the patients above 80 years, where the mortality rates are increased. The one- and five-year relative survival for prostate cancer improved significantly for all age groups over the time period from 1980 to 2012. ConclusionThe incidence, prevalence, and survival of elderly prostate cancer patients has increased over the observed period but with unchanged mortality rates, except in patients above 80 years, where the mortality rates were increasing. [ABSTRACT FROM PUBLISHER]

BackgroundThe aim of this study was to examine the trends in incidence, mortality, survival, and prevalence of cancers of the urinary bladder and urinary tract in Denmark from 1980 to 2012 with particular focus on elderly patients over age 70 years. DesignCancer of the urinary bladder and urinary tract was defined as ICD-10 codes C67.9, D09.0, D41.4. Data were derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry. ResultsThe average annual number of bladder cancers increased from 1478 to 1810 (22%) from 1980 to 2012, with close to 60% occurring in the elderly population. The incidence rates were 7–10 times higher in persons aged 70 years or more compared with younger persons. Mortality rates were decreasing with time in all age groups but 90+-year-old men. The one- and five-year relative survival improved significantly with time for all age groups both in men and women. The prevalence increased two times from 6014 in 1980 to 12 359 in 2012 among men and from 1974 to 4454 among women. There was a relatively higher proportional increase in prevalence among elderly men compared to younger patients. ConclusionMore prospective data are needed, preferably as randomized clinical trials, for determining the influence of age on the decisions of the surgical approach as well as chemo/radiotherapy for the elderly patients with urothelial cancers compared to younger patients. [ABSTRACT FROM PUBLISHER]

BackgroundTumors in the central nervous system (CNS) comprise a heterogeneous group of tumors with different treatment strategies and prognoses. Current treatment regimens are based on studies on patients mainly younger than 70 years. The aim of the present study was to analyze and describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on patients older than 70 years. Material and methodsTumors in the CNS were defined as ICD-10 codes C70-72, D32-33 and D42-43. Data with comparable data on cancer incidence, mortality, prevalence and relative survival derived from the NORDCAN database were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. ResultsDuring the period 1980–2012 the number of patients with CNS tumors increased from 603 to 1378 patients. The increase is seen mainly in the elderly patients, and especially in women aged 84–89 and 90 + at the time of diagnosis. During the same time period, the mortality rates increased within all age groups, most significantly in patients aged 70 years or older. This may reflect an increased focus on and identification of these patients. Noteworthy; the number of patients living with a CNS tumor increased from 2952 in 1980 to 12 147 patients in 2010. ConclusionThis study suggests that the current treatment strategies in general may have improved survival in patients with CNS tumors, but in order to improve survival further in the increasing group of elderly patients more knowledge about treatment of these patients is needed. [ABSTRACT FROM PUBLISHER]

BackgroundAge is the strongest risk factor for developing cancer. The aim of the present analysis is to give an overview of the trends in cancer incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years. Material and methodsData derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries. The Danish data originate from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. ResultsIncidence and mortality rates of all sites, but non-melanoma skin cancer, were higher and relative survival was lower among persons aged 70 years or more than those aged less than 70 years. The age distribution (age group-specific percentages of total number of incident cases) remained constant over time while the percentage of persons dying from cancer decreased with time up to the age of 79 years but increased for those aged 80 years or more, in whom about a third of all cancer deaths occurred in 2012. In 2003–2007, the five-year relative survival was 48% for men aged 70–79 years, 38% for men aged 80–89 years, and 29% for men aged 90 years or more and the corresponding figures for women were 46%, 39%, and 36%, respectively. There was a substantial increase in the number of prevalent cancer cases aged 70 years or older, especially among those aged 90 years or more. ConclusionAn increase in elderly cancer patients is expected over the coming 20 years due to an increasing elderly population. Healthcare providers need to focus on developing specific strategies for treatment of elderly cancer patients in the future. [ABSTRACT FROM PUBLISHER]

BackgroundCancers of the liver, bile duct, gall bladder and pancreas (HPB-c) are a heterogeneous group, united almost exclusively by a poor prognosis. As the number of elderly in the Western world continues to rise and HPB-c are associated with age, we wanted to examine changes in incidence, mortality, prevalence and relative survival for these cancers. Materials and methodsHBP-c was defined as ICD-10 codes C22 (liver), C23-24 (gall bladder), and C25 (pancreas). Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. ResultsThe incidence and mortality rates of cancer of the liver and pancreas increased over time while the rates of cancer of the gall bladder and bile duct decreased. All HBP-c were more frequent in persons over the age of 70 than in younger persons. The relative one- and five-year survival rose in most HPB-c, but mainly occurring in the younger population of 0–69 years with only small to no gains in the 80 + group. ConclusionAs the number of persons aged 80 years or more will increase dramatically in the following years, and our results show a gap in relative survival, it is important to continue to study this population in order to improve management and outcome. [ABSTRACT FROM PUBLISHER]

BackgroundSquamous cell carcinoma of the head and neck (HNSCC) comprises a variety of malignant tumors. Due to the rarity of each individual malignant entity, knowledge of epidemiological changes and trends over time may be derived from data compiled in regional and national registries. This study analyzed the development in incidence rates and mortality in elderly HNSCC patients in Denmark between 1980 and 2012 with specific attention to compliance to radiotherapy, the main treatment modality of HNSCC in Denmark. Material and methodsHNSCC consisting of more than 25 patients per year over the age of 70 years were analyzed. This included cancer of the oral cavity defined as ICD-codes C00.3-4, C02-04, C05.0, C06; oropharynx as C01, C05.1-9, C09-10; and larynx as C32 recorded in the NORDCAN database. Additional data from the DAHANCA database was added to assess differences in compliance to treatment between younger and older patient groups. ResultsHNSCC was predominant in younger patients. Only 17% were older than 70 years. The median age was 60 years. Generally, incidence rates rose for cancer of the oral cavity and oropharynx between 1980 and 2012 and stabilized for laryngeal cancer. Mortality rates had a shallower increase, especially in younger age groups, which translated into improved age-specific survival rates. Compliance to radiotherapy was high for all age groups. Failure to receive at least 60 Gy during radical radiation treatment was 2.3% despite a significant increase in patients with poor WHO performance status over time. ConclusionHNSCC is a rare disease in patients above 70 years accounting for only 17% of all HNSCC patients. Incidence rates increased over time, but age-specific survival rates improved, especially in younger patients. Failure rates to comply with radiation treatment, however, were low in both young and elderly patients. [ABSTRACT FROM PUBLISHER]

Epidemiological cancer data shed light on key questions within basic science, clinical medicine and public health. For decades, Denmark has had linkable health registers that contain individual level data on the entire population with virtually complete follow-up. This has enabled high quality studies of cancer epidemiology and minimized the challenges often faced in many countries, such as uncertain identification of the study base, age misreporting, and low validity of the cancer diagnoses. However, methodological challenges still remain to be addressed, especially in cancer epidemiology studies among the elderly and the oldest-old. For example, a characteristic pattern for many cancer types is that the incidence increases up to a maximum at about ages 75–90 years and is then followed by a decline or a leveling off at the oldest ages. It has been suggested that the oldest individuals may be asymptomatic, or even insusceptible to cancer. An alternative interpretation is that this pattern is an artifact due to lower diagnostic intensity among the elderly and oldest-old caused by higher levels of co-morbidities in this age group. Currently, the available cancer epidemiology data are not able to provide clear evidence for any of these hypotheses. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 31 year old female patient who was diagnosed with stage four, estrogen receptor positive, progesterone receptor negative, HER-2 positive infiltrating ductal carcinoma which was metastatic to her liver and bones. A discussion of rapid clinical and radiographic improvement which was seen in the patient after receiving intrathecal trastuzumab and methotrexate is presented.

The article discusses research conducted to correlate two dimensional parameters with more modern lung and heart dose-volume histograms (DVH) parameters to allow ongoing follow-up/evaluation of patients treated with radiation many years ago for breast cancer and compare with patients treated with modern planning. Researchers evaluated the records of 204 women. They found that the clinical outcome and the estimation of the radiation related sequelae were related to radiation dose and the volume of the tissue irradiated.

Objective. To evaluate the relationship between osteopontin (OPN) in serum and plasma and parathyroid hormone-related protein (PTHrP) in serum, plasma and tumour tissue, and to assess the prognostic impact of OPN and PTHrP in human renal cell carcinoma (RCC). Material and methods. The study included 269 patients with RCC. In 189 patients, immuno-histochemical (IHC) PTHrP tumour tissue expression was evaluated, and OPN and PTHrP in serum were assessed. In 80 patients, plasma OPN and PTHrP were analysed. Tumour type, TNM stage, nuclear grade and RCC-specific survival were also registered. In a sub-group, IHC expression of CD 31 was assessed. The prognostic information of the factors was analysed using uni- and multivariate analyses. Results.The median OPN level was 2.3 times higher in plasma than in serum. Serum OPN was significantly higher in patients with papillary RCC compared to clear cell RCC and chromophobe RCC. Both serum and plasma OPN levels were positively correlated to TNM stage and nuclear grade. Multivariate analysis showed that serum and plasma OPN levels were independent prognostic factors for RCC-specific survival, along with TNM stage. Immunohistochemical expression of PTHrP associated to TNM stage but not to nuclear grade or serum OPN. Furthermore, IHC expression of PTHrP was positively correlated to serum PTHrP but inversely to tumour CD31 expression. Plasma PTHrP was increased in 20% of the patients and related to TNM stage but not to nuclear grade. Plasma OPN was significantly higher in patients with increased PTHrP levels, compared to those with normal levels. Conclusion. Plasma OPN levels differed between RCC types, and in clear cell RCC, both serum and plasma OPN levels were independent predictors of survival. We found no evidence for prognostic value related to circulating levels or the IHC expression of PTHrP. [ABSTRACT FROM AUTHOR]

Background. This study aims at comparing the morbidity and oncologic outcomes in normal weight, overweight, and obese women with locally advanced cervical cancers (LACC) submitted to radical surgery after chemoradiation. Methods. A review of LACC patients with body mass index (BMI)⩾18.5 kg/m2 who underwent neoadjuvant chemoradiation followed by radical surgery between January 1996 and December 2010 was performed. BMI categories were created according to the World Health Organization (WHO) classification. Results. Two hundred sixty-eight women met the inclusion criteria: 118 (44.0%) were normal weight, 100 (37.3%) overweight and 50 (18.7%) obese.The median follow-up was 42 months. Higher BMI was associated with older age (p = 0.0041), while there were no differences among the three groups in Charlson comorbidity score, tumor characteristics, radiotherapy dosing, type of surgery, and pathological response. There were no differences among the three groups in the intraoperative and postoperative complications as well as rate of patients requiring adjuvant treatments: 21 (7.8%) patients experienced grade 3-4 toxicity, including six normal weight, 12 overweight and three obese patients (p = 0.14). Only the rate of grade 1-2 skin toxicity was higher in obese (14%) with respect to overweight (1%) and normal women (0%) (p = 0.00001). There were no differences in the five-year DFS (74%, 77%, and 84% for normal weight, overweight, and obese women, respectively, p = n.s.), and five-year OS (76%, 78%, and 78% for normal weight, overweight, and obese women, respectively, p = n.s.). Conclusions. The role of obesity should not be overestimated when evaluating the chance of enrolment of LACC patients into preoperative chemoradiation protocols. [ABSTRACT FROM AUTHOR]

Re-irradiation using high-precision radiation techniques has been established within the clinical routine for patients with recurrent gliomas. In the present work, we developed a practical prognostic score to predict survival outcome after re-irradiation. Patients and methods. Fractionated stereotactic radiotherapy (FSRT) was applied in 233 patients. Primary histology included glioblastoma (n = 89; 38%), WHO Grade III gliomas (n = 52; 22%) and low-grade glioma (n = 92; 40%). FSRT was applied with a median dose of 36 Gy in 2 Gy single fractions. We evaluated survival after re-irradiation as well as progression-free survival after re-irradiation; prognostic factors analyzed included age, tumor volume at re-irradiation, histology, time between initial radiotherapy and re-irradiation, age and Karnofsky Performance Score. Results. Median survival after FSRT was 8 months for glioblastoma, 20 months for anaplastic gliomas, and 24 months for recurrent low-grade patients.The strongest prognostic factors significantly impacting survival after re-irradiation were histology (p < 0.0001 ) and age (< 50 vs. ⩾ 50, p < 0.0001) at diagnosis and the time between initial radiotherapy and re-irradiation ⩽ 12 vs. > 12 months (p< 0.0001). We generated a four-class prognostic score to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3-4 points) survival after re-irradiation. The difference in outcome was highly significant (p<0.0001). Conclusion. We generated a practical prognostic score index based on three clinically relevant factors to predict the benefit of patients from re-irradiation. This score index can be helpful in patient counseling, and for the design of further clinical trials. However, individual treatment decisions may include other patient-related factors not directly influencing outcome. [ABSTRACT FROM AUTHOR]

Working as a physician at an oncology department has some distinctive characteristics that may lead to a stressful work environment. The present study was conducted to provide a nationwide description of the work conditions of all oncologists in Denmark. By comparing the results of the present study with those of a similar study carried out in 2006, the aim was furthermore to elucidate changes in the psychosocial work environment over time. Material and methods. From May to September 2009, 330 physicians employed at six oncology centres and seven community based oncology departments were invited to participate in a survey based on the short version of the COPSOQ II questionnaire. The results were compared with data from a representative section of Danish employees and with data from the 2006 survey. Results. Two hundred and twenty of the 330 invited physicians returned the questionnaire (response rate 67%). Concerning the aspects quantitative demands, work pace, emotional demands, influence, burnout and stress, the oncologists reported worse work conditions than the average Danish employee. However, with regard to possibilities for development, meaning of work and commitment to workplace, the oncologists reported better work conditions. Between 2006 and 2009, substantial improvement was seen concerning several of the assessed work environment aspects within the group of young physicians at the oncology centres. Conclusion. Though substantial improvement of the work conditions has been achieved between 2006 and 2009, certain aspects of the psychosocial work environment at Danish oncology departments still require attention. [ABSTRACT FROM AUTHOR]

Background. Anxiety and depression in cancer patients are associated with poor health-related quality of life (HRQOL). Clinical interventions to detect and support patients with these symptoms need to be developed and evaluated. We investigated the feasibility of screening with the Hospital Anxiety and Depression Scale (HADS) in a clinical oncology setting. In patients with anxiety or depression symptoms (HADS >7) we explored the use of clinical assessment and psychosocial support and described the development of anxiety, depression and HRQOL during a six-month period. Material and methods. Four hundred and ninety-five consecutive patients were screened for anxiety and depression at the time of their first visit at an oncology department (baseline). Half of the patients with HADS >7 on any of the two HADS subscales were referred to clinical assessment and psychosocial support (intervention group, IG) and half received standard care (SCG) using a historical control group design. HADS and EORTC QLQ-C30 were completed at baseline and after one, three and six months. Results. One hundred and seventy-six (36%) of 495 patients had anxiety or depression symptoms at screening, HRQOL at baseline was clearly impaired for them. Thirty-six (43%) of 84 IG patients attended clinical assessment, resulting in subsequent psychosocial support for 20 (24%) of them. In the SCG, only five (5%) patients attended clinical assessment after self referral, two received subsequent psychosocial support. Anxiety and depression decreased and HRQOL increased statistically significantly over time although anxiety was frequent and HRQOL impaired during the entire six month period. There were no differences between the SCG and IG regarding anxiety, depression or HRQOL at any time point. Conclusion. Systematic screening with HADS is feasible for oncology patients in clinical settings; it identifies patients with persistent symptoms and increases referral to clinical assessment and utilisation of psychosocial support. [ABSTRACT FROM AUTHOR]

Context. Cancer patients are at increased risk for distress. The Distress Thermometer (DT) and problem list (PL) are short-tools validated and recommended for distress screening in cancer patients. Objective. To investigate the level of distress and problems experienced by survivors of differentiated non-medullary thyroid carcinoma (DTC), using the DT and PL and whether this correlates with clinical and demographical variables. Participants, design and setting. All 205 DTC patients, under follow-up at the outpatient clinic of our university hospital, were asked to fill in the DT and PL, hospital anxiety and depression scale (HADS), illness cognition questionnaire (ICQ) and an ad hoc questionnaire. Receiver Operator Characteristic analysis (ROC) was used to establish the optimal DT cut-off score according to HADS. Correlations of questionnaires scores with data on diagnosis, treatment and follow-up collected from medical records were analyzed. Results. Of the 159 respondents, 145 agreed to participate [118 in remission, median follow-up 7.2 years (range 3 months-41 years)]. Of these, 34.3% rated their distress score ⩾5, indicating clinically relevant distress according to ROC analysis. Patients reported physical (86%) over emotional problems (76%) as sources of distress. DT scores correlated with HADS scores and ICQ subscales. No significant correlations were found between DT scores and clinical or demographical characteristics except for employment status. Conclusion. Prevalence of distress is high among patients with DTC even after long-term remission and cannot be predicted by clinical and demographical characteristics. DT and PL are useful screening instruments for distress in DTC patients and could easily be incorporated into daily practice. [ABSTRACT FROM AUTHOR]

Background. Male breast cancer (MBC) is an uncommon disease and mere is limited information on the prognostic impact of routinely used clinicopathological parameters. Material and methods. In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stain-ings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event. Results. Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size >20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition. Conclusion. MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC. [ABSTRACT FROM AUTHOR]

Background. The degree of trust in and satisfaction with the physician has been shown to have important implications for treatment outcomes. This study aims to examine individual differences in patients' trust, satisfaction and general distress from an attachment theoretical perspective. Material and methods. One hundred and thirty recently diagnosed cancer patients of three medical hospitals were extensively interviewed by trained psychologists to assess attachment style. Patients completed standardized questionnaires three and nine months after diagnosis to assess trust, satisfaction and distress, t-tests and repeated measures ANOVAs were used to examine differences between securely and insecurely attached patients and changes over time. A mediation model based on a bootstrapping method was used to examine whether trust mediated between attachment and satisfaction, and attachment and distress. Results. Insecurely attached patients (N = 45, 35%) reported less trust in and satisfaction with their physician, and reported more general distress dian securely attached patients three and nine months after diagnosis (p < 0.05).Trust and distress levels did not change over time.Trust mediated between attachment and satisfaction, but not between attachment and distress. Conclusion. Insecurely attached patients trusted their physician less than securely attached patients, and in turn were less satisfied with their physician. Their higher levels of general distress were not related to their lower levels of trust. Attachment theory provides a framework to interpret differences in patients' trust, satisfaction and distress, and may help physicians respond in such a way that their patients feel secure, which in turn is expected to result in better health outcomes. [ABSTRACT FROM AUTHOR]

Background. The role of tissue inhibitor of metalloproteinases-1 (TIMP- 1) in estrogen receptor (ER) positive breast cancer remains to be fully elucidated. We evaluated TIMP-1 as a prognostic marker in patients treated with adjuvant tamoxifen and investigated TIMP-is association with Ki67 and ER/progesterone receptor (PR)Ihuman epidermal growth factor receptor 2 (HER2) profiles. Material and methods. TIMP-1 expression was evaluated by immunohistochemistry (IHC) on formalin fixed paraffin embedded primary tumor tissue in two independent cohorts comprised of 236 and 192 patients, respectively. Results. No differences in disease free survival (HR 0.98; 95% CI 0.63-1.53; p=O.92) and overall survival (HR 0.94; 95% CI 0.63-1.43; p = 0.79) were observed according to TIMP-1 status. A significant negative association between TIMP- 1 and Ki67 was identified (p = 0.015). TIMP- 1 expression did not differ significantly according to ERJPRJ HER2 profiles. When analyzed as separate variables PR and HER2 status tended to have a positive but non-significant association with TIMP-1 (PR: p=O.O8; OR 2.54; 95% CI 0.91-7.10, HER2: pO.O8; OR 0.48; 95% CI 0.21-1.08) whereas ER status was not associated withTIMP-1 expression (p = 0.48; OR 0.68; 95% CI 0.23-1.99). Conclusion. TIMP-1 does not appear to be prognostic in breast cancer patients receiving adjuvant tamoxifen.We identified a negative association between TIMP-1 and Ki67. We did not confirm our previous in vitro findings of a negative association between TIMP-1 and PR. [ABSTRACT FROM AUTHOR]

Introduction. Over-treatment of low-risk early breast cancer patients with adjuvant systemic therapies is an important clinical challenge. Better techniques are required which can be used to distinguish between the large group of patients with no residual disease after surgery and consequently no benefit of adjuvant treatment, from the smaller group with high relapse risk. A better integration of available prognostic factors might contribute to improved prediction of clinical outcome. Material and methods. The current study included 346 unselected pTlpNO patients who did not receive adjuvant systemic treatment. In Norway, no patients with this stage were recommended systemic treatment at the time of the study (1995-1998). Histological type, tumour size, grade, vascular invasion (VI), hormone receptor (HR) status, HER2 and Ki67 (cutoff 10%) were analysed. Median follow-up was 86 months for relapse and 101 months for death. Results. Thirty-eight patients experienced relapse, 31 with distant metastasis. Twenty-one patients died of breast cancer. In univariate analysis grade, HER2, HR, VI and Ki67 had impact on clinical outcome (p<0.005, log rank). In multivariate analysis, only grade 1-2 vs. grade 3, HER2, VI, and Ki67 status were significant for disease free survival, distant disease free survival, and/or breast cancer specific survival. These factors were used in combination, to separate patients into groups based on the number of unfavourable factors present [combined prognostic score (CPS) 0-4]. Close to 2/3 of the patients (61.4%) had no unfavourable factor (CPS0), whilst 18.4% had CPS ⩾ 2. Only 3.6% of those with CPS0 developed metastasis (p < 0.001). The outcome was clearly worse for patients with CPS ⩾ 2 (p < 0.001), systemic relapse was detected in approximately 40%. Conclusions. This study indicates that the combined use of grade, VI, HER2 and Ki67 identifies a subgroup of breast cancer patients with a relapse risk that may question the benefit of adjuvant systemic therapy. [ABSTRACT FROM AUTHOR]

Background. To study the incidence of local recurrence (LR) of early breast cancer in the ipsilateral thoracic wall after mastectomy and outcome of patients with LR. Material and methods. A retrospective cohort study based on 2220 consecutive breast cancer patients treated at the Helsinki University Central Hospital, Finland, in 2000 to 2003. A subset of 755 (34.0%) patients had mastectomy which was usually followed by postoperative radiotherapy (51.2%) and/or systemic adjuvant therapy (79.2%). Results. During a median follow-up of 89 months, 22 (2.9%) patients treated with mastectomy had LR. The median time to LR was 27 months. None of the 12 patient- or tumour-related standard risk factors studied were independently associated with LR-free survival in a multivariate model. Six (27.3%) of the 22 patients with LR had distant metastases diagnosed either prior to or simultaneously with LR. The subset of 16 patients who were diagnosed with LR without concomitant distant recurrence had five-year breast cancer-specific survival of 77.5% as calculated from the date of LR detection, and overall survival of 59.2%. Conclusions. LR after mastectomy has become a rare event. Most women with isolated LR survive for five years after LR. [ABSTRACT FROM AUTHOR]

Background. Approximately 10% of breast cancer (BC) patients are over the age of 80. We present the first comprehensive review on this particular group of patients. Patients and methods. The treatments and disease courses of an unselected cohort of patients, whose age at first diagnosis was>80 years (n= 151), were compared to those of a group of women, who were aged 56-66 years (n = 372). Results. The group of elderly patients had larger tumors at first diagnosis (25 mm vs. 18 mm, p<0.001) and higher disease stages (I: 31.1% vs. 44.1%, IV: 11.9% vs. 5.4%; each p<0.001).There were no significant differences between both groups in terms of histologic subtype, grading, hormonal receptor status and HER2 status. The tumors of older patients were more often detected by clinical examination (38.9% vs. 17.0%, p< 0.001) and less often by mammography/sonography (10.4% vs. 29.9%, p<0.001).The rate of patients who died of BC were similar in both groups (21.2% vs. 21.5%, p= 1.00). In the patients who had no evidence of metastases and who opted for primary non-surgical management (n = 21), the tumor could be stabilized without considerable morbidity in only 42.9%. Persistence to adjuvant endocrine therapy was comparable (83.0% vs. 88.3%, p = 0.357). In the adjuvant as well as in the palliative settings, elderly patients received less chemotherapy than younger ones (adjuvant: 1.6% vs. 23.3%; palliative: 32.3% vs. 68.4%; each p<0.001). For palliative treatments only, elderly patients received fewer treatment regimens (⩾3 therapy lines: 16.0% vs. 54.9%, p< 0.001). In those patients who died of BC, elderly women had inferior overall (25 vs. 54.5 months, p< 0.001) as well as metastatic-disease survival (11.5 vs. 19 months, p = 0.062). Conclusion. It must be ensured that appropriate standard therapies should not be routinely withheld in older patients based on erroneous perceptions regarding the biological nature of BC in the elderly and lack of knowledge about available therapy regimens. Physicians should consider that preservation of current life circumstances and maintenance of quality of life are frequently more important than "classical" hard medical facts such as survival times. [ABSTRACT FROM AUTHOR]

Background. Long-term data on breast cancer detection in mammography screening programs are warranted to better understand the mechanisms by which screening changes the breast cancer pattern in the population. We aimed to analyze 17 years of breast cancer detection rates inside and outside screening in two Danish regions, emphasizing the influence of organizational differences of screening programs on the outcomes. Material and methods. We used data from two longstanding population-based mammography screening programs, Copenhagen and Fyn, in Denmark. Both programs offered biennial screening to women aged 50-69 years. We identified targeted, eligible, invited and participating women. We calculated screening detection and interval cancer rates for participants, and breast cancer incidence in non-screened women (= targeted women excluding participants) by biennial invitation rounds. Tumor characteristics were tabulated for each of the three groups of cancers. Results. Start of screening resulted in a prevalence peak in participants, followed by a decrease to a fairly stable detection rate in subsequent invitation rounds. A similar pattern was found for breast cancer incidence in non-screened women. In Fyn, non-screened women even had a higher rate than screening participants during the first three invitation rounds. The interval cancer rate was lower in Copenhagen than in Fyn, with an increase over time in Copenhagen, but not in Fyn. Screen-detected cancers showed tumor features related with a better prognosis than tumors detected otherwise, as more than 80% were smaller than 20 mm and estrogen receptor positive. Conclusion. Data from two long-standing population-based screening programs in Denmark illustrated that even if background breast cancer incidence and organization were rather similar, performance indicators of screening could be strongly influenced by inclusion criteria and participation rates. Detection rates should be interpreted with caution as they may be biased by selection into the screening population [ABSTRACT FROM AUTHOR]

Background. More than 50% of breast cancer patients are diagnosed before the age of 65. Returning to work after treatment is, therefore, of interest for both the individual and society. The aim was to study the effect of support group intervention on sick leave and health care utilization in economic terms. Material and methods. Of 382 patients with newly diagnosed breast cancer, 191 + 191 patients were randomized to an intervention group or to a routine control group, respectively. The intervention group received support intervention on a residential basis for one week, followed by four days of follow-up two months later. The support intervention included informative-educational sections, relaxation training, mental visualization and non-verbal communication. Patients answered a questionnaire at baseline, two, six and 12 months about sick leave and health care utilization. Results. There was a trend towards longer sick leave and more health care utilization in the intervention group. The difference in total costs was statistically significantly higher in the intervention group after 12 months (p = 0.0036). Conclusion. Costs to society were not reduced with intervention in its present form. [ABSTRACT FROM AUTHOR]

Background. Lung cancer and mesothelioma are malignant tumors with generally dismal prognosis and therefore palliative pain treatment constitutes a challenge for the clinician. Objectives. The aim of this study was to compare the outcomes of pain treatment with opioids among mesothelioma and lung cancer patients treated for palliation and assess factors which confound to optimal treatment. Patients and methods. A sub-cohort of 373 lung cancer and 22 mesothelioma patients was identified in multi-center European Pharmacogenetic Opioid Study (EPOS) cohort. A nested case-control (1:4) setting was designed to estimate the pain and other covariates distinguishing 22 mesothelioma- (= cases) and 88 lung cancer patients (controls), analyzed using univariate- and multivariate conditional (fixed-effects) logistic regression models. Results. The mean total daily dose of opioids varied from 30.0 to 960.0 mg (mean 275, median 160 mg, SD 293) in mesothelioma, and from 10 to 5072 mg (mean 414, median 175, SD 788) in lung cancer patients (p = 0.420). In both groups, pain was mostly experienced as moderate and severe and it was frequently accompanied by depression, poor sleep, anxiety and fatigue. Four mesothelioma patients (18%) and seven lung cancer patients (10%) experienced complete pain relief with opioids by self-assessment. Assessments of pain severity by the patients and their physicians deviated significantly in mesothelioma (p = 0.039 McNemar test), as well as in lung cancer (p = 0.0001). In conditional logistic regression, no significant differences were found in distribution of pain covariates between lung cancer and mesothelioma patients. Conclusion. Pain perception by the patients was associated frequently with other symptoms and complete pain control with opioids was achieved only with minority of patients both with mesothelioma and advanced lung cancer. Adequate pain control requires continuous monitoring and tailoring the dose to patient's individual needs and tolerance, recognition of accompanying symptoms such as depression and poor sleep, and their management. [ABSTRACT FROM AUTHOR]

Introduction. Somatic mutations in plant homeodomain finger protein 6 (PHF6) gene have recently been reported in T-cell acute lymphoblastic leukemia (T-ALL), strongly suggesting its role in the pathogenesis of human cancers. Materials and methods. To see whether the PHF6 mutation occurs in other malignancies, we analyzed entire coding sequences of PHF6 in 231 hematologic malignancies [105 acute myelogenous leukemias (AML), 66 pre-B-ALL, 23 T-ALL, one undifferentiated acute leukemia and 36 multiple myelomas] by single-strand conformation polymorphism assay. Also, we analyzed the mutation in 236 solid cancers, including 41 lung, 39 hepatocellular (HCC), 36 breast, 40 colorectal, 40 gastric and 40 prostate carcinomas. Results. In the hematologic malignancies, there were 11 PHF6 mutations that were detected not only in TALL (34.7%) (five adult and three childhood T-ALL), but also in two AML (1.9%) (one acute monocytic leukemia and one AML minimally differentiated). In addition, there was a PHF6 mutation in the HCC (2.6%). The PHF6 mutations were detected in both male and female patients, and consisted of six frameshift, three nonsense and two intron mutations. Conclusion. Our data suggest that PHF6 mutation might play a role in tumorigenesis not only of TALL, but also of AML and HCC. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate whether the drug gefitinib could delay prostate specific antigen (PSA) progression, increase PSA doubling time (PSADT) and postpone the need for hormonal or radiation salvation therapy in patients with rising PSA. Researchers found that gefitinib appeared to increase the PSA doubling time (PSADT) in most patients.

The article presents a case study of a 31 year old female patient who presented to physicians with symptoms of large volume diarrhea accompanied by crampy abdominal pain and mild dyspnea. A discussion of diagnostic testing which was conducted on the patient, and resulted in her receiving a diagnosis of pulmonary neuroendocrine carcinoma and severe systemic vasoconstriction starting with acute limb ischemia, is presented.

Aim. To obtain reference values for health-related quality of life (HRQL) measured with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) in a random sample of the adult Swedish population. Methods. A population-based survey of a random sample of 7002 Swedish adults aged 40-79 years, frequency-matched to reflect the age and sex distribution of upper gastrointestinal cancer patients. Scales were scored on a 0-100 metric according to standard procedures. Functions and symptoms were dichotomized into "poor" versus "good" function, and "symptomatic" and "no or minor symptoms", respectively. The results were stratified for age and gender. Results. The questionnaire was completed by 4910 (70.5%) of 6969 eligible participants. Missing values were limited. HRQL was found to vary according to age and sex. Generally, men reported better functioning and fewer symptoms than women. The most common symptoms were fatigue, pain, and insomnia. Conclusion. The reference values provided can be used as a surrogate baseline measure in HRQL research, and when evaluating the effect of interventions on HRQL in cancer patients. [ABSTRACT FROM AUTHOR]

Background. The costs for loco-regional treatment of peritoneal carcinomatosis from gastric cancer are not well investigated. The aims of this study were to evaluate the costs and clinical outcome of systemic chemotherapy followed by cytoreductive surgery and intraperitoneal chemotherapy compared to systemic chemotherapy only in patients with peritoneal carcinomatosis from gastric cancer. Material and methods. Ten patients were scheduled for systemic chemotherapy followed by loco-regional treatment. A reference group of 10 matched control patients treated with systemic chemotherapy only were used and both groups were evaluated with respect to clinical outcome and cost. Results. The mean overall cost in the loco-regional group was $145 700 (range 849 900-$487 800) and $59 300 (range $23 000-$94 800) for the control group. The mean overall survival for the loco-regional group was 17.4 months (range 6.0-34.3), and 11.1 months (range 0.1-24.2) for the systemic chemotherapy only group. The gain in life-years was 0.52 and in quality-adjusted life-years 0.49, leading to incremental cost per life-year and quality-adjusted life-years gained of $166 716 and $175 164, for loco-regional group compared to systemic chemotherapy. Discussion. Treatment of peritoneal carcinomatosis from gastric cancer is costly irrespective of treatment modality. If the survival benefit from adding loco-regional treatment to systemic chemotherapy indicated from this comparison is true, the incremental cost is considered high. [ABSTRACT FROM AUTHOR]

Background. Leucine-rich and immunoglobulin-like domains 1-3 (LRIG1-3) proteins have been implicated in the regulation of EGFR signalling. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG 1-3 in oesophageal carcinoma, as well as the correlation between their expression levels and the chemosensitivity of oesophageal carcinoma cell lines. Patients and methods. Tumours from 80 patients with oesophageal carcinoma were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Oesophageal carcinoma cell lines were investigated for their expression of EGFR and LRIG1, 2, and 3 by quantitative real time RT-PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay. Results and discussion: Based on a total score of intensity and expression rates, a trend towards survival difference was found for EGFR (p = 0.09) and LRIG2 (p = 0.18) whereas for LRIG1 and -3 there was no trend towards any association with survival. Correlation analysis revealed a correlation with the clinical expression of EGFR and LRIG3 (p = 0.0007). Significant correlations were found between LRIG1 expression levels and sensitivity to cisplatin (r = --0.74), docetaxel (r = --0.69), and vinorelbine (r = --0.82) in oesophageal carcinoma cell lines. EGFR and the LRIG proteins may be functionally involved in oesophageal carcinoma, but larger materials are needed to fully elucidate the clinical implication. [ABSTRACT FROM AUTHOR]

Background. Little is known about how well guidelines about adjuvant chemotherapy in colon cancer are followed in daily practice. We evaluated the current guideline, which is based on the MOSAIC trial, by examining implementation, treatment patterns and disease-free survival. Material and methods. We analysed a population-based cohort of 391 patients treated with adjuvant chemotherapy for stage III colon cancer in 2005-2006. Data were gathered from the Dutch Cancer Registry and medical records of 19 hospitals. Patients were classified according to whether or not they fulfilled MOSAIC trial eligibility criteria. Results. The administered regimens were: fluorouracil-leucovorin (17 patients), capecitabine (93), fluorouracil-leucovorin plus oxaliplatin (145), and capecitabine plus oxaliplatin (136). After its inclusion in national guidelines, oxaliplatin was prescribed in 16 hospitals within six months. Patients receiving oxaliplatin were younger and had less comorbidity than other patients. Dose schedules corresponded well with guidelines. Two-year disease-free survival probability of oxaliplatin patients meeting MOSAIC eligibility criteria was 78.4% (95% CI 72.5-84.3), which was comparable to MOSAIC trial results. Conclusion. Guidelines for adjuvant chemotherapy in stage III colon cancer are generally well followed in daily practice. However, uncertainty remains regarding the optimal treatment of elderly patients and patients with comorbidities, which underscores the need for practical clinical trials including these patients. [ABSTRACT FROM AUTHOR]

Background. The Swedish Patient Registry provides data about diagnoses and surgical procedures for research purposes. There are, however, almost no validation studies of the data on surgical procedures, and none of oesophageal cancer surgery. Material and methods. This was a validation study of the accuracy of codes representing oesophageal cancer resection, surgical approach and oesophageal substitute in the Swedish Patient Registry during the period 1987-2005. The registered data were compared with a thorough review of the corresponding operation charts collected from medical records. Results. Among 1358 patients with a code representing oesophageal resection in the Patient Registry, the positive predictive value was 99.6%. The dominant surgical procedures in terms of surgical approach (transthoracic) and type of oesophageal substitute (gastric conduit) had positive predictive values of 99.8% and 99.4%, respectively. The more rare procedures with regards to approach (transhiatal) and substitute (bowel) had lower positive predictive values of 68.8% and 68.5%, respectively. Conclusion. The high accuracy of the data regarding oesophageal cancer resection in the Swedish Patient Registry stresses its appropriateness for research purposes. [ABSTRACT FROM AUTHOR]

Background. A crucial factor concerning the utility of Cancer Registries is the data quality with respect to comparability, completeness, validity and timeliness. However, the data quality of the registration of premalignant lesions has rarely been addressed. High grade vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VaIN) are premalignant lesions which may develop into cancer, and are often associated with infection with the human papillomarvirus (HPV). The aim was to evaluate die quality of registration of VIN and VaIN at the Cancer Registry of Norway (CRN). Material and methods. We re-collected all notifications with high grade VIN and VaIN diagnoses during 2002 to 2007 from pathology laboratories, and compared these to the data in the CRN database so as to quantitatively measure die completeness, validity and timeliness of the data. Results. Over die period 2002 to 2007 we estimated the completeness of the 1556 VIN and 297 VaIN notifications to be 95.0% and 92.9%, respectively. The original and reabstracted topography codes showed major discrepancies for 12 of 642 (1.9%) VIN and 7 of 128 (5.5%) VaIN notifications. The original and reabstracted morphology codes for VIN and VaIN were identical for 724 out of 814 notifications. Sixteen notifications had a major discrepancy. For the period 2002 to 2007 the median time elapsed between date of diagnosis and date of registration were 436 and 441 days for VIN and VaIN cases, respectively. Discussion. Based on the present analysis of the comparability, completeness, validity and timeliness of premalignant lesions of vulva and vagina, we conclude that the Cancer Registry of Norway is able to monitor such premalignant lesions satisfactorily. [ABSTRACT FROM AUTHOR]

Background. Monitoring and evaluation of cancer screening programmes require accurate data on invitations, visits, test results, diagnoses and management. The purpose of this study was to evaluate the completeness and accuracy of histological diagnoses (cervical precancerous lesions and cancer) in the Finnish cervical cancer screening register by comparing data with the cancer register and the administrative hospital discharge register. Material and methods. Screening data covering all 16 353 screening episodes that resulted in a referral for colposcopy over the period of 1998-2007 were individually linked with hospital discharge and cancer register data using the unique personal identifier. Agreement between registers, as well as sensitivity, coverage and positive predictive values (PPV) for the screening register and the hospital discharge register diagnosis, were estimated. Invasive cases in the cancer register and pooled cases of precancerous lesions were used as reference case populations. Results. The sensitivity of the screening register for cervical cancer was 69%, the coverage 100% and the PPV 77%. Corresponding values for the hospital discharge register were 81%, 100% and 83%, respectively. Sensitivity of the screening register for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) against the pooled case population was 89% and coverage 99%. Corresponding values for the hospital discharge register were 78% and 93%. Kappa-values for pair-wise agreement between the three registers ranged between 0.73 and 0.79, often the lesion grade was lower in the screening register than in the other two registers. Conclusions. The data in the screening register has high coverage and is thus useful for statistical and evaluation purposes. However, in order to improve the accuracy of diagnostic information, there are grounds to consider data retrieval through systematic linkage to other health care registers. [ABSTRACT FROM AUTHOR]

Background. Estimates of cancer patient survival from traditional cohort-based methods may be heavily influenced by the survival experience of patients diagnosed many years ago and may not therefore be relevant to recently diagnosed patients. Period-based analysis provides better predictions of survival for recently diagnosed patients than cohort analysis. The first aim of this study is to provide predictions of the long-term survival of patients diagnosed in 2005-2009 using period analysis and to compare these estimates to the latest available cohort estimates. The second aim is to evaluate predictions published in 2004 regarding the future survival of patients diagnosed 2000-2002. Material and methods. We studied survival among patients diagnosed 1985-2009 reported to the nationwide, population-based Swedish Cancer Registry. Predictions of the future relative survival for recently diagnosed patients were made using period analysis with a window of 2005-2009. Results. The predictions made using period analysis and published in 2004 agreed well with the subsequently observed survival, with common sites showing a better agreement than less common sites. Updated predictions suggest that patients diagnosed today can expect improved survival for many forms of cancer. Conclusions. Period, rather than cohort, survival analysis should be used if the primary aim is to predict the future survival of recently diagnosed patients. Recently diagnosed cancer patients can, for many forms of cancer, expect an improved survival compared to patients diagnosed only a few years earlier. [ABSTRACT FROM AUTHOR]

Recent advances in the understanding of castrate-resistant prostate cancer (CRPC) have lead to a growing number of experimental therapies, many of which are directed against the androgen-receptor (AR) signaling axis. These advances generate the need for reliable molecular imaging biomarkers to non-invasively determine efficacy, and to better guide treatment selection of these promising AR-targeted drugs. Methods. We draw on our own experience, supplemented by review of the current literature, to discuss the systematic development of imaging biomarkers for use in the context of CRPC, with a focus on bone scintigraphy, F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) and PET imaging of the AR signaling axis. Results. The roadmap to biomarker development mandates rigorous standardization and analytic validation of an assay before it can be qualified successfully for use in an appropriate clinical context. The Prostate Cancer Working Group 2 (PCWG2) criteria for "radiographic"progression by bone scintigraphy serve as a paradigm of this process. Implemented by the Prostate Cancer Clinical Trials Consortium (PCCTC), these consensus criteria may ultimately enable the co-development of more potent and versatile molecular imaging biomarkers. Purported to be superior to single-photon bone scanning, the added value of Na 18 F-PET for imaging of bone metastases is still uncertain. FDG-PET already plays an integral role in the management of many diseases, but requires further evaluation before being qualified in the context of CRPC. PET tracers that probe the AR signaling axis, such as 18 F-FDHT and 89 Zr-591, are now under development as pharmacodynamic markers, and as markers of efficacy, in tandem with FDG-PET. Semi-automated analysis programs for facilitating PET interpretation may serve as a valuable tool to help navigate the biomarker roadmap. Conclusions. Molecular imaging strategies, particularly those that probe the AR signaling axis, have the potential to accelerate drug development in CRPC. The development and use of analytically valid imaging biomarkers will increase the likelihood of clinical qualification, and ultimately lead to improved patient outcomes. patient outcomes. [ABSTRACT FROM AUTHOR]

It is very attractive, due to the assumed low alfa/beta ratio of prostate cancer (PC), to construct new treatment schedules for prostate cancer using only a few large fractions of radiation (hypofractionation). This will widen the therapeutic window since the ratio for PC might be lower than that of the organs at risk (OAR). PC is an extremely variable disease and often contains both highly and poorly differentiated cells. It is reasonable to assume that different cells have different patterns of radiosensitivity, i.e. alfa/beta ratios and proliferation. In this study we will simulate the effect on the outcome of the treatment with different fractionations and different ratios. Material and methods. In this simulation we use an extension of the Linear Quadratic (LQ)/Biological Effective Dose (BED) formula called the dose volume inhomogenity corrected BED (DVIC-BED). In the formula the tumour volume is divided in 50 subvolumes (step of 2%) and it is possible to calculate the relative effect of the treatment with different ratios (1.5, 4 and 6.5) in different subvolumes. Results. The simulations demonstrate that only a small portion (5 -10%) of cells with a higher ratio will dramatically change the effect of the treatment. Increasing the total dose can compensate this, but this will on the other hand increase the dose to the OAR and also the risk for severe side effects. Conclusion. These simulations highlight possible reasons for concerns about the use of hypofractionation for pathologically heterogeneous tumours, such as prostate cancer, and also demonstrate the need for testing new treatment schedules using both high and low ratios. [ABSTRACT FROM AUTHOR]

Surgery or radiation therapy remain the standard curative treatments for newly diagnosed prostate cancer patients. Nonetheless, these aggressive treatments are associated with decreased quality of life with altered sexual and urinary functions. The objective was a systematic review of active surveillance protocols to investigate the role of histopathology and molecular markers in the active surveillance of prostate cancer. Medline was searched using the following terms: prostate cancer, active surveillance and expectant management. Selection criteria, follow-up strategies and outcomes. Using modern risk stratification, several centres have gained significant experience in identifying patients with a low risk of prostate cancer progression and have adopted an active surveillance program with delayed curative therapy. Interestingly, only limited numbers of patients under active surveillance require additional treatment. Recent data suggest that delayed treatment does not appear to alter the clinical outcome among those highly selected patients. The future and conclusions. A better understanding of the molecular determinants of prostate cancer behaviour would not only enable healthcare professionals to identify which cases need aggressive treatment but, perhaps more importantly, would also indicate potential targets for the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]