The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK: An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH: General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION: Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make.

Exercise for women receiving adjuvant therapy for breast cancer.

BACKGROUND: A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence and mortality rates. On the other hand, adjuvant and neoadjuvant therapy with chemotherapy and radiotherapy impacts on quality of life due to substantial short- and long-term side effects. A number of studies have evaluated the effect of exercise interventions on those side effects. This is an updated version of the original Cochrane review published in 2006. The original review identified some benefits of physical activity on physical fitness and the resulting capacity for performing activities of daily life. It also identified a lack of evidence for other outcomes, providing clear justification for an updated review. OBJECTIVES: To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side effects such as physical deterioration, fatigue, diminished quality of life, depression, and cognitive dysfunction. SEARCH METHODS: We carried out an updated search in the Cochrane Breast Cancer Group Specialised Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2015), MEDLINE (1966 to 30 March 2015), and EMBASE (1966 to 30 March 2015). We did not update the original searches in CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE (1880 to 2004), and ProQuest Digital Dissertations (1861 to 2004). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 30 March 2015. We screened references in relevant reviews and published clinical trials. SELECTION CRITERIA: We included randomised controlled trials that examined aerobic or resistance exercise or both in women undergoing adjuvant treatment for breast cancer. Published and unpublished trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction, assessed trials, and graded the methodological quality using Cochrane's 'Risk of bias' tool. Any disagreements were resolved through discussion or by consulting the third review author. We entered data into Review Manager for analysis. For outcomes assessed with a variety of instruments, we used the standardised mean difference (SMD) as a summary statistic for meta-analysis; for those assessed with the same instrument, we used the mean difference (MD). MAIN RESULTS: For this 2015 update we included a total of 32 studies with 2626 randomised women, 8 studies from the original search and 24 studies from the updated search. We found evidence that physical exercise during adjuvant treatment for breast cancer probably improves physical fitness (SMD 0.42, 95% confidence interval (CI) 0.25 to 0.59; 15 studies; 1310 women; moderate-quality evidence) and slightly reduces fatigue (SMD -0.28, 95% CI -0.41 to -0.16; 19 studies; 1698 women; moderate-quality evidence). Exercise may lead to little or no improvement in health-related quality of life (MD 1.10, 95% CI -5.28 to 7.48; 1 study; 68 women; low-quality evidence), a slight improvement in cancer site-specific quality of life (MD 4.24, 95% CI -1.81 to 10.29; 4 studies; 262 women; low-quality evidence), and an improvement in cognitive function (MD -11.55, 95% CI -22.06 to -1.05; 2 studies; 213 women; low-quality evidence). Exercise probably leads to little or no difference in cancer-specific quality of life (SMD 0.12, 95% CI 0.00 to 0.25; 12 studies; 1012 women; moderate-quality evidence) and little or no difference in depression (SMD -0.15, 95% CI -0.30 to 0.01; 5 studies; 674 women; moderate-quality evidence). Evidence for other outcomes ranged from low to moderate quality. Seven trials reported a very small number of adverse events. AUTHORS' CONCLUSIONS: Exercise during adjuvant treatment for breast cancer can be regarded as a supportive self care intervention that probably results in less fatigue, improved physical fitness, and little or no difference in cancer-specific quality of life and depression. Exercise may also slightly improve cancer site-specific quality of life and cognitive function, while it may result in little or no difference in health-related quality of life. This review is based on trials with a considerable degree of clinical heterogeneity regarding adjuvant cancer treatments and exercise interventions. Due to the difficulty of blinding exercise trials, all included trials were at high risk for performance bias. Furthermore, the majority of trials were at high risk for detection bias, largely due to most outcomes being self reported.The findings of the updated review have enabled us to make a more precise conclusion that both aerobic and resistance exercise can be regarded as beneficial for individuals with adjuvant therapy-related side effects. Further research is required to determine the optimal type, intensity, and timing of an exercise intervention. Furthermore, long-term evaluation is required due to possible long-term side effects of adjuvant treatment.

Rectal cancer: assessment of response to neoadjuvant chemoradiation by dynamic contrast-enhanced MRI.

PURPOSE: To assess pretreatment functional and morphological tumor characteristics with magnetic resonance imaging (MRI) in advanced rectal carcinoma and to identify factors predicting response to neoadjuvant chemoradiation. MATERIALS AND METHODS: In a prospective study, 95 patients with rectal carcinoma underwent dynamic contrast-enhanced MRI before and after chemoradiation. Quantitative parameters were derived from a pharmacokinetic two-compartment model. Tumors were also characterized with regard to mucinous status at pretreatment high-resolution MRI as nonmucinous or mucinous. Response to treatment was defined as a downshift in the local tumor stage. RESULTS: The parameter k21 (contrast medium exchange rate) was higher at pretreatment MRI in nonmucinous compared with mucinous carcinomas (P < 0.001). The effect of chemoradiation on dynamic MR parameters was higher in nonmucinous carcinomas than in the mucinous subtype (P < 0.001). A higher rate of response to treatment was linked with nonmucinous morphology (P < 0.001). Multivariate analysis revealed an association between mucinous tumor morphology and poor response (odds ratio [95% confidence interval]: 0.113 [0.032-0.395], P < 0.001) as well as an association between a high 75th percentile of k21 and a higher response rate (odds ratio: 1.043 [1.001-1.086], P = 0.019). CONCLUSION: Functional and morphological parameters of pretreatment MRI can assess tumor characteristics associated with the effectiveness of chemoradiation before treatment initiation.

Rectal cancer: mucinous carcinoma on magnetic resonance imaging indicates poor response to neoadjuvant chemoradiation.

PURPOSE: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). METHODS AND MATERIALS: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). RESULTS: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p ≤ 0.001). Positive resection margins (ypCRM ≤ 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p ≤ 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). CONCLUSION: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy.

Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome-based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250-mediated immunotherapy. Flow cytometry revealed G250 surface expression in approximately 40% of RCC cell lines, but not in the normal kidney epithelium cell lines. G250 expression levels significantly varied thereby distinguishing between low, medium and high G250 expressing cell lines. Comparisons of two-dimensional gel electrophoresis expression profiles of untreated RCC cell lines versus RCC cell lines treated with a mAb directed against G250 and the characterization of differentially expressed proteins by mass spectrometry and/or Edman sequencing led to the identification of proteins such as chaperones, antigen processing components, transporters, metabolic enzymes, cytoskeletal proteins and unknown proteins. Moreover, some of these differentially expressed proteins matched with immunoreactive proteins previously identified by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, a technique called PROTEOMEX. Immunohistochemical analysis of a panel of surgically removed RCC lesions and corresponding normal kidney epithelium confirmed the heterogeneous expression pattern found by proteome-based technologies. In conclusion, conventional proteome analysis as well as PROTEOMEX could be successfully employed for the identification of markers which may allow the selection of patients prior to specific immunotherapy.