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Background: Nomograms can help in estimating the nodal status among clinically node-negative patients. Yet their validity in external cohorts over time is unknown. If the nodal stage can be estimated preoperatively, the need for axillary dissection can be decided. Objectives: The aim of this study was to validate three existing nomograms predicting 4 or more axillary lymph node metastases. Method: The risk for ≥4 lymph node metastases was calculated for n = 529 eligible breast cancer patients using the nomograms of Chagpar et al. [Ann Surg Oncol. 2007;14:670–7], Katz et al. [J Clin Oncol. 2008;26(13):2093–8], and Meretoja et al. [Breast Cancer Res Treat. 2013;138(3):817–27]. Discrimination and calibration were calculated for each nomogram to determine their validity. Results: In this cohort, the AUC values for the Chagpar, Katz, and Meretoja models were 0.79 (95% CI 0.74–0.83), 0.87 (95% CI 0.83–0.91), and 0.82 (95% CI 0.76–0.86), respectively, showing good discrimination between patients with and without high nodal burdens. Conclusion: This study presents support for the use of older breast cancer nomograms and confirms their current validity in an external population.

BACKGROUND International guidelines do not recommend magnetic resonance imaging (MRI) for all breast cancer patients at primary diagnostics. This study aimed to understand which patient or tumor characteristics are associated with the use of MRI. The role of MRI among other preoperative imaging methods in clinically node negative breast cancer was studied. MATERIAL AND METHODS Patient and tumor characteristics were analyzed in association with the use of MRI by multivariable logistic regression analysis in 461 patients. Primary tumor size was compared between MRI, mammography (MGR), ultrasound (US) and histopathology by Spearman correlation. The delays in surgery and diagnosis were analyzed among patients with or without MRI, and axillary reoperations were evaluated. RESULTS Age (p

Background The aim of the study was to assess patient dose from whole-body computed tomography (CT) in association with patient size, automatic exposure control (AEC) and intravenous (IV) contrast agent. Patients and methods Sixty-five testicular cancer patients (mean age 28 years) underwent altogether 279 whole-body CT scans from April 2000 to April 2011. The mean number of repeated examinations was 4.3. The GE LightSpeed 16 equipped with AEC and the Siemens Plus 4 CT scanners were used for imaging. Whole-body scans were performed with (216) and without (63) IV contrast. The ImPACT software was used to determine the effective and organ doses. Results Patient doses were independent (p < 0.41) of patient size when the Plus 4 device (mean 7.4 mSv, SD 1.7 mSv) was used, but with the LightSpeed 16 AEC device, the dose (mean 14 mSv, SD 4.6 mSv) increased significantly (p < 0.001) with waist cirfumference. Imaging with the IV contrast agent caused significantly higher (13% Plus 4, 35% LightSpeed 16) exposure than non-contrast imaging (p < 0.001). Conclusions Great caution on the use of IV contrast agent and careful set-up of the AEC modulation parameters is recommended to avoid excessive radiation exposure on the whole-body CT imaging of young patients.

Background/aim Sentinel lymph node (SLN) biopsy has become the standard procedure to identify metastases in axillary nodes in breast cancer. Even after careful SLN examination additional micrometastases and isolated tumor cells (ITCs) are sometimes found, resulting in a need for delayed axillary lymph node dissection (ALND). This study was undertaken to assess prognostic factors identifying additional axillary lymph node (ALN) metastases at delayed ALND. Patients and methods To define the impact of late ALND regarding their outcome, 162 breast cancer patients with 169 operated breasts treated between 2010 and 2012 were evaluated, with follow-up through 2016. Data were collected on the patients, histology and biologic profile of the cancer, lymph node involvement, recurrence of breast cancer and adverse effects of ALND. Results With thorough examination and immunohistochemical stainings twenty-nine of 168 SLN biopsies (28 patients, 17% of the patients) showed micrometastases or ITC, and a full ALND was performed at a later time. During these ALNDs 13 to 31 lymph nodes were removed. Additional ALN metastases were found in three (10%) patients. Two (7%) of the 28 patients with triple-negative cancer deceased of metastatic breast cancer. Three patients (11%) reported adverse effects of ALND requiring physiotherapy due to pain, stiffness, swelling or arm oedema. Tumor factors such as molecular subtype (p=0.002), tumor size (p=0.004), and proliferation index (Ki-67) (p=0.003) correlated with higher numbers of ALN metastases. Conclusion Since most patients with micrometastases found in the primary operation showed no additional positive lymph nodes, completion ALND may not be required in patients with micrometastases or ITCs in the SLN. In our study, the predictive factors for additional ALN metastases were tumur size, molecular subtype and proliferation index. It is conceivable that the features of the primary tumor, rather than the amount of cancer cells in the SLN, might serve to identify patients in whom ALDN can be avoided.

The fourth workshop of the Multidisciplinary European Low Dose Initiative (MELODI) was organised by STUK—Radiation and Nuclear Safety Authority of Finland. It took place from 12 to 14 September 2012 in Helsinki, Finland. The meeting was attended by 179 scientists and professionals engaged in radiation research and radiation protection. We summarise the major scientific findings of the workshop and the recommendations for updating the MELODI Strategic Research Agenda and Road Map for future low dose research activities.

Background A study of the computed tomography (CT) imaging related effective doses and radiation-related cancer death risk. Patients and methods Estimate effective doses were computed from CT scans of testicular cancer patients treated and followed-up in Turku University Hospital, South Western Finland. Association between effective doses from follow-up CT scans and radiation-induced cancer death was examined using United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2008 formula. Results Mean effective dose per CT abdomen was 9.32 (standard deviation, SD 3.89) mSv and for whole-body CT it was 14.24 (SD 6.84) mSv. During follow-up of 6 years, the patients were estimated to undergo 12 to 14 abdominal/whole-body CTs and the corresponding risk estimates were 0.11 and 1.14, respectively. The risk of estimated radiation-induced cancer deaths (RICD in %) computed for mean effective doses was lower in patients diagnosed at older age, being 0.61 for 10-19 years age and 0.04 for 40-49 years age at the diagnosis. Conclusion Patient radiation exposure in CT imaging is associated with the type of CT device and imaging protocols, which should be periodically updated and reviewed to minimize individual exposure. Using the UNSCEAR modelling 2 % risk for radiation related cancer death was attributed to diagnostic exposure of study patients. Age at the diagnosis was associated with CT imaging related radiation exposure. The highest exposure was estimated to the youngest patients.

This study assessed the symptoms and health-related quality of life (HRQOL) of patients with advanced non-small cell lung cancer (NSCLC) and examined the symptom-associated characteristics.The symptoms of 122 patients with NSCLC scheduled for chemotherapy before starting treatment were surveyed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and Edmonton Symptom Assessment Scale (ESAS).The most prevalent symptoms were coughing (EORTC score 41.7), dyspnea (33.9), fatigue (31.9), insomnia (30.3) and pain (21.8). The mean EORTC score for global QoL was 56.9 (SD=23.5). Physical, cognitive and emotional functioning, insomnia, diarrhea, and dyspnea had a significant influence on the HRQOL (p0.05). ESAS assessment correlated with these results and thus was an easy-to-use tool for symptom assessment (correlation coefficient range=0.546-0.865, p0.0001 for all symptoms).Patients with advanced NSCLC suffer from multiple symptoms influencing HRQOL. ESAS provides a symptom assessment tool that is as reliable as but simpler to use than the EORTC questionnaire.

Computed tomography (CT) imaging contributes to a major part of medical radiation exposure. With regard to patients safety, frequent CT examinations (CTEs) performed on the same patient are of particular concern. Tools for tracking the individual patient radiation exposure history and cumulative dose assessment may become important. Here, the applicability of the NRPB-SR250 software was assessed in a retrospective analysis of radiation doses from CTE made consecutively in male patients. Most of the examinations focused on the abdomen or the whole body. The mean number of CTs per patient was 6.8. Significant cumulative effective doses were observed: 76 (66 %) patients received an effective dose higher than 50 mSv, while the maximum was ∼280 mSv. A more than 3-fold effective dose difference was observed between scanners, depending on the scanning protocols. The NRPB-SR250 software proved to be a robust tool for the assessment of organ doses and the effective radiation dose from CT, while challenges were encountered in finding the precise imaging data in retrospective protocols.

The aim of this study was to examine the expression of the molecular markers cyclooxygenase-2 (COX-2), Ki-67, cyclin A, and p27 in patients with esophageal squamous cell carcinoma (ESCC), to ascertain the relationship of these makers with the clinicopathological significance of the patients, and to assess the additional prognostic value of the expression profile of these proteins for ESCC patients. The expression levels of COX-2, Ki-67, cyclin A, and p27 proteins of a series of primarily resected ESCC samples were determined by immunohistochemistry method. Clinicopathological and molecular factors affecting survival were analyzed by multivariate analysis. A total of 78 specimens were included in this study. Expression of COX-2 was observed in 43 (55.1%) cases, and high levels of expression of Ki-67, p27, and cyclin A were observed in 57 (73.0%), 33 (42.3%), 43 (55.1%) cases, respectively. The results of univariate survival analysis indicated that more advanced tumor stage, lymph node involvement, systemic dissemination, the levels of expression of COX-2, Ki-67, cyclin A, and p27 were associated with survival (all P-value < 0.05). Multifactorial survival analysis revealed that only lymph node involvement, over-expression of cyclin A, and low p27 expression were associated with the survival of the patients (hazard ratios = 2.83, 4.7, 2.9, respectively; P= 0.025, 0.042, 0.005, respectively). Among the molecular markers assessed, the expression of cell proliferation markers cyclin A and p27 are independent prognostic factors in patients with ESCC, whereas neither COX-2 nor Ki-67 is of independent prognostic value.

This phase II study assessed the clinical response and short-term quality of life of patients receiving first-line chemotherapy with epirubicin-docetaxel combination for metastatic breast cancer. Thirty-one breast cancer patients were treated with epirubicin (75 mg/m2 for 15 minutes) followed one hour later by a one-hour infusion of docetaxel (75 mg/m2) q3w. EORTC QLQ-C30 and EORTC QLQ-BR23 forms were filled in at baseline, and at the second and eighth cycle of chemotherapy. The combination of epirubicin and docetaxel provided a high degree of clinical benefit. Clinical response was observed in 17 patients (55%), including five (16%) complete responses and 12 (39%) partial responses. Of responding and stable patients 23 (74%) maintained the same status for at least six months (clinical benefit). The mean survival time was 40.8 months. During the treatment the emotional functioning improved and the concerns about the future were relieved. Some aspects of quality of life were impaired, with slightly decreased physical and cognitive functioning, distress related to body image and hair loss, and adverse effects of chemotherapy. Overall, the global quality of life was maintained.

Purpose The article summarises the current use of radiotherapy (RT) in childhood cancer and suggests methods to improve current practice in regions where outcomes of paediatric cancer patients are inferior to those of high-income countries. Methods and materials The International Atomic Energy Agency (IAEA) is supporting low- and mid-income countries (LMICs) in upgrading cancer care where nuclear applications, particularly RT, are used. A consensus meeting of experts was invited to advise IAEA on the needs for RT in paediatric cancer patients. The current indications for RT were reviewed, together with regional differences in access, practice and outcome. Results Regional variations in the use of evidence-based multidisciplinary care including RT were associated with varying outcomes of paediatric cancer patients. The contribution of modern and investigational technology to these differences is uncertain and should be determined in clinical trials. Adequate resources are required to support children through the acute phase of treatment and to permit early recognition and management of late effects. An IAEA sponsored project for prospective data collection to assess the current and future status of radiation treatment in childhood cancer in LMICs has commenced. Conclusion RT remains an essential component of the multidisciplinary management of many paediatric cancers. Excessive variations in outcome are inappropriate and call for action on harmonising training programmes and compliance with evidence-based recommendations. Training projects targeting paediatric cancer care are being implemented and clinical studies comparing new technologies against evidence-based approaches are needed to achieve this goal. The IAEA has an important role in these activities and has commenced prospective data collection in 13 LMICs to monitor trends in treatment techniques and outcomes.

Epidemiological studies indicate beneficial effects of flavonoids on cardiovascular disease (CVD) risk. To study the effect of flavonoid-rich sea buckthorn berry (SBB) on circulating lipid markers associated with CVD risk and plasma flavonol concentration. Also investigated was whether changes in the circulating flavonol concentrations correlate with the SBB induced changes in C-reactive protein (CRP) concentration observed previously. In all 229 healthy participants completed the randomized double-blind study and consumed daily 28 g of SBB or placebo for 3 months. Fasting blood samples for the analysis of lipid markers and flavonols were obtained at the beginning and end of the study. Compared to the placebo, the consumption of SBB increased the plasma concentration of the flavonols quercetin and isorhamnetin significantly [treatment differences 3.0 ng/ml (P = 0.03) and 3.9 ng/ml (P

Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. (Less)

Based on randomized studies bone-marrow supported (BMS) high-dose chemotherapy (HDCT) is not superior to conventional CT as adjuvant treatment for high-risk breast cancer. To compare the cost-effectiveness of these treatments we examined the data of Finnish patients in the SBG9401 trial 1. Patients were randomized to receive either dose-escalated (de FEC) (group A, n =59) or FEC and HDCT+BMS (group B, n =70). They received adjuvant radiotherapy (RT) + tamoxifen. All direct health care costs of first line treatment at the oncology units were considered as well as productivity costs within the first 3 years of follow-up. Effectiveness was measured by the number of survival days during 5 years of follow-up. The mean direct health care costs were significantly higher in group B (25829 euro in group A vs. 36605 euro in group B, p0.001), mainly due to a higher number of hospital days. Half of the costs in group A was due to the use of filgrastim (15335 euro in A and 2969 euro in B, p0.001). The costs of RT were only 5% of total costs. There was no statistically significant difference between the groups in the number of survival days, but sensitivity analysis based on bootstrapping suggested that treatment A would be a less costly and more effective alternative in a great majority of cases.

Background In vitro and in vivo studies suggest that selected strains of probiotic bacteria can form tight complexes with aflatoxin B(1) and other carcinogens. Objective The aim of the present study was to determine whether administration of probiotic bacteria could block the intestinal absorption of aflatoxin B(1) and thereby lead to reduced urinary excretion of aflatoxin B(1)-N(7)-guanine (AFB-N(7)-guanine), a marker for a biologically effective dose of aflatoxin exposure. Elevated urinary excretion of this aflatoxin-DNA adduct is associated with an increased risk of liver cancer. Design Ninety healthy young men from Guangzhou, China, were randomly assigned to 2 groups; one group received a mixture of Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii subsp. shermanii strains 2 times/d for 5 wk, and the other group received a placebo preparation. The subjects provided 4 urine samples: at baseline, at 3 and 5 wk after starting the supplementation, and at the end of the 5-wk postintervention period. Results The percentage of samples with negative AFB-N(7)-guanine values tended to be higher in the probiotic group than in the placebo group during the 5-wk intervention period (odds ratio: 2.63, P = 0.052), and a statistically significant decrease in the concentration of urinary AFB-N(7)-guanine was observed in the probiotic group. The reduction was 36% at week 3 and 55% at week 5. The geometric means for the probiotic and placebo groups were 0.24 and 0.49 ng AFB-N(7)-guanine/mL, respectively, during the intervention period (P = 0.005). Conclusion A probiotic supplement reduces the biologically effective dose of aflatoxin exposure and may thereby offer an effective dietary approach to decrease the risk of liver cancer.

BACKGROUND The adverse effects of hormonal manipulation in prostate carcinoma need to be established in view of its increasing use as an adjuvant treatment. This prospective study investigated the association of androgen deprivation-induced estradiol decline with cognition in prostate carcinoma. METHODS Cognitive testing of prostate carcinoma patients was carried out at baseline and at 6 and 12 months on androgen deprivation (AD). Cognitive performances were evaluated with standardized measures of information processing, including working memory and attention, visual and verbal skills, and memory performances in 31 tests. Testosterone and estradiol changes during AD were measured with the DELFIA® (PerkinElmer, Inc., Wellesley, MA) system. Associations between changes in cognitive performances and estradiol decline were studied. RESULTS Cognitive performances, which were significantly associated with decline in estradiol, included visual memory of figures (r = −0.52; P = 0.022) and recognition speed of numbers, which were impaired, (r = −0.57; P = 0.030) at 6 months, and improvement in verbal fluency (r = −0.52; P = 0.019) at 12 months. Other cognitive domains appeared unaffected by estradiol decline. The character of change (impairment or improvement) depended on the magnitude of estradiol decline. CONCLUSIONS The cognitive domains of verbal fluency, visual recognition, and visual memory were associated with decline in estradiol during androgen deprivation. The results suggest selective associations among testosterone decline, estradiol, and cognitive performance. Documentation of these associations has implications for informed patient support in hormonally treated prostate carcinoma. Cancer 2005. © 2005 American Cancer Society.

Our study was designed to assess the fecal and urinary excretion of 3 aflatoxin B1 (AFB1) metabolites, aflatoxins M1 (AFM1) and Q1 (AFQ1) and aflatoxin B1-N7-guanine (AFB-N7-guanine) that are produced by the predominant forms of cytochrome P450 enzymes responsible for the biotransformation of AFB1. Fecal and urinary AFM1, AFQ1 and urinary AFB-N7-guanine were assessed in 83 young Chinese males selected from a larger population (n = 300) based on detectable urinary AFM1. The concentration of fecal AFQ1 (median 137 ng/g fresh weight, IQR 9.1 to 450) was approximately 60 times higher than that of AFM1 (2.3 ng/g, IQR 0.0 to 7.3). In urine, the median AFQ1 was 10.4 ng/ml (IQR 3.4 to 23.3), and the median AFM1 and AFB-N7-guanine 0.04 ng/ml (IQR 0.01 to 0.33) and 0.38 ng/ml (IQR 0.0 to 2.15), respectively. A subgroup (n = 14) with hepatitis B virus (HBV) infection had significantly higher fecal concentrations of AFQ1 (p = 0.043) and AFM1 (p = 0.001) than those who were hepatitis B-virus antigen (HBsAg) negative, and the respective differences in urinary AFQ1 and AFM1 concentrations approached statistical significance (p = 0.054, p = 0.138). Our study demonstrates that AFQ1 is excreted in urine and feces at higher levels than AFM1, and feces are an important route of excretion of these AFB1 metabolites. AFQ1 should be further assessed for its predictive value as a marker for exposure and risk of dietary aflatoxins.

Androgen deprivation (AD) used in the treatment of prostate cancer is known to alter concentrations of sex hormones and their binding globulins. Less is known as to its effect on thyroid hormones. In this prospective study the effects of AD on thyroid function were clarified. Levels of serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid binding globulin concentrations were measured in prostate cancer patients treated with either radical radiotherapy and androgen deprivation for 12 months (AD) or radical radiotherapy alone (RT). Measurements were made at baseline, and at 3, 6 and 12 months. At baseline and at 3 months the results of thyroid function tests did not differ significantly between groups. A significant decline in serum testosterone in the AD group was accompanied by a significant decline in FT4 at 6 and 12 months, while no significant changes in thyroid function were observed in the RT group. The decline in FT4 among AD patients did not evoke a normal TSH response. Prolonged use of AD hampers the interpretation of thyroid test results. This finding has substantial implications for the follow-up of patients in hormonally treated prostate cancer.

Androgen deprivation (AD) is commonly used in neoadjuvant and adjuvant setting with prostate cancer (PC) radiotherapy. This prospective study assessed whether cognitive functioning is impaired during 12 months of AD therapy. Longitudinal testing of 25 patients treated with AD and curative radiotherapy was undertaken at baseline, and at 6 and 12 months. CogniSpeed software was used for measuring attentional performances. Other cognitive performances were evaluated using verbal, visuomotor and memory tests. The Beck depression inventory was employed to evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL). During longitudinal testing of the AD group, no impairment in cognitive performances was found. Instead, improvement was observed in object recall (immediate, P=0.035; delayed, P

The aim was to evaluate clinical and subclinical cardiac toxicity of epirubicin-docetaxel (ET) combination. Breast cancer patients were given epirubicin (75 mg/m 2 for 15 min), followed 1 h later by a 1-h infusion of docetaxel (75 mg/m 2 ) q3w as first-line treatment Cardiac function was monitored using a 24-h ambulatory electrocardiogram (ECG), left ventricular ejection fraction (LVEF), physical examination and chest radiography. The median LVEF did not decrease during the course of the treatment: median LVEF was 64% prior to treatment and 68% after cycle 8. The 24-h ECG did not reveal any significant changes in heart rate variability. The number of extrasystoles or cardiac arrhythmia did not increase with the ET treatment No patient experienced congestive heart failure during treatment or the mean follow-up of 34 months. We conclude that first-line ET caused no major cardiac changes during 6 months of treatment (8 cycles) or during follow-up. Twenty-four-hour ECG, combined with echocardiography to measure LVEF, was a feasible method for the close monitoring of the cardiac effects during chemotherapy.

The purpose of this investigation was to evaluate the efficacy and toxicity of 6 months' treatment with the combination of epirublcin and docetaxel in metastatic breast cancer. Thirty-eight women (mean age 51 years, range35-72) with metastatic breast cancer were treated with a regimen of epirubicin 75 mg/m 2 and docetaxel 75 mg/m 2 every 3 weeks, given 4 times if progression was seen upon evaluation after 4 courses or 8 times in responding/stable patients. The patients received 285 cycles of combination treatment and two treatments with docetaxel or epirubicin alone. When neutropenia with fever was observed, further cycles were given with dose reduction. The median cumulative docetaxel dose was 462 mg/m 2 (range 199-600) and that of epirubicin 476 mg/m 2 (range 199-740). The overall response rate was 54% (95% CI 37-71), with a median duration of response of 14.8 months (95% CI 8.8-27.8). Median time to progression was 12 months, median survival 26 months. Neutropenia below 0.5 × 10 9 /l occurred following 113 (39%) of the total of 285 cycles given; 21 patients (55%) were hospitalized for febrile neutropenia. We conclude that dose tailoring is required in treatment with an epirubicin and docetaxel regimen to avoid grade 3/4 adverse effects In a significant number of patients treated for metastatic breast cancer.

The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

The aim of this study was to investigate FDG-PET (fluorodeoxyglucose positron emission tomography) imaging in the management of prostate cancer. Twenty-two patients were studied during different disease phases of prostate cancer, for staging or restaging to clarify specific clinical questions. FDG-PET was performed encompassing the thorax, abdomen and pelvis using the Penn PET 300H scanner. Scanning was begun 60 min after 18F fluorodeoxyglucose marker. Patients were catheterized and administered diuretics to minimize urinary activity. Information obtained with FDG-PET was concordant with findings from other investigations in 7/22 (32%) patients, discordant in 15/22 (68%) patients and equivalent in one patient (4%). PET indicated progressive disease in five patients with prostate-specific antigen (PSA)4 ng/L. The impact on management of the patients was high in 46% of cases, low in 41% and for 14% there was no impact on management. The accuracy of FDG-PET was 72% (95% CI 50-89) as confirmed by invasive diagnostics/follow-up. FDG-PET can provide useful information and improve the clinician's decision on further management procedures in selected patients with low PSA and bone or lymph node changes. A negative PET scan in prostate cancer should be interpreted with caution.

In order to reach a dose rate of ca. 20 Gy/min with a typical 60Co radiotherapy unit, lactic acid bacteria (LAB) are irradiated at a 20 cm source-to-specimen distance (SSD). By choosing an SSD which is a fourth part of the conventional 80 cm, the dose rate in the specimen is increased by a factor of ca. 16. A Monte Carlo simulation of the CGR Alcyon II 60Co radiotherapy unit at 20 cm SSD is performed using a BEAM-EGS4 Monte Carlo code. As a result of calculations, relative dose distributions in a solid-water phantom are shown, together with measured thermoluminescence dosimetry (TLD) data. An additional scattering component due to the sideways scattering from the beam limiting device structures of the radiotherapy unit is seen in the beginning of the BEAM data.

Cancer pain management in a hospice setting was studied in the present article. Drug treatments were studied at five time points: at the time of transfer to hospice, at 2nd day, two weeks, and two months following transfer to hospice care, as well as one day before death.Records of 138 consecutive cancer patients treated in hospice in 2010 were studied regarding the drugs given during their stay. The most common cancer was gastro-intestinal cancer (33%), followed by lung (16%) and breast cancer (11%). Data were collected from patients' records and coded in a validated manner for statistical analysis.The median length of stay in hospice was 14 days (range=2-376 days). Upon transfer, 63% of patients were administered regularly-dosed opioids, 76.8% during the second day at hospice, and 89.9% of the patients received opioids one day prior to death. A significant change was observed in the more frequent subcutaneous administration during hospice stay (p0.0001). Break-through pain was recorded on the second day in hospice by 52 % of patients, and by 76% on the day prior to death.Individual patients' needs determined the dose range, but this was not the case for administration route of strong opioids during hospice care.

SUMMARY Thallium-201 (Tl-201) single photon emission computed tomography (SPECT) is funded for evaluation of malignancy in Australia and may have utility for staging of non-small cell lung cancer (NSCLC) if CT results are equivocal. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) is superior to CT for staging NSCLC but is more expensive and less widely available than Tl-201 SPECT. Therefore, these techniques were prospectively compared in 27 radical radiation therapy candidates. Patients were allocated a conventional, PET and Tl-201 stage. Tumour to background ratios (TBR) were recorded for the primary on both techniques. Metastatic disease was confirmed by surgical pathology, serial imaging or clinical follow up. Tumour to background ratios were consistently higher for FDG PET than Tl-201 SPECT (P < 0.0001). Positron emission tomography detected all known primary tumours but Tl-201 failed to image four primary tumours (15%). In 10 of 18 cases of discordance between PET and Tl-201 SPECT regarding stage, corroboration was available from pathology or disease progression. Positron emission tomography was shown to have a 100% positive predictive value, including all three patients with PET-detected distant metastases (P = 0.002). Results indicate that PET is superior to Tl-201 SPECT scanning in the staging of NSCLC for radical radiation therapy, and that the low sensitivity for detection of local and metastatic disease is likely to limit the clinical impact and cost-effectiveness of this technique despite its lower cost.

BACKGROUND Interferon-α has proven effective in the treatment of metastatic renal cell carcinoma. However, the optimal schedule has not yet been determined. The authors have studied the efficacy and toxicity of prolonged use interferon-α2a (IFN-α) in metastatic renal cell carcinoma (RCC). Interferon-α was administered intermittently for outpatients. METHODS Seventy-five patients with metastatic RCC without prior biochemotherapy were treated. During the first month, the IFN-α dose was increased from 4.5 to 18 million units (MU) 3 times a week to define the individual maximal tolerated dose for each patient. The treatment was continued at the maximal tolerated dose with a 1-week pause each month until either progression or intolerable toxicity was observed or up to 2 years. RESULTS The overall response rate (5 complete response [CRs] and 8 partial responses [PRs]) was 17% (95% confidence interval, 10–28%). Stable disease was observed in 32 patients (43%). Three late objective responses (4%) occurred after 12 months treatment. The median progression free time of all patients was 12.3 months, and median survival time was 19.3 months. The median duration of response in CR/PR patients was 16 months. In multivariate analysis independent prognostic factors were poor performance status (P = 0.004), presence of bone metastases (P = 0.001), and time to metastases less than 24 months (P = 0.003), which predicted poor survival. Six patients (8%) discontinued the treatment because of fatigue, elevation of liver enzymes, or cardiac arrhythmias. No life-threatening side effects were observed. CONCLUSIONS Prolonged and intermittently administered IFN-α2a three times per week in 3 weekly cycles in metastatic RCC is a feasible and effective therapy. A prolonged treatment duration of more than 12 months for stable and responding patients is beneficial and may improve the outcome of patients with RCC. Cancer 2001;92:761–7. © 2001 American Cancer Society.

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor– and/or progesterone receptor–positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. RESULTS: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P = .0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P = .0006), as was the rate of clinical benefit (49% v 38%; P = .001). Survival data are currently immature and not reported here. Both treatments were well tolerated. CONCLUSION: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.

The risk of a new primary cancer (NPC) among 77548 Finnish lung cancer patients from 1953 to 1995 was analysed by the histological type of the lung cancer. The relative risks were expressed as standardised incidence ratios (SIR, ratio of the observed and expected numbers of cases). During the follow-up, 1148 NPCs were observed among men and 152 among women. After exclusion of lung cancers, the risk of NPC was elevated in both males (SIR 1.07; 95% confidence interval (CI) 1.00-1.14) and females (SIR 1.21; 95% CI 1.02-1.42). The excess was larger among lung cancer patients with small-cell carcinoma and adenocarcinoma than those with squamous-cell carcinoma. In all major histological groups of lung cancer, significant excess risks were found for cancers of the larynx (SIRs 2.94-4.25), and bladder (SIRs 2.16-2.86). Significantly elevated SIRs were also found for cancers of the stomach (SIR 1.42; 95% CI 1.12-1.76) and kidney (SIR 2.18; 95% CI 1.56-2.97) in squamous-cell carcinoma; for brain tumours (SIR 3.26; 95% CI 1.20-7.09) in small-cell carcinoma; and for cancers of the prostate (SIR 1.68; 95% CI 1.21-2.27) and thyroid (SIR 3.79; 95% CI 1.23-8.85), and brain tumours (SIR 2.34; 95% CI 1.07-4.43) in adenocarcinoma. The risk of contracting NPC at sites where the majority of tumours are adenocarcinomas was elevated among patients with adenocarcinoma of the lung, but not among squamous-cell or small-cell carcinoma patients. In adenocarcinoma, the excess risks of several smoking-related cancers tended to be somewhat lower than those in the other two histological categories. The relative risk of a NPC among patients diagnosed with lung cancer in 1985-1995 was higher than that of patients from earlier periods in all comparable follow-up categories (up to 10 years), possibly suggesting that the increased use of cytostatic drugs had increased the risk of NPC.

Lung cancer is currently the leading cause of cancer-related death in both men and women in most Western countries. Although 5-year survival rates have doubled from 1960s, they are low compared with survival rates for other cancer types. Tumour stage is the strongest prognostic factor and the most important parameter that guides treatment decision making. Metabolic imaging with fluorodeoxyglucose-labelled positron emission tomography (FDG-PET) has proved superior to conventional imaging for staging of non-small-cell lung cancer. This new imaging modality permits more accurate planning of treatment with surgery and radiotherapy and provides information of greater prognostic significance than what can be obtained with conventional approaches. FDG-PET has been approved in the USA and the UK as a basic and invaluable tool in the management of lung cancer. This paper reviews current trends in clinical practice on the applications of FDG-PET in the management of non-small-cell lung cancer.

This study investigated the outcome of testicular cancer treatment in Finland.Data on 88 testicular cancer patients treated in Turku University Central Hospital between 1976 and 1992 were studied to analyse outcome and survival.The histological diagnosis was seminoma for 39 patients and non-seminoma for 49 patients. Two seminoma patients relapsed (5%) and one patient died of progressive disease (3%; initially stage II seminoma). Eleven non-seminoma patients relapsed (22%), nine of whom were cured with chemotherapy. Four non-seminoma patients died of progressive disease (8%; initially one stage I non-seminoma and three stage III non-seminomas). The median time to relapse after the completion of treatment was 9 months (range 3-50 months). Non-seminoma patients had significantly more relapses than seminoma patients (p = 0.03). Most relapses (73% of the non-seminoma relapses) were found among the stage I non-seminoma patients who had not received adjuvant chemotherapy, while none of the stage I seminoma patients relapsed (p = 0.007).Close surveillance is important for all non-seminoma patients to guarantee the early detection and treatment of recurrent disease. Treatment and surveillance should be covered by national guidelines and be conducted in centres with special interest in this rare but mostly curable cancer.

The cell cycle is a complex event in which multiple regulator-proteins participate. The G 1/S checkpoint of the cell cycle is controlled by pRb protein, which functions in its hypophosphorylated form as a negative regulator of growth. p27 (Kip1), a member of CIP/KIP family of cyclin inhibitory proteins, participates in inhibition of forming complexes that allow pRb to phosphorylate and lead the cell into mitosis. The expression of these important cell cycle regulator proteins was studied in a total of 96 non-Hodgkin’s lymphoma (NHL) samples, which were classified according to the REAL classification. The expression of p27, pRb and the cell proliferation marker Ki-67 (MIB-1) was evaluated in lymphomas using immunohistochemistry. This study showed that there were coordinate changes in the expression of p27 and pRb in NHL. When compared to low-grade lymphomas, high-grade lymphomas showed significantly reduced expression of p27 and inversely pRb expression was increased (P < 0.001). Increase in expression of Ki-67 was parallel with pRb expression, and was mainly seen in cells that lacked p27 expression (P < 0.0001). This study suggests that changes in the control of the cell cycle closely relate to the pathobiology of NHL. © 2000 Cancer Research Campaign

Summary Background Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. Methods 525 women younger than 60 years of age with highrisk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stemcell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. Findings At a median follow-up of 34·3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0·04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0·12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p Interpretation Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.

It has been suggested that probiotics should be viable in order to elicit beneficial health effects. Inactivation of probiotics has been suggested to interfere with the binding to the mucosa and thereby with the immune modulating activity of probiotics. The effect of different inactivation methods on the mucus adhesion of nine probiotic strains was studied. Inactivation by heat or gamma-irradiation generally decreased the adhesive abilities. However, heat treatment increased the adhesion of Propionibacterium freudenreichii and gamma-irradiation enhanced the adhesion of Lactobacillus casei Shirota. Inactivation by u.v. was not observed to modulate the adhesion of the tested strains and it was concluded to be the most appropriate method for studying non-viable probiotics and preparing control products.

BACKGROUND Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied. METHODS Twenty-four-hour ambulatory electrocardiogram measurements were recorded twice from 14 women with breast or ovarian carcinoma: once before paclitaxel treatment and once on the day after the second chemotherapy course. Heart rate variability (HRV) was assessed with spectral analysis. For the frequency domain analysis, HRV was assessed in the very low (0.005–0.040 hertz [Hz]), low (0.040–0.150 Hz), and high frequency (0.150–0.400 Hz) spectral components. RESULTS The ratio between low frequency and high frequency HRV decreased (daytime values of 2.7% [standard deviation (SD) 1.6] vs. 1.7% [SD 0.9]; P = 0.0098) after 2 courses of paclitaxel. The circadian fluctuation of HRV also decreased in all studied frequency components. CONCLUSIONS The observed changes in spectral characteristics suggest that autonomic modulation of the heart rate is impaired after paclitaxel therapy. However, from these data it is not clear whether the observed changes are permanent or whether autonomic cardiac function returns to normal some time after treatment. Further studies are needed to examine whether these indices based on HRV can be used to detect those patients at risk for cardiac side effects during chemotherapy. Cancer 2000;88:2149–53. © 2000 American Cancer Society.

Cumulative inactivation of tumor suppressor genes and/or amplification of oncogenes lead to progressively more malignant astrocytic tumors. We have analyzed the significance of tumor suppressor genes p53, p21, p16 and retinoblastoma protein (pRb) and proliferative activity for survival in 77 high grade astrocytic tumors. After operation, the patients--25 anaplastic astrocytomas (AA) and 52 glioblastomas (GBs)--were treated with similar radiotherapy. The expression of the suppressor genes and the proliferative activity were analyzed immunohistochemically. p53 immunopositivity was found in 44% of AAs and 46% of GBs. Tumors with aberrant p53 expression had lower proliferation indices than p53 immunonegative tumors. Neither p53 expression nor p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival. p16 immunostaining was negative in 16% of AAs and in 44% of GBs, and it correlated inversely with survival in both uni- and multivariate analyses. pRb immunostaining was negative only in 8% of both AAs and GBs and the absence of p16 and pRb were mutually exclusive. Ki-67 labelling index (LI) was significantly higher in GBs (26.8%) than in AAs (20.3%), and in multivariate analysis it was an independent prognostic factor for survival. In 48% of AAs Ki-67 LI exceeded 20% and this subset of AAs had similar prognosis as GB. In high grade astrocytic tumors p16 immunonegativity was an independent indicator of poor prognosis in addition to the previously established patient's age, histopathology and Ki-67 LI. Furthermore, there was a subset of AAs with a high proliferation rate (> 20%) in which the histopathological hallmarks of GB were lacking, but which had similarly dismal prognosis as GB.

The testis is an immunologically privileged site. Very little is known about the factors regulating formation of immune responses elicited by a neoplasm in the testis. We have studied the immune response of the host testis against experimental testicular teratoma in mouse by localizing adhesion molecules (CD106, CD54, CD49d/CD29, CD44, CD18, CD8 and CD4), cytokines (IL-2, IL-4, IL-6, IL-10 and IL-12), T-cell costimulators (CD80, CD86) and the lipid antigen presenting molecule CD1d in the testis of 129/SvJ mice with and without experimental testicular teratoma. The testicular teratomas were induced by grafting male gonadal ridges from 12-day-old 129/SvJ mouse fetuses into testes of adult mice from the same strain. The tumors cultured intratesticularly for 2, 3, 4 and 8 weeks (three animals per time point) were used for immunocytochemistry. CD1d was detected in Sertoli cells and in some degenerated tubules of the host testis surrounding the graft. In the tumor, CD1d was detected in glandular epithelia, smooth muscle and in thin fibers of neural origin. IL-2 was observed in some blood vessels of the host testis and of the tumor and in occasional cell infiltrates around these vessels. Some tubular structures of the tumor were also positive for IL-2. IL-6 was detected in Sertoli cells of the normal testis and in Sertoli cells and in solitaryinterstitial cells as well as in the walls of some blood vessels of the host testis. The reaction for IL-6 was more prominent in the tubules apparently damaged by the growing tumor. In the tumor IL-6 was detected in epithelial structures, muscle cells, in thin fibers of neural origin and in some blood vessels. IL-10 was detected in individual cells in the interstitium and in degenerating tubules of the host testis. In the tumor the epithelial structures were positive for IL-10. The interstitium of the host testis was positive for CD106 and the embryonic testicular cords in the graft were also positive, but the tumor was negative. CD44 and CD18 were observed in some blood vessels and in degenerated tubules of the host testis. In the tumor CD44 and CD18 were occasionally observed in cartilage and in epithelial structures. The results of the present study suggest that cytokine microenvironment in the testis containing neoplastic tissue promotes activation of humoral immune responses. In addition, as the damaged seminiferous tubules expressed increased amounts of two cytokines promoting humoral immune responses, IL-6 and IL-10, it is possible that also in other conditions with damage to the tubules, humoral immune responses predominate.

The records of the Finnish Cancer Registry from 1953 to 1994 were used to assess the risk of subsequent primary cancer among 14493 brain tumour patients. They had been treated with surgery only ( n =9804), radiotherapy ( n =4099), chemotherapy and radiotherapy ( n =493) or chemotherapy alone ( n =97). By the end of 1994, 403 subsequent primary cancers were registered in these patients, whilst the expected number based on national incidence was 332. The standardised incidence ratio (SIR) was 1.2 (95% confidence interval (CI) 1.1–1.3). A significant excess risk of tumours in the central nervous system (CNS) including meningeomas (SIR 2.6, 95% CI 1.7–3.8), non-Hodgkin's lymphoma (SIR 2.6, 95% CI 1.6–4.1) and skin melanoma (SIR 1.9, 95% CI 1.0–3.1) was observed. CNS tumours were observed in excess among patients treated with surgery alone (SIR 2.0, 95% CI 1.2–3.2) and with radiotherapy (SIR 5.1, 95% CI 2.5–9.4). In conclusion, brain tumours are associated with an increased risk of both CNS second tumours and non-CNS second cancers, especially non-Hodgkin's lymphoma and melanoma. A moderately increased risk of second tumours in the CNS was observed among brain tumour patients treated with surgery only and a larger excess among those treated with radiotherapy.

Information on biological day-to-day variation is needed for detecting within-subject changes over time. In this study the daytime changes and the biological day-to-day variation of serum testosterone, follitropin, lutropin and oestradiol-17β concentrations were investigated in 31 healthy males. To analyse daytime changes, blood specimens were taken at 0800 h, 1200 h, 1600 h and 2000 h during one day (n=31) and two days (n=8). The day-to-day variation was analysed from blood specimens collected at 0800 h on days 1 and 2 (n=31) and additionally on days 3, 4, 6 and 9 (n=8). The evaluation of the day-to-day variation was based on calculations of the within-subject (CVA+I) and between-subject (CVG) coefficients of variation. When the within-subject day-to-day variances were not too heterogeneous, they were used for the calculation of 95 % reference change limits. Serum testosterone and oestradiol-17βconcentrations showed a significant daytime variation; testosterone had higher serum concentrations at 0800 and 1200 h. A peak in the serum concentration of oestradiol-17β occurred at 1200 h with a decrease towards the evening. There were no clear daytime changes in the serum concentrations of follitropin or lutropin. For different analytes the reference change limits were: serum testosterone ± 32.0 %, serum follitropin ± 24.1 % and serum oestradiol-17β ± 38.3 %. The reference change limit was not calculated for serum lutropin, as a high degree of heterogeneity and individuality was found. The interpretation of the results of hormone measurements requires recognition of the biological daytime and day-to-day changes of hormones. The reference change limits determine what changes are significant when monitoring the patient.

Aims A novel non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, was entered into an open dose-escalation study. The objective of this study was to investigate the tolerability and efficiency of this new compound with assessment of the hormonal effects after study drug administration. Methods MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, after which ten subjects received the 300 mg dose and eight subjects the highest 600 mg dose of MPV-2213ad. Results Serum oestradiol levels were suppressed by 58–65% when MPV-2213ad was given at doses between 0.3 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone, LH and FSH were also observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfort. Conclusions MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity.

In this study, health- related quality of life (HRQoL) and its determinants were assessed in breast cancer patients undergoing postoperative adjuvant radiotherapy. The aim was to improve our understanding of patient’s situation at the end of adjuvant treatment, as the return to every day life approaches after breast cancer surgery and adjuvant chemo- and radiotherapy. Health- related quality of life was measured by the 15D instrument. Self-administered questionnaires were distributed to patients undergoing postoperative radiotherapy. Out of 389 consecutive breast cancer patients, 273 comprised the final study group. The results were compared to 15D results for an age-standardized sample of the female general population in Finland (n = 3,335). Determinants of HRQoL were assessed by a multivariate model. In patients

Purpose : The outcome of treatment of 98 over 70-year-old patients with nonHodgkin's lymphoma (NHL) is presented. Methods and Materials : Analysis of treatment outcome of non-Hodgkin's lymphoma patients age 70 years and more was carried thorugh with special emphasis on fatal complications occurring during treatment. Study patients mainly represented intermediate or high degree of malignancy. Results : Complete response rate (CR) was 54% after combination chemotherapy, 22% after single agent chemotherapy, and 56% after radiotherapy (used for local disease). The overall 5-year survival was 38% for all patients and 57% for CR patients. Stage had a significant effect on both the complete response rate and survival. Survival was also significantly influenced by the malignancy grade. Fifteen patients (15%) died during treatment, many of them had another predisposing disease and markers of poor prognosis. Conclusion : The evaluation of individual prognostic features of each old patient should be completed prior to treatment planning.

The risk of a second cancer among lung cancer patients was investigated using Finnish Cancer Registry data from 1953 to 1989. Among the 36 528 patients with a primary cancer of the lung, 504 new cancers were diagnosed six months or more after the diagnosis of lung cancer, yielding a standardized incidence ratio significantly lower than expected (SIR = 0.81). A significant excess of cancers of the larynx (SIR = 2.10) and urinary bladder (SIR = 1.35) was observed. Among lung cancer patients below 60 years of age, the risks of oesophageal cancer (SIR = 2.47) and kidney cancer (SIR = 2.48) were also significantly elevated. The risk of a second cancer among lung cancer patients increased with the length of follow-up, and there was some indication of an excess risk of oesophageal cancer and leukaemia among lung cancer patients subject to radiotherapy.

Lung cancer and mesothelioma are malignant tumors with generally dismal prognosis and therefore palliative pain treatment constitutes a challenge for the clinician.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.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.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.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.

The risk of smoking-related secondary cancers developing in bladder cancer patients was studied. The study population consisted of 10,014 bladder cancer patients reported to the Finnish Cancer Registry between 1953 and 1989. The risk of contracting a new primary cancer was estimated as a standardized incidence ratio, defined as the ratio of the observed and expected numbers of cases. Of 660 secondary cancers (6.6%) observed (standardized incidence ratio 0.96) 44% were considered to be smoking-related. Lung cancer was the most common secondary cancer (30% overall), and it occurred significantly more often than expected (standardized incidence ratio 1.31, 95% confidence interval 1.13 to 1.50). Also, larynx cancer among men (standardized incidence ratio 1.67, 95% confidence interval 0.95 to 2.79) and kidney cancer among women (standardized incidence ratio 3.55, 95% confidence interval 1.84 to 6.20) were found more often than expected. These excess risks were observed up to 20 years after diagnosis of bladder cancer. Therefore, bladder cancer patients experience an excess risk of smoking-related new tumors, which must be acknowledged during the initial evaluation and regular followup of such patients.

Adhesion to the intestinal mucosa is one of the main selection criteria for probiotic strains. The adhesion of commonly used probiotic strains to human intestinal tissue pieces and mucus was assessed. The strains tested adhered to the intestinal tissue at low levels and adhered to the intestinal mucus at higher levels.