Assessing the effectiveness of a national protected area network for carnivore conservation.

Protected areas (PAs) are essential to prevent further biodiversity loss yet their effectiveness varies largely with governance and external threats. Although methodological advances have permitted assessments of PA effectiveness in mitigating deforestation, we still lack similar studies for the impact of PAs on wildlife populations. Here we use an innovative combination of matching methods and hurdle-mixed models with a large-scale and long-term dataset for Finland's large carnivore species. We show that the national PA network does not support higher densities than non-protected habitat for 3 of the 4 species investigated. For some species, PA effects interact with region or time, i.e., wolverine densities decreased inside PAs over the study period and lynx densities increased inside eastern PAs. We support the application of matching methods in combination of additional analytical frameworks for deeper understanding of conservation impacts on wildlife populations. These methodological advances are crucial for preparing ambitious PA targets post-2020.

Feeling lucky: hierarchies of suffering and stories of endometrial cancer in a Danish context.

Illness stories are a prime analytical way of understanding patient perspectives on cancer. Nevertheless, limited studies have focused on stories of endometrial cancer. An ethnographic study including participant observation and interviews among 18 Danish women with endometrial cancer was conducted to examine prevalent stories and the ways the women responded to them. In this article, the analysis focuses on two exemplary cases, which present a line of issues related to the kinds of experiences that suffering includes. Findings illustrate that feelings of luck were central to the experience of being diagnosed, treated and cured, which was related to the way health professionals framed endometrial cancer as favourable through notions of curable/incurable, trivial and gentle/invasive and brutal, and aggressive/non-aggressive. Drawing upon the concept of a 'hierarchy of suffering', we exemplify how women tended to scale own experiences of suffering against others', leading some to believe they were not in a legitimate position to draw attention to themselves nor seek help and support, despite adverse physical, psychosocial effects. Thus, feelings of being lucky were intertwined with a sense of ambivalence. We conclude by discussing how suffering arises within a moral context, suggesting that the ways we speak of cancer may make some experiences unspeakable. This calls for increased clinical attention to more diverse narratives of cancer.

General practitioners' experience of using a questionnaire when assessing cancer patients' needs: a qualitative study.

BACKGROUND: International guidelines recommend health care professionals to use supportive tools like questionnaires when assessing cancer patients' needs. Little is known about GPs' perspectives and experience in this regard. OBJECTIVE: To examine how GPs experience to involve a short questionnaire, completed by patients' prior to a consultation, when addressing the patients' problems and needs. The aim is to contribute to the knowledge concerning the use of questionnaires as part of clinical cancer care in general practice. METHODS: Semi-structured individual interviews with 11 GPs in the Region of Southern Denmark purposefully sampled with regard to gender, years working in general practice and practice form. Interviews were analyzed using systematic text condensation. RESULTS: Most GPs found that using the questionnaire provided a supportive structure to the consultation. The questionnaire helped to bring forward issues of importance to the patients, which might otherwise not have been mentioned and enhanced a patient-centered approach. A few GPs found the use of the questionnaire to be restraining, detracting focus from the patient and impede usual practice. CONCLUSIONS: This study shows that using questionnaires may have the potential to improve clinical cancer care in general practice in relation to needs assessment of cancer patients and the results support current recommendations.

Informed choice about Down syndrome screening - effect of an eHealth tool: a randomized controlled trial.

INTRODUCTION: The aim of this study was to evaluate the effect of an eHealth intervention (interactive website) on pregnant women's ability to make an informed choice about Down syndrome screening. MATERIAL AND METHODS: The study was designed as a randomized controlled trial with allocation to an intervention group and a control group in a ratio of 1:1. Subsequent subgroup analysis was conducted. Participants were recruited from 5 August 2013 to 25 April 2014 at Odense University Hospital, Denmark. Inclusion criteria were: pregnant women aged ≥18 years who were invited to participate in Down syndrome screening. Exclusion criteria were: high risk of abortion, psycho-socially vulnerable women, late referral, inability to speak Danish and women declining to participate. The primary outcome was informed choice about Down syndrome screening. The Multidimensional Measure of Informed Choice was used to assess whether the choice was informed or uninformed. RESULTS: A total of 1150 participants were included in the study, of which 910 (79%) completed the questionnaire. Only a minority (30% of the women in the intervention group) actually used the website. There was no significant difference in the groups with respect to making an informed choice. The mean knowledge scores were significantly higher for those in the intervention group who used the intervention. CONCLUSIONS: An interactive website with information about Down syndrome screening had no direct effect on making an informed choice. However, the majority of the pregnant women who used the website were satisfied with the website and would recommend it to others.

How GPs implement clinical guidelines in everyday clinical practice--a qualitative interview study.

BACKGROUND: Clinical guidelines are considered to be essential for improving quality and safety of health care. However, interventions to promote implementation of guidelines have demonstrated only partial effectiveness and the reasons for this apparent failure are not yet fully understood. OBJECTIVE: To investigate how GPs implement clinical guidelines in everyday clinical practice and how implementation approaches differ between practices. METHODS: Individual semi-structured open-ended interviews with seven GPs who were purposefully sampled with regard to gender, age and practice form. Interviews were recorded, transcribed verbatim and then analysed using systematic text condensation. RESULTS: Analysis of the interviews revealed three different approaches to the implementation of guidelines in clinical practice. In some practices the GPs prioritized time and resources on collective implementation activities and organized their everyday practice to support these activities. In other practices GPs discussed guidelines collectively but left the application up to the individual GP whilst others again saw no need for discussion or collective activities depending entirely on the individual GP's decision on whether and how to manage implementation. CONCLUSION: Approaches to implementation of clinical guidelines vary substantially between practices. Supporting activities should take this into account.

Providing information about prenatal screening for Down syndrome: a systematic review.

BACKGROUND: In recent decades there have been advances in the options for prenatal screening. Screening programmes for Down syndrome are well established in many countries. It is important that pregnant women are well informed about the benefits and risks of screening. A variety of interventions has been introduced to support pregnant women in their choice of prenatal screening. OBJECTIVE: To summarize the literature using randomized controlled trials to compare the effects of different interventions to provide pregnant women with the information necessary to make an informed choice about screening for Down syndrome. DESIGN: Systematic review METHODS: A systematic search was performed using the PUBMED and EMBASE databases. The search terms included MeSH terms and free text and were combined by Boolean terms (AND, OR) with no restriction on language or time. MAIN OUTCOME MEASURES: Knowledge, informed choice, patient satisfaction, anxiety, depression, conflict and worries. RESULTS: Twelve studies were included in the review. All were characterised by having one or more interventions designed to improve the level of information about prenatal screening for Down syndrome. A positive effect on knowledge and satisfaction from the information received was found in the majority of the studies. The studies were heterogeneous with respect to interventions, methodology and outcome measurements. CONCLUSIONS: Interventions aimed at providing pregnant women with specific information about prenatal screening for Down syndrome can improve their ability to make an informed choice.

Training in motivational interviewing in obstetrics: a quantitative analytical tool.

OBJECTIVE: To examine whether a 3-day training course in motivational interviewing, which is an approach to helping people to change, could improve the communication skills of obstetric healthcare professionals in their interaction with obese pregnant women. DESIGN: Intervention study. SETTING: The Region of Southern Denmark. METHODS: Eleven obstetric healthcare professionals working with obese pregnant women underwent a 3-day course in motivational interviewing techniques and were assessed before and after training to measure the impact on their overall performance as well as the effect on specific behavioral techniques observed during interviews. FINDINGS: With a few exceptions, the participants changed their behavior appropriate to the motivational interviewing technique. The participants made more interventions towards the principles of motivational interviewing (adherent and nonadherent interventions). Furthermore, the participants asked fewer closed and more open questions before training in motivational interview. In the assessment of proficiency and competency, most of the participants scored higher after the training in motivational interviewing. CONCLUSIONS: Training in motivational interviewing improves healthcare professionals' proficiency and competency when communicating with obese pregnant women, albeit that the effect was not universal.

Climatic, ecological and socioeconomic factors as predictors of Sindbis virus infections in Finland.

Mosquito-borne Sindbis virus (SINV) causes rash-arthritis syndrome in Finland. Major outbreaks with approximately 7-year cycles have caused substantial burden of illness. Forest dwelling grouse are suspected to be amplifying hosts, with the infection transmitted to humans by mosquito bites. SINV infection surveillance data for 1984­2010 were used to create a negative binomial hurdle model, with seasonality, long-term cycles, climatic, ecological and socioeconomic variables. Climatic factors during early summer and amount of snow in April described the occurrence and incidence of SINV infections. Regulated water shore and hatch-year black grouse density described the occurrence, while population working in agriculture, agricultural land(negative) and income (negative) described the incidence of the disease. The prediction for 2009 was 85 cases (95% prediction interval 2-1187), while the actual occurrence was 106. We identified novel and known risk factors. The prevention of SINV infections in regulated water areas by infected mosquito populations should be targeted.

Is there any interaction between domestic radon exposure and air pollution from traffic in relation to childhood leukemia risk?

BACKGROUND: In a recent population-based case-control study using 2,400 cases of childhood cancer, we found a statistically significant association between residential radon and acute lymphoblastic leukemia risk. HYPOTHESIS: Traffic exhaust in the air enhances the risk association between radon and childhood leukemia. METHODS: We included 985 cases of childhood leukemia and 1,969 control children. We used validated models to calculate residential radon and street NO(x) concentrations for each home. Conditional logistic regression analyses were used to analyze the effect of radon on childhood leukemia risk within different strata of air pollution and traffic density. RESULTS: The relative risk for childhood leukemia in association with a 10(3) Bq/m(3)-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NO(x) and 1.23 (0.79, 1.91) for those exposed to low levels of NO(x) (p(interaction,) 0.17). Analyses for different morphological subtypes of leukemia and within different strata of traffic density showed a non-significant pattern of stronger associations between radon and childhood leukemia within strata of higher traffic density at the street address. INTERPRETATION: Air pollution from traffic may enhance the effect of radon on the risk of childhood leukemia. The observed tendency may also be attributed to chance.

Top predators, mesopredators and their prey: interference ecosystems along bioclimatic productivity gradients.

1. The Mesopredator Release Hypothesis (MRH) suggests that top predator suppression of mesopredators is a key ecosystem function with cascading impacts on herbivore prey, but it remains to be shown that this top-down cascade impacts the large-scale structure of ecosystems. 2. The Exploitation Ecosystems Hypothesis (EEH) predicts that regional ecosystem structures are determined by top-down exploitation and bottom-up productivity. In contrast to MRH, EEH assumes that interference among predators has a negligible impact on the structure of ecosystems with three trophic levels. 3. We use the recolonization of a top predator in a three-level boreal ecosystem as a natural experiment to test if large-scale biomass distributions and population trends support MRH. Inspired by EEH, we also test if top-down interference and bottom-up productivity impact regional ecosystem structures. 4. We use data from the Finnish Wildlife Triangle Scheme which has monitored top predator (lynx, Lynx lynx), mesopredator (red fox, Vulpes vulpes) and prey (mountain hare, Lepus timidus) abundance for 17 years in a 200 000 km(2) study area which covers a distinct productivity gradient. 5. Fox biomass was lower than expected from productivity where lynx biomass was high, whilst hare biomass was lower than expected from productivity where fox biomass was high. Hence, where interference controlled fox abundance, lynx had an indirect positive impact on hare abundance as predicted by MRH. The rates of change indicated that lynx expansion gradually suppressed fox biomass. 6. Lynx status caused shifts between ecosystem structures. In the 'interference ecosystem', lynx and hare biomass increased with productivity whilst fox biomass did not. In the 'mesopredator release ecosystem', fox biomass increased with productivity but hare biomass did not. Thus, biomass controlled top-down did not respond to changes in productivity. This fulfils a critical prediction of EEH. 7. We conclude that the cascade involving top predators, mesopredators and their prey can determine large-scale biomass distribution patterns and regional ecosystem structures. Hence, interference within trophic levels has to be taken into account to understand how terrestrial ecosystem structures are shaped.

Domestic radon and childhood cancer in Denmark.

BACKGROUND: Higher incidence rates of childhood cancer and particularly leukemia have been observed in regions with higher radon levels, but case-control studies have given inconsistent results. We tested the hypothesis that domestic radon exposure increases the risk for childhood cancer. METHODS: We identified 2400 incident cases of leukemia, central nervous system tumor, and malignant lymphoma diagnosed in children between 1968 and 1994 in the Danish Cancer Registry. Control children (n = 6697) were selected from the Danish Central Population Registry. Radon levels in residences of children and the cumulated exposure of each child were calculated as the product of exposure level and time, for each address occupied during childhood. RESULTS: Cumulative radon exposure was associated with risk for acute lymphoblastic leukemia (ALL), with rate ratios of 1.21 (95% confidence interval = 0.98-1.49) for levels of 0.26 to 0.89 x 10(3) Bq/m3-years and 1.63 (1.05-2.53) for exposure to >0.89 x 10(3) Bq/m3-years, when compared with <0.26 x 10(3) Bq/m3-years. A linear dose-response analysis showed a 56% increase in the rate of ALL per 10(3) Bq/m3-years increase in exposure. The association with ALL persisted in sensitivity analyses and after adjustment for potential confounders. No association was found with the other types of childhood cancer. CONCLUSIONS: This study suggests that domestic radon exposure increases the risk for ALL during childhood but not for other childhood cancers.

No genetic evidence of sex-biased dispersal in a lekking bird, the capercaillie (Tetrao urogallus).

Sex-biased dispersal is often connected to the mating behaviour of the species. Even if patterns of natal dispersal are reasonably well documented for monogamous birds, only a few data are available for polygynous and especially lekking species. We investigated the dispersal of the capercaillie (Tetrao urogallus) by examining sex-specific gene flow among the leks. Genetic information was extracted using nuclear and mitochondrial molecular markers for sexed faecal samples and analysed by novel Bayesian statistical methods. Contrary to the traditional view that the males are highly philopatric and female is the dispersing sex, we found roughly equivalent gross and effective dispersal of the sexes. The level of polygamy has a strong influence on the effective population size and on the effective dispersal. The results do not support the theories that dispersal evolves solely as a result of resource competition or other advantages to males obtained through kin selection in lekking species.

Predation as a landscape effect: the trading off by prey species between predation risks and protection benefits.

1. Predators impose costs on their prey but may also provide benefits such as protection against other (e.g. nest) predators. The optimal breeding location in relation to the distance from a nesting raptor varies so as to minimize the sum of costs of adult and nest predation. We provide a conceptual model to account for variation in the relative predation risks and derive qualitative predictions for how different prey species should respond to the distance from goshawk Accipiter gentilis nests. 2. We test the model predictions using a comprehensive collection of data from northern Finland and central Norway. First, we carried out a series of experiments with artificial bird nests to test if goshawks may provide protection against nest predation. Second, we conducted standard bird censuses and nest-box experiments to detect how the density or territory occupancy of several prey species varies with distance from the nearest goshawk nest. 3. Nest predation rate increased with distance from goshawk nest indicating that goshawks may provide protection for birds' nests against nest predation. Abundance (or probability of presence) of the main prey species of goshawks peaked at intermediate distances from goshawk nests, reflecting the trade-off. The abundance of small songbird species decreased with distance from goshawk nests. The goshawk poses little risk to small songbirds and they may benefit from goshawk proximity in protection against nest predation. Finally, no pattern with distance in pied flycatcher territory (nest box) occupation rate or the onset of egg-laying was detected. This is expected, as flycatchers neither suffer from marked nest predation risk nor are favoured goshawk prey. 4. Our results suggest that territory location in relation to the nest of a predator is a trade-off situation where adult birds weigh the risk of themselves being predated against the benefits accrued from increased nest survival. Prey species appear able to detect and measure alternative predation risks, and respond adaptively. From the prey perspective, the landscape is a mosaic of habitat patches the quality of which varies according to structural and floristic features, but also to the spatial distribution of predators.

Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial.

BACKGROUND: Breast-conserving therapy (BCT) has been shown to be as effective as mastectomy in the treatment of tumors 2 cm or smaller. However, evidence of its efficacy, over the long term, in patients with tumors larger than 2 cm is limited. From May 1980 to May 1986, the European Organization for Research and Treatment of Cancer carried out a randomized, multicenter trial comparing BCT with modified radical mastectomy for patients with tumors up to 5 cm. In this analysis, we investigated whether the treatments resulted in different overall survival, time to distant metastasis, or time to locoregional recurrence. METHODS: Of 868 eligible breast cancer patients randomly assigned to the BCT arm or to the modified radical mastectomy arm, 80% had a tumor of 2.1-5 cm. BCT comprised lumpectomy with an attempted margin of 1 cm of healthy tissue and complete axillary clearance, followed by radiotherapy to the breast and a supplementary dose to the tumor bed. The median follow-up was 13.4 years. All P values are two-sided. RESULTS: At 10 years, there was no difference between the two groups in overall survival (66% for the mastectomy patients and 65% for the BCT patients; P =.11) or in their distant metastasis-free rates (66% for the mastectomy patients and 61% for the BCT patients; P =.24). The rate of locoregional recurrence (occurring before or at the same time as distant metastasis) at 10 years did show a statistically significant difference (12% of the mastectomy and 20% of the BCT patients; P =. 01). CONCLUSIONS: BCT and mastectomy demonstrate similar survival rates in a trial in which the great majority of the patients had stage II breast cancer.

Value of estrogenic recruitment before chemotherapy: first randomized trial in primary breast cancer.

PURPOSE: Several preclinical studies showed that short-term pretreatment of breast cancer cells with estrogens can increase the antitumor efficacy of different cytotoxic drugs. Some early clinical studies in patients with advanced breast cancer did seem to support these findings. Therefore, the efficacy of estrogenic recruitment followed by chemotherapy was compared with that of chemotherapy alone in a randomized phase III study in women with lymph node-positive primary breast cancer. PATIENTS AND METHODS: Three hundred twenty-eight patients with stage II/IIIA breast cancer who were younger than 66 years of age were randomly allocated to chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) or FAC plus pretreatment with ethinyl estradiol (EE(2)). FAC (500, 50, and 500 mg/m(2), respectively) was administered intravenously once every 4 weeks for four cycles. EE(2) (0.5 mg) was administered orally, both 24 hours and immediately preceding FAC chemotherapy. RESULTS: Patient and tumor characteristics and chemotherapy dosages were comparable in both treatment groups. Of 318 assessable patients, with a median follow-up of 6.8 years, 177 patients had a relapse and 127 died. No significant differences were observed between the two treatment groups with respect to relapse-free, local recurrence-free, and overall survival according to univariate and multivariate analyses adjusted for age, menopausal status, tumor size, grade, number of positive nodes, and steroid-receptor status. The power for the detection of an increase of 50% in the median relapse-free survival was 80%. CONCLUSION: Estrogenic recruitment of breast cancer cells before FAC chemotherapy did not influence the efficacy of adjuvant chemotherapy in stage II/IIIA breast cancer patients after a follow-up of 6.8 years.

Reirradiation combined with hyperthermia in recurrent breast cancer results in a worthwhile local palliation.

Both experimental and clinical research have shown that hyperthermia (HT) gives valuable additional effects when applied in combination with radiotherapy (RT). The purpose of this study was evaluation of results in patients with recurrent breast cancer, treated at the Daniel den Hoed Cancer Center (DHCC) with reirradiation (re-RT; eight fractions of 4 Gy twice weekly) combined with HT. All 134 patients for whom such treatment was planned were included in the analysis. The complete response rate in 119 patients with macroscopic tumour was 71%. Including the 15 patients with microscopic disease, the local control rate was 73%. The median duration of local control was 32 months, and toxicity was acceptable. The complete response (CR) rate was higher, and the toxicity was less with the later developed 433-MHz HT technique compared with the 2450-MHz technique used initially. With this relatively well-tolerated treatment, palliation by local tumour control of a worthwhile duration is achieved in the majority of patients. The technique used for hyperthermia appeared to influence the achieved results. The value of HT in addition to this re-RT schedule has been confirmed by a prospective randomized trial in a similar patient group. In The Netherlands, this combined treatment is offered as standard to patients with breast cancer recurring in previously irradiated areas.

Creativity: the key to breakthrough changes, how teaming can harness collective knowledge.

Our nation's industries do not want for concepts, philosophies or ideas to improve effectiveness. Just-in-Time, continuous improvement, re-engineering, world-class manufacturing, time compression, manufacturing excellence, total quality control, and theory of constraints are examples of approaches to improving our businesses. All have merit and are, to some degree, related.

Abundances of red fox and pine marten in relation to the composition of boreal forest landscapes.

The effects of human-caused fragmentation of boreal forest on the abundance of red fox Vulpes vulpes L. and pine marten Martes martes L. were studied by combining the Finnish wildlife-triangle snow-track data (1990-94) with land-use and forest resources data employing the GIS. Two study areas (each 45 000 km(2) ) located in northern and southern Finland were selected for the investigation. The extent of landscape that best explained predator abundance (tracks per 10 km 24 h(-1) ) was the same (about 100 km(2) ) in both species and study areas. The decreasing proportion of older forest and the increasing proportions of young forest and agricultural land in the landscape positively affected track density of red fox. The relationship between agricultural land and fox abundance, however, was characterized by a convex curve peaking at 20-30% of agricultural land. With the habitat classification used, landscape composition explained 26% and 11% of the spatial variation in fox abundance in the northern and southern study area, respectively. The relationship between landscape composition and pine marten abundance was not as clear as in that of red fox. Landscape composition explained 10% and 6% of spatial variation in pine marten abundance in the northern and southern study area, respectively. In both areas a positive impact occurred with the increasing proposition of young forest in the landscape, but in the northern area the negative effect of increasing proportion of agricultural land was dominant. The abundances of red fox and pine marten were not negatively correlated, indicating that competition or intraguild predation by red fox do not determine abundance of pine marten on a landscape scale. A general increase in predation pressure by generalist predators in fragmented forest landscapes has been an intensively discussed conservation problem during recent years. We conclude that the red fox is a species potentially able to cause elevated predation pressure in boreal landscapes fragmented by human activities, but that the evidence against the pine marten is weaker.

Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192.

PURPOSE: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. METHODS AND MATERIALS: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. RESULTS: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient. CONCLUSIONS: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare.

A randomized study of high-dose split course radiotherapy preceded by high-dose chemotherapy versus high-dose radiotherapy only in locally advanced non-small-cell lung cancer. An EORTC Lung Cancer Cooperative Group trial.

BACKGROUND: The treatment results of radiotherapy in stage III non-small-cell lung cancer are very poor. Several phase II studies showed that neoadjuvant chemotherapy followed by radiotherapy was feasible in this patient group and suggested that treatment outcome might improve. A randomized phase II study was performed addressing the response rate and morbidity of high-dose split course radiotherapy (RT) versus the same radiotherapy preceded by high-dose chemotherapy (CT) in patients with stage III non-small-cell lung cancer. PATIENTS AND METHODS: Seventy eligible patients were randomized in this study. CT consisted of cisplatin 100 mg/m2 days 1 and 22, and vindesine 3 mg/m2 on days 1, 8, 22 and 29. Radiotherapy started on day 43 in the combined arm and immediately in the RT-only arm. The primary tumour and the regional nodes were treated by 30 Gy/10 fractions/2 weeks and after the split by a second course of 25 Gy/10 fractions/2 weeks. In the combined arm a third CT cycle was planned during the split between RT courses. RESULTS: In the CT + RT arm 34 patients were evaluable for response and toxicity and 30 patients in the RT only arm. After completion of treatment 7 patients had a complete response (2 in the CT plus RT arm, 5 in the RT alone arm) and 26 patients a partial response (13 in the CT plus RT arm, 13 in the RT alone arm) for an overall response rate of 52% (95% CI 39%-65%). Acute toxicity was worse in the combined treatment arm with grade 4 leucocytopenia in 8 patients and thrombocytopenia grade 4 in one patient. Three patients had reversible renal toxicity grade 2. There was one toxic death in the RT plus CT arm. There was no enhancement of acute or late radiation pulmonary or oesophageal toxicity. Time to progressive disease (median 30 vs. 35 weeks) and overall survival time (median 12 months) were equal in both treatment arms. CONCLUSION: High-dose radiotherapy preceded by high-dose chemotherapy was more toxic than radiotherapy alone and did not result in this study in any benefit in terms of response rate, time to progressive disease and overall survival.