A medication diary-book for pediatric patients with acute lymphoblastic leukemia in Indonesia.

BACKGROUND: Event-free survival of pediatric patients with acute lymphoblastic leukemia (ALL) in Yogyakarta, Indonesia was low (20%). The aim of the study was to evaluate the effectiveness of using a medication diary-book on the treatment outcome of childhood ALL. PROCEDURE: A randomized study was conducted with 109 pediatric patients with ALL in a pediatric oncology center in Yogyakarta, Indonesia. Both intervention and control groups received a structured parental education program and donated chemotherapy. The intervention group received a medication diary-book to remind parents and families to take oral chemotherapy and present for scheduled appointments or admissions. Event-free survival estimate (EFS) at 3 years was assessed. RESULTS: Among pediatric patients with ALL with highly educated mothers (senior high school or higher), the EFS-estimate at 3 years of the intervention group was significantly higher than the EFS-estimate at 3 years of the control group (62% vs. 29%, P = 0.04). Among pediatric patients with ALL with low-educated mothers, no significant difference was found in the EFS-estimates at 3 years between the intervention and control group (26% vs. 18%, P = 0.86). CONCLUSIONS: We conclude that a medication diary-book might be useful to improve the survival of pediatric patients with ALL in resource-limited settings, particularly in patients with highly educated mothers.

Chemotherapy-induced nausea and vomiting in daily clinical practice: a community hospital-based study.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. This study investigated: (1) the impact of CINV on patients' health-related quality of life (HRQL) in daily clinical practice; (2) the association between patient characteristics and type of antiemetics and CINV; and (3) the role of CINV in physicians' decisions to modify antiemetic treatment. PATIENTS AND METHODS: This prospective, multicenter study was conducted in nine general hospitals in the Netherlands. During three consecutive chemotherapy cycles, patients used a diary to record episodes of nausea, vomiting and antiemetic use. For each cycle, these ratings were made 1 day prior to and 7 days after having received chemotherapy. The influence of CINV on patients' HRQL was evaluated with the Functional Living Index-Emesis (FLIE) questionnaire at day 6 of each treatment cycle. (Changes in) antiemetic use were recorded by the treating nurse. Patient inclusion took place between May 2005 and May 2007. RESULTS: Two hundred seventy-seven patients were enrolled in the study. Acute and delayed nausea during the first treatment cycle was reported by 39% and 68% of the patients, respectively. The comparable figures for acute and delayed vomiting were 12% and 23%. During the first and subsequent treatment cycle, approximately one-third of the patients indicated that CINV had a substantial impact on their daily lives. Female patients and younger patients reported significantly more CINV than male and older patients. At all treatment cycles, patients receiving treatment with moderately emetogenic chemotherapy, containing anthracycline, reported more acute nausea than patients receiving highly emetogenic chemotherapy. Acute vomiting was associated significantly with change in (i.e., additional) antiemetic treatment. Delayed CINV did not influence antiemetic treatment. CONCLUSION: CINV continues to be a problem that adversely affects the daily lives of patients. CINV is worse in women and in younger patients. In daily clinical practice, acute CINV, but not delayed CINV, results in changes in antiemetic treatment. In view of the effects of not only acute, but also delayed CINV on daily life, more attention should be paid to adjustment of antiemetic treatment to cover CINV complaints, later during the chemotherapy cycle.

Comparing higher order models for the EORTC QLQ-C30.

PURPOSE: To investigate the statistical fit of alternative higher order models for summarizing the health-related quality of life profile generated by the EORTC QLQ-C30 questionnaire. METHODS: A 50% random sample was drawn from a dataset of more than 9,000 pre-treatment QLQ-C30 v 3.0 questionnaires completed by cancer patients from 48 countries, differing in primary tumor site and disease stage. Building on a "standard" 14-dimensional QLQ-C30 model, confirmatory factor analysis was used to compare 6 higher order models, including a 1-dimensional (1D) model, a 2D "symptom burden and function" model, two 2D "mental/physical" models, and two models with a "formative" (or "causal") formulation of "symptom burden," and "function." RESULTS: All of the models considered had at least an "adequate" fit to the data: the less restricted the model, the better the fit. The RMSEA fit indices for the various models ranged from 0.042 to 0.061, CFI's 0.90-0.96, and TLI's from 0.96 to 0.98. All chi-square tests were significant. One of the Physical/Mental models had fit indices superior to the other models considered. CONCLUSIONS: The Physical/Mental health model had the best fit of the higher order models considered, and enjoys empirical and theoretical support in comparable instruments and applications.

Treatment of vulvar intraepithelial neoplasia with topical imiquimod: seven years median follow-up of a randomized clinical trial.

OBJECTIVE: Recently we reported on the efficacy of imiquimod for treating vulvar intraepithelial neoplasia (VIN) in a placebo-controlled, double-blinded randomized clinical trial (RCT). Four weeks after treatment, a complete response was observed in 35% of patients and a partial response in 46%. All complete responders remained disease-free at 12 months follow-up. In the current investigations, we assessed long-term follow-up at least 5 years after the initial RCT. METHODS: Twenty-four of 26 imiquimod-treated patients who had participated in the initial RCT were seen for follow-up. Primary endpoint was durability of clinical response to imiquimod assessed by naked eye vulvar examination and histology. Long-term clinical response was correlated to lesion size before start of the initial RCT. Secondary endpoints were mental health, global quality of life, body image and sexual function in relation with long-term clinical response. RESULTS: Median follow-up period was 7.2 years (range 5.6-8.3 years). VIN recurred in one of nine complete responders. Of the initial partial responders, two became disease-free after additional imiquimod treatment. In the other partial responders, VIN recurred at least once after the initial RCT. In long-term complete responders, lesion size at study entry was smaller and these patients had a significantly better global quality of life at follow-up than patients with residual disease and/or recurrence after imiquimod treatment. CONCLUSIONS: In case of a complete response, imiquimod is effective in the long-term. Furthermore, patients with a long-term complete response had a significantly better global quality of life than patients who recurred after imiquimod treatment.

Psychological distress and quality of life of partners of individuals with familial adenomatous polyposis.

OBJECTIVE: Familial adenomatous polyposis (FAP) is a genetic condition characterized by the development of multiple adenomas in the colorectum that could lead to colorectal cancer. Our aim was to assess levels and predictors of psychological distress and quality of life (QOL) among partners of FAP-patients. METHODS: A nationwide, cross-sectional survey using validated self-report questionnaires assessing psychological distress and QOL. RESULTS: One hundred and twenty-nine partners completed the questionnaire (84% response rate), 30% of whom reported moderate-to-severe levels of distress. The partners' distress was associated significantly with the patients' distress, having children, and feelings of guilt. Fifty-seven percent of the partners with moderate-to-severe distress levels had received professional psychosocial support. Partners did not differ significantly from the general population in QOL. However, 9-21% reported that FAP had affected their work, leisure time activities, and relationships. CONCLUSIONS: Clinicians should be particularly alert for heightened distress levels in partners of patients who are themselves distressed, and among those with children.

Predictors of neuropsychological improvement following cognitive rehabilitation in patients with gliomas.

This study investigated the specific patient factors that predict responsiveness to a cognitive rehabilitation program. The program has previously been demonstrated to be successful at the group level in patients with gliomas, but it is unclear which patient characteristics optimized the effect of the intervention at the individual level. Four categories of possible predictors of improvement were selected for evaluation: sociodemographic and clinical variables, self-reported cognitive symptoms, and objective neuropsychological test performance. Hierarchical logistic regression analyses were conducted, beginning with the most accessible (sociodemographic) variables and ending with the most difficult (baseline neuropsychological) to identify in clinical practice. Nearly 60% of the participants of the intervention were classified as reliably improved. Reliable improvement was predicted by age (p = .003) and education (p = .011). Additional results suggested that younger patients were more likely to benefit specifically from the cognitive rehabilitation program (p = .001), and that higher education was also associated with improvement in the control group (p = .024). The findings are discussed in light of brain reserve theory. A practical implication is that cognitive rehabilitation programs should take the patients' age into account and, if possible, adapt programs to increase the likelihood of improvement among older participants.

Cancer-related fatigue: clinical practice versus practice guidelines.

PURPOSE: This study investigated adherence to treatment guidelines on cancer-related anaemia and fatigue (CRA/CRF) and factors influencing the choice of intervention. METHODS: In this prospective, observational study, 136 cancer patients being treated with chemotherapy in a large community hospital completed a questionnaire at consecutive outpatient visits assessing fatigue (the Functional Assessment of Chronic Illness Therapy-Fatigue) and fatigue-related counselling and advice received. Data on administration of chemotherapy and use of epoetin or blood transfusions were abstracted from the medical records. RESULTS: Fifty-three percent of patients with severe anaemia (Hb < 10 g/dl) and 6% of patients with less severe anaemia (Hb levels 10-12 g/dl) received treatment (epoetin and/or blood transfusions). Half of the patients with less severe anaemia reported clinically relevant levels of fatigue. More than 50% of all patients received fatigue-related counselling, primarily at the start of chemotherapy. Most counselling was directed at energy conservation. Fatigue was not associated significantly with the use of epoetin or blood transfusion. Patients receiving palliative treatment (17%), male patients (16%) and patients with a low Hb level (<6.2 g/dl, 38%) were treated significantly more often with epoetin. CONCLUSIONS: In daily clinical practice, guidelines concerning the use of epoetin or blood transfusion in severe CRA are adhered to in about half of the cases. In patients with less severe anaemia, the level of fatigue did not play a significant role in the use of epoetin. According to current guidelines, counselling on CRF should be directed primarily at activity enhancement. However, only a minority of patients receive such counselling.

The impact of different definitions and reference groups on the prevalence of cognitive impairment: a study in postmenopausal breast cancer patients before the start of adjuvant systemic therapy.

OBJECTIVE: Several prospective studies into the effects of adjuvant systemic therapy on cognitive functioning suggest that a proportion of breast cancer patients show cognitive deficits already before the start of systemic therapy. Owing to, among others, methodological inconsistency, studies report different rates of this pre-treatment cognitive impairment. We examined the impact of four different criteria of cognitive impairment and two types of reference groups (a study-specific healthy reference group versus published normative data) on the prevalence of cognitive impairment. METHODS: Two hundred and five postmenopausal breast cancer patients underwent a battery of neuropsychological tests before the start of endocrine therapy, 124 healthy subjects underwent the same tests. Proportions of cognitive impaired patients were calculated for each of four criteria for cognitive impairment, using (1) study-specific healthy controls and (2) published norms of healthy controls as reference groups. RESULTS: The prevalence of cognitive impairment varied greatly with the strictness of the criterion, as expected, but also was dependent on the reference group used. Cognitive impairment, relative to published norms, ranged from 1% for the strictest to 36.6% for the less strict criterion, cognitive impairment relative to study-specific healthy controls, ranged from 13.7 to 45.4% for the same criteria. CONCLUSION: This study highlights contrasting proportions of cognitive impairment by using different criteria for cognitive impairment and different reference groups. (Dis)advantages of the methods using a criterion for cognitive impairment, and of the use of published norms versus a study-specific reference group are discussed.

Psychological distress and use of psychosocial support in familial adenomatous polyposis.

OBJECTIVE: Familial adenomatous polyposis (FAP) is characterized by multiple adenomas in the colorectum with a high risk to develop colorectal cancer. It is unclear whether individuals at risk of FAP experience distress due to this potentially life-threatening disease. This nationwide study assessed: (1) the prevalence of psychological distress; and (2) the need for and use of specialized professional psychosocial support. METHODS: In this cross-sectional study, all individuals from families at high risk for FAP registered at the Netherlands Foundation for the Detection of Hereditary Tumours were invited to complete a questionnaire assessing, among other issues, generalized, cancer-specific and FAP-specific distress. RESULTS: In total, 525 individuals completed the questionnaire. Approximately 20% of the respondents had moderate to severe levels of FAP-specific distress. Levels of generalized distress were comparable to the general Dutch population. Significantly more individuals with a FAP diagnosis had frequent cancer worries than those at risk of FAP or non-carriers (p=0.02). Distress levels were more strongly associated with psychosocial variables (e.g. perceived cancer risk), than with sociodemographic or clinical variables. Up to 43% of the variance in distress could be explained by all variables combined. Of those moderately to severely distressed, 26% had received specialized professional psychosocial support, while 30% of those did not receive the support they wanted. CONCLUSIONS: A substantial minority of individuals reported moderate to severe distress levels associated with FAP. However, only one-third of those received specialized professional psychosocial support. We recommend the use of a screening questionnaire to identify individuals in need of such support.

Effects of mode of administration (MOA) on the measurement properties of the EORTC QLQ-C30: a randomized study.

BACKGROUND: While modern electronic data collection methods (e.g., computer touch-screen or web-based) hold much promise, most current studies continue to make use of more traditional data collection techniques, including paper-and-pencil administration and telephone interviews. The present randomized trial investigated the measurement properties of the EORTC QLQ-C30 under three different modes of administration (MOA's). METHODS: A heterogeneous sample of 314 cancer patients undergoing treatment at a specialized treatment center in Amsterdam were randomized to one of three MOA's for the QLQ-C30: paper-and-pencil at home via the mail, telephone interview, and paper-and-pencil at the hospital clinic. Group differences in internal consistency reliabilities (Cronbach's alpha coefficient) for the scale scores were compared. Differences in mean scale scores were also compared by means of ANOVA, with adjustment for potential confounders. RESULTS: Only one statistically significant, yet minor, difference in Cronbach's alpha between the MOA groups was observed for the Role Functioning scale (all 3 alphas >0.80). Significant differences in group means -after adjustment- were found for the Emotional Functioning (EF) scale. Patients completing the written questionnaire at home had significantly lower levels of EF as compared to those interviewed via the telephone; EF scores of those completing the questionnaire at the clinic fell in-between those of the other two groups. These differences, however, were small in magnitude. CONCLUSIONS: MOA had little effect on the reliability or the mean scores of the EORTC QLQ-C30, with the possible exception of the EF scale.

Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study.

BACKGROUND: Previous studies have indicated that a subset of cancer patients treated with chemotherapy show cognitive deficits and/or experience cognitive complaints, whereas literature about the influence of hormonal therapies on cognition is sparse. Because of the accumulating knowledge about the importance of estrogen for cognitive functioning, there is growing concern about adjuvant hormonal therapy for breast cancer (BC) affecting cognition. We examined the cognitive functioning of postmenopausal BC patients who were, following doxorubicin/cyclophosphamide (AC) chemotherapy, randomized to tamoxifen or exemestane, and compared their performance with that of non-cancer controls. MATERIALS AND METHODS: Thirty BC patients using tamoxifen and 50 patients using exemestane underwent interviews, questionnaires and cognitive tests, on average two years after completion of AC chemotherapy. Forty eight healthy controls were tested with similar measures. RESULTS: Memory complaints were reported by 28% of AC/tamoxifen users, 24% of AC/exemestane users and 6% of healthy controls (p=0.02). Cognitive testing revealed no statistically significant differences between tamoxifen and exemestane users, but suggested that tamoxifen use is possibly related to worse verbal functioning, while exemestane use is possibly related to slower manual motor speed. Both patient groups performed significantly worse than healthy controls on verbal fluency and information processing speed. DISCUSSION: Our findings show that sequential treatment of AC-chemotherapy and hormonal therapy in postmenopausal, primary BC is associated with lower test scores for certain cognitive functions, and provide indications for possibly distinctive associations for different types of hormonal treatment. Future research with larger groups is recommended to obtain a more definite picture.

Health-care providers' compliance with childhood acute lymphoblastic leukemia protocol in Indonesia.

BACKGROUND: Non-compliance with childhood acute lymphoblastic leukemia (ALL) protocol is an important determinant of poor treatment outcome. Non-compliance with protocol may not only concern parents or patients, but may also concern health-care providers (HCP). Our study examines the accuracy of leukemia risk classification and attitude of HCP toward protocol compliance in Indonesia. PROCEDURE: A combined retrospective study of medical records (MR) and a cross-sectional questionnaire study with HCP were conducted. Accurate ALL risk classification in MR was assessed. HCP' knowledge of risk classification and their attitude toward protocol compliance were examined. RESULTS: A total of 164 MR patients with ALL were assessed and 97 HCP were interviewed. The protocol criteria for high-risk (HR) were not complete in 82 MR (50%). Of 97 HCP, 95% did not mention all five protocol criteria for HR. Both in the MR as well as in the questionnaires lymphoblast count on day 8 of chemotherapy, as early response to treatment, was the most frequently missed item (missing in 35% of MR and 85% of questionnaires). Only 14% of respondents actually checked with parents whether they administered the prescribed medicines. CONCLUSIONS: Our study shows that HCP should improve their knowledge and assessment of childhood ALL risk classification, especially lymphoblast count on day 8 of chemotherapy. Proper risk classification and subsequent correct treatment may enable more children to be cured of leukemia.

Attitude of health-care providers toward childhood leukemia patients with different socio-economic status.

BACKGROUND: Treatment results differ significantly between poor and prosperous children with leukemia in Indonesia. The objective of this study was to determine whether parental socio-economic status influences beliefs, attitude, and behavior of health-care providers (hcp) treating childhood leukemia in Indonesia. PROCEDURE: A self-administered semi-structured questionnaire was filled in by 102 hcp (69 doctors, 28 nurses, 2 psychologists, 2 hematology technicians, 1 administrator). RESULTS: Most hcp (98%) asked parents about their financial situation. The decision to start treatment was influenced by parental socio-economic status (86%), motivation of parents (80%), and motivation of doctors (76%). Health-care providers stated that prosperous patients comply better with treatment (64%), doctors comply better with treatment for the prosperous (53%), most patients cannot afford to complete treatment (58%), less extensive explanations are given toward poor families (60%), and communication is impeded by differences in status (67%). When dealing with prosperous families a minority of hcp stated that they pay more attention (27%), work with greater accuracy (24%), take more interest (23%), and devote more time per visit (22%). Most hcp denied differences in the quality of medical care (93%) and the chances of cure (58%) between poor and prosperous patients. CONCLUSIONS: Beliefs, attitude, and behavior of hcp toward poor versus prosperous patients appeared to differ. These differences may contribute to the immense drop-out rate and slight chances of survival among poor patients with leukemia in developing countries.

Health-related quality of life assessment in Indonesian childhood acute lymphoblastic leukemia.

BACKGROUND: Most studies on Health-related Quality of Life (HRQOL) in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL) patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL. METHODS: After cultural linguistic validation, a cross-sectional study of HRQOL was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scale and the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module. RESULTS: Ninety-eight guardians and 55 patients participated. The internal consistency of both scales ranged from 0.57 to 0.92. HRQOL of Indonesian patients was comparable with those in developed countries. There were moderate to good correlations between self-reports and proxy-reports, however guardians tended to report worse HRQOL than patients. Children of the 2-5 year-group significantly had more problems in procedural anxiety, treatment anxiety and communication subscales than in older groups (p < 0.05). In the non-intensive phase HRQOL was significantly better than in the intensive phase, both in patient self-reports and proxy-reports. CONCLUSION: Younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided to children and their parents to facilitate their coping with disease and its treatment.

Parental experiences of childhood leukemia treatment in indonesia.

In our study, we examined socioeconomic, treatment-related, and psychologic experiences of parents during the acute lymphoblastic leukemia treatment of their children in an academic hospital in Indonesia. Children were treated with the WK-ALL-2000 protocol and received donated chemotherapy. From November 2004 to April 2006, 51 parents were interviewed by psychologists using semi-structured questionnaires. The family income had decreased (69%) since the start of treatment. Parents lost their jobs (29% of fathers and 8% of mothers), most of whom stated that this loss of employment was caused by the leukemia of their child (87% of fathers and 100% of mothers). Treatment costs resulted in financial difficulties (78%), debts (65%), and forced parents either to postpone or withdraw from parts of treatment (18%). Parents mentioned needing more information (86%) from and contact (77%) with doctors. The parent organization did not pay any visits (69%) during hospitalization, nor did they give information (59%) or emotional support (55%). We have concluded that the socioeconomic impact of leukemia treatment was profound. Communication between parents and doctors requires improving. The role of the parent organization was insignificant and must be ameliorated.

Observer variation of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography in mediastinal staging of non-small cell lung cancer as a function of experience, and its potential clinical impact.

PURPOSE: To test the extent of variation among nuclear medicine physicians with respect to staging non-small cell lung cancer with positron emission tomography (PET). PROCEDURES: Two groups of nuclear medicine physicians with different levels of PET experience reviewed 30 PET scans. They were requested to identify and localize suspicious mediastinal lymph nodes (MLN) using standardized algorithms. Results were compared between the two groups, between individuals, and with expert reading. RESULTS: Overall we found good interobserver agreement (kappa 0.65). Experience with PET translated into a better ability to localize MLN stations (68% vs. 51%, respectively), and experienced readers appeared to be more familiar with translating PET readings into clinically useful statements. CONCLUSIONS: Although our results suggest that clinical experience with PET increases observers' ability to read and interpret results from PET adequately, there is room for improvement. Experience with PET does not necessarily improve the accuracy of image interpretation.

FDG PET in lymphoma: the need for standardization of interpretation. An observer variation study.

OBJECTIVE: To measure and describe patterns of interobserver variation in visual interpretation of 18-FDG PET in malignant lymphoma. METHODS: Eleven nuclear medicine physicians with different levels of PET experience independently reviewed 37 18F-FDG PET scans of lymphoma patients (10 obtained at presentation, 27 during or after therapy). They were requested to identify and localize suspicious lymphoma sites and to assign a stage to the baseline scans, and to interpret the remaining scans for the presence of viable lymphoma. Individual (extra-)nodal regions were assessed for the likelihood of malignancy as positive, negative or equivocal. These results were compared to expert readings after dichotomization in conservative and sensitive reading classifications. RESULTS: Sixty-one percent and 56% (using sensitive and conservative reading, respectively) of the baseline scans were scored in accordance with the experts. Fourteen of the 27 scans obtained for therapy evaluation with viable tumour sites were scored in accordance with the experts in 82% and 94% of the patients, using conservative and sensitive reading, respectively. The 13 negative scans were scored in agreement with the experts in only 45% of the cases. False positivity pertained especially to the neck, periclavicular, axilla, mediastinum, lung and bone marrow. More experienced observers tended to have fewer false negative scores. CONCLUSION: There are substantial disparities among nuclear medicine physicians' interpretations of FDG PET scans of lymphoma patients, which may affect patient care and results of multi-institutional clinical trials. A well-defined set of criteria is urgently needed to improve consistency.

Expression of the apoptosis inhibitor protease inhibitor 9 predicts clinical outcome in vaccinated patients with stage III and IV melanoma.

PURPOSE: There have been reports of successful treatment of metastatic melanoma patients with active specific immunotherapy (ASI) using irradiated autologous tumor cell vaccination. It is still unknown why some patients respond and others do not. Tumor cells can evade the immune system, for example through interference with antigen presentation by down-regulation of MHC molecules or expressing proteins interfering with cytotoxic lymphocyte-induced apoptosis like the granzyme B antagonist protease inhibitor 9 (PI-9). EXPERIMENTAL DESIGN: PI-9 expression was detected in melanoma cell lines. To investigated if PI-9 is important in the response to ASI, paraffin-embedded tissues from stage III or IV melanoma patients were stained. RESULTS: PI-9 is expressed in melanoma cells and expression in metastasized melanoma cells is, in this group of patients, an adverse prognostic marker with regard to overall and disease-free survival. Moreover, loss of MHC-1 expression frequently occurs during tumor progression but is not associated with poor clinical outcome. Interestingly, melanoma patients with a favorable clinical outcome after ASI therapy usually have high percentages of activated (granzyme B-positive) tumor-infiltrating lymphocytes at time of first diagnosis and low percentages of activated lymphocytes at time of recurrent tumor. CONCLUSIONS: Expression of PI-9 in metastatic melanoma cells is associated with unfavorable clinical outcome whereas MHC-1 down-regulation is not. Although it cannot be proven that PI-9 expression is directly responsible for failure of immunotherapy, these data suggest that expression of PI-9 could be an important immune escape mechanism and that modulation of this inhibitor may enhance the efficacy of immunotherapy.

Effectiveness of a Minimal Intervention for Stress-related mental disorders with Sick leave (MISS); study protocol of a cluster randomised controlled trial in general practice [ISRCTN43779641].

BACKGROUND: The main aims of this paper are to describe the setting and design of a Minimal Intervention in general practice for Stress-related mental disorders in patients on Sick leave (MISS), as well as to ascertain the study complies with the requirements for a cluster randomised controlled trial (RCT). The potential adverse consequences of sick leave due to Stress-related Mental Disorders (SMDs) are extensive, but often not recognised. Since most people having SMDs with sick leave consult their general practitioner (GP) at an early stage, a tailored intervention given by GPs is justified. We provide a detailed description of the MISS; that is more accurate assessment, education, advice and monitoring to treat SMDs in patients on sick leave. Our hypothesis is that the MISS will be more effective compared to the usual care, in reducing days of sick leave of these patients. METHODS: The design is a pragmatic RCT. Randomisation is at the level of GPs. They received the MISS-training versus no training, in order to compare the MISS vs. usual care at patient level. Enrollment of patients took place after screening in the source population, that comprised 20-60 year old primary care attendees. Inclusion criteria were: moderately elevated distress levels, having a paid job and sick leave for no longer than three months. There is a one year follow up. The primary outcome measure is lasting full return to work. Reduction of SMD- symptoms is one of the secondary outcome measures. Forty-six GPs and 433 patients agreed to participate. DISCUSSION: In our study design, attention is given to the practical application of the requirements for a pragmatic trial. The results of this cluster RCT will add to the evidence about treatment options in general practice for SMDs in patients on sick leave, and might contribute to a new and appropriate guideline. These results will be available at the end of 2006.

Patient-reported quality of life after stereotactic ablative radiotherapy for early-stage lung cancer.

BACKGROUND: Deterioration in health-related quality of life (HRQOL) is frequently observed after surgery for stage I non-small-cell lung cancer. As stereotactic ablative radiotherapy (SABR) can result in local control percentages exceeding 90%, we studied baseline and post-treatment HRQOL in SABR patients. METHODS: HRQOL data were collected prospectively using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire in 382 consecutive patients treated with SABR. Patients were referred from 68 Dutch centers, with 86% judged unfit for surgery, and 14% declining surgery. An SABR dose of 60 Gy was delivered in three-, five-, or eight treatment fractions, depending on tumor diameter and location. HRQOL data were available for 382 patients at baseline (pre-SABR), and for 282, 212, 144, 56, and 43 patients at 3, 6, 12, 18, and 24 months post-SABR, respectively. RESULTS: Median survival was 40 months, with a 2-year survival of 66%. Local, regional, and distant failure percentages at 2 years were 6%, 13%, and 22%, respectively. Mean baseline global HRQOL and physical functioning scores were 62.9 ± 1.1 and 61.7 ± 1.1, respectively. Baseline symptom scores were highest for dyspnea (47.1 ± 1.7) and fatigue (37.4 ± 1.3). Except for a nonsignificant decrease in 2 to 3 points per year in physical functioning, no statistically or clinically significant worsening of any of the HRQOL functioning or symptom scores at any follow-up time point was observed. CONCLUSIONS: Patients referred for SABR have substantially worse baseline HRQOL scores than those reported in the surgical literature. Clinically relevant deteriorations in HRQOL subscale scores were not observed after SABR.