Prediction Of Therapy Outcome Research Articles

Abstract 2693: MDR1 and ERCC1 expression predict outcome in patients with locally advanced bladder cancer and adjuvant chemotherapy

Abstract Aims: Patients with locally advanced bladder cancer show a poor prognosis and can benefit from adjuvant chemotherapy. It was previously shown that expression of MDR1 and ERCC1 is linked to resistance against platinum-based chemotherapy in several cancer types. The aim of the present study was to evaluate the impact of classical histological, new immunohistochemical and molecular markers on prognosis of patients with locally advanced bladder cancer undergoing cystectomy (pT3a-4a and/or pN+) and response to chemotherapy within a randomized, multicenter, phase III trial (AUO-AB 05/95). Methods: Clinico-pathological parameters were assessed retrospectively after histopathological review in 204 patients randomized to adjuvant systemic chemotherapy with cisplatin and methotrexate (CM) vs. methotrexate, vinblastine, epirubicin, and cisplatin (M-VEC) after radical cystectomy. Tissue microarrays were constructed to study the immunohistochemical expression of ERCC1, BSG (Emmprin/CD147) CAV1, phospho-CAV1 (Y14), RRM1, BRCA1, BRCA2, BIRC5 (Survivin), and KISS1. Tumor samples from 108 patients were analyzed for MDR1 and ERCC1 mRNA expression by quantitative real-time RT-PCR using formalin-fixed and paraffin embedded tumor tissue. Results: Expression of MDR1 and ERCC1 were independently associated with overall and progression-free survival (p=0.001, 2.9 exp[b]; p=0.01, 2.24 exp[b]). In contrast to ERCC1 expression, MDR1 separated patients receiving M-VEC with higher sensitivity and specificity than those receiving CM (ROC Analysis p=0.008; [AUC]=0.71). These results could be partially confirmed by immunohistochemical analysis of 204 patients. ERCC1 and RRM1 expression correlated significantly with shorter overall survival in both therapy arms by univariate analysis. Multivariate analysis showed that ERCC1 expression was an independent prognostic factor for shorter overall survival (HR=2.3, 95%CI=1.18-4.43, p=0.014). Positive nodal status (pN1-3), histologic blood vessel invasion (V1), and positive BIRC5 immunoreactivity were significant as well. Conclusion: Our results suggest a predictive value of ERCC1 and MDR1 expression levels for therapy response and outcome in patients with locally advanced bladder cancer which allows the identification of patients who are likely to benefit from adjuvant platinum-based chemotherapy. The qPCR analysis is feasible in studying paraffin-embedded material from clinical bladder cancer trials. In addition, standard histopathological variables in combination with immunohistochemical and molecular prognostic markers can be used to predict therapy outcome in bladder cancer, irrespective of the mode of chemotherapy. Prospective studies are warranted to define a role for MDR1, ERCC1 and RRM1 in individualizing multimodality treatment in locally advanced bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2693.

Impact of Dynamic 18F-FDG PET on the Early Prediction of Therapy Outcome in Patients with High-Risk Soft-Tissue Sarcomas After Neoadjuvant Chemotherapy: A Feasibility Study

Dynamic PET (dPET) studies with (18)F-FDG were performed in patients with soft-tissue sarcomas who received neoadjuvant chemotherapy early in the course of therapy. The goal of the study was to evaluate the impact of early dPET studies and assess their value with regard to the therapy outcome using histopathologic data. The evaluation included 31 patients with nonmetastatic soft-tissue sarcomas, who were treated with neoadjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin. Patients were examined before the onset of therapy and after the completion of the second cycle. Histopathologic response served for reference and was available for 25 of 31 patients. Response was defined as less than 10% viable tumor tissue in the resected tumor tissue. The following parameters were retrieved from dPET studies: standardized uptake value (SUV); fractal dimension; 2-compartment model with computation of K(1), k(2), k(3), and k(4) (unit, 1/min); fractional blood volume; and influx according to Patlak. The mean SUV was 4.6 before therapy and 2.8 after 2 cycles. The mean influx was 0.059 before therapy and 0.043 after 2 cycles. The mean SUV was 3.9 in the responders and 5.5 in the nonresponders before therapy. After therapy, responders revealed a mean SUV of 2.5, whereas nonresponders had a mean SUV of 3.5. We used linear discriminant analysis to categorize the patients into 2 groups: response (n = 12) and nonresponse (n = 13). The correct classification rate of the responders (positive predictive value) was generally higher (>67%) than that for the nonresponders. Finally, the combined use of the 2 predictor variables, namely SUV and influx, of each study led to the highest accuracy of 83%. This combination was particularly useful for the prediction of responders (positive predictive value, 92%). The use of the percentage change in maximum SUV led to an accuracy of 58%. On the basis of these results, only a multiparameter analysis based on kinetic (18)F-FDG data of a baseline study and after 2 cycles is helpful for the early prediction of chemosensitivity in patients with soft-tissue sarcomas receiving neoadjuvant chemotherapy.

Radioiodine therapy dosimetry in benign thyroid disease and differentiated thyroid carcinoma

Traditionally, nuclear medicine has been regarded mainly as a diagnostic specialty in which the administration of radioactive substances yields information whose importance far outweighs any potential risk to normal tissue. Now, however, therapeutic applications of radionuclide-based approaches are at last gaining the prominence they deserve. In this field, individual patient dosimetry is essential both for optimising the administered activity through the establishment of minimum effective and maximum tolerated absorbed doses and for determining a dose-response relationship as a basis for predicting tumour response [2]. Unfortunately, the lack of comprehensive clinical trials designed to bring out the value of radionuclide dosimetry in predicting therapy outcome has fed a general belief that dosimetry methods are daunting, prone to a large degree of uncertainty, and liable to generate increased costs, and thus held back their progress. This is, indeed, why Flux and colleagues remarked “radionuclide therapy remains the Cinderella of cancer treatment modalities, under-utilised with respect to more conventional treatments” [3]. Now, however, the availability of new technologies (e.g. PET/CT) and radioisotope pairs for diagnosis and therapy (e.g. I and I or Y and Y), supported by a new generation of personal computer software for internal dose assessment, is at last leading to an increase in the use of dosimetry in clinical therapeutic applications. To show the appreciable progress now being made in this field we here take a look at a sample of the most recent literature on dosimetry for radioiodine treatment of benign thyroid disease and differentiated thyroid carcinoma.

Predicting Therapy Outcome in Patients with Early and Late Obsessive-Compulsive Disorder (EOCD and LOCD)

Increasing attention has been given to subtyping OCD with respect to different clinical profiles, response to drug treatments, comorbidity and age of onset. There are a number of studies looking at predictors of treatment outcome in OCD, but so far not for OCD subtypes. Prediction of outcome after cognitive-behavioural therapy was evaluated in 63 inpatients with early obsessive-compulsive disorder (EOCD < or = 12 years of age) and 191 patients with late obsessive-compulsive disorder (LOCD > 15 years of age). For EOCD patients factors predicting a good outcome included high motivation and high initial Y-BOCS scores. Factors associated with a bad outcome were higher age at assessment, a longer duration of psychiatric inpatient treatment before assessment and a low level of social functioning (BSS). For LOCD patients living in a stable relationship, high motivation and completing treatment predicted a favourable therapy outcome, while a low level of psychological functioning (BSS) and a longer duration of inpatient psychiatric treatment before assessment were associated with an undesirable therapy outcome. Subtyping OCD patients according to age of onset seems to be a promising avenue towards improving and developing more specified treatment programs.

The value of physical performance tests for predicting therapy outcome in patients with subacute low back pain: a prospective cohort study

Considering the enormous costs of intensive multidisciplinary treatment, predictive tests for therapy outcome are needed to evaluate patients' performance potential and increase cost effectiveness. Somatic parameters are commonly used to evaluate health status and serve as an additional means of forecasting the prognosis, yet little is known of their validity. In this study, we investigated the prognostic value of somatic parameters regarding the outcome of multidisciplinary treatment in patients with subacute low back pain. The study was designed as a prospective cohort study of 162 patients. Somatic parameters were assessed with three physical performance tests (Villiger test, Oesch test, Biering-Sørensen test) before treatment (T0), after 3 weeks' inpatient therapy (T1) and at 6-month follow-up (T2). Psychometric characteristics of subjective pain perception (VAS), a pain disability index (PDI) and a physical capability index (FFbH-R) were recorded. Correlation coefficients between the physical performance test scores and psychometric characteristics were calculated. To predict therapy outcome, discriminant analyses were performed. A control group (n = 30) was evaluated at similar time points without receiving any therapy. Our results demonstrate good discrimination between patients and controls by means of the investigated performance tests and exhibit a significant negative correlation with the psychometric data. Lower outcome values at study entry correlated with higher pain intensity and disability after multidisciplinary treatment. However, the statistical magnitude of correlation was relatively low and further discriminant analysis did not reveal any predictive value. Consequently the physical performance tests do not have a prognostic value regarding therapy outcome.

Weiterbildung CME: Depersonalisation/Derealisation - Krankheitsbild, Diagnostik und Therapie

The present state of knowledge about depersonalization (DP) and derealization (DR) is reviewed with respect to classification, epidemiology, etiology, and therapy. Mild and transient DP-DR are considered to be common phenomena. The prevalence of depersonalization-derealization disorder (DP-DR-D) is estimated to be approx. 1-2% of the general population in the Western hemisphere. DP-DR-D is probably severely underdiagnosed. DP-DR-D is strongly associated with depression and anxiety disorders. It is suggested that symptoms of DP-DR indicate disease severity and negatively predict therapy outcome. Neurobiological and psychological models have shown that a disordered body schema and emotional and autonomic blunting are essential components of the disorder. Despite the frequency of DPDR and its clinical relevance, there is a considerable lack of empirical research on DP-DR with respect to the health-care situation of depersonalized patients and with regard to treatment options.

SPECAM-1 and sVCAM-1: Role in Pathogenesis and Diagnosis of Chronic Hepatitis C and Association with Response to Antiviral Therapy.

To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC). The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy. sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p<001). sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage (p =0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1 levels decreased significantly (p<001) with no difference between responders and nonre-sponders. sPECAM-1 correlated positively with inflammatory activity (p = 0.02), fibrosis stage (p<001), sVCAM-1 (r=0.56, p<001) and alanine aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic curve analysis showed a good discriminant power of serum sPECAM-1 concentrations for detection of liver fibrosis - stage 0 versus stage 1-3, AUC 0.81; cut-off 221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis, AUC 0.78; cut-off 237.1 ng/ml. Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.

Anti‐angiogenic perfluorocarbon nanoparticles for diagnosis and treatment of atherosclerosis

Complementary developments in nanotechnology, genomics, proteomics, molecular biology and imaging offer the potential for early, accurate diagnosis. Molecularly-targeted diagnostic imaging agents will allow noninvasive phenotypic characterization of pathologies and, therefore, tailored treatment close to the onset. For atherosclerosis, this includes anti-angiogenic therapy with specifically-targeted drug delivery systems to arrest the development of plaques before they impinge upon the lumen. Additionally, monitoring the application and effects of this targeted therapy in a serial fashion will be important. This review covers the specific application of alpha(nu)beta(3)-targeted anti-angiogenic perfluorocarbon nanoparticles in (1) the detection of molecular markers for atherosclerosis, (2) the immediate verification of drug delivery with image-based prediction of therapy outcomes, and (3) the serial, noninvasive observation of therapeutic efficacy.

Narcissism Predicts Therapy Outcome in Psychosomatic Patients

Narcissism can be seen along a continuum of adjustment with well-defended narcissism on the adjusted end, and poorly-defended narcissism on the maladjusted end. Poorly-defended narcissism is associated with negative emotions, and somatic preoccupations. The present study investigated whether aspects of poorly-defended narcissism can be changed during hospital treatment and if the change predicts therapy outcome. Data from 1442 psychosomatic in-patients (70% women, mean age 40.1 years) at admission and discharge were analyzed. Narcissism, mood and quality of life were assessed with standardized instruments. Patients with somatoform, anxiety, depressive or adjustment disorders differed significantly in narcissistic aspects. During inpatient treatment, narcissistic aspects decreased, and mood and quality of life increased. Changes in threatened self were associated with an improvement on all mood dimensions. Psychosomatic hospital treatment can help patients with poorly-defended narcissism to regulate aspects of threatened self with subsequent positive impact on mood and quality of life.

PW04-01 Volumetric changes in PTSD and in a subgroup of PTSD patients not responding to EMDR psychotherapy

Background:Several studies have reported limbic structures volume decrease in Post-Traumatic Stress Disorder (PTSD). However, in PTSD the effect of therapy on brain structures has seldom been investigated. The aim of the study was to evaluate the grey matter (GM) loss in occupational related PTSD and to assess the volumetric differences between patients responding (R) and non-responding (NR) to psychotherapy.Methods:Pre-EMDR MRI data of 21 train drives who did develop PTSD (S) and 22 who did not develop PTSD (NS) after person-under-the-train accidents were compared. Within S further comparisons were made between 10 R to Eye Movement Desensitisation Reprocessing (EMDR) therapy and 5 NR. Data were analysed by optimised voxel-based morphometry as implemented in Statistical Parametric Mapping.Results:As compared to NS, S showed a significant GM volume reduction in precuneus, lingual gyrus, posterior cingulate and parahippocampal cortex. The R&gt;NR comparison highlighted a significant GM reduction in NR in bilateral posterior cingulate, left middle frontal cortex and right parahippocampal, insular and temporal cortices.Conclusions:Comparing two large groups of subjects significant GM volumetric reductions were found in PTSD in posterior limbic structures. NR showed, as compared to R, volume reduction in cortical structures including posterior cingulate and parahippocampal cortex. These latter two structures seem to be the hallmark for both PTSD diagnosis and therapy outcome prediction.

P03-58 Volumetric changes in PTSD and in a subgroup of PTSD patients not responding to EMDR psychotherapy

Background:Several studies have reported limbic structures volume decrease in Post-Traumatic Stress Disorder (PTSD). However, in PTSD the effect of therapy on brain structures has seldom been investigated. the aim of the study was to evaluate the grey matter (GM) loss in occupational related PTSD and to assess the volumetric differences between patients responding (R) and non-responding (NR) to psychotherapy.Methods:Pre-EMDR MRI data of 21 train drives who did develop PTSD (S) and 22 who did not develop PTSD (NS) after person-under-the-train accidents were compared. Within S further comparisons were made between 10 R to Eye Movement Desensitisation Reprocessing (EMDR) therapy and 5 NR. Data were analysed by optimised voxel-based morphometry as implemented in Statistical Parametric Mapping.Results:As compared to NS, S showed a significant GM volume reduction in precuneus, lingual gyrus, posterior cingulate and parahippocampal cortex. the R&gt;NR comparison highlighted a significant GM reduction in NR in bilateral posterior cingulate, left middle frontal cortex and right parahippocampal, insular and temporal cortices.Conclusions:Comparing two large groups of subjects significant GM volumetric reductions were found in PTSD in posterior limbic structures. NR showed, as compared to R, volume reduction in cortical structures including posterior cingulate and parahippocampal cortex. These latter two structures seem to be the hallmark for both PTSD diagnosis and therapy outcome prediction.

Treatment Attitude and Therapy Outcome in Patients With Borderline Personality Disorder

This study investigated the degree to which two ways of defining attitude toward treatment (i.e., attitude toward talking with a therapist about problems, expectation for improvement) predicted therapy outcome. The sample consisted of 28 patients who participated in an open clinical trial evaluating the efficacy of cognitive therapy for borderline personality disorder and who completed assessments at baseline and 12-month follow-up (Brown, Newman, Charlesworth, Crits-Cristoph, &amp; Beck, 2004). When attitude toward treatment was defined as attitude toward talking with a therapist, this variable predicted suicide ideation and scores on two measures of depression at the 12-month assessment. When attitude toward treatment was defined as expectation for improvement, this variable predicted scores on one measure of depression and number of borderline personality disorder criteria met at the 12-month assessment. These results provide preliminary evidence that positive attitudes toward treatment are associated with more clinical improvement, although future research should replicate this finding with a better developed measure of treatment attitudes.

Positron emission tomography as a tool for early prediction of therapy outcome in patients with soft tissue sarcoma

10572 Background: We used 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with soft tissue sarcoma (STS). Treatment effect was assessed with regard to prediction of therapy outcome. Methods: The evaluation includes 27 patients with high risk STS receiving chemotherapy consisting of doxorubicin 75 mg/m2/day 1 and ifosfamide 1,500 mg/m2/day 1–4 (AI-G regimen) or etoposide 125 mg/m2/day 1+4, ifosfamide 1,500 mg/m2/day 1–4 and doxorubicin 50 mg/m2/day 1 (EIA regimen). Patients were examined using PET prior to onset of therapy and after completion of the first cycle of AI-G and after two cycles of EIA chemotherapy, respectively. Restaging according to RECIST criteria using computed tomography and magnetic resonance tomography was performed after six cycles of AI-G or four cycles of EIA chemotherapy and served for reference. Results: Clinical outcome of 27 evaluable patients was as follows: two patients with no evidence of disease, seven with partial remission, 14 with stable disease, and four patients with progressive disease. Median average standard uptake value (SUV) prior to onset of chemotherapy was 3.5 [range: 0 - 27.9] in comparison to 2.4 [range: 0 - 9.9] after chemotherapy treatment. Median SUVmax was 11.5 [range: 0 - 44.7] prior to chemotherapy in comparison to 7.9 [range: 0 - 21.7] following therapy. A significant difference of the progression-free survival for patients with a decrease in SUV (responders) in comparison to patients with an increase or stable SUV (non-responders) could be demonstrated (p = 0.0187). Conclusions: On the basis of these data, PET can be used as an easily measurable tool for early prediction of chemosensitivity of the tumor and moreover of the therapy outcome. Moreover, PET may even complement the existing RECIST criteria for tumor response evaluation. No significant financial relationships to disclose.

Transcranial direct current stimulation (tDCS) for the prediction of VNS therapy outcome in pediatric patients

Transcranial direct current stimulation (tDCS) for the prediction of VNS therapy outcome in pediatric patients

Cognitive-behavioral group treatment for pathological gambling: Analysis of effectiveness and predictors of therapy outcome

Cognitive-behavioral group treatment for pathological gambling: Analysis of effectiveness and predictors of therapy outcome

Early Prediction of Therapy Outcome in Patients with High-Risk Soft Tissue Sarcoma Using Positron Emission Tomography

Background: We used 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with soft tissue sarcoma (STS). Treatment effect was assessed with regard to prediction of therapy outcome. Patients and Methods: The ongoing evaluation includes 27 patients with high-risk STS receiving chemotherapy consisting of doxorubicin and ifosfamide (AI-G regimen), or etoposide, ifosfamide and doxorubicin (EIA regimen). Patients were examined using PET prior to onset of therapy, and after completion of the first cycle of AI-G and after 2 cycles of EIA chemotherapy, respectively. Restaging according to RECIST was performed after 6 cycles of AI-G or 4 cycles of EIA chemotherapy and served as reference. Results: Clinical outcome of 27 evaluable patients was as follows: 2 patients with no evidence of disease, 7 with partial remission, 14 with stable disease, and 4 patients with progressive disease. A significant difference of the progression-free survival for patients with a decrease in the standardised uptake value (SUV; responders) in comparison to patients with an increase or stable SUV (non-responders) could be demonstrated (p = 0.0187). Conclusion: On the basis of these data, prediction of chemo-sensitivity of the tumour and moreover of the therapy outcome might be possible.

Radionuclide Imaging of Apoptosis in Malignancies: Promise and Pitfalls of 99mTc-Hynic-rh-Annexin V Imaging

Radionuclide detection of apoptosis with of (99m)Tc-Hynic-rh-Annexin V scintigraphy is an effective tool for in vivo visualisation and monitoring of apoptosis in various malignant tumour. Early therapy-induced increase of the tumour tracer uptake correlates with favourable outcome, whereas stable or decreased uptake correlates with stable disease or tumour progression. Therefore sequential (99m)Tc-Hynic-rh-Annexin V scintigraphy could be used to predict therapy outcome on a patient-to-patient basis within 48 hours after the start of treatment. However, moderate tumour-to-background ratio and therapy-induced changes in normal tissues could confound image analysis. To assure accurate interpretation of Annexin V scans, the awareness of the biophysiological and biochemical properties contributing to the tracer distribution is essential. In with manuscript we discuss the patterns of Annexin V tumour uptake and illustrate the most frequent pitfalls associated with Annexin V imaging in correlation with CT and MRI imaging.

Prophylaxe und Therapie der Hüftgelenksluxation bei infantiler Zerebralparese (ICP): statomotorische, radiologische und klinische Ergebnisse nach subkutaner Adduktorentenotomie

The current study assessed the clinical and radiological outcome and motor function improvement after subcutaneous adductor tenotomy in children with cerebral palsy (ICP). It was also analysed if groups with different preoperative hip functions and radiological hip migrations differed in their final clinical, radiological and motor function outcome. A prospective study of 91 children with infantile cerebral palsy (ICP, mean age 4.9 years, range: 1.1 - 15.8) with 141 hip dislocations or subluxations analysed preoperatively the hip abduction and radiologically the migration percentage (MP). Depending on the preoperative status, all patients were grouped into 3 abduction and 3 MP groups. Additionally, the motor function was classified according to the Rancho los Amigos scale. A subcutaneous adductor tenotomy was performed mono- or bilaterally and all patients were treated for 4 - 6 weeks with a hip abduction splint. Patients were assessed annually for 4 years; clinical and radiological results and the motor function were analysed according to their preoperative status. The mean hip abduction was preoperatively 30.3 +/- 1.2 degrees and was significantly improved to 50.3 +/- 1.3 degrees 1 year and to 43.3 +/- 2.2 degrees 4 years post surgery. The preoperative mean MP was preoperatively 42.3 +/- 1.3 % and was significantly improved to 34.6 % 1 year and to 31.9 % 4 years post surgery. After 4 years, 41 % had undergone a motor function improvement and 52 % no change in motor function. After 4 years, patients with a hip abduction <or= 20 degrees showed the most improvement; other abduction groups also improved significantly but to a lesser extent. The 4-year MP was significantly and to a relatively large extent improved in the groups with a preoperative MP between 25 % and 50 % and above 50 %. With a preoperative MP <or= 25 %, there was a significant but only slight improvement. The motor function was improved when the preoperative hip abduction was most restricted and the preoperative MP was high. CONCLUSION The subcutaneous adductor tenotomy in hip dislocation and subluxation of children with cerebral palsy is a safe procedure that can treat and prevent hip dislocation/subluxation in 76 % of the cases. In appropriately selected patients, the number of individuals that are "freely walking" and "walking with aid" can be doubled. MP and hip abduction are both predictors of therapy outcome.

Prognostic significance of drug-regulated genes in high-grade osteosarcoma

About 25–45% of patients with high-grade osteosarcoma poorly respond to chemotherapy with an increased risk of relapse and the development of metastasis. Therefore, the aim of this study was the evaluation of the prognostic value of eight previously identified drug-regulated candidate genes on osteosarcoma therapy outcome. Gene expression of 8 candidate genes was analyzed in 35 formalin-fixed, paraffin-embedded, laser-microdissected osteosarcoma biopsies. The prognostic value of these genes was evaluated by the correlation of gene expression with therapy outcome, overall survival and event-free survival in univariate and multivariate analysis. Upon univariate analysis, the expression of MALAT-1, IMPDH2, FTL and RHOA significantly correlated with response to chemotherapy. Expression of all four genes was increased in the poor responder group. Upon multivariate analysis, IMPDH2 maintained its independent prognostic value (P=0.025). Concerning the overall survival of the patients, we observed a significant association with the expression of FTL, PHB, ATAD2, ACTN1 and RRM2 as well as lactate dehydrogenase serum levels. In the subgroups of patients with high expression of these genes and those with elevated lactate dehydrogenase levels, the mean overall survival was decreased 1.7-, 1.9-, 2.2-, 2.4-, 1.5- and 4.5-fold, respectively. Except RRM2, all genes and lactate dehydrogenase serum levels remained significant in the multivariate analysis. In addition, the event-free survival was significantly decreased in the subgroups of patients with high FTL, ATAD2 and IMPDH2 expression (1.8-, 6.3- and 2.4-fold, respectively). These data demonstrate that among the identified genes are valuable markers for the prediction of osteosarcoma therapy outcome. Especially IMPDH2 and FTL are promising candidates for the stratification of osteosarcoma patients into low- and high-risk groups. Owing to their involvement in drug action these genes may further be potential targets for the modulation of drug sensitivity.

Cognitive–behavioral group treatment for pathological gambling: analysis of effectiveness and predictors of therapy outcome

The authors sought to examine short- and mid-term effectiveness of a group cognitive–behavioral therapy (CBT) in pathological gambling (PG) and to analyze predictors of therapy outcome. Two hundred ninety PG patients participated in the current study, all diagnosed on the basis of Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria, and were given manualized outpatient group CBT (16 weekly sessions). Specific assessment before and after the therapy and at 1, 3, and 6months follow-up was conducted. Logistic regression and survival analyses were applied. Outpatient group CBT was found to be effective, with abstinence rates of 76.1% by the end of therapy and 81.5% at 6months follow-up. The dropout rate during treatment decreased significantly after the fifth treatment session. Psychopathological distress (p=.040) and obsessive–compulsive symptoms were identified as factors predicting relapse and dropout, respectively. These findings suggest that group CBT is effective for treating pathological gamblers. Several psychopathological and personality traits were identified as outcome predictors.