Predictive Value For Treatment Response Research Articles

The dynamics of plasma transforming growth factor beta 1 (TGF-β1) level during radiotherapy with or without simultaneous chemotherapy in advanced head and neck cancer

To assess the plasma TGF-beta1 level during radio(chemo)therapy and to test the predictive power of TGF-beta1 for treatment response in patients with advanced head and neck cancer. Twenty nine patients with advanced head and neck cancer were treated with curative radio(chemo)therapy. Plasma TGF-beta1 level was established at the beginning, in the middle and at the end of the therapy. The dynamics of the TGF-beta1 level was assessed separately for patients with and without chemotherapy. Treatment response was correlated to the TGF-beta1 level. Eighteen patients achieved complete remission, eight partial remission and three patients progressed. Patients treated with radiotherapy had significantly higher initial plasma TGF-beta1 level compared to radiochemotherapy patients (p=0.044). During the treatment, there was a significant decrease in patients treated with radiochemotherapy (p=0.008) but not in radiotherapy patients (p=0.34). Tumor burden did not correlate with plasma TGF-beta1 level (p=0.07). TGF-beta1 has no predictive value for treatment response (CR vs. PR and PD, p=0.12). The combination of radiotherapy and chemotherapy significantly decreases plasma TGF-beta1 level in patients with advanced head and neck cancer. Treatment response cannot be predicted using TGF-beta1.

Vascular endothelial growth factor in esophageal cancer.

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis of many solid malignancies. The influence of angiogenesis and VEGF expression on progression and recurrence of esophageal cancer has been investigated over the last years. This article reviews the prognostic significance of VEGF expression, microvessel density (MVD), and lymphangiogenic factors in squamous cell carcinoma (SCC), Barrett's dysplasia, and adenocarcinoma (AC) of the esophagus, their predictive value for treatment response to chemo-radiotherapy and new anti-angiogenic treatment strategies.

Granulocyte colony-stimulating factor-supported combined immunosuppressive therapy (antilymphocyte globulin, cyclosporine, and methylprednisolone) in patients with aplastic anemia: tolerability, efficacy, and changes in the progenitor cell compartment.

Neutropenic infections are the major cause of morbidity and mortality in the treatment of aplastic anemia (AA) with antilymphocyte globulin (ALG), cyclosporin A (CSA), and methylprednisolone (MP). Recent data suggest a beneficial effect of administering G-CSF as an adjunct to immunosuppression. We have treated 11 consecutive patients with AA using a combined immunosuppressive regimen including ALG, CSA, and MP plus G-CSF at a dose of 5 microg/kg/day until neutropoietic recovery. In addition to measuring routine hematological parameters we have performed serial determinations of reticulocyte counts and in vitro progenitor cell cultures before and after therapy in order to assess their predictive value for treatment response and to determine the impact of therapy on early hematopoiesis. One patient died on day 34 of neutropenic septicemia. At 1 year, 81% of patients showed response to treatment. The median time to ANC values >0.5 and >1.0 x 10(9)/l were 19 and 35 days, respectively. Reticulocyte counts started to recover after 6 weeks, and transfusion independence was observed on day 52 for red blood cell transfusions and on day 53 for platelet concentrates. All patients with detectable colony formation in peripheral blood achieved a complete hematological remission, as compared with only one of five patients without progenitor cell growth. Although normal ranges were rarely achieved, there was a small but definitive improvement in progenitor cell numbers as compared with baseline values in most patients. Our results confirm the good tolerability and high efficacy of this G-CSF-supported combined immunosuppressive therapy for AA. Detectable colony growth at diagnosis seems to predict a high chance for complete hematological response.

Severity of esophageal eosinophilia predicts response to conventional gastroesophageal reflux therapy.

Pediatric patients who present with symptoms of gastroesophageal reflux and severe eosinophilic esophagitis may be unresponsive to aggressive anti-reflux medical therapy. In order to determine whether the degree of eosinophilia predicts anti-reflux treatment response and possibly distinguishes different etiologies, we reviewed the initial biopsies of patients with esophageal eosinophilia and compared the number of eosinophils with the response to anti-reflux treatment. Over a 1-year period, 102 patients with a biopsy demonstrating at least 1 intraepithelial eosinophil were identified among patients undergoing initial endoscopy for symptoms of reflux. All patients were treated with H2 blockers and prokinetic agents. Treatment response was classified into three categories: improvement, relapse, and failure. There were significant differences between the group who improved (mean eosinophil count [MEC] 1.1 +/- 0.3 SEM) and those who failed (24.5 +/- 6.1 SEM, P < 0.0025) or relapsed 6.4 +/- 2.4 SEM, P < 0.05). A threshold MEC value of > or = 7 provided a sensitivity of 61.3%, a specificity of 95.7%, and a predictive value for treatment failure of 86.1. A MEC value of < 7 provided an 85% predictive value of successful therapy. From these data we made the following conclusions: (1) The number of eosinophils has a predictive value of treatment response with > or = 7 per high power field offering a valuable clinical threshold for predicting outcome of conventional therapy. (2) The variable response to conventional reflux treatment may reflect different etiologies. (3) Alternate medical treatment modalities may be appropriate in the presence of severe eosinophilia, before considering surgical intervention.

Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment—Neurobiological and psychometric assessment of course

The present study was designed to investigate the clinical efficacy of trimipramine with adjunct sleep deprivation (SD) or bright light (BL) and to evaluate psychometric and neurobiological variables that might be of predictive value for treatment response. We used (1) the combined dexamethasone-corticotropin releasing hormone test (DEX-CRH test) to characterize alterations of the hypothalamic-pituitary-adrenal (HPA) system; (2) polysomnography to evaluate sleep disturbances; and (3) a standardized test battery to assess cognitive psychomotor functions after study initiation and after 5 weeks of treatment. The overall response rate (≥50% decrease in score on Hamilton Rating Scale for Depression [HRS] was 55% ( N = 42). The response rate in the group with trimipramine monotherapy ( N = 14) was 79%, whereas in the groups with adjunct SD ( N = 14) and BL ( N = 14), respectively, it was only 43%. All three groups showedsignificant improvement at the end of the third week of treatment. Neither of the adjunct treatments hastened the onset of antidepressant action as measured by HRS. A significantly higher proportion of nonresponders than responders ( p<.05) had HPA dysregulation, disturbed rapid eye movement (REM) sleep (REM latency, REM% first third of night) and decreased non-REM sleep (% stage 2). The nonresponders showed significantly more corticotropin (ACTH) secretion after CRH stimulation in the DEX-CRH test than the responders and a less rapid normalization of the neuroendocrine dysregulation (cortisol secretion) ( p<.01). In addition, REM latency was significantly shorter in the BL group than in the monotherapy group and estimated duration of illness significantly longer in the SD group than in the monotherapy group. REM latency, percentage of REM sleep during the first third of the total sleep period, percentage of non-REM sleep stage 2 and ACTH release after a DEX-CRH challenge predicted response across all three treatment groups. The neurobiological symptoms were unevenly distributed, among the three groups, thus creating heterogeneity in these measures. This heterogeneity may have contributed to the different treatment response rates as defined by psychopathology (HRS). In contrast, the neuropsychological tests and some of the sleep-EEG investigations revealed different response patterns for different groups: The onset of improvement is simple cognitive functions and in sleep continuity was earlier in the adjunct treatment groups. This study underlines the need for a multidimensional approach including use of neurobiological and neuropsychological measures to identify the therapeutic profiles of different treatment strategies and predictors of outcome.