NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial)

Contains fulltext : 70883.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. METHODS/DESIGN: Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy). DISCUSSION: The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice. TRIAL REGISTRATION: ISRCTN45750457

Eosinophils in childhood asthma

ln this thesis several aspects of the contribution of the eosinophil to the pathophysiology of childhood asthma have been studied and described. ln the 1st chapter the pathophysiology of asthma is discussed, with special emphasis on the contribution of the eosinophil.ln the 2nd chapter we describe a possible relationship between age and both IgE and the number of eosinophils in childhood asthma. ... Zie: Summary

Klinisch denken en beslissen in de praktijk: een pasgeborene met dyspnoe

markdownabstractPatiënt A, een meisje van 2 dagen oud, werd opgenomen op de afdeling Kinderintensivecare wegens dreigende respiratoire insufficiëntie. De zwangerschap en partus waren ongecompliceerd verlopen, het geboortegewicht was 3500 g. De ademhaling was vanaf de geboorte snel en ging gepaard met intrekkingen. Gedurende de eerste 2 dagen werd de borstvoeding met pauzes gedronken, maar goed verdragen. De baby was opvallend snel moe, had moeite met huilen en neigde tot hypothermie. Zij vertoonde geen tekenen van cyanose of transpireren. De familieanamnese leverde geen bijzonderheden op. Wegens progressieve dyspnoe en tachypnoe werd patiëntje verwezen naar een ziekenhuis. Aldaar werd een ernstig dyspnoïsche zuigeling gezien met een versnelde ademhaling en hartslag en een marginale lichaamstemperatuur, bij wie niet-afwijkende harttonen zonder souffles en een symmetrisch ademgeruis werden gehoord. Er was geen stridor aanwezig. Arteriële pulsaties en capillaire vulling waren niet-afwijkend. De saturatie bleek 75% en de bloeddruk was 70/44 mmHg. Bij palpatie van de buik werden geen afwijkingen opgemerkt, met name geen hepatosplenomegalie. Er waren geen dysmorfe kenmerken en ook het neurologisch onderzoek toonde geen afwijkingen

Evaluating positron emission tomography in non-small cell lung cancer. Moving beyond accuracy to outcome

This chapter evaluates the diagnostic accuracy of positron emission tomography in non-small cell lung cancer (NSCLC). In NSCLC, evaluation of the extent of disease in the mediastinum is an important step in deciding about further therapy. In general, patients with preoperative identifiable N2 disease are excluded from thoracotomy. Conventional work-up of the mediastinum often includes noninvasive imaging with computed tomography (CT), followed by invasive exploration through mediastinoscopy. In a meta-analysis of 18 studies, including more than a thousand patients, the negative predictive value of PET was found to be 93%, which is at least as good as that of mediastinoscopy in daily clinical practice. In oncology, stored surgical specimens can also provide useful information on the potential impact of a diagnostic test. Decision analysis models the cost-effectiveness of a new diagnostic device. The model can combine results of clinical studies that cover different health-care steps. In the presence of many alternative diagnostic strategies, decision analysis can help to identify the most promising diagnostic tests or algorithms for further research. Several aspects are of particular importance for randomized controlled trials (RCT) involving diagnostic imaging. In therapeutic RCT the outcome is usually measured in terms of patient mortality and morbidity. However, diagnostic tests serve to allocate appropriate therapy to patients. A reasonable outcome measure for such studies is the extent to which appropriate therapy is applied, depending on the condition that the new test does not alter the definitions of staging and treatment for each stage that is already established

Van Anda, Texada Island

Fine-needle aspiration (FNA) of thyroid nodules has markedly reduced the role of thyroid scintigraphy. This is often limited to nondiagnostic or follicular (tumor) FNA classifications. In this study, we evaluated the efficacy and cost of such a strategy in a university center. From 1992-1998, 995 aspirations were done in 667 patients with palpable nodules. FNA was classified as malignant, suspicious, follicular, benign or inadequate. The Gold standard was surgery or extended follow-up, including physical examination, FNA, and/or ultrasound (US) with a time interval of half a year. Cost analysis was limited to operated patients. The first FNA yielded inadequate results in 28%, decreasing to 6% after 4 aspirations (n = 42). The other final classifications were: 76%, benign; 14%, follicular; 2%, suspicious; 1%, malignant (n = 7). Scintigraphy (99mTc) suggested a hyperfunctioning autonomous nodule (adenoma) in 12% and 3% of the inadequate and follicular subset, respectively. Surgery for diagnostic reasons (n = 105) yielded 24 malignancies (23%): in 47% of suspicious, 12% of the follicular, and in all with malignant FNA. Postoperative morbidity occurred in 14 (5 laryngeal nerve paralyses) with benign histology. Major cost drivers were surgery and hospitalization: mean costs per patient amounting to Euro 3.311 in case of benign histology. We conclude that current work-up is still unable to prevent unnecessary surgery for benign thyroid nodules. Thyroid scintigraphy proved most productive in the inadequate FNA category. Improvement of the diagnostic process using immunohistochemistry and/or imaging is needed from the patient's and society's perspective

Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET

PET using 18F-FDG is a promising technique to monitor response in oncology. Unfortunately, a multitude of analytic methods is in use. To date, it is not clear whether simplified methods could replace complex quantitative methods in routine clinical practice. The aim of this study was to select those methods that would qualify for further assessment in a future prospective response-monitoring study by comparing results with patient outcome. Methods: Dynamic 18F-FDG PET scans were obtained on 2 groups of patients. First, 10 patients with advanced non-small cell lung cancer (NSCLC) were scanned on consecutive days before treatment to assess test-retest variability. Second, 30 scans were obtained on 19 patients with locally advanced NSCLC as part of an ongoing response-monitoring study. These scans were analyzed by 2 observers to assess observer variability. In addition, these studies were used to compare various methods with the gold standard, full kinetic analysis (nonlinear regression [NLR]). Results: Using an imagederived input function, NLR showed excellent test-retest and observer agreement confirming that it could be used as a gold standard method. From a total of 34 analytic methods, 10 showed good correlation with NLR. Taking into account the degree of complexity of the methods, 4 remain for further evaluation. Conclusion: The optimal method for analysis of 18F-FDG PET data was determined for several levels of complexity. Four methods need to be evaluated further to determine the optimal trade-off between simplicity and accuracy for routine clinical practice

A randomized trial of PET scanning to improve diagnostic yield of direct laryngoscopy in patients with suspicion of recurrent laryngeal carcinoma after radiotherapy

The RELAPS study (REcurrent LAryngeal carcinoma PET Study) was designed to determine whether FDG-PET is of value in the selection of patients for direct laryngoscopy under general anesthesia in patients with suspicion of recurrent laryngeal carcinoma after radiotherapy. In a randomized controlled clinical trial the current diagnostic practice, i.e. all patients undergo direct laryngoscopy, will be compared to a strategy in which FDG-PET selects the patients for laryngoscopy. All eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group NWHHT will participate in this multicenter trial. The study population consists of patients with clinical suspicion of recurrent T2-T4 laryngeal carcinoma after radiotherapy (without obvious signs of tumor) in whom a direct laryngoscopy under general anesthesia with taking of biopsies is indicated by the local physician. The primary efficacy endpoint is the difference in the number of futile indications for direct laryngoscopy between the conventional diagnostic arm and the FDG-PET based diagnostic arm. An indication for laryngoscopy is classified as futile if this laryngoscopy was negative and no recurrence was diagnosed within 6 months follow-up (gold standard). The FDG-PET based strategy may increase the risk of missing recurrent tumor compared to current practice. Safety endpoints include survival and morbidity due to laryngoscopy with taking of biopsies. Survival rates of both groups will have to be collected outside the time frame of the funded trial. Resectability of recurrent tumor and tumor negative surgical margins after total laryngectomy will be used as proxy endpoints. The trial will also compare quality of life and direct medical costs between both arms

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET

PURPOSE: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. MATERIAL AND METHODS: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17). FDG uptake was quantitatively assessed by standardized uptake values. RESULTS: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median -44% (-75 to 2); in non-responders, it decreased by a median of -15% (-46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. CONCLUSION: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermi

Traditional versus up-front [18F] fluorodeoxyglucose-positron emission tomography staging of non-small-cell lung cancer: A Dutch cooperative randomized study

Purpose: We investigated whether application of positron emission tomography (PET) immediately after first presentation might simplify staging while maintaining accuracy, as compared with traditional strategy in routine clinical setting. Methods: At first presentation, patients with a provisional diagnosis of lung cancer without overt dissemination were randomly assigned to traditional work-up (TWU) according to international guidelines or early PET followed by histologic/cytologic verification of lesions, or imaging and follow-up. Patients with [18F] fluorodeoxyglucose (18FDG) -avid, noncentral tumors without suspicion of mediastinal or distant metastases on PET proceeded directly to thoracotomy. Follow-up in presumed benign lesions was at least 12 months. In patients treated with surgery or neoadjuvant therapy, the quality of staging was measured by comparing the clinical stage to the final stage (combination of peroperative staging and 6 months of follow-up). To investigate test substitution, we analyzed the number of (non)invasive tests to achieve clinical TNM staging, and its associated costs. Results: Between 1999 and 2001, 465 patients (233 TWU, 232 PET) were enrolled at 22 hospitals. The mean (standard deviation) number of procedures to finalize staging was equal in the TWU arm and the PET arm: 7.9 (2.0) v 7.9 (1.9), P = .90, respectively. Mediastinoscopies occurred significantly less often in the PET arm. Agreement between clinical and final stage was good in both arms (K = .85 v .78; P = .07). Costs did not differ significantly. Conclusion: Up-front 18FDG-PET in patients with (suspected) lung cancer does not reduce the overall number of diagnostic test, but it maintains quality of TNM staging with the use of less invasive surgery