UZ Leuven

Lymph node staging in non-small cell lung cancer with FDG-PET scan: A prospective study on 690 lymph node stations from 68 patients. Vansteenkiste JF, Stroobants SG, De Leyn PR, Bogaert J, Dupont PJ, Maes A, Deneffe GJ, Nackaerts KL, Verschakelen JA, Lerut TE, Mortelmans LA, Demedts MG. J Clin Oncol 1998;16:2142-2149. Abstract: PURPOSE: To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS: ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION: PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.

Prognostic importance of the Standardized Uptake Value on FDG-PET-scan in non-small cell lung cancer: An analysis of 125 cases. Vansteenkiste JF, Stroobants SG, De Leyn PR, Dupont PJ, Verbeken EK, Deneffe GJ, Mortelmans LA, Demedts MG, The Leuven Lung Cancer Group. J Clin Oncol 1999;10:3201-3206. Abstract: PURPOSE: The amount of radio-labeled (18)F-fluoro- 2-deoxy-glucose (FDG) uptake, a measurement of the increased glucose metabolism of non-small-cell lung cancer (NSCLC) cells, has recently been correlated with proliferation capacity. The Standardized Uptake Value (SUV), a semi-quantitative measurement of FDG uptake on positron emission tomography (PET) scan, could thus be of prognostic significance. PATIENTS AND METHODS: We analyzed the follow-up of 125 potentially operable NSCLC patients, previously included in three of our prospective PET protocols. Performance status, maximal tumor diameter, tumorcell type, SUV, and final staging were analyzed for their possible association with survival. RESULTS: Sixty-five patients had stage I or II NSCLC, 37 had stage IIIA, and 23 had stage IIIB. Treatment was complete resection in 91 cases. In a univariate analysis, performance status (P =.002), stage (P =.001), tumor diameter (P =.06), tumor-cell type (P =.03), and SUV greater than 7 (P =.001) were correlated with survival. For SUV,group dichotomy with a cut-off SUV of 7 had the best discriminative value for prognosis, both in the total and surgical cohort. A multivariate Cox analysis identified performance status (P =.02), stage (P =.01), and SUV (P =.007) as important for the prognosis. In the surgical group, patients with a resected tumor less than 3 cm had an expected 2-year survival of 86%, if the SUV was below 7, and 60%, if above 7. Nearly all resected tumors larger than 3 cm had SUV’s greater than 7 and an expected 2-year survival of 43%. CONCLUSION: We conclude that the FDG uptake in primary NSCLC on PET has an important prognostic value and could be complementary to other well-known factors in the decision on adjuvant treatment protocols.

Doubleblind, placebo-controlled, randomized phase 3 trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. Vansteenkiste J, Pirker R, Massuti B, Barata F, Rosell R, Gastl G, Siena S, Gateley J, Tomita D, Colowick AB, Musil J, ARANESP 980297 Study Group. J Natl Cancer Inst 2002;94:1211- 1220. Abstract: BACKGROUND: Patients receiving chemotherapy often develop anemia. Darbepoetin alfa (Aranesp(TM)) is an erythropoiesis-stimulating glycoprotein that has been shown, in dose-finding studies, to be safe and clinically active when administered to patients with cancer every 1, 2, or 3 weeks. This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy. METHODS: In this multicenter, double-blind, placebo-controlled study, 320 anemic patients (hemoglobin or=25% improvement; mean difference= 13%; 95% CI = 2% to 23%, P =.019) than patients receiving placebo. Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug. Adverse events were similar between the groups. CONCLUSIONS: Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy. Darbepoetin alfa decreased blood transfusion requirements, increased hemoglobin concentration, and decreased fatigue. Although no conclusions can be drawn about survival from this study, the potential salutary effect on disease outcome warrants further investigation in a prospectively designed study.

Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. The International Adjuvant Lung Cancer Trial Collaborative Group, by Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J.N Engl J of Med 2004;350:351-360. Abstract: BACKGROUND: On the basis of a previous metaanalysis, the International Adjuvant Lung Cancer Trial was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer. METHODS: We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation. Before randomization, each center determined the pathological stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to be combined with cisplatin), and its postoperative radiotherapy policy. The main end point was overall survival. RESULTS: A total of 1867 patients underwent randomization; 36.5 percent had pathological stage I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in 11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy, 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation (44.5 percent vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95 percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy also had a significantly higher disease-free sur-vival rate than those assigned to observation (39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83; 95 percent confidence interval, 0.74 to 0.94; P <0.003). There were no significant interactions with prespecified factors. Seven patients (0.8 percent) died of chemotherapy-induced toxic effects. CONCLUSIONS: Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer. Copyright 2004 Massachusetts Medical Society </p/>

Positron-emission tomography in prognostic and therapeutic assessment of lung cancer: systematic review. Vansteenkiste J, Fischer BM, Dooms C, Mortensen J. Lancet Oncol 2004;5:531-540. Abstract: Positron-emission tomography (PET) with 18-fluorodeoxyglucose has a role in the diagnosis and staging of lung cancer, but is also appealing for assessment of prognosis and treatment. A systematic search of the published work shows good evidence that [(18)F]FDG uptake on PET has independent prognostic value in newly diagnosed non-small-cell lung cancer. PET is a sensitive method of measuring the biological effects of anticancer therapy, but until better standardisation and large-scale experience is available, it should only be used for additional assessments of early response in clinical trials. Further studies are needed to define the role of [(18)F]FDG-PET in restaging after induction therapy in multimodality approaches for locally advanced lung cancer. The assessment of prognosis by [(18)F]FDG-PET is less substantiated in treated lung cancer than in newly diagnosed patients. Good prospective evidence documents the effectiveness of [(18)F]FDG-PET over CT in the correct identification of recurrent lung cancer.

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