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Sigrid Stroobants

Publications and source records attributed to Sigrid Stroobants.

12 recordsLinked to original sources

Prospective comparative study of integrated positron emission tomography-computed tomography scan compared with remediastinoscopy in the assessment of residual mediastinal lymph node disease after induction chemotherapy for mediastinoscopy-proven stage IIIA-N2 Non-small-cell lung cancer: a Leuven Lung Cancer Group Study.

PURPOSE: Mediastinal restaging after induction therapy for non-small-cell lung cancer remains a difficult and controversial issue. The goal of this prospective study was to compare the performance of integrated positron emission tomography (PET)--computed tomography (CT) and remediastinoscopy in the evaluation of mediastinal lymph node metastasis after induction chemotherapy. PATIENTS AND METHODS: Thirty consecutive stage IIIA-N2 non-small-cell lung cancer patients surgically treated at our institution were entered onto this prospective study. N2 disease was proven by cervical mediastinoscopy, at which a mean number of 3.8 lymph node levels were biopsied. After completion of induction chemotherapy, the mediastinum was reassessed by integrated PET-CT and remediastinoscopy. All patients underwent thoracotomy with attempted complete resection and systematic nodal dissection. RESULTS: PET-CT showed no evidence of nodal disease (N0) in 13 patients, Hilar nodal disease (N1) disease in three patients, and residual mediastinal disease (N2) in 14 patients. Remediastinoscopy was positive in only five patients. The preinduction involved lymph node level could be accurately re-evaluated in 18 patients. This was not the case in the other 12 because of extensive fibrosis and adhesions. In 17 patients, persistent N2 disease was found at thoracotomy. The sensitivity, specificity, and accuracy of PET-CT were 77%, 92%, and 83%, respectively. These parameters for remediastinoscopy were 29%, 100%, and 60%, respectively. Sensitivity (P < .0001) and accuracy (P = .012) were significantly better for PET-CT. CONCLUSION: After a thorough staging mediastinoscopy, postinduction remediastinoscopy had a disappointing sensitivity because of adhesions and fibrosis. Integrated PET-CT yielded a better result than that obtained in previous studies with side-by-side PET and CT images.

Aged↗

The current status of FDG-PET in tumour volume definition in radiotherapy treatment planning.

Positron emission tomography (PET) scan, mainly using 18 F-fluoro-deoxyglucose (FDG) as a tracer, is currently widely accepted as a diagnostic tool in oncology. It may lead to a change in staging and therefore in treatment management. PET can also be used to define the target volume in radiation treatment planning and to evaluate treatment response. In this review, we focused on issues concerning the role of PET in target volume delineation, both for the primary tumour and regional lymph nodes. A literature search was performed using MEDLINE. Furthermore, the following questions were addressed: does PET allow accurate tumour delineation and does it improve the outcome of radiotherapy, in terms of reduced toxicity or a higher tumour control probability? Combined computer tomography (CT) and PET information seems to influence target volume delineation. Using (CT-) PET scan, interobserver variability is being reduced. Only few studies compared delineation based on PET with pathologic examination, showing a complex relation. Preliminary results concerning incorporation of PET information in to target volume delineation varies in different tumour sites. In the field of lung cancer, incorporation of PET seems to improve tumour coverage and spare normal tissues, which may lead to less toxicity or the possibility to escalate dose. In oesophageal cancer and in lymphoma, PET scan can be used to include PET positive lymph nodes in the target volume. In most other tumour sites not enough data are currently available to draw definitive conclusions about the role of PET in radiation treatment planning.

Fluorodeoxyglucose F18↗

Hodgkin's lymphoma: evolving concepts with implications for practice.

Hodgkin's lymphoma is a unique neoplasm of B lymphocytes. Recent data provide new understandings of the pathogenesis and options for staging and therapy of the disease. Three specific topics are addressed in this chapter. In Section I, Dr. Richard Ambinder reviews implications of the relationship of Epstein-Barr virus (EBV) and Hodgkin's lymphoma. This relation includes varying geographic epidemiologic associations, including varying associations with the clinical syndrome of infectious mononucleosis. There are plausible mechanisms, including processes initiated by viral proteins, by which EBV might lead to tumorigenesis. These mechanisms include promotion of genetic instability and alteration of normal processes of apoptosis. In addition to an epidemiologic association and potential role in pathogenesis, viral antigens may pose theoretical targets for anti-cancer therapies, including vaccination. In Section II, Dr. Sigrid Stroobants describes the potential role of positron emission tomographic (PET) scanning. By assessing differences in the metabolic activities of cancer cells, PET scanning may be superior to computerized tomographic scanning, which is limited to showing structural anatomical abnormalities. In patients with Hodgkin's and non-Hodgkin's lymphoma, PET scanning has been tested as an initial staging tool, to assess the rate of therapeutic response from a prognostic perspective, and to differentiate residual tumor from fibrotic masses in patients who have completed therapy. Particularly in assessing the nature of a residual mass seen with other post-therapeutic imaging modalities, PET scanning may provide unique information; very high negative predictive values have been reported. However, before this technology can be recommended for incorporation into standard management, properly conducted prospective trials are required to better evaluate the clinical utility of PET with respect to eventual patient outcomes. In Section III, Dr. Ralph Meyer reviews current data regarding the management of patients with limited-stage Hodgkin's lymphoma. Over the past decade, standard treatment has evolved to consist of combined-modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation. As this therapy continues to include radiation therapy, patients will remain at risk of long-term toxicities that include the development of second cancers and cardiovascular events. These "late-effects" now account for more deaths than those attributed to progressive Hodgkin's lymphoma. Comparative data testing the role of chemotherapy alone are now available and demonstrate that omission of radiation therapy results in small but statistically significant reduction in disease control, but no detectable differences in overall survival. Further follow-up will clarify whether chemotherapy alone is the preferred treatment option; at present patients should be informed of the trade-offs involved in choosing between this option and combined modality therapy.

Combined Modality Therapy↗

Positron emission tomography with [(18)F]FDG for therapy response monitoring in lymphoma patients.

Lymphomas are a heterogeneous group of diseases with differing histopathology, clinical behaviour, response to therapy and outcome. Lymphomas are highly sensitive to chemotherapy and radiotherapy, and the recent developments in treatment have considerably improved clinical outcome. However, there is increasing recognition that this has been at the cost of long-term treatment-related effects in a relatively young patient population. Thus, one of the most challenging aspects in the imaging of lymphoma patients is tailoring the intensity of the treatment to the individual patient. This paper reviews recently published data concerning the use of fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) for therapy monitoring in lymphoma patients and highlights the shortcomings and future directions. A temporary strategy for the implementation of [(18)F]FDG-PET in the management of lymphoma patients is proposed.

Female↗

Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation.

The study assessed the prognostic value of fluorine 18-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) after salvage chemotherapy before high-dose chemotherapy with stem cell transplantation (HDT/SCT) in patients with induction failure or relapsing chemosensitive lymphoma. Retrospective analysis of the clinical and conventional imaging data of 60 patients scheduled for HDT/SCT was performed in parallel with the analysis of the [18F]FDG-PET results. To determine the ability of [18F]FDG-PET to predict clinical outcome, PET images were reread without knowledge of conventional imaging and clinical history. Presence or absence of abnormal [18F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Thirty patients showed a negative [18F]FDG-PET scan before HDT/SCT; 25 of those remained in complete remission, with a median follow-up of 1510 days. Two patients died due to a treatment-related mortality but without evidence of recurrent disease at that time (228-462 days). Only 3 patients had a relapse (median PFS, 1083 days) after a negative [18F]FDG-PET scan. Persistent abnormal [18F]FDG uptake was seen in 30 patients and 26 progressed (median PFS, 402 days); of these 26, 16 died from progressive disease (median OS, 408 days). Four patients are still in complete remission after a positive scan. Comparison between groups indicated a statistically significant association between [18F]FDG-PET findings and PFS (P <.000001) and OS (P <.00002). [18F]FDG-PET has an important prognostic role in the pretransplantation evaluation of patients with lymphoma and enlarges the concept of chemosensitivity used to select patients for HDT/SCT.

Adolescent↗

[(18)F]FDG PET monitoring of tumour response to chemotherapy: does [(18)F]FDG uptake correlate with the viable tumour cell fraction?

Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [(18)F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [(18)F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5 x 10(6) Daudi cells. When the tumour measured 15-20 mm, Endoxan was given intravenously. At different time points [1-15 days (d1-d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [(18)F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [(18)F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [(18)F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [(18)F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [(18)F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells.

Animals↗

Value of FDG-PET in the management of non-small cell lung cancer.

In the past 5 years, metabolic imaging with positron emission tomography (PET) using 18F-fluoro-2-deoxy-glucose (FDG) has become an important imaging modality in lung cancer patients. FDG-PET consistently proved to be superior to structure-based imaging modalities in both the diagnosis and staging of lung cancer. At this moment the use of FDG-PET in these indications needs further validation in multi-centre large-scale randomised studies, focusing mainly on treatment outcome parameters, survival and cost-efficacy. More recently, interesting findings have also been reported in the response assessment to cytotoxic treatments providing information of greater prognostic significance than can be obtained using conventional approaches. This review focuses on the potential role of FDG-PET in the diagnosis of lung nodules and masses, and in locoregional and extrathoracic staging of non-small cell lung cancer. Emphasis is put on the potential clinical implementation of the numerous data of the last decade.

Carcinoma, Non-Small-Cell Lung↗

Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group.

In a phase I study conducted by the EORTC Soft Tissue and Bone Sarcoma Group, 40 patients with advanced soft tissue sarcomas, most of whom had gastrointestinal stromal tumors (GISTs), received imatinib at doses of 400 mg q.d., 300 mg b.i.d., 400 mg b.i.d., or 500 mg b.i.d. Dose-limiting toxicities, including severe nausea, vomiting, edema and rash, were seen at the highest dose level; the maximum tolerated dose was therefore 400 mg b.i.d. Imatinib was active in the group of 35 patients with GISTs, producing partial responses in 19 (54%) patients and stable disease in 13 patients (37%). Responding patients have now been followed for a minimum of 10 months. The most common side effects seen in patients continuing on therapy have been periorbital edema (40%), peripheral edema (37.5%), fatigue (30%), skin rash (30%) and nausea/vomiting (25%). Severe late myelosuppression has also been seen occasionally. Eighteen (51%) GIST patients continue to have partial responses and 11 (31%) continue with stable disease. Thus, 82% of patients with GISTs are still obtaining clinically important benefits with continued imatinib therapy. Some patients showed accelerated progressive disease shortly after starting imatinib. On the other hand, following drug withdrawal, 2 patients had reductions in tumor burden and remain alive without drug therapy. In summary, imatinib is generally well tolerated and has significant activity during long-term treatment of patients with advanced GISTs.

Adult↗

Reducing loss of image quality because of the attenuation artifact in uncorrected PET whole-body images.

UNLABELLED: In whole-body PET, it is not unusual to shorten the study time by omitting the transmission scan and to ignore attenuation during reconstruction. If a transmission scan is available, many centers reconstruct the images with, but also without, attenuation correction. Although ignoring attenuation leads to an artifact in the reconstructed images, these images still provide valuable diagnostic information in oncologic applications. Several authors have reported that the attenuation artifact may actually increase the tumor-to-background ratio. In this study, we analyzed the causes of the artifact and proposed a new algorithm to reduce the adverse effects on visual image quality. METHODS: We analyzed the causes of the attenuation artifact mathematically and numerically, and we examined its effect on tumor-to-background ratio and on signal-to-noise ratio. In addition, we showed that the attenuation artifact may lead to loss of image detail in conventional maximum-likelihood expectation maximization (MLEM) reconstruction. A new maximum-likelihood algorithm allowing negative reconstruction values (NEG-ML) was derived to reduce this loss. RESULTS: The attenuation artifact consists of 2 components. The first component is the well-known scaling effect: The apparent activity is reduced because attenuation decreases the fraction of detected photons. The second component is a relatively smooth negative contribution that is added to attenuated regions surrounded by activity. The second component tends to increase the tumor-to-background ratio. However, a simulation experiment shows that this increase in signal may be entirely offset by an increase in noise. The negative contribution can interfere with the nonnegativity constraint of the MLEM algorithm, leading to loss of image detail in regions of high attenuation. The new NEG-ML algorithm avoids the problem by allowing negative pixel values. The algorithm is similar to MLEM in the suppression of the streak artifact but provides more anatomic information. In our department, it is in routine clinical use for reconstruction of PET whole-body images without attenuation correction. CONCLUSION: Ignoring attenuation may increase the tumor-to-background ratio, but this increase does not imply improved tumor detection. The NEG-ML algorithm reduces the adverse effect of the attenuation artifact on visual image quality.

Algorithms↗

Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to imatinib by small animal positron emission tomography.

BACKGROUND: Gastrointestinal stromal tumours (GIST) predominantly express activating mutations of the KIT tyrosine kinase receptor and are successfully treated with imatinib mesylate, a KIT inhibitor. As resistance to imatinib causes therapy failure, our aim was to develop an in vivo GIST model to evaluate KIT inhibitors and monitor therapy with small animal positron emission tomography (PET). MATERIALS AND METHODS: The first mouse model of GIST xenografts was successfully established by injecting GIST882 cells subcutaneously into nude mice. RESULTS: Using the small animal PET, FDG up-take in xenografts was significantly decreased after 24 h of treatment with imatinib, which correlated with a response to treatment, e.g., with a decrease in tumour volume, the inhibition of KIT and downstream intermediate phosphorylation and arrest of tumour cell proliferation as evaluated after 7 days of treatment. CONCLUSION: This model is useful to study imatinib resistance and to evaluate novel targeted therapies.

Animals↗