Actualités thérapeutiques en oncologie sénologique: place actuelle et perspectives des traitements cibles
Jerusalem, Guy ; Rorive, Andrée ; Gennigens, Christine et al
in Revue Médicale de Liège (2007), 62 Spec No
The introduction of targeted therapies has largely modified the treatment strategies in oncology. Two targets are currently used for defining the systemic treatment of breast cancer: hormone receptors and ... [more ▼]
The introduction of targeted therapies has largely modified the treatment strategies in oncology. Two targets are currently used for defining the systemic treatment of breast cancer: hormone receptors and HER2 overexpression. Trastuzumab, a monoclonal antibody, is the only registered antiHER2 treatment in Belgium. The association of trastuzumab with chemotherapy is now the recommended adjuvant treatment for early breast cancer overexpressing HER2. Other antiHER2 medications are available and some will probably be registered soon. Angiogenesis is another potential target for improving the treatment results. The CHU Liege, as a reference center for the systemic treatment of solid tumors, participates in many international trials in order to validate these new approaches. The highest quality of care is required to be in compliance with the conduct of these clinical trials. Another benefit for the patient is the easy access to last generation medical treatments, generally not accessible in our health care system in Belgium outside of clinical trials. [less ▲]Detailed reference viewed: 103 (6 ULg)
Tomographie a emission de positons: un premier bilan.
Jerusalem, Guy ; Withofs, Nadia ; Rorive, Andrée et al
in Revue du Praticien (La) (2007), 57(17), 1864-70
Positron emission tomography (PET) has been widely used for several years for staging and response evaluation in oncology. It is time to critically review its role in routine patient care. [18F]-labelled ... [more ▼]
Positron emission tomography (PET) has been widely used for several years for staging and response evaluation in oncology. It is time to critically review its role in routine patient care. [18F]-labelled fluorodeoxyglucose ([18F]-FDG) remains the radiotracer of choice in most indications. Its high sensitivity, the half-life of 110 minutes and the easy production of this radiotracer explain its routine use although the specificity is not very good. Infectious or inflammatory processes can mimic tumours. Appropriate selection of patients studied in the recommended indications and interpretation of images by an experienced team having access to both clinical information and other diagnostic studies allows reducing the risk of false positives. Although PET is highly accurate, not all patients suffering from cancer need a PET study. Major improvements were also observed with conventional imaging techniques over the past 10 years. It is important to avoid long waiting lists because otherwise treatment delay may counterbalance the benefit of PET studies. [less ▲]Detailed reference viewed: 34 (2 ULg)
Actualites therapeutiques en oncologie: l'essor des therapeutiques ciblees
Gennigens, Christine ; Sautois, Brieuc ; Rorive, Andrée et al
in Revue Médicale de Liège (2007), 62(5-6, May-Jun), 391-8
Over the last decades, significant advances were make in basic research as concerns the malignant transformation of normal cells. As a result, new targets for treatment were identified. "Targeted ... [more ▼]
Over the last decades, significant advances were make in basic research as concerns the malignant transformation of normal cells. As a result, new targets for treatment were identified. "Targeted therapies" indicates that treatments are directed against specific molecular targets that play a major role in the activation of cell division and in the growth and dissemination of tumors. In particular, targeted therapies were developed against epithelial growth factor receptors and angiogenesis. We can expect specifise therapies against many other targets in the near future. Several drugs have obtained a marketing license. Predictive factors for tumor response and long term outcome should be developed for a better selection of the patient population who will benefit from these treatments. New imaging techniques are under development in order to assess the molecular response to these new approaches. [less ▲]Detailed reference viewed: 97 (8 ULg)
Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC).
; ; et al
in European Journal of Cancer (2007), 43(4), 725-35
AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional ... [more ▼]
AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional predictive markers. The following markers could be implicated in response to T: (1) the magnitude of Her-2 gene amplification; (2) the co-expression of the other HER family receptors, possibly responsible for HER-2 trans-activation; (3) the activated status of HER-2; (4) the activated status of downstream effectors as mitogen-activated protein kinases (MAPKs), p38 and p27. METHODS: Medical files of patients with MBC treated with T either as a single agent or in combination with chemotherapy (CT) were reviewed. HER family members (EGFR, HER-2, HER-3, HER-4), the phosphorylated forms of EGFR (p-EGFR), HER-2 (p-HER-2) and of the downstream effectors were evaluated in the archival tumours. The correlation between clinical outcome and the expression of these markers was investigated. RESULTS: (1) Increasing values of Her-2 amplification were associated with a higher probability of achieving an objective response; (2) no statistical significant correlation between the expression of the HER family receptors was found; (3) p-HER-2 was predictive of response in patients treated with T+CT; (4) a statistically significant correlation between p-ERK 1/2, p-p38 and p-HER-2 emerged, pointing to the activated vertical pathway p-HER-2-->p-MAPKs. CONCLUSIONS: p-HER-2 and the magnitude of Her-2 amplification were predictive of response to T and their role deserves to be analysed in larger and more homogenous T-treated populations such as those from large phase III trials. [less ▲]Detailed reference viewed: 11 (1 ULg)
FDG-PET for the routine follow-up in NHL: First prospective evaluation
Jerusalem, Guy ; ; Beguin, Yves et al
in Journal of Clinical Oncology (2006, June 20), 24(18, Part 1 Suppl. S), 439Detailed reference viewed: 24 (6 ULg)
The place of positron emission tomography imaging in the management of patients with malignant lymphoma.
Jerusalem, Guy ; Beguin, Yves
in Haematologica (2006), 91(4), 442-4Detailed reference viewed: 10 (4 ULg)
Diagnostic and therapeutic management of carcinoma of unknown primary: radio-imaging investigations.
Jerusalem, Guy ; Rorive, Andrée ; et al
in Annals of Oncology (2006), 17 Suppl 10Detailed reference viewed: 7 (2 ULg)
Sequential positron emission tomography using [18F]fluorodeoxyglucose for monitoring response to chemotherapy in metastatic breast cancer.
; Jerusalem, Guy ; et al
in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2006), 12(21), 6437-43
PURPOSE: To evaluate the clinical value of positron emission tomography (PET) for monitoring chemotherapy in metastatic breast cancer. EXPERIMENTAL DESIGN: Twenty patients with hormonorefractory or ... [more ▼]
PURPOSE: To evaluate the clinical value of positron emission tomography (PET) for monitoring chemotherapy in metastatic breast cancer. EXPERIMENTAL DESIGN: Twenty patients with hormonorefractory or hormonoreceptor-negative multimetastatic breast cancer were prospectively included. PET studies were done at baseline, at day 21 after the first cycle and at day 21 after the third cycle of chemotherapy. Metabolic response was defined based on visual and various modes of standardized uptake value (SUV) analysis of sequential PET studies. RESULTS: After one cycle, PET indicated a partial response in 12 patients, stable disease in 7 patients, and progressive disease in 1 patient, according to the visual analysis. After three cycles, PET showed a complete response in 5 patients, partial response in 11 patients, stable disease in 3 patients, and progressive disease in 1 patient. Seventy-five percent of the patients showing a metabolic response on visual analysis effectively responded to the treatment. The average SUV decreased on both the second and the third PET study, but only changes measured after three cycles of chemotherapy predicted the clinical response to chemotherapy and the overall survival. All methods for calculating the SUV (normalized for body weight, body surface area, or lean body mass) provided similar results. CONCLUSION: Semiquantitative analysis of [18F]fluorodeoxyglucose-PET studies done after three cycles of chemotherapy is useful for monitoring the response to chemotherapy in metastatic breast cancer. [less ▲]Detailed reference viewed: 20 (6 ULg)
F-18-FDG PET in children with lymphomas
Depas, Gisèle ; ; Jerusalem, Guy et al
in European Journal of Nuclear Medicine and Molecular Imaging (2005), 32(1), 31-38
Purpose: The aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with F-18-fluorodeoxyglucose (F-18-FDG) in children with lymphomas, at various stages ... [more ▼]
Purpose: The aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with F-18-fluorodeoxyglucose (F-18-FDG) in children with lymphomas, at various stages of their disease. Methods: Twenty-eight children (mean age 12.5 years, 14 girls, 14 boys) with Hodgkin's disease (HD, n=17) or non-Hodgkin's lymphoma (NHL, n= 11) were evaluated. Patients were investigated at initial staging (n=19), early in the course of treatment (n=19), at the end of treatment (n=16) and during long-term follow-up (n=19). A total of 113 whole-body PET studies were performed on dedicated scanners. PET results were compared with the results of conventional methods (CMs) such as physical examination, laboratory studies, chest X-rays, computed tomography, magnetic resonance imaging, ultrasonography and bone scan when available. Results: At initial evaluation (group 1), PET changed the disease stage and treatment in 10.5% of the cases. In early evaluation of the response to treatment (group 2), PET failed to predict two relapses and one incomplete response to treatment. In this group, however, PET did not show any false positive results. There were only 4/75 false positive results for PET among patients studied at the end of treatment (group 3, specificity 94%) or during the systematic follow-up (group 4, specificity 95%), as compared with 27/75 for CMs (specificity 54% and 66%, respectively). Conclusion: F-18-FDG-PET is a useful tool for evaluating children with lymphomas. Large prospective studies are needed to appreciate its real impact on patient management. [less ▲]Detailed reference viewed: 38 (4 ULg)
Evaluation of therapy for lymphoma.
Jerusalem, Guy ; Hustinx, Roland ; Beguin, Yves et al
in Seminars in Nuclear Medicine (2005), 35(3), 186-96
Positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) is the best noninvasive imaging technique for to assess response in patients suffering from lymphoma. Early response ... [more ▼]
Positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) is the best noninvasive imaging technique for to assess response in patients suffering from lymphoma. Early response evaluation ("interim PET") after one, a few cycles, or at midtreatment can predict response, progression-free survival, and overall survival. We calculated from data of 7 studies an overall sensitivity to predict treatment failure of 79%, a specificity of 92%, a positive predictive value (PPV) of 90%, a negative predictive value (NPV) of 81%, and an accuracy of 85%. Although it is not yet indicated to change patient management based on residual (18)F-FDG uptake on interim scan in chemotherapy-sensitive patients, prospective studies evaluating the role of an interim PET in patient management clearly are warranted. (18)F-FDG PET also has an important prognostic role in relapsing patients after reinduction chemotherapy before high-dose chemotherapy (HCT) followed by autologous stem cell transplantation (ASCT). However, all chemotherapy-sensitive patients remain candidates for HCT followed by ASCT, even if (18)F-FDG PET showed residual (18)F-FDG uptake. We calculated from data of 3 studies an overestimated risk of relapse in 16% of all PET-positive patients. Some patients with residual (18)F-FDG uptake will have a good outcome after HCT followed by ASCT. (18)F-FDG PET is the imaging technique of choice for end-of-treatment evaluation. However, (18)F-FDG is not specific for tumoral tissue. Active inflammatory lesions and infectious processes can be falsely interpreted as malignant residual cells. However, a negative (18)F-FDG PET cannot exclude minimal residual disease. Consequently, it is always indicated to correlate PET findings with clinical data, other imaging modalities, and/or a biopsy. We calculated, from data of 17 studies in end-of-treatment evaluation, a sensitivity of 76%, a specificity of 94%, a PPV of 82%, a NPV 92%, and an accuracy of 89%. [less ▲]Detailed reference viewed: 24 (3 ULg)
Positron emission tomography imaging for lymphoma.
Jerusalem, Guy ; Hustinx, Roland ; Beguin, Yves et al
in Current Opinion in Oncology (2005), 17(5), 441-5
PURPOSE OF REVIEW: To review the current role and the limitations of F-fluorodeoxygenase positron emission tomography in the management of lymphoma, with a particular focus on studies published since ... [more ▼]
PURPOSE OF REVIEW: To review the current role and the limitations of F-fluorodeoxygenase positron emission tomography in the management of lymphoma, with a particular focus on studies published since January 2004. RECENT FINDINGS: F-fluorodeoxygenase positron emission tomography should be routinely performed at the initial diagnosis of patients with suffering from Hodgkin's disease because it adds useful informations to conventional staging techniques. Residual F-fluorodeoxygenase uptake is an important prognostic factor after one or a few cycles of chemotherapy, but it is clearly too early to change patient treatment on the basis of F-fluorodeoxygenase positron emission tomography results. F-fluorodeoxygenase positron emission tomography is the best noninvasive imaging technique after treatment; however, it is always indicated to correlate positron emission tomography findings with clinical data, other imaging modalities, a biopsy, or all three to reduce the risk of false positive results. There are some concerns about the positive predictive value of positron emission tomography after treatment, especially in childhood lymphoma. Clinicians should be aware of positron emission tomography findings in specific clinical conditions in this patient population. F-fluorodeoxygenase positron emission tomography combined with computed tomography offers advantages over the two used separately and read side by side. It may be particularly useful for the planning of radiation therapy or for the planning of a surgical biopsy. Several studies have shown that F-fluorodeoxygenase positron emission tomography is definitively superior to Ga scintigraphy. New radiotracers such as F-fluorothymidine may be useful for the noninvasive assessment of proliferation in vivo. SUMMARY: F-fluorodeoxygenase positron emission tomography has become the most important nuclear medicine imaging modality in the field of lymphoma. It should be routinely used in the treatment of lymphoma patients. [less ▲]Detailed reference viewed: 18 (4 ULg)
Whole-Body Positron Emission Tomography using 18F-Fluorodeoxyglucose for Staging Response Assessment in Hodgkin's Disease
Jerusalem, Guy ; Hustinx, Roland ; Beguin, Yves et al
in Heinz, Beverley C. (Ed.) Trends in Hodgkin's Disease Research (2005)
Hodgkin's disease, sometimes called Hodgkin's lymphoma, is a cancer that starts in lymphatic tissue. Lymphatic tissue includes the lymph nodes and related organs that are part of the body's immune and ... [more ▼]
Hodgkin's disease, sometimes called Hodgkin's lymphoma, is a cancer that starts in lymphatic tissue. Lymphatic tissue includes the lymph nodes and related organs that are part of the body's immune and blood-forming systems. The lymph nodes are small, bean-shaped organs found underneath the skin in the neck, underarm, and groin. They are also found in many other places in the body such as inside the chest, abdomen, and pelvis. Lymph nodes make and store infection-fighting white blood cells, called lymphocytes. They are connected throughout the body by lymph vessels (narrow tubes similar to blood vessels). These lymph vessels carry a colourless, watery fluid (lymphatic fluid) that contains lymphocytes. Eventually the lymphatic fluid is emptied into the blood vessels in the left upper chest. There are 5 different types of Hodgkin's lymphoma: Nodular sclerosing Hodgkin's lymphoma; Mixed cellularity Hodgkin's lymphoma; Lymphocyte depletion Hodgkin's lymphoma; Lymphocyte-rich classical Hodgkin's lymphoma; Nodular lymphocyte-predominant Hodgkin's lymphoma. This volume examines and presents leading-edge research in this field. Preface; What Causes Hodgkin’s Disease? A Review of Analytical Epidemiology; Progress in Hodgkin’s Disease Research; New Insights in Pediatric Hodgkin’s Disease; Hodgkin’s Lymphoma and Infection; Roles of CD30 Signal Transduction in the Biology of Classic Hodgkin’s Lymphoma; Whole-Body Positron Emission Tomography Using 18F-Fluorodeoxyglucose for Staging and Response Assessment in Hodgkin’s Disease; The Clinical Value of Nuclear Medicine in the Assessment of Radio-and Chemotherapy Related Pulmonary and Cardiac Normal Tissue Damage in Patients with Hodgkin’s Disease; Cell Fusion and Carcinogenesis. Hodgkin and Reed-Sternberg Cells as Paradigm of Cell Fusion and Cell Cancerisation; Existential and Psychosocial Issues for Hodgkin’s Disease Survivors; Index. [less ▲]Detailed reference viewed: 17 (2 ULg)
Metabolic monitoring of chemosensitivity with 18FDG PET.
Jerusalem, Guy ;
in Methods in Molecular Medicine (2005), 111
Accurate and early evaluation of tumor response to chemotherapy is a growing clinical need for optimal management of oncology patients. This is even more warranted by the lack of appropriate response ... [more ▼]
Accurate and early evaluation of tumor response to chemotherapy is a growing clinical need for optimal management of oncology patients. This is even more warranted by the lack of appropriate response evaluation criteria to new molecularly targeted anticancer therapies. In the two last decades, new developments in the field of nuclear oncology have allowed the introduction of various radiopharmaceuticals to be used on dedicated imaging devices. In the present chapter, we report the added value that positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) may offer to assess tumor response to treatment. PET is a high-end imaging technology using 18FDG as metabolic tracer that mimics the biochemical behavior of the natural glucose molecule. Because most tumor types exhibit increased glucose metabolism, the imaging of 18FDG uptake within cancer tissues prior to any treatment enables the metabolic technique to follow tumor responsiveness sequentially after one or several courses of chemotherapy. Moreover, metabolic tumor response evaluated by 18FDG PET often precedes morphological tumor changes measured by computed tomography or magnetic resonance imaging. So far, the suboptimal proper ties of 18FDG tracer and the lack of standardized methodology in PET imaging remain objective limitations for qualitative and quantitative assessment of chemosensitivity using the metabolic method. [less ▲]Detailed reference viewed: 10 (2 ULg)
Sequential administration of epirubicin and paclitaxel for advanced breast cancer. A phase I randomised trial.
; ; et al
in Anticancer Research (2005), 25(2B), 1211-7
Forty-six previously untreated patients with advanced breast cancer were eligible for the present randomised phase I study. It aimed to evaluate the toxicity and activity of a therapeutic sequence with ... [more ▼]
Forty-six previously untreated patients with advanced breast cancer were eligible for the present randomised phase I study. It aimed to evaluate the toxicity and activity of a therapeutic sequence with epirubicin on day 1 followed by paclitaxel on day 2 (sequence A) or the reverse sequence, ie., paclitaxel on day 1 followed by epirubicin on day 2 (sequence B). The starting doses of epirubicin and paclitaxel, administered either according to sequence A or B, (level 1 cohort) were 90 mg/m2 and 175 mg/m2, respectively. Per cohort of 3 patients, the dose of paclitaxel was increased by 25 mg/m2 (levels 2 and 4) and of epirubicin by 10 mg/m2 (levels 3 and 5). Treatment was repeated with 3-week intervals. The maximal tolerated dose (MTD) was achieved at level 1 in sequence B (paclitaxel first) and level 3 (epirubicin 100 mg/m2 followed by paclitaxel 200 mg m2) in sequence A. Dose limiting toxicity (DLT) was neutropenia (+/- febrile) in both sequences. Cardiac events occurred in 28% of the patients; significant decrease in left ventricular ejection function (LVEF) was observed in 8/33 and in 2/13 patients in sequence A and B, respectively. This was associated with 5 and 1 cardiac heart failure (CHF), respectively. In 43 evaluable patients, 10 CR and 25 PR were observed (overall response rate 81%). In the 20 patients with locally advanced disease (LABC), the respective numbers were 7 CR and 11 PR; in the 23 metastatic (MBC) patients, 3 CR and 14 PR were recorded. The median survival of the both groups was not reached at 33 + months. In conclusion , the combination of epirubicin and paclitaxel has significant activity in breast cancer. The recommended sequence of both drugs in combination therapy, mainly to avoid neutropenia, is epirubicin day 1 followed by paclitaxel on day 2. Cardiac toxicity remains problematic in either sequence of administration. [less ▲]Detailed reference viewed: 25 (1 ULg)
L'image du mois. Tumeur de Merkel : reponse majeure a la chimiotherapie. "Il n'y a pas que la neige qui fond au soleil"...
Polus, Marc ; Piront, Patricia ; Jerusalem, Guy et al
in Revue Médicale de Liège (2004), 59(2), 67-8Detailed reference viewed: 348 (4 ULg)
CD34+ cell dose predicts costs after autologous peripheral blood stem cell transplantation for breast cancer.
Baron, Frédéric ; ; Baudoux, Etienne et al
in Haematologica (2004), 89(9), 1146-8
We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for ... [more ▼]
We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for patients receiving a CD34+ cell dose <5 x 10(6) cells/kg versus 22,339.4+/- 5471.1 for those receiving >5 x 10(6) CD34+ cells/kg (p=0.0065). [less ▲]Detailed reference viewed: 30 (7 ULg)
Traitement du cancer du sein chez la personne âgée
Gillain, Sophie ; Gennigens, Christine ; Sautois, Brieuc et al
in Revue Médicale Suisse (2004), 62
Le cancer du sein représente chez la personne âgée une pathologie fréquente. Le choix du traitement dépend de l'âge physiologique, des pathologies et comorbidités associées ainsi que du niveau de vie et d ... [more ▼]
Le cancer du sein représente chez la personne âgée une pathologie fréquente. Le choix du traitement dépend de l'âge physiologique, des pathologies et comorbidités associées ainsi que du niveau de vie et d'autonomie. De plus, selon les facteurs histopronostiques (récepteurs aux oestrogènes et à la progestérone, la surexpression du cerb-B2) on décidera éventuellement du schéma thérapeutique le plus approprié. Chez la personne âgée, la chirurgie (mastectomie ou tumorectomie), la radiothérapie et l'hormonothérapie trouvent leur place. Au-delà de 70 ans, la place de la chimiothérapie est incertaine. En effet, les patientes de plus de 70 ans sont sous-représentées dans les études randomisées. [less ▲]Detailed reference viewed: 222 (4 ULg)