References of "JERUSALEM, Guy"
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See detailMulticenter implementation of geriatric assessment in Belgian patients with cancer: A survey on treating physicians' general experiences and expectations.
Kenis, Cindy; Heeren, Pieter; Bron, Dominique et al

in Journal of geriatric oncology (in press)

OBJECTIVES: The aim of this study is to identify treating physicians' general experiences and expectations regarding geriatric assessment (GA) in older patients with cancer. MATERIALS AND METHODS: A ... [more ▼]

OBJECTIVES: The aim of this study is to identify treating physicians' general experiences and expectations regarding geriatric assessment (GA) in older patients with cancer. MATERIALS AND METHODS: A survey was carried out in 9 Belgian hospitals, which participated in a national GA implementation project focusing on older patients with cancer. A newly developed questionnaire was completed by their treating physicians. Data collection comprised of reviewing hospital data, general respondent data, and treating physicians' general experiences and expectations regarding GA. Descriptive statistics were calculated. RESULTS: Eighty-two physicians from 9 hospitals participated. The GA team composition can vary substantially, with a nurse as core member. Ideally, all older patients with cancer in whom a treatment decision is necessary, should benefit from the GA. Nearly all GA domains are reported as very important. Availability of GA results can be improved. Treating physicians want geriatricians to coordinate geriatric recommendations related to the identified GA problems, and expect from trained healthcare workers (THCWs) to collect GA data, to report GA results, and to follow-up the implementation of geriatric recommendations. CONCLUSION: This study identifies relevant information for improving the implementation of GA in older patients with cancer in Belgium and reveals priorities for a THCW from the treating physician's point of view. To increase the effectiveness of GA, further efforts are needed to improve the implementation of geriatric recommendations. [less ▲]

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See detailNeoadjuvant chemotherapy in breast cancer induces miR-34a and miR-122 expression
FRERES, Pierre ULg; JOSSE, Claire ULg; Bovy, Nicolas ULg et al

in Journal of Cellular Physiology (2014)

Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti-cancer drugs on their expression levels. In this article, we ... [more ▼]

Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti-cancer drugs on their expression levels. In this article, we describe the modifications of circulating miRNAs profile after neoadjuvant chemotherapy (NAC) for breast cancer. The expression of 188 circulating miRNAs was assessed in the plasma of 25 patients before and after NAC by RT-qPCR. Two miRNAs, miR- 34a and miR-122, that were significantly increased after NAC, were measured in tumor tissue before and after chemotherapy in 7 patients with pathological partial response (pPR) to NAC. These 2 chemotherapy-induced miRNAs were further studied in the plasma of 22 patients with adjuvant chemotherapy (AC) as well as in 12 patients who did not receive any chemotherapy. Twenty-five plasma miRNAs were modified by NAC. Among these miRNAs, miR-34a and miR-122 were highly upregulated, notably in pPR patients with aggressive breast cancer. Furthermore, miR-34a level was elevated in the remaining tumor tissue after NAC treatment. Studying the kinetics of circulating miR-34a and miR-122 expression during NAC revealed that their levels were especially increased after anthracycline-based chemotherapy. Comparisons of the plasma miRNA profiles after NAC and AC suggested that chemotherapy-induced miRNAs originated from both tumoral and non-tumoral compartments. This study is the first to demonstrate that NAC specifically induces miRNA expression in plasma and tumor tissue, which might be involved in the anti-tumor effects of chemotherapy in breast cancer patients. [less ▲]

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See detailImpact de la double stigmatisation en oncogériatrie : Etat des lieux
Schroyen, Sarah ULg; Adam, Stéphane ULg; JERUSALEM, Guy ULg et al

in Gériatrie et Psychologie Neuropsychiatrie du Vieillissement (2014), 12(2), 131-8

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See detailL'âgisme et ses conséquences cliniques en oncogériatrie: état des lieux et pistes d'interventions
Schroyen, Sarah ULg; Adam, Stéphane ULg; Jerusalem, Guy ULg et al

in Revue Médicale de Liège (2014), 69(5-6), 395-401

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See detailFinal Overall Survival: Fulvestrant 500 mg vs 250 mg in the Randomized CONFIRM Trial.
Leo, Angelo Di; Jerusalem, Guy ULg; Petruzelka, Lubos et al

in Journal of the National Cancer Institute (2014), 106(1), 337

BACKGROUND: At the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial ... [more ▼]

BACKGROUND: At the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial, approximately 50% of patients had died. A final analysis of OS was subsequently planned for when 75% of patients had died. METHODS: Patients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (+/-3) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections (one fulvestrant and one placebo [identical in appearance to study drug]) on days 0, 14 (two placebo injections only), and 28 and every 28 (+/-3) days thereafter. OS was analyzed using an unadjusted log-rank test. No adjustments were made for multiplicity. Serious adverse events (SAEs) and best response to subsequent therapy were also reported. All statistical tests were two-sided. RESULTS: In total, 736 women (median age = 61.0 years) were randomly assigned to fulvestrant 500mg (n = 362) or 250mg (n = 374). At the final survival analysis, 554 of 736 (75.3%) patients had died. Median OS was 26.4 months for fulvestrant 500mg and 22.3 months for 250mg (hazard ratio = 0.81; 95% confidence interval = 0.69-0.96; nominal P = .02). There were no clinically important differences in SAE profiles between the treatment groups; no clustering of SAEs could be detected in either treatment group. Type of first subsequent therapy and objective responses to first subsequent therapy were well balanced between the two treatment groups. CONCLUSIONS: In patients with locally advanced or metastatic estrogen receptor-positive breast cancer, fulvestrant 500mg is associated with a 19% reduction in risk of death and a 4.1-month difference in median OS compared with fulvestrant 250mg. Fulvestrant 500mg was well tolerated, and no new safety concerns were identified. [less ▲]

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See detailPhase Ib study of Buparlisib plus Trastuzumab in patients with HER2-positive advanced or metastatic breast cancer that has progressed on Trastuzumab-based therapy.
Saura, Cristina; Bendell, Johanna; Jerusalem, Guy ULg et al

in Clinical cancer research : an official journal of the American Association for Cancer Research (2014), 20(7), 1935-45

PURPOSE: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2(+)) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose ... [more ▼]

PURPOSE: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2(+)) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose of this study was to determine the clinical activity of the PI3K inhibitor buparlisib (BKM120) in patients with HER2(+) advanced/metastatic breast cancer resistant to trastuzumab-based therapy. EXPERIMENTAL DESIGN: In the dose-escalation portion of this phase I/II study, patients with trastuzumab-resistant locally advanced or metastatic HER2(+) breast cancer were treated with daily oral doses of buparlisib and weekly intravenous trastuzumab (2 mg/kg). Dose escalation was guided by a Bayesian logistic regression model with overdose control. RESULTS: Of 18 enrolled patients, 17 received buparlisib. One dose-limiting toxicity of grade 3 general weakness was reported at the 100-mg/day dose level (the single-agent maximum tolerated dose) and this dose level was declared the recommended phase II dose (RP2D) of buparlisib in combination with trastuzumab. Common (>25%) adverse events included rash (39%), hyperglycemia (33%), and diarrhea (28%). The pharmacokinetic profile of buparlisib was not affected by its combination with trastuzumab. At the RP2D, there were two (17%) partial responses, 7 (58%) patients had stable disease (>/=6 weeks), and the disease control rate was 75%. Pharmacodynamic studies showed inhibition of the PI3K/AKT/mTOR and RAS/MEK/ERK pathways. CONCLUSIONS: In this patient population, the combination of buparlisib and trastuzumab was well tolerated, and preliminary signs of clinical activity were observed. The phase II portion of this study will further explore the safety and efficacy of this combination at the RP2D. Clin Cancer Res; 20(7); 1935-45. (c)2014 AACR. [less ▲]

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See detailLE DÉFI DU CONTRÔLE LOCAL DANS LE CANCER PULMONAIRE NON A PETITES CELLULES, LOCALEMENT AVANCE, NON OPERABLE
BARTHELEMY, Nicole ULg; LENNERTS, Evelyne ULg; MEYNS, Mia ULg et al

in Revue Médicale de Liège (2014), 69(Supp 1), 75-80

Le cancer broncho-pulmonaire non à petites cellules (CBNPC) est fréquent. Pour près d’un patient sur cinq, au moment du diagnostic, la maladie est déjà localement avancée et inopérable. A ce stade, le ... [more ▼]

Le cancer broncho-pulmonaire non à petites cellules (CBNPC) est fréquent. Pour près d’un patient sur cinq, au moment du diagnostic, la maladie est déjà localement avancée et inopérable. A ce stade, le pronostic de cette affection est mauvais, caractérisé, entre autres, par un taux élevé de réci - dive locale, malgré la chimiothérapie et la radiothérapie. Le but de cette revue est de décrire l’hétérogénéité de ce groupe de patients, de clarifier les modalités de traitement combinant la chimiothérapie et la radiothérapie et de préciser l’intérêt des techniques modernes de radiothérapie pour améliorer le contrôle local [less ▲]

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See detailEverolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial.
Andre, Fabrice; O'Regan, Ruth; Ozguroglu, Mustafa et al

in The lancet oncology (2014)

BACKGROUND: Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to ... [more ▼]

BACKGROUND: Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapy. Eligible patients were randomly assigned (1:1) using a central patient screening and randomisation system to daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m2) or to placebo plus trastuzumab plus vinorelbine, in 3-week cycles, stratified by previous lapatinib use. The primary endpoint was progression-free survival (PFS) by local assessment in the intention-to-treat population. We report the final analysis for PFS; overall survival follow-up is still in progress. This trial is registered with ClinicalTrials.gov, number NCT01007942. FINDINGS: Between Oct 26, 2009, and May 23, 2012, 569 patients were randomly assigned to everolimus (n=284) or placebo (n=285). Median follow-up at the time of analysis was 20.2 months (IQR 15.0-27.1). Median PFS was 7.00 months (95% CI 6.74-8.18) with everolimus and 5.78 months (5.49-6.90) with placebo (hazard ratio 0.78 [95% CI 0.65-0.95]; p=0.0067). The most common grade 3-4 adverse events were neutropenia (204 [73%] of 280 patients in the everolimus group vs 175 [62%] of 282 patients in the placebo group), leucopenia (106 [38%] vs 82 [29%]), anaemia (53 [19%] vs 17 [6%]), febrile neutropenia (44 [16%] vs ten [4%]), stomatitis (37 [13%] vs four [1%]), and fatigue (34 [12%] vs 11 [4%]). Serious adverse events were reported in 117 (42%) patients in the everolimus group and 55 (20%) in the placebo group; two on-treatment deaths due to adverse events occurred in each group. INTERPRETATION: The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated, HER2-positive, advanced breast cancer. The clinical benefit should be considered in the context of the adverse event profile in this population. FUNDING: Novartis Pharmaceuticals Corporation. [less ▲]

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See detailA phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease.
Coleman, Robert; Aksnes, Anne-Kirsti; Naume, Bjorn et al

in Breast cancer research and treatment (2014)

Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study ... [more ▼]

Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was -10.1 nmol bone collagen equivalents/mmol creatinine (-32.8 %; P = 0.0124); median bALP change was -16.7 ng/mL (-42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (>/=25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease. [less ▲]

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See detailLe traitement multidisciplinaire du glioblastome
BARTHELEMY, Nicole ULg; GENNIGENS, Christine ULg; Scholtes, Félix ULg et al

in Revue Médicale de Liège (2014), 69

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See detailDisease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.
Andre, Fabrice; Neven, Patrick; Marinsek, Nina et al

in Current medical research and opinion (2014)

Abstract Background: International guidelines for hormone-receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (BC) recommend sequential lines of ... [more ▼]

Abstract Background: International guidelines for hormone-receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. Methods: We conducted a retrospective chart review of 355 postmenopausal women with HR+, HER2- advanced BC who progressed on >/=1 line of HT (adjuvant or advanced) and completed >/=1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Results: Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Conclusions: Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR+, HER2- advanced BC who responded to HT may not be achieved. [less ▲]

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See detailBOLERO-3 : Everolimus plus Trastuzumab and Vinorelbine in asian patients with HER2-positive metastatic breast cancer
Toi, Masakazu; Masuda, Norikazu; ANDRE, Fabrice et al

Poster (2013, December)

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See detailmTOR inhibitors in advanced breast cancer: ready for prime time?
Martin, Lesley-Ann; Andre, Fabrice; Campone, Mario et al

in Cancer Treatment Reviews (2013), 39(7), 742-52

Current therapeutic approaches for advanced breast cancer frequently target receptors mediating cell survival and proliferation, such as the estrogen receptor and/or progesterone receptor and human ... [more ▼]

Current therapeutic approaches for advanced breast cancer frequently target receptors mediating cell survival and proliferation, such as the estrogen receptor and/or progesterone receptor and human epidermal growth factor receptor-2. Although these approaches are effective for many patients, treatment resistance is common. Therefore, new treatment approaches are needed for patients with advanced breast cancer. Mammalian target of rapamycin is a highly conserved serine-threonine kinase that acts as a major signaling hub that integrates and synergizes with cellular proliferation, survival, and/or motility signals mediated by estrogen receptor, human epidermal growth factor receptor-2, and other receptor tyrosine kinases. Dysregulation of mammalian target of rapamycin signaling occurs in various tumor types, including breast cancer, and has been associated with cancer pathogenesis, disease progression, and treatment resistance. Recent clinical trials show that combined inhibition of mammalian target of rapamycin and estrogen receptor represents an effective strategy for treating hormone receptor-positive advanced breast cancer progressing on nonsteroidal aromatase inhibitor therapy, and data from ongoing trials combining mammalian target of rapamycin inhibition with human epidermal growth factor receptor-2-targeted therapy are awaited. This review focuses on the molecular rationale underlying strategies to enhance sensitivity to treatment in hormone receptor-positive and human epidermal growth factor receptor-2-positive advanced breast cancer, the clinical efficacy of such approaches, and future perspectives. [less ▲]

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See detailEvaluation of Everolimus (EVE) in HER2+ advanced breast cancer (BC) with activated PI3K/mTOR pathway : exploratory biomarker observations from the BOLERO-3 trial
JERUSALEM, Guy ULg; ANDRE, Fabrice; CHEN, David et al

in European Journal of Cancer (2013, September), 49(Supplement 3), 8

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