Guy Jerusalem

University of Liège | ulg · Department of Medical Oncology

Despite screening programs for early detection and the approval of human papillomavirus vaccines, around 6% of women with cervical cancer (CC) are discovered with primary metastatic disease. Moreover, one-third of the patients receiving chemoradiation followed by brachytherapy for locally advanced disease will have a recurrence. At the end, the vas...

Background: Indocyanine green (ICG) is a promising tracer for sentinel lymph node biopsy in early breast cancer. This randomized study was conducted to evaluate sentinel lymph node biopsy with ICG compared with blue dye as a tracer in woman with early breast cancer without any sign of lymph node invasion. Methods: Between January 2019 and Novemb...

(250 words) BACKGROUND: MONALEESA-3 demonstrated an overall survival (OS) benefit for ribociclib plus fulvestrant (R+F) in postmenopausal women with hormone receptor (HR) positive, HER2 negative advanced breast cancer (ABC). This study estimated quality-adjusted (QA) survival outcomes for patients receiving R+F vs placebo (P)+F in MONALEESA-3. METH...

Background: Since the end of the last century, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as standard of care for axillary staging in early breast cancer in patients without any clinical sign of axillary lymph node infiltration. The worldwide most frequently used mapping method consists in the injection of...

Background: Despite that breast conservative therapy became the standard of care in breast cancer, modified radical mastectomy, a large mutilating surgery, is still required for an important number of patients. In order to improve the quality of life and the psychological aspects of a surgery involving the femininity of woman, we developed a new l...

Purpose: Cancer patients often report low self-esteem and high emotional distress. Two factors seem particularly linked to these symptoms: emotion regulation strategies and mindfulness. The interest of hypnosis and self-care to relieve these symptoms is not well documented. Our randomized controlled trial aimed at assessing the effect of a group i...

Colorectal cancer (CRC) cells are traditionally considered unresponsive to TGFβ due to mutations in the receptors and/or downstream signaling molecules. TGFβ influences CRC cells only indirectly via stromal cells, such as cancer-associated fibroblasts. However, CRC cell ability to directly respond to TGFβ currently remains unexplored. This represen...

Introduction: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSC...

Objective Cancer has a lot of consequences such as fatigue, sleep disturbances, emotional distress, cognitive impairment and reduced physical activity. Some hypnosis‐based psychological interventions showed positive effects on fatigue, sleep and emotional distress, but generally focussed on breast cancer patients. Our study aimed at assessing the e...

Objectives We aimed to determine the prognostic value of baseline Health-Related Quality Of Life (HRQOL) and geriatric assessment (GA) to predict three-month mortality in older patients with cancer undergoing treatment. Methods Logistic regressions analysed HRQOL, as measured with the EORTC Global Health Status (GHS) scale, and geriatric informati...

Background The addition of everolimus to exemestane therapy significantly improves progression-free survival in postmenopausal patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant breast cancer. However, the safety profile of this schedule still might be optimized.Methods Patients included in the BALLET trial were assessed...

Background: The APHINITY trial demonstrated that pertuzumab, when added to adjuvant trastuzumab and chemotherapy, modestly but statistically significantly improved invasive disease-free survival (IDFS) among patients with HER2-positive, operable breast cancer. From November 2011 until August 2013, 2400 patients were randomly assigned to receive per...

Background: In animal models of hormone receptor positive (HR+) breast cancer, acquired resistance to continued letrozole was shown to be reversed by estrogen-induced apoptosis. We hypothesized that the rise in estrogen levels during short treatment interruptions would resensitize breast cancer cells to letrozole and improve treatment outcome. SOLE...

Objective: Several studies show that self-perception of aging (SPA) is a significant predictor of mental and physical health. In this study, we analyze the effect of SPA on mortality in the specific context of geriatric oncology. Methods: The sample constituted of 140 individuals aged 65 years and older suffering from a recent nonmetastatic canc...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Here we report the results of a pr...

In December 2017, ESMO Open—Cancer Horizons convened a round-table discussion on the background and latest data regarding cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy (ET) in the treatment of endocrine-sensitive breast cancer (BC). A review on this discussion was published in summer 2018 ( https://esmoopen.bmj.com/content/3/5/...

Introduction/Background Cancer-mediated inflammation and immunosuppression together with concomitant chemoradiation (CCRT) affects the hematological profile of patients treated for locally advanced cervical cancer (LACC). We investigated the predictive value of a low hemoglobin (Hb) and lymphocytes counts on the outcome of patients receiving CCRT f...

Background Ribociclib in combination with endocrine therapy (ET) is the current standard of care in first-line for HR+/HER2- aBC. An increasing proportion of patients who are candidates for ribociclib are older (≥70 years of age). The number of older patients who have participated thus far in ribocicib trials is, however, small, and little data is...

Background Abemaciclib, a selective CDK4 & 6 inhibitor, demonstrated single-agent activity in NSCLC and melanoma (Patnaik et al., 2016). Clinical data demonstrate abemaciclib penetrates the blood brain barrier resulting in comparable concentrations in tissues and plasma (Sahebjam et al., 2016). Methods Study JPBO is a Simon 2-stage trial evaluatin...

Background The phase III MONALEESA-3 trial (NCT02422615; N = 726) investigated RIB, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, + FUL as first-line (1L) or second-line (2L) treatment for postmenopausal pts with HR+/HER2− ABC. Here we report OS and 1L progression-free survival (PFS) results. Methods Postmenopausal pts with HR+/HER2− ABC were...

Background: Breast cancer is a leading cause of death for women worldwide, with incidence increasing in lower-income countries. For patients with human epidermal growth factor receptor-2-positive (HER2+) breast cancer, widespread availability of several agents targeting the HER2 receptor has resulted in survival gains over the past decades. Howeve...

Background: Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatme...

Background: Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and tryptophan and their ratio in breast cancer patients and...

Purpose To characterize the pharmacokinetics (PK) of, and perform an exploratory exposure–response (E–R) analysis for, pertuzumab in patients with HER2-positive early breast cancer (EBC) within the APHINITY study (NCT01358877, BIG 4–11/BO25126/TOC4939G). Methods A previously developed pertuzumab two-compartment linear population pharmacokinetic (p...

Introduction: Durvalumab is a selective, high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) binding to programmed death 1. Here we report safety and clinical activity in the NSCLC cohort of a phase I/II trial that included multiple tumor types (Study 1108; NCT01693562). Methods: Patients...

Background: In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL). Methods: In the SOLE QoL sub-...

Objectives: This study aims to investigate health-related quality of life (HRQOL) at baseline and at follow-up in older patients with cancer and to determine prognostic factors for HRQOL decline. Methods: A prospective Belgian multicentre (n = 22) study was performed. Patients ≥70 years with a malignant tumor and abnormal G8 (≤14/17) screening t...

Purpose To prevent febrile neutropenia (FN), European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommend primary prophylaxis with granulocyte colony-stimulating factors (PPG) for patients at high risk (≥ 20%) of FN. In Belgium, the use of PPG is restricted by specific reimbursement criteria. The impact of these criteria...

Purpose Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baselin...

Background Olaparib, a potent oral poly(ADP-ribose) polymerase inhibitor, is partially renally cleared. We investigated the pharmacokinetics and safety of olaparib in patients with mild or moderate renal impairment to provide dosing recommendations. Methods This phase I open-label study assessed the pharmacokinetics, safety and tolerability of sin...

Background Abemaciclib is a selective CDK4 & 6 inhibitor approved on a continuous dosing schedule for HR+, HER2- advanced breast cancer (ABC) as monotherapy (MONARCH 1) and in combination with endocrine therapy (ET). A previous Phase 1b (NCT01394016) cohort of HR+ ABC patients (pts) demonstrated efficacy of abemaciclib monotherapy (150mg and 200mg...

Background: In the Phase III MONALEESA-3 (NCT02422615) study, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + fulvestrant (FUL) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + FUL in postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we present MON...

Background: Xentuzumab (Xen), an IGF-1/-2-neutralizing Ab, binds IGF-1 and IGF-2, inhibits their growth-promoting signaling, and suppresses AKT activation by everolimus (Ev). This Phase 1b/2 trial evaluates Xen in combination with Ev and exemestane (Ex) in HR+/HER2− LA/mBC. Methods: The two-arm, open-label, randomized Phase 2 part enrolled female p...

Background: The international guidelines support upfront use of endocrine therapies (HT), with or without new targeted agents (TA), in HR+ve/HER2-ve mBC. However, routine administration of regimens containing chemotherapy (CT) is still common, even in the absence of visceral crisis. Unfortunately, robust data from head-to-head direct comparisons am...

Background: HER2-positive breast cancers usually contain large amounts of T-cell infiltrate. We hypothesised that trastuzumab resistance in HER2-positive breast cancer could be mediated by immune mechanisms. We assessed the safety and anti-tumour activity of pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, added to trastuzumab in...

Background: Chemotherapy plays an important role in the treatment of early breast cancer (EBC). Granulocyte-colony stimulating factors (G-CSF) can reduce the risk of febrile neutropenia as primary prophylaxis (PP) or secondary prophylaxis (SP). The BRONS study investigated the incidence of serious neutropenic events (SNE) and G-CSF use in a Belgian...

CT-based regimens are not significantly superior to HT-based therapies as 1 st /2 nd line treatments for postmenopausal HR+ve/HER2-ve mBC. • HT+TA including CDK 4/6i and eve are significantly superior to HT alone and to many 1 st /2 nd line CT regimens. • The three CDK4/6i combined with HT did not differ significantly among each other. Our data str...

Purpose: Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triple-negative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), and retinoblastoma protein (RB). Experimental Design: IHC analyses were conduc...

Background Cancer has a lot of consequences on patients’ quality of life (such as cancer-related fatigue (CRF), sleep difficulties and emotional distress) and on patients’ partners and their relationship, such as distress and communication difficulties. These consequences are undertreated, and interventions based on hypnosis often focus on breast c...

Introduction The PARP inhibitor olaparib is efficacious as monotherapy and has potential application in combination with endocrine therapy for the treatment of breast cancer. This phase I study assessed the safety and pharmacokinetic (PK) profiles of olaparib combined with tamoxifen, anastrozole or letrozole in patients with advanced solid tumours....

Introduction: Trebananib, a peptide-Fc fusion protein, blocks angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. Trebananib plus trastuzumab and paclitaxel was evaluated in human epidermal growth factor receptor 2-positive breast cancer in an open-label phase 1b clinical study. Patients and methods: Wome...

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating lymphocytes. Additionally, circulating immune cells are also often linked to chemotherapy response. We performed a retrospective analysis on a cohort of 11...

Background: We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between th...

Aims: Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination...

Reprogramming of mRNA translation has a key role in cancer development and drug resistance 1 . However, the molecular mechanisms that are involved in this process remain poorly understood. Wobble tRNA modifications are required for specific codon decoding during translation2,3. Here we show, in humans, that the enzymes that catalyse modifications o...

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this...

Importance Everolimus plus exemestane and capecitabine are approved second-line therapies for advanced breast cancer. Objective A postapproval commitment to health authorities to estimate the clinical benefit of everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor–positive, human epidermal growth factor recept...

Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a...

Introduction Triple negative breast cancer (TNBC) comprises heterogeneous agressive tumours. The standard treatment relies entirely on chemotherapy. While EGFR is expressed in 50%–75% of TNBC, clinical trials with erlotinib or cetuximab fail to show clinical benefit. Recently, we demonstrated that EGFR interacts with MT4-MMP, the membrane-type 4 ma...