Laurence Collette

• European Organisation for Research and Treatment of Cancer

Background and objective Patient-reported outcome measures (PROMs) are increasingly being used to capture the patients’ perspective of their functional status and quality of life (QoL). Big data can help us better understand patient-reported outcomes (PROs). Using prospectively collected data from the Prostate Cancer Diagnosis and Treatment Enhance...

Levels of the serum tumor markers (STMs) α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are used in staging classification for metastatic germ-cell cancers and support decisions on the intensity of first-line treatment for patients with nonseminoma. Use of preorchiectomy instead of prechemotherapy STM levels can lead to inad...

Background Active surveillance after orchiectomy is the preferred management in clinical stage I (CSI) germ-cell tumours (GCT) associated with a 15 to 30% relapse rate. Patients and methods In the IGCCCG Update database, we compared the outcomes of gonadal disseminated GCT relapsing from initial CSI to outcomes of patients with de novo metastatic...

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects...

Background Missing data may lead to loss of statistical power and introduce bias in clinical trials. The Covid-19 pandemic has had a profound impact on patient health care and on the conduct of cancer clinical trials. Although several endpoints may be affected, progression-free survival (PFS) is of major concern, given its frequent use as primary e...

Objectives: As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa). Design: We performed a systematic review to identify validated and non-validated studies. Data sources:...

Objective To evaluate the representativeness of Dutch patients participating in the EORTC boost-no boost trial to the target breast cancer patient population. Study design and setting All female breast cancer patients diagnosed between 1989-1996, aged≤70 years, treated with breast-conserving surgery and radiation therapy, were selected from the Ne...

Objective To analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN ar...

Context Our prior systematic review and meta-analysis of individual participant data (IPD) suggesting a benefit of adjuvant chemotherapy for muscle-invasive bladder cancer was limited by the number and size of included randomised trials. We have updated results to include additional trials, providing the most up-to-date and reliable evidence of the...

Missing data may lead to loss of statistical power and introduce bias in clinical trials. The ongoing Covid-19 pandemic has had a profound impact on patient health care and on the conduct of cancer clinical trials. Restricted access to sites, medication and evaluations brings challenges to the analysis of clinical trials due to missing data. Althou...

Background: Prostate specific membrane antigen (PSMA) positron emission tomography computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) outperform standard imaging technology for the detection of metastasis in prostate cancer (PCa). There are few direct comparisons between both modalities. This paper compares the diagnos...

Purpose To analyse the prognostic impact of isolated local recurrence (ILR) on long-term outcome for early-breast cancer patients treated with breast-conserving therapy. Material and methods The data of the EORTC 22881–10882 ‘boost-no boost’ and 22922–10925 ‘IM-MS’ trials were used to analyse the prevalence and outcome following ILR. A multistate...

PURPOSE The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 ( NCT00021450 ) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiother...

Importance Increased prostate-specific antigen (PSA) levels after treatment (PSA failure) may have different associations with outcomes for men with locally advanced vs localized prostate cancer. Objective To evaluate whether the association between PSA failure and death may be different in locally advanced vs localized prostate cancer. Design, S...

PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etopos...

Purpose To externally validate previously published Normal Tissue Complication Probability (NTCP) models developed by separate teams for grade 3 oral mucositis (g3OM). Materials and methods Two models were validated: a logistic model, based on 144 head and neck cancer (HNC) patients receiving induction chemotherapy followed by chemo-IMRT; a multiv...

Purpose: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. Materials and m...

PURPOSE: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND MET...

Generalized pairwise comparisons (GPCs) are a statistical method used in randomized clinical trials to simultaneously analyze several prioritized outcomes. This procedure estimates the net benefit (Δ). Δ may be interpreted as the probability for a random patient in the treatment group to have a better overall outcome than a random patient in the co...

Introduction As part of the PIONEER (Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe) Consortium, we will explore which diagnostic and prognostic factors (DPFs) are currently being researched to previously defined clinical and patient-reported outcomes for prostate cancer (PCa). Methods and analysis This...

Objectives Multicenter oncology trials increasingly include MRI examinations with apparent diffusion coefficient (ADC) quantification for lesion characterization and follow-up. However, the repeatability and reproducibility (R&R) limits above which a true change in ADC can be considered relevant are poorly defined. This study assessed these limits...

Purpose: Optimal timing of surgery after neoadjuvant chemoradiotherapy (Nad-CRT) is still controversial in locally advanced rectal cancer (LARC). The primary goal of this study was to determine the best surgical interval (SI) to achieve the highest rate of pathological complete response (pCR) and secondly to evaluate the effect on surgical complic...

In survival analysis with competing risks, the treatment effect is typically expressed using cause-specific or subdistribution hazard ratios, both relying on proportional hazards assumptions. This paper proposes a nonparametric approach to analyze competing risks data based on generalized pairwise comparisons (GPC). GPC estimate the net benefit, de...

PURPOSE Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)–based composite end point, may further...

Re-instatement of normal imaging workload after a pandemic [29] requires administrative support and planning adaptation, with extended scanning hours and appointments through a workflow that retains social distancing practices and incorpo- rates additional hygiene processes. A reduced throughput for clinical imaging studies will inevitably impact t...

Background: The impact of kidney dysfunction on long-term outcomes of patients with advanced cancer remains unclear. Methods: Patients with advanced cancer included in trials conducted by the European Organisation for Research and Treatment of Cancer were eligible for this retrospective analysis. Acute kidney injury (AKI) was identified using se...

Objectives There are more than 12 million long-term survivors of cancer in Europe. Yet, research on outcomes of cancer treatment has not reached its full potential due to operational, regulatory and methodological constrains. The current study aims to show the complementary roles between clinical research and population-based cancer registry in thi...

386 Background: Extrapulmonary visceral metastases were the only adverse prognostic factor among 660 advanced seminomas in the original classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) treated between 1975 and 1990 and published 1997. Outcomes may have improved with current era management and additional prognostic f...

703 Background: SURTIME compared immediate CN followed by sunitinib 50mg/day (4/2 weeks on-off) 4 weeks after surgery (n=50) versus 3 cycles sunitinib followed by CN in the absence of progression and continued sunitinib 4 weeks after surgery (n=49). In the intention to treat analysis, the hazard ratio of the secondary endpoint overall survival (OS)...

Patient-reported outcomes (PROs), such as symptoms, function, and other health-related quality-of-life aspects, are increasingly evaluated in cancer randomised controlled trials (RCTs) to provide information about treatment risks, benefits, and tolerability. However, expert opinion and critical review of the literature showed no consensus on optima...

Background: Data generated by phase I trials is richer than the classical binary DLT measured at the first cycle used as primary endpoints. Several works developed designs for more informative endpoints, e.g. ordinal toxicity grades and/or longitudinal data which relied however on strong assumptions, in particular the proportional odds (PO) assump...

Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the ident...

Purpose To compare the diagnostic performance of MRI and ¹⁸F-FDG-PET/CT in detecting bone marrow involvement (BMI) in patients with multiple myeloma (MM). Materials and methods This retrospective study was approved by our Institutional Review Board. Two radiologists and two nuclear medicine specialists independently and blindly reviewed 84 pairs o...

Importance: Both α-emitting and β-emitting bone-targeted radioisotopes (RIs) have been developed to treat men with metastatic castration-resistant prostate cancer (CRPC). Only 1 phase 3 randomized clinical trial has demonstrated an overall survival (OS) benefit from an α-emitting RI, radium 223 (223Ra), vs standard of care. Yet no head-to-head com...

Background: The importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown. Objective: To evaluate the clinical implications of LF after definitive RT. Design, setting, and participants: Individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG...

Background: In the era of molecularly targeted agents (MTAs), it is recommended to account for toxicity over several cycles to identify the recommended phase II dose (RP2D). We investigated the relationship between the risk of toxicity at cycle 1 and the cumulative incidence of toxicity over subsequent cycles in trials of single MTAs. Methods: O...

Introduction et but de l’étude La radiothérapie externe avec chimiothérapie concomitante (5-fluoro-uracile–mitomycine C) est le traitement de référence du cancer de canal anal. Une analyse des données de sept essais a été faite pour quantifier l’effet des paramètres relié avec la radiothérapie externe sur les résultats thérapeutiques. Matériel et...

Background The International Germ Cell Cancer Collaborative Group (IGCCCG) has been the reference classification for assessing prognosis in men with advanced non-seminomatous germ-cell tumors (NSGCT) for more than 20 years and it relied on 5202 cases treated between 1975 and 1990. Methods An international consortium (30 centers/groups) contributed...

Purpose: Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer. Materials a...

This work focuses on the modification of two classical phase II trials designs, the A’Hern design, a single-arm single-stage design, and the Sargent and Goldberg design introduced in the context of flexible screening designs. In the first part of the paper, we have proposed a drift-adjusted A’Hern design, a hybrid design combining the A’Hern design...

The European Organisation for Research and Treatment of Cancer SURTIME trial explored timing of sunitinib, a tyrosine kinase inhibitor (TKI), and cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. Previous retrospective studies suggest increased surgery-related adverse events (AEs) after presurgical TKI. We report surg...

5007 Background: Skeletal fractures, pathological or not, are a frequent and underestimated side-effect of systemic treatment of metastatic castration resistant prostate cancer (mCRPC). The ERA223 trial (NCT02043678) was recently unblinded following the report of a significant increase in the fracture rates when abiraterone is combined with Ra223....

Introduction L’agence européenne du médicament recommande que « les toxicités de faible grade sur de longues périodes qui affectent la tolérance (…) soient considérées dans la définition de la toxicité dose-limitantes (DLT) et de la dose recommandée pour les phase II (RP2D) » dans les essais de phase précoce. En particulier, les toxicités répétées...

Background: Meta-analysis of randomized controlled trials (RCTs) has been widely conducted for the evaluation of surrogate endpoints in oncology, but little attention has been given to the adequacy of reporting and interpretation. This review evaluated the reporting quality of published meta-analyses on surrogacy evaluation and developed recommend...

Surgery and radiotherapy, two locoregional cancer treatments, are essential to help improve cancer outcomes, control, and palliation. The continued evolution in treatment processes, techniques, and technologies—often at substantially increased costs—demands for direction on outcomes that are most valued by patients, and the evidence that is require...

Background: Gonadotropin releasing hormone (GnRH) antagonists suppress follicle-stimulating hormone (FSH) to lower levels than GnRH agonists. This may partially explain the differences between these agents on prostate cancer outcomes. In this post-hoc analysis, FSH and prostate specific antigen (PSA) responses and the impact of cross-over from leup...

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Importance In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown. Objective To examine whether a period of sunitinib therapy before CN improves outcome compared with immedia...

Importance Brain metastases are a common source of morbidity for patients with cancer, and limited data exist to support the local therapeutic choice between surgical resection and stereotactic radiosurgery (SRS). Objective To evaluate local control of brain metastases among patients treated with SRS vs surgical resection within the European Organ...

International/intercontinental collaboration is necessary to set up new innovative clinical trials for cancer treatment. However, the infrastructure, especially Asia-Europe academic partnerships, to enable such collaboration has not been fully structured and differences and similarities between the research groups have not been well studied. In 201...

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further m...

Importance: Androgen deprivation therapy (ADT) improves survival outcomes in patients with high-risk prostate cancer (PCa) treated with radiotherapy (RT). Whether this benefit differs between patients with Gleason grade group (GG) 4 (formerly Gleason score 8) and GG 5 (formerly Gleason score 9-10) disease remains unknown. Objective: To determine...

Background We sought to evaluate local control of brain metastases among patients treated with stereotactic radiosurgery (SRS) versus neurosurgical resection within EORTC 22952. Material and Methods We performed a post-hoc analysis of EORTC 22952 and included patients treated per-protocol who had 1–2 brain metastases <4 cm. The primary endpoint wa...

Although patient-reported outcomes (PROs), such as health-related quality of life, are important endpoints in randomised controlled trials (RCTs), there is little consensus about the analysis, interpretation, and reporting of these data. We did a systematic review to assess the variability, quality, and standards of PRO data analyses in advanced br...

Background: There is currently a lack of consensus on how health-related quality of life and other patient-reported outcome measures in cancer randomized clinical trials are analyzed and interpreted. This makes it difficult to compare results across randomized controlled trials (RCTs) synthesize scientific research, and use that evidence to inform...

Purpose: The therapeutic strategy for non-benign meningiomas is controversial. The objective of this study was to prospectively investigate the impact of high dose radiation therapy (RT) on the progression-free survival (PFS) rate at 3 years in WHO grade II and III meningioma patients. Materials and methods: In this multi-cohorts non-randomized...

Background None Objectives To compare the diagnostic value of DWI and STIR sequences as part of WB-MRI studies in AxSpA patients. Methods 20 consecutive patients (P) with confirmed diagnosis of active AxSpA and 20 controls (C) referred for metastatic cancer screening were investigated with identical WB-MRI protocols including DWI and STIR images....

Background Clear-cell sarcoma (CCSA) is an orphan malignancy, characterized by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic CCSA. Patients and methods P...

Purpose: To compare the diagnostic accuracy of DWI and STIR sequences in Whole body (WB) MRI of SpA patients. Materials and methods: Twenty consecutive patients with confirmed active SpA and 20 controls were investigated with identical WB MRI protocols, including DWI and STIR images. Two observers recorded 'lesions' (high signal intensity foci o...

The drastic improvement in early detection, cancer treatment and supportive care has changed cancer from a lethal disease to a manageable condition for many patients. In Europe, more than half of cancer patients live beyond the 5th year after diagnosis. The prolonged survival of patients plead for a better care and support in the life after cancer....

TPS390 Background: α-emitting radiopharmaceutical Ra-223 reduces the risk of death by 30% vs placebo in phase 3 ALSYMPCA (Parker et al. NEJM 2013). Ra-223’s favourable safety profile and lack of significant toxicity support combining it with other agents. The ALSYMPCA trial was developed to add Ra-223 on the contemporary standard of care that did n...

TPS406 Background: Androgen deprivation therapy (ADT) by LHRH analogues aims to lower serum testosterone. ADT is associated with several side effects that include hot flushes, depression, loss of libido, metabolic disturbances leading to an increase risk of cardiovascular disease, increased bone resorption leading to increased risk of osteoporosis...

352 Background: Among bone-targeted radio-isotopes (RI), Radium-223 (an α-emitter) is the only one with clearly demonstrated overall survival (OS) benefit in men with castration-resistant prostate cancer (CRPC). The aim of this meta-analysis is to estimate the OS impact of RI in men with CRPC. Methods: An individual patient data meta-analysis was c...

OBJECTIVE We sought to evaluate local control of brain metastases among patients treated with stereotactic radiosurgery (SRS) versus neurosurgical resection within EORTC 22952. METHODS We performed a post-hoc analysis of EORTC 22952 and included patients treated per-protocol who had 1–2 brain metastases <4 cm. The primary endpoint was local recurr...

Objective: The prognostic relevance of primary location of urothelial carcinoma (UC) on survival has been poorly investigated. Methods: The prospectively collected data from three EORTC advanced UC studies 30924 (M-VAC versus high dose M-VAC), 30986 (MCAVI versus GC arm, among patients unfit for CDDP) and 30987 (GC-Paclitaxel versus GC, among pa...

Background The absence of a survival benefit for whole brain radiotherapy (WBRT) among randomized trials has been attributed to a competing risk of death from extracranial disease. We re-analyzed EORTC 22952 to assess the impact of WBRT on survival for patients with controlled extracranial disease or favorable prognoses. Patients and methods We ut...

Background: Clear cell sarcoma (CCSA) is an orphan malignancy, characterised by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor (TKI) crizotinib in patients with advanced or metastatic CCSA. Patients and...

Purpose Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were coll...

Background: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm an...

The most commonly used method for dose finding, the 3 + 3, has poor performance. New adaptive designs are more efficient. Nevertheless, they have reached a maximum performance level, and further improvement requires either larger sample sizes or outcomes measures richer than the simplistic severe toxicity measured at cycle 1. Clin Cancer Res; 23(15...

e16034 Background: The prognostic relevance of the primary location of urothelial cell carcinoma (UCC) on outcomes is poorly documented. This parameter has been studied in 3 EORTC trials in advanced UCC that included patients with different initial primary tumor locations. Methods: We used the data prospectively collected in three EORTC advanced UC...

TPS3633 Background: For patients with initially unresectable colorectal liver metastases (CRLM) with good clinical response to chemotherapy, the presence of disappearing liver metastases (DLMs) diagnosed by CT is a major independent prognostic factor. DW-MRI as well as contrast enhanced (CE)-MRI is recommended to detect and characterize CRLM. Howev...

Background Understanding of the physical, functional and psychosocial health problems and needs of cancer survivors requires cross-national and cross-cultural standardization of health-related quality of life (HRQoL) questionnaires that capture the full range of issues relevant to cancer survivors. To our knowledge, only one study has investigated...

Objective: To assess the survival benefit of whole brain radiotherapy (WBRT) for patients with controlled extra-cranial disease and those with favorable diagnosis-specific graded prognostic assessment (dsGPA) scores within EORTC 22952. Methods: In the EORTC 22952 trial, patients with 1–3 brain metastases with stable systemic disease or asymptomatic...

The purpose of this correspondence is to discuss the TrialsTracker, presented by Powell-Smith and Goldacre in their article ‘TrialsTracker: Automated ongoing monitoring of failure to share clinical trial results by all major companies and research institutions’ (2016) as a tool to discover publication bias in clinical trial results. The findings fr...