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Researches:

Article title: Training in advanced pelvic malignancy across Europe and beyond – an EYSAC snapshot analysis
Authors: Andreas Brandl, Dara Lundon, Laura Lorenzon, Yvonne Schrage, Carmela Caballero, Carl Jacob Holmberg, Nada Santrac, Mariela Vasileva-Slaveva, Giacomo Montagna, Helen Mohan, Olivia Sgarbura, Raza Sayyed, Almog Ben-Yaacov, Johnny Henry Hererra Kok, Ina Breinl, Tibor Kovacs, Domenico D'Ugo, Sergio Sandrucci, Wim Ceelen
Publication title: European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 48(2):e41-e42, February 2022

Abstract:
The multimodal treatment of patients with advanced pelvic malignancies (APM) is often challenging and surgical expertise for these malignancies is usually concentrated in highly specialised centres. As the standard of care vary throughout the different European countries, surgical training represents a cornerstone in the complex therapy of these patients today and in the future. The aim of this study is to describe the availability of and current standard of surgical training for APM across Europe.
Full text available upon request to the author

Article title: Standards in surgical training in advanced pelvic malignancy across Europe and beyond – A Snapshot analysis
Authors: Andreas Brandl, Dara Lundon, Laura Lorenzon, Yvonne Schrage, Carmela Caballero, Carl Jacob Holmberg, Nada Santrac, Mariela Vasileva-Slaveva, Giacomo Montagna, Olivia Sgarbura, Raza Sayyed, Almog Ben-Yaacov, Johnn Henry Herrera Kok, Ina Suppan, Helen Mohan, Tibor Kovacs, Domenico D'Ugo, Sergio Sandrucci,Wim Ceelen
Publication title: European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, January 2022

Abstract:
Introduction Multimodal treatment of patients with advanced pelvic malignancies (APM) is challenging and surgical expertise is usually concentrated in highly specialised centres. Given significant regional variation in APM surgery, surgical training represents a cornerstone in standardising and future-proofing of this complex therapy. The aim of this study was to describe the availability and current satisfaction levels with surgical training for APM. Material and methods An online questionnaire was developed and distributed through the Redcap© platform with 32 questions addressing participant and institution demographics, and training in APM surgeries. The survey was electronically disseminated in 2021 to surgical networks across Europe including all specialities treating APM via the European Society of Surgical Oncology (ESSO). All statistical analysis were performed using R. Results The survey received 280 responses from surgeons across 49 countries, representing general surgery (36%), surgical oncology (30%), gynaeoncology (15%), colorectal surgery (14%) and urology (5%). Fifty-three percent of participants report performing >25 APM procedures/year. Respondents were departmental chiefs (12%), consultants (34%), specialist surgeons (40%) and fellows (15%). 34% were happy/very happy with their training with 70% satisfaction about their exposure to surgical procedures. Respondents reported a lack of standardised training (72%), monitoring tools (41%) and mentorship (56%). 57% rated attended courses as useful for training, while 80% rated visiting expert centres as useful. Conclusion This study has identified a learning need for improved structured training in APM, with low current satisfaction levels with exposure to APM training. Organisations such as ESSO provide an important platform for visiting expert centres, courses, and structured training.
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Article title: Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab (P+T) in the APHINITY trial.
Authors: Evandro de Azambuja, Daniel Eiger, Marion Jennifer Procter, Noam Falbel Ponde, Sebastien Guillaume, Damien Parlier, Matteo Lambertini, Antoine Desmet, Carmela Aves Caballero, Christian Aguila, Guy Heinrich Maria Jerusalem, Janice Maria Walshe, Elizabeth S. Frank, Jose Bines, Sibylle Loibl, Martine J. Piccart-Gebhart, Michael S. Ewer, Susan Faye Dent, Chris Plummer, Thomas M Suter
Publication title: Journal of Clinical Oncology 39(15_suppl):510-510, May 2021

Abstract:
Trastuzumab (T) increases the incidence of cardiac events (CEs) in patients (pts) with early breast cancer (BC). Dual blockade with P+T improves BC outcomes and is the standard of care for high-risk HER2-positive BC pts following the phase 3 APHINITY trial that evaluated the addition of P or placebo (Pla) to T and chemotherapy (CT). We analyzed the cardiac safety of P+T in APHINITY. Methods: APHINITY eligibility required a left ventricular ejection fraction (LVEF) ≥55% at study entry. LVEF assessment was performed every 3 months (mos) during treatment, every 6 mos up to month 36, and yearly thereafter. Primary CE was defined as heart failure (HF) class III/IV and a significant decrease in LVEF of at least 10 percentage points from baseline and to <50%, or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF or CEs confirmed by the cardiac advisory board. Results: The safety analysis population consists of 4,769 pts. With 74 mos median follow-up (FU), CEs were observed in 159 pts (3.3%): 83 (3.5%) in the P+T and 76 (3.2%) in Pla+T arms, respectively. Most CEs occurred during anti-HER2 therapy: 123/159 (77.4%) and were asymptomatic or mildly symptomatic LVEF decrease (133/159; 83.6%) (Table 1). There were 2 cardiac deaths in each arm (0.1%). More CEs occurred in pts receiving an anthracycline-based CT compared to those receiving non-anthracycline CT (139 vs. 20 CEs, respectively). Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 pts (81.9%). Conclusions: Dual blockade with P+T does not increase the risk of CE compared to Pla+T alone. The use of anthracycline-based CT increases the risk of a CE; hence non-anthracycline CT may be considered particularly in pts with other cardiovascular risk factors.
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Article title: Treatment patterns in older patients with locally advanced head and neck squamous cell carcinoma: Results from an EORTC led survey
Authors: Sjoukje F. Oosting, Isacco Desideri, Dominiek Staelens, Carmela Caballero, Silke Tribius, Christian Simon, Susanne Singer, Vincent Grégoire, Catherine Fortpied, Andrea Luciani
Publication title: Journal of Geriatric Oncology 12(Suppl; abstr 6003), May 2021

Abstract:
We aimed to assess patterns of care delivered to older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), and to analyze the use of geriatric assessment (GA) and assessment of quality of life (QoL). Materials and methods Members of the head and neck cancer group and the older task force of the European Organisation for Research and Treatment of Cancer (EORTC), members the European Head and Neck Society and members of national groups in Europe were asked to complete a questionnaire about treatment delivered, use of GA, and QoL assessment in older patients with LA-HNSCC. Results Investigators from 111 centers replied, including 90 (81.1%) academic centers, 16 (14.4%) community hospitals, and 5 (4.5%) private clinics. Large differences in treatment patterns were found. For instance, for oropharyngeal carcinoma, one third of the centers indicated that they treat <5% of older patients with chemoradiation, while 18 centers (16.2%) treat >40% of older patients with chemoradiation. Fourteen centers (12.6%) routinely perform GA, while 43 centers (38.7%) never do, and 39 centers (35.1%) sometimes do. QoL is assessed on a routine basis in one fifth of the centers. Conclusions Large differences exist across institutions in the patterns of care delivered to older patients with LA-HNSCC. Prospective studies are required to learn how GA can guide treatment decisions, and how QoL and treatment outcome can be improved. For that, consensus on standard of care is essential.
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Article title: Road Map to Safe and Well-Designed De-escalation Trials of Systemic Adjuvant Therapy for Solid Tumors
Authors: Martine J. Piccart, PhD, Florentine S. Hilbers, MSc, Judith M. Bliss, MSc; Carmela Caballero , MD; Elizabeth S. Frank, EdM; Patrick Renault, BSc; Rachida Naït Kaoudjt, PhD; Eva Schumacher, BSc; Patricia A. Spears, BSc; Meredith M. Regan , ScD; Richard D. Gelber, PhD; Nancy E. Davidson, MD; Larry Norton , MD; and Eric P. Winer
Publication title: Journal of Clinical Oncology 38(34):JCO.20.01382, October 2020

Abstract:
An important challenge in the field of cancer is finding the balance between delivering effective treatments and avoiding adverse effects and financial toxicity caused by innovative, yet expensive, drugs. To address this, several treatment de-escalation trials have been conducted, but only a few of these have provided clear answers. A few trials had poor accrual or had design flaws that led to conflicting results. Members of the Breast International Group (BIG) and North American Breast Cancer Group (NABCG) believe the way forward is to understand the lessons from these trials and listen more carefully to what truly matters to our patients. We reviewed several adjuvant trials of different cancer types and developed a road map for improving the design and implementation of future de-escalation trials. The road map incorporates patients’ insights obtained through focused group discussions across the BIG-NABCG networks. Considerations for the development of de-escalation trials for systemic adjuvant treatment, including noninferiority trial design, choice of end points, and prioritization of a patient’s perspectives, are presented in this consensus article.
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Article title: 148P Surgery (Sx) of the primary tumour in de novo metastatic breast cancer (BC) patients (pts) is associated with increased survival: A nationwide population-based study by the Belgian Cancer Registry (BCR) and the Belgian Society of Medical Oncology (BSMO)
Authors: M.D.R.A. Brandão, C. de Angelis, P. Vuylsteke, R.D. Gelber, N. Van Damme, E. Van Eycken, J. Verbeeck, L. van Walle, C. Colpaert, M. Lambertini, F. Poggio, D. Verhoeven, A. Barbeaux, F.P. Duhoux, K. Punie, H. Wildiers, C. Caballero, A.H. Awada, M. Piccart, E. de Azambuja
Publication title: Annals of Oncology 31:S69, May 2020

Abstract:
Background: The role of Sx of the primary tumor remains highly debatable in de novo stage IV BC. We aimed to assess Overall Survival (OS) among de novo metastatic BC pts who underwent Sx of the primary tumor ≤9 months (m) after diagnosis vs pts who did not, adjusting for prognostic factors.

Methods: This is a retrospective population-based study on 2627 pts diagnosed with de novo metastatic BC from 2010-2014, with data obtained from the BCR and linked with administrative health care databases. A 9m landmark analysis excluding pts who died/were lost to follow-up <9m after diagnosis was performed. Baseline pts characteristics and treatment received were compared between Sx vs No Sx groups using Chi2 and t tests. OS was estimated using Kaplan-Meier method and compared using log-rank test and adjusted Cox proportional hazards models. Subgroup analysis for OS and a sensitivity analysis were performed.

Results: 1985 pts were included in the 9m landmark analysis (534 with Sx vs 1451 with No Sx). Pts receiving Sx were younger, had better performance status (PS) at diagnosis and higher rate of HER2+ subtype. Median OS was 41.9 m in the No Sx group vs 60.1 m in the Sx group (adjusted hazard ratio 0.56; 95% confidence interval 0.49-0.64). Survival differences were larger in pts with PS 0-1, ER+/HER2- or HER2+ BC (Table). OS was not better among pts with PS 2-4, while absolute differences were small among pts with triple negative BC. Sensitivity analysis showed similar results.
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Article title: Important considerations prior to elimination of breast cancer surgery after neoadjuvant systemic therapy: Listening to what our patients want
Authors: C. Caballero and M. Piccart
Publication title: Annals of Oncology 31(8), April 2020

Abstract:
No available
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Article title: Missed opportunities and challenges for surgical breast cancer research in the era of personalized cancer treatment
Authors: Isabel T. Rubio, Michalis Kontos, MTFD Vrancken-Peeters, Roman Rouzier, Anita R Skandarajah, Viviana Galimberti, Niels Kroman, Carmela Caballero, Shinji Ohno, BIG Task Force Surgical Trials
Publication title: European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 46(4 Pt A), November 2019

Abstract:
Surgery is the cornerstone of breast cancer treatment and has a major impact on survival and quality of life of patients. Through trials, surgery achieved better locoregional control, better cosmetic results and lower morbidity [ [1] , [2] ]. It has been demonstrated that patients who participate in clinical trials have improved outcomes compared to those who receive their treatment outside of evidence-based medicine.
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Article title: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group
Authors: Anna Dorothea Wagner, Heike I. Grabsch, Murielle Mauer, Sandrine Marreaud, Carmela Caballero, Peter Thuss-Patience, Lothar Mueller, Annelie Elme, Markus Hermann Moehler, Uwe Martens, Yoon-Koo Kang, Sun Young Rha, Annemieke Cats, Masanori Tokunaga & Florian Lordick
Publication title: BMC Cancer 19(1), May 2019

Abstract:
Background 10–20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) was added to neoadjuvant T and CT, a significant increase in histopathological complete response rate was observed in HER2+ breast cancer. This study aims to investigate the added benefit of using both HER2 targeting drugs (T alone or the combination of T + P), in combination with perioperative CT for localized HER2+ GC. Methods This is a prospective, randomized, open-label, phase II trial. HER2 status from patients with resectable GC (UICC TNM7 tumor stage Ib-III) will be centrally determined. Two hundred and-fifteen patients from 52 sites in 14 countries will be centrally randomized (1:2:2 ratio) to one of the following treatment arms:Standard: CT alone. CT regimens will be FLOT (5-FU, leucovorin, oxaliplatin, taxotere) CapOx (capecitabine, oxaliplatin) or FOLFOX (5-FU, leucovorin, oxaliplatin) according to investigator’s choice in Europe, and cisplatin/capecitabine in Asia. Experimental arm 1: CT as in control group, plus T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) at day 1, independent of CT chosen for 3 cycles of 3 weeks before and after surgery. Experimental arm 2: CT plus T as in experimental arm 1, plus P (840 mg every 3 weeks) on day 1. Adjuvant treatment with T or T + P will continue for 17 cycles in total. Stratification factors are: histology (intestinal/non-intestinal); region (Asia vs Europe); location (GEJ vs non-GEJ); HER2 immunohistochemistry score (IHC 3+ vs IHC 2+/FISH+) and chemotherapy regimen. Primary objective is to detect an increase in the major pathological response rate from 25 to 45% either with CT plus T alone, or with CT plus the combination of T and P. Discussion Depending on the results of the INNOVATION trial, the addition of HER2 targeted treatment with either T or T and P to CT may inform future study designs or become a standard in the perioperative management HER2+ GC. Trial registration This article reports a health care intervention on human participants and was registered on July 10, 2014 under ClinicalTrials.gov identifier: NCT02205047; EudraCT: 2014–000722-38.
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Article title: European Society of Surgical Oncology's strategy for clinical research: Paving the way for a culture of research in cancer surgery
Authors: S. Evrard, C. van de Velde, I. Noordhoek, C. Caballero, W. Ceelen, K. Polom, A. Kolacinska, W. Allum, D. D'Ugo, H.Z. Malik, I.T. Rubio, L. Wyld, M. Leidenius, M. Rivoire, O. Zoras, W. Polkowski, G.J. Poston, R.A. Audisio, T. Kovacs, S. González-Moreno
Publication title: European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 45(9), May 2019

Abstract:
As part of its mission to promote the best surgical care for cancer patients, the European Society of Surgical Oncology (ESSO) has been developing multiple programmes for clinical research along with its educational portfolio. This position paper describes the different research activities of the Society over the past decade and an action plan for the upcoming five years to lead innovative and high quality surgical oncology research. ESSO proposes to consider pragmatic research methodologies as a complement to randomised clinical trials (RCT), advocates for increased funding and operational support in conducting research and aims to enable young surgeons to be active in research and establish partnerships for translational research activities.
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Article title: Building a collaboration to improve surgical research through EORTC/ESSO 1409-CLIMB study: A prospective liver metastasis database with an integrated quality assurance program
Authors: Carmela Caballero, Susen Burock, Lucia Carrion-Alvarez, Henrik Nilsson, Theo Ruers, Perrine Senellart, Michel Rivoire, Stefan Stattner, Florian Primavesi, Roberto Troisi, Thomas Gruenberger, Jan Heil, Andreas A. Schnitzbauer, Nuh N. Rahbari, Rutger-Jan Swijnenburg, Hassan Malik, Mladjan Protic, Kozo Kataoka, Murielle Mauer, Michel Ducreux, Graeme Poston, Serge Evrard
Publication title: European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 45(10), May 2019

Abstract:
The challenges of conducting surgical oncology trials have resulted to low quantity and poor quality research [1,2]. Considering the definitive role of surgery to offer cure, immediate response to improve surgical research is needed [3]. The European Organization for Research and Treatment of Cancer (EORTC) and the European Society of Surgical Oncology (ESSO) share the vision to achieve excellent surgical research and care for cancer patients. Building on their complimentary expertise, they embarked on a pilot project to map out challenges and initiate a sustainable collaboration to advance cancer surgery research in Europe. This pilot project is EORTC-ESSO 1409 GITCG/ ESSO-01: A Prospective Colorectal Liver Metastasis Database with an Integrated Quality Assurance Program (CLIMB). This article will describe the challenges, milestones and vision of both organizations in setting up this collaboration.
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Article title: EORTC 1409 GITCG / ESSO 01 - A prospective colorectal liver metastasis database with an integrated quality assurance program (CLIMB): Primary analysis of variations in European clinical practices and surgical complications after complex liver metastasis surgeries
Authors: C.I. Caballero, L. Carrion Alvarez, H. Nilsson, T. Ruers, P. Senellart, M. Rivoire, S. Staettner, F. Primavesi, R. Troisi, T. Gruenberger, J. Heil, A. Schnitzbauer, N. Rahbari
R.J. Swijnenburg, H. Malik, M. Protic, A. Neven, M. Mauer, G. Poston, S. Evrard
Publication title: European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 45(2):e20, February 2019

Abstract:
EORTC & ESSO developed an infrastructure for surgical quality assurance (QA) in clinical trials (SURCARE) to advance the surgical research agenda in Europe. The first project is CLIMB, a prospective study to benchmark practices for unresectable or borderline resectable colorectal liver metastasis (CRLM) surgery. Quality indicators included multidisciplinary team (MDT), use of biomarker testing, type of chemotherapy regimen, imaging used pre-surgery and complications rates.
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Article title: Implementing Integrated Quality Assurance (SURCARE) for EORTC-JCOG 1527 / ESSO 02: Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Assessment of Liver Metastasis to Improve Surgical Planning (DREAM)
Authors: K. Kataoka, C.I. Caballero, T. Suto, M. Shiozawa, S. Evrard
Publication title: European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 45(2):e7-e8, February 2019

Abstract:
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. However, correlation between radiological and pathological complete response has not been fully investigated using the latest imaging and pathology techniques. DW-MRI and contrast enhanced (CE)-MRI are recommended to detect and characterise CRLM. Our main aim is to demonstrate the added value of DW-MRI, CE-MRI and CT scan to provide precise assessment of the viability of DLMs. In addition, we aim to improve prognostication and treatment strategies for CRLM patients using parenchymal sparing surgery (PSS). No large scale study has been conducted to date to determine the predictive value of DW-MRI combined with CE-MRI in confirming sites of DLMs and assessing their true status. This is the first collaborative study between EORTC, ESSO and JCOG with an integrated quality assurance (QA) program for imaging, surgery and pathology. Together, we also developed an infrastructure for surgical QA in clinical trials (SURCARE) to advance the surgical oncology research agenda in Europe and Asia.
Full text available upon request to the author

Article title: An international survey-based study on colorectal cancer pathology reporting - guidelines versus local practice.
Authors: Maria Urbanowicz, Heike I. Grabsch, Frederic Fiteni, Yan Liu, Carmela Caballero & Jean-François Fléjou
Publication title: Virchows Archiv 473(6), December 2018

Abstract:
Different guidelines for colorectal cancer (CRC) pathology reporting have been published. We aimed to identify differences between publicly available CRC reporting guidelines and to survey pathologists from different countries to establish the degree of guideline implementation in local routine practice. We compared all core and non-core items of CRC reporting guidelines to identify discrepancies. We then created a survey, which was sent out to 782 pathologists practicing in 30 different countries. It included questions on the demographics of the reporting pathologist as well as resection specimen handling and microscopic evaluation, grading, staging, and additional techniques, such as immunohistochemistry or molecular pathology. First, core and non-core items of five national CRC reporting guidelines were compared and 12 items were found to differ. Different items are considered core or non-core by different guidelines and more than one TNM staging edition was applied across guidelines. The survey was completed by 143 pathologists from 30 countries. We identified differences between local practice and guidelines with potential clinical impact, e.g., tumor budding was never reported by 28.7% of responders, although it has prognostic value for survival in stage II CRC. This is the first international study comparing CRC pathology reporting guidelines with real-world local practices. There are differences in CRC pathology reporting guidelines and in guideline implementation into local practice, both with potential impact on patient care. Harmonization of datasets, use of templates, and audits of local pathology practice are needed to ensure best possible quality of CRC pathology reporting.
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Article title: Responding to the challenges of international collaborations between the east and the west - report of the first JCOG-EORTC symposium and a perspective from young JCOG and EORTC investigators
Authors: Kozo Kataoka, Orit Kaider-Person, Bernd Kasper, Patrick Starlinger, Carmela Caballero, Jessica Menis, Lizza E Hendriks, Mitsumi Terada, Laurence Collette, Kenichi Nakamura, Denis Lacombe, Haruhiko Fukuda
Publication title: Japanese Journal of Clinical Oncology 49(1), November 2018

Abstract:
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 2015, collaboration started between the biggest cancer research organizations in Asia and EU, Japan Clinical Oncology Group (JCOG) and European Organisation for Research and Treatment of Cancer (EORTC). Following the first pilot collaboration study, the first scientific symposium took place in December 2017 in Tokyo. Before the symposium, a working visit for EORTC investigators from the Early Career Investigator initiative (ECI), willing to develop projects within the JCOG–EORTC partnership, was held. In addition to the digest of the working visit and symposium, we aimed to describe the differences and similarities between the two groups and to identify key factors for collaboration from the perspective of the young investigators of the networks. These findings are described in this article.
Full text link https://tinyurl.com/2p8pyfcj

Article title: Parenchymal sparing surgery brings treatment of colorectal liver metastases into the precision medicine era
Authors: Serge Evrard, Guido Torzilli, Carmela Caballero, Benjamin Bonhomme
Publication title: European journal of cancer (Oxford, England: 1990) 104:195-200, November 2018

Abstract:
The treatment of advanced colorectal liver metastases (CRLMs) follows the biphasic pattern characteristic of oncological surgery. A phase of escalation—the therapeutic aggressiveness—is followed by a phase of de-escalation aimed at decreasing the morbidity, while preserving the gains in survival. From a maximum of three lesions, the rule no longer limits the number, provided the intervention does not cause lethal liver failure. Technically feasible non-anatomical resections, two-stage hepatectomies, portal vein obliteration and so forth, have pushed the boundaries of surgery far. However, the impact and the biology of metastatic processes have been long ignored. Parenchymal sparing surgery (PSS) is a de-escalation strategy that targets only metastasis by minimising the risk of stimulating tumour growth, while enabling iterative interventions. Reducing the loss of healthy parenchyma increases the tolerance of the liver to interval chemotherapy. Technically, PSS could use any type of hepatectomy, providing it is centred on the metastatic load alongside intraoperative ablation. The PSS concept sometimes wrongly comes across as a debate between minor versus major hepatectomies. Hence, we propose a clear definition, both quantitative and qualitative, of what PSS is and what it is not. Conversely, the degree of selectivity of PSS as a percentage of the volume of resected metastases versus the volume of total liver removed has not been stopped to date and should be the subject of prospective studies. Ultimately, the treatment of advanced CRLMs, of which PSS is a part, needs to be personalised by the multidisciplinary team by adapting its response to each new recurrence.
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Article title: "Personalized biomarker-based treatment strategy for patients with squamous cell carcinoma of the head and neck: EORTC position and approach."
Authors: R. Galot, C. Le Tourneau, J. Guigay, L. Licitra, I. Tinhofer, A. Kong, C. Caballero, C. Fortpied, J. Bogaerts, A.-S. Govaerts, D. Staelens, T. Raveloarivahy, L. Rodegher, J.-F. Laes, E. Saada-Bouzid, J.-P. Machiels
Publication title: Annals of Oncology 29(12), October 2018

Abstract:
The molecular landscape of squamous cell carcinoma of the head and the neck (SCCHN) has been characterized and actionable or targetable genomic alterations have been identified. However, targeted therapies have very limited activity in unselected SCCHN and the current treatment strategy is still based on tumor location and disease stage and not on tumor biology.Trying to select upfront the patients who will benefit from a specific treatment might be a way to improve patients' outcome. With the objective of optimizing the activity of targeted therapies and immunotherapy, we have designed an umbrella biomarker-driven study dedicated to recurrent and/or metastatic SCCHN patients (EORTC-1559-HNCG, NCT03088059).In this paper, we review the different trial designs for biomarker-driven studies with their respective advantages and opportunities but also the potential pitfalls that led to the design of the EORTC-1559-HNCG protocol. We also discuss the scientific and logistic challenges of biomarker-driven trials.
Full text link https://tinyurl.com/55hz8p8y

Article title: Perspectives on window of opportunity trials in head and neck cancer: lessons from the EORTC 90111-24111-NOCI-HNCG study
Authors: Sandra Schmitz, Carmela Caballero, Laura D. Locati
Publication title: European journal of cancer (Oxford, England: 1990) 104, October 2018

Abstract:
Assessing tumour response using a traditional phase I, II and III trial approach is not without limitations, particularly when targeted therapies are involved. Window of opportunity trials, performed presurgically but differing from neoadjuvant studies, were developed in an attempt to overcome the limitations of the traditional approach. A recent window of opportunity trial, the EORTC 90111-24111-NOCI-HNCG study, evaluated afatinib in treatment-naive patients with squamous cell carcinoma of the head and neck. While this study was the first to demonstrate the activity of afatinib in this setting and to define its potential predictive biomarkers, it also highlighted the challenges associated with the window of opportunity trial design, including the impact of patient selection, tumour site, and other organisational issues. This report details the key learnings from the EORTC 90111-24111-NOCI-HNCG study and provides recommendations to overcome the challenges of this particular trial design.
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Article title: 1086PCombined analysis of gene expression profiles in 2 preoperative trials with afatinib and cetuximab in head and neck squamous cell carcinoma
Authors: P. Bossi, S. Schmitz, J.-P. Machiels, L.F. Licitra, C. Fortpied Lefevre, C. Caballero, S. Canevari, L. De Cecco
Publication title: Annals of Oncology 29(suppl_8), October 2018

Abstract:
Background: Only a minority of head and neck squamous cell carcinoma (HNSCC) patients (pts) respond to targeted agents acting on epidermal growth factor pathway. We investigated the changes of gene expression profiles in 2 preoperative window of opportunity trials, to allow a further investigation in mechanisms of response.
Methods: Thirty and 20 pts with similar characteristics were treated for 2 weeks before surgery with afatinib (EORTC 90111-24111 NOCI HNCG trial, Ann Oncology 2017) and cetuximab (Schmitz S, Ann Oncology 2013), respectively. The gene expression profile obtained by microarray platform was compared by a paired analysis pre and post treatment. Gene sets were defined according to GSEA and only sets with q-value FDR < 0.05 differences were considered. Clinical response was analysed according to primary endpoint of the trials (FDG-PET response).
Results: Pre- and post-targeted treatment paired histological samples from 20 and 15 pts were evaluable for gene expression, from afatinib and cetuximab series, respectively. The following gene sets were commonly downregulated by the treatment: G2M checkpoint, MYC and E2F targets and MTORC. On the opposite, the gene sets which resulted upregulated were: angiogenesis, epithelial-mesenchymal transition, inflammatory response and NOTCH signalling. A substantial overlapping of molecular alteration between the 2 series has been observed, thus allowing a further meta-analysis combining the 2 datasets to analyse profiles associated to response. Preliminary data in afatinib series showed a strong downregulation of hypoxia gene signature only in responding pts.
Conclusions: In 2 independent studies with afatinib and cetuximab in window of opportunity setting, we observed similar molecular alterations induced by the drugs. Further insights in the pathways involved in response to both drugs are ongoing.

Article title: 1106PTreatment patterns in elderly patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC): Results from an EORTC led survey
Authors: S. Oosting, I. Desideri, D. Staelens, C. Caballero, S. Tribius, C. Simon, S. Singer, V. Gregoire, C. Fortpied, A. Luciani
Publication title: Annals of Oncology 29(suppl_8), October 2018

Abstract:
Background: An increase in the number of elderly patients diagnosed with head and neck cancer is expected, but there is no consensus on what is the optimal treatment for patients >70 years with locally advanced disease. Geriatric assessment (GA) is recommended but not validated for guiding treatment decisions. We hypothesized that significant heterogeneity will exist across institutions in patterns of care delivered to elderly patients with LA-HNSCC and in the use of GA and assessment of quality of life (QoL).
Methods: Members of the EORTC, the European Head and Neck Society and national groups in Europe were asked to complete a questionnaire about treatment delivered and use of GA and QoL assessment in elderly patients with LA-HNSCC.
Results: Investigators from 111 centers replied, including 90 (81.1%) academic centers, 16 (14.4%) community hospitals and 5 (4.5%) private clinics. Large differences in treatment patterns were found. For instance, for oropharyngeal carcinoma, one third of the centers indicate that they treat <5% of elderly patients with chemoradiation, while 18 centers (16.2%) treat >40% of elderly patients with chemoradiation. More than half of the centers hardly or never use cetuximab in elderly patients with hypopharyngeal carcinoma, while one in five centers treat >20% of the elderly patients with cetuximab. Furthermore, 3 centers (2.7%) treat <5% of elderly patients with oral cavity cancer with surgery and postoperative radiotherapy, while 73 centers (65.7%) offer this to at least 40% of their elderly patients. Fourteen centers (12.6%) routinely perform GA while 43 centers (38.7%) never do, and 39 centers (35.1%) sometimes do. QoL is assessed on a routine basis in one fifth of the centers.
Conclusions: Large differences exist across institutions in the patterns of care delivered to elderly patients with LA-HNSCC. Prospective studies are required in this population to learn how to use GA, how to improve QoL and ultimately improve treatment outcome. For that, consensus on standard of care is essential.
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Article title: Surgical quality assurance in head and neck cancer trials: an EORTC Head and Neck Cancer Group position paper based on the EORTC 1420 'Best of' and 24954 'larynx preservation' study
Authors: Christian Simon, Carmela Caballero, Vincent Gregoire, Dietmar Thurnher, Petri Koivunen, Philippe Ceruse, Giuseppe Spriano, Piero Nicolai, Lisa Licitra, Jean-Pascal Machiels
Marc Hamoir, Guy Andry, Hisham Mehanna, Keith D. Hunter, Andreas Dietz 1, C. René Leemans
Publication title: European journal of cancer (Oxford, England: 1990) 103:69-77, September 2018

Abstract:
Quality improvement of care for patients with head and neck cancer remains a constant objective for the multidisciplinary team of physicians managing these patients. The purpose of quality assurance (QA) for head and neck surgical oncology and surgical trials however differs. While QA for the general head and neck patient aims to improve global outcome through structural changes of health-care systems, QA for surgical trials pursues the goal to help providing meaningful results from a clinical trial through the definition of structure, process and outcome measures within the trial. Establishing a QA program for surgical trials is challenging largely due to the variation in the execution of surgical techniques. Within this article, we describe the surgical QA program, which was developed for the phase III European Organisation for Research and Treatment of Cancer (EORTC) 1420 study, a trial assessing swallowing function after transoral surgery compared with radiation therapy. We propose based on our experience to further develop surgical QA for surgical clinical trials by introducing two separate components, one adaptable and one non-adaptable. The adaptable is tailored to the scientific question and specific procedure; the non-adaptable consists of minimal structural requirements of the clinical unit to participate in surgical trials at EORTC as well as guidelines and incentives for protocol adherence based on our experience in EORTC 24954. Finally, we strongly believe that surgical QA designed for clinical trials may serve as a basis for the development of QA surgical guidelines in clinical practice.
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Article title: Lapatinib with ECF/X in the first-line treatment of metastatic gastric cancer according to HER2neu and EGFR status: a randomized placebo-controlled phase II study (EORTC 40071)
Authors: Markus Moehler, Arno Schad, Annett Maderer, Ajlan Atasoy, Murielle E. Mauer, Carmela Caballero, Thomas Thomaidis, Jestinah M. Mahachie John, Istvan Lang, Eric Van Cutsem, João Freire, Manfred P. Lutz, Arnaud Roth
Publication title: Cancer Chemotherapy and Pharmacology 82(2), August 2018

Abstract:
Purpose HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. Methods Tumors from chemotherapy-naïve patients were screened centrally by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or HER2neu expression or amplification were allocated to three strata based on EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B), with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was progression-free survival (PFS) in stratum 3. Results 29 of 72 screened patients were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu−: by FISH/+ by IHC, n = 5) and 3 (HER2neu−/EGFR+, n = 18), of which 28 patients were eligible (14 per arm). Enrollment was curtailed after announcement of the negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86, 95% CI 0.37–1.99) in the per protocol population, and 8.0 versus 6.3 months (HR = 0.85, 95% CI 0.30–2.46) for stratum 3, in the lapatinib versus placebo arm respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95% CI 0.35–2.27). There were no safety concerns. Conclusions Central EGFR and HER2neu stratification by IHC and FISH can be used for further pan-HER strategies. Lapatinib with ECF/X was well tolerated, but did not show clear activity in patients with metastatic GC.
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Article title: Quality Assurance and Improvement in Head and Neck Cancer Surgery: From Clinical Trials to National Healthcare Initiatives
Authors: Christian Simon MD & Carmela Caballero MD
Publication title: Current Treatment Options in Oncology 19(7):34, May 2018

Abstract:
Opinion statement: It is without question in the best interest of our patients, if we can identify ways to improve the quality of care we deliver to them. Great progress has been made within the last 25 years in terms of development and implementation of quality-assurance (QA) platforms and quality improvement programs for surgery in general, and within this context for head and neck surgery. As of now, we have successfully identified process indicators that impact outcome of our patients and the quality of care we deliver as surgeons. We have developed risk calculators to determine the risk for complications of individual surgical patients. We have created perioperative guidelines for complex head and neck procedures. We have in Europe and North America created audit registries that can gather and analyze data from institutions across the world to better understand which processes need change to obtain good outcomes and improve quality of care. QA platforms can be tested within the clearly defined environment of prospective clinical trials. If positive, such programs could be rolled out within national healthcare systems, if feasible. Testing quality programs in clinical trials could be a versatile tool to help head neck cancer patients benefit directly from such initiatives on a global level.
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Article title: BEST OF: A phase III study assessing the best of radiotherapy (Intensity Modulated RadioTherapy, IMRT) compared to the best of surgery (Trans-Oral Surgery, TOS) in patients with T1-T2, N0 oropharyngeal squamous cell carcinoma (OPSCC).
Authors: Christian Simon, Carmela Aves Caballero, Catherine Fortpied, Mererid Evans, Petri Koivunen, Jean-Jacques Stelmes, Maria Urbanowicz, Jean Bourhis, Frank Zimmermann, Jens Peter Klussmann, Andreas Dietz, Giuseppe Spriano, C. Rene Leemans, Susanne Singer, Inge Tinhofer, Joanne Patterson, Silvana Quaglini, Keith Hunter, Vincent Gregoire
Publication title: Journal of Clinical Oncology 36(15_suppl):TPS6098-TPS6098, May 2018

Abstract:
Background: The incidence of OPSCC has increased dramatically in the last 15 years. The standard treatment for early stage disease is either surgery or radiotherapy, both with comparable high tumor control rates but with different side effect profiles and technical constraints. Treatment choice is generally based on expert or center experience. It is still unclear whether they differ in terms of functional outcome. To clarify this, we proposed a randomised trial with the primary objective to assess and compare the patient-reported swallowing function over the first year after randomisation to either IMRT or TOS among patients with early stage OPSCC. Clinician and patient-reported outcomes will be used to assess treatment. Methods: This is a phase III randomised trial (NCT02984410) that will primarily assess the MD Anderson Dysphagia Inventory (MDADI) score reported by the patients at months 4.5, 6, 9, and 12 after randomisation. MDADI is composed of 19 questions on emotional, functional, and physical aspects, all related to swallowing, wherein scores range between 20 (poorest function) and 100 (best function). BEST OF is powered to detect a clinically significant difference in MDADI score at each of these time points: 4.5, 6, 9, and 12 months with a planned sample size of 170 patients. Key secondary endpoints include treatment response at 6 months after randomization, oncologic outcomes at year 1 and 5, toxicities based on CTCAE, quality of life (QOL) based on QLQ-C30 and HN43 and out-of-pocket costs. QOL domains will be ranked based on patient's priorities. Eligible cases are resectable T1 or T2, N0, M0 OPSCC assessed by a multidisciplinary team. The EORTC quality assurance program (QA) for surgery and pathology (SURCARE) and radiotherapy (RTQA) was implemented in the study. This integrated QA will be the model for future EORTC Head and Neck Cancer trials. BEST OF was opened for recruitment since December 2017 in Belgium and Switzerland and will soon open in France, UK, Germany, Poland, Italy and Portugal through a collaboration with EORTC HNCG and ROG, SAKK, NCRI, GORTEC, and IAG-KHT.
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Article title: EORTC 1559-HNCG: A pilot study of personalized biomarker-based treatment strategy or immunotherapy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN)—"UPSTREAM"
Authors: Rachel Galot, Lisa F. Licitra, Christophe Le Tourneau, Joel Guigay, Inge Tinhofer, Anthony Hee Kong, Carmela Aves Caballero, Catherine Fortpied, Anne-Sophie Govaerts, Dominiek Staelens, Tiana Raveloarivahy, Jean-Francois Laes, Jean-Luc Re Canon, Stéphanie Henry, Esma Saada-Bouzid, Jean-Pascal H. Machiels
Publication title: Journal of Clinical Oncology 36(15_suppl):TPS6095-TPS6095, May 2018

Abstract:
Background: The treatment of R/M SCCHN includes platinum-based chemotherapy, cetuximab, and anti-PD-1 compounds. Some genetic alterations have been identified, making SCCHN attractive for molecular targeted therapies. However, when these agents are given to unselected SCCHN patients (pts), only limited activity is observed. EORTC 1559 is a biomarker-driven umbrella trial for R/M SCCHN that investigates the activity of immunotherapy or targeted agents in tumors harboring pre-defined biomarker(s). Methods: Pts with R/M SCCHN progressing after platinum-based chemotherapy are enrolled. Inclusion criteria are: ECOG 0-1 and measurable disease by RECISTv1.1. Previous treatment with anti-PD(L)1 is allowed. Before inclusion, a fresh tumor biopsy is taken and analyzed in a certified central laboratory (OncoDNA, Belgium). We designed a custom theranostic test that includes IHC, NGS and gene fusions. Based on a pre-defined algorithm, pts are allocated to different treatment cohorts: afatinib (one cohort for p16- cases with either EGFR or HER2 mutation/amplification or PTEN H-score > 150 and another cohort for p16- cetuximab naïve pts), palbociclib (p16- and cyclin D1 amplification), niraparib (one cohort for p16+ oropharyngeal cancer and another cohort for p16- platinum sensitive disease) and entrectinib (NTRK1/NTRK3 or ROS1 fusions). Pts not eligible for the biomarker-driven cohorts are included in 1 of the immunotherapy cohorts (monalizumab monotherapy or monalizumab + durvalumab). Each cohort is designed as a phase II trial with its own statistical hypothesis. The 10 endpoint is either PFS or ORR depending on the investigated drug, cohort sizes range from 32 to 76 pts. The study is designed to allow the addition of new treatment cohorts based on new biomarker hypotheses. We are currently working on adding FGFR inhibitors cohorts. The EORTC HN1559 Upstream trial is the 1st international umbrella trial with a personalized treatment strategy or immunotherapy for pts with SCCHN. The study is open since November 2017 in Belgium and France with 12 first patients enrolled. We plan to open Italy, UK and Germany
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Article title: EORTC-ESSO 1409 GITCG: A prospective colorectal liver metastasis database with an integrated quality assurance program (CLIMB).
Authors: Carmela Aves Caballero, Lucia Carrion Alvarez, Henrik Nilsson, Theo Ruers, Perrine Senellart, Michel Rivoire, Stefan Stattner, Florian Primavesi, Roberto Troisi, Thomas Gruenberger, Jan Heil, Andreas Schnitzbauer, Nuh N. Rahbari, Rutger-Jan Swijnenburg, Hassan Zakria Malik, Mladjan Protic, Anouk Neven, Murielle E. Mauer, Graeme John Poston, Serge Evrard
Publication title: Journal of Clinical Oncology 36(15_suppl):3558-3558, May 2018

Abstract:
Background: The European Organization for Research & Treatment of Cancer & European Society of Surgical Oncology joined forces to build an infrastructure for surgical quality assurance (QA) in clinical trials (SURCARE) and advance the surgical research agenda in Europe. Benchmarking is a critical step to achieve this. Their first project is CLIMB, a prospective study to evaluate complications and identify indicators for improvement in surgery for unresectable or borderline resectable colorectal liver metastasis (CRLM). Methods: CLIMB (NCT02218801) opened in 2015 in 9 countries and 14 specialised centers for liver surgery. Eligible patients were registered after multidisciplinary evaluation and before surgery. Primary endpoint was 30 and 90 day surgical complication rate. On-site visits and central review ensured prospective data inclusion of the following: biomarker, imaging, chemotherapy, surgery, complications graded by Clavien-Dindo classification and survival. Data until post op day 90 were analysed but long term outcome will be reported after all patients were followed for two years after registration. Results: Among 210 patients registered, 126 (60%) who had at least one liver surgery were analysed. 73% had left-sided or rectal primary tumor, 95.2% had synchronous primary and liver metastasis, 19.8% had extra-hepatic lesions and CRLM. Most patients (N = 95, 75.4%) had one stage liver surgery while 30 (23.8%) had two stage liver surgery, 10 of whom had ALPSS. Over-all complication rates for one stage was 53.7% (95% CI [43%, 64%]), 17.9% (95% CI [11%, 27%]) with grade≥3 and 93.3% (95% CI [78%, 99%]) for two stage, 46.7% (95% CI [28%, 66%]) with grade≥3 including two deaths. Intra-abdominal, wound and urinary tract infections, bile leak and post hepatectomy liver failure grade A were most commonly reported over-all. Conclusions: CLIMB prospectively collected data from complex surgery for unresectable CRLM. Two stage surgery had more grade≥3 complications. Harmonizing standards in multidisciplinary evaluation, biomarker testing and imaging may improve this outcome. SURCARE will use these indicators to develop trials with enhanced QA methods to improve cancer surgery.
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Article title: Hope for salivary gland cancer (SGC): EORTC HNCG/UKCRN 1206 randomized phase II study to evaluate the efficacy and safety of chemotherapy (CT) vs androgen deprivation therapy (ADT) inpatients with recurrent and/or metastatic androgen receptor (AR) expressing SGC (NCT01969578).
Authors: Laura Locati, Carmela Aves Caballero, Catherine Fortpied, Federica Perrone, Pasquale Quattrone, Kevin Harrington, Vincent Gregoire, Lisa F. Licitra
Publication title: Journal of Clinical Oncology 36(15_suppl):TPS6099-TPS6099, May 2018

Abstract:
Background: SGCs are rare and heterogeneous tumors ( < 1% of all malignancies in Europe). Among more than 20 histotypes, only salivary duct carcinoma (SDC) and adenocarcinoma NOS express AR. These variants are aggressive and associated with poor prognosis. Surgery is the main curative treatment but upon relapse, patients are left with very few options. This study (NCT01969578) aims to evaluate the efficacy and safety of ADT (experimental arm) vs chemotherapy (standard arm) in patients with recurrent and/or metastatic, AR overexpressing SDC and adenocarcinoma, NOS by demonstrating a 15% improvement in Progression Free Survival (PFS) rate at 6 months in favor of ADT. Methods: Trial design: In this multicenter, randomized, phase II intergroup study a total of 76 treatment patients (Cohort A) are planned to be randomized to receive ADT or platinum-based chemotherapy. Patients previously treated with chemotherapy will be enrolled in a separate Cohort B to receive ADT. Patients from Cohort A randomized to chemotherapy can also enter in Cohort B at disease progression. The primary endpoint is PFS for Cohort A and best overall response for Cohort B. AR overexpression is mandatory at study entry. Mechanisms of AR activation and resistance will be studied. This study is led by EORTC Head and Neck Cancer Group with UNICANCER/REFCOR, International Rare Cancer Initiative UK Salivary Gland Cancer Group and RARECARENet. It will run in 35 sites in 10 countries: Austria, Belgium, France, Germany, Greece, Hungary, Italy, Portugal, The Netherlands, and United Kingdom. Sites from the EURACAN European Reference Network are participating. On 9 th February 2018, 54 patients are registered; 27 have been enrolled, of which 17 have been randomized in Cohort A. Identification of AR as a treatment target in SGC can be practice changing.
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Article title: ECCO Essential Requirements for Quality Cancer Care: Oesophageal and Gastric Cancer
Authors: William Alluma, Florian Lordick, Maria Alsina, Elisabeth Andritsch, Ahmed Ba-Ssalamah,Marc Beishon, Marco Braga, Carmela Caballero, Fatima Carneiro, Fernando Cassinello,Jan Willem Dekker, Roberto Delgado-Boltonl, Karin Haustermans, Geoffrey Henning, Bettina Hutter, József Lövey, Irena Štenglová Netíková, Radka Obermannová, Simon Oberst, Siri Rostoft, Tiina Saarto, Thomas Seufferlein, Sapna Sheth, Venetia Wynter-Blyth, Alberto Costa, Peter Naredi
Publication title: Critical Reviews in Oncology/Hematology 122, January 2018

Abstract:
Background: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Oesophageal and gastric: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality OG cancer service. The ERQCC expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with OG cancer.
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Article title: Multidisciplinary quality assurance and control in oncological trials: Perspectives from European Organisation for Research and Treatment of Cancer (EORTC)
Authors: Members of EORTC QAC and Working Groups of Scientific Experts
Publication title: European journal of cancer (Oxford, England: 1990) 86:91-100, November 2017

Abstract:
Quality assurance (QA) programmes are one of the mainstays of clinical research and constitute the pillars on which European Organisation for Research Treatment of Cancer (EORTC) delivers multidisciplinary therapeutic progress. Changing practice treatments require solid evidence-based data, which can only be achieved if integral QA is part of the infrastructure sustaining research projects. Cancer treatment is a multimodality approach, which is often applied either in sequence and/or in combination. Each modality plays a key role in cancer control. The modalities by which QA is applied varies substantially within and across the disciplines. In addition, translational and diagnostic disciplines take an increasing role in the era of precision medicine. Building on the structuring effect of clinical research with fully integrated multidisciplinary QA programmes associated with the solutions addressing the chain of custody for biological material and data integrity as well as compliance ensure at the same time validity of clinical research output but also have a training effect on health care providers, who are more likely to apply such principles as routine. The principles of QA are therefore critical to be embedded in multidisciplinary infrastructure to guarantee therapeutic progress. These principles also provide the basis for the functioning of multidisciplinary tumour board. However, technical, operational and economic challenges which go with the implementation of such programmes require optimal know-how and the coordination of the multiple expertise and such efforts are best achieved through centralised infrastructure.
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Article title: 1106TiPHope for salivary gland cancer (SGC): EORTC HNCG/UKCRN 1206 randomized phase II study to evaluate the efficacy and safety of Chemotherapy (CT) vs androgen deprivation therapy (ADT) in patients with recurrent and/or metastatic androgen receptor (AR) expressing SGC
Authors: L.D. Locati, C. Caballero, C. Fortpied, F. Perrone, S. Pilotti, K.J. Harrington, V. Grégoire, L. Licitra
Publication title: Annals of Oncology 28(suppl_5), September 2017

Abstract:
Background: SGCs are rare and heterogenous tumors (<1% of all malignancies in Europe). Among more than 20 histotypes, only salivary duct carcinoma (SDC) and adenocarcinoma NOS expresses AR. These variants are aggressive and associated with poor prognosis. Surgery is the main curative treatment but upon relapse, patients are left with very few options. There is an urgent need to understand their biology to enable progress in this rare disease. This study (NCT01969578) aims to evaluate the efficacy and safety of ADT (experimental arm) vs chemotherapy (standard arm) in patients with recurrent and/or metastatic, AR overexpressing SDC and adenocarcinoma, NOS by demonstrating a 15% improvement in Progression Free Survival (PFS) rate at 6 months in favor of ADT.
Full text available upon request to the author

Article title: EORTC1527/JCOG1609INT: Diffusion-weighted MRI (DW-MRI) assessment of liver metastasis to improve surgical planning (DREAM).
Authors: Kozo Kataoka, Carmela Aves Caballero, Laurence Collette, Kenichi Nakamura, Yoji Kishi, Patrick Starlinger, Hiroaki Onaya, Takeshi Suto, Michel Ducreux, Yasuhiro Shimada, Sabine Tejpar, Laura Rubbia-brandt, Gina Brown, Manabu Shiozawa, Serge Evrard
Publication title: Journal of Clinical Oncology 35(15_suppl):TPS3633-TPS3633, May 2017

Abstract:
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. However, the correlation between radiological and pathological complete response has not been fully investigated using these latest imaging and pathology techniques. Our main aim is to demonstrate the added value of DW-MRI, CE-MRI to that of CT alone to provide precise assessment of the viability of DLMs. In addition, we aim to optimize the therapeutic management of CRLM patients. No prospective study has been conducted to determine the predictive value of DW-MRI combined with CE-MRI in confirming sites of DLMs and assessing their true status. Methods: This is the first collaborative study between EORTC, ESSO and JCOG with an integrated quality assurance program for imaging, surgery and pathology. Patients with unresectable CRLM will receive standard systemic chemotherapy and liver resection if resectable. Both CT and MRI (DW-MRI, CE-MRI and T1/T2) will be used to identify confirmed DLMs (cDLMs). cDLMs will be either resected or, if resection is not possible, followed-up without resection until 2 years after surgery to evaluate the true status of the cDLMs. The primary endpoint is negative predictive value (NPV) of DW-MRI, CE-MRI, T1/T2 and CT in confirming the status of cDLMs using as reference either the histopathological complete response or the absence of a local recurrence at the site of cDLMs during the follow up period of 2 years. The study aims at excluding a NPV≤0.85 and is powered under the alternative that the NPV≥0.95. The planned sample size is 92 evaluable (resected or left behind) cDLMs, with a 1-sided alpha of 5% and a power of 90% adjusting for within-patient correlation between cDLMs of 0.2 and an average number of 2 cDLMs per patient. Approximately 400 patients will be registered from European, Japanese and US sites over 3 years. As of February 2017, 2 patients have been enrolled. Clinical trial information: NCT02781935.
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Article title: Collaboration between EORTC and JCOG-how to accelerate global clinical research partnership
Authors: Kozo Kataoka, Kenichi Nakamura, Carmela Caballero, Serge Evrard, Anastassia Negrouk, Manabu Shiozawa, Laurence Collette, Haruhiko Fukuda, Denis Lacombe
Publication title: Japanese Journal of Clinical Oncology 47(2), October 2016

Abstract:
The demand for international collaboration in cancer clinical trials has grown stronger to maximize efficiency, avoid duplication of effort and to achieve effective implementation of research results into medical practice. Infrastructures that could facilitate intercontinental collaboration not only between Europe and United States but also between Europe and Asia are urgently needed. The European Organisation for Research and Treatment of Cancer, one of the major cancer clinical research infrastructure in Europe, initiated collaboration with the Japan Clinical Oncology Group, the largest cancer research cooperative group in Japan. Their first pilot trial on unresectable colorectal liver metastasis will commence on fourth quarter of 2016. With similar goals and strategies as well as with similar structures, the two research organizations have a great potential for efficient collaboration that could deliver faster and global therapeutic improvement to cancer patients. However, international collaboration requires careful and structured approach to harmonize activities to ensure success. This article focuses on specific intercontinental differences and the necessary requirements to ensure a successful partnership between European Organisation for Research and Treatment of Cancer and Japan Clinical Oncology Group. This could serve as a model to build more global international academic trials between the East and the West.
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