Champalimaud Cancer Center

Lisbon, Portugal

Champalimaud Cancer Center

Lisbon, Portugal
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Carvalho C.,Champalimaud Cancer Center | Glynne-Jones R.,Mount Vernon Hospital
The Lancet Oncology | Year: 2017

For patients with high-risk stage II or stage III colon cancer, adjuvant chemotherapy with fluoropyrimidine monotherapy reduces the risk of recurrence and death by approximately 20–30%. Additional improvements have been reported in three phase 3 colon cancer trials when oxaliplatin was added to the chemoradiation regimen, although the effect was mainly on disease-free survival. However, patients with rectal cancer were specifically excluded from these landmark studies because of potential toxicity and the confounding impact of radiotherapy and chemoradiation. Hence, despite evidence from smaller individual postoperative adjuvant phase 3 trials, meta-analyses, retrospective analyses, reviews, and population studies, the precise benefit of adjuvant chemotherapy for patients with rectal cancer following radiotherapy or chemoradiation remains unclear. Consequently, clinical guidelines offer inconsistent recommendations for the management of this patient population. In this Review, we suggest that the available data do not robustly support the routine use of postoperative adjuvant chemotherapy for patients with rectal cancer treated with preoperative chemoradiation. We discuss sources of bias and offer potential reasons to explain this observation, as well as propose a recommended schema for a randomised phase 3 trial that might potentially answer this question definitively. © 2017 Elsevier Ltd

Drukker C.A.,Netherlands Cancer Institute | Schmidt M.K.,Netherlands Cancer Institute | Rutgers E.J.T.,Netherlands Cancer Institute | Cardoso F.,Champalimaud Cancer Center | And 8 more authors.
Breast Cancer Research and Treatment | Year: 2014

Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007-2011, who participated in the national screening program (biennial screening ages 50-75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p < 0.0001; 95 % CI 1.73-3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM. © 2014 The Author(s).

Glynne-Jones R.,Mount Vernon Center for Cancer Treatment | Carvalho C.,Champalimaud Cancer Center
Seminars in Radiation Oncology | Year: 2016

Preoperative radiotherapy has an accepted role in reducing the risk of local recurrence in locally advanced resectable rectal cancer, particularly when the circumferential resection margin is breached or threatened, according to magnetic resonance imaging. Fluoropyrimidine-based chemoradiation can obtain a significant down-sizing response and a curative resection can then be achieved. Approximately, 20% of the patients can also obtain a pathological complete response, which is associated with less local recurrences and increased survival. Patients who achieve a sustained complete clinical response may also avoid radical surgery. In unresectable or borderline resectable tumors, around 20% of the patients still fail to achieve a sufficient down-staging response with the current chemoradiation schedules. Hence, investigators have aspired to increase pathological complete response rates, aiming to improve curative resection rates, enhance survival, and potentially avoid mutilating surgery. However, adding additional cytotoxic or biological agents have not produced dramatic improvements in outcome and often led to excess surgical morbidity and higher levels of acute toxicity, which effects on compliance and in the global efficacy of chemoradiation. © 2016 Elsevier Inc.

Cardoso F.,Champalimaud Cancer Center | Bischoff J.,Otto Von Guericke University of Magdeburg | Brain E.,Hopital Rene Huguenin Institute Curie | Brain E.,HopitalReneHuguenin Institute Curie | And 6 more authors.
Cancer Treatment Reviews | Year: 2013

Endocrine therapy is the corner stone treatment for postmenopausal women with hormone receptor-positive metastatic breast cancer (MBC). Besides tamoxifen and many older agents, recently developed endocrine agents for the treatment of MBC include the third generation aromatase inhibitors (AI) - anastrozole, exemestane, letrozole - and the pure oestrogen receptor antagonist fulvestrant. As treatment of breast cancer evolves, both tamoxifen and the AIs are being increasingly used in the adjuvant setting. As such, a significant proportion of patients with hormone receptor-positive MBC will have previously received tamoxifen, an AI or both, as adjuvant treatment. This has changed the metastatic landscape and has an impact on treatment choices for patients with hormone receptor-positive MBC. In this review, we evaluate the available evidence supporting the use of endocrine therapy for the treatment of hormone receptor-positive MBC. Additionally, we consider the effect of prior adjuvant therapy on treatment choice in the metastatic setting and the optimal treatment sequence. Finally, we discuss endocrine-responsive HER2 positive tumours and the ongoing research initiatives which aim to improve outcomes for patients with MBC. © 2012 Elsevier Ltd.

Oliveira H.P.,INESC Porto | Cardoso J.S.,INESC Porto | Magalhaes A.,University of Porto | Cardoso M.J.,Champalimaud Cancer Center
Proceedings - International Conference on Image Processing, ICIP | Year: 2012

Breast Cancer Conservative Treatment (BCCT) is now the preferred technique for breast cancer treatment. The limited reproducibility of standard aesthetic evaluation methods led to the development of objective methods, such as Breast Cancer Conservative Treatment.cosmetic results (BCCT.core) software tool. Although the satisfying results, there are still limitations concerning complete automation and the inability to measure volumetric information. With the fundamental premise of maintaining the system as a low-cost tool, the incorporation of the Microsoft Kinect sensor in BCCT evaluations was studied. The aim with this work is to enable the simultaneous detection of breast contour and breast peak points using depth-map data. Experimental results show that the proposed algorithm is accurate and robust for a wide number of patients. Additionally, comparatively to previous research, the procedure for detecting prominent points was automated. © 2012 IEEE.

Lacombe D.,EORTC Headquarters | Tejpar S.,U.Z. Leuven Campus Gasthuisberg | Salgado R.,Institute Jules Bordet | Cardoso F.,Champalimaud Cancer Center | And 5 more authors.
Nature Reviews Clinical Oncology | Year: 2014

Health systems and the clinical research landscape evolve continuously owing to increased risk aversion, scrutiny by funding bodies, and costs of clinical trials. In this context, however, current drug development procedures are far from optimal, as exemplified by the late-stage failure of several drugs. The identification of new drugs urgently requires approaches based on a solid understanding of cancer biology, and that will support the design of robust confirmatory trials. The complexity and the costs of drug development are now beyond the knowledge and operational capacity of single organisations, therefore, a drastic deviation from the traditional path of drug discovery and new forms of multidisciplinary partnerships are needed to succeed in this sector. The European Organisation for Research and Treatment of Cancer (EORTC) proposes the use of collaborative molecular screening platforms (CMSPs) as a new approach to tackle this issue. These CMSPs have the advantage of optimizing the expertise of several partners and combining efforts alongside with cost-sharing models for efficient patient selection. This article describes some of the challenges to advancing drug development and improving medical treatments and how these hurdles can be overcome. © 2014 Macmillan Publishers Limited. All rights reserved.

Moser E.C.,Champalimaud Cancer Center
European Oncology and Haematology | Year: 2013

Over the past decades, survival rates of cancer patients have increased impressively through the introduction of screening, new drugs and more personalised multi-modality treatments. This success in treating cancer has resulted in a large and rapidly increasing number of cancer survivors. Unfortunately, now that cancer is controlled in many patients, it has become clear that the life expectancy and quality of life of cancer survivors may be compromised by a spectrum of late adverse treatment effects. Some cancer survivors encounter second malignancies, severe cardiovascular or other morbidities which impair normal life in an important way. Some patients may be confronted with difficulties such as societal discrimination due to slower performance, chronic fatigue or partial inability, acceptance for work, education, insurance or credit history. To address these new issues, the EORTC is launching a variety of initiatives. Early in 2013, the EORTC Cancer Survivorship Task Force was created. The 1st EORTC Cancer Survivorship Summit will take place 30-31 January 2014 to facilitate interaction between clinicians, researchers, social workers, patients, insurers, bankers and policy makers. This summit will address the situation and needs of cancer survivors and guide future research and health policies in Europe in this field. © Touch medical media 2013.

Breast-conserving therapy, including whole breast irradiation, has become a well-established alternative to mastectomy in early-stage breast cancer patients, with similar survival rates and better cosmetic outcome. However, many women are still treated with mastectomy, due to logistical issues related to the long course of radiotherapy (RT). To reduce mastectomy rates and/or omission of RT after breast-conserving surgery, shorter, hypofractionated RT treatments have been introduced. More recently, the necessity of routinely treating the entire breast in all patients has been questioned, leading to the development of partial breast radiotherapy. With accelerated partial breast irradiation (APBI) these two approaches have been combined: the tumor bed with a 1-2 cm margin is irradiated either intra-operatively (single fraction) or postoperatively over 5-15 days. Different techniques have been developed, including interstitial brachytherapy, intra-cavity brachytherapy, intra-operative radiotherapy and external beam radiotherapy. These techniques are being evaluated in several ongoing phase III studies. Since its introduction, APBI has been the subject of continuous debate. ASTRO and GEC-ESTRO have published guidelines for patient selection for APBI, and strongly recommend that APBI be carried out within ongoing clinical trials. Recently, the patient selection criteria for APBI have also been up for debate, following the publication of results from different groups that do/do not confirm a difference in recurrence risk among the ASTRO defined risk groups. This paper reviews the different APBI techniques, current recommendations for patient selection, available clinical data and ongoing clinical trials. A case report is included to illustrate the need for careful follow-up of patients treated with APBI. © 2012 Elsevier Ltd.

Moser E.C.,Champalimaud Cancer Center | Meunier F.,EORTC Headquarters
European Journal of Cancer, Supplement | Year: 2014

Over the past decades, early diagnosis, new drugs and more personalised multi-modality treatment have led to impressive increases in survival rates of patients with cancer. This success in treating cancer has resulted in a large and rapidly increasing number of cancer survivors, yet life after cancer is often compromised by a broad spectrum of late adverse treatment effects. Some encounter cardiovascular, second malignancies, cognitive or other morbidities which impair normal life in an important way. Some patients are confronted with societal discrimination due to slower performance, chronic fatigue or partial inability and these things can adversely affect employment, education, insurance or mortgage opportunities.In 2012, the European Organisation of Research and Treatment of Cancer (EORTC) Survivorship Task Force was created to focus research efforts on late morbidity of cancer treatment and its impact on society. On 30-31st January 2014, the 1st EORTC Cancer Survivorship Summit was organised to facilitate interaction between clinicians, researchers, social workers, patients, insurers, bankers and policy makers. This important event addressed the needs of cancer survivors, and new collaborations between academic groups, patient advocates, financial and political representatives were formed to guide future European research and health policies in this field. This special issue of the European Journal of Cancer is entirely dedicated to this Summit and addresses, respectively, second malignancies, cardiovascular disease, cognitive dysfunction, infertility/sexuality and psycho-social problems following cancer treatment. © 2014.

Bedard P.L.,University of Toronto | Cardoso F.,Champalimaud Cancer Center
Nature Reviews Clinical Oncology | Year: 2011

Adjuvant chemotherapy reduces the risk of relapse and mortality for women with early-stage breast cancer. However, many women diagnosed with early-stage breast cancer experience the toxic effects associated with adjuvant chemotherapy without any meaningful benefit. There are a variety of clinicopathological factors-including hormone receptor expression, histology, and proliferation markers such as Ki-67-that can be used to try to identify patients who can safely avoid adjuvant chemotherapy. In addition, novel molecular tools, including the intrinsic molecular subtypes, prognostic multigene assays, and levels of urokinase-type plasminogen activator, provide further prognostic and predictive information to the standard clinicopathological factors thereby improving the accuracy of risk-of-relapse estimation and of the likelihood of response to cytotoxic chemotherapy. © 2011 Macmillan Publishers Limited. All rights reserved.

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