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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.

Lacombe D.,EORTC Headquarters | Tejpar S.,UZ 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.

Santarpia M.,Messina University | Gil N.,Champalimaud Cancer Center | Rosell R.,Precision for Medicine | Rosell R.,Germans Trias i Pujol Health science Institute and Hospital | And 2 more authors.
Expert Review of Clinical Pharmacology | Year: 2015

The use of molecularly targeted agents has dramatically improved the prognosis of defined subsets of patients with non-small-cell lung cancer harboring somatically activated oncogenes, such as mutant EGFR or rearranged ALK. However, after initial marked responses to EGFR or ALK tyrosine kinase inhibitors (TKIs), almost all patients inevitably progress due to development of acquired resistance. Multiple molecular mechanisms of resistance have been identified; the best characterized are secondary mutations in the tyrosine kinase domain of the oncogene, such as T790M in EGFR and L1196M in ALK, which prevent target inhibition by the corresponding TKI. Other mechanisms include copy number gain of the ALK fusion gene and the activation of bypass signaling pathways that can maintain downstream proliferation and survival signals despite inhibition of the original drug target. Here, the authors provide an overview of the known mechanisms of resistance to TKIs and outline the therapeutic strategies, including new investigational agents and targeted therapies combinations, that have been developed to overcome resistance. © 2015 Informa UK, 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.

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.

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