Cet article passe en revue les avantages et les limites de l'utilisation des particules chargées dans le traitement des cancers localisés et fait le point sur les futurs axes de recherche

Charged particle therapy-optimization, challenges and future directions

Loeffler, Jay S. ; Durante, Marco

The use of charged particle therapy to control tumours non-invasively offers advantages over conventional radiotherapy. Protons and heavy ions deposit energy far more selectively than X-rays, allowing a higher local control of the tumour, a lower probability of damage to healthy tissue, low risk of complications and the chance for a rapid recovery after therapy. Charged particles are also useful for treating tumours located in areas that surround tissues that are radiosensitive and in [...]

Cet article fait le point sur les principes fondamentaux et les applications de la chirurgie guidée par l'image dans le traitement des cancers

Optical Image-Guided Cancer Surgery: Challenges and Limitations

Keereweer, Stijn ; Van Driel, Pieter B.A.A. ; Snoeks, Thomas JA ; Kerrebijn, Jeroen D.F. ; Baatenburg de Jong, Robert J ; Vahrmeijer, Alexander L ; Sterenborg, Henricus J.C.M. ; Lowik, Clemens W.G.M.

Optical image-guided cancer surgery is a promising technique to adequately determine tumor margins by tumor-specific targeting, potentially resulting in complete resection of tumor tissue with improved survival. However, identification of the photons coming from the fluorescent contrast agent is complicated by autofluorescence, optical tissue properties, and accurate fluorescent targeting agents and imaging systems. These factors all have an important influence on the image that is presented to [...]

Menée sur 88 patients atteints d'un mésothéliome pleural traité entre 2002 et 2011 par pleurectomie radicale puis chimioradiothérapie, cette étude rétrospective évalue l'effet d'une pleurectomie radicale incomplète sur la survie des patients ainsi que l'intérêt de compléter le traitement par une pneumonectomie extrapleurale

Radical pleurectomy and chemoradiation for malignant pleural mesothelioma: The outcome of incomplete resections

Bolukbas, Servet ; Eberlein, Michael ; Fisseler-Eckhoff, Annette ; Schirren, Joachim

Background : The type of surgery (radical pleurectomy (RP) vs. extrapleural pneumonectomy (EPP)) remains controversial for malignant pleural mesothelioma (MPM). Macroscopic complete resection (MCR) is a key prognostic factor. It is unclear, if patients undergoing incomplete RP within a standardized multimodality treatment protocols have any advantage in terms of survival and if EPP could theoretically have avoided incomplete resections (R2). Methods : Eighty-eight patients underwent RP followed [...]

Cet article fait le point sur les stratégies thérapeutiques permettant de réduire le risque de lésions rectales associées à une radiothérapie externe pour traiter un cancer de la prostate

Reducing rectal injury during external beam radiotherapy for prostate cancer

Valdagni, Riccardo ; Rancati, Tiziana

Rectal bleeding and faecal incontinence are serious injuries that men with prostate cancer who receive radiotherapy can experience. Although technical advances—including the use of intensity-modulated radiotherapy coupled with image-guided radiotherapy—have enabled the delivery of dose distributions that conform to the shape of the tumour target with steep dose gradients that reduce the dose given to surrounding tissues, radiotherapy-associated toxicity can not be avoided completely. Many [...]

A partir d'une revue systématique de la littérature publiée entre 2000 et 2012 (12 articles, 1 360 patients), cette étude évalue, du point de vue de données intra- et post-opératoires et de la survie sans récidive biochimique à 3 ans, l'intérêt d'une prostatectomie radicale assistée par robot et d'un curetage ganglionnaire pelvien pour traiter un cancer de la prostate à haut risque de récidive

The Role of Robot-assisted Radical Prostatectomy and Pelvic Lymph Node Dissection in the Management of High-risk Prostate Cancer: A Systematic Review

Bertram, Yuh ; Walter, Artibani ; Axel, Heidenreich ; Simon, Kimm ; Mani, Menon ; Giacomo, Novara ; Ashutosh, Tewari ; Karim, Touijer ; Timothy, Wilson ; Kevin, C. Zorn ; Scott, E. Eggener

Context : The role of robot-assisted radical prostatectomy (RARP) for men with high-risk (HR) prostate cancer (PCa) has not been well studied. Objective : To evaluate the indications for surgical treatment, technical aspects such as nerve sparing (NS) and lymph node dissection (LND), and perioperative outcomes of men with HR PCa treated with RARP. Evidence acquisition : A systematic expert review of the literature was performed in October 2012, searching the Medline, Web of Science, and Scopus [...]

Menée sur 101 patients présentant une métastase cérébrale de grande taille traitée entre 2005 et 2012 (durée médiane de suivi : 16 mois), cette étude évalue l'efficacité, du point de vue du contrôle local, du taux d'échec à distance et de la survie, et la toxicité d'un traitement combinant chirurgie et radiothérapie stéréotaxique multidose par accélérateur linéaire de la cavité de résection (taille > 3 cm)

Multidose Stereotactic Radiosurgery (9 Gy × 3) of the Postoperative Resection Cavity for Treatment of Large Brain Metastases

Minniti, Giuseppe ; Esposito, Vincenzo ; Clarke, Enrico ; Scaringi, Claudia ; Lanzetta, Gaetano ; Salvati, Maurizio ; Raco, Antonino ; Bozzao, Alessandro ; Maurizi Enrici, Riccardo

To evaluate the clinical outcomes with linear accelerator-based multidose stereotactic radiosurgery (SRS) to large postoperative resection cavities in patients with large brain metastases. Between March 2005 to May 2012, 101 patients with a single brain metastasis were treated with surgery and multidose SRS (9 Gy × 3) for large resection cavities (>3 cm). The target volume was the resection cavity with the inclusion of a 2-mm margin. The median cavity volume was 17.5 cm3 (range, 12.6-35.7 cm3). [...]

Menée à l'aide d'un modèle animal (lapin VX2) et sur quelques patients atteints d'une tumeur solide, cette étude évalue l'activité antitumorale d'un vaccin oncolytique appelé Pexa-Vec

Oncolytic and Immunotherapeutic Vaccinia Induces Antibody-Mediated Complement-Dependent Cancer Cell Lysis in Humans

Kim, Mi Kyung ; Breitbach, Caroline J. ; Moon, Anne ; Heo, Jeong ; Lee, Yu Kyoung ; Cho, Mong ; Lee, Jun Woo ; Kim, Seong-Geun ; Kang, Dae Hwan ; Bell, John C. ; Park, Byeong Ho ; Kirn, David H. ; Hwang, Tae-Ho

Oncolytic viruses cause direct cytolysis and cancer-specific immunity in preclinical models. The goal of this study was to demonstrate induction of functional anticancer immunity that can lyse target cancer cells in humans. Pexa-Vec (pexastimogene devacirepvec; JX-594) is a targeted oncolytic and immunotherapeutic vaccinia virus engineered to express human granulocyte-macrophage colony-stimulating factor (GM-CSF). Pexa-Vec demonstrated replication, GM-CSF expression, and tumor responses in [...]

Menée sur un modèle murin, cette étude évalue l'efficacité d'un composé immuno-modulateur (AS101) pour préserver la fertilité des patientes atteintes d’un cancer traité par cyclophosphamide

Cyclophosphamide Triggers Follicle Activation and “Burnout”; AS101 Prevents Follicle Loss and Preserves Fertility

Kalich-Philosoph, Lital ; Roness, Hadassa ; Carmely, Alon ; Fishel-Bartal, Michal ; Ligumsky, Hagai ; Paglin, Shoshana ; Wolf, Ido ; Kanety, Hannah ; Sredni, Benjamin ; Meirow, Dror

Premature ovarian failure and infertility are major side effects of chemotherapy treatments in young cancer patients. A more thorough understanding of the mechanism behind chemotherapy-induced follicle loss is necessary to develop new methods to preserve fertility in these patients. We show that the alkylating agent cyclophosphamide (Cy) activates the growth of the quiescent primordial follicle population in mice, resulting in loss of ovarian reserve. Despite the initial massive apoptosis [...]

Cet article passe en revue les perspectives offertes par des stratégies visant à normaliser le micro-environnement tumoral pour améliorer l'efficacité de traitements anticancéreux

Normalizing Tumor Microenvironment to Treat Cancer: Bench to Bedside to Biomarkers

Jain, Rakesh K.

For almost four decades, my work has focused on one challenge: improving the delivery and efficacy of anticancer therapeutics. Working on the hypothesis that the abnormal tumor microenvironment—characterized by hypoxia and high interstitial fluid pressure—fuels tumor progression and treatment resistance, we developed an array of sophisticated imaging technologies and animal models as well as mathematic models to unravel the complex biology of tumors. Using these tools, we demonstrated that the [...]

Menée sur des lignées cellulaires de cancer du poumon non à petites cellules ne présentant pas de mutations du gène LKB1, cette étude met en évidence des mécanismes par lesquels la metformine renforce l'activité antitumorale du gefitinib

Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines

Morgillo, Floriana ; Sasso, Ferdinando Carlo ; Della Corte, Carminia Maria ; Vitagliano, Donata ; D'aiuto, Elena ; Troiani, Teresa ; Martinelli, Erika ; De Vita, Ferdinando ; Orditura, Michele ; De Palma, Raffaele ; Ciardiello, Fortunato

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been found to be effective against lung cancer, but clinical resistance to these agents has developed as their usage has increased. Metformin is a widely used antidiabetic drug and also displays significant growth inhibitory and pro apoptotic effects in several cancer models, alone or in combination with chemotherapeutic drugs. Experimental design: The effects of gefitinib, a selective EGFR-TKI, and [...]

Menée in vitro, cette étude met en évidence des mécanismes par lesquels la protéine Src joue un rôle dans l'apparition d'une résistance à l'erlotinb chez les patients, fumeurs actuels ou anciens, atteints d'un cancer du poumon non à petites cellules

Src mediates cigarette smoke-induced resistance to tyrosine kinase inhibitors in NSCLC cells

Filosto, Simone ; Baston, David S ; Chung, Samuel ; Becker, Cathleen R ; Goldkorn, Tzipora

The EGF Receptor (EGFR) is a proto-oncogene commonly dysregulated in several cancers including non-small cell lung cancer (NSCLC) and, thus, is targeted for treatment using tyrosine kinase inhibitors (TKIs) such as Erlotinib. However, despite the efficacy observed in NSCLC patients harboring oncogenic variants of the EGFR, general ineffectiveness of TKIs in NSCLC patients who are current and former smokers necessitates identification of novel mechanisms to overcome this phenomenon. Previously, [...]

Menée sur des lignées cellulaires et à l'aide d'un modèle murin, cette étude met en évidence des mécanismes permettant de rendre compte de l'association entre la prise de metformine et l'amélioration de la survie chez des patients atteints d'un cancer de la prostate

Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism

Fendt, Sarah-Maria ; Bell, Eric L ; Keibler, Mark A. ; Davidson, Shawn M ; Wirth, Gregory J ; Fiske, Brian ; Mayers, Jared R ; Schwab, Matthias ; Bellinger, Gary ; Csibi, Alfredo ; Patnaik, Akash ; Blouin, Marie-Jose ; Cantley, Lewis C ; Guarente, Leonard P. ; Blenis, John ; Pollak, Michael N. ; Olumi, Aria F ; Vander Heiden, Matthew ; Stephanopoulos, Gregory

Metformin inhibits cancer cell proliferation and epidemiology studies suggest an association with increased survival in cancer patients taking metformin, however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine [...]

Menée sur des lignées cellulaires de chrondrosarcome et à l'aide de xénogreffes, cette étude évalue des mécanismes par lesquels une inhibition de la signalisation CXCR4 agit sur l'angiogenèse tumorale et le processus métastatique

CXCR4-targeted Therapy Inhibits VEGF Expression and Chondrosarcoma Angiogenesis and Metastasis

Sun, Xiaojuan ; Charbonneau, Cherie ; Wei, Lei ; Yang, Wentian ; Chen, Qian ; Terek, Richard M

Chondrosarcoma is notable for its lack of response to conventional cytotoxic chemotherapy, propensity for developing lung metastases, and poor survival. Therefore, a better understanding of angiogenic and metastatic pathways is needed. Multiple pathways regulate angiogenesis and metastasis, including chemokines and their receptors. In this study, we investigated CHEMOKINE (C-X-C MOTIF) RECEPTOR 4 (CXCR4) signaling in chondrosarcoma and tested the hypotheses that CXCR4 inhibition suppresses [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'intérêt de combiner un inhibiteur de mTOR et un inhibiteur d'AKT pour le traitement de tumeurs du sein "basal-like" n'exprimant pas le gène PTEN

Combined Targeting of mTOR and AKT is an Effective Strategy for Basal-like Breast Cancer in Patient-derived Xenograft Models

Xu, Siguang ; Li, Shunqiang ; Guo, Zhanfang ; Luo, Jingqin ; Elllis, Matthew J. ; Ma, Cynthia X

Basal-like breast cancer is an aggressive disease, for which targeted therapies are lacking. Recent studies demonstrated that basal-like breast cancer is frequently associated with an increased activity of the phosphatidylinositol 3-kinase (PI3K) pathway, which is critical for cell growth, survival and angiogenesis. To investigate the therapeutic potential of PI3K pathway inhibition in the treatment of basal-like breast cancer, we evaluated the anti-tumor effect of the mTOR inhibitor MK-8669 [...]

A partir d'une revue de la littérature publiée entre 2001 et 2011 (24 essais identifiés), cette méta-analyse évalue les risques de complications métaboliques associées aux traitements à l'aide d'inhibiteurs de mTOR (temsirolimus, everolimus et ridaforolimus)

Metabolic complications with the use of mTOR inhibitors for cancer therapy

Sivendran, Shanthi ; Agarwal, Neeraj ; Gartrell, Benjamin ; Ying, Jian ; Boucher, Kenneth M. ; Choueiri, Toni K. ; Sonpavde, Guru ; Oh, William K. ; Galsky, Matthew D.

mTOR inhibitors are now approved by regulatory agencies for the treatment of a variety of malignancies. The risk of metabolic complications with these agents is not well characterized. PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating temsirolimus, everolimus, and ridaforolimus in patients with all solid tumor malignancies. Sixteen eligible phase II clinical trials and 8 randomized controlled clinical trials were [...]

Mené sur 80 patients atteints d'un mélanome métastatique, cette étude évalue l'efficacité d'un transfert adoptif de lymphocytes infiltrant les tumeurs, en combinaison ou non avec l'ipilimumab

Adoptive Transfer of Tumor Infiltrating Lymphocytes in Metastatic Melanoma Patients: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies

Besser, Michal J ; Shapira-Frommer, Ronnie ; Itzhaki, Orit ; Treves, Avraham J ; Zippel, Dov ; Levy, Daphna ; Kubi, Adva ; Shoshani, Noa ; Zikich, Dragoslav ; Ohayon, Yaara ; Ohayon, Daniel ; Shalmon, Bruria ; Markel, Gal ; Yerushalmi, Ronit ; Apter, Sara ; Ben-Nun, Alon ; Ben-Ami, Eytan ; Shimoni, Avichai ; Nagler, Arnon ; Schachter, Jacob

Purpose: Adoptive Cell Transfer (ACT) using autologous Tumor Infiltrating Lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic melanoma patients. Here we present the intent-to-treat analysis of TIL ACT and analyze parameters predictive to response as well as the impact of other immunotherapies. Experimental Design: Eighty stage IV melanoma patients were enrolled, of which 57 were treated with Unselected/Young TIL and high-dose IL-2 following non-myeloablative [...]

Mené sur 275 patients atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase III évalue, du point de vue de la survie sans progression, l'efficacité de diverses combinaisons de gemcitabine, docétaxel, carcoplatine et vinorelbine en fonction du niveau d'expression des protéines ERCC1 et RRM1

Randomized International Phase III Trial of ERCC1 and RRM1 Expression–Based Chemotherapy Versus Gemcitabine/Carboplatin in Advanced Non–Small-Cell Lung Cancer

Bepler, Gerold ; Williams, Charles ; Schell, Michael J. ; Chen, Wei ; Zheng, Zhong ; Simon, George ; Gadgeel, Shirish ; Zhao, Xiuhua ; Schreiber, Fred ; Brahmer, Julie ; Chiappori, Alberto ; Tanvetyanon, Tawee ; Pinder-Schenck, Mary ; Gray, Jhanelle ; Haura, Eric ; Antonia, Scott ; Fischer, Juergen R.

Purpose We assessed whether chemotherapy selection based on in situ ERCC1 and RRM1 protein levels would improve survival in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Eligible patients were randomly assigned 2:1 to the trial’s experimental arm, which consisted of gemcitabine/carboplatin if RRM1 and ERCC1 were low, docetaxel/carboplatin if RRM1 was high and ERCC1 was low, gemcitabine/docetaxel if RRM1 was low and ERCC1 was high, and docetaxel/vinorelbine if [...]

Mené sur 750 patients atteints d'un cancer colorectal métastatique sans mutation du gène K-RAS, cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, de l'ajout du brivanib au cetuximab après l'échec d'une chimiothérapie

Phase III Randomized, Placebo-Controlled Study of Cetuximab Plus Brivanib Alaninate Versus Cetuximab Plus Placebo in Patients With Metastatic, Chemotherapy-Refractory, Wild-Type K-RAS Colorectal Carcinoma: The NCIC Clinical Trials Group and AGITG CO.20 Trial

Siu, Lillian L. ; Shapiro, Jeremy D. ; Jonker, Derek J. ; Karapetis, Chris S. ; Zalcberg, John R. ; Simes, John ; Couture, Felix ; Moore, Malcolm J. ; Price, Timothy J. ; Siddiqui, Jehan ; Nott, Louise M. ; Charpentier, Danielle ; Liauw, Winston ; Sawyer, Michael B. ; Jefford, Michael ; Magoski, Nadine M. ; Haydon, Andrew ; Walters, Ian ; Ringash, Jolie ; Tu, Dongsheng ; O’Callaghan, Chris J.

Purpose The antiepidermal growth factor receptor monoclonal antibody cetuximab has improved survival in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer. The addition of brivanib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor and fibroblast growth factor receptor, to cetuximab has shown encouraging early clinical activity. Patients and Methods Patients with metastatic colorectal cancer previously treated with combination [...]

A partir d'une revue systématique de la littérature publiée entre décembre 2007 et décembre 2012, cet article propose des recommandations sur la prévention et le traitement d'une thromboembolie veineuse chez les patients atteints de cancer

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

Lyman, Gary H. ; Khorana, Alok A. ; Kuderer, Nicole M. ; Lee, Agnes Y. ; Arcelus, Juan Ignacio ; Balaban, Edward P. ; Clarke, Jeffrey M. ; Flowers, Christopher R. ; Francis, Charles W. ; Gates, Leigh E. ; Kakkar, Ajay K. ; Key, Nigel S. ; Levine, Mark N. ; Liebman, Howard A. ; Tempero, Margaret A. ; Wong, Sandra L. ; Prestrud, Ann Alexis ; Falanga, Anna

Purpose To provide recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. Prophylaxis in the outpatient, inpatient, and perioperative settings was considered, as were treatment and use of anticoagulation as a cancer-directed therapy. Methods A systematic review of the literature published from December 2007 to December 2012 was completed in MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed evidence to determine which [...]

En prenant l'exemple du bevacizumab, cet article analyse les forces et les faiblesses des modèles précliniques et cliniques permettant d'évaluer le degré de biosimilarité des anticorps monoclonaux utilisés en oncologie

Measures of biosimilarity in monoclonal antibodies in oncology: The case of bevacizumab

Ebbers, Hans C. ; Mantel-Teeuwisse, Aukje K. ; Leufkens, Hubert G. M. ; Moors, Ellen H. M. ; Schellekens, Huub ; van Meer, Peter J. K.

Biosimilars have been available on the European market since 2006 and experience with their use is increasing. The next wave of biopharmaceuticals that are about to lose patent protection consists of more-complicated products, including many monoclonal antibodies. Guidance has been released on the particulars of a biosimilarity exercise involving these products. Considerable challenges are posed by anticancer products and there is ongoing controversy regarding which basis to establish [...]