Menée sur 136 patientes présentant 1 à 3 métastases cérébrales ayant pour origine un cancer du sein, cette étude évalue, du point de vue du taux d'échec local ou régional à 1 an ou de la survie globale, l'efficacité d'une radiochirurgie stéréotaxique définitive, puis identifie les facteurs pronostiques associés

Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

Yang, T. Jonathan ; Oh, Jung Hun ; Folkert, Michael R. ; Gupta, Gaorav ; Shi, Weiji ; Zhang, Zhigang ; Morikawa, Aki ; Seidman, Andrew ; Brennan, Cameron ; Yamada, Yoshiya ; Chan, Timothy A. ; Beal, Kathryn

Background : With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials : We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess [...]

Menée sur 2 233 patients atteints d'un lymphome folliculaire et ayant reçu une greffe autologue de cellules souches hématopoïétiques entre 1995 et 2007 (durée médiane de suivi : 73 mois), cette étude évalue, par rapport à une chimiothérapie de conditionnement de type BEAM, l'effet d'une irradiation corporelle totale sur la mortalité sans récidive à 5 et 10 ans et sur le risque de syndrome myelodysplasique ou de leucémie myéloblastique aiguë liés au traitement

The impact of total body irradiation on the outcome of patients with follicular lymphoma treated with autologous stem cell transplantation in the modern era. A retrospective study of the EMBT lymphoma working party

El-Najjar, I. ; Boumendil, A. ; Luan, J.J. ; Bouabdallah, R. ; Thomson, K. ; Mohty, M. ; Colombat, P. ; Biron, P. ; Tilly, H. ; Pfreundschuh, M. ; Cordonnier, C. ; Sureda, A. ; Cahn, J.Y. ; Vernant, J.P. ; Gribben, J. ; Cook, G. ; Haynes, A.P. ; Ferrant, A. ; Finel, H. ; Montoto, S. ; Dreger, P.

Background : The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem cell transplantation (ASCT) in a recent time period. Patients : Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation-containing regimen (TBI) or BEAM, of which 47% were autografted in first remission. Results : After a median observation time of 73 months (interquartile [...]

Menée à partir de données portant sur 965 patientes atteintes d'un cancer du sein de stade précoce diagnostiqué entre 1989 et 2003 (âge : 20 à 39 ans ; durée médiane de suivi : 14,4 ans), cette étude compare, du point de vue de la survie spécifique et de la survie globale à 15 ans, l'efficacité d'une mastectomie radicale et d'un traitement chirurgical conservateur en combinaison avec une radiothérapie du sein entier

Should Women Younger Than 40 Years of Age With Invasive Breast Cancer Have a Mastectomy?: 15-Year Outcomes in a Population-Based Cohort

Cao, Jeffrey Q. ; Truong, Pauline T. ; Olivotto, Ivo A. ; Olson, Robert ; Coulombe, Genevieve ; Keyes, Mira ; Weir, Lorna ; Gelmon, Karen ; Bernstein, Vanessa ; Woods, Ryan ; Speers, Caroline ; Tyldesley, Scott

Purpose : Optimal local management for young women with early-stage breast cancer remains controversial. This study examined 15-year outcomes among women younger than 40 years treated with breast-conserving surgery plus whole-breast radiation therapy (BCT) compared with those treated with modified radical mastectomy (MRM). Methods and Materials : Women aged 20 to 39 years with early-stage breast cancer diagnosed between 1989 and 2003 were identified in a population-based database. Primary [...]

A partir d'une revue de la littérature (51 publications), cet article analyse le rôle, l'efficacité et les limites de la chirurgie actuelle dans la prise en charge thérapeutique d'un gliome de bas grade

Low-grade glioma management: a contemporary surgical approach

Riva, Marco ; Bello, Lorenzo

Purpose of review : The primary treatment of low-grade gliomas is still claimed to lack robust supporting evidence. Yet, several investigations were performed in the last 2 decades. To critically review these studies could help in further clarifying the role of surgery aimed at maximal resection. Recent findings : Despite the lack of randomized clinical trials hampering the performance of appropriate meta-analyses, the increasing amount of evidence pointed toward an aggressive surgical strategy [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes par lesquels, en augmentant l'angiogenèse tumorale et en inhibant l'immunité antitumorale, des nanoparticules sous forme de liposomes contenant des molécules cytotoxiques sont paradoxalement susceptibles de favoriser la croissance tumorale

Liposome promotion of tumor growth is associated with angiogenesis and inhibition of antitumor immune responses

Sabnani, Manoj K. ; Rajan, Robin ; Rowland, Bradley ; Mavinkurve, Vikram ; Wood, Laurence M. ; Alberto A, Gabizon ; La-Beck, Ninh M.

Liposomes have tremendous potential as drug carriers in the treatment of cancer. However, despite enhanced tumor drug delivery and decreased toxicity, patient survival rates have not improved significantly compared to corresponding free drug treatments. Importantly, we found that a liposomal nanoparticle currently used as a drug carrier in cancer patients enhanced tumor growth in an immune competent murine model of cancer. This was associated with increased tumor angiogenesis and suppression of [...]

Cet article passe en revue les perspectives thérapeutiques offertes par les connaissances sur le rôle de la protéase TMPRSS4 dans les processus biologiques des tumeurs solides

TMPRSS4: an emerging potential therapeutic target in cancer

de Aberasturi, A. L. ; Calvo, A.

Altered expression and activity of proteases is a key event in cancer, particularly in relation to invasion, modification of the extracellular matrix and metastasis. The transmembrane protease, serine 4 (TMPRSS4) is closely related to other cancer-associated proteases, such as hepsin, TMPRSS2 and matriptase. We review in this study up-to-date information about expression, role, regulation and clinical relevance of TMPRSS4 in cancer. Increased expression of this protease is associated with [...]

Menée à partir de données relatives à des patients atteints d'une leucémie lymphocytaire chronique, cette étude évalue les performances d'un modèle numérique de nature évolutionniste pour prédire l'apparition d'une résistance à l'ibrutinib

Evolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL)

Komarova, Natalia L. ; Burger, Jan A. ; Wodarz, Dominik

The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib is a new targeted therapy for patients with chronic lymphocytic leukemia (CLL). Ibrutinib is given orally on a continuous schedule and induces durable remissions in the majority of CLL patients. However, a small proportion of patients initially responds to the BTKi and then develops resistance. Estimating the frequency, timing, and individual risk of developing resistance to ibrutinib, therefore, would be valuable for long-term management of [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude suggère l'intérêt d'une molécule appelée MEDI-573, un anticorps anti IGF-1 et IGF-2, seul ou en combinaison avec un inhibiteur de mTOR pour le traitement des patients pédiatriques atteints d'un sarcome d'Ewing

MEDI-573 Alone or in Combination with Mammalian Target of Rapamycin Inhibitors, Targets the Insulin-like Growth Factor Pathway in Sarcomas

Zhong, Haihong ; Fazenbaker, Christine ; Breen, Shannon ; Chen, Cui ; Huang, Jiaqi ; Morehouse, Christopher ; Yao, Yihong ; Hollingsworth, Robert E.

MEDI-573 is a human antibody that neutralizes insulin-like growth factor (IGF)-1 and IGF-2. IGFs are over-expressed in multiple types of cancer; their over-expression is a potential mechanism for resistance to IGF-1 receptor (IGF-1R)-targeting therapy. Effects of IGF on cell proliferation, differentiation, and survival are mediated through its binding to and activation of IGF-1R or insulin receptor A (IR-A). In this study, we measured the mRNA levels of IGF-1, IGF-2 and IGF-1R in human [...]

Mené sur 64 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I/IIa évalue la toxicité et l'activité clinique du lucitanib

Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors

Soria, J-C. ; DeBraud, F. ; Bahleda, R. ; Adamo, B. ; André, F. ; Dientsmann, R. ; Delmonte, A. ; Cereda, R. ; Isaacson, Jeff ; Litten, J. ; Allen, A. ; Dubois, F. ; Saba, C. ; Robert, R. ; Camboni, Maria Gabriella ; Tabernero, J.

Background : Lucitanib is a potent, oral inhibitor FGFR1/2, VEGFR1-3 and PDGFRA/B, which are essential kinases for tumor growth, survival, migration, and angiogenesis. Several tumor types, including breast carcinoma, demonstrate amplification of FGF-related genes. There are no approved drugs for molecularly defined FGF-aberrant (FGFR1 or FGF3/4/19 amplified) tumors. Methods : This open-label phase I/IIa study involved a dose-escalation phase to determine maximum tolerated dose (MTD), [...]

A partir d'une revue systématique de la littérature, cet article présente des recommandations pour le traitement des patients atteints d'un cancer de la prostate résistant à la castration et de stade métastatique

Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline

Basch, Ethan ; Loblaw, D. Andrew ; Oliver, Thomas K. ; Carducci, Michael ; Chen, Ronald C. ; Frame, James N. ; Garrels, Kristina ; Hotte, Sebastien ; Kattan, Michael W. ; Raghavan, Derek ; Saad, Fred ; Taplin, Mary-Ellen ; Walker-Dilks, Cindy ; Williams, James ; Winquist, Eric ; Wootton, Ted ; Rumble, R. Bryan ; Dusetzina, Stacie B. ; Virgo, Katherine S.

Purpose : To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). Methods : The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. Results : When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone [...]

Menée sur 228 patients atteints d'un cancer gastrique traité par résection D2 (âge : 25 à 74 ans ; 81 femmes et 147 hommes), cette étude évalue l'efficacité, du point de vue du taux de survie sans maladie et du taux de survie globale à 5 ans, et la toxicité d'une chimiothérapie adjuvante par fluorouracile en combinaison avec une radiothérapie concomitante

Adjuvant chemoradiotherapy after D2 resection in gastric cancer: a single-center observational study

Kaytan Saglam, Esra ; Yucel, Serap ; Balik, Emre ; Saglam, Sezer ; Asoglu, Oktar ; Yamaner, Sumer ; Bugra, Dursun ; Oral, EthemN ; Kizir, Ahmet ; Kapran, Yersu ; Sakar, Burak ; Akyuz, Ali ; Gulluoglu, Mine

Purpose : Previous studies demonstrated survival benefits in association with the addition of chemoradiotherapy after surgery in gastric cancer. This study aimed to examine the efficacy in terms of loco-regional control and survival and safety of 5-FU-based adjuvant chemoradiotherapy after D2 curative surgery. Methods : This study included 228 patients (81 female, 147 male) treated for gastric cancer with curative surgery plus adjuvant chemoradiotherapy. Majority of the patients underwent at [...]

Mené en Chine sur 127 patients atteints d'un carcinome hépatocellulaire, cet essai évalue, du point de vue des taux de récidive à 1 et 2 ans, l'intérêt du métuximab-I131 après une ablation percutanée par radiofréquence

Randomized Trial of [131I] Metuximab in Treatment of Hepatocellular Carcinoma After Percutaneous Radiofrequency Ablation

Bian, Huijie ; Zheng, Jia-Sheng ; Nan, Gang ; Li, Rui ; Chen, Changsheng ; Hu, Cai-Xia ; Zhang, Yang ; Sun, Bin ; Wang, Xi-Long ; Cui, Shi-Chang ; Wu, Jiao ; Xu, Jing ; Wei, Ding ; Zhang, Xiaoyong ; Liu, Haichun ; Yang, Wuwei ; Ding, Yong ; Li, Jing ; Chen, Zhi-Nan

To assess the efficacy of combining radioimmunoconjugate [131I] metuximab with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) treatment compared with RFA alone, a single-center randomized controlled trial was conducted on 127 patients with Barcelona Clinic Liver Cancer staging system (BCLC) classifications of 0–B stage. Patients received either RFA followed by [131I] metuximab (n = 62) or RFA alone (n = 65). The primary outcome was overall tumor recurrence. Statistical tests [...]

A partir de données portant sur 7 776 essais cliniques de traitements d'un cancer chez des patients adultes (date d'ouverture des inclusions : entre 2005 et 2011), cette étude évalue le nombre d'essais qui n'ont pas réussi à inclure le nombre de patients nécessaire

Adult Cancer Clinical Trials That Fail to Complete: An Epidemic?

Stensland, Kristian D. ; McBride, Russell B. ; Latif, Asma ; Wisnivesky, Juan ; Hendricks, Ryan ; Roper, Nitin ; Boffetta, Paolo ; Hall, Simon J. ; Oh, William K. ; Galsky, Matthew D.

The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent [...]

Cet article résume les conclusions d'un colloque, organisé en commun par le National Cancer Institute et le National Heart, Lung and Blood Institute, sur les toxicités cardiovasculaires associées aux traitements des cancers

Cancer Treatment–Related Cardiotoxicity: Current State of Knowledge and Future Research Priorities

Shelburne, Nonniekaye ; Adhikari, Bishow ; Brell, Joanna ; Davis, Myrtle ; Desvigne-Nickens, Patrice ; Freedman, Andrew ; Minasian, Lori ; Force, Thomas ; Remick, Scot C.

Cardiotoxicity resulting from direct myocyte damage has been a known complication of cancer treatment for decades. More recently, the emergence of hypertension as a clinically significant side effect of several new agents has been recognized as adversely affecting cancer treatment outcomes. With cancer patients living longer, in part because of treatment advances, these adverse events have become increasingly important to address. However, little is known about the cardiovascular pathogenic [...]

A partir d'une analyse de la littérature publiée jusqu'en mars 2014, cette étude identifie un petit nombre d'articles présentant une nouvelle analyse de données d'essais cliniques randomisés ayant déjà fait l'objet d'une publication

Reanalyses of randomized clinical trial data

Ebrahim, S. ; Sohani, Z. N. ; Montoya, L. ; et al.,

Importance  : Reanalyses of randomized clinical trial (RCT) data may help the scientific community assess the validity of reported trial results. Objectives  : To identify published reanalyses of RCT data, to characterize methodological and other differences between the original trial and reanalysis, to evaluate the independence of authors performing the reanalyses, and to assess whether the reanalysis changed interpretations from the original article about the types or numbers of patients who [...]

A partir de données portant sur 99 essais cliniques de phase III en oncologie, cette étude évalue l'association entre des indicateurs de toxicité et des indicateurs de survie

Association between treatment toxicity and outcomes in oncology clinical trials

Abola, M.V. ; Prasad, V. ; Jena, A.B.

Background : Whether or not toxicity predicts clinical outcomes has long been a question regarding cancer treatments. While prior studies have focused on specific cancers, therapies, and toxicities, no comprehensive evidence exists on whether treatment toxicity predicts favorable outcomes. Methods : We abstracted treatment toxicity and clinical outcome data from a sample of phase III oncology randomized clinical trials (n=99 trials). We investigated whether treatments with relatively greater [...]

Cet article présente les données ayant servi de base à la Food and Drug Administration pour autoriser, en septembre 2013, la mise sur le marché du pertuzumab dans le traitement néoadjuvant d'un cancer du sein HER2+

First FDA Approval of Neoadjuvant Therapy for Breast Cancer: Pertuzumab for the Treatment of Patients with HER2-Positive Breast Cancer

Amiri-Kordestani, Laleh ; Wedam, Suparna ; Zhang, Lijun ; Tang, Shenghui ; Tilley, Amy ; Ibrahim, Amna ; Justice, Robert ; Pazdur, Richard ; Cortazar, Patricia

On September 30, 2013, the FDA granted accelerated approval to pertuzumab (PERJETA, Genentech, Inc.) for use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. The approval was based in part on a randomized multicenter trial in the indicated population that [...]