Cet article passe en revue les études récentes concernant l'utilisation de la chirurgie assistée par robot pour traiter des cancers gynécologiques, puis analyse ses avantages et ses inconvénients

Robotic surgery in gynecologic oncology

Fleming, Nicole D. ; Ramirez, Pedro T.

Purpose of review: The objective of this article is to review the recently published literature on the use of robotic surgery in the management of gynecologic malignancies. Recent findings: Retrospective data collected from many institutions support the use of robotic surgery in the management of cervical, endometrial, and early-stage ovarian cancer. Benefits to robotic surgery include decreased blood loss, fewer perioperative complications, and decreased length of hospital stay, especially [...]

Cet article passe en revue les avancées concernant les techniques d'imagerie et analyse leur rôle dans le traitement des patients atteints d'un cancer de la prostate avec métastases ganglionnaires

Management of prostate cancer patients with lymph node involvement: A rapidly evolving paradigm

Créhange, Gilles ; Chen, Chien Peter ; Hsu, Charles C. ; Kased, Norbert ; Coakley, Fergus V. ; Kurhanewicz, John ; Roach, Mack

Although widespread PSA screening has inevitably led to increased diagnosis of lower risk prostate cancer, the number of patients with nodal involvement at baseline remains high (nearly 40% of high risk patients initially staged cN0). These rates probably do not reflect the true incidence of prostate cancer with lymph node involvement among patients selected for external beam radiotherapy (EBRT), as patients selected for surgery often have more favorable prognostic features. At many [...]

Menée sur 69 patientes atteintes d'un carcinome canalaire invasif ou in situ de stade précoce et traitées par tumorectomie (âge : 50 ans ou plus), cette étude multicentrique évalue, du point de vue du taux de récidive, de la nature et de la gravité des événements indésirables, les résultats cliniques associés à une brachythérapie électronique ainsi que la qualité de vie des patientes un an après l'opération

Postsurgical Treatment of Early-stage Breast Cancer With Electronic Brachytherapy: Outcomes and Health-related Quality of Life at 1 Year

Patel, Rakesh R. ; Beitsch, Peter D. ; Nichols, Timothy D. ; Lorenzetti, John D. ; Wurzer, James C. ; Tucker, James C. ; Nunn, George W. ; Laduzinsky, Susan J. ; Kugler, Morris A. ; Simmons, Dwelvin L. ; Gilligan, Michael S. ; Roy, Tapan ; Foley, Jonathon K. ; Thropay, John P. ; Odou, Mark William ; Bornstein, Bruce A. ; Tito, Elizabeth P. ; Chadha, Manjeet ; Boolbol, Susan K. ; Lane, Steven C. ; White, Julie G.

Objectives: This multicenter registry followed up patients with early-stage breast cancer treated with breast-conserving surgery and electronic brachytherapy (EBT). This report provides 1- and 2-year updates to the initial publication. Methods: Patients were of age 50 years or more with invasive carcinoma or ductal carcinoma in situ, tumor size <=3 cm, and negative surgical margins. After lumpectomy, patients received EBT in 10 fractions over 5 days (34 Gy total). Results: Of the 69 patients [...]

Menée sur 103 patients atteints d'un cancer, cette étude rétrospective évalue, du point de vue de la survie globale et de la survie sans récidive intra-crânienne, l'intérêt d'une radiochirurgie stéréotaxique par Gamma Knife pour traiter 5 métastases cérébrales ou plus

Survival and Intracranial Control of Patients With 5 or More Brain Metastases Treated With Gamma Knife Stereotactic Radiosurgery

Raldow, Ann C. ; Chiang, Veronica L. ; Knisely, Jonathan P. ; Yu, James B.

Purpose: Limited data are available to help inform decisions about stereotactic radiosurgery for patients with >=5 brain metastases. We therefore performed a retrospective analysis of patients treated for >5 brain metastases. Materials/Methods: Patients who underwent treatment for >=5 brain metastases from October 2000 to September 2010 were identified. Overall survival (OS) for each patient was calculated from the date of first treatment of >=5 metastases. Intracranial recurrence-free survival [...]

Menée sur 196 patients atteints d'un cancer de la vessie traité entre 2003 et 2011, cette étude évalue la fréquence, la nature et la gravité des complications post-opératoires associées à une cystectomie radicale assistée par robot

Standardized Analysis of Frequency and Severity of Complications After Robot-assisted Radical Cystectomy

Bertram, E. Yuh ; Michael, Nazmy ; Nora, H. Ruel ; Jason, T. Jankowski ; Anita, R. Menchaca ; Robert, R. Torrey ; Jennifer, A. Linehan ; Clayton, S. Lau ; Kevin, G. Chan ; Timothy, G. Wilson

Background : Comprehensive and standardized reporting of adverse events after robot-assisted radical cystectomy (RARC) and urinary diversion for bladder cancer is necessary to evaluate the magnitude of morbidity for this complex operation. Objective : To accurately identify and assess postoperative morbidity after RARC using a standardized reporting system. Design, setting, and participants : A total of 241 consecutive patients underwent RARC, extended pelvic lymph node dissection, and urinary [...]

Menée sur 52 patients atteints d'un cancer des voies biliaires extra-hépatiques et ayant subi une intervention chirurgicale entre 2000 et 2010, cette étude monocentrique évalue, du point de vue de la survie globale, du contrôle locorégional de la maladie et de la présence de métastases distantes, l'efficacité d'une radiothérapie adjuvante pour traiter des micro- tumeurs résiduelles

Impact of Adjuvant Radiation Therapy for Microscopic Residual Tumor After Resection of Extrahepatic Bile Duct Cancer

Matsuda, Takeru ; Fujita, Hirofumi ; Harada, Naoki ; Kunimoto, Yukihiro ; Tanaka, Tomohiro ; Kimura, Taisei ; Kitaoka, Hironori ; Asano, Eisuke ; Hosono, Masayoshi ; Hayashi, Tomomi ; Ogino, Kazunori

Objectives: The effect of adjuvant radiation therapy (RT) in extrahepatic bile duct (EHBD) cancer patients with microscopic-positive resection margins (R1 resection) is still controversial. Methods: Between January 2000 and March 2010, 52 patients with EHBD cancer underwent surgery at our institution, of whom 36 were subjected to a retrospective analysis. Eleven patients received adjuvant RT after resection [surgery (S)+RT group], which included 9 patients with R1 resection and 2 with [...]

Menée in vitro et à l'aide de trois modèles murins, cette étude évalue l'activité antitumorale d'une nouvelle immunocytokine, formée par un anticorps et l'interleukine 12, en combinaison avec du paclitaxel

The antibody-based delivery of interleukin-12 to the tumor neo-vasculature eradicates cancer in combination with paclitaxel

Pasche, Nadine ; Wulhfard, Sarah ; Pretto, Francesca ; Carugati, Elisa ; Neri, Dario

Purpose:Interleukin-12 (IL12) is a potent proinflammatory cytokine with antitumor activity. Its heterodimeric nature makes it compatible with a large variety of different immunocytokine formats. Here we report the design, production and characterization of a novel immunocytokine, based on the fusion of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker of tumor neo-vasculature) with IL12 (termed IL12-F8-F8). Experimental Design:We developed a novel [...]

Menée in vitro et in vivo, cette étude évalue les effets d'un composé appelé WZB117, qui inhibe le transport de glucose, sur la croissance de cellules tumorales

A small molecule inhibitor of glucose transporter 1 down-regulates glycolysis, induces cell cycle arrest, and inhibits cancer cell growth in vitro and in vivo

Liu, Yi ; Cao, Yanyan ; Zhang, Weihe ; Bergmeier, Stephen ; Qian, Yanrong ; Akbar, Huzoor ; Colvin, Robert ; Ding, Juan ; Tong, Lingying ; Wu, Shiyong ; Hines, Jennifer ; Chen, Xiaozhuo

The functional and therapeutic importance of the Warburg effect is increasingly recognized and glycolysis has become a target of anticancer strategies. We recently reported the identification of a group of novel small compounds that inhibit basal glucose transport and reduce cancer cell growth by a glucose deprivation-like mechanism. We hypothesized that the compounds target Glut1 and are efficacious in vivo as anticancer agents. Here we report that a novel representative compound WZB117 not [...]

Mené sur 84 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la toxicité et l'activité antitumorale d'un composé appelé PX-866, un inhibiteur de PI3K

A Multicenter Phase 1 Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors

Hong, David S. ; Bowles, Daniel W ; Falchook, Gerald S. ; Messersmith, Wells A. ; George, Goldy C. ; O'Bryant, Cindy L. ; Vo, Alex CH ; Klucher, Kevin ; Herbst, Roy S. ; Eckhardt, S. Gail ; Peterson, Scott ; Hausman, Diana F ; Kuzrock, Razelle ; Jimeno, Antonio

Purpose: The objectives of the study were to evaluate the maximum tolerated dose (MTD), safety, pharmacodynamics, pharmacokinetics (PK), and antitumor activity of PX-866 in patients with incurable cancers. Patients and Methods: This was a phase 1, open-label, dose-escalation study. Drug was administered orally once per day either on an intermittent (Arm 1; days 1-5 and 8-12 of a 28-day cycle) or continuous (Arm 2; days 1-28 of a 28-day cycle) schedule. Additional patients were treated at the [...]

Menée in vitro, cette étude suggère que les petites molécules inhibant l'activité tyrosine kinase des gènes de la famille JAK ont également des effets de nature immunologique

Tyrosine kinase pathways modulate tumor susceptibility to natural killer cells

Bellucci, Roberto ; Nguyen, Hong-Nam ; Martin, Allison ; Heinrichs, Stefan ; Schinzel, Anna C. ; Hahn, William C. ; Ritz, Jerome

Natural killer (NK) cells are primary effectors of innate immunity directed against transformed tumor cells. In response, tumor cells have developed mechanisms to evade NK cell–mediated lysis through molecular mechanisms that are not well understood. In the present study, we used a lentiviral shRNA library targeting more than 1,000 human genes to identify 83 genes that promote target cell resistance to human NK cell–mediated killing. Many of the genes identified in this genetic screen belong to [...]

Menée in vitro et à l'aide de xénogreffes, cette étude suggère que la combinaison du lénalidomide et de l'ibrutinib, un inhibiteur de BTK, mettrait en oeuvre un mécanisme de létalité synthétique efficace pour le traitement du sous-type ABC des lymphomes diffus à grandes cellules B

Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma

Yang, Yibin ; Shaffer, Arthur L ; Emre, N. C.  Tolga ; Ceribelli, Michele ; Zhang, Meili ; Wright, George ; Xiao, Wenming ; Powell, John ; Platig, John ; Kohlhammer, Holger ; Young, Ryan M ; Zhao, Hong ; Yang, Yandan ; Xu, Weihong ; Buggy, Joseph J ; Balasubramanian, Sriram ; Mathews, Lesley A ; Shinn, Paul ; Guha, Rajarshi ; Ferrer, Marc ; Thomas, Craig ; Waldmann, Thomas A ; Staudt, Louis M

Knowledge of oncogenic mutations can inspire therapeutic strategies that are synthetically lethal, affecting cancer cells while sparing normal cells. Lenalidomide is an active agent in the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), but its mechanism of action is unknown. Lenalidomide kills ABC DLBCL cells by augmenting interferon ² (IFN²) production, owing to the oncogenic MYD88 mutations in these lymphomas. In a cereblon-dependent fashion, lenalidomide [...]

Menée à l'aide de modèles murins de mélanome, cette étude suggère que le vémurafenib, un inhibiteur de l'oncogène BRAFV600E, renforce l'efficacité d'une immunothérapie par transfert adoptif de cellules

BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy

Koya, Richard C. ; Mok, Stephen ; Otte, Nicholas ; Blacketor, Kevin J ; Comin-Anduix, Begona ; Tumeh, Paul C ; Minasyan, Aspram ; Graham, Nicholas ; Graeber, Thomas G ; Chodon, Thinle ; Ribas, Antoni

Combining immunotherapy with targeted therapy blocking oncogenic BRAFV600 may result in improved treatments for advanced melanoma. Here, we developed a BRAFV600E-driven murine model of melanoma, SM1, which is syngeneic to fully immunocompetent mice. SM1 cells exposed to the BRAF inhibitor vemurafenib (PLX4032) showed partial in vitro and in vivo sensitivity resulting from the inhibition of MAPK pathway signaling. Combined treatment of vemurafenib plus adoptive cell transfer (ACT) therapy with [...]

Menée à l'aide de xénogreffes de cancer ovarien, cette étude évalue l'activité antitumorale d'un traitement combinant le bévacizumab et le cixutumumab, un anticorps bloquant la signalisation IGF-1

Targeting the Insulin Growth Factor and the Vascular Endothelial Growth Factor Pathways in Ovarian Cancer

Shao, Minghai ; Hollar, Stacy ; Chambliss, Daphne ; Schmitt, Jordan ; Emerson, Robert ; Chelladurai, Bhadrani ; Perkins, Susan ; Ivan, Mircea ; Matei, Daniela

Antiangiogenic therapy is emerging as a highly promising strategy for the treatment of ovarian cancer, but the clinical benefits are usually transitory. The purpose of this study was to identify and target alternative angiogenic pathways that are upregulated in ovarian xenografts during treatment with bevacizumab. For this, angiogenesis-focused gene expression arrays were used to measure gene expression levels in SKOV3 and A2780 serous ovarian xenografts treated with bevacizumab or control. [...]

Cet article décrit l'état de l'art en matière de traitement des lymphomes hodgkiniens

State of the art in the treatment of Hodgkin lymphoma

Borchmann, Peter ; Eichenauer, Dennis A. ; Engert, Andreas

Hodgkin lymphoma (HL) has become one of the most easily curable malignancies in oncology. More than 80% of patients can be cured with risk-adapted treatment that includes chemotherapy and radiotherapy. This progress is mainly due to the development of multi-agent chemotherapy and improved radiation techniques; however, severe, life-threatening treatment-related side effects occur, which include organ toxicity and secondary malignancies. Thus, the treatment approaches must be carefully balanced [...]

Menée sur un modèle murin, cette étude évalue la toxicité aiguë d'un traitement combinant un anticorps anti-VEGF et une radiothérapie

Normal tissues toxicities triggered by combined anti-angiogenic and radiation therapies: hurdles might be ahead

Mangoni, M. ; Vozenin, M. C. ; Biti, G. ; Deutsch, E.

Background : Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. This study is the first systematic evaluation of normal tissue toxicity triggered by anti-angiogenic agents combined with radiation therapy in mice. Methods : Effect of a mouse [...]

Menée sur 52 patientes atteintes d'un cancer du sein traité par chimiothérapie néoadjuvante puis résection chirurgicale (durée médiane de suivi : 10 ans), cette étude prospective française évalue la toxicité et l'efficacité d'une chimioradiothérapie concomitante adjuvante par rapport à une radiothérapie seule

Prospective and Comparative Evaluation of the Toxicity of Adjuvant Concurrent Chemoradiotherapy After Neoadjuvant Chemotherapy for Breast Cancer

Marchand, Virginie ; Angelergues, Antoine ; Gobaux, Vanessa ; Hajage, David ; Kirova, Youlia M. ; Campana, François ; Dendale, Rémi ; Reyal, Fabien ; Pierga, Jean-Yves ; Fourquet, Alain ; Bollet, Marc A.

Purpose: The lack of pathologic breast cancer response to neoadjuvant chemotherapy (NCT), a negative prognostic factor, has prompted the addition of chemotherapy to adjuvant radiotherapy. This study aims to investigate prospectively the toxicities of adjuvant concurrent chemoradiotherapy versus radiotherapy alone. Patients and Methods: Two groups of patients treated for breast cancer between 1997 and 2002 by NCT, surgery, and radiotherapy with or without concurrent chemotherapy, were matched on [...]

Menée sur 240 patients atteints d'un carcinome rhinopharyngé loco-régional de stade avancé, cette étude chinoise compare, du point de vue de la survie globale à 3 ans, de la survie sans maladie ou sans métastases distantes, l'efficacité et la toxicité de trois protocoles de chimioradiothérapie séquentielle à base de cisplatine combinée ou non avec la gemcitabine ou le fluorouracile

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma

Gu, Mo-Fa ; Liu, Li-Zhi ; He, Long-Jun ; Yuan, Wen-Xin ; Zhang, Rong ; Luo, Guang-Yu ; Xu, Guo-Liang ; Zhang, Hua-Man ; Yan, Chao-Xian ; Li, Jian-jun

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin–gemcitabine (GC) regimen (800 mg/m2 gemcitabine on Days 1 and 8 and 20 mg/m2 cisplatin on Days 1–5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a [...]

A partir de données portant sur 570 patients inclus dans 24 essais cliniques de phase I conduits au Centre MD Anderson entre 2004 et 2009, cette étude met en évidence une corrélation linéaire entre l'évolution de la tumeur mesurée par les critères RECIST et la survie globale des patients

Change in Tumor Size by RECIST Correlates Linearly With Overall Survival in Phase I Oncology Studies

Jain, Rajul K. ; Lee, J. Jack ; Ng, Chaan ; Hong, David ; Gong, Jing ; Naing, Aung ; Wheler, Jennifer ; Kurzrock, Razelle

Purpose RECIST is used to quantify tumor changes during exposure to anticancer agents. Responses are categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Clinical trials dictate a patient's management options based on the category into which his or her response falls. However, the association between response and survival is not well studied in the early trial setting.Patients And methods To study the correlation between response as [...]

Cet article passe en revue les arguments qui, d'un point de vue évolutionniste, permettent de rendre compte de l'apparition d'une résistance à une thérapie ciblée

Evolutionary dynamics of carcinogenesis and why targeted therapy does not work

Gillies, Robert J. ; Verduzco, Daniel ; Gatenby, Robert A.

All malignant cancers, whether inherited or sporadic, are fundamentally governed by Darwinian dynamics. The process of carcinogenesis requires genetic instability and highly selective local microenvironments, the combination of which promotes somatic evolution. These microenvironmental forces, specifically hypoxia, acidosis and reactive oxygen species, are not only highly selective, but are also able to induce genetic instability. As a result, malignant cancers are dynamically evolving clades [...]