Mené sur 20 patients atteints d'un cancer localisé de la prostate et devant recevoir une radiothérapie, cet essai multicentrique évalue la précision et la toxicité d'un système de positionnement utilisant un implant contenant un traceur radioactif, l'iridium 192

Patient Positioning Based on a Radioactive Tracer Implanted in Patients With Localized Prostate Cancer: A Performance and Safety Evaluation

de Kruijf, Willy J. M. ; Verstraete, Jan ; Neustadter, David ; Corn, Benjamin W. ; Hol, Sandra ; Venselaar, Jack L. M. ; Davits, Rob J. ; Wijsman, Bart P. ; Van den Bergh, Laura ; Budiharto, Tom ; Oyen, Raymond ; Haustermans, Karin ; Poortmans, Philip M. P.

To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 (192Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. [...]

Menée sur 8 patients atteints d'un cancer localisé de la prostate, cette étude évalue la faisabilité de 3 protocoles comportant une radiothérapie avec modulation d'intensité et dosage à l'aide d'une tomographie par émission de positrons à base de 11C-choline

Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using 11C-choline Positron Emission Tomography Scans

Chang, Joe H. ; Lim Joon, Daryl ; Lee, Sze Ting ; Gong, Sylvia J. ; Anderson, Nigel J. ; Scott, Andrew M. ; Davis, Ian D. ; Clouston, David ; Bolton, Damien ; Hamilton, Christopher S. ; Khoo, Vincent

To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using 11C-choline positron emission tomography PET scans in patients with localized prostate cancer. This was an RT planning study of 8 patients with prostate cancer who had 11C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV60% and SUV70%). [...]

Menée sur 20 patientes atteintes d'un cancer du sein et ayant subi un traitement chirurgical conservateur, cette étude évalue la précision d'un système tridimensionnel de capture d'images pour guider une radiothérapie en inspiration profonde bloquée

Accuracy Evaluation of a 3-Dimensional Surface Imaging System for Guidance in Deep-Inspiration Breath-Hold Radiation Therapy

Alderliesten, Tanja ; Sonke, Jan-Jakob ; Betgen, Anja ; Honnef, Joeri ; van Vliet-Vroegindeweij, Corine ; Remeijer, Peter

To investigate the applicability of 3-dimensional (3D) surface imaging for image guidance in deep-inspiration breath-hold radiation therapy (DIBH-RT) for patients with left-sided breast cancer. For this purpose, setup data based on captured 3D surfaces was compared with setup data based on cone beam computed tomography (CBCT). Twenty patients treated with DIBH-RT after breast-conserving surgery (BCS) were included. Before the start of treatment, each patient underwent a breath-hold CT scan for [...]

A partir d'une revue systématique de la littérature publiée entre janvier 2008 et août 2011 (17 séries de cas, 34 études), cette méta-analyse évalue la prévalence d'une incontinence urinaire après une prostatectomie radicale assistée par robot et identifie les facteurs de risque associés

Systematic Review and Meta-analysis of Studies Reporting Urinary Continence Recovery After Robot-assisted Radical Prostatectomy

Vincenzo, Ficarra ; Giacomo, Novara ; Raymond, C. Rosen ; Walter, Artibani ; Peter, R. Carroll ; Anthony, Costello ; Mani, Menon ; Francesco, Montorsi ; Vipul, Patel ; Jens-Uwe, Stolzenburg ; Henk Van der, Poel ; Timothy, G. Wilson ; Filiberto, Zattoni ; Alexandre, Mottrie

Context : Robot-assisted radical prostatectomy (RARP) was proposed to improve functional outcomes in comparison with retropubic radical prostatectomy (RRP) or laparoscopic radical prostatectomy (LRP). In the initial RARP series, 12-mo urinary continence recovery rates ranged from 84 % to 97%. However, the few available studies comparing RARP with RRP or LRP published before 2008 did not permit any definitive conclusions about the superiority of any one of these techniques in terms of urinary [...]

Mené sur 42 patients atteints d'un cancer du rectum ou du canal anal, cet essai de phase III montre qu'un pansement de nylon plaqué argent, appliqué dès la première séance de radiothérapie et jusqu'à 2 semaines après la fin du traitement, peut prévenir la survenue de dermatites liées aux rayonnements ionisants

Silver Clear Nylon Dressing is Effective in Preventing Radiation-Induced Dermatitis in Patients With Lower Gastrointestinal Cancer: Results From a Phase III Study

Niazi, Tamim M. ; Vuong, Té ; Azoulay, Laurant ; Marijnen, Corrie ; Bujko, Kryzstof ; Nasr, Elie ; Lambert, Christine ; Duclos, Marie ; Faria, Sergio ; David, Marc ; Cummings, Bernard

For patients with anal canal and advanced rectal cancer, chemoradiation therapy is a curative modality or an important adjunct to surgery. Nearly all patients treated with chemoradiation experience some degree of radiation-induced dermatitis (RID). Prevention and effective treatment of RID, therefore, is of considerable clinical relevance. The present phase III randomized trial compared the efficacy of silver clear nylon dressing (SCND) with that of standard skin care for these patients. A [...]

Mené sur 98 patientes atteintes d'un cancer du sein de stade I (âge médian : 61 ans ; durée médiane de suivi : 71 mois), cet essai prospectif multicentrique analyse, selon les caractéristiques tumorales et sur une période de 5 ans, les résultats cliniques d'une irradiation partielle accélérée du sein (32 Grays délivrés en 8 doses biquotidiennes)

External Beam Accelerated Partial-Breast Irradiation Using 32 Gy in 8 Twice-Daily Fractions: 5-Year Results of a Prospective Study

Pashtan, Itai M. ; Recht, Abram ; Ancukiewicz, Marek ; Brachtel, Elena ; Abi-Raad, Rita F. ; D'Alessandro, Helen A. ; Levy, Antonin ; Wo, Jennifer Y. ; Hirsch, Ariel E. ; Kachnic, Lisa A. ; Goldberg, Saveli ; Specht, Michelle ; Gadd, Michelle ; Smith, Barbara L. ; Powell, Simon N. ; Taghian, Alphonse G.

External beam accelerated partial breast irradiation (APBI) is an increasingly popular technique for treatment of patients with early stage breast cancer following breast-conserving surgery. Here we present 5-year results of a prospective trial. From October 2003 through November 2005, 98 evaluable patients with stage I breast cancer were enrolled in the first dose step (32 Gy delivered in 8 twice-daily fractions) of a prospective, multi-institutional, dose escalation clinical trial of [...]

A partir de données administratives portant sur une cohorte de 2 000 patients présentant des métastases au cerveau traitées entre 1991 et 2008, cette étude rétrospective évalue l'incidence des complications au moins 3 ans après une radiochirurgie stéréotaxique par Gamma Knife et identifie les facteurs prédictifs associés (167 cas ; 89 femmes et 78 hommes ; âge : entre 19 et 88 ans)

Delayed Complications in Patients Surviving at Least 3 Years After Stereotactic Radiosurgery for Brain Metastases

Yamamoto, Masaaki ; Kawabe, Takuya ; Higuchi, Yoshinori ; Sato, Yasunori ; Nariai, Tadashi ; Barfod, Bierta E. ; Kasuya, Hidetoshi ; Urakawa, Yoichi

Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 [...]

A partir de l'analyse de 120 échantillons tumoraux prélevés sur 112 patients présentant des métastases du cerveau traitées par radiochirurgie stéréotaxique entre 1998 et 2009, cette étude prospective évalue l'intérêt d'ajouter 2 mm de marge d'exérèse à la cavité de résection pour éviter l'irradiation totale du cerveau et améliorer le contrôle local de la maladie

Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

Choi, Clara Y. H. ; Chang, Steven D. ; Gibbs, Iris C. ; Adler, John R. ; Harsh, Griffith R. ; Lieberson, Robert E. ; Soltys, Scott G.

Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. We retrospectively evaluated [...]

Cet article évalue l'intérêt d'un modèle murin comportant une deuxième mutation du récepteur Kit pour étudier le mécanisme de résistance à l'imatinib dans les tumeurs stromales gastro-intestinales

Imatinib resistance and microcytic erythrocytosis in a KitV558Δ;T669I/+ gatekeeper-mutant mouse model of gastrointestinal stromal tumor

Bosbach, Benedikt ; Deshpande, Shayu ; Rossi, Ferdinand ; Shieh, Jae-Hung ; Sommer, Gunhild ; de Stanchina, Elisa ; Veach, Darren R. ; Scandura, Joseph M. ; Manova-Todorova, Katia ; Moore, Malcolm A. S. ; Antonescu, Cristina R. ; Besmer, Peter

Most gastrointestinal stromal tumors (GISTs) harbor a gain-of-function mutation in the Kit receptor. GIST patients treated with the tyrosine kinase inhibitor imatinib frequently develop imatinib resistance as a result of second-site Kit mutations. To investigate the consequences of second-site Kit mutations on GIST development and imatinib sensitivity, we engineered a mouse model carrying in the endogenous Kit locus both the KitV558Δ mutation found in a familial case of GIST and the KitT669I [...]

Cette étude identifie des gènes du pavot à opium impliqués dans la biosynthèse de la noscapine, un alcaloïde aux propriétés antitumorales

A Papaver somniferum 10-Gene Cluster for Synthesis of the Anticancer Alkaloid Noscapine

Winzer, Thilo ; Gazda, Valeria ; He, Zhesi ; Kaminski, Filip ; Kern, Marcelo ; Larson, Tony R. ; Li, Yi ; Meade, Fergus ; Teodor, Roxana ; Vaistij, Fabián E. ; Walker, Carol ; Bowser, Tim A. ; Graham, Ian A.

Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F2 mapping population indicated the genes are tightly [...]

Mené sur 15 patients atteints d'une tumeur solide avancée, cet essai de phase I évalue un composé appelé CA4P, qui perturbe le réseau vasculaire, en combinaison avec le bévacizumab

Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer

Nathan, Paul ; Zweifel, Martin ; Padhani, Anwar R. ; Koh, Dow-Mu ; Ng, Matthew ; Collins, David J. ; Harris, Adrian ; Carden, Craig ; Smythe, Jon ; Fisher, Nita ; Taylor, N. Jane ; Stirling, J. James ; Lu, Shiao-Ping ; Leach, Martin O. ; Rustin, Gordon J.S. ; Judson, Ian

Purpose: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity.Experimental Design: Patients with advanced solid malignancies received CA4P at 45, 54, or 63 mg/m2 on day 1, day 8, and then every 14 days. Bevacizumab 10 mg/kg was given [...]

Cet article passe en revue les perspectives offertes par des anticorps monoclonaux ciblant la voie de signalisation de l'interleukine 6 pour le traitement des cancers

Interleukin-6 signaling pathway in targeted therapy for cancer

Guo, Yuqi ; Xu, Feng ; Lu, TianJian ; Duan, Zhenfeng ; Zhang, Zhan

Interleukin-6 (IL-6) is a multifunctional cytokine which plays an important role in a wide range of biologic activities in different types of cell including tumor cells. IL-6 is involved in the host immune defense mechanism as well as the modulation of growth and differentiation in various malignancies. These effects are mediated by several signaling pathways, in particular the signal transducer and transcription activator 3 (Stat3). There exists abundant evidence demonstrating that deregulated [...]

Cette étude analyse le mécanisme d'action d'un anticorps monoclonal, mAb806, qui cible un épitope du récepteur EGFR spécifique des cellules tumorales et, ainsi, n'engendre pas de toxicité dans les tissus sains

Targeting of a Conformationally Exposed, Tumor-Specific Epitope of EGFR as a Strategy for Cancer Therapy

Gan, Hui K. ; Burgess, Antony W. ; Clayton, Andrew H. A. ; Scott, Andrew M.

Epidermal growth factor receptor (EGFR) and its most common extracellular mutant, EGFRvIII, are important therapeutic targets in multiple cancer types. A number of monoclonal antibodies and small-molecule inhibitors against these receptors are now used for anticancer treatments. New insights into the structure and function of these receptors illustrate how they can be targeted in novel ways, with expected improvements in the therapeutic efficacy. Monoclonal antibody 806 (mAb806) is an antibody [...]

Mené sur 22 patients d'âge inférieur à 21 ans et atteints d'une leucémie lymphoblastique aiguë récidivante, cet essai de phase II évalue le bortezomib en combinaison avec une chimiothérapie à base de vincristine, dexaméthasone, asparaginase pégylée et doxorubicine

Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia Lymphoma (TACL) Study

Messinger, Yoav H. ; Gaynon, Paul S. ; Sposto, Richard ; van der Giessen, Jeannette ; Eckroth, Elena ; Malvar, Jemily ; Bostrom, Bruce C.

Therapy of relapsed pediatric acute lymphoblastic leukemia (ALL) is hampered by low remission rates and high toxicity, especially in 2nd and subsequent relapse. The TACL phase I study, T2005-003 showed that combination of bortezomib with vincristine, dexamethasone, pegylated asparaginase and doxorubicin has acceptable toxicity. The TACL consortium conducted the phase II expansion of this combination in relapsed ALL patients who failed 2-3 prior regimens. Twenty-two patients with relapsed ALL [...]

Menée sur des lignées cellulaires de myélome multiple présentant une mutation de p53, cette étude montre qu'un composé appelé AZD7762, un inhibiteur de Chk1/2, augmente l'efficacité de divers agents de chimiothérapie

The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy Induced Apoptosis of p53 Mutated Multiple Myeloma Cells

Landau, Heather J ; McNeely, Samuel C ; Nair, Jayasree S ; Comenzo, Raymond L. ; Asai, Takashi ; Friedman, Hillel ; Jhanwar, Suresh C. ; Nimer, Stephen D ; Schwartz, Gary K.

DNA cross-linking agents are frequently used in the treatment of multiple myeloma (MM) generating lesions which activate checkpoint kinase 1 (Chk1), a critical transducer of the DNA damage response. Chk1 activation promotes cell survival by regulating cell cycle arrest and DNA repair following genotoxic stress. The ability of AZD7762, an ATP-competitive Chk1/2 inhibitor to increase the efficacy of the DNA damaging agents bendamustine, melphalan and doxorubicin was examined using four human [...]

A partir d'observations sur un patient atteint d'un cancer avancé du poumon non à petites cellules et inclus dans un essai clinique d'évaluation du dasatinib, cette étude identifie une mutation du gène BRAF en association avec la réponse thérapeutique

Kinase-Impaired BRAF Mutations in Lung Cancer Confer Sensitivity to Dasatinib

Sen, Banibrata ; Peng, Shaohua ; Tang, Ximing ; Erickson, Heidi S. ; Galindo, Hector ; Mazumdar, Tuhina ; Stewart, David J. ; Wistuba, Ignacio ; Johnson, Faye M.

During a clinical trial of the tyrosine kinase inhibitor dasatinib for advanced non–small cell lung cancer (NSCLC), one patient responded dramatically and remains cancer-free 4 years later. A comprehensive analysis of his tumor revealed a previously undescribed, kinase-inactivating BRAF mutation (Y472CBRAF); no inactivating BRAF mutations were found in the nonresponding tumors taken from other patients. Cells transfected with Y472CBRAF exhibited CRAF, MEK (mitogen-activated or extracellular [...]

Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence un mécanisme par lequel la trifluopérazine, une molécule anti-psychotique, interagit avec la voie de signalisation du récepteur EGFR et restaure la sensibilité à l'erlotinib de tumeurs d'un adénocarcinome pulmonaire

Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response

Sangodkar, Jaya ; Dhawan, Neil S. ; Melville, Heather ; Singh, Varan J. ; Yuan, Eric ; Rana, Huma ; Izadmehr, Sudeh ; Farrington, Caroline ; Mazhar, Sahar ; Katz, Suzanna ; Albano, Tara ; Arnovitz, Pearlann ; Okrent, Rachel ; Ohlmeyer, Michael ; Galsky, Matthew ; Burstein, David ; Zhang, David ; Politi, Katerina ; DiFeo, Analisa ; Narla, Goutham

EGFR activation is both a key molecular driver of disease progression and the target of a broad class of molecular agents designed to treat advanced cancer. Nevertheless, resistance develops through several mechanisms, including activation of AKT signaling. Though much is known about the specific molecular lesions conferring resistance to anti-EGFR–based therapies, additional molecular characterization of the downstream mediators of EGFR signaling may lead to the development of new classes of [...]

Cet article passe en revue les différentes stratégies de découverte et de développement des traitements d'un cancer métastatique du sein

Strategies for the discovery and development of therapies for metastatic breast cancer

Eckhardt, Bedrich L. ; Francis, Prudence A. ; Parker, Belinda S. ; Anderson, Robin L.

Nearly all deaths caused by solid cancers occur as a result of metastasis — the formation of secondary tumours in distant organs such as the lungs, liver, brain and bone. A major obstruction to the development of drugs with anti-metastatic efficacy is our fragmented understanding of how tumours 'evolve' and metastasize, at both the biological and genetic levels. Furthermore, although there is significant overlap in the metastatic process among different types of cancer, there are also marked [...]

Cet article passe en revue les travaux récents sur l'intérêt d'une chimiothérapie néoadjuvante ou adjuvante dans le cancer invasif de la vessie

A Systematic Review of Neoadjuvant and Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer

Joshua, J. Meeks ; Joaquim, Bellmunt ; Bernard, H. Bochner ; Noel, W. Clarke ; Siamak, Daneshmand ; Matthew, D. Galsky ; Noah, M. Hahn ; Seth, P. Lerner ; Malcolm, Mason ; Thomas, Powles ; Cora, N. Sternberg ; Guru, Sonpavde

Context: Muscle-invasive bladder cancer (MIBC) is a disease with a pattern of predominantly distant and early recurrences. Neoadjuvant cisplatin-based combination chemotherapy has demonstrated improved outcomes for MIBC. Objective: To review the data supporting perioperative chemotherapy and emerging regimens for MIBC. Evidence acquisition: Medline databases were searched for original articles published before April 1, 2012, with the search terms bladder cancer, urothelial cancer, radical [...]

Menée entre 2003 et 2010 sur une cohorte de 87 patients atteints d'un cancer du poumon non à petites cellules traité par chimioradiothérapie concomitante à base de cisplatine, cette étude monocentrique évalue l'incidence de cavitations tumorales et / ou d'abcès liés à la tumeur après le traitement et analyse les résultats cliniques

Tumor Cavitation in Patients With Stage III Non-Small-Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy: Incidence and Outcomes

Phernambucq, Erik C. J. ; Hartemink, Koen J. ; Smit, Egbert F. ; Paul, Marinus A. ; Postmus, Pieter E. ; Comans, Emile F. I. ; Senan, Suresh

Introduction: Commonly reported complications after concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC) include febrile neutropenia, radiation esophagitis, and pneumonitis. We studied the incidence of tumor cavitation and/or "tumor abscess" after CCRT in a single-institutional cohort. Methods: Between 2003 and 2010, 87 patients with stage III NSCLC underwent cisplatin-based CCRT and all subsequent follow-up at the VU University Medical Center. [...]

Mené sur 161 patients pédiatriques atteints d'un médulloblastome métastatique et ayant subi une intervention chirurgicale (âgé médian : 8,7 ans), cet essai de phase I/II évalue la faisabilité et l'intérêt d'ajouter le carboplatine à une radiothérapie crânio-spinale pour améliorer la réponse des cellules tumorales aux rayonnements ionisants

Outcome of Children With Metastatic Medulloblastoma Treated With Carboplatin During Craniospinal Radiotherapy: A Children's Oncology Group Phase I/II Study

Jakacki, Regina I. ; Burger, Peter C. ; Zhou, Tianni ; Holmes, Emiko J. ; Kocak, Mehmet ; Onar, Arzu ; Goldwein, Joel ; Mehta, Minesh ; Packer, Roger J. ; Tarbell, Nancy ; Fitz, Charles ; Vezina, Gilbert ; Hilden, Joanne ; Pollack, Ian F.

Purpose We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB.Patients and Methods After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m2/dose), along with [...]

Signé par deux responsables de la Food and Drug Administration, cet article présente les enjeux associés à la prise en compte du critère de réponse pathologique complète dans la procédure accélérée d’autorisation de mise sur le marché des traitements néoadjuvants d'un cancer du sein

Pathological Complete Response and Accelerated Drug Approval in Early Breast Cancer

Prowell, Tatiana M. ; Pazdur, Richard

New drugs for breast cancer have historically been approved first for patients with metastatic disease who have few remaining options for systemic treatment. Approval for an adjuvant indication occurs years later, after large, randomized trials with prolonged follow-up have been conducted in patients with early-stage disease. Recently, neoadjuvant trials have introduced new drugs preoperatively in patients with localized breast cancer. Such treatment aims to render locally advanced cancers [...]