Menée à partir de données portant sur 308 patients âgés de 90 ans ou plus et traités pour un cancer entre 2003 et 2012, cette étude française évalue la faisabilité d'une radiothérapie dans cette population

Feasibility of radiation therapy in patients 90 years of age and older : A French multicentre analysis

Chargari, Cyrus ; Moriceau, Guillaume ; Auberdiac, Pierre ; Guy, Jean-Baptiste ; Assouline, Avi ; Tinquaut, Fabien ; Falk, Alexander Tuan ; Eddekkaoui, Houda ; Bourmaud, Aurélie ; Coscas, Yvan ; Annede, Pierre ; Rivoirard, Romain ; Mery, Benoite ; Trone, Jane-Chloé ; Otmezguine, Yves ; Pacaut, Cécile ; Bauduceau, Olivier ; Vedrine, Lionel ; Merrouche, Yacine ; Magne, Nicolas

Background : There are only scarce data on the management of patients aged 90 years or older with cancer, and more particularly on the place of radiation therapy (RT). We report the first large study on patients (pts) aged 90 years or older receiving RT. Methods and materials : Records from RT departments from five institutions were reviewed to identify pts 90 years of age and older who underwent RT for various malignant tumours treated between 2003 and 2012. Tumours’ characteristics were [...]

Menée sur 447 patients atteints d'un cancer de la prostate de stade précoce (durée de suivi : 23,2 ans), cette étude évalue, du point de vue de la mortalité toutes causes confondues, de la mortalité spécifique et du risque de métastases, l'intérêt d'une prostatectomie radicale par rapport à une surveillance médicale après diagnostic

Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer

Bill-Axelson, Anna ; Holmberg, Lars ; Garmo, Hans ; Rider, Jennifer R. ; Taari, Kimmo ; Busch, Christer ; Nordling, Stig ; Häggman, Michael ; Andersson, Swen-Olof ; Spångberg, Anders ; Andrén, Ove ; Palmgren, Juni ; Steineck, Gunnar ; Adami, Hans-Olov ; Johansson, Jan-Erik

Background : Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. Methods Between : 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of [...]

Mené sur 58 patientes atteintes d'un adénocarcinome du col utérin de stade IIB, IIIB ou IVA traité entre 1998 et 2010 (durée médiane de suivi : 38 mois), cet essai de phase 1/2 évalue l'efficacité, du point de vue du taux de contrôle local de la maladie et du taux de survie globale à 5 ans, et la toxicité d'une radiothérapie par ions carbone

Clinical outcomes of carbon ion radiotherapy for locally advanced adenocarcinoma of the uterine cervix in phase 1/2 clinical trial (protocol 9704)

Wakatsuki, Masaru ; Kato, Shingo ; Ohno, Tatsuya ; Karasawa, Kumiko ; Kiyohara, Hiroki ; Tamaki, Tomoaki ; Ando, Ken ; Tsujii, Hirohiko ; Nakano, Takashi ; Kamada, Tadashi ; Shozu, Makio ; The Working Group of the Gynecological, Tumor

BACKGROUND : This study sought to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced adenocarcinoma of the uterine cervix in a phase 1/2 clinical trial. METHODS : The treatment consisted of whole-pelvic irradiation of 36.0 gray equivalents (GyE) in 12 fractions and local boost with dose escalation from 26.4 to 38.4 GyE in 8 fractions. The dose escalation was performed with careful observation of acute normal tissue responses. Total dose to the cervical [...]

A partir d'une revue systématique de la littérature (51 articles), cette étude évalue, du point de vue de données péri-opératoires, de données oncologiques et de résultats fonctionnels, l'efficacité d'une cystectomie radicale assistée par robot (RARC) avec reconstruction intracorporelle complète par rapport à une cystectomie radicale par voie ouverte et à une cystectomie radicale RARC standard avec dérivation urinaire extrapéritonéale

Totally intracorporeal robot-assisted radical cystectomy: optimizing total outcomes

Collins, Justin W. ; Wiklund, N. Peter

We performed a systematic literature review to assess the current status of a totally intracorporeal robot-assisted radical cystectomy (RARC) approach. The current ‘gold standard’ for radical cystectomy remains open radical cystectomy. RARC has lagged behind robot-assisted prostatectomy in terms of adoption and perceived patient benefit, but there are indications that this is now changing. There have been several recently published large series of RARC, both with extracorporeal and with [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels le gène TMEM98 favorise la résistance à une chimiothérapie dans le traitement d'un carcinome hépatocellulaire

Identification of transmembrane protein 98 as a novel chemoresistance-conferring gene in hepatocellular carcinoma

Ng, Kevin Tak-Pan ; Lo, Chung Mau ; Guo, Dong Yong ; Qi, Xiang ; Li, Chang Xian ; Geng, Wei ; Liu, Xiao-Bing ; Ling, Chang Chun ; Ma, Yuen Yuen ; Yeung, Wai Ho ; Shao, Yan ; Poon, Ronnie Tung-Ping ; Fan, Sheung Tat ; Man, Kwan

Chemoresistance is one of the major obstacles in systemic chemotherapy and targeted therapy for patients with advanced hepatocellular carcinoma (HCC). To identify novel chemoresistance-associated targets in HCC, chemoresistant HCC cell lines were established. By comparing the global gene expression profiles between chemoresistant and chemosensitive cell lines, eight novel chemoresistance-associated genes were identified to be significantly associated with the commonly augmented chemoresistance [...]

Menée in vitro et in vivo, cette étude met en évidence l'intérêt d’un virus oncolytique (NDV) pour surmonter la résistance à une immunothérapie anti-PD1 dans les mélanomes

Localized Oncolytic Virotherapy Overcomes Systemic Tumor Resistance to Immune Checkpoint Blockade Immunotherapy

Zamarin, Dmitriy ; Holmgaard, Rikke B. ; Subudhi, Sumit K. ; Park, Joon Seok ; Mansour, Mena ; Palese, Peter ; Merghoub, Taha ; Wolchok, Jedd D. ; Allison, James P.

Preexisting lymphocytic infiltration of tumors is associated with superior prognostic outcomes in a variety of cancers. Recent studies also suggest that lymphocytic responses may identify patients more likely to benefit from therapies targeting immune checkpoints, suggesting that therapeutic efficacy of immune checkpoint blockade can be enhanced through strategies that induce tumor inflammation. To achieve this effect, we explored the immunotherapeutic potential of oncolytic Newcastle disease [...]

Menée sur des drosophiles, cette étude montre que, si certains agents de chimiothérapie inhibent bien la croissance des cellules souches cancéreuses de l'intestin, ils favorisent de façon paradoxale la prolifération des cellules souches non cancéreuses

Systematic screen of chemotherapeutics in Drosophila stem cell tumors

Markstein, Michele ; Dettorre, Samantha ; Cho, Julio ; Neumüller, Ralph A. ; Craig-Müller, Sören ; Perrimon, Norbert

Here we report the development of an in vivo system to study the interaction of stem cells with drugs using a tumor model in the adult Drosophila intestine. Strikingly, we find that some Food and Drug Administration-approved chemotherapeutics that can inhibit the growth of Drosophila tumor stem cells can paradoxically promote the hyperproliferation of their wild-type counterparts. These results reveal an unanticipated side effect on stem cells that may contribute to tumor recurrence. We propose [...]

Menée in vivo, cette étude analyse les mécanismes d'action d'un inhibiteur sélectif de PI3Kalpha (NVP-BYL719) puis, in vitro, identifie une association entre la présence d'une mutation du gène PI3KCA et la réponse thérapeutique

Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials

Fritsch, Christine ; Huang, Alan ; Chatenay-Rivauday, Christian ; Schnell, Christian ; Reddy, Anupama ; Liu, Manway ; Kauffmann, Audrey ; Guthy, Daniel ; Erdmann, Dirk ; De Pover, Alain ; Furet, Pascal ; Gao, Hui ; Ferretti, Stephane ; Wang, Youzhen ; Trappe, Joerg ; Brachmann, Saskia M ; Maira, Sauveur-Michel ; Wilson, Christopher J. ; Boehm, Markus ; Garcia-Echeverria, Carlos ; Chene, Patrick ; Wiesmann, Marion ; Cozens, Robert ; Lehar, Joseph ; Schlegel, Robert ; Caravatti, Giorgio ; Hofmann, Francesco ; Sellers, William R.

Somatic PIK3CA mutations are frequently found in solid tumors raising the hypothesis that selective inhibition of PI3Kalpha may have robust efficacy in PIK3CA-mutant cancers while sparing patients the side-effects associated with broader inhibition of the class I PI3K family. Here we report the biological properties of the 2-aminothiazole derivative NVP-BYL719, a selective inhibitor of PI3Kalpha and its most common oncogenic mutant forms. The compound selectivity combined with excellent [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'activité du fedratinib, un inhibiteur sélectif de JAK2, pour le traitement d'un lymphome hodgkinien classique ou d'un lymphome primitif du médiastin à grandes cellules B

Selective JAK2 Inhibition Specifically Decreases Hodgkin Lymphoma and Mediastinal Large B-cell Lymphoma Growth In Vitro and In Vivo

Hao, Yansheng ; Chapuy, Bjoern ; Monti, Stefano ; Sun, Heather H. ; Rodig, Scott J. ; Shipp, Margaret A.

Purpose: Classical Hodgkin lymphoma (cHL) and primary mediastinal large B-cell lymphoma (MLBCL) share similar histological, clinical and genetic features. In recent studies, we found that disease-specific chromosome 9p24.1/JAK2 amplification increased JAK2 expression and activity in both cHL and MLBCL. This prompted us to assess the activity of a clinical grade JAK2 selective inhibitor, fedratinib (SAR302503/TG101348), in in vitro and in vivo model systems of cHL and MLBCL with defined JAK2 [...]

Menée à l'aide d'un modèle murin d'adénocarcinome canalaire du pancréas, cette étude met en évidence l'intérêt d'agents antiangiogéniques (bevacizumab ou sunitinib) pour augmenter l'efficacité d'un traitement à l'aide de nab-paclitaxel

Enhancement of Nab-paclitaxel Antitumor Activity through Addition of Multitargeting Antiangiogenic Agents in Experimental Pancreatic Cancer

Awasthi, Niranjan ; Zhang, Changhua ; Schwarz, Anna M. ; Hinz, Stefan ; Schwarz, Margaret A ; Schwarz, Roderich E.

Nab-paclitaxel (NPT) has recently shown efficacy in pancreatic ductal adenocarcinoma (PDAC). Targeting tumor angiogenesis is a sensible combination therapeutic strategy for cancer including PDAC. We tested the hypothesis that nab-paclitaxel response in PDAC can be enhanced by the mechanistically different antiangiogenic agents, bevacizumab (Bev) or sunitinib (Su), despite its inherently increased tumor penetration and drug delivery. Compared to controls (19 days) median animal survival was [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en inhibant l'expression de l'enzyme USP9X et en favorisant la dégradation de la protéine ERG, un composé appelé WP1130 exerce une activité antitumorale dans les tumeurs de la prostate surexprimant ERG

Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer

Wang, Shan ; Kollipara, Rahul K. ; Srivastava, Nishi ; Li, Rui ; Ravindranathan, Preethi ; Hernandez, Elizabeth ; Freeman, Eva ; Humphries, Caroline G. ; Kapur, Payal ; Lotan, Yair ; Fazli, Ladan ; Gleave, Martin E. ; Plymate, Stephen R. ; Raj, Ganesh V. ; Hsieh, Jer-Tsong ; Kittler, Ralf

The transcription factor E-twenty-six related gene (ERG), which is overexpressed through gene fusion with the androgen-responsive gene transmembrane protease, serine 2 (TMPRSS2) in ∼40% of prostate tumors, is a key driver of prostate carcinogenesis. Ablation of ERG would disrupt a key oncogenic transcriptional circuit and could be a promising therapeutic strategy for prostate cancer treatment. Here, we show that ubiquitin-specific peptidase 9, X-linked (USP9X), a deubiquitinase enzyme, binds [...]

Cet article passe en revue les travaux récents sur les mécanismes d'action du T-DM1 (trastuzumab emtasine) et les stratégies susceptibles de surmonter une résistance au T-DM1 chez les patientes atteintes d'un cancer du sein de stade avancé

Trastuzumab emtansine: mechanisms of action and drug resistance

Barok, Mark ; Joensuu, Heikki ; Isola, Jorma

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that is effective and generally well tolerated when administered as a single agent to treat advanced breast cancer. Efficacy has now been demonstrated in randomized trials as first line, second line, and later than the second line treatment of advanced breast cancer. T-DM1 is currently being evaluated as adjuvant treatment for early breast cancer. It has several mechanisms of action consisting of the anti-tumor effects of trastuzumab [...]

Mené sur 37 patients atteints d'un lymphome T périphérique ou d'un lymphome T cutané récidivant , cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du mogamulizumab, un anticorps monoclonal anti-CCR4

Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CC Chemokine Receptor 4 Antibody, in Patients With Relapsed Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma

Ogura, Michinori ; Ishida, Takashi ; Hatake, Kiyohiko ; Taniwaki, Masafumi ; Ando, Kiyoshi ; Tobinai, Kensei ; Fujimoto, Katsuya ; Yamamoto, Kazuhito ; Miyamoto, Toshihiro ; Uike, Naokuni ; Tanimoto, Mitsune ; Tsukasaki, Kunihiro ; Ishizawa, Kenichi ; Suzumiya, Junji ; Inagaki, Hiroshi ; Tamura, Kazuo ; Akinaga, Shiro ; Tomonaga, Masao ; Ueda, Ryuzo

Purpose : CC chemokine receptor 4 (CCR4) is expressed by peripheral T-cell lymphomas (PTCLs) and is associated with poor outcomes. Mogamulizumab (KW-0761) is a defucosylated humanized anti-CCR4 antibody engineered to exert potent antibody-dependent cellular cytotoxicity. This multicenter phase II study evaluated the efficacy and safety of mogamulizumab in patients with relapsed PTCL and cutaneous T-cell lymphoma (CTCL). Patients and Methods : Mogamulizumab (1.0 mg/kg) was administered [...]

Menée sur un patient atteint d'un mélanome présentant la mutation V600K du gène BRAF et ayant développé une leucémie avec mutation du gène NRAS à la suite d'un traitement par vémurafenib, cette étude met en évidence l'efficacité d'une administration intermittente de cobimetinib, un inhibiteur de MEK, en complément du vémurafenib

Efficacy of intermittent combined RAF and MEK inhibition in a patient with concurrent BRAF and NRAS mutant malignancies

Abdel-Wahab, Omar ; Klimek, Virginia M ; Gaskell, Alisa ; Viale, Agnes ; Cheng, Donavan ; Kim, Eunhee ; Rampal, Raajit ; Bluth, Mark ; Harding, James J ; Callahan, Margaret K. ; Merghoob, Taha ; Berger, Michael F ; Solit, David B ; Rosen, Neal ; Levine, Ross L. ; Chapman, Paul B.

Vemurafenib, a RAF inhibitor, extends survival in patients with BRAFV600-mutant melanoma but activates ERK signaling in RAS-mutant cells. In a patient with a BRAFV600K-mutant melanoma responding to vemurafenib, we observed accelerated progression of a previously unrecognized NRAS-mutant leukemia. We hypothesized that combining vemurafenib with a MEK inhibitor would inhibit ERK activation in the melanoma and prevent ERK activation by vemurafenib in the leukemia and thus suppress both [...]

Cet article fait le point sur l'utilisation conjointe de la radiothérapie et d'anti-androgènes pour traiter un cancer de la prostate localisé ou localement avancé et présentant un risque intermédiaire ou élevé de récidive

Current trends for the use of androgen deprivation therapy in conjunction with radiotherapy for patients with unfavorable intermediate-risk, high-risk, localized, and locally advanced prostate cancer

Roach, Mack

Androgen deprivation therapy (ADT) is now a well-established standard of care in combination with definitive radiotherapy for patients with unfavorable intermediate-risk to high-risk locally advanced prostate cancer. It is also well established that combination modality treatment with ADT and radiotherapy is superior to either of these modalities alone for the treatment of patients with high-risk locally advanced disease. Current treatment guidelines for prostate cancer in the United States are [...]