Menée sur des lignées cellulaires d'adénocarcinome du poumon résistantes au docétaxel, cette étude montre que l'acquisition de la chimio- ou radiorésistance des cellules tumorales et les phénotypes associés à leur transition épithélio-mésenchymateuse sont liés à une réduction de l'expression de Let-7c

Acquisition of Chemo- or Radioresistance and Epithelial to Mesenchymal Transition (EMT) Phenotypes in Docetaxel-Resistant Lung Adenocarcinoma Cells was Linked with Downregulation of Let-7c

Cui, Shi-Yun ; Huang, Jia-Yuan ; Chen, Yi-Tian ; Song, Hai-Zhu ; Feng, Bing ; Huang, Gui-Chun ; Wang, Rui ; Chen, Long-Bang ; De, Wei

MicroRNA (miRNA) expression and functions have been reported to contribute to phenotypic features of tumor cells. Although targets and functional roles for many microRNAs have been described in lung adenocarcinoma (LAD), their pathophysiologic roles in phenotypes of chemoresistant LAD cells are still largely unclear. Previously, docetaxel-resistant LAD cell lines (SPC-A1/DTX and H1299/DTX) were established by our lab and displayed chemoradioresistance and mesenchymal features with enhanced [...]

Menée sur 9 patients atteints d'un carcinome à cellules rénales récidivant localement après une néphrectomie radicale, cette étude évalue, du point de vue de données opératoires (durée de l'intervention, perte de sang, qualité des marges de résection) et des complications intra- et post-opératoires, la faisabilité et l'efficacité d'un traitement chirurgical par voie laparoscopique

Feasibility and oncological outcomes of laparoscopic treatment for local relapse of renal cell carcinoma

El Hajj, Albert ; Thanigasalam, Ruban ; Molinié, Vincent ; Massoud, Walid ; Fourati, Mohamed ; Girard, Frederic ; Escudier, Bernard ; Baumert, Hervé

What's known on the subject? and What does the study add? * Local relapse of renal cell carcinoma following radical nephrectomy is rare, and surgical removal provides the only opportunity for cure. Open surgery has been established as the usual approach for these tumours. It is, however, associated with significant morbidity. * Our study describes the largest series of laparoscopic treatment of local relapse of renal cell carcinoma with the longest follow-up. We show that the laparoscopic [...]

Menée sur 109 patients âgés d'au moins 80 ans et atteints d'un cancer du poumon non à petites cellules de stade T1-2N0M0 traité entre 2005 et 2012 (durée médiane de suivi après traitement : 24 mois), cette étude évalue, du point de vue de la toxicité, du taux de survie sans métastases distantes et de la survie globale, la faisabilité d'une radiothérapie corporelle ablative stéréotaxique

Stereotactic Ablative Body Radiation Therapy for Octogenarians With Non-Small Cell Lung Cancer

Takeda, Atsuya ; Sanuki, Naoko ; Eriguchi, Takahisa ; Kaneko, Takeshi ; Morita, Satoshi ; Handa, Hiroshi ; Aoki, Yousuke ; Oku, Yohei ; Kunieda, Etsuo

To retrospectively investigate treatment outcomes of stereotactic ablative body radiation therapy (SABR) for octogenarians with non-small cell lung cancer (NSCLC). Between 2005 and 2012, 109 patients aged ≥80 years with T1-2N0M0 NSCLC were treated with SABR: 47 patients had histology-unproven lung cancer; 62 patients had pathologically proven NSCLC. The prescribed doses were either 50 Gy/5 fractions for peripheral tumors or 40 Gy/5 fractions for centrally located tumors. The treatment outcomes, [...]

Menée sur 1 655 patients atteints d'un cancer localisé de la prostate à risque élevé ou intermédiaire de récidive et traité entre 1998 et 2008 (âge ≤ 60 ans ; durée médiane de suivi : 83 mois), cette étude montre que des protocoles thérapeutiques comportant une curiethérapie permettent, du point de vue de la survie sans récidive biochimique, de la toxicité génito-urinaire ou gastrointestinale et de la fonction érectile, d'obtenir des résultats favorables à long terme

Favourable long-term outcomes with brachytherapy-based regimens in men ≤60 years with clinically localized prostate cancer

Kollmeier, Marisa A. ; Fidaleo, Anthony ; Pei, Xin ; Cohen, Gil'ad ; Zaider, Marco ; Mo, Quincy ; Cox, Brett ; Yamada, Yoshiya ; Zelefsky, Michael J.

What's known on the subject? and What does the study add? * Brachytherapy (BT)-based treatment for clinically localized prostate cancer is a well-accepted treatment strategy; however, there is concern that long-term outcomes and morbidity may not be acceptable in young patients (≤60 years). * We report our long-term experience with BT in men aged ≤ 60 years with a minimum of 2 years of post-treatment follow-up. Our results show low treatment-related morbidity and excellent long-term outcomes [...]

A partir des données1995-2007 d'un registre américain portant sur 577 hommes présentant des métastases ganglionnaires détectées après une prostatectomie radicale, cette étude évalue, du point de vue de la survie spécifique et de la survie globale, l'intérêt d'une radiothérapie adjuvante

Patterns of care and outcomes of radiotherapy for lymph node positivity after radical prostatectomy

Kaplan, Joshua R. ; Kowalczyk, Keith J. ; Borza, Tudor ; Gu, Xiangmei ; Lipsitz, Stuart R. ; Nguyen, Paul L. ; Friedlander, David F. ; Trinh, Quoc-Dien ; Hu, Jim C.

Objective * To evaluate the use and outcomes of adjuvant radiation therapy (ART) for men with lymph node (LN)-positive disease after radical prostatectomy (RP) using a population-based approach. Patients and Methods * Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 1995 to 2007 was used to identify 577 men with LN metastases discovered during RP and absence of distant metastases, of which 177 underwent ART ≤1 year of RP. * Propensity score models were used to [...]

Menée sur 220 patients présentant une tumeur rénale de diamètre supérieur à 4 cm (âge médian lors de l'opération chirurgicale : 62 ans ; durée médiane de suivi : 26 mois), cette étude multicentrique française évalue, du point de vue de données intra- et post- opératoires (durée de l'intervention, perte de sang, durée d'hospitalisation), des complications selon la classification de Clavien et de la survie sans progression à 2 ans, l'efficacité d'une chirurgie laparoscopique assistée par robot avec conservation du néphron

Robot-assisted laparoscopic nephron sparing surgery for tumors over 4 cm : Operative results and preliminary oncologic outcomes from a multicentre French study

Masson-Lecomte, A. ; Yates, D. R. ; Bensalah, K. ; Vaessen, C. ; de la Taille, A. ; Roumiguié, M. ; Doumerc, N. ; Bruyère, F. ; Soustelle, L. ; Droupy, S. ; Rouprêt, M.

Objective To assess operative and pathological results obtained after robot-assisted partial nephrectomy (RAPN) in renal masses over 4 cm. Patients and methods Between 2007 and 2011, 220 robotic nephron-sparing surgeries (NSS) were performed at six French urology departments. Data were prospectively collected: age, BMI, pre and post-operative eGFR (MDRD), operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), length of hospital stay (LOS), Clavien complications, pathological [...]

A partir d'une revue de la littérature (35 articles), cet article compare, du point de vue de la récidive et de la survie globale, l'efficacité de différentes stratégies thérapeutiques pour traiter un cancer du sein récidivant après une chirurgie conservatrice

Treatment of Recurrent Breast Cancer Following Breast Conserving Surgery

Burger, Amy E. E. ; Pain, Simon J. ; Peley, Gabor

Patients with isolated ipsilateral breast cancer recurrence face completion mastectomy in the majority of cases. Selected patients may derive good outcomes from repeat breast conservation surgery and indeed repeat irradiation may be employed using one of many different modalities. Tumor biology rather than salvage surgery method is likely to influence outcome. Patients with isolated breast tumor recurrence are treated in the majority of cases with completion mastectomy, when for selected [...]

Cet article passe en revue les travaux récents sur le développement d'immunothérapies des cancers à base de récepteurs d'antigènes chimériques

The Basic Principles of Chimeric Antigen Receptor Design

Sadelain, Michel ; Brentjens, Renier ; Riviere, Isabelle

Chimeric antigen receptors (CAR) are recombinant receptors that provide both antigen-binding and T-cell-activating functions. A multitude of CARs has been reported over the past decade, targeting an array of cell surface tumor antigens. Their biologic functions have dramatically changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. These have recently shown clinical benefit in patients treated with CD19-targeted autologous T [...]

Menée in vitro et in vivo, cette étude suggère l'efficacité d'un traitement combinant le trioxyde d'arsenic et une thérapie ciblée sur EGFR pour les tumeurs solides sans mutation du gène EGFR

Synergistic anticancer activity of arsenic trioxide with erlotinib is based on inhibition of EGFR-mediated DNA double strand break repair

Kryeziu, Kushtrim ; Jungwirth, Ute ; Hoda, Mir Alireza ; Ferk, Franziska ; Knasmuller, Siegfried ; Karnthaler-Benbakka, Claudia ; Kowol, Christian R. ; Berger, Walter ; Heffeter, Petra

Arsenic trioxide (ATO), one of the oldest remedies used in traditional medicine, was recently rediscovered as anticancer drug and approved for treatment of relapsed acute promyelocytic leukemia. However, its activity against non-hematologic cancers is rather limited so far. Here, we show that inhibition of ATO-mediated epidermal growth factor receptor (EGFR) activation can be used to potently sensitize diverse solid cancer types against ATO. Thus, combination of ATO and the EGFR inhibitor [...]

Menée à l'aide de xénogreffes de mélanome et de glioblastome, cette étude suggère l'efficacité d'une stratégie thérapeutique basée sur l'inhibition de la kinase DGKα

Diacylglycerol kinase alpha is a critical signaling node and novel therapeutic target in glioblastoma and other cancers

Dominguez, Charli L. ; Floyd, Desiree H. ; Xiao, Aizhen ; Mullins, Garrett R. ; Kefas, Benjamin A ; Xin, Wenjun ; Yacur, Melissa N. ; Abounader, Roger ; Lee, Jae K. ; Mustata Wilson, Gabriela ; Harris, Thurl E. ; Purow, Benjamin W.

While Diacylglycerol kinase alpha (DGKα) has been linked to several signaling pathways related to cancer cell biology, it has been neglected as a target for cancer therapy. The attenuation of DGKα activity via DGKα-targeting siRNA and small-molecule inhibitors, R59022 and R59949, induced caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacked toxicity in non-cancerous cells. We determined that mTOR and HIF-1α are key targets of DGKα inhibition, in addition to its [...]

Menée in vitro et à l'aide de xénogreffes de divers types de tumeurs, cette étude évalue l'activité antitumorale d'un composé appelé T-1840383, un inhibiteur des récepteurs à activité tyrosine kinase c-Met et VEGFR

A Novel Inhibitor of c-Met and VEGF Receptor Tyrosine Kinases with a Broad Spectrum of In Vivo Antitumor Activities

Awazu, Yoshiko ; Nakamura, Kazuhide ; Mizutani, Akio ; Kakoi, Yuichi ; Iwata, Hidehisa ; Yamasaki, Seiji ; Miyamoto, Naoki ; Imamura, Shinichi ; Miki, Hiroshi ; Hori, Akira

The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are dysregulated in a wide variety of human cancers and are linked with tumorigenesis and metastatic progression. Vascular endothelial growth factor (VEGF) also plays a key role in tumor angiogenesis and progression by stimulating the proangiogenic signaling of endothelial cells via activation of VEGF receptor tyrosine kinases (VEGFRs). Therefore, inhibiting both HGF/c-Met and VEGF/VEGFR signaling may provide a [...]

Menée in vitro, cette étude suggère l'efficacité d'un composé appelé AGI-6780 pour le traitement de leucémies présentant des mutations du gène IDH2

Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation

Wang, Fang ; Travins, Jeremy ; DeLaBarre, Byron ; Penard-Lacronique, Virginie ; Schalm, Stefanie ; Hansen, Erica ; Straley, Kimberly ; Kernytsky, Andrew ; Liu, Wei ; Gliser, Camelia ; Yang, Hua ; Gross, Stefan ; Artin, Erin ; Saada, Veronique ; Mylonas, Elena ; Quivoron, Cyril ; Popovici-Muller, Janeta ; Saunders, Jeffrey O. ; Salituro, Francesco G. ; Yan, Shunqi ; Murray, Stuart ; Wei, Wentao ; Gao, Yi ; Dang, Lenny ; Dorsch, Marion ; Agresta, Sam ; Schenkein, David P. ; Biller, Scott A. ; Su, Shinsan M. ; de Botton, Stéphane ; Yen, Katharine E.

A number of human cancers harbor somatic point mutations in the genes encoding isocitrate dehydrogenases- 1 and -2 (IDH1, IDH2). These mutations alter residues in the enzyme active sites and confer a gain-of-function in cancer cells, resulting in the accumulation and secretion of the oncometabolite R (-)-2-hydroxyglutarate (2HG). We developed a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q. A crystal structure of AGI-6780 complexed with [...]

Cet article passe en revue les perspectives thérapeutiques offertes par les travaux récents sur les mécanismes moléculaires du développement d'un carcinome à cellules claires de l'ovaire

New perspectives on molecular targeted therapy in ovarian clear cell carcinoma

Tan, D. S. P. ; Miller, R. E. ; Kaye, S. B.

Ovarian clear cell carcinomas (OCCCs) account for about 5–13% of all epithelial ovarian carcinomas in Western populations. It is characterised by resistance to conventional platinum-based chemotherapy, and new therapeutic strategies are urgently required. This article will focus on how recent discoveries have enhanced our understanding of the molecular pathogenesis of OCCCs, leading to new therapeutic opportunities. These include mutations in ARID1A, which provides a link to endometriosis, [...]

Menée sur des lignées cellulaires de cancer de l'ovaire, cette étude suggère l'intérêt de développer des inhibiteurs de la kinase ATR en combinaison avec un inhbiteur de PARP

ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status

Huntoon, Catherine J. ; Flatten, Karen S. ; Wahner Hendrickson, Andrea E. ; Huehls, Amelia M ; Sutor, Shari L ; Kaufmann, Scott H. ; Karnitz, Larry M

Replication stress and DNA damage activate the ATR-CHK1 checkpoint signaling pathway that licenses repair and cell survival processes. In this study, we examined the respective roles of the ATR and CHK1 kinases in ovarian cancer cells using genetic and pharmacological inhibitors of in combination with cisplatin, topotecan, gemcitabine and the poly(ADP-ribose)-polymerase (PARP) inhibitor veliparib (ABT-888), four agents with clinical activity in ovarian cancer. RNAi-mediated depletion or [...]

Cet article passe en revue les perspectives thérapeutiques offertes par les inhibiteurs de la signalisation mTOR dans le cancer du sein de stade avancé

mTOR inhibitors in advanced breast cancer: Ready for prime time?

Martin, Lesley-Ann ; Andre, Fabrice ; Campone, Mario ; Bachelot, Thomas ; Jerusalem, Guy

Current therapeutic approaches for advanced breast cancer frequently target receptors mediating cell survival and proliferation, such as the estrogen receptor and/or progesterone receptor and human epidermal growth factor receptor-2. Although these approaches are effective for many patients, treatment resistance is common. Therefore, new treatment approaches are needed for patients with advanced breast cancer. Mammalian target of rapamycin is a highly conserved serine-threonine kinase that acts [...]

Menée sur des lignées cellulaires de gliomes présentant une mutation du gène IDH1, cette étude suggère l'efficacité d'un composé appelé AGI-5198 sur la croissance tumorale

An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells

Rohle, Dan ; Popovici-Muller, Janeta ; Palaskas, Nicolaos ; Turcan, Sevin ; Grommes, Christian ; Campos, Carl ; Tsoi, Jennifer ; Clark, Owen ; Oldrini, Barbara ; Komisopoulou, Evangelia ; Kunii, Kaiko ; Pedraza, Alicia ; Schalm, Stefanie ; Silverman, Lee ; Miller, Alexandra ; Wang, Fang ; Yang, Hua ; Chen, Yue ; Kernytsky, Andrew ; Rosenblum, Marc K. ; Liu, Wei ; Biller, Scott A. ; Su, Shinsan M. ; Brennan, Cameron W. ; Chan, Timothy A. ; Graeber, Thomas G. ; Yen, Katharine E. ; Mellinghoff, Ingo K.

The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1), which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen blocked, in a dose-dependent manner, the ability of [...]

Mené sur 93 patients atteints d'un carcinome hépatocellulaire MTA1+, cet essai cas-témoins évalue l'efficacité de l'interféron pégylé, en traitement adjuvant après une résection curative, pour prévenir la récidive de la maladie

Safety and efficacy of adjuvant pegylated interferon therapy for metastatic tumor antigen 1-positive hepatocellular carcinoma

Lee, Danbi ; Chung, Young-Hwa ; Kim, Jeong A. ; Park, Won Hyung ; Jin, Young-Joo ; Shim, Ju Hyun ; Ryu, Soo Hyung ; Jang, Myoung Kuk ; Yu, Eunsil ; Lee, Young Joo

BACKGROUND Metastatic tumor antigen 1 (MTA1) overexpression is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). It has been suggested that pegylated interferon (Peg-IFN) can prevent the occurrence of HCC in patients who have chronic viral hepatitis. In this study, the authors examined whether postoperative adjuvant Peg-IFN therapy can reduce the recurrence of MTA1-positive HCC after curative surgical resection. METHODS In this case-control study, 93 patients [...]

A partir de données des registres américains SEER et de la base d'assurance maladie Medicare portant sur 15 318 patients ayant reçu un diagnostic de cancer du poumon non à petites cellules de stade IIIB ou IV entre 2000 et 2007, cette étude compare l'efficacité des trois protocoles de chimiothérapie les plus communément administrés (carboplatine-paciltaxel, carboplatine-gemcitabine et carboplatine-docétaxel)

Comparative effectiveness of three platinum-doublet chemotherapy regimens in elderly patients with advanced non–small cell lung cancer

Zhu, Junya ; Sharma, Dhruv B. ; Chen, Aileen B. ; Johnson, Bruce E. ; Weeks, Jane C. ; Schrag, Deborah

BACKGROUND Randomized trials report equivalent efficacy among various combinations of platinum-based regimens in advanced non–small cell lung cancer (NSCLC). Their relative effectiveness and comparability based on squamous versus nonsquamous histology is uncertain. METHODS The authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data to identify first-line chemotherapy agents administered to Medicare beneficiaries with stage IIIB or IV NSCLC diagnosed from 2000 to [...]

Mené sur 48 patients atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase II évalue l'efficacité et la toxicité d'un traitement de première ligne combinant S-1, carboplatine et bevacizumab suivi par un traitement d'entretien à l'aide de S-1 et de bevacizumab

Phase 2 study of S-1 and carboplatin plus bevacizumab followed by maintenance S-1 and bevacizumab for chemotherapy-naive patients with advanced nonsquamous non–small cell lung cancer

Urata, Yoshiko ; Okamoto, Isamu ; Takeda, Masayuki ; Hattori, Yoshihiro ; Okuno, Keiko ; Shimada, Temiko ; Kurata, Takayasu ; Kaneda, Hiroyasu ; Miyazaki, Masaki ; Terashima, Masaaki ; Tanaka, Kaoru ; Morita, Satoshi ; Nakagawa, Kazuhiko ; Negoro, Shunichi ; Satouchi, Miyako

BACKGROUND A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S-1 (an oral fluoropyrimidine) and carboplatin compared with combined paclitaxel and carboplatin as first-line treatment for advanced non–small cell lung cancer (NSCLC). In the current study, the authors evaluated the efficacy and safety of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab in chemotherapy-naive patients with advanced nonsquamous [...]

Mené sur 99 patients ayant reçu plusieurs lignes de traitement pour un cancer avancé du poumon non à petites cellules, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 16 semaines, et la toxicité du ganetespib, un inhibiteur de la protéine de choc thermique Hsp90, en fonction de la présence de réarrangements du gène ALK

A multicenter Phase II study of ganetespib monotherapy in patients with genotypically-defined advanced non-small cell lung cancer

Socinski, Mark A ; Goldman, Jonathan ; El-Hariry, Iman ; Koczywas, Marianna ; Vukovic, Vojo ; Horn, Leora ; Paschold, Eugene ; Salgia, Ravi ; West, Howard ; Sequist, Lecia V. ; Bonomi, Philip ; Brahmer, Julie R ; Chen, Lin-Chi ; Sandler, Alan B ; Belani, Chandra P. ; Webb, Timothy R ; Harper, Harry ; Huberman, Mark ; Ramalingham, Suresh ; Wong, Kwok-Kin ; Teofilovici, Florentina ; Guo, Wei ; Shapiro, Geoffrey I.

Purpose:Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated non-small cell lung cancer (NSCLC) patients. Experimental Design:Patients were enrolled into Cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m2 ganetespib by intravenous infusion (IV) once [...]

Mené sur 34 patients atteints d'un cancer métastatique de la prostate résistant à la castration, cet essai évalue l'efficacité et la toxicité de trois dosages du cabozantinib en prévention du développement de métastases osseuses

A dose-ranging study of cabozantinib in men with castration-resistant prostate cancer and bone metastases

Lee, Richard J. ; Saylor, Philip J. ; Michaelson, M. Dror ; Rothenberg, Stephen M ; Smas, Malgorzata E. ; Miyamoto, David T. ; Gurski, Carol A. ; Xie, Wanling ; Maheswaran, Shyamala ; Haber, Daniel A. ; Goldin, Jonathan G. ; Smith, Matthew R.

Background Cabozantinib is an oral MET/VEGFR2 inhibitor. A recent phase II study of cabozantinib (100mg daily) demonstrated improved bone scans in subjects with metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AEs) caused frequent dose reductions. This study was designed to determine the efficacy and tolerability of cabozantinib at lower starting doses. Patients and Methods An adaptive design was used to determine the lowest active daily dose among 60mg, 40mg, and [...]

Mené sur 1 535 patients atteints d'un cancer de la prostate métastatique hormonosensible, cet essai compare deux modalités d'administration, de façon intermittente ou continue, de médicaments anti-adrogènes (durée médiane de suivi : 9,8 ans)

Intermittent versus Continuous Androgen Deprivation in Prostate Cancer

Hussain, Maha ; Tangen, Catherine M. ; Berry, Donna L. ; Higano, Celestia S. ; Crawford, E. David ; Liu, Glenn ; Wilding, George ; Prescott, Stephen ; Kanaga Sundaram, Subramanian ; Small, Eric Jay ; Dawson, Nancy Ann ; Donnelly, Bryan J. ; Venner, Peter M. ; Vaishampayan, Ulka N. ; Schellhammer, Paul F. ; Quinn, David I. ; Raghavan, Derek ; Ely, Benjamin ; Moinpour, Carol M. ; Vogelzang, Nicholas J. ; Thompson, Ian M.

Background : Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. Methods : Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone–releasing hormone [...]

Menée sur 73 patients atteints d'un cancer localement avancé du pancréas et ayant reçu une chimiothérapie d'induction (durée médiane de suivi : 10,5 mois), cette étude rétrospective montre que la radiothérapie corporelle stéréotaxique est efficace et bien tolérée chez les patients présentant une tumeur à la limite de la résécabilité

Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated

Chuong, Michael D. ; Springett, Gregory M. ; Freilich, Jessica M. ; Park, Catherine K. ; Weber, Jill M. ; Mellon, Eric A. ; Hodul, Pamela J. ; Malafa, Mokenge P. ; Meredith, Kenneth L. ; Hoffe, Sarah E. ; Shridhar, Ravi

Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity. A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique [...]

Menée sur 155 patients atteints d'un cancer de la prostate à risque élevé de récidive et traités entre 2003 et 2011 (durée médiane de suivi : 62 mois ; PSA avant traitement ≥20 ng/ml), cette étude évalue, du point de vue de la survie sans métastases distantes, de la survie spécifique et de la survie globale, l'efficacité d'une radiothérapie externe radicale en combinaison avec un traitement anti-androgénique

Radical radiotherapy in high-risk prostate cancer patients with high or ultra-high initial PSA levels: a single institution analysis

Guarneri, Alessia ; Botticella, Angela ; Filippi, AndreaRiccardo ; Ruggieri, Andrea ; Piva, Cristina ; Munoz, Fernando ; Ragona, Riccardo ; Gontero, Paolo ; Ricardi, Umberto

Purpose : Purpose of this study is to analyze outcomes and pre-treatment prognostic factors in high-risk prostate cancer patients with initial PSA ≥20 ng/mL, treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) in a single institution. Methods : Between March 2003 and December 2011, 155 consecutive high-risk prostate cancer patients (a) presenting with pre-treatment PSA level ≥20 ng/mL, (b) treated with definitive EBRT, and (c) with a minimum follow-up [...]

Menée sur 372 patientes atteintes d'un cancer du col de l'utérus, cette étude rétrospective évalue les effets de la durée d'un traitement combinant ou non une radiothérapie avec une chimiothérapie concomitante sur le taux de récidive, de survie sans maladie et de survie globale

Effects of Treatment Duration During Concomitant Chemoradiation Therapy for Cervical Cancer

Shaverdian, Narek ; Gondi, Vinai ; Sklenar, Kathryn L. ; Dunn, Emily F. ; Petereit, Daniel G. ; Straub, Margaret R. ; Bradley, Kristin A.

To determine whether extended treatment duration (TD) impacts in-field relapse and survival in the setting of concomitant chemoradiation therapy (CRT) for cervical cancer. A total of 480 consecutive cervical cancer patients treated with radiation therapy (RT) alone or concomitant CRT for curative intent were retrospectively analyzed. Relapse was defined as in-field with respect to external beam radiation therapy fields. The effects of TD on in-field relapse, disease-free survival (DFS), and [...]

Cet article propose de nouvelles approches pour faciliter l'autorisation de mise sur le marché de nouveaux traitements en oncologie

Reevaluating the Accelerated Approval Process for Oncology Drugs

Wilson, Wyndham H ; Schenkein, David P ; Jernigan, Cheryl L ; Woodcock, Janet ; Schilsky, Richard

In order for a new therapy to qualify for the accelerated approval pathway, it must treat a serious disease for which there is "unmet medical need"-- defined as providing a therapy where none exists or providing a therapy which may be potentially superior to existing therapy. The increasing number of available therapies, coupled with the lack of accepted endpoints considered "reasonably likely to predict clinical benefit" and the lack of clarity early in development regarding circumstances in [...]

Cet article passe en revue les travaux récents sur la biologie des tumeurs apparaissant spontanément chez les chiens et analyse les perspectives offertes par ces connaissances pour développer de nouvelles approches thérapeutiques chez les humains

A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies

Ranieri, G. ; Gadaleta, C. D. ; Patruno, R. ; Zizzo, N. ; Daidone, M. G. ; Hansson, M. G. ; Paradiso, A. ; Ribatti, D.

Murine cancer models have been extremely useful for analyzing the biology of pathways involved in cancer initiation, promotion, and progression. Interestingly, several murine cancer models also exhibit heterogeneity, genomic instability and an intact immune system. However, they do not adequately represent several features that define cancer in humans, including long periods of latency, the complex biology of cancer recurrence and metastasis and outcomes to novel therapies. Therefore, [...]