Menée sur 11 patientes atteintes d'un cancer gynécologique (vagin, col de l'utérus ou endomètre) traité par radiothérapie en combinaison ou non avec une chimiothérapie et ayant subi une hystérectomie pour des lésions cancéreuses ou non (âge médian : 55 ans), cette étude évalue la toxicité aiguë d'une radiothérapie par faisceaux de protons de l'ensemble de la région pelvienne, puis compare les avantages dosimétriques de ce traitement par rapport à une radiothérapie avec modulation d'intensité

Initial report of pencil beam scanning proton therapy for posthysterectomy patients with gynecologic cancer

Lin, Lilie L. ; Kirk, Maura ; Scholey, Jessica ; Taku, Nicolette ; Kiely, Janid B. ; White, Benjamin ; Both, Stefan

Purpose : To report the acute toxicities associated with pencil beam scanning proton beam radiotherapy (PBS) for whole pelvis radiotherapy in women with gynecologic cancers and a dosimetric comparison of PBS vs intensity modulated radiation therapy (IMRT) plans. Methods and Materials : Eleven patients with gynecologic cancer who were posthysterectomy received PBS to the whole pelvis. Patients received a dose of 45-50.4 Gy relative biological effectiveness (RBE) in 1.8 Gy(RBE) daily fractions. [...]

Cet article passe en revue les conclusions d'un groupe de travail américain sur les avancées technologiques en matière de radiothérapie oncologique et de leur intérêt pour améliorer la sécurité et l'efficacité des traitements ionisants administrés

Technology for Innovation in Radiation Oncology

Chetty, Indrin J. ; Martel, Mary K. ; Jaffray, David A. ; Benedict, Stanley H. ; Hahn, Stephen M. ; Berbeco, Ross ; Deye, James ; Jeraj, Robert ; Kavanagh, Brian ; Krishnan, Sunil ; Lee, Nancy ; Low, Daniel A. ; Mankoff, David ; Marks, Lawrence B. ; Ollendorf, Daniel ; Paganetti, Harald ; Ross, Brian ; Siochi, Ramon Alfredo C. ; Timmerman, Robert D. ; Wong, John W.

Radiotherapy is an effective, personalized cancer treatment that has benefited from technological advances associated with growing ability to identify and target tumors with accuracy and precision. As these advances have played a central role in the success of radiation therapy as a major component of comprehensive cancer care, the American Society of Therapeutic Radiation Oncology (ASTRO), the American Association of Physicists in Medicine (AAPM) and the National Cancer Institute (NCI) [...]

Menée à partir des données du registre national américain des cancers portant sur 29 752 patients atteints d'un lymphome hodgkinien classique de stade I/II diagnostiqué entre 1998 et 2011, cette étude évalue l'effet d'une radiothérapie de consolidation sur la survie globale des patients

Early-Stage Classical Hodgkin Lymphoma: The Utilization of Radiation Therapy and Its Impact on Overall Survival

Parikh, Rahul R. ; Grossbard, Michael L. ; Harrison, Louis B. ; Yahalom, Joachim

Purpose : Treatment for early-stage classical Hodgkin lymphoma (HL) includes combined modality therapy (CMT) of chemotherapy followed by consolidation radiation therapy (RT), but use of RT has not been universal. We examined the association between RT utilization and overall survival for patients with early-stage HL. Methods and Materials : Using the National Cancer Database (NCDB), we evaluated clinical features and survival outcomes among patients diagnosed with Stage I/II HL from 1998 to [...]

Menée sur 67 patients traités entre 2009 et 2013 pour un cancer localisé de la prostate (âge moyen : 70,2 ans ; durée médiane de suivi : 12 mois), cette étude évalue l'efficacité, du point de vue du contrôle de la maladie, et les complications génito-urinaires associées à l'ablation du lobe prostatique impliqué par ultrasons focalisés de haute intensité

Focal High-intensity Focused Ultrasound Targeted Hemiablation for Unilateral Prostate Cancer: A Prospective Evaluation of Oncologic and Functional Outcomes

Feijoo, Ernesto R. Cordeiro ; Sivaraman, Arjun ; Barret, Eric ; Sanchez-Salas, Rafael ; Galiano, Marc ; Rozet, François ; Prapotnich, Dominique ; Cathala, Nathalie ; Mombet, Annick ; Cathelineau, Xavier

Background : In selected patients with unilateral, organ-confined prostate cancer (PCa), hemiablation of the affected lobe might be feasible to achieve acceptable cancer control with fewer complications. Objectives : To assess the oncologic and functional outcomes of focal high-intensity focused ultrasound (HIFU) hemiablation in unilateral organ-confined PCa. Design, setting and patients : Single-center prospective evaluation of HIFU hemiablation for unilateral organ-confined PCa was performed [...]

Mené en France sur 23 chiens atteints d'un lymphome de stade III/IV, cet essai de phase I évalue l'efficacité et la toxicité d'un composé appelé F14512, un inhibiteur de la topoisomérase II actuellement en essai clinique chez des patients atteints d'une leucémie myéloïde aiguë

Phase 1 clinical pharmacology study of F14512, a new polyamine-vectorized anti-cancer drug, in naturally occurring canine lymphoma

Tierny, Dominique ; Serres, Francois ; Segaoula, Zacharie ; Bemelmans, Ingrid ; Bouchaert, Emmanuel ; Petain, Aurelie ; Brel, Viviane ; Couffin, Stephane ; Marchal, Thierry ; Nguyen, Laurent ; Thuru, Xavier ; Ferre, Pierre ; Guilbaud, Nicolas ; Gomes, Bruno

Purpose: F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in Phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication. Because of the many similarities between human and dog lymphomas, we sought to determine the tolerance, efficacy, PK/PD relationship of F14512 in [...]

Menée sur des lignées cellulaires de divers types de cancer, notamment de cancer de l'épithélium ovarien, cette étude analyse les mécanismes d'activité antitumorale d'un composé à base d'osmium et met en évidence son efficacité pour surmonter une résistance à un traitement aux sels de platine

Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

Hearn, Jessica M. ; Romero-Canelón, Isolda ; Munro, Alison F. ; Fu, Ying ; Pizarro, Ana M. ; Garnett, Mathew J. ; McDermott, Ultan ; Carragher, Neil O. ; Sadler, Peter J.

The organometallic “half-sandwich” compound [Os(η6-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH [...]

Menée in vitro et in vivo sur des modèles de cancer métastatique de l'ovaire, cette étude évalue l'efficacité d'une stratégie à base d'exosomes pour capturer les cellules métastatiques disséminées dans la cavité péritonéale

M-Trap: Exosome-Based Capture of Tumor Cells as a New Technology in Peritoneal Metastasis

de la Fuente, Alexandre ; Alonso-Alconada, Lorena ; Costa, Clotilde ; Cueva, Juan ; Garcia-Caballero, Tomas ; Lopez-Lopez, Rafael ; Abal, Miguel

Background: Remodeling targeted tissues for reception of tumor cells metastasizing from primary lesions is a consequence of communication between the tumor and the environment that governs metastasis. This study describes a novel approach that aims to disrupt the process of metastasis by interfering with this intense dialogue. Methods: Proteomics and adhesion assays identified exosomes purified from the ascitic fluid of ovarian cancer patients (n = 9) as intermediaries of tumor cell attachment. [...]

Menée in vitro et in vivo sur des modèles de cancer du poumon non à petites cellules, cette étude met en évidence l'activité antitumorale d'un composé appelé UNC2025, un inhibiteur de MERTK

Small molecule inhibition of MERTK is efficacious in non-small cell lung cancer models independent of driver oncogene status

Cummings, Christopher T ; Zhang, Weihe ; Davies, Kurtis D ; Kirkpatrick, Gregory D ; Zhang, Dehui ; DeRyckere, Deborah ; Wang, Xiaodong ; Frye, Stephen V ; Earp, H Shelton ; Graham, Douglas K

Treatment of non-small cell lung cancer (NSCLC) has been transformed by targeted therapies directed against molecular aberrations specifically activated within an individual patient's tumor. However, such therapies are currently only available against a small number of such aberrations, and new targets and therapeutics are needed. Our laboratory has previously identified the MERTK receptor tyrosine kinase (RTK) as a potential drug target in multiple cancer types, including NSCLC. We have [...]

Menée à l'aide de xénogreffes de cancer du sein, cette étude met en évidence des mécanismes par lesquels une chimiothérapie augmente l'efficacité d'un traitement anti-angiogénique

Potential Pro-invasive or Metastatic Effects of Preclinical Antiangiogenic Therapy Are Prevented by Concurrent Chemotherapy

Paez-Ribes, Marta ; Man, Shan ; Xu, Ping ; Kerbel, Robert S

Purpose: To resolve a controversy involving the therapeutic impact of antiangiogenic drugs and particularly antibodies targeting the VEGF pathway, namely, a body of preclinical mouse therapy studies showing such drugs can promote invasion and/or distant metastasis when used as monotherapies. In contrast, clinical studies have not shown such pro-malignancy effects. However, most such clinical studies have involved patients also treated with concurrent chemotherapy highlighting the possibility [...]

Menée à l'aide de xénogreffes de cancer du sein, cette étude met en évidence des mécanismes par lesquels le récepteur de la progestérone régule l'activité du récepteur alpha des estrogènes

Progesterone receptor modulates ERalpha action in breast cancer

Mohammed, Hisham ; Russell, I. Alasdair ; Stark, Rory ; Rueda, Oscar M. ; Hickey, Theresa E. ; Tarulli, Gerard A. ; Serandour, Aurelien A. A. ; Birrell, Stephen N. ; Bruna, Alejandra ; Saadi, Amel ; Menon, Suraj ; Hadfield, James ; Pugh, Michelle ; Raj, Ganesh V. ; Brown, Gordon D. ; D/'Santos, Clive ; Robinson, Jessica L. L. ; Silva, Grace ; Launchbury, Rosalind ; Perou, Charles M. ; Stingl, John ; Caldas, Carlos ; Tilley, Wayne D. ; Carroll, Jason S.

Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-

Mené sur 77 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la toxicité et l'activité antitumorale du lenvatinib

Phase I dose-escalation study of the multikinase inhibitor lenvatinib in patients with advanced solid tumors and in an expanded cohort of patients with melanoma

Hong, David ; Kurzrock, Razelle ; Wheler, Jennifer J. ; Naing, Aung ; Falchook, Gerald S. ; Fu, Siqing ; Kim, Kevin B ; Davies, Michael A. ; Nguyen, Ly M ; George, Goldy C. ; Xu, Lucy ; Shumaker, Robert ; Ren, Min ; Mink, Jennifer ; Bedell, Cynthia ; Andresen, Corina ; Sachdev, Pallavi ; O'Brien, James P ; Nemunaitis, John

Purpose: This "3+3" phase I study evaluated the safety, biologic, and clinical activity of lenvatinib, an oral multikinase inhibitor, in patients with solid tumors. Experimental Design: Ascending doses of lenvatinib were administered po bid in 28-day cycles. Safety and response were assessed for all patients. Angiogenic and apoptotic factors were tested as possible biomarkers in an expanded melanoma cohort. Results: Seventy-seven patients were treated in 3 cohorts: 18 with intermittent bid [...]

Mené au Japon sur 307 patients atteints d'un cancer non épidermoïde du poumon non à petites cellules de stade IIIB/IV ne présentant pas de mutation du gène EGFR, cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout de tivantinib à l'erlotinib

A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV non-squamous non-small-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study)

Yoshioka, H. ; Azuma, K. ; Yamamoto, N. ; Takahashi, T. ; Nishio, M. ; Katakami, N. ; Ahn, M.J. ; Hirashima, T. ; Maemondo, M. ; Kim, S.W. ; Kurosaki, M. ; Akinaga, S. ; Park, K. ; Tsai, C.M. ; Tamura, T. ; Mitsudomi, T. ; Nakagawa, K.

Backgrounds : A previous randomized phase II study demonstrated that the addition of a c-Met inhibitor tivantinib to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib might prolong progression-free survival (PFS) in patients with previously treated, non-squamous non-small-cell lung cancer (NSCLC). On a subset analysis, the survival benefit was greater in patients with wild-type EGFR (WT-EGFR) than in those with activating EGFR mutations. Herein, this phase III study [...]

Mené sur 1 048 patients atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout du tivantinib à l'erlotinib en traitement de deuxième ou troisième ligne

Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-Cell Lung Cancer

Scagliotti, Giorgio ; von Pawel, Joachim ; Novello, Silvia ; Ramlau, Rodryg ; Favaretto, Adolfo ; Barlesi, Fabrice ; Akerley, Wallace ; Orlov, Sergey ; Santoro, Armando ; Spigel, David ; Hirsh, Vera ; Shepherd, Frances A. ; Sequist, Lecia V. ; Sandler, Alan ; Ross, Jeffrey S. ; Wang, Qiang ; Von Roemeling, Reinhard ; Shuster, Dale ; Schwartz, Brian

Purpose : Tivantinib, a MET receptor tyrosine kinase inhibitor, demonstrated increased anticancer activity in preclinical and early clinical studies when combined with erlotinib. Our study aimed to confirm efficacy and safety of the combination in previously treated patients with non–small-cell lung cancer (NSCLC). Patients and Methods : Patients with advanced nonsquamous NSCLC previously treated with one to two systemic regimens, including a platinum doublet, were randomly assigned at a 1:1 [...]

Mené sur 120 patientes ménopausées atteintes d'un cancer du sein HR+ opérable, cet essai randomisé évalue l'efficacité, du point de vue du pourcentage de patientes ayant bénéficié d'une chirurgie conservatrice du sein, et la toxicité d'un traitement néoadjuvant à base d'anastrozole ou de fulvestrant

Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer

Quenel-Tueux, Nathalie ; Debled, Marc ; Rudewicz, Justine ; MacGrogan, Gaëtan ; Pulido, Marina ; Mauriac, Louis ; Dalenc, Florence ; Bachelot, Thomas ; Lortal, Barbara ; Breton-Callu, Christelle ; Madranges, Nicolas ; de Lara, Christine Tunon ; Fournier, Marion ; Bonnefoi, Hervé ; Soueidan, Hayssam ; Nikolski, Macha ; Gros, Audrey ; Daly, Catherine ; Wood, Henry ; Rabbitts, Pamela ; Iggo, Richard

Background: The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment. Methods: One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number [...]

Menés sur 31 patients adultes et 12 patients pédiatriques atteints d'un médulloblastome récidivant, ces deux essais de phase II évaluent l'efficacité et la toxicité du vismodegib, un inhibiteur de la signalisation Sonic Hedgehog

Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog–Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032

Robinson, Giles W. ; Orr, Brent A. ; Wu, Gang ; Gururangan, Sridharan ; Lin, Tong ; Qaddoumi, Ibrahim ; Packer, Roger J. ; Goldman, Stewart ; Prados, Michael D. ; Desjardins, Annick ; Chintagumpala, Murali ; Takebe, Naoko ; Kaste, Sue C. ; Rusch, Michael ; Allen, Sariah J. ; Onar-Thomas, Arzu ; Stewart, Clinton F. ; Fouladi, Maryam ; Boyett, James M. ; Gilbertson, Richard J. ; Curran, Tom ; Ellison, David W. ; Gajjar, Amar

Purpose : Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB). Patients and Methods : Adult patients enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns [...]

Menée sur des lignées de cellules cancéreuses humaines et à l'aide de xénogreffes, cette étude montre que AMG 232, une petite molécule inhibant l'interaction entre les protéines MDM2 et p53, augmente l'efficacité antitumorale des rayonnements ionisants

Small molecule inhibition of MDM2-p53 interaction augments radiation response in human tumors

Werner, Lauryn R ; Huang, Shyhmin ; Francis, David M. ; Armstrong, Eric A. ; Ma, Fang ; Li, Chunrong ; Iyer, Gopal ; Canon, Jude ; Harari, Paul M.

MDM2-p53 interaction and downstream signaling impacts cellular response to DNA damage. AMG 232 is a potent small molecule inhibitor that blocks the interaction of MDM2 and p53. We examined the capacity of AMG 232 to augment radiation response across a spectrum of human tumor cell lines and xenografts. AMG 232 effectively inhibited proliferation and enhanced radiosensitivity via inhibition of damage repair signaling. Combined AMG 232 and radiation treatment resulted in the accumulation of

Mené en France sur 192 patients atteints d'un cancer de stade T3-N0/N1-M0 situé dans la zone thoracique de l'œsophage, cet essai de phase III évalue, du point de vue de la survie globale, l'intérêt d'un traitement chirurgical après l'échec d'une chimioradiothérapie

Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone

Vincent, Julie ; Mariette, Christophe ; Pezet, Denis ; Huet, Emmanuel ; Bonnetain, Franck ; Bouche, Olivier ; Conroy, Thierry ; Roullet, Bernard ; Seitz, Jean-François ; Herr, Jean-Philippe ; Di Fiore, Frédéric ; Jouve, Jean-Louis ; Bedenne, Laurent

Background : Two randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if [...]

Cet article présente la mise à jour des recommandations de l'"American Society of Clinical Oncology" sur l'utilisation des facteurs de stimulation des colonies pour la prévention du risque de neutropénie fébrile

Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update

Smith, Thomas J. ; Bohlke, Kari ; Lyman, Gary H. ; Carson, Kenneth R. ; Crawford, Jeffrey ; Cross, Scott J. ; Goldberg, John M. ; Khatcheressian, James L. ; Leighl, Natasha B. ; Perkins, Cheryl L. ; Somlo, George ; Wade, James L. ; Wozniak, Antoinette J. ; Armitage, James O.

Purpose : To update the 2006 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSFs). Methods : The American Society of Clinical Oncology convened an Update Committee and conducted a systematic review of randomized clinical trials, meta-analyses, and systematic reviews from October 2005 through September 2014. Guideline recommendations were based on the review of the evidence by the Update Committee. Results : Changes to previous [...]