Cet article analyse le rôle du microARN miR-34a dans la réponse des cellules tumorales aux rayonnements ionisants ou la toxicité de ces derniers à l'égard des tissus sains

Emergence of miR-34a in radiation therapy

Lacombe, Jérôme ; Zenhausern, Frederic

Expressions of many microRNAs (miRNAs) in response to ionizing radiation (IR) have already been investigated and some of them seem to play an important role in the tumor radioresistance, normal tissue radiotoxicity or as predictive biomarkers to radiation. MiR-34a is an emerging miRNA in recent radiobiology studies. Here, we review this miR-34 family member by detailing its different roles in radiation response and we will discuss about the role that it can play in radiation treatment. Thus, we [...]

Menée à partir de données portant sur 67 patients pédiatriques atteints d'un neuroblastome à haut risque de récidive traité par chirurgie entre 2003 et 2014 (âge médian : 3,3 ans ; durée médiane de suivi : 4,5 ans), cette étude évalue, en fonction de la dose de rayonnements administrée et de critères pathologiques (présence d'un envahissement ganglionnaire, d'une maladie résiduelle ou de marges de résection positives), l'effet d'une radiothérapie de consolidation sur le contrôle de la maladie et la survie des patients

Favorable local control from consolidative radiotherapy in high-risk neuroblastoma despite gross residual disease, positive margins, or nodal involvement

Ferris, Matthew J. ; Danish, Hasan ; Switchenko, Jeffrey M. ; Deng, Claudia ; George, Bradley A. ; Goldsmith, Kelly C. ; Wasilewski, Karen J. ; Cash, W. Thomas ; Khan, Mohammad K. ; Eaton, Bree R. ; Esiashvili, Natia

Purpose : Radiotherapy (RT) has an established role in consolidative treatment of high-risk neuroblastoma. In addition to the standard 21.6 Gy delivered to the primary site following surgical resection, recent cooperative group guidelines incorporate a 14.4 Gy boost in the instance of residual gross disease. Here we report the influence of RT dose and surgical pathology variables on disease control and overall survival (OS) in patients treated at a single institution. Methods : We conducted a [...]

Mené sur 27 patientes atteintes d'un carcinome canalaire infiltrant du sein de stade précoce (durée médiane de suivi : 3,6 ans), cet essai de phase II évalue, du point de vue de l'échec local ou régional, de la réponse pathologique complète et des résultats esthétiques, la faisabilité d'une irradiation partielle accélérée du sein par radiothérapie conformationnelle 3D avant une lumpectomie

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer : Preliminary Results of a Prospective Phase II Trial

Nichols, Elizabeth ; Kesmodel, Susan B. ; Bellavance, Emily ; Drogula, Cynthia ; Tkaczuk, Katherine ; Cohen, Randi J. ; Citron, Wendla ; Morgan, Michelle ; Staats, Paul ; Feigenberg, Steven ; Regine, William F.

Introduction : Assess the feasibility of utilizing 3D conformal APBI in the pre-operative setting followed by standard breast conserving therapy. Methods and Materials : This is a prospective trial testing the feasibility of pre-operative APBI followed by lumpectomy for patients with early stage invasive ductal breast cancer. Eligible patients had T1-T2 (< 3 cm), N0 tumors Patients received 38.5 Gray (Gy) in 3.85 Gy fractions delivered twice daily. Surgery was performed > 21 days after [...]

Menée à partir de données portant sur 140 patientes atteintes d'une tumeur phyllode du sein traité par chirurgie entre 1998 et 2010, cette étude évalue le taux de récidive en fonction de la largeur des marges de résection

How Wide Should Margins Be for Phyllodes Tumors of the Breast?

Tremblay-LeMay, Rosemarie ; Hogue, Jean-Charles ; Provencher, Louise ; Poirier, Brigitte ; Poirier, Éric ; Laberge, Sophie ; Diorio, Caroline ; Desbiens, Christine

The surgical management of phyllodes tumors (PTs) is still controversial. Some studies have suggested surgical margins ≥1 cm, but recent studies suggested that negative margins could be appropriate regardless of their width. To evaluate recurrence rates of PTs following surgery according to margins. Retrospective study of women who attended a tertiary breast cancer reference center between 1998 and 2010 : 142 patients with a PT diagnosis, either at minimally invasive breast biopsy or at [...]

Menée à l'aide de trois modèles syngéniques murins, cette étude met en évidence des mécanismes par lesquels des kinases de la voie de signalisation Hippo inhibent la réponse antitumorale du système immunitaire

The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity

Moroishi, Toshiro ; Hayashi, Tomoko ; Pan, Wei-Wei ; Fujita, Yu ; Holt, Matthew V ; Qin, Jun ; Carson, Dennis A ; Guan, Kun-Liang

Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. [...]

Cet article passe en revue les travaux récents sur les mécanismes de résistance aux immunothérapies anti PD1/PDL1

Resistance to PD1/PDL1 checkpoint inhibition

O’Donnell, Jake S. ; Long, Georgina V. ; Scolyer, Richard A. ; W. L. Teng, Michele ; Smyth, Mark J.

For the first time in decades, patients with difficult-to-treat cancers such as melanoma are being offered a glimpse of hope in the form of immunotherapies. By targeting factors that foster the development and maintenance of an immunosuppressive microenvironment within tumors, these therapies release the breaks on the host’s own immune system; allowing cure of disease. Indeed, phase III clinical trials have revealed that therapies such as ipilimumab and pembrolizumab which target the CTLA4 and [...]

Menée à l'aide de deux modèles murins de leucémie chronique lymphoïde, cette étude évalue l'activité antitumorale de l'acalabrutinib, un inhibiteur de BTK

The Bruton's tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia

Herman, Sarah E. M. ; Montraveta, Arnau ; Niemann, Carsten U. ; Mora-Jensen, Helena ; Gulrajani, Michael ; Krantz, Fanny ; Mantel, Rose ; Smith, Lisa L. ; McClanahan, Fabienne ; Harrington, Bonnie ; Colomer, Dolors ; Covey, Todd ; Byrd, John C. ; Izumi, Raquel ; Kaptein, Allard ; Ulrich, Roger ; Johnson, Amy ; Lannutti, Brian J. ; Wiestner, Adrian ; Woyach, Jennifer A.

Purpose: Acalabrutinib (ACP-196) is a novel, potent, and highly selective BTK inhibitor, which binds covalently to Cys481 in the ATP-binding pocket of BTK. We sought to evaluate the anti-tumor effects of acalabrutinib treatment in two established mouse models of chronic lymphocytic leukemia (CLL). Experimental Design: Two distinct mouse models were used, the TCL1 adoptive transfer model where leukemic cells from Eμ-TCL1 transgenic mice are transplanted into C57BL/6 mice, and the human NSG [...]

Menée sur des lignées cellulaires de divers types de leucémie myéloïde aiguë et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'un composé appelé T-3775440, un inhibiteur de l'histone déméthylase LSD1

A novel LSD1 inhibitor T-3775440 disrupts GFI1B-containing complex leading to transdifferentiation and impaired growth of AML cells

Ishikawa, Yoshinori ; Gamo, Kanae ; Yabuki, Masato ; Takagi, Shinji ; Toyoshima, Kosei ; Nakayama, Kazuhide ; Nakayama, Akiko ; Morimoto, Megumi ; Miyashita, Hitoshi ; Dairiki, Ryo ; Hikichi, Yukiko ; Tomita, Naoki ; Tomita, Daisuke ; Imamura, Shinichi ; Iwatani, Misa ; Kamada, Yusuke ; Matsumoto, Satoru ; Hara, Ryujiro ; Nomura, Toshiyuki ; Tsuchida, Ken ; Nakamura, Kazuhide

Dysregulation of the histone demethylase LSD1, also known as KDM1A, has been implicated in the development of various cancers, including leukemia. Here we describe the anti-leukemic activity and mechanism of action of T-3775440, a novel irreversible LSD1 inhibitor. Cell growth analysis of leukemia cell lines revealed that acute erythroleukemia (AEL) and acute megakaryoblastic leukemia cells (AMKL) were highly sensitive to this compound. T-3775440 treatment enforced transdifferentiation of [...]

Menée à l'aide de modèles murins de mélanome métastatique, cette étude met en évidence l'activité antitumorale d'un anticorps monoclonal anti interleukine 2 (NARA1) qui, en bloquant CD25, favorise une réponse antitumorale du système immunitaire

Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2

Arenas-Ramirez, Natalia ; Zou, Chao ; Popp, Simone ; Zingg, Daniel ; Brannetti, Barbara ; Wirth, Emmanuelle ; Calzascia, Thomas ; Kovarik, Jiri ; Sommer, Lukas ; Zenke, Gerhard ; Woytschak, Janine ; Regnier, Catherine H. ; Katopodis, Andreas ; Boyman, Onur

Interleukin-2 (IL-2) binds to receptors on multiple different types of T cells. CD8 T cells, which can kill tumor cells, have IL-2 receptors with two subunits. When IL-2 binds to these, it promotes the T cells’ activation. In contrast, regulatory T cells dampen the antitumor immune response, and they express a different type of IL-2 receptor, which contains CD25 in addition to the other two subunits. CD25 binds IL-2 tightly but does not signal. To address this, Arenas-Ramirez et al. developed [...]

Menée sur des lignées cellulaires et à l'aide de modèles murins de mélanome, cette étude met en évidence des mécanismes par lesquels la voie de signalisation de l'interféron favorise la résistance aux immunothérapies ciblant les points de contrôle immunitaire (PD-1, PD-L1, CTLA4)

Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade

Benci, Joseph L ; Xu, Bihui ; Qiu, Yu ; Wu, Tony J ; Dada, Hannah ; Twyman-Saint Victor, Christina ; Cucolo, Lisa ; Lee, David S M. ; Pauken, Kristen E ; Huang, Alexander C ; Gangadhar, Tara C ; Amaravadi, Ravi K ; Schuchter, Lynn M ; Feldman, Michael D ; Ishwaran, Hemant ; Vonderheide, Robert H ; Maity, Amit ; Wherry, E.  John ; Minn, Andy J

Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell [...]

Cet article analyse les travaux récents sur le rôle des progestatifs dans le traitement des patientes atteintes d'un cancer du sein

Deciphering the divergent roles of progestogens in breast cancer

Carroll, Jason S. ; Hickey, Theresa E. ; Tarulli, Gerard A. ; Williams, Michael ; Tilley, Wayne D.

Most breast cancers are driven by oestrogen receptor-[alpha]. Anti-oestrogenic drugs are the standard treatment for these breast cancers; however, treatment resistance is common, necessitating new therapeutic strategies. Recent preclinical and historical clinical studies support the use of progestogens to activate the progesterone receptor (PR) in breast cancers. However, widespread controversy exists regarding the role of progestogens in this disease, hindering the clinical implementation of [...]

Cette étude analyse la prévalence des séquelles neurologiques chez des patients atteints de cancer et ayant reçu une thérapie ciblée ou une immunothérapie

Neurological sequelae of cancer immunotherapies and targeted therapies

Wick, Wolfgang ; Hertenstein, Anne ; Platten, Michael

Neurological complications of cancer and of anticancer treatments can be substantially disabling to patients, especially with classic chemotherapies. As a rare but important complication, targeted therapies might also result in similar unwanted effects, partly because inhibition of VEGF is a common downstream effect. Therapeutic antibodies, such as the CD20-depleting antibody rituximab, and underlying haematological malignancies, can induce long-lasting cellular immunosuppression, predisposing [...]

Menée à partir de données portant sur 853 patients adultes atteints d'une leucémie myéloïde aiguë en phase de rémission complète, cette étude rétrospective compare l'efficacité, du point de vue du risque de récidive, de la survie sans progression, de la survie globale et de la mortalité sans récidive, d'un traitement combinant busulfan et melphalan et d'un traitement combinant busulfan and cyclophosphamide, avant une greffe autologue de cellules souches

Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission—Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: A retrospective study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Gorin, Norbert-Claude ; Labopin, Myriam ; Czerw, Tomasz ; Pabst, Thomas ; Blaise, Didier ; Dumas, Pierre-Yves ; Nemet, Damir ; Arcese, William ; Trisolini, Silvia Maria ; Wu, Depei ; Huynh, Anne ; Zuckerman, Tsila ; Meijer, Ellen ; Cagirgan, Seckin ; Cornelissen, Jan ; Houhou, Mohamed ; Polge, Emmanuelle ; Mohty, Mohamad ; Nagler, Arnon

BACKGROUND: Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS: From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first [...]

Mené sur 214 patients atteints d'un adénocarcinome gastro-œsophagien MET+, cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, de l'ajout de l'onartuzumab à un traitement de première ligne combinant fluorouracile, leucovorine et oxaliplatine

Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, met-positive gastroesophageal adenocarcinoma: The METgastric randomized clinical trial

Shah, M. A. ; Bang, Y. ; Lordick, F. ; et al.,

Importance : Dysregulation of the mesenchymal-epithelial transition (MET) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma (GEC). We report results of METGastric, a phase 3 trial of the MET inhibitor onartuzumab plus standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC. Objective : To determine whether the addition of onartuzumab to first-line fluorouracil, leucovorin, and oxaliplatin [...]

Menée sur 186 patients d'origine asiatique atteints d'un cancer du poumon non à petites cellules EGFR+ de stade avancé et inclus dans l'essai de phase III IPASS, cette étude compare l'efficacité, du point de vue de la survie sans progression et du taux de réponse objective, du géfitinib et d'un traitement combinant carboplatine et paclitaxel, en traitement de première ligne

Efficacy according to blind independent central review: post-hoc analyses from the Phase III, randomized, multicenter, IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced NSCLC

Wu, Yi-Long ; Saijo, Nagahiro ; Thongprasert, Sumitra ; Yang, James Chih-Hsin ; Han, Baohui ; Margono, Benjamin ; Chewaskulyong, Busayamas ; Sunpaweravong, Patrapim ; Ohe, Yuichiro ; Ichinose, Yukito ; Yang, Jin-ji ; Mok, Tony S. K. ; Young, Helen ; Haddad, Vincent ; Rukazenkov, Yuri ; Fukuoka, Masahiro

Objective : The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR [...]

Mené sur 101 patients atteints d'un carcinome à cellules claires du rein de stade métastatique, cet essai randomisé évalue l'intérêt, pour prolonger le délai avant la progression de la maladie ou avant le décès, d'alterner le pazopanib et l'évérolimus ou de traiter par pazopanib de façon continue

Alternating treatment with pazopanib and everolimus vs continuous pazopanib to delay disease progression in patients with metastatic clear cell renal cell cancer: The ROPETAR randomized clinical trial

Cirkel, G. A. ; Hamberg, P. ; Sleijfer, S. ; et al.,

Importance : To our knowledge, this is the first randomized clinical trial evaluating an alternating treatment regimen in an attempt to delay disease progression in clear cell renal cell carcinoma. Objective : To test our hypothesis that an 8-week rotating treatment schedule with pazopanib and everolimus delays disease progression, exhibits more favorable toxic effects, and improves quality of life when compared with continuous treatment with pazopanib. Design, Setting, and Participants : This [...]

Mené sur 94 patientes atteintes d'un cancer du sein HER2+, cet essai randomisé évalue l'efficacité et les effets indésirables du périndropil et du bisoprolol pour prévenir les cardiotoxicités du trastuzumab pendant toute la durée de la thérapie adjuvante

Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101–Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity

Edith Pituskin ; John R. Mackey ; Sheri Koshman ; Davinder Jassal ; Marshall Pitz ; Mark J. Haykowsky ; Joseph J. Pagano ; Kelvin Chow ; Richard B. Thompson ; Larissa J. Vos ; Sunita Ghosh ; Gavin Y. Oudit ; Justin A. Ezekowitz ; D. Ian Paterson

Purpose : The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2–overexpressing (HER2-positive) breast cancer is dose-independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure. We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity. Patients and Methods : In this double-blinded, placebo-controlled trial, [...]

Mené sur 101 patients atteints d'un carcinome épidermoïde de la tête et du cou récidivant et/ou métastatique, cet essai de phase II compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du cabazitaxel et du méthotrexate, après un traitement de première ligne à base de sels de platine

Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-Based Therapy

Machiels, Jean-Pascal Henry ; Van Maanen, Aline ; Vandenbulcke, Jean-Marie ; Filleul, Bertrand ; Seront, Emmanuel ; Henry, Stéphanie ; D’Hondt, Lionel ; Lonchay, Christophe ; Holbrechts, Stéphane ; Boegner, Petra ; Brohee, Dany ; Dequanter, Didier ; Louviaux, Ingrid ; Sautois, Brieuc ; Whenham, Nicolas ; Berchem, Guy ; Vanderschueren, Brigitte ; Fontaine, Christel ; Schmitz, Sandra ; Gillain, Aline ; Schoonjans, Joelle ; Rottey, Sylvie

Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia [...]

Mené sur 150 patients atteints d'un cancer rectal de stade II à III traité entre 2007 et 2013 (durée médiane de suivi : 39,7 mois), cet essai évalue, du point de vue du taux de réponse complète et de la régression du stade de la maladie, l'efficacité d'une chimioradiothérapie conventionnelle pré-opératoire par rapport à une radiothérapie de courte durée suivie d'une chirurgie différée

Preoperative conventional chemoradiotherapy versus short-course radiotherapy with delayed surgery for rectal cancer: results of a randomized controlled trial

Latkauskas, Tadas ; Pauzas, Henrikas ; Kairevice, Laura ; Petrauskas, Aleksandras ; Saladzinskas, Zilvinas ; Janciauskiene, Rasa ; Gudaityte, Jurate ; Lizdenis, Paulius ; Svagzdys, Saulius ; Tamelis, Algimantas ; Pavalkis, Dainius

Background : There still is no evidence which neoadjuvant therapy regimen for stage II–III rectal cancer is superior. The aim of this study was to compare results achieved after long-course chemoradiotherapy (CRT) with short-term radiotherapy (RT) followed by delayed surgery. Methods : A randomized trial was carried out between 2007–2013. One hundred fifty patients diagnosed with stage II–III rectal cancer were randomized into one of two neoadjuvant treatment arms: conventional [...]

Cet article présente les recommandations de l'"American Society for Radiation Oncology", complétées et adoptées par l'"American Society of Clinical Oncology", concernant l'utilisation de la radiothérapie, combinée au témozolomide, pour traiter un glioblastome

Radiation Therapy for Glioblastoma : American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Guideline

Sulman, Erik P. ; Ismaila, Nofisat ; Armstrong, Terri S. ; Tsien, Christina ; Batchelor, Tracy T. ; Cloughesy, Tim ; Galanis, Evanthia ; Gilbert, Mark ; Gondi, Vinai ; Lovely, Mary ; Mehta, Minesh ; Mumber, Matthew P. ; Sloan, Andrew ; Chang, Susan M.

Purpose : The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy for glioblastoma. Because of its relevance to the ASCO membership, ASCO reviewed the guideline and applied a set of procedures and policies used to critically examine guidelines developed by other organizations. Methods : The ASTRO guideline on radiation therapy for glioblastoma was reviewed for developmental rigor by methodologists. An ASCO endorsement panel updated the [...]

Menée auprès de 78 patients atteints d'un cancer invasif de la vessie (durée médiane de suivi : 15,9 mois), cette étude évalue la tolérabilité d'une chimiothérapie par gemcitabine en combinaison avec une radiothérapie concomitante et précédée ou non d'une chimiothérapie néo-adjuvante

Tolerability of Concurrent Chemoradiotherapy with Gemcitabine (GemX), with and without prior Neoadjuvant Chemotherapy in Muscle Invasive Bladder Cancer

Thompson, Catherine ; Joseph, Nuradh ; Sanderson, Benjamin ; Logue, John ; Wylie, James ; Elliott, Tony ; Lyons, Jeanette ; Anandadas, Carmel ; Choudhury, Ananya

Purpose : The aim of this study is to assess the tolerability of concurrent chemoradiotherapy with gemcitabine (GemX) in muscle invasive bladder cancer (MIBC) following neoadjuvant chemotherapy (neoGemX) using patient and provider reported outcomes. Materials and Methods : Seventy eight patients were treated with GemX. Thirty-eight received prior neoadjuvant chemotherapy (NAC). Patients were prospectively assessed during treatment and at 6 weeks and 12 months post treatment completion. [...]

Cet article analyse les enjeux associés à l'évaluation de thérapies ciblées dans le cadre d'essais de type "panier", pour lesquels seule la présence d'une cible moléculaire est requise, indépendamment de la localisation de la tumeur

Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency

Cunanan, Kristen M. ; Gonen, Mithat ; Shen, Ronglai ; Hyman, David M. ; Riely, Gregory J. ; Begg, Colin B. ; Iasonos, Alexia

The current oncology drug development landscape is dominated by efforts to create therapies that are mechanistically designed to improve outcomes for patients with cancers that harbor specific molecular aberrations, which often occur across a variety of tumor types. In the evaluation of targeted therapies, basket trials have emerged as an approach to test the hypothesis that targeted therapies may be effective independent of tumor histology, as long as the molecular target is present. However, [...]

A partir de données portant sur 2 823 essais randomisés de phase III ou IV enregistrés dans la base clinicaltrials.gov en juin 2015, cette étude évalue la proportion des essais dont les résultats affichés comportent un effet thérapeutique statistiquement significatif

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials

Dechartres, Agnes ; Bond, Elizabeth G. ; Scheer, Jordan ; Riveros, Carolina ; Atal, Ignacio ; Ravaud, Philippe

Background : Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. Methods : We searched ClinicalTrials.gov in [...]

Cet article analyse les enjeux associés à l'amélioration de la pertinence clinique des essais contrôlés et randomisés en oncologie

Relevance of randomised controlled trials in oncology

Tannock, Ian F. ; Amir, Eitan ; Booth, Christopher M. ; Niraula, Saroj ; Ocana, Alberto ; Seruga, Bostjan ; Templeton, Arnoud J. ; Vera-Badillo, Francisco

Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather [...]