Cet article passe en revue les études concernant l'utilisation de nanoparticules d'or pour sensibiliser les cellules tumorales aux rayonnements ionisants, puis décrit les différentes étapes qui seront nécessaires avant de pouvoir utiliser en routine ce type de radiothérapie

A Roadmap for a New Academic Pathway for Global Radiation Oncology

J. Schuemann, ; R. Berbeco, ; D. Chithrani, ; S. Cho, ; R. Kumar, ; S. McMahon, ; S. Sridhar, ; S. Krishnan

The past decade has seen a dramatic increase in interest in the use of Gold Nanoparticles (GNPs) as radiation sensitizers for radiotherapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs’ efficacy at sensitizing tumors in both in vitro and in vivo systems to [...]

Menée à partir de données portant sur 408 patients atteints d'un cancer rectal traité entre 2003 et 2013, cette étude évalue, du point de vue des complications et de la mortalité, l'intérêt d'une résection laparoscopique et d'une intervention chirurgicale par voie ouverte en fonction de l'âge des patients (âge inférieur ou supérieur à 80 ans)

Morbidity after laparoscopic and open rectal cancer surgery: a comparative analysis of morbidity in octogenarians and younger patients

Landi, Filippo ; Vallribera, Francesc ; Rivera, Jose Pablo ; Bertoli, Paolo ; Armengol, Manuel ; Espin, Eloy

Aim : Although the oncological adequacy of laparoscopic rectal resection (LR) appears equivalent to open (OR), its benefit is controversial in the elderly. The aim of this study was to investigate the influence of LR on morbidity and mortality in octogenarians. Method : This was a retrospective analysis of all patients who underwent rectal surgery for cancer between 2003 and 2013 in a teaching hospital. The primary aim of this study was to assess the influence of surgical approach on mortality [...]

Cet article passe en revue les avancées récentes de la radiothérapie dans le traitement des cancers du sein puis analyse les bénéfices thérapeutiques associés

Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes

Currey, Adam D. ; Bergom, Carmen ; Kelly, Tracy R. ; Wilson, J. Frank

Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of [...]

Cet article analyse les avantages et les inconvénients des techniques chirurgicales utilisées pour le traitement des cancers primitifs du sein non détectables par la palpation, puis identifie des orientations futures pour le développement de nouvelles technologies

Surgical treatment of nonpalpable primary invasive and in situ breast cancer

Ahmed, Muneer ; Rubio, Isabel T. ; Klaase, Joost M. ; Douek, Michael

Breast cancer is the most-common cancer among women worldwide, and over one-third of all cases diagnosed annually are nonpalpable at diagnosis. The increasingly widespread implementation of breast-screening programmes, combined with the use of advanced imaging modalities, such as magnetic resonance imaging (MRI), will further increase the numbers of patients diagnosed with this disease. The current standard management for nonpalpable breast cancer is localized surgical excision combined with [...]

Menée sur 85 patientes atteintes d'un cancer du col utérin de stade localement avancé et traitées entre 2007 et 2014 (durée moyenne de suivi : 36 mois), cette étude évalue l'efficacité, du point de vue du contrôle local de la maladie, de la survie spécifique et de la survie globale, et la toxicité d'un traitement comportant une radiothérapie externe, une chimiothérapie concomitante par cisplatine puis une curiethérapie adaptative guidée par l'IRM

Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: A mono-institutional experience

Lakosi, Ferenc ; de Cuypere, Marjoelin ; Viet Nguyen, Paul ; Jansen, Nicolas ; Warlimont, Bernard ; Gulyban, Akos ; Gennigens, Christine ; Seidel, Laurence ; Delbecque, Katty ; Coucke, Philippe ; Hermesse, Johanne ; Kridelka, Frederic

Background. To evaluate efficacy and toxicity of radio-chemotherapy (RCT) and MR-guided pulsed-dose-rate (PDR) adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC). Material and methods. Between 2007 and 2014 85 patients with FIGO stage 1B1 N+ or ≥ 1B2 cervical cancer were treated with RCT+ IGABT. The treatment consisted of a pelvic± paraaortic external beam radiotherapy (EBRT) (45–50.4 Gy ± 10 Gy boost to primary tumor and/or to pathologic lymph nodes) with concurrent [...]

Cet article passe en revue les études concernant l'efficacité, la sécurité et les limites de la radiothérapie corporelle stéréotaxique dans le traitement des cancers de la tête et du cou

Stereotactic body radiotherapy for head and neck cancer: an addition to the armamentarium against head and neck cancer

Karam, Irene ; Poon, Ian ; Lee, Justin ; Liu, Stanley ; Higgins, Kevin ; Enepekides, Danny ; Sahgal, Arjun ; Lo, Simon S.

In the recent years, stereotactic body radiation therapy (SBRT) has emerged as a potential therapy for head and neck malignancies. Although early results appear to be promising, serious acute and late effects have been observed, mainly in patients who have had prior external beam radiotherapy. This review will discuss the radiobiology of SBRT, clinical rationale and outcomes for SBRT in head and neck cancers and focus on the benefits and potential limitations in both de novo and re-irradiation [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes suggérant l'intérêt de développer des inhibiteurs de la kinase d'adhésion focale pour le traitement des patients atteints d'un carcinome épidermoïde

Nuclear FAK Controls Chemokine Transcription, Tregs, and Evasion of Anti-tumor Immunity

Serrels, Alan ; Lund, Tom ; Serrels, Bryan ; Byron, Adam ; McPherson, Rhoanne C ; von Kriegsheim, Alexander ; Gómez-Cuadrado, Laura ; Canel, Marta ; Muir, Morwenna ; Ring, Jennifer E ; Maniati, Eleni ; Sims, Andrew H ; Pachter, Jonathan A ; Brunton, Valerie G ; Gilbert, Nick ; Anderton, Stephen M ; Nibbs, Robert J B. ; Frame, Margaret C

Focal adhesion kinase (FAK) promotes anti-tumor immune evasion. Specifically, the kinase activity of nuclear-targeted FAK in squamous cell carcinoma (SCC) cells drives exhaustion of CD8+ T cells and recruitment of regulatory T cells (Tregs) in the tumor microenvironment by regulating chemokine/cytokine and ligand-receptor networks, including via transcription of Ccl5, which is crucial. These changes inhibit antigen-primed cytotoxic CD8+ T cell activity, permitting growth of FAK-expressing [...]

Menée in vitro et in vivo sur des modèles de leucémie myéloïde aiguë, cette étude met en évidence des mécanismes suggérant l'intérêt de développer des thérapies ciblées sur les kinases du complexe Mediator

Mediator kinase inhibition further activates super-enhancer-associated genes in AML

Pelish, Henry E. ; Liau, Brian B. ; Nitulescu, Ioana I. ; Tangpeerachaikul, Anupong ; Poss, Zachary C. ; Da Silva, Diogo H. ; Caruso, Brittany T. ; Arefolov, Alexander ; Fadeyi, Olugbeminiyi ; Christie, Amanda L. ; Du, Karrie ; Banka, Deepti ; Schneider, Elisabeth V. ; Jestel, Anja ; Zou, Ge ; Si, Chong ; Ebmeier, Christopher C. ; Bronson, Roderick T. ; Krivtsov, Andrei V. ; Myers, Andrew G. ; Kohl, Nancy E. ; Kung, Andrew L. ; Armstrong, Scott A. ; Lemieux, Madeleine E. ; Taatjes, Dylan J. ; Shair, Matthew D.

Super-enhancers (SEs), which are composed of large clusters of enhancers densely loaded with the Mediator complex, transcription factors and chromatin regulators, drive high expression of genes implicated in cell identity and disease, such as lineage-controlling transcription factors and oncogenes. BRD4 and CDK7 are positive regulators of SE-mediated transcription. By contrast, negative regulators of SE-associated genes have not been well described. Here we show that the Mediator-associated [...]

Cet article passe en revue les perspectives thérapeutiques offertes par le développement des immunothérapies ciblées sur les points de contrôle immunitaire pour les patients atteints d'un mésothéliome

Targeting immune checkpoints: new opportunity for mesothelioma treatment?

Marcq, Elly ; Pauwels, Patrick ; Van Meerbeeck, Jan P. ; Smits, Evelien L. J.

Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. [...]

Menée à l'aide de modèles murins de cancer du poumon non à petites cellules avec réarrangements ALK, cette étude met en évidence l'activité antitumorale d'un vaccin thérapeutique contre ALK, seul ou en combinaison avec une thérapie ciblée anti ALK

Efficacy of a cancer vaccine against ALK-rearranged lung tumors

Voena, Claudia ; Menotti, Matteo ; Mastini, Cristina ; Di Giacomo, Filomena ; Longo, Dario L ; Castella, Barbara ; BoggioMerlo, Maria Elena ; Ambrogio, Chiara ; Wang, Qi ; Minero, Valerio Giacomo ; Poggio, Teresa ; Martinengo, Cinzia ; D'Amico, Lucia ; Panizza, Elena ; Mologni, L. ; Cavallo, Federica ; Altruda, Fiorella ; Butaney, Mohit ; Capelletti, Marzia ; Inghirami, Giorgio ; Jänne, Pasi A. ; Chiarle, Roberto

Non-Small Cell Lung Cancer (NSCLC) harboring Anaplastic Lymphoma Kinase (ALK) gene rearrangements is successfully treated with ALK tyrosine kinase inhibitors (TKIs) for only a limited amount of time as most cases relapse due to the development of drug resistance. Here we show that a vaccine against ALK induced a strong and specific immune response that impaired the growth of ALK-positive lung tumors in mouse models prophylactically and therapeutically. The ALK vaccine was efficacious also in [...]

Mené sur 48 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale du pévonédistat, un inhibiteur de l'enzyme activatrice de NEDD8

Phase I Study of the Investigational NEDD8-activating Enzyme Inhibitor Pevonedistat (TAK-924/MLN4924) in Patients with Advanced Solid Tumors

Sarantopoulos, John ; Shapiro, Geoffrey I. ; Cohen, Roger B. ; Clark, Jeffrey W ; Kauh, John S ; Weiss, Glen J ; Cleary, James M. ; Mahalingam, Devalingam ; Pickard, Michael D. ; Faessel, Helene ; Berger, Allison J ; Burke, Kristine ; Mulligan, George ; Dezube, Bruce J ; Harvey, R. Donald

Purpose: To determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the investigational NEDD8-activating enzyme (NAE) inhibitor pevonedistat (TAK-924/MLN4924), and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with advanced non-hematological malignancies Experimental Design: Pevonedistat was administered via 60-minute intravenous infusion on Days 1-5 (schedule A, n=12), or Days 1, 3, and 5 (schedules B, n=17, and C, n=19) of 21-day [...]

Mené sur 252 patients atteints d'une leucémie myéloïde aiguë (âge compris entre 40 et 65 ans), cet essai de phase III compare l'efficacité, du point de vue de la mortalité à 1 an, et la toxicité de deux combinaisons (busulfan-cyclophosphamide et busulfan-fludarabine) pour le conditionnement à une greffe allogénique de cellules souches hématopoïétiques

Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial

Rambaldi, Alessandro ; Grassi, Anna ; Masciulli, Arianna ; Boschini, Cristina ; Micò, Maria Caterina ; Busca, Alessandro ; Bruno, Benedetto ; Cavattoni, Irene ; Santarone, Stella ; Raimondi, Roberto ; Montanari, Mauro ; Milone, Giuseppe ; Chiusolo, Patrizia ; Pastore, Domenico ; Guidi, Stefano ; Patriarca, Francesca ; Risitano, Antonio M. ; Saporiti, Giorgia ; Pini, Massimo ; Terruzzi, Elisabetta ; Arcese, William ; Marotta, Giuseppe ; Carella, Angelo Michele ; Nagler, Arnon ; Russo, Domenico ; Corradini, Paolo ; Alessandrino, Emilio Paolo ; Torelli, Giovanni Fernando ; Scimè, Rosanna ; Mordini, Nicola ; Oldani, Elena ; Marfisi, Rosa Maria ; Bacigalupo, Andrea ; Bosi, Alberto

Background : The standard busulfan–cyclophosphamide myeloablative conditioning regimen is associated with substantial non-relapse mortality in patients older than 40 years with acute myeloid leukaemia who are undergoing allogeneic stem-cell transplantation. Because the combination of busulfan plus fludarabine has been proposed to reduce non-relapse mortality, we aimed to compare this treatment with busulfan plus cyclophosphamide as a preparative regimen in these patients. Methods : We did an [...]

Mené sur 529 patients atteints d'un mélanome métastatique, cet essai randomisé de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du nab-paclitaxel et de la dacarbazine en traitement de première ligne

A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma

Hersh, E. M. ; Del Vecchio, M. ; Brown, M. P. ; Kefford, R. ; Loquai, C. ; Testori, A. ; Bhatia, S. ; Gutzmer, R. ; Conry, R. ; Haydon, A. ; Robert, C. ; Ernst, S. ; Homsi, J. ; Grob, J. J. ; Kendra, K. ; Agarwala, S. S. ; Li, M. ; Clawson, A. ; Brachmann, C. ; Karnoub, M. ; Elias, I. ; Renschler, M. F. ; Hauschild, A.

Background : The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. Patients and methods : Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m2 on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m2 every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). [...]

Mené sur 150 patientes atteintes d'un cancer de l'épithélium ovarien entre 1990 et 1995 (durée médiane de suivi : 19,1 ans), cet essai international randomisé évalue l'efficacité, du point de vue de la survie globale, d'une hormonothérapie adjuvante

Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial

Eeles, Rosalind A. ; Morden, James P. ; Gore, Martin ; Mansi, Janine ; Glees, John ; Wenczl, Miklos ; Williams, Christopher ; Kitchener, Henry ; Osborne, Richard ; Guthrie, David ; Harper, Peter ; Bliss, Judith M.

Purpose : To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Patients and Methods : Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, [...]

Mené sur 582 patients atteints d'un cancer non épidermoïde du poumon non à petites cellules ayant progressé après une chimiothérapie à base de sels de platine, cet essai randomisé international de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité du nivolumab par comparaison avec le docétaxel

Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

Borghaei, Hossein ; Paz-Ares, Luis ; Horn, Leora ; Spigel, David R. ; Steins, Martin ; Ready, Neal E. ; Chow, Laura Q. ; Vokes, Everett E. ; Felip, Enriqueta ; Holgado, Esther ; Barlesi, Fabrice ; Kohlhäufl, Martin ; Arrieta, Oscar ; Burgio, Marco Angelo ; Fayette, Jérôme ; Léna, Hervé ; Poddubskaya, Elena ; Gerber, David E. ; Gettinger, Scott N. ; Rudin, Charles M. ; Rizvi, Naiyer ; Crino, Lucio ; Blumenschein, George R. ; Antonia, Scott J. ; Dorange, Cécile ; Harbison, Christopher T. ; Graf Finckenstein, Friedrich ; Brahmer, Julie R.

BACKGROUND : Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, disrupts PD-1–mediated signaling and may restore antitumor immunity. METHODS : In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non–small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of [...]

Mené en Espagne sur 1 384 patientes atteintes d'un cancer du sein opérable avec envahissement ganglionnaire, cet essai évalue l'efficacité, du point de vue de la survie sans récidive invasive, et la toxicité de l'ajout de capécitabine à un traitement adjuvant combinant épirubicine et docétaxel (durée médiane de suivi : 6,6 ans)

Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study

Martin, Miguel ; Ruiz Simón, Amparo ; Ruiz Borrego, Manuel ; Ribelles, Nuria ; Rodríguez-Lescure, Álvaro ; Muñoz-Mateu, Montserrat ; González, Sonia ; Margelí Vila, Mireia ; Barnadas, Agustí ; Ramos, Manuel ; Del Barco Berron, Sonia ; Jara, Carlos ; Calvo, Lourdes ; Martínez-Jáñez, Noelia ; Mendiola Fernández, César ; Rodríguez, César A. ; Martínez de Dueñas, Eduardo ; Andrés, Raquel ; Plazaola, Arrate ; de la Haba-Rodríguez, Juan ; López-Vega, José Manuel ; Adrover, Encarna ; Ballesteros, Ana Isabel ; Santaballa, Ana ; Sanchez-Rovira, Pedro ; Baena-Cañada, José M. ; Casas, Maribel ; del Carmen Cámara, María ; Carrasco, Eva Maria ; Lluch, Ana

Purpose : Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC. Patients and Methods : Patients with operable node-positive BC (T1-3/N1-3) were eligible. After surgery, 1,384 patients were randomly assigned to receive epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m2, respectively, × four cycles), followed by docetaxel (100 [...]

Menée en France sur 123 patientes atteintes d'un cancer du sein ER+ HER2- de type luminal ayant développé une résistance à des traitements hormonaux, cette étude analyse l'efficacité et la toxicité de l'évérolimus administré en pratique clinique, par comparaison avec les résultats obtenus dans le cadre de l'essai Bolero-2

Efficacy and tolerance of everolimus in 123 consecutive advanced ER positive, HER2 negative breast cancer patients. A two center retrospective study

Chocteau-Bouju, D. ; Chakiba, C. ; Mignot, L. ; Madranges, N. ; Pierga, J. Y. ; Beuzeboc, P. ; Quenel-Tueux, N. ; Dieras, V. ; Bonnefoi, H. ; Debled, M. ; Cottu, P.

Background : Since the publication of the Bolero-2 trial, everolimus has entered the routine care for advanced endocrine resistant luminal breast cancer (BC). We evaluated our practice 2 years after the French marketing authorization (July 2012). Methods : One hundred and twenty three consecutive patients were treated with everolimus combined with endocrine treatment in two French Cancer Centers. All patients had luminal (ER positive, HER2 negative) BC and had been previously treated with [...]

Menée à partir des données de deux essais incluant au total 119 patients atteints d'un cancer invasif de la vessie (durée médiane de suivi : 5,9 ans), cette étude évalue, du point de vue du taux de cystectomie de sauvetage, de la survie spécifique et de la survie globale, l'intérêt d'un traitement conservateur multimodal suivi d'une chimioradiothérapie de consolidation chez les patients dont la réponse tumorale à une chimioradiothérapie d'induction est presque complète

Long-term Outcomes among Patients Who Achieve Complete or Near-complete Responses after the Induction Phase of Bladder Preserving Combined Modality Therapy for Muscle-invasive Bladder Cancer: A Pooled Analysis of NRG Oncology/RTOG 9906 and 0233

Mitin, Timur ; George, Asha ; Zietman, Anthony L. ; Heney, Niall M. ; Kaufman, Donald S. ; Uzzo, Robert G. ; Dreicer, Robert ; Wallace, H. James, III ; Souhami, Luis ; Dobelbower, M. Chris ; Sandler, Howard M. ; Shipley, William U.

Purpose : Bladder preserving combined-modality therapy for muscle-invasive bladder cancer (MIBC) includes transurethral resection and concurrent chemo-RT given in two phases. After the induction phase with chemo-RT to 40 Gy the tumor response is assessed by cystoscopic biopsies and urine cytology. Early salvage cystectomy is promptly offered in case of persistent disease, otherwise patients proceed to consolidation chemo-RT to 64 Gy. Two NRG Oncology RTOG bladder protocols allowed patients with [...]

Cet article passe en revue les études sur les mécanismes biologiques expliquant la résistance des cellules souches cancéreuses aux rayonnements ionisants

Radiation resistance: Cancer stem cells (CSCs) and their enigmatic pro-survival signaling

Skvortsova, Ira ; Debbage, Paul ; Kumar, Vinod ; Skvortsov, Sergej

Despite the fact that radiation therapy is a highly effective therapeutic approach, a small intratumoral cell subpopulation known as “cancer stem cells” (CSCs) is radiation-resistant and possesses specific molecular properties protecting it against radiation-induced damage. The exact mechanisms of this radioresistance are still not fully elucidated, but they relate to these cells’ enhanced DNA repair capacities and their low intracellular ROS concentrations, resulting from their up-regulation [...]

Cet article passe en revue les études concernant les effets des rayonnements ionisants sur la capacité des cellules cancéreuses à envahir les tissus sains, puis présente les voies moléculaires et les variations génétiques qui peuvent affecter ces effets

Irradiation induces diverse changes in invasive potential in cancer lines

Fujita, Mayumi ; Yamada, Shigeru ; Imai, Takashi

Cancer patients without metastasis are generally considered as candidates for curative localized radiation therapy. However, while the benefits of localized radiation have been demonstrated by many clinical studies, recurrences or distant metastases that develop after local treatment remain a major therapeutic challenge. Several in vitro and in vivo studies have reported that irradiation may subsequently alter tumor aggression by reducing or promoting the invasiveness of the remaining cancer [...]

Cet article passe en revue les travaux récents sur l'évaluation préclinique de traitements anticancéreux à l'aide de modèles murins

Preclinical Mouse Cancer Models: A Maze of Opportunities and Challenges

Day, Chi-Ping ; Merlino, Glenn ; Van Dyke, Terry

Significant advances have been made in developing novel therapeutics for cancer treatment, and targeted therapies have revolutionized the treatment of some cancers. Despite the promise, only about five percent of new cancer drugs are approved, and most fail due to lack of efficacy. The indication is that current preclinical methods are limited in predicting successful outcomes. Such failure exacts enormous cost, both financial and in the quality of human life. This Primer explores the current [...]

Cet article présente les caractéristiques de l'essai britannique appelé "National Lung Matrix Trial" visant à évaluer l'efficacité de diverses combinaisons de thérapies ciblées, choisies sur la base de biomarqueurs moléculaires identifiés par des techniques de séquençage à haut débit, pour le traitement de patients atteints d'un cancer avancé du poumon non à petites cellules

The National Lung Matrix Trial: Translating the Biology of Stratification in Advanced Non-Small Cell Lung Cancer

Middleton, G. ; Crack, L.R. ; Popat, S. ; Swanton, C. ; Hollingsworth, S. J. ; Buller, R. ; Walker, I. ; Carr, H. ; Wherton, D. ; Billingham, L.J.

The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. The Cancer Research UK (CRUK) Stratified Medicine Programme 2 (SMP2) is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation there are 8 drugs are being used to target 17 molecular cohorts. The aim is to determine whether [...]

Menée aux Etats-Unis à partir des données du registre national des cancers portant sur 46 803 patients atteints d'un cancer du poumon non à petites cellules de stade IV diagnostiqué entre 2004 et 2012, cette étude analyse l'utilisation inappropriée d'une radiothérapie thoracique palliative, puis identifie les facteurs prédictifs associés

Prevalence and Predictors of Inappropriate Delivery of Palliative Thoracic Radiotherapy for Metastatic Lung Cancer

Koshy, Matthew ; Malik, Renuka ; Mahmood, Usama ; Husain, Zain ; Weichselbaum, Ralph R. ; Sher, David J.

Background : High-level evidence has established well-recognized standard treatment regimens for patients undergoing palliative chest radiotherapy (RT) for stage IV non–small cell lung cancer (NSCLC), including treating with fewer than 15 fractions of RT, and not delivering concurrent chemoradiation (CRT) because of its increased toxicity and limited efficacy in the palliative setting. Methods : The study included patients in the National Cancer Database from 2004 to 2012 with stage IV lung [...]

Cet article passe en revue les défis posés par la définition de critères de jugement intermédiaires dans les essais cliniques d'un traitement adjuvant chez des patients atteints d'un cancer de la prostate

The Development of Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP)

ICECaP Working Group

New systemic therapies have prolonged the lives of men with metastatic castration-resistant prostate cancer (mCRPC). Use of these therapies in the adjuvant setting when the disease may be micrometastatic and potentially more sensitive to therapies may decrease mortality from prostate cancer. However, the conduct of adjuvant prostate cancer clinical trials is hampered by taking longer than a decade to reach the meaningful endpoint of overall survival (OS) and the fact that many men never die [...]