Cet article décrit les principaux mécanismes du système immunitaire en réponse aux rayonnements ionisants et analyse les stratégies possibles pour exploiter au mieux cette réponse immunitaire radio-induite dans le cadre d'un traitement multimodal antitumoral

Radiotherapy in the age of cancer immunology : current concepts and future developments

Loi, Mauro ; Desideri, Isacco ; Greto, Daniela ; Mangoni, Monica ; Sottili, Mariangela ; Meattini, Icro ; Becherini, Carlotta ; Terziani, Francesca ; Paoli, Camilla Delli ; Olmetto, Emanuela ; Bonomo, Pierluigi ; Livi, Lorenzo

Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may [...]

A partir d'une revue systématique de la littérature publiée jusqu'en 2014 (13 essais incluant au total 8 189 patientes), cette méta-analyse compare, du point de vue du contrôle de la maladie, de la survie à 3 ans et de la toxicité, l'intérêt d'une radiothérapie avec fractionnement accéléré par rapport à une radiothérapie avec fractionnement standard chez les patientes atteintes d'un cancer du sein de stade précoce et ayant subi une tumorectomie

Hypofractionated whole breast radiotherapy in breast conservation for early-stage breast cancer: a systematic review and meta-analysis of randomized trials

Valle, Luca F. ; Agarwal, Surbhi ; Bickel, Kathleen E. ; Herchek, Haley A. ; Nalepinski, David C. ; Kapadia, Nirav S.

Purpose : Breast conservation therapy (BCT) for early-stage breast cancer involves lumpectomy followed by whole breast radiotherapy, which can involve either standard fractionation (SRT) or accelerated fractionation (ART). This systematic review and meta-analysis was performed to determine whether any benefit exists for ART or SRT. Materials and methods : We searched MEDLINE (1966–2014), all seven databases of the Cochrane Library (1968–2014), EMBASE (1974–2014), clinicaltrials.gov, ISRCTN, WHO [...]

A partir d'une revue de la littérature, cette étude identifie de nouveaux traitements dans le cancer de l'estomac

New Agents on the Horizon in Gastric Cancer

F. Lordick ; K. Shitara ; Y. Y. Janjigian

Background : Conventional cytotoxic chemotherapy has been the backbone of advanced gastric cancer treatment for decades and still represents a key element of the therapeutic armamentarium. However, only small increments in survival outcomes have been reached. A better understanding of genetic alterations and molecular signatures of gastric cancer has been reached in the last years. It will serve as a roadmap for better treatment stratification and future drug development. Materials and methods [...]

Menée à l'aide d'un modèle mathématique, cette étude met en évidence l'intérêt de normaliser le réseau vasculaire tumoral pour optimiser l'efficacité d'une chimiothérapie métronomique

Role of vascular normalization in benefit from metronomic chemotherapy

Mpekris, Fotios ; Baish, James W. ; Stylianopoulos, Triantafyllos ; Jain, Rakesh K.

Metronomic dosing of chemotherapy—defined as frequent administration at lower doses—has been shown to be more efficacious than maximum tolerated dose treatment in preclinical studies, and is currently being tested in the clinic. Although multiple mechanisms of benefit from metronomic chemotherapy have been proposed, how these mechanisms are related to one another and which one is dominant for a given tumor–drug combination is not known. To this end, we have developed a mathematical model that [...]

Menée in vitro, in vivo et à l'aide de l'algorithme DeMAND (Detecting Mechanism of Action based Network Dysregulation), cette étude identifie, pour les leucémies lymphoblastiques aiguës à lymphocytes T, des traitements ayant un effet synergique avec des inhibiteurs de NOTCH1

Synergistic antileukemic therapies in NOTCH1-induced T-ALL

Sanchez-Martin, Marta ; Ambesi-Impiombato, Alberto ; Qin, Yue ; Herranz, Daniel ; Bansal, Mukesh ; Girardi, Tiziana ; Paietta, Elisabeth ; Tallman, Martin S. ; Rowe, Jacob M. ; De Keersmaecker, Kim ; Califano, Andrea ; Ferrando, Adolfo A.

The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with

Menée sur des lignées cellulaires de cancer du côlon et à l'aide de xénogreffes sur des modèles murins, cette étude met en évidence l'intérêt d'une immunothérapie consistant à injecter par voie intraveineuse une souche atténuée de la bactérie Salmonella typhimurium, modifiée par génie génétique pour sécréter dans la tumeur la flagelline de la bactérie Vibrio vulnificus

Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin

Zheng, Jin Hai ; Nguyen, Vu H. ; Jiang, Sheng-Nan ; Park, Seung-Hwan ; Tan, Wenzhi ; Hong, Seol Hee ; Shin, Myung Geun ; Chung, Ik-Joo ; Hong, Yeongjin ; Bom, Hee-Seung ; Choy, Hyon E. ; Lee, Shee Eun ; Rhee, Joon Haeng ; Min, Jung-Joon

We report a method of cancer immunotherapy using an attenuated Salmonella typhimurium strain engineered to secrete Vibrio vulnificus flagellin B (FlaB) in tumor tissues. Engineered FlaB-secreting bacteria effectively suppressed tumor growth and metastasis in mouse models and prolonged survival. By using Toll-like receptor 5 (TLR5)–negative colon cancer cell lines, we provided evidence that the FlaB-mediated tumor suppression upon bacterial colonization is associated with TLR5-mediated host [...]

Mené sur 695 patients atteints d'une tumeur stromale gastro-intestinale de stade avancé, cet essai de phase II ré-évalue l'efficacité sur le long terme, du point de vue de la survie globale, de l'imatinib en fonction de la présence d'une mutation des gènes KIT ou PDGFRA, révélée grâce à une technologie de séquençage à haut débit

Correlation of long-term results of imatinib in advanced gastrointestinal stromal tumors with next-generation sequencing results: Analysis of Phase 3 SWOG Intergroup Trial S0033

Heinrich, M. ; Rankin, C. ; Blanke, C. D. ; et al.,

Importance : After identification of activating mutations of the KIT gene in gastrointestinal stromal tumor (GIST)—the most common sarcomaof the gastrointestinal tract—a phase 2 study demonstrated efficacy of imatinib mesylate in patients with metastatic GIST harboring a KIT exon 11 mutation. Initial results of long-term follow-up have found a survival benefit in this subgroup of patients. Obective : To assess the long-term survival of patients with GIST who were treated in SWOG study S0033 and [...]

Menée en France à partir de données médicales portant sur 131 patients atteints d'un cancer traité par anti-PD-1/PD-L1 dans le cadre d'un essai de phase I, cette étude met en évidence, chez certains de ces patients, une progression inhabituelle de la maladie se caractérisant notamment par une croissance tumorale accélérée

Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1

Champiat, Stéphane ; Dercle, Laurent ; Ammari, Samy ; Massard, Christophe ; Hollebecque, Antoine ; Postel-Vinay, Sophie ; Chaput, Nathalie ; Eggermont, Alexander ; Marabelle, Aurelien ; Soria, Jean-Charles ; Ferte, Charles

Purpose : While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history, and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown. Experimental Design : Medical records from all patients (N = 218) prospectively [...]

A partir d'une revue systématique de la littérature en matière d'essais cliniques ayant évalué le sorafénib avant sa mise sur le marché, cette étude analyse les bénéfices cliniques observés et les risques encourus par les 11 355 patients ayant participé à ces multiples essais

Inefficiencies and Patient Burdens in the Development of the Targeted Cancer Drug Sorafenib: A Systematic Review

Mattina, James ; Carlisle, Benjamin ; Hachem, Yasmina ; Fergusson, Dean ; Kimmelman, Jonathan

Failure in cancer drug development exacts heavy burdens on patients and research systems. To investigate inefficiencies and burdens in targeted drug development in cancer, we conducted a systematic review of all prelicensure trials for the anticancer drug, sorafenib (Bayer/Onyx Pharmaceuticals). We searched Embase and MEDLINE databases on October 14, 2014, for prelicensure clinical trials testing sorafenib against cancers. We measured risk by serious adverse event rates, benefit by objective [...]

Mené sur 23 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée, l'activité antitumorale et la toxicité de l'émibétuzumab, un anticorps bivalent inhibant la voie de signalisation MET, en monothérapie et en combinaison avec l'erlotinib

A First-in-Human Phase I Study of a Bivalent MET Antibody, Emibetuzumab (LY2875358), as Monotherapy and in Combination with Erlotinib in Advanced Cancer

Rosen, Lee S. ; Goldman, Jonathan W. ; Algazi, Alain P. ; Turner, P. Kellie ; Moser, Brian ; Hu, Tianle ; Wang, Xuejing Aimee ; Tuttle, Jay ; Wacheck, Volker ; Wooldridge, James E. ; Banck, Michaela

Purpose: The MET/HGF pathway regulates cell proliferation and survival and is dysregulated in multiple tumors. Emibetuzumab (LY2875358) is a bivalent antibody that inhibits HGF-dependent and HGF-independent MET signaling. Here, we report dose escalation results from the first-in-human phase I trial of emibetuzumab. Experimental Design: The study comprised a 3+3 dose escalation for emibetuzumab monotherapy (Part A) and in combination with erlotinib (Part A2). Emibetuzumab was administered i.v. [...]

Menée à partir de données portant sur 40 patients atteints d'une leucémie lymphoïde chronique (dont 21 présentant une délétion 17p; âge médian : 65 ans), cette étude analyse l'efficacité, du point de vue du taux de réponse globale, de la survie sans progression et de la survie globale, d'un traitement combinant ibrutinib et rituximab (durée médiane de suivi : 47 mois)

Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia

Jain, Preetesh ; Keating, Michael J. ; Wierda, William G. ; Sivina, Mariela ; Thompson, Philip A. ; Ferrajoli, Alessandra ; Estrov, Zeev ; Kantarjian, Hagop ; O’Brien, Susan ; Burger, Jan A.

Background: Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with TP53 mutations. Ibrutinib is broadly indicated for the treatment of patients with CLL and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents remains controversial. Methods: We report the long-term outcome [median follow-up of 47 months (range, 36–51 months)] [...]

Menée aux Etats-Unis à partir de données portant sur 320 patients atteints d'une leucémie lymphoïde chronique et inclus dans des essais cliniques évaluant l'efficacité de l'ibrutinib entre 2010 et 2015, cette étude rétrospective analyse les facteurs associés à l'arrêt du traitement, puis évalue l'impact de cet arrêt sur la survie

Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib

Jain, Preetesh ; Thompson, Philip A. ; Keating, Michael ; Estrov, Zeev ; Ferrajoli, Alessandra ; Jain, Nitin ; Kantarjian, Hagop ; Burger, Jan A. ; O'Brien, Susan ; Wierda, William G.

BACKGROUND: Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. METHODS: Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively [...]

Mené sur 34 patients atteints d'un lymphome T cutané réfractaire ou récidivant, cet essai de phase I/II évalue la dose maximale tolérée et la dose recommandée de pralatrexate combiné au bexarotène dispensé par voie orale

Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrexate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma

Duvic, Madeleine ; Kim, Youn H. ; Zinzani, Pier Luigi ; Horwitz, Steven

Purpose:Pralatrexate is a folic acid analog metabolic inhibitor similar to methotrexate,that has shown tolerability and efficacy with an overall response rate of 45% in a phase 1 dose de-escalation study of patients with relapsed/refractory cutaneous T-cell lymphoma CTCL. Experimental Design: The object of this phase I/II open-label, multi-center clinical trial was to determine the maximum tolerated dose (MTD) and recommended dose of pralatrexate plus oral bexarotene in 34 patients with [...]

Mené sur 43 patients atteints d'un carcinome du canal anal de stade avancé exprimant PD-L1, cet essai de phase Ib évalue l'efficacité, du point de vue du taux de réponse complète, et la toxicité du pembrolizumab, un anticorps monoclonal ciblant le récepteur PD-1

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal

P. A. Ott; ; S. A. Piha-Paul; ; P. Munster; ; M. J. Pishvaian; ; E. M. J. van Brummelen; ; R. B. Cohen; ; C. Gomez-Roca; ; S. Ejadi; ; M. Stein; ; E. Chan

Background: Safety and efficacy of pembrolizumab, a humanized programmed death 1 (PD-1) monoclonal antibody, was assessed in KEYNOTE-028, a multicohort, phase Ib trial for patients with programmed death ligand 1 (PD-L1)–positive advanced solid tumors. We report results for the cohort of patients with advanced carcinoma of the anal canal. Patients and methods: Patients with PD-L1–positive tumors (≥1%) received intravenous pembrolizumab 10 mg/kg once every 2 weeks for up to 2 years or until [...]

Mené sur 101 patients atteints d'un cancer du poumon non à petites cellules exprimant PD-L1, cet essai de phase I analyse l'efficacité, du point de vue du taux de réponse objective, et la toxicité du pembrolizumab en traitement de première ligne

Pembrolizumab as first-line therapy for patients with PD-L1–positive advanced non–small cell lung cancer: a phase 1 trial

R. Hui; ; E. B. Garon; ; J. W. Goldman; ; N. B. Leighl; ; M. D. Hellmann; ; A. Patnaik; ; L. Gandhi; ; J. P. Eder; ; M.-J. Ahn; ; L. Horn

Background: Pembrolizumab improved survival as first- and second-line therapy compared with chemotherapy in patients with highly programmed death ligand 1 (PD-L1) expressing advanced non–small cell lung cancer (NSCLC). We report the long-term safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy. Patients and methods: In the open-label phase 1b KEYNOTE-001 trial, treatment-naive patients [...]

Mené sur 39 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'une chimiothérapie métronomique à base de paclitaxel et gemcitabine en combinaison avec du bévacizumab

Pilot Phase II Study of Metronomic Chemotherapy in Combination with Bevacizumab in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

Benjamin S. Jones ; Mary S. Jerome ; Deborah Miley ; Bradford E. Jackson ; Mollie R. DeShazo ; Vishnu V.B. Reddy ; Karan P. Singh ; Olivia C. Brown ; Francisco Robert

Introduction : The goal of this study was to explore the efficacy and tolerability of metronomic chemotherapy, a novel anti-angiogenic treatment strategy, in combination with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC) Methods : Subjects with newly diagnosed stage IV NSCLC were treated with 4-week cycles of paclitaxel 80 mg/m2 and gemcitabine 300 mg/m2 weekly for three weeks, plus bevacizumab 10 mg/kg every two weeks. Radiologic assessments were performed every 8 [...]

A partir d'une revue des essais cliniques incluant des patients atteints d'un cancer du poumon non à petites cellules, cette étude analyse le rapport bénéfices cliniques/risques associés à des agents anti-angiogéniques, puis passe en revue les travaux récents sur l'identification de biomarqueurs prédictifs d'une réponse thérapeutique

Exploring the Benefit/Risk Associated with Antiangiogenic Agents for the Treatment of Non–Small Cell Lung Cancer Patients

Kurzrock, Razelle ; Stewart, David J.

Following the approval of bevacizumab, an antibody targeting VEGF-A, for advanced non-squamous non–small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)–targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti–VEGFR-1/2/3, platelet-derived growth factor [...]

Mené sur 158 patients atteints d'un cancer du poumon non à petites cellules de stade avancé ou métastatique (âge médian : 63 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du véliparib à un traitement de première intention combinant carboplatine et paclitaxel

Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non–Small Cell Lung Cancer

Suresh S. Ramalingam, ; Normand Blais, ; Julien Mazieres, ; Martin Reck, ; C. Michael Jones, ; Erzsebet Juhasz, ; Laszlo Urban, ; Sergey Orlov, ; Fabrice Barlesi, ; Ebenezer Kio, ; Ulrich Keiholz, ; Qin Qin, ; Jiang Qian, C ; aroline Nickner, ; Juliann Dziubinski, ; Hao Xiong, ; Peter Ansell, ; Mark McKee, ; Vincent Giranda, ; Vera Gorbunova

Purpose: PARP plays an important role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum compounds and has been safely combined with carboplatin and paclitaxel. The primary endpoint of this phase II trial determined whether addition of veliparib to carboplatin and paclitaxel improved progression-free survival (PFS) in previously untreated patients with advanced/metastatic non–small cell lung cancer. Experimental Design: Patients were randomized 2:1 to carboplatin and [...]

A partir de données portant sur 66 patientes atteintes d'un cancer du sein HER2+ de stade précoce (âge médian: 46 ans), cette étude rétrospective analyse le taux de réponse complète à une chimiothérapie néo-adjuvante à hautes doses de doxorubicine et cyclophosphamide suivie de paclitaxel, trastuzumab et pertuzumab

Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2-Positive Early Stage Breast Cancer: A Single Center Experience

Singh, Jasmeet C. ; Mamtani, Anita ; Barrio, Andrea ; Morrow, Monica ; Sugarman, Steven ; Jones, Lee W. ; Yu, Anthony F. ; Argolo, Daniel ; Smyth, Lilian M. ; Modi, Shanu ; Schweber, Sarah ; Boafo, Camilla ; Patil, Sujata ; Norton, Larry ; Baselga, Jose ; Hudis, Clifford A. ; Dang, Chau

Trastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 ‐positive patients. A retrospective analysis was performed of patients treated with dose‐dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported.An electronic medical record review was conducted of [...]

Cet article présente les mécanismes biologiques pouvant expliquer l'effet synergique de la radiothérapie et de l'immunothérapie, puis identifie des biomarqueurs susceptibles de prédire la réponse à ce type de traitement combiné

The synergistic effect of radiotherapy and immunotherapy : A promising but not simple partnership

Chajon, Enrique ; Castelli, Joël ; Marsiglia, Hugo ; Crevoisier, Renaud de

Radiotherapy (RT) is one of the main components in the treatment of cancer. The better understanding of the immune mechanisms associated with tumor establishment and how RT affects inflammation and immunity has led to the development of novel treatment strategies. Several preclinical studies support the use of RT in combination with immunotherapy obtaining better local and systemic tumor control. Current ongoing studies will provide information about the optimal RT approach, but the development [...]

Cet article analyse les données sur la neurotoxicité de divers traitements systémiques (chimiothérapies, thérapies ciblées, immunothérapies) en combinaison avec une radiothérapie crânienne pour traiter des métastases cérébrales ayant pour origine une tumeur solide

Use of Systemic Therapy Concurrent With Cranial Radiotherapy for Cerebral Metastases of Solid Tumors

Verduin, Maikel ; Zindler, Jaap D. ; Martinussen, Hanneke M. A. ; Jansen, Rob L. H. ; Croes, Sander ; Hendriks, Lizza E. L. ; Eekers, Danielle B. P. ; Hoeben, Ann

The incidence of brain metastases of solid tumors is increasing. Local treatment of brain metastases is generally straightforward: cranial radiotherapy (e.g., whole‐brain radiotherapy or stereotactic radiosurgery) or resection when feasible. However, treatment becomes more complex when brain metastases occur while other metastases, outside of the central nervous system, are being controlled with systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies). It is [...]

Menée à l'aide d'un modèle murin de cancer du poumon, cette étude montre que la suppression de la voie de signalisation de l'interféron de type I dans les cellules tumorales induit une résistance aux traitements anti-PD1 qui peut être levée par les rayonnements ionisants

Suppression of Type I IFN Signaling in Tumors Mediates Resistance to Anti-PD-1 Treatment That Can Be Overcome by Radiotherapy

Wang, Xiaohong ; Schoenhals, Jonathan E. ; Li, Ailin ; Valdecanas, David R. ; Ye, Huiping ; Zang, Fenglin ; Tang, Chad ; Tang, Ming ; Liu, Chang-Gong ; Liu, Xiuping ; Krishnan, Sunil ; Allison, James P. ; Sharma, Padmanee ; Hwu, Patrick ; Komaki, Ritsuko ; Overwijk, Willem W. ; Gomez, Daniel R. ; Chang, Joe Y. ; Hahn, Stephen M. ; Cortez, Maria Angelica ; Welsh, James W.

Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passaging of Kras-mutated, p53-deficient murine lung cancer cells (p53R172HΔg/+K-rasLA1/+) in a syngeneic host exposed to repetitive dosing with anti-mouse PD-1 antibodies. PD-L1 (CD274) [...]

Ce numéro spécial de la revue Cell présente un ensemble d'articles soulignant les récentes avancées majeures en matière de recherches sur les cancers

Cancer : The Road Ahead

Fighting cancer has been the life mission for generations of biologists and clinicians, and to this effort we dedicate this issue of Cell. This reviews issue highlights the converging paths in cancer research that are enabling changes in clinical treatment and removing obstacles between patients in need and access to effective care. Empowered by these breakthroughs, it is possible to imagine major gains against cancer’s relentless advance. In thinking about the scope of cancer research today, [...]

Cet article décrit la nécessité de mener, dans le cadre de la médecine personnalisée en cancérologie, des essais cliniques randomisés incluant 2 bras de randomisation, notamment dans le processus de développement et d'évaluation de nouvelles thérapies ciblées en association avec des biomarqueurs

Precision medicine needs randomized clinical trials

Saad, Everardo D. ; Paoletti, Xavier ; Burzykowski, Tomasz ; Buyse, Marc

The advent of precision medicine has prompted profound changes in clinical cancer research, and the rising numbers of new therapeutic agents pose challenges in terms of the most appropriate trial designs and effects on the drug-approval process. In the past 5 years, some remarkably efficacious drugs have been approved based on evidence from uncontrolled phase I trials. We challenge the view that the expected benefits from new drugs are generally sufficient to forgo a randomized trial with [...]

Cet article présente les recommandations, issues d'une conférence internationale de consensus, sur la prise en charge d'un chordome ayant récidivé loco-régionalement

Best practices for the Management of Local-regional Recurrent Chordoma. A Position Paper by the Chordoma Global Consensus Group

S. Stacchiotti ; A. Gronchi ; P. Fossati ; T. Akiyama ; C. Alapetite ; M. Baumann ; J. Y. Blay ; S. Bolle ; S. Boriani ; P. Bruzzi ; R. Capanna ; A. Caraceni ; R. Casadei ; V. Colia ; J. Debus ; T. Delaney ; A. Desai ; P. Dileo ; S. Dijkstra ; F. Doglietto ; A. Flanagan ; S. Froelich ; P. A. Gardner ; H. Gelderblom ; Z. L. Gokaslan ; R. Haas ; C. Heery ; N. Hindi ; P. Hohenberger ; F. Hornicek ; R. Imai ; L. Jeys ; R. L. Jones ; B. Kasper ; A. Kawai ; M. Krengli ; A. Leithner ; I. Logowska ; J. Martin Broto ; D. Mazzatenta ; C. Morosi ; P. Nicolai ; O. J. Norum ; S. Patel ; N. Penel ; P. Picci ; S. Pilotti ; S. Radaelli ; F. Ricchini ; P. Rutkowski ; S. Scheipl ; C. Sen ; E. Tamborini ; K. A. Thornton ; B. Timmermann ; V. Torri ; P. U. Tunn ; M. Uhl ; Y. Yamada ; D. C. Weber ; D. Vanel ; P. P. Varga ; C. LA Vleggeert-Lankamp ; P. G. Casali ; J. Sommer

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus [...]