A partir d'une revue systématique de la littérature publiée entre 1976 et 2015 (71 articles), cette étude analyse les indications de la radiothérapie dans le traitement d'un cancer cutané hors mélanome (lymphome, sarcome ou carcinome) et suggère, pour chacun des six types de cancer cutané abordé, le protocole thérapeutique le plus performant

Role of radiation therapy in non-melanoma cancers, lymphomas and sarcomas of the skin: systematic review and best practice in 2015

Fort, Magali ; Guet, Saada ; Colson-Durand, Laurianne ; Auzolle, Claire ; Belkacémi, Yazid

Radiotherapy has been used for the treatment of skin cancers since very early after the discovery of x-rays. Indications for radiotherapy in non-melanoma cancers are controversial, and are usually decided according to the tumor type and the possibility of curing the patient with surgery. The introduction of sophisticated surgery techniques and the information of the general population on potential late radiation-induced toxicity and carcinogenesis have led to limiting radiation indications in [...]

Mené sur 30 patients atteints d'un cancer localisé de la prostate à risque faible ou intermédiaire de récidive (âge médian : 69 ans ; durée de suivi : 12 mois), cet essai de phase I évalue la sécurité et la faisabilité d'une ablation transurétrale de l'ensemble de la prostate par ultrasons sous guidage IRM

Magnetic Resonance Imaging–Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial

Chin, Joseph L. ; Billia, Michele ; Relle, James ; Roethke, Matthias C. ; Popeneciu, Ionel V. ; Kuru, Timur H. ; Hatiboglu, Gencay ; Mueller-Wolf, Maya B. ; Motsch, Johann ; Romagnoli, Cesare ; Kassam, Zahra ; Harle, Christopher C. ; Hafron, Jason ; Nandalur, Kiran R. ; Chronik, Blaine A. ; Burtnyk, Mathieu ; Schlemmer, Heinz-Peter ; Pahernik, Sascha

Background : Magnetic resonance imaging–guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. Objective : To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). Design, setting, and participants : A single-arm prospective phase 1 study was [...]

A partir d'une revue systématique de la littérature publiée jusqu'en août 2015 (7 études incluant au total 1 724 patients), cette méta-analyse évalue le bénéfice, en termes de survie globale, d'une radiothérapie chez les patients atteints d'un thymome de stade II à IV (selon la classification de Masaoka)

Survival impact of adjuvant radiotherapy in Masaoka stage II-IV thymomas – A systematic review and meta-analysis

Lim, Yu Jin ; Kim, Eunji ; Kim, Hak Jae ; Wu, Hong-Gyun ; Yan, Jinchun ; Liu, Qin ; Patel, Shilpen

Purpose : Due to the lack of randomized evidence, no conclusion has been made concerning the role of postoperative radiotherapy (PORT) in thymomas. This systematic review and meta-analysis evaluated the survival impact of PORT in stage II-IV thymomas. Methods and Materials : A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without [...]

Menée à partir de données portant sur 1 502 patientes atteintes d'un cancer de l'endomètre (durée médiane de suivi : 78 mois), cette étude multicentrique évalue, en fonction de l'agressivité de la tumeur et du point de vue de la survie globale, l'intérêt d'une lymphadénectomie des régions pelvienne et aortique par rapport à une lymphadénectomie pelvienne seule ou à l'absence de lymphadénectomie

Survival advantage of lymphadenectomy in endometrial cancer

Eggemann, Holm ; Ignatov, Tanja ; Kaiser, Katharina ; Burger, Elke ; Costa, SerbanDan ; Ignatov, Atanas

Background : The lymphadenectomy in the treatment of endometrial cancer is a topic of ongoing debate. The direct comparison between no lymphadenectomy, pelvic lymphadenectomy, and pelvic/para-aortic lymphadenectomy regarding overall survival of patients with endometrial cancer is missing. Methods : We performed a multicenter, retrospective, registry-based study of 1502 patients with endometrial cancer treated with no lymphadenectomy (n = 697), systemic pelvic lymphadenectomy (n = 543) and [...]

Cet article passe en revue les études concernant l'utilisation de la radiothérapie pour traiter un cancer invasif de la vessie dans le cadre d'une stratégie thérapeutique conservatrice

Bladder Preservation for Muscle Invasive Bladder Cancer

Mirza, Arafat ; Choudhury, Ananya

The standard treatment for muscle invasive bladder cancer (MIBC) has been considered to be radical cystectomy (RC) with pelvic lymphadenectomy. However morbidity and impact on quality of life is significant. Radiotherapy has been used in MIBC patients who choose bladder preservation or who are unfit for RC with comparable outcomes. Evidence from some prospective and large retrospective series supports the use of radiotherapy as an attractive alternative option. In this paper we review the [...]

Menée sur des lignées cellulaires de mélanome et de leucémie, cette étude met en évidence des mécanismes permettant de rendre compte, via la signalisation de l'apoptose, de l'activité antitumorale des inhibiteurs de BET

Preclinical anticancer efficacy of BET bromodomain inhibitors is determined by the apoptotic response

Conery, Andrew R ; Centore, Richard C ; Spillane, Kerry L ; Follmer, Nicole E ; Bommi-Reddy, Archana ; Hatton, Charlie ; Bryant, Barbara M ; Greninger, Patricia ; Amzallag, Arnaud ; Benes, Cyril H. ; Mertz, Jennifer A ; Sims, Robert J

Small molecule inhibitors of the bromodomain and extraterminal (BET) family of proteins are being tested in clinical trials for a variety of cancers, but patient selection strategies remain limited. This challenge is partly attributed to the heterogeneous responses elicited by BET inhibition (BETi), including cellular differentiation, senescence, and death. In this study, we performed phenotypic and gene expression analyses of treatment-naive and engineered tolerant cell lines representing [...]

Cet article passe en revue les obstacles à franchir avant que les immunothérapies à base de lymphocytes T modifiés ne bénéficient à une majorité de patients atteints d'une tumeur solide

Prospects for gene-engineered T cell immunotherapy for solid cancers

Klebanoff, Christopher A. ; Rosenberg, Steven A. ; Restifo, Nicholas P.

Adoptive transfer of receptor-engineered T cells has produced impressive results in treating patients with B cell leukemias and lymphomas. This success has captured public imagination and driven academic and industrial researchers to develop similar 'off-the-shelf' receptors targeting shared antigens on epithelial cancers, the leading cause of cancer-related deaths. However, the successful treatment of large numbers of people with solid cancers using this strategy is unlikely to be [...]

Menée à l'aide de modèles murins, cette étude met en évidence l'activité antitumorale d'une immunothérapie duale (anti CD134 et anti CTLA4) en combinaison avec un vaccin thérapeutique

Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice

Linch, Stefanie N. ; Kasiewicz, Melissa J. ; McNamara, Michael J. ; Hilgart-Martiszus, Ian F. ; Farhad, Mohammad ; Redmond, William L.

Immunotherapy is gathering momentum as a primary therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and benefit only a subset of patients. Combination therapies targeting multiple pathways can augment an immune response to improve survival further. Here, we demonstrate that dual aOX40 (anti-CD134)/aCTLA-4 (anti–cytotoxic T-lymphocyte–associated protein 4) immunotherapy generated a potent antigen-specific CD8 T-cell response, enhancing expansion, [...]

Menée in vitro sur des modèles de cancer présentant la mutation G12C du gène KRAS, cette étude met en évidence des mécanismes par lesquels, en inhibant la signalisation KRASG12C, une molécule (ARS853) exerce une activité antitumorale

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

Lito, Piro ; Solomon, Martha ; Li, Lian-Sheng ; Hansen, Rasmus ; Rosen, Neal

It is believed that KRAS oncoproteins are constitutively active because their GTPase activity is disabled. With this in mind, drugs targeting the inactive or GDP-bound conformation are not expected to be effective. We now describe a mechanism that enables such drugs to inhibit KRASG12C-signaling and cancer cell growth. Inhibition requires intact GTPase activity and occurs because drug-bound KRASG12C is insusceptible to nucleotide exchange factors and thus trapped in its inactive state. Indeed, [...]

Menée in vitro et in vivo, cette étude évalue la faisabilité et l'intérêt d'une méthode de fabrication permettant de réduire la toxicité associée aux thérapies à base de lymphocytes T modifiés pour exprimer un récepteur antigénique chimérique

Versatile strategy for controlling the specificity and activity of engineered T cells

Ma, Jennifer S. Y. ; Kim, Ji Young ; Kazane, Stephanie A. ; Choi, Sei-hyun ; Yun, Hwa Young ; Kim, Min Soo ; Rodgers, David T. ; Pugh, Holly M. ; Singer, Oded ; Sun, Sophie B. ; Fonslow, Bryan R. ; Kochenderfer, James N. ; Wright, Timothy M. ; Schultz, Peter G. ; Young, Travis S. ; Kim, Chan Hyuk ; Cao, Yu

The adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a promising cancer therapy. Despite impressive clinical efficacy, the general application of current CAR–T-cell therapy is limited by serious treatment-related toxicities. One approach to improve the safety of CAR-T cells involves making their activation and proliferation dependent upon adaptor molecules that mediate formation of the immunological synapse between the target cancer [...]

Menée in vitro et in vivo sur des modèles de lymphome, cette étude met en évidence des mécanismes par lesquels, en ciblant une enzyme (l'héparanase) dans le micro-environnement tumoral, des anticorps monoclonaux exercent une activité antitumorale

Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis

Weissmann, Marina ; Arvatz, Gil ; Horowitz, Netanel ; Feld, Sari ; Naroditsky, Inna ; Zhang, Yi ; Ng, Mary ; Hammond, Edward ; Nevo, Eviatar ; Vlodavsky, Israel ; Ilan, Neta

Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of proteoglycans, resulting in disassembly of the extracellular matrix underlying endothelial and epithelial cells and associating with enhanced cell invasion and metastasis. Heparanase expression is induced in carcinomas and sarcomas, often associating with enhanced tumor metastasis and poor prognosis. In contrast, the function of heparanase in hematological malignancies (except myeloma) was not investigated in depth. [...]

A partir d'échantillons sanguins prélevés sur 40 patients âgés atteints d'un myélome multiple inclus dans un essai espagnol, puis menée in vitro, cette étude met en évidence des mécanismes de sélection clonale permettant de rendre compte de l'apparition d'une résistance à une chimiothérapie

Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance

Paiva, Bruno ; Corchete, Luis A. ; Vidriales, María-Belén ; Puig, Noemí ; Maiso, Patricia ; Rodriguez, Idoia ; Alignani, Diego ; Burgos, Leire ; Sanchez, Maria Luz ; Bárcena, Paloma ; Echeveste, Maria-Asuncion ; Hernandez, Miguel T. ; Garcia-Sanz, Ramon ; Ocio, Enrique M. ; Oriol, Albert ; Gironella, Mercedes ; Palomera, Luis ; de Arriba, Felipe ; González, Yolanda ; Johnson, Sarah K. ; Epstein, Joshua ; Barlogie, Bart ; Lahuerta, Juan-José ; Bladé, Joan ; Orfao, Alberto ; Mateos, María-Victoria ; San Miguel, Jesús F.

We report for the first time the biologic features of MRD cells in MM and unravel that clonal selection is already present at the MRD stage.MRD cells show a singular phenotypic signature that may result from persisting clones with different genetic and gene expression profiles. Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) is associated with inferior survival in multiple myeloma (MM). Thus, characterization of the minor MRD subclone may represent a unique model [...]

Menée in vitro et in vivo, cette étude suggère que les patients atteints d'un cancer du poumon non à petites cellules présentant des mutations du gène ABL1 sont susceptibles de bénéficier d'un traitement à l'aide d'imatinib

Somatically mutated ABL1 is an actionable and essential NSCLC survival gene

Testoni, Ewelina ; Stephenson, Natalie L. ; Torres-Ayuso, Pedro ; Marusiak, Anna A. ; Trotter, Eleanor W. ; Hudson, Andrew ; Hodgkinson, Cassandra L. ; Morrow, Christopher J. ; Dive, Caroline ; Brognard, John

The lack of actionable mutations in patients with non-small cell lung cancer (NSCLC) presents a significant hurdle in the design of targeted therapies for this disease. Here, we identify somatically mutated ABL1 as a genetic dependency that is required to maintain NSCLC cell survival. We demonstrate that NSCLC cells with ABL1 mutations are sensitive to ABL inhibitors and we verify that the drug-induced effects on cell viability are specific to pharmacological inhibition of the ABL1 kinase. [...]

Menée à l'aide de modèles murins et à partir d'échantillons tumoraux prélevés sur 33 patients atteints d'un médulloblastome, cette étude montre que, lors d'une récidive de la maladie après une thérapie ciblée, le clone dominant résulte de l'expansion d'un clone mineur présent dès le diagnostic

Divergent clonal selection dominates medulloblastoma at recurrence

Morrissy, A. Sorana ; Garzia, Livia ; Shih, David J. H. ; Zuyderduyn, Scott ; Huang, Xi ; Skowron, Patryk ; Remke, Marc ; Cavalli, Florence M. G. ; Ramaswamy, Vijay ; Lindsay, Patricia E. ; Jelveh, Salomeh ; Donovan, Laura K. ; Wang, Xin ; Luu, Betty ; Zayne, Kory ; Li, Yisu ; Mayoh, Chelsea ; Thiessen, Nina ; Mercier, Eloi ; Mungall, Karen L. ; Ma, Yusanne ; Tse, Kane ; Zeng, Thomas ; Shumansky, Karey ; Roth, Andrew J. L. ; Shah, Sohrab ; Farooq, Hamza ; Kijima, Noriyuki ; Holgado, Borja L. ; Lee, John J. Y. ; Matan-Lithwick, Stuart ; Liu, Jessica ; Mack, Stephen C. ; Manno, Alex ; Michealraj, K. A. ; Nor, Carolina ; Peacock, John ; Qin, Lei ; Reimand, Jüri ; Rolider, Adi ; Thompson, Yuan Y. ; Wu, Xiaochong ; Pugh, Trevor ; Ally, Adrian ; Bilenky, Mikhail ; Butterfield, Yaron S. N. ; Carlsen, Rebecca ; Cheng, Young ; Chuah, Eric ; Corbett, Richard D. ; Dhalla, Noreen ; He, An ; Lee, Darlene ; Li, Haiyan I. ; Long, William ; Mayo, Michael ; Plettner, Patrick ; Qian, Jenny Q. ; Schein, Jacqueline E. ; Tam, Angela ; Wong, Tina ; Birol, Inanc ; Zhao, Yongjun ; Faria, Claudia C. ; Pimentel, José ; Nunes, Sofia ; Shalaby, Tarek ; Grotzer, Michael ; Pollack, Ian F. ; Hamilton, Ronald L. ; Li, Xiao-Nan ; Bendel, Anne E. ; Fults, Daniel W. ; Walter, Andrew W. ; Kumabe, Toshihiro ; Tominaga, Teiji ; Collins, V. Peter ; Cho, Yoon-Jae ; Hoffman, Caitlin ; Lyden, David ; Wisoff, Jeffrey H. ; Garvin, James H. ; Stearns, Duncan S. ; Massimi, Luca ; Schüller, Ulrich ; Sterba, Jaroslav ; Zitterbart, Karel ; Puget, Stéphanie ; Ayrault, Olivier ; Dunn, Sandra E. ; Tirapelli, Daniela P. C. ; Carlotti, Carlos G. ; Wheeler, Helen ; Hallahan, Andrew R. ; Ingram, Wendy ; MacDonald, Tobey J. ; Olson, Jeffrey J. ; Van Meir, Erwin G. ; Lee, Ji-Yeoun ; Wang, Kyu-Chang ; Kim, Seung-Ki ; Cho, Byung-Kyu ; Pietsch, Torsten ; Fleischhack, Gudrun ; Tippelt, Stephan ; Ra, Young Shin ; Bailey, Simon ; Lindsey, Janet C. ; Clifford, Steven C. ; Eberhart, Charles G. ; Cooper, Michael K. ; Packer, Roger J. ; Massimino, Maura ; Garre, Maria Luisa ; Bartels, Ute ; Tabori, Uri ; Hawkins, Cynthia E. ; Dirks, Peter ; Bouffet, Eric ; Rutka, James T. ; Wechsler-Reya, Robert J. ; Weiss, William A. ; Collier, Lara S. ; Dupuy, Adam J. ; Korshunov, Andrey ; Jones, David T. W. ; Kool, Marcel ; Northcott, Paul A. ; Pfister, Stefan M. ; Largaespada, David A. ; Mungall, Andrew J. ; Moore, Richard A. ; Jabado, Nada ; Bader, Gary D. ; Jones, Steven J. M. ; Malkin, David ; Marra, Marco A. ; Taylor, Michael D.

The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon–driven, functional genomic mouse model of medulloblastoma with ‘humanized’ in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic [...]

Cet article passe en revue les travaux récents sur les traitements des patients atteints d'un lymphome à cellules du manteau

Mantle Cell Lymphoma

Cheah, Chan Yoon ; Seymour, John F. ; Wang, Michael L.

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma previously considered to have a poor prognosis. Large gains were made in the first decade of the new century when clinical trials established the importance of high-dose therapy and autologous stem-cell rescue and high-dose cytarabine in younger patients and the benefits of maintenance rituximab and bendamustine in older patients. In particular, greater depth of understanding of the molecular pathophysiology of MCL has [...]

Mené sur 25 patients atteints d'un lymphome diffus à grandes cellules B réfractaire/récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du blinatumomab

Phase 2 study of bispecific T-cell engager (BiTE®) antibody blinatumomab in relapsed/refractory diffuse large B cell lymphoma

Viardot, Andreas ; Goebeler, Marie-Elisabeth ; Hess, Georg ; Neumann, Svenja ; Pfreundschuh, Michael ; Adrian, Nicole ; Zettl, Florian ; Libicher, Martin ; Sayehli, Cyrus ; Stieglmaier, Julia ; Zhang, Alicia ; Nagorsen, Dirk ; Bargou, Ralf C.

Among evaluable patients with relapsed/refractory DLBCL who received blinatumomab 112 µg/day, overall response was 43% (CR was 19%).Blinatumomab continuous infusion was feasible with weekly stepwise dose escalation (9-28-112 µg/day) and dexamethasone prophylaxis. Few patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) achieve prolonged disease-free survival. Blinatumomab is a bispecific T-cell engaging (BiTE®) antibody construct that transiently links CD3-positive T cells to [...]

Mené sur 109 patientes atteintes d'un cancer de l'ovaire résistant aux sels de platine ou réfractaire, cet essai français de phase II compare l'efficacité, du point de vue du taux de contrôle de la maladie à 24 semaines, et la toxicité du volasertib par rapport à une chimiothérapie

Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study

Pujade-Lauraine, Eric ; Selle, Frédéric ; Weber, Béatrice ; Ray-Coquard, Isabelle-Laure ; Vergote, Ignace ; Sufliarsky, Jozef ; Del Campo, Josep Maria ; Lortholary, Alain ; Lesoin, Anne ; Follana, Philippe ; Freyer, Gilles ; Pardo, Beatriz ; Vidal, Laura ; Tholander, Bengt ; Gladieff, Laurence ; Sassi, Mouna ; Garin-Chesa, Pilar ; Nazabadioko, Serge ; Marzin, Kristell ; Pilz, Korinna ; Joly, Florence

Purpose : Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients and Methods : Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an [...]

Mené sur 375 patients atteints d'un cancer métastatique de la prostate résistant à la castration, cet essai randomisé international de phase II compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'enzalutamide par rapport au bicalutamide

Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study

Shore, Neal D. ; Chowdhury, Simon ; Villers, Arnauld ; Klotz, Laurence ; Siemens, D. Robert ; Phung, De ; van Os, Steve ; Hasabou, Nahla ; Wang, Fong ; Bhattacharya, Suman ; Heidenreich, Axel

Background : Enzalutamide is an oral androgen-receptor inhibitor that has been shown to improve survival in two placebo-controlled phase 3 trials, and is approved for patients with metastatic castration-resistant prostate cancer. The objective of the TERRAIN study was to compare the efficacy and safety of enzalutamide with bicalutamide in patients with metastatic castration-resistant prostate cancer. Methods : TERRAIN was a double-blind, randomised phase 2 study, that recruited asymptomatic or [...]

Mené sur 44 patients atteints d'un cancer colorectal de stade localement avancé ou métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement de première ligne combinant le nécitumumab et une chimiothérapie FOLFOX6 modifiée

Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer

Elez, E. ; Hendlisz, A. ; Delaunoit, T. ; Sastre, J. ; Cervantes, A. ; Varea, R. ; Chao, G. ; Wallin, J. ; Tabernero, J.

Background: This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC). Methods: Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m−2, folinic acid 400 mg m−2, and 5-fluorouracil (400 mg m−2 bolus then 2400 mg m−2 over 46 h). Radiographic evaluation was performed every 8 weeks until progression. [...]

Mené sur 108 patients atteints d'un carcinome rénal métastatique à cellules non claires, cet essai randomisé de phase II compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'évérolimus et du sunitinib

Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial

Armstrong, Andrew J. ; Halabi, Susan ; Eisen, Tim ; Broderick, Samuel ; Stadler, Walter M. ; Jones, Robert J. ; Garcia, Jorge A. ; Vaishampayan, Ulka N. ; Picus, Joel ; Hawkins, Robert E. ; Hainsworth, John D. ; Kollmannsberger, Christian K. ; Logan, Theodore F. ; Puzanov, Igor ; Pickering, Lisa M. ; Ryan, Christopher W. ; Protheroe, Andrew ; Lusk, Christine M. ; Oberg, Sadie ; George, Daniel J.

Background : Non-clear cell renal cell carcinomas are histologically and genetically diverse kidney cancers with variable prognoses, and their optimum initial treatment is unknown. We aimed to compare the mTOR inhibitor everolimus and the VEGF receptor inhibitor sunitinib in patients with non-clear cell renal cell carcinoma. Methods : We enrolled patients with metastatic papillary, chromophobe, or unclassified non-clear cell renal cell carcinoma with no history of previous systemic treatment. [...]

Mené sur 70 patients atteints d'un carcinome rénal métastatique, cet essai de phase Ia évalue la toxicité et l'activité antitumorale d'un anticorps anti PD-L1, l'atézolizumab

Atezolizumab, an Anti–Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study

McDermott, David F. ; Sosman, Jeffrey A. ; Sznol, Mario ; Massard, Christophe ; Gordon, Michael S. ; Hamid, Omid ; Powderly, John D. ; Infante, Jeffrey R. ; Fassò, Marcella ; Wang, Yan V. ; Zou, Wei ; Hegde, Priti S. ; Fine, Gregg D. ; Powles, Thomas

Purpose : The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized programmed death-ligand 1 (PD-L1) antibody, in renal cell carcinoma (RCC). Exploratory biomarkers were analyzed and associated with outcomes. Patients and Methods : Seventy patients with metastatic RCC, including clear cell (ccRCC; n = 63) and non–clear cell (ncc; n = 7) histologies, received atezolizumab intravenously every 3 weeks. PD-L1 expression was scored at four diagnostic [...]

Menée à partir de données portant sur 16 623 patients pédiatriques atteints d'une leucémie lymphoblastique aiguë traitée entre 1996 et 2007 (âge : 1 à 18 ans), cette méta-analyse évalue, en fonction des caractéristiques clinico-pathologiques des patients, l'effet d'une radiothérapie crânienne prophylactique sur la survie sans événement et le risque de récidive, notamment au niveau du système nerveux central et de la moelle osseuse

Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy

Vora, Ajay ; Andreano, Anita ; Pui, Ching-Hon ; Hunger, Stephen P. ; Schrappe, Martin ; Moericke, Anja ; Biondi, Andrea ; Escherich, Gabriele ; Silverman, Lewis B. ; Goulden, Nicholas ; Taskinen, Mervi ; Pieters, Rob ; Horibe, Keizo ; Devidas, Meenakshi ; Locatelli, Franco ; Valsecchi, Maria Grazia

Purpose : We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL). Patients and Methods : We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was [...]

Mené sur 34 patients atteints d'un cancer de la prostate avec récidive biochimique après prostatectomie radicale, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 24 mois, et la toxicité d'un traitement par docétaxel-prednisone-sunitinib suivi par une radiothérapie de sauvetage ciblant le lit tumoral

A phase 2 multimodality trial of docetaxel/prednisone with sunitinib followed by salvage radiation therapy in men with PSA recurrent prostate cancer after radical prostatectomy

Armstrong, A. J. ; Halabi, S. ; Healy, P. ; Lee, W. R. ; Koontz, B. F. ; Moul, J. W. ; Mundy, K. ; Creel, P. ; Wood, S. ; Davis, K. ; Carducci, M. A. ; Stein, M. ; Hobbs, C. ; Reimer, B. ; Nguyen, M. ; Anand, M. ; Bratt, L. ; Kim, S. ; Tran, P. T. ; George, D. J. ; on behalf of Department of Defense Prostate Cancer Clinical Trials, Consortium

Background : In men with high Gleason PC and rapid PSA progression after surgery, failure rates remain unacceptably high despite salvage radiation. We explored a novel multimodality approach of docetaxel with anti-angiogenic therapy before salvage radiotherapy (RT). Methods : This was a phase 2 single-arm prospective open-label trial with historic controls. Eligible men had a rising PSA of 0.1–3.0 ng ml−1 within 4 years of radical prostatectomy, no metastases except resected nodal disease, no [...]

A partir de données portant sur 1 004 patients inclus dans 30 essais de phase I entre 2005 et 2009 (dont 315 patients d'âge supérieur à 65 ans), cette étude évalue l'intérêt du score de pronostic du Royal Marsden Hospital pour inclure les patients âgés dans ces essais de phase précoce

Phase I trial outcomes in older patients with advanced solid tumours

Khan, K. H. ; Yap, T. A. ; Ring, A. ; Molife, L. R. ; Bodla, S. ; Thomas, K. ; Zivi, A. ; Smith, A. ; Judson, I. ; Banerji, U. ; de Bono, J. S. ; Kaye, S. B.

Background: This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients. Methods: Clinico-pathological characteristics and treatment outcomes of all patients treated consecutively from 2005 to 2009 in phase I trials at the RMH were recorded. All toxicity [...]

Cet article analyse les enjeux associés à la protection des données personnelles collectées dans le cadre du projet "CancerLinQ" de l'"American Society of Clinical Oncology"

Building a Rapid Learning Health Care System for Oncology: Why CancerLinQ Collects Identifiable Health Information to Achieve Its Vision

Shah, Alaap ; Stewart, Andrew K. ; Kolacevski, Andrej ; Michels, Dina ; Miller, Robert

The ever-increasing volume of scientific discoveries, clinical knowledge, novel diagnostic tools, and treatment options juxtaposed with rising costs in health care challenge physicians to identify, prioritize, and use new information rapidly to deliver efficient and high-quality care to a growing and aging patient population. CancerLinQ, a rapid learning health care system in oncology, is an initiative of the American Society of Clinical Oncology and its Institute for Quality that addresses [...]