Menée à partir des données des registres américains des cancers portant sur 13 292 patients atteints d'un cancer du poumon non à petites cellules de stade III traité entre 2003 et 2005, cette étude évalue le bénéfice, en termes de survie, d'une radiothérapie conformationnelle après une chimioradiothérapie

Influence of conformal radiotherapy technique on survival after chemoradiotherapy for patients with stage III non-small cell lung cancer in the National Cancer Data Base

Sher, David J. ; Koshy, Matthew ; Liptay, Michael J. ; Fidler, Mary Jo

BACKGROUND : Definitive chemoradiotherapy is a core treatment modality for patients with stage III non-small cell lung cancer (NSCLC). Although radiotherapy (RT) technologies have advanced dramatically, to the authors' knowledge relatively little is known regarding the importance of irradiation technique on outcome, particularly given the competing risk of distant metastasis. The National Cancer Data Base was used to determine predictors of overall survival (OS) in patients with AJCC stage III [...]

A partir d'une revue systématique de la littérature publiée entre 2000 et 2012 (7 articles), cette étude analyse le rôle d'une lymphadénectomie de sauvetage dans le traitement des patients atteints d'un cancer de la prostate récidivant après une prostatectomie radicale

Contemporary Role of Salvage Lymphadenectomy in Patients with Recurrence Following Radical Prostatectomy

Firas Abdollah, ; Alberto Briganti, ; Francesco Montorsi, ; Arnulf Stenzl, ; Christian Stief, ; Bertr, ; Tombal, ; Hein Van Poppel, ; Karim Touijer

Context : Prostate cancer (PCa) patients with isolated clinical lymph node (LN) relapse, limited to the regional and/or retroperitoneal LNs, may represent a distinct group of patients who have a more favorable outcome than men with progression to the bone or to other visceral organs. Some data indirectly denote a beneficial impact of pelvic LN dissection on survival in these patients. Objective : To provide an overview of the currently available literature regarding salvage LN dissection (SLND) [...]

Cet article présente les recommandations de deux sociétés savantes américaines (The Society of Surgical Oncology, The American Society for Radiation Oncology), complétées et adoptées par l'ASCO (The American Society of Clinical Oncology), sur la délimitation des marges de résection et le suivi des résultats thérapeutiques dans le cadre d'un traitement combinant chirurgie conservatrice et radiothérapie du sein entier chez les patientes atteintes d'un cancer invasif du sein de stade I ou II

Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: American Society of Clinical Oncology Endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology Consensus Guideline

Buchholz, Thomas A. ; Somerfield, Mark R. ; Griggs, Jennifer J. ; El-Eid, Souzan ; Hammond, M. Elizabeth H. ; Lyman, Gary H. ; Mason, Ginny ; Newman, Lisa A.

Purpose : The Society of Surgical Oncology (SSO)/American Society for Radiation Oncology (ASTRO) guideline on surgical margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer was considered for endorsement. Methods : The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing practice guidelines developed by other organizations. ASCO staff reviewed the SSO/ASTRO guideline for developmental rigor; an ASCO [...]

Menée sur 13 patients atteints d'un carcinome anaplasique de la thyroïde traités entre 2008 et 2011 (âge : de 43 à 75 ans ; 10 hommes et 3 femmes ; durée médiane de suivi : 9 mois), cette étude chinoise analyse les résultats oncologiques associés à une radiothérapie avec modulation d'intensité en combinaison avec une chimiothérapie et/ou un traitement chirurgical

Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma

He, Xiayun ; Li, Duanshu ; Hu, Chaosu ; Wang, Zhuoying ; Ying, Hongmei ; Wu, Yi

Background : Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC Methods : 13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + [...]

Menée à partir des données des registres américains des cancers portant sur 1 227 patients atteints d'un carcinome urothélial des voies urinaires supérieures de stade précoce et de grade faible ou modéré et traités entre 1992 et 2008 (âge moyen : 70,2 ans ; 63 % d'hommes), cette étude évalue, du point de vue de la mortalité spécifique et de la mortalité toutes causes confondues, l'intérêt d'un traitement chirurgical préservant le néphron par rapport à une néphro-urétérectomie radicale

Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma

Simhan, Jay ; Smaldone, Marc C. ; Egleston, Brian L. ; Canter, Daniel ; Sterious, Steven N. ; Corcoran, Anthony T. ; Ginzburg, Serge ; Uzzo, Robert G. ; Kutikov, Alexander

Objective : To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset. Patients and Methods : Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt d'un inhibiteur de la signalisation Akt pour le traitement de seconde ligne des patients atteints d'un carcinome hépatocellulaire résistant au sorafenib

Inhibition of Akt reverses the acquired resistance to sorafenib by switching protective autophagy to autophagic cell death in hepatocellular carcinoma

Zhai, Bo ; Hu, Fengli ; Jiang, Xian ; Xu, Jun ; Zhao, Dali ; Liu, Bing ; Pan, Shangha ; Dong, Xuesong ; Tan, Gang ; Wei, Zheng ; Qiao, Haiquan ; Jiang, Hongchi ; Sun, Xueying

Sorafenib is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), but the acquired resistance to sorafenib results in limited benefits. Activation of Akt is thought to be responsible for mediating the acquired resistance to sorafenib. The present study aims to examine the underlying mechanism and seek potential strategies to reverse this resistance. Two sorafenib-resistant HCC cell lines, which had been established from human HCC HepG2 and Huh7 cells, were [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en bloquant les signalisations VEGFR2 et MET, le cabozantinib agit sur la croissance tumorale et le processus métastatique d'un carcinome hépatocellulaire

Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET

Xiang, Qingfeng ; Chen, Weiqiang ; Ren, Men ; Wang, Jingnan ; Zhang, Hongwu ; Deng, David Y.B. ; Zhang, Lei ; Chen, Yajin ; Shang, Changzhen

Purpose: MET signaling has been suggested a potential role in hepatocellular carcinoma (HCC) and associated with pro-metastasis during anti-angiogenesis therapy. We investigated the potential association between MET expression and therapeutic response to sorafenib in HCC patients. Anti-tumor effects of cabozantinib, a dual inhibitor of MET and VEGFR2, were examined in cultured HCC cells as well as in vivo models. Experimental Design: Total MET and phosphorylated MET (p-MET) were measured in 29 [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'un conjugué anticorps-médicament comprenant un anticorps anti mésothéline et un inhibiteur de la polymérisation de la tubuline

Anetumab Ravtansine - a Novel Mesothelin-Targeting Antibody-Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect

Golfier, Sven ; Kopitz, Charlotte ; Kahnert, Antje ; Heisler, Iring ; Schatz, Christoph A. ; Stelte-Ludwig, Beatrix ; Mayer-Bartschmid, Anke ; Unterschemmann, Kerstin ; Bruder, Sandra ; Linden, Lars ; Harrenga, Axel ; Hauff, Peter ; Scholle, Frank-Detlef ; Müller-Tiemann, Beate ; Kreft, Bertolt ; Ziegelbauer, Karl

Mesothelin is a tumor differentiation antigen frequently overexpressed in tumors such as mesothelioma, ovarian, pancreatic, and lung adenocarcinomas while showing limited expression in nonmalignant tissues. Mesothelin is therefore an attractive target for cancer therapy using antibody-drug conjugates (ADC). This study describes the detailed characterization of anetumab ravtansine, here referred to as BAY 94-9343, a novel ADC consisting of a human anti-mesothelin antibody conjugated to the [...]

Menée à l'aide d'un modèle murin transgénique, cette étude suggère l'intérêt des inhibiteurs de la signalisation MAPK pour le traitement d'un carcinome anaplasique de la thyroïde

p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

McFadden, David G. ; Vernon, Amanda ; Santiago, Philip M. ; Martinez-McFaline, Raul ; Bhutkar, Arjun ; Crowley, Denise M. ; McMahon, Martin ; Sadow, Peter M. ; Jacks, Tyler

Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an [...]

Menée à partir d'échantillons tumoraux prélevés sur 180 patients atteints d'un carcinome épidermoïde de la tête et du cou, puis sur des lignées cellulaires et à l'aide d'un modèle murin transgénique, cette étude met en évidence des mécanismes de résistance au cetuximab

RAS/ PI3K crosstalk and cetuximab resistance in head and neck squamous cell carcinoma

Rampias, Theodore ; Giagini, Athina ; Siolos, Spiros ; Matsuzaki, Hiroumi ; Sasaki, Clarence T ; Scorilas, Andreas ; Psyrri, Amanda

Purpose:Cetuximab, an antibody directed against the epidermal growth factor receptor (EGFR), is an effective clinical therapy for patients with head and neck squamous cell cancer (HNSCC). Despite great clinical promise, intrinsic or acquired cetuximab resistance hinders successful treatment outcomes but little is known about the underlying mechanism. Experimental Design:To study the role of oncogenic HRAS in cetuximab resistance in HNSCC, the frequency of oncogenic HRAS mutations was determined [...]

Menée à l'aide de modèles murins, puis sur une cohorte de 20 patients atteints d'un mélanome ou d'un cancer de la prostate de stade avancé, cette étude met en évidence un mécanisme rendant compte de l'induction d'une inflammation chronique de l'hypophyse par l'ipilimumab

Pituitary Expression of CTLA-4 Mediates Hypophysitis Secondary to Administration of CTLA-4 Blocking Antibody

Iwama, Shintaro ; De Remigis, Alessandra ; Callahan, Margaret K. ; Slovin, Susan F. ; Wolchok, Jedd D. ; Caturegli, Patrizio

Hypophysitis is a chronic inflammation of the pituitary gland of unknown (primary forms) or recognizable (secondary forms) etiology, such as the use of ipilimumab in cancer immunotherapy. Ipilimumab, which blocks the T cell inhibitory molecule CTLA-4 (cytotoxic T lymphocyte antigen-4), induces hypophysitis in about 4% of patients through unknown mechanisms. We first established a model of secondary hypophysitis by repeated injections of a CTLA-4 blocking antibody into SJL/J or C57BL/6J mice, [...]

Mené sur 58 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I en escalade de dose évalue la dose maximale tolérée de l'ombrabuline en combinaison avec le docétaxel

A phase I pharmacokinetic study of the vascular disrupting agent ombrabulin (AVE8062) and docetaxel in advanced solid tumours

Eskens, F. A. L. M. ; Tresca, P. ; Tosi, D. ; Van Doorn, L. ; Fontaine, H. ; Van der Gaast, A. ; Veyrat-Follet, C. ; Oprea, C. ; Hospitel, M. ; Dieras, V.

Background: The vascular disrupting agent ombrabulin shows synergy with docetaxel in vivo. Recommended phase II doses were determined in a dose escalation study in advanced solid tumours. Methods: Ombrabulin (30-min infusion, day 1) followed by docetaxel (1-h infusion, day 2) every 3 weeks was explored. Ombrabulin was escalated from 11.5 to 42 mg m−2 with 75 mg m−2 docetaxel, then from 30 to 35 mg m−2 with 100 mg m−2 docetaxel. Recommended phase II dose cohorts were expanded. Results: [...]

A partir d'une revue de la littérature publiée jusqu'en décembre 2013 (11 essais, 1 605 patients), cette méta-analyse compare l'efficacité, du point de vue de la survie sans progression, d'une chimiothérapie et d'un inhibiteur de l'activité tyrosine kinase d'EGFR de première génération chez les patients atteints d'un cancer avancé du poumon non à petites cellules ne présentant pas de mutation du gène EGFR

Epidermal growth factor receptor tyrosine kinase inhibitors vs conventional chemotherapy in non–small cell lung cancer harboring wild-type epidermal growth factor receptor: A meta-analysis

Lee, J. ; Hahn, S. ; Kim, D. ; et al.,

Importance  : Current guidelines recommend both epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy drugs as standard treatment options for patients with wild-type (WT) EGFR who were previously treated for non–small cell lung cancer (NSCLC). However, it is not clear that EGFR TKIs are as efficacious as chemotherapy in patients with WT EGFR. Objective  : To determine the association between first-generation EGFR TKI vs chemotherapy and survival in [...]

Mené sur 257 patients atteints d'un cancer colorectal avec métastases hépatiques résécables ne présentant pas de mutation dans l'exon 2 du gène KRAS, cet essai randomisé évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du cetuximab en complément d'une chimiothérapie conventionnelle

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial

Primrose, John ; Falk, Stephen ; Finch-Jones, Meg ; Valle, Juan ; O'Reilly, Derek ; Siriwardena, Ajith ; Hornbuckle, Joanne ; Peterson, Mark ; Rees, Myrddin ; Iveson, Tim ; Hickish, Tamas ; Butler, Rachel ; Stanton, Louise ; Dixon, Elizabeth ; Little, Louisa ; Bowers, Megan ; Pugh, Siân ; Garden, O. James ; Cunningham, David ; Maughan, Tim ; Bridgewater, John

Background : Surgery for colorectal liver metastases results in an overall survival of about 40% at 5 years. Progression-free survival is increased with the addition of oxaliplatin and fluorouracil chemotherapy. The addition of cetuximab to these chemotherapy regimens results in an overall survival advantage in patients with advanced disease who have the KRAS exon 2 wild-type tumour genotype. We aimed to assess the benefit of addition of cetuximab to standard chemotherapy in patients with [...]

Mené sur 278 patients atteints d'un cancer colorectal métastatique ne présentant pas de mutation dans l'exon 2 du gène KRAS, cet essai de phase II compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du panitumumab et du bevacizumab en complément d'une chimiothérapie mFOLFOX6

PEAK: A Randomized, Multicenter Phase II Study of Panitumumab Plus Modified Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or Bevacizumab Plus mFOLFOX6 in Patients With Previously Untreated, Unresectable, Wild-Type KRAS Exon 2 Metastatic Colorectal Cancer

Schwartzberg, Lee S. ; Rivera, Fernando ; Karthaus, Meinolf ; Fasola, Gianpiero ; Canon, Jean-Luc ; Hecht, J. Randolph ; Yu, Hua ; Oliner, Kelly S. ; Go, William Y.

Purpose : To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevavcizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS. Patients and Methods : Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one [...]

Mené sur 114 patients atteints d'un carcinome rénal de stade métastatique ou avancé, cet essai randomisé compare le pazopanib et le sunitinib du point de vue des préférences exprimées par les patients

Randomized, Controlled, Double-Blind, Cross-Over Trial Assessing Treatment Preference for Pazopanib Versus Sunitinib in Patients With Metastatic Renal Cell Carcinoma: PISCES Study

Escudier, Bernard ; Porta, Camillo ; Bono, Petri ; Powles, Thomas ; Eisen, Tim ; Sternberg, Cora N. ; Gschwend, Jurgen E. ; De Giorgi, Ugo ; Parikh, Omi ; Hawkins, Robert ; Sevin, Emmanuel ; Négrier, Sylvie ; Khan, Sadya ; Diaz, Jose ; Redhu, Suman ; Mehmud, Faisal ; Cella, David

Purpose : Patient-reported outcomes may help inform treatment choice in advanced/metastatic renal cell carcinoma (RCC), particularly between approved targeted therapies with similar efficacy. This double-blind cross-over study evaluated patient preference for pazopanib or sunitinib and the influence of health-related quality of life (HRQoL) and safety factors on their stated preference. Patients and Methods : Patients with metastatic RCC were randomly assigned to pazopanib 800 mg per day for 10 [...]

Mené sur 40 patientes atteintes d'un cancer du sein HER2+ de stade avancé, cet essai de phase I en escalade de dose évalue les concentrations plasmatiques de différentes doses de lapatinib

Phase I Dose-Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer

Chien, A. Jo ; Munster, Pamela N. ; Melisko, Michelle E. ; Rugo, Hope S. ; Park, John W. ; Goga, Andrei ; Auerback, Glenna ; Khanafshar, Elham ; Ordovas, Karen ; Koch, Kevin M. ; Moasser, Mark M.

Purpose : The highly effective treatment of human epidermal growth factor receptor (HER) 2–amplified breast cancer has proven challenging because of a signal buffering capacity inherent in the functionally relevant HER2-HER3 target. HER2-HER3 signaling can be inactivated by doses of lapatinib that fully inactivate the HER2 kinase. In mouse models, such doses are not tolerable in continuous administration, but they are tolerable and highly effective in intermittent dosing. We pursued the [...]

Mené sur 38 patients pédiatriques atteints d'un neuroblastome réfractaire ou récidivant (âge médian : 7,2 ans), cet essai de phase I évalue la dose maximale tolérée et le profil de toxicité d'un nouvel anticorps monoclonal anti-GD2

Phase I Trial of a Novel Anti-GD2 Monoclonal Antibody, Hu14.18K322A, Designed to Decrease Toxicity in Children With Refractory or Recurrent Neuroblastoma

Navid, Fariba ; Sondel, Paul M. ; Barfield, Raymond ; Shulkin, Barry L. ; Kaufman, Robert A. ; Allay, Jim A. ; Gan, Jacek ; Hutson, Paul ; Seo, Songwon ; Kim, KyungMann ; Goldberg, Jacob ; Hank, Jacquelyn A. ; Billups, Catherine A. ; Wu, Jianrong ; Furman, Wayne L. ; McGregor, Lisa M. ; Otto, Mario ; Gillies, Stephen D. ; Handgretinger, Rupert ; Santana, Victor M.

Purpose : The addition of immunotherapy, including a combination of anti-GD2 monoclonal antibody (mAb), ch14.18, and cytokines, improves outcome for patients with high-risk neuroblastoma. However, this therapy is limited by ch14.18-related toxicities that may be partially mediated by complement activation. We report the results of a phase I trial to determine the maximum-tolerated dose (MTD), safety profile, and pharmacokinetics of hu14.18K322A, a humanized anti-GD2 mAb with a single point [...]

Cet article fait le point sur la prise en charge thérapeutique du cancer du poumon à petites cellules et sur les traitements en cours de développement

Treatment of Small Cell Lung Cancer

Morabito, Alessandro ; Carillio, Guido ; Daniele, Gennaro ; Piccirillo, Maria Carmela ; Montanino, Agnese ; Costanzo, Raffaele ; Sandomenico, Claudia ; Giordano, Pasqualina ; Normanno, Nicola ; Perrone, Francesco ; Rocco, Gaetano ; Di Maio, Massimo

Treatment of small cell lung cancer (SCLC) remains a significant challenge for the oncologists. Attemps to improve the results of first-line treatment have all failed so far and no real progress has been made in last years, emphasizing the need for novel strategies of treatment and the development of validated biomarkers. Patients with limited disease and good performance status should be considered for concomitant chemoradiotherapy, followed by prophylactic cranial irradiation. Patients with [...]

Mené sur 113 patients atteints d'un cancer rectal de stade localement avancé, cet essai de phase III évalue, du point de vue de la survie sans maladie, de la survie globale à 3 ans et de la toxicité, l'intérêt d'une chimiothérapie adjuvante par capécitabine plus oxaliplatine après une chimioradiothérapie néoadjuvante et un traitement chirurgical

Chronicle: Results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (Xelox) versus control

Glynne-Jones, R. ; Counsell, N. ; Quirke, P. ; Mortensen, N. ; Maraveyas, A. ; Meadows, H.M. ; Ledermann, J. ; Sebag-Montefiore, D.

Background : In stage III colon cancer oxaliplatin/5FU-based adjuvant chemotherapy (FOLFOX) improves disease-free survival (DFS) and overall survival (OS). In rectal adenocarcinoma following neoadjuvant chemoradiation (CRT), we examined the benefit of postoperative adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy. Methods : Eligible patients were randomly assigned following fluoropyrimidine-based CRT and curative resection to observation or 6 cycles of XELOX. The primary endpoint was [...]

Mené sur 120 patients atteints d'un glioblastome non résécable (âge : 18 à 70 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement néo-adjuvant ou adjuvant par bévacizumab et irinotécan en combinaison avec une chimioradiothérapie à base de témozolomide

Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared to temozolomide-chemoradiation for unresectable glioblastoma. Final results of the TEMAVIR study from ANOCEF

Chauffert, B. ; Feuvret, L. ; Bonnetain, F. ; Taillandier, L. ; Frappaz, D. ; Taillia, H. ; Schott, R. ; Honnorat, J. ; Fabbro, M. ; Tennevet, I. ; Ghiringhelli, F. ; Guillamo, J.S. ; Durando, X. ; Castera, D. ; Frenay, M. ; Campello, C. ; Dalban, C. ; Skrzypski, J. ; Chinot, O.

Background : Prognosis of unresectable glioblastoma remains poor despite temozolomide-based chemoradiation. Activity of bevacizumab (BEV) and irinotecan (IRI) has been reported in recurrent disease. We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with temozolomide-based chemoradiation for unresectable glioblastoma. Patients and Methods : Patients with unresectable glioblastoma, age 18-70, IK>50 were eligible. The experimental arm (BEV/IRI) consisted of neo-adjuvant [...]