Mené sur 250 patients atteints d'un mélanome traité par résection et lymphadénectomie entre 2003 et 2007 (durée médiane de suivi : 73 mois), cet essai randomisé international de phase III évalue l'efficacité, du point de vue de la récidive ganglionnaire, et les effets indésirables d'une radiothérapie adjuvante ciblant les régions ganglionnaires atteintes

Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial

Henderson, Michael A. ; Burmeister, Bryan H. ; Ainslie, Jill ; Fisher, Richard ; Di Iulio, Juliana ; Smithers, B. Mark ; Hong, Angela ; Shannon, Kerwin ; Scolyer, Richard A. ; Carruthers, Scott ; Coventry, Brendon J. ; Babington, Scott ; Duprat, Joao ; Hoekstra, Harald J. ; Thompson, John F.

Background : Adjuvant radiotherapy is recommended for patients with melanoma after lymphadenectomy. We previously showed this treatment reduced risk of repeat lymph-node field cancer in patients with a high risk of recurrence but had no effect on overall survival. Here, we aim to update the relapse and survival data from that trial and assess quality of life and toxic effects. Methods : In the ANZMTG 01.02/TROG 02.01 randomised controlled trial, we enrolled patients who had undergone [...]

Mené sur 94 patients inopérables atteints d'un cancer non à petites cellules de la région périphérique du poumon et de stade I (durée médiane de suivi : 30,2 mois), cet essai de phase II compare, du point de vue du taux de survie sans maladie et du taux de survie globale à 2 ans, l'efficacité de deux protocoles de radiothérapie stéréotaxique corporelle

NRG Oncology RTOG 0915 (NCCTG N0927): A Randomized Phase II Study Comparing 2 Stereotactic Body Radiation Therapy (SBRT) Schedules for Medically Inoperable Patients with Stage I Peripheral Non-Small Cell Lung Cancer

Videtic, Gregory M. M. ; Hu, Chen ; Singh, Anurag K. ; Chang, Joe Y. ; Parker, William ; Olivier, Kenneth R. ; Schild, Steven E. ; Komaki, Ritsuko ; Urbanic, James J. ; Choy, Hak

Purpose : To compare 2 stereotactic body radiotherapy (SBRT) schedules for medically inoperable early-stage lung cancer to determine which produces the lowest rate of grade ≥ 3 protocol-specified adverse events (psAEs) at 1 year. Methods : Patients with biopsy-proven peripheral (greater than 2 cm from the central bronchial tree) T1/T2, N0 (clinically node negative by positron emission tomography), M0 tumors were eligible. Patients were randomized to receive either 34 Gy in one fraction (Arm 1) [...]

Menée à partir de données portant sur 119 patients atteints d'un cancer récidivant de la prostate et présentant 1 ou 3 oligométastases, cette étude évalue l'efficacité, du point de vue de la survie sans progression de la maladie, et la toxicité d'une radiothérapie stéréotaxique corporelle ciblant les métastases

Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis

Ost, Piet ; Jereczek-Fossa, Barbara Alicja ; As, Nicholas Van ; Zilli, Thomas ; Muacevic, Alexander ; Olivier, Kenneth ; Henderson, Daniel ; Casamassima, Franco ; Orecchia, Roberto ; Surgo, Alessia ; Brown, Lindsay ; Tree, Alison ; Miralbell, Raymond ; De Meerleer, Gert

The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer [...]

Menée à partir de données portant sur 216 patients présentant des tumeurs rénales complexes traitées entre 2008 et 2014, cette étude compare l'efficacité, du point de vue de données péri-opératoires (durée de l'opération, perte de sang, ...), de la préservation de la fonction rénale et du taux de survie sans récidive à 3 ans, et les complications d'une néphrectomie partielle assistée par robot et d'une néphrectomie laparoscopique standard

Comparison of robot-assisted and laparoscopic partial nephrectomy for complex renal tumours with a RENAL nephrometry score ≥7: peri-operative and oncological outcomes

Wang, Yubin ; Ma, Xin ; Huang, Qingbo ; Du, Qingshan ; Gong, Huijie ; Shang, Jiwen ; Zhang, Xu

Objective : To evaluate the peri-operative, functional and oncological outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for moderately or highly complex tumours (defined as RENAL nephrometry score ≥7). Patients and Methods : We retrospectively analysed the medical charts of 216 patients with complex tumours who underwent LPN (n = 135) or RAPN (n = 81) between 2008 and 2014. Peri-operative data, pathological variables, complications, functional and [...]

Menée sur 50 patients atteints d'un carcinome à cellules rénales traité par néphrectomie et ayant récidivé au niveau d'un ganglion rétropéritonéal, cette étude évalue, du point de vue de la survie sans progression à 3 et 5 ans, le bénéfice d'une métastasectomie en fonction des caractéristiques clinicopathologiques de la tumeur primitive et du délai entre néphrectomie et récidive

Oncological control associated with surgical resection of isolated retroperitoneal lymph node recurrence of renal cell carcinoma

Russell, Christopher M. ; Lue, Kathy ; Fisher, John ; Kassouf, Wassim ; Schwaab, Thomas ; Sexton, Wade J. ; Tanguay, Simon ; Psutka, Sarah P. ; Thompson, Robert Houston ; Leibovich, Bradley C. ; Hanzly, Michael I. ; Spiess, Philippe E. ; Boorjian, Stephen A.

Objective : To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node (RPLN) recurrence of renal cell carcinoma (RCC) using a multicentre international cohort. Patients and Methods : In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pTanyNanyM0 disease. Progression-free (PFS) and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method. Cox [...]

Menée sur 521 patientes atteintes d'un cancer du sein de stade II-III traité par chimiothérapie néoadjuvante, chirurgie et radiothérapie, cette étude évalue l'intérêt d'une irradiation de la chaîne mammaire interne pour améliorer la survie des patientes

Does internal mammary node irradiation affect treatment outcome in clinical stage II–III breast cancer patients receiving neoadjuv ant chemotherapy?

Kim, KyungHwan ; Noh, JaeMyoung ; Kim, YongBae ; Chang, JeeSuk ; Keum, KiChang ; Huh, SeungJae ; Choi, DooHo ; Park, Won ; Suh, Chang-Ok

The purpose of this study is to assess the value of internal mammary node irradiation (IMNI) in patients receiving postoperative radiotherapy after neoadjuvant chemotherapy (NAC) using modern systemic therapy. Between 2001 and 2009, 521 consecutive patients with clinical stage II–III breast cancer received NAC and postoperative radiotherapy. With a consistent policy, the treating radiation oncologist either included (N = 284) or excluded (N = 237) the internal mammary node in the treatment [...]

Menée à l'aide de modèles murins de cancer colorectal ou rénal, cette étude évalue l'activité antitumorale de plusieurs traitements combinant une immunothérapie bloquant un point de contrôle immunitaire (PD-1, PD-L1, CTLA4,...) et un virus oncolytique

Defining Effective Combinations of Immune Checkpoint Blockade and Oncolytic Virotherapy

Rojas, Juan ; Sampath, Padma ; Hou, Weizhou ; Thorne, Stephen H.

Purpose; Recent data from randomized clinical trials with oncolytic viral therapies and with cancer immunotherapies have finally recapitulated the promise these platforms demonstrated in pre-clinical models. Perhaps the greatest advance with oncolytic virotherapy has been the appreciation of the importance of activation of the immune response in therapeutic activity. Meanwhile, the understanding that blockade of immune checkpoints (with antibodies that block the binding of PD1 to PDL1 or CTLA4 [...]

Menée in vitro et in vivo, cette étude évalue la faisabilité d'une technologie d'ingéniérie des génomes (TALEN) pour fabriquer des immunothérapies adoptives à base de lymphocytes T allogènes modifiés pour exprimer un récepteur antigénique chimérique

Multiplex genome edited T-cell manufacturing platform for "off-the-shelf" adoptive T-cell immunotherapies

Poirot, Laurent ; Philip, Brian ; Schiffer-Mannioui, Cécile ; Le Clerre, Diane ; Chion-Sotinel, Isabelle ; Derniame, Sophie ; Bas, Cécile ; Potrel, Pierrick ; Lemaire, Laetitia ; Duclert, Aymeric ; Galetto, Roman ; Lebuhotel, Céline ; Eyquem, Justin ; Cheung, Gordon W ; Gouble, Agnès ; Arnould, Sylvain ; Peggs, Karl S. ; Pule, Martin ; Scharenberg, Andrew ; Smith, Julianne

Adoptive immunotherapy using autologous T-cells endowed with chimeric antigen receptors (CARs) has emerged as a powerful means of treating cancer. However, a limitation of this approach is that autologous CAR T-cells must be generated on a custom-made basis. Here we show that electroporation of transcription activator-like effector nuclease (TALEN) mRNA allows highly-efficient multiplex gene editing in primary human T-cells. We use this TALEN-mediated editing approach to develop a process for [...]

Menée in vitro et à l'aide de modélisations moléculaires, cette étude suggère que les mutations du gène MPS1 conférant une résistance aux inhibiteurs de MPS1 sont déjà présentes dans des cellules cancéreuses avant l'administration de la thérapie ciblée

Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance

Gurden, Mark D. ; Westwood, Isaac M. ; Faisal, Amir ; Naud, Sébastien ; Cheung, Kwai-Ming J. ; McAndrew, Craig ; Wood, Amy ; Schmitt, Jessica ; Boxall, Kathy ; Mak, Grace ; Workman, Paul ; Burke, Rosemary ; Hoelder, Swen ; Blagg, Julian ; Van Montfort, Rob L.M. ; Linardopoulos, Spiros

Acquired resistance to therapy is perhaps the greatest challenge to effective clinical management of cancer. With several inhibitors of the mitotic checkpoint kinase MPS1 in preclinical development, we sought to investigate how resistance against these inhibitors may arise so that mitigation or bypass strategies could be addressed as early as possible. Toward this end, we modeled acquired resistance to the MPS1 inhibitors AZ3146, NMS-P715, and CCT251455, identifying five point mutations in the [...]

Menée in vitro et in vivo, cette étude française met en évidence des mécanismes suggèrant l'intérêt de développer des inhibiteurs de la glutaminase C pour le traitement, en combinaison avec un inhibiteur de BCL-2, des patients atteints d'une leucémie myéloïde aiguë

Targeting glutaminolysis has anti-leukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition

Jacque, Nathalie ; Ronchetti, Anne Marie ; Larrue, Clément ; Meunier, Godelieve ; Birsen, Rudy ; Willems, Lise ; Saland, Estelle ; Decroocq, Justine ; Trovati Maciel, Thiago ; Lambert, Mireille ; Poulain, Laury ; Hospital, Marie Anne ; Sujobert, Pierre ; Joseph, Laure ; Chapuis, Nicolas ; Lacombe, Catherine ; Cruz Moura, Ivan ; Demo, Susan ; Sarry, Jean Emmanuel ; Recher, Christian ; Mayeux, Patrick ; Tamburini, Jérôme ; Bouscary, Didier

Genetic or compound CB-839-induced GAC inhibition reduces OXPHOS and has antileukemic activity in AML.GAC inhibition synergizes with BCL-2 inhibition by compound ABT-199. Cancer cells require glutamine to adapt to increased biosynthetic activity. The limiting step in intracellular glutamine catabolism involves its conversion to glutamate by glutaminase (GA). Different GA isoforms are encoded by the genes GLS1 and GLS2 in humans. Herein, we show that glutamine levels control mitochondrial [...]

Cet article passe en revue les travaux récents sur les modèles mathématiques de nature évolutionniste permettant d'améliorer la prise en charge des patients atteints de cancer, notamment dans la prescription de thérapies ciblées pour une leucémie lymphocytaire chronique

Preventing clonal evolutionary processes in cancer: Insights from mathematical models

Rodriguez-Brenes, Ignacio A. ; Wodarz, Dominik

Clonal evolutionary processes can drive pathogenesis in human diseases, with cancer being a prominent example. To prevent or treat cancer, mechanisms that can potentially interfere with clonal evolutionary processes need to be understood better. Mathematical modeling is an important research tool that plays an ever-increasing role in cancer research. This paper discusses how mathematical models can be useful to gain insights into mechanisms that can prevent disease initiation, help analyze [...]

Cet article passe en revue les travaux récents sur les mécanismes d'action du lénalidomide lorsqu'il est administré seul ou en combinaison chez des patients atteints d'un lymphome non hodgkinien à cellules B

Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma

Gribben, John G. ; Fowler, Nathan ; Morschhauser, Franck

Lenalidomide is an orally active immunomodulatory drug that has direct antineoplastic activity and indirect effects mediated through multiple types of immune cells found in the tumor microenvironment, including B, T, natural killer (NK), and dendritic cells. Recently, the E3 ubiquitin ligase cereblon was identified as a molecular target that may underlie the effects of lenalidomide on tumor cells, as well as on cells in the tumor microenvironment. Decreases in cereblon attenuate these effects [...]

A partir d'échantillons de polypes prélevés dans le côlon et l'estomac de 7 patients atteints d'un mélanome traité à l'aide d'inhibiteurs de BRAF, puis menée à l'aide de modèles murins, cette étude suggère que ces thérapies ciblées sont susceptibles d'augmenter le risque de développer des polypes gastrointestinaux et, en raison du risque de transformation maligne, soulève la question de pratiquer des endoscopies de surveillance chez ces patients

Multiple gastrointestinal polyps in patients treated with BRAF inhibitors

Amaravadi, Ravi K ; Hamilton, Kathryn E. ; Ma, Xiaohong ; Piao, Shengfu ; Del Portillo, Armando ; Nathanson, Katherine L. ; Carlino, Matteo S ; Long, Georgina V. ; Puzanov, Igor ; Xu, Xaiowei ; Morrissette, Jennifer D ; Tsai, Kenneth Y ; Flaherty, Keith T. ; Sosman, Jeffrey ; Goodman, Grant R ; McArthur, Grant A ; Rustgi, Anil K. ; Metz, David C ; Schuchter, Lynn M. ; Chapman, Paul B. ; Seuplveda, Antonia R

Purpose: BRAF inhibitors (BRAFi) extend survival in BRAF mutant melanoma but can promote the growth of Ras mutant neoplasms. This study determined if gastrointestinal polyps found in BRAFi-treated patients harbored Ras mutations. Experimental Design: Colonic and gastric polyps were resected from BRAFi-treated melanoma patients. Next generation sequencing (NGS) was performed on polyps. The ability of BRAFi to promote polyp formation was functionally characterized in Apc Min +/- mice. MAPK and [...]

A partir d'échantillons tumoraux prélevés sur 174 patients atteints d'un carcinome à cellules rénales, puis menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude suggère l'intérêt de développer des thérapies ciblées sur Axl

Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma

Yu, H. ; Liu, R. ; Ma, B. ; Li, X. ; Yen, H. y ; Zhou, Y. ; Krasnoperov, V. ; Xia, Z. ; Zhang, X. ; Bove, A. M. ; Buscarini, M. ; Parekh, D. ; Gill, I. S. ; Liao, Q. ; Tretiakova, M. ; Quinn, D. ; Zhao, J. ; Gill, P. S.

Background: Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC). Methods: Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were [...]

Menée sur des lignées cellulaires d'ostéosarcome et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en régulant la voie de signalisation NF-kappaB, l'aspirine inhibe le processus métastatique

Aspirin suppresses the growth and metastasis of osteosarcoma through the NF-κB pathway

Kang, Tiebang ; Liao, Dan ; Zhong, Li ; Duan, Tingmei ; Zhang, Ruhua ; Wang, Xin ; Wang, Gang ; Hu, kaishun ; Lv, Xiaobing

Purpose: Aspirin has recently been reported to reduce both the incidence and the risk of metastasis in colon cancer. However, there is no evidence at the cellular levels or in the animal models for such an effect of Aspirin on cancer metastasis. Experimental Design: MTT assay, colony formation assay and apoptosis assay were employed to analyze the effects of Aspirin on the osteosarcoma (OS) cell viability in vitro. The NF-kB activity was measured by the NF-kB p65 luciferase reporter. Western [...]

Mené sur 21 patientes atteintes d'un cancer du sein, de l'ovaire ou de la trompe de Fallope (dont 16 présentant un gène BRCA muté), cet essai évalue la toxicité et l'activité antitumorale de l'olaparib en monothérapie après une chimiothérapie combinant carboplatine et paclitaxel (durée médiane du traitement : 52 semaines)

Long-term safety and anti-tumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer

van der Noll, Ruud ; Marchetti, Serena ; Steeghs, Neeltje ; Beijnen, Jos H. ; Mergui-Roelvink, Marja W. J. ; Harms, Emmy ; Rehorst, Harriet ; Sonke, Gabe S. ; Schellens, Jan H. M.

Background: Olaparib (AZD2281), a PARP-1/2 inhibitor, has been extensively investigated in clinical trials. However, limited clinical data are available about its long-term safety and anti-tumour activity. Methods: Patients had first participated in a phase I study of olaparib combined with carboplatin and/or paclitaxel. They continued with olaparib monotherapy in their best interest if they failed to tolerate the combination due to the treatment-related adverse events (TRAEs). Safety data were [...]

Mené sur 43 patients atteints d'une tumeur germinale de stade avancé et réfractaire (âge moyen : 30 ans), cet essai évalue l'efficacité, du point de vue de la survie sans récidive à 2 ans, et la toxicité d'un traitement combinant bévacizumab et une chimiothérapie à haute dose

Bevacizumab/High-Dose Chemotherapy with Autologous Stem-Cell Transplant for Poor-Risk Relapsed or Refractory Germ-Cell Tumors

Nieto, Y. ; Tu, S-M. ; Bassett, R. ; Jones, R. B. ; Gulbis, A. M. ; Tannir, N. ; Kingham, A. ; Ledesma, C. ; Margolin, K. ; Holmberg, L. ; Champlin, R. ; Pagliaro, L.

Background : High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab [...]

Mené sur 32 patients atteints d'un mycosis fongoïde ou d'un syndrome de Sézary de stade avancé ou réfractaire, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du brentuximab vedotin

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project

Kim, Youn H. ; Tavallaee, Mahkam ; Sundram, Uma ; Salva, Katrin A. ; Wood, Gary S. ; Li, Shufeng ; Rozati, Sima ; Nagpal, Seema ; Krathen, Michael ; Reddy, Sunil ; Hoppe, Richard T. ; Nguyen-Lin, Annie ; Weng, Wen-Kai ; Armstrong, Randall ; Pulitzer, Melissa ; Advani, Ranjana H. ; Horwitz, Steven M.

Purpose : In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods : In this phase II study, patients with MF or SS with negligible to 100% CD30 expression [...]

Mené sur 80 patients atteints d'un lymphome diffus à grandes cellules B récidivant ou réfractaire, cet essai de phase I/II évalue la toxicité et l'activité antitumorale de l'ibrunitib en fonction du sous-type de la maladie (ABC ou GCB)

Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma

Wilson, Wyndham H. ; Young, Ryan M. ; Schmitz, Roland ; Yang, Yandan ; Pittaluga, Stefania ; Wright, George ; Lih, Chih-Jian ; Williams, P. Mickey ; Shaffer, Arthur L. ; Gerecitano, John ; de Vos, Sven ; Goy, Andre ; Kenkre, Vaishalee P. ; Barr, Paul M. ; Blum, Kristie A. ; Shustov, Andrei ; Advani, Ranjana ; Fowler, Nathan H. ; Vose, Julie M. ; Elstrom, Rebecca L. ; Habermann, Thomas M. ; Barrientos, Jacqueline C. ; McGreivy, Jesse ; Fardis, Maria ; Chang, Betty Y. ; Clow, Fong ; Munneke, Brian ; Moussa, Davina ; Beaupre, Darrin M. ; Staudt, Louis M.

The two major subtypes of diffuse large B cell lymphoma (DLBCL)—activated B cell–like (ABC) and germinal center B cell–like (GCB)—arise by distinct mechanisms, with ABC selectively acquiring mutations that target the B cell receptor (BCR), fostering chronic active BCR signaling. The ABC subtype has a ~40% cure rate with currently available therapies, which is worse than the rate for GCB DLBCL, and highlights the need for ABC subtype-specific treatment strategies. We hypothesized that ABC, but [...]

Mené sur 20 patients atteints d'un myélome multiple, cet essai de phase I/II évalue la toxicité et l'activité antitumorale d'un traitement à base de lymphocytes T autologues modifiés pour exprimer un récepteur reconnaissant un peptide commun aux antigènes NY-ESO-1 et LAGE-1

NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma

Rapoport, Aaron P. ; Stadtmauer, Edward A. ; Binder-Scholl, Gwendolyn K. ; Goloubeva, Olga ; Vogl, Dan T. ; Lacey, Simon F. ; Badros, Ashraf Z. ; Garfall, Alfred ; Weiss, Brendan ; Finklestein, Jeffrey ; Kulikovskaya, Irina ; Sinha, Sanjoy K. ; Kronsberg, Shari ; Gupta, Minnal ; Bond, Sarah ; Melchiori, Luca ; Brewer, Joanna E. ; Bennett, Alan D. ; Gerry, Andrew B. ; Pumphrey, Nicholas J. ; Williams, Daniel ; Tayton- Martin, Helen K. ; Ribeiro, Lilliam ; Holdich, Tom ; Yanovich, Saul ; Hardy, Nancy ; Yared, Jean ; Kerr, Naseem ; Philip, Sunita ; Westphal, Sandra ; Siegel, Don L. ; Levine, Bruce L. ; Jakobsen, Bent K. ; Kalos, Michael ; June, Carl H.

Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 [times] 109 engineered T cells 2 d after autologous stem cell transplant. [...]

Mené au Japon sur 17 patients atteints d'une tumeur osseuse à cellules géantes, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du dénosumab

Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase 2 trial

Ueda, T. ; Morioka, H. ; Nishida, Y. ; Kakunaga, S. ; Tsuchiya, H. ; Matsumoto, Y. ; Asami, Y. ; Inoue, T. ; Yoneda, T.

Background : Giant cell tumor of bone (GCTB) is a rare primary bone tumor, characterized by osteoclast-like giant cells that express receptor activator of nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. A RANKL specific inhibitor, denosumab, was predicted to reduce osteolysis and control disease progression in patients with GCTB. Patients and methods : Seventeen patients with GCTB were enrolled. Patients were treated [...]

Cet article présente les données ayant servi de base à la "Food and Drug Administration" pour autoriser la mise sur le marché de l'olaparib dans le traitement des patientes atteintes d'un cancer avancé de l'ovaire présentant des mutations constitutionnelles d'un gène BRCA

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy

Kim, Geoffrey ; Ison, Gwynn ; McKee, Amy E ; Zhang, Hui ; Tang, Shenghui ; Gwise, Thomas ; Sridhara, Rajeshwari ; Lee, Eunice ; Tzou, Abraham ; Philip, Reena ; Chiu, Haw-Jyh ; Ricks, Tiffany K. ; Palmby, Todd ; Russell, Anne Marie ; Ladouceur, Gaetan ; Pfuma, Elimika ; Li, Hongshan ; Zhao, Liang ; Liu, Qi ; Venugopal, Rajesh ; Ibrahim, Amna ; Pazdur, Richard

On December 19, 2014, the FDA approved olaparib capsules (Lynparza™, AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx™ (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international, multicenter, single-arm trial enrolled 137 patients with measurable, gBRCAm-associated ovarian cancer treated with [...]

Mené en France sur 27 patients atteints d'un chordome de stade localement avancé ou métastatique, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de survie sans progression à 9 mois, et la toxicité du sorafénib

Sorafenib in patients with locally advanced and metastatic chordomas: a phase II trial of the French Sarcoma Group (GSF/GETO)

Bompas, E. ; Le Cesne, A. ; Tresch-Bruneel, E. ; Lebellec, L. ; Laurence, V. ; Collard, O. ; Saada-Bouzid, E. ; Isambert, N. ; Blay, J.Y. ; Amela, E.Y. ; Salas, S. ; Chevreau, C. ; Bertucci, F. ; Italiano, A. ; Clisant, S. ; Penel, N.

Purpose : There is no consensual treatment for locally advanced or metastatic chordomas. Methods : We conducted a multicenter, open-label, uncontrolled phase II trial of sorafenib (800 mg/d). The primary endpoint was the 9-month progression-free rate according to RECIST 1.1. All patients had documented progressive disease at the time of study entry. Results : Twenty-seven patients were enrolled between May 2011 and January 2014. The median age was 64 (range, 30-86). There were 17 men and 10 [...]

Menée sur 62 patients traités entre 2004 et 2012 pour un lymphome NK/T extra-ganglionnaire de type nasal et de stade localisé (durée médiane de suivi : 49 mois), cette étude évalue l'efficacité, du point de vue de la réponse complète, et la toxicité d'un traitement comportant une chimioradiothérapie concomitante suivie d'une chimiothérapie de consolidation

Concurrent Chemo-radiotherapy Followed by Consolidation Chemotherapy for Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal-type

Oh, Dongryul ; Ahn, Yong Chan ; Kim, Seok Jin ; Kim, Won Seog ; Ko, Young Hyeh

Purpose : To evaluate the effectiveness of concurrent chemo-radiotherapy (CCRT) with 40 Gy followed by consolidation chemotherapy for localized extranodal natural killer (NK)/T cell lymphoma (ENKTL), nasal-type. Patients and Methods : Between August 2004 and August 2012, a total of 62 patients with newly diagnosed stage IE-IIE ENKTL were treated with CCRT followed by consolidation chemotherapy. The median RT dose was 40 Gy. Cisplatin with 30 mg/m2 was administered weekly during RT course. [...]

Menée à partir des données du registre national américain des cancers portant sur 2 539 patients atteints d'un lymphome à cellules du manteau de stade I-II diagnostiqué entre 1998 et 2012 (durée médiane de suivi : 42,8 mois), cette étude analyse l'évolution de l'utilisation de la chimiothérapie et/ou de la radiothérapie, puis évalue, du point de vue de la survie, l'efficacité de différentes stratégies thérapeutiques

Management trends and outcomes for stage I-II mantle cell lymphoma using the National Cancer Data Base (NCDB): Ascertaining the ideal treatment paradigm

Gill, Beant S. ; Vargo, John A. ; Pai, Sarah S. ; Balasubramani, Goundappa K. ; Beriwal, Sushil

Purpose/objective(s) : Mantle cell lymphoma (MCL) is a rare albeit aggressive subset of non-Hodgkin’s lymphoma, resulting in varied treatment approaches. Given the paucity of data defining optimal management for early stage MCL, we conducted an analysis using the National Cancer Data Base (NCDB) to identify practice patterns and outcomes. Methods and materials : The NCDB was queried for patients with stage I-II MCL diagnosed from 1998-2012 receiving chemotherapy (CT), radiotherapy (RT) or both [...]

Menée à partir de données portant sur 848 patients atteints d'un cancer de l'œsophage traité entre 2000 et 2010 par chimioradiothérapie néoadjuvante et résection chirurgicale, cette étude multicentrique française évalue l'intérêt, du point de vue de la survie sans maladie, de la survie globale à 3 ans et des complications, d'une œsophagectomie de sauvetage

Salvage Surgery After Chemoradiotherapy in the Management of Esophageal Cancer: Is It a Viable Therapeutic Option?

Markar, Sheraz ; Gronnier, Caroline ; Duhamel, Alain ; Pasquer, Arnaud ; Théreaux, Jérémie ; du Rieu, Mael Chalret ; Lefevre, Jérémie H. ; Turner, Kathleen ; Luc, Guillaume ; Mariette, Christophe

Purpose : The aim of this large multicenter study was to assess the impact of salvage esophagectomy after definitive chemoradiotherapy (SALV) on clinical outcome. Patients and Methods : Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000 to 2010 were collected. First, groups undergoing SALV (n = 308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS; n = 540) were compared. Second, patients who benefited from [...]

Mené sur 36 patients atteints d'un sarcome des tissus mous des extrémités à haut risque de récidive (durée médiane de suivi : 6,2 ans), cet essai de phase I évalue la dose maximale tolérée de la gemcitabine en combinaison avec une radiothérapie concomitante néoadjuvante

Phase 1 adaptive dose-finding study of neoadjuvant gemcitabine combined with radiation therapy for patients with high-risk extremity and trunk soft tissue sarcoma

Tseng, William W. ; Zhou, Shouhao ; To, Christina A. ; Thall, Peter F. ; Lazar, Alexander J. ; Pollock, Raphael E. ; Lin, Patrick P. ; Cormier, Janice N. ; Lewis, Valerae O. ; Feig, Barry W. ; Hunt, Kelly K. ; Ballo, Matthew T. ; Patel, Shreyaskumar ; Pisters, Peter W. T.

BACKGROUND : This study was performed to determine the maximum tolerated dose (MTD) of gemcitabine given concurrently with preoperative, fixed-dose external-beam radiation therapy (EBRT) for patients with resectable, high-risk extremity and trunk soft tissue sarcoma (STS). METHODS : Gemcitabine was administered on days 1, 8, 22, 29, 43, and 50 with EBRT (50 Gy in 25 fractions over 5 weeks). The gemcitabine MTD was determined with a toxicity severity weight method (TSWM) incorporating 6 toxicity [...]

Cet article présente les recommandations de l'"American Society of Clinical Oncology" pour augmenter l'inclusion des patients âgés dans les essais cliniques de traitements anticancéreux

Improving the Evidence Base for Treating Older Adults With Cancer: American Society of Clinical Oncology Statement

Hurria, Arti ; Levit, Laura A. ; Dale, William ; Mohile, Supriya G. ; Muss, Hyman B. ; Fehrenbacher, Louis ; Magnuson, Allison ; Lichtman, Stuart M. ; Bruinooge, Suanna S. ; Soto-Perez-de-Celis, Enrique ; Tew, William P. ; Postow, Michael A. ; Cohen, Harvey J.

The American Society of Clinical Oncology (ASCO) convened a subcommittee to develop recommendations on improving the evidence base for treating older adults with cancer in response to a critical need identified by the Institute of Medicine. Older adults experience the majority of cancer diagnoses and deaths and make up the majority of cancer survivors. Older adults are also the fastest growing segment of the US population. However, the evidence base for treating this population is sparse, [...]

Cet article présente les recommandations de l'"European Society for Medical Oncology" en matière de diagnostic, de prise en charge thérapeutique et de suivi médical dans les cancers de la prostate

Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Parker, C. ; Gillessen, S. ; Heidenreich, A. ; Horwich, A.

Subclinical prostate cancer is common in men >50 years of age. Population-based screening of men aged between 55 and 69 years, using prostate-specific antigen (PSA) testing, has been evaluated in randomised trials. After a median follow-up of 13 years, the European screening trial demonstrated a relative reduction in the risk of prostate cancer mortality of 21% (29% if adjusted for non-compliance). However, 781 men needed to be invited for screening and 27 patients needed to be treated to [...]

Menée à partir des données des registres américains des cancers portant sur 7 057 patients atteints d'un cancer colorectal de stade II/III diagnostiqué entre 1990 et 2010 (âge : 20 ans ou plus), cette étude analyse l'évolution de l'utilisation de la chimiothérapie et de la radiothérapie, puis identifie les facteurs associés à cette utilisation

Patterns of Colorectal Cancer Care in the United States: 1990–2010

Murphy, Caitlin C. ; Harlan, Linda C. ; Lund, Jennifer L. ; Lynch, Charles F. ; Geiger, Ann M.

Background : Colorectal cancer (CRC) mortality has declined in the United States, in part because of advances in treatment. Few studies have evaluated the adoption of therapies and temporal changes in patterns of care. Methods : Patients age 20 years and older diagnosed with stages II/III CRC were randomly sampled from the population-based Surveillance, Epidemiology, and End Results (SEER) program in 1990–1991, 1995, 2000, 2005, and 2010 (n = 7057). Therapy was obtained from medical records and [...]