Menée sur 22 patients présentant des métastases spinales et traités entre juillet 2009 et avril 2011, cette étude évalue la précision et la toxicité d'une radiothérapie stéréotaxique corporelle basée sur la tomothérapie hélicoïdale

Is helical tomotherapy accurate and safe enough for spine stereotactic body radiotherapy?

Chung, Yoonsun ; Yoon, Hong ; Kim, Joo ; Nam, Ki ; Koom, Woong

Purpose We assessed the accuracy and safety of spine stereotactic body radiation therapy (SBRT) using helical tomotherapy (HT) via evaluating intrafractional patient movement. Methods From July 2009 to April 2011, 22 patients with spine lesions received SBRT using HT, with a total of 61 fractions. To evaluate intrafractional movement, we compared post-treatment megavoltage CT scans with planning CT images and obtained translational [lateral ( X ), craniocaudal ( Y ), anterioposterior ( Z )] [...]

A partir d'une revue systématique de la littérature publiée jusqu'en janvier 2012 (27 études, 8 809 patients), cette méta-analyse évalue l'efficacité et la toxicité de particules chargées (protons, ions hélium, ions carbone) pour traiter un mélanome de l'uvée

Charged Particle Radiation Therapy for Uveal Melanoma: A Systematic Review and Meta-Analysis

Wang, Zhen ; Nabhan, Mohammed ; Schild, Steven E. ; Stafford, Scott L. ; Petersen, Ivy A. ; Foote, Robert L. ; Murad, M. Hassan

Charged particle therapy (CPT) delivered with either protons, helium ions, or carbon ions, has been used to treat uveal melanoma. The present analysis was performed to systematically evaluate the efficacy and adverse effects of CPT for uveal melanoma. We searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus and cross-referenced recent systematic reviews through January 2012. Two independent reviewers identified [...]

Menée in vitro, cette étude met en évidence un mécanisme d'action du sorafenib, un inhibiteur de plusieurs protéines-kinases utlisé dans le traitement du carcinome hépatocellulaire

Sorafenib-mediated targeting of the AAA+ ATPase p97/VCP leads to disruption of the secretory pathway, endoplasmic reticulum stress and hepatocellular cancer cell death

Yi, Ping ; Higa, Arisa ; Taouji, Said ; Bexiga, Mariana G ; Marza, Esther ; Arma, Daniela ; Castain, Claire ; Le Bail, Brigitte ; Simpson, Jeremy ; Rosenbaum, Jean ; Balabaud, Charles ; Bioulac-Sage, Paulette ; Blanc, Jean-Frederic ; Chevet, Eric

The molecular mechanisms and cellular targets of Sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma (HCC), remain to be fully characterized. Recent studies have shown that Sorafenib induces tumor cell death through the activation of endoplasmic reticulum (ER) stress signaling and/or autophagy in various cellular models. Using liver cancer-derived cell lines, we specifically demonstrate that the IRE1 and PERK arms of the Unfolded Protein Response (UPR) become [...]

Menée in vitro et in vivo, cette étude montre que, par rapport à la protéine ERK2, ERK1 joue un rôle prédominant dans la mort celullaire induite par un traitement au cisplatine d'un carcinome hépatocellulaire

MAPK signalling in cisplatin-induced death: predominant role of ERK1 over ERK2 in human hepatocellular carcinoma cells

Guégan, Jean-Philippe ; Ezan, Frédéric ; Théret, Nathalie ; Langouët, Sophie ; Baffet, Georges

Hepatocellular carcinoma treatment by arterial infusion of cisplatin exhibits certain therapeutic efficacy. However, optimizations are required and the mechanisms underlying cisplatin pro-apoptotic effect remain unclear. The mitogen-activated protein kinase (MAPK) pathway plays a key role in cell response to cisplatin and the functional specificity of the isoform MEK1/2 and ERK1/2 could influence this response. The individual contribution of each kinase on cisplatin-induced death was thus [...]

Menée in vitro et à l'aide de modèles murins transgéniques, cette étude montre qu'un vaccin thérapeutique universel à base de peptides dérivés de la sous-unité TERT de la télomérase induit une réponse immunitaire antitumorale dans différents types de cancer

Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor

Dosset, Magalie ; Godet, Yann ; Vauchy, Charline ; Beziaud, laurent ; Lone, Yu Chun ; Sedlik, Christine ; Liard, Christelle ; Levionnois, Emeline ; Clerc, Bertrand ; Sandoval, Federico ; Daguindau, Etienne ; Wain-Hobson, Simon ; Tartour, Eric ; Langlade-Demoyen, Pierre ; Borg, Christophe ; ADOTEVI, Olivier

Purpose:To evaluate CD4+ helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT). Experimental Design: To evaluate the widespread immunogenicity of UCPs in human, spontaneous T cell responses against UCPs were measured in various types of cancer using T cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice was used to study CD4+ helper effects of UCPs on antitumor CTL [...]

Menée in vitro et in vivo, cette étude montre que des inhibiteurs de l'exportation nucléaire ciblant spécifiquement la protéine XPO1 sont suceptibles d'induire une apoptose des cellules de leucémie lymphocytaire chronique

Selective inhibitors of nuclear export (SINE) show that CRM1/XPO1 is a target in chronic lymphocytic leukemia

Lapalombella, Rosa ; Sun, Qingxiang ; Williams, Katie ; Tangeman, Larissa ; Jha, Shruti ; Zhong, Yiming ; Goettl, Virginia ; Mahoney, Emilia ; Berglund, Caroline ; Gupta, Sneha ; Farmer, Alicia ; Mani, Rajeswaran ; Johnson, Amy J. ; Lucas, David ; Mo, Xiaokui ; Daelemans, Dirk ; Sandanayaka, Vincent ; Shechter, Sharon ; McCauley, Dilara ; Shacham, Sharon ; Kauffman, Michael ; Chook, Yuh Min ; Byrd, John C.

The nuclear export protein XPO1 is over-expressed in cancer, leading to the cytoplasmic mislocalization of multiple tumor suppressor proteins. Existing XPO1-targeting agents lack selectivity and have been associated with significant toxicity. Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of XPO1, thereby [...]

Menée sur des lignées cellulaires, sur 242 échantillons tumoraux prélevés sur des patients atteints d'un mélanome et à l'aide de xénogreffes, cette étude suggère que l'inhibition des kinases IRAK-1/4 permet d'augmenter la réponse à un traitement par vinblastine

Augmentation of therapeutic responses in melanoma by inhibition of IRAK-1,-4

Srivastava, Ratika ; Geng, Degui ; Liu, Yingjia ; Zheng, Liqin ; Li, Zhaoyang ; Joseph, Mary Ann ; McKenna, Colleen ; Bansal, Navneeta ; Ochoa, Augusto C ; Davila, Eduardo

Toll-like receptors (TLR) are expressed by a variety of cancers, including melanoma, but their functional contributions in cancer cells are uncertain. To approach this question, we evaluated the effects of stimulating or inhibiting the TLR/IL-1 receptor-associated kinases IRAK-1 and IRAK-4 in melanoma cells where their functions are largely unexplored. TLRs and TLR-related proteins were variably expressed in melanoma cell lines, with 42% expressing activated phospho-IRAK-1 constitutively and [...]

Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'intérêt d'un micro-ARN de synthèse, miR-34a, pour le traitement des myélomes multiples

Synthetic miR-34a mimics as a novel therapeutic agent for Multiple Myeloma: in vitro and in vivo evidence

Di Martino, Maria T. ; Leone, Emanuela ; Amodio, Nicola ; Foresta, Umberto ; Lionetti, Marta ; Pitari, Maria Rita ; Gallo Cantafio, Maria E. ; Gullà, Annamaria ; Conforti, Francesco ; Morelli, Eugenio ; Tomaino, Vera ; Rossi, Marco ; Negrini, Massimo ; Ferrarini, Manlio ; Caraglia, Michele ; Shammas, Masood A. ; Munshi, Nikhil C. ; Anderson, Kenneth C. ; Neri, Antonino ; Tagliaferri, Pierosandro ; Tassone, Pierfrancesco

Purpose:Deregulated expression of microRNAs (miRNAs) has been demonstrated in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a Experimental Design:Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo Results:Either transient expression of miR-34a synthetic mimics or [...]

Menée sur des lignées cellulaires de cancer du pancréas, cette étude évalue l'activité antitumorale d'un nouvel inhibiteur de la kinase Aurora A, CYC3, en combinaison avec le paclitaxel

Paclitaxel and CYC3, an aurora kinase A inhibitor, synergise in pancreatic cancer cells but not bone marrow precursor cells

Lin, Y. ; Richards, F. M. ; Krippendorff, B. F. ; Bramhall, J. L. ; Harrington, J. A. ; Bapiro, T. E. ; Robertson, A. ; Zheleva, D. ; Jodrell, D. I.

Background: Amplification of aurora kinase A (AK-A) overrides the mitotic spindle assembly checkpoint, inducing resistance to taxanes. RNA interference targeting AK-A in human pancreatic cancer cell lines enhanced taxane chemosensitivity. In this study, a novel AK-A inhibitor, CYC3, was investigated in pancreatic cancer cell lines, in combination with paclitaxel. Methods: Western blot, flow cytometry and immunostaining were used to investigate the specificity of CYC3. Sulforhodamine B staining, [...]

Menée sur des lignées cellulaires de cancer du poumon à petites cellules, cette étude suggère l'intérêt d'un traitement basé sur l'inhibition de la kinase Aurora B

A framework for identification of actionable cancer genome dependencies in small cell lung cancer

Sos, Martin L. ; Dietlein, Felix ; Peifer, Martin ; Schöttle, Jakob ; Balke-Want, Hyatt ; Muller, Christian ; Koker, Mirjam ; Richters, André ; Heynck, Stefanie ; Malchers, Florian ; Heuckmann, Johannes M. ; Seidel, Danila ; Eyers, Patrick A. ; Ullrich, Roland T. ; Antonchick, Andrey P. ; Vintonyak, Viktor V. ; Schneider, Peter M. ; Ninomiya, Takashi ; Waldmann, Herbert ; Büttner, Reinhard ; Rauh, Daniel ; Heukamp, Lukas C. ; Thomas, Roman K.

Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. The prognosis of SCLC patients is devastating and no biologically targeted therapeutics are active in this tumor type. To develop a framework for development of specific SCLC-targeted drugs we conducted a combined genomic and pharmacological vulnerability screen in SCLC cell lines. We show that SCLC cell lines capture the genomic landscape of primary SCLC tumors and provide genetic predictors for activity of clinically [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'intérêt d'une thérapie génique à base d'un vecteur lentiviral pour le traitement d'un adénocarcinome du poumon

Oxidative stress-regulated lentiviral TK/GCV gene therapy for lung cancer treatment

Leinonen, Hanna M ; Ruotsalainen, Anna-Kaisa ; Määttä, Ann-Marie ; Laitinen, Heidi M ; Kuosmanen, Suvi M ; Kansanen, Emilia ; Pikkarainen, Jere T ; Lappalainen, Jari P ; Samaranayake, Haritha ; Lesch, Hanna P ; Levonen, Anna-Liisa ; Kaikkonen, Minna U ; Ylä-Herttuala, Seppo

NRF2 is a transcription factor that regulates protection against a wide variety of toxic insults to cells, including cytotoxic cancer chemotherapeutic drugs. Many lung cancer cells harbor a mutation in either NRF2 or its inhibitor KEAP1 resulting in permanent activation of NRF2 and chemoresistance. In this study, we sought to examine whether this attribute could be exploited in cancer suicide gene therapy by using a lentiviral (LV) vector expressing herpes simplex virus thymidine kinase [...]

Cet article passe en revue les perspectives offertes par les travaux récents en génomique des cancers du rein pour le développement de nouveaux traitements

Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics

Linehan, W. Marston

Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), [...]

Menée in vitro et sur des modèles murins de glioblastome multiforme, cette étude évalue l'efficacité du géfinitib et du sunitinib, seuls ou en combinaison

Evaluation of Tyrosine Kinase Inhibitor Combinations for Glioblastoma Therapy

Joshi, Avadhut D. ; Loilome, Watcharin ; Siu, I. Mei ; Tyler, Betty ; Gallia, Gary L. ; Riggins, Gregory J.

Glioblastoma multiforme (GBM) is the most common intracranial cancer but despite recent advances in therapy the overall survival remains about 20 months. Whole genome exon sequencing studies implicate mutations in the receptor tyrosine kinase pathways (RTK) for driving tumor growth in over 80% of GBMs. In spite of various RTKs being mutated or altered in the majority of GBMs, clinical studies have not been able to demonstrate efficacy of molecular targeted therapies using tyrosine kinase [...]

Menée in vitro et à l'aide de xénogreffes, cette étude montre que la dexaméthasone, une hormone glucocorticoïde souvent prescrite pour réduire la toxicité d'une chimiothérapie chez les patients atteints d'un cancer avancé de la vessie, est susceptible de favoriser la prolifération cellulaire en inhibant l'apoptose

Contrary Regulation of Bladder Cancer Cell Proliferation and Invasion by Dexamethasone-Mediated Glucocorticoid Receptor Signals

Zheng, Yichun ; Izumi, Koji ; Li, Yi ; Ishiguro, Hitoshi ; Miyamoto, Hiroshi

In patients with advanced bladder cancer, glucocorticoids are frequently given to reduce acute toxicity, particularly hyperemesis, during chemotherapy, as well as to improve cachectic conditions. However, it remains unclear whether glucocorticoids directly affect the development and progression of bladder cancer through the glucocorticoid receptor (GR) pathway. GR expression was first investigated in human bladder cancer lines and tissue microarrays. Then, the effects of dexamethasone on GR [...]

Cet article passe en revue les travaux récents sur la détection et la prévention des complications cardiaques des chimiothérapies anticancéreuses

Detection and prevention of cardiac complications of cancer chemotherapy

Monsuez, Jean-Jacques

Summary Despite continuous improvements in management of patients with cancer, cardiac side-effects still account for a substantial limitation of chemotherapy. Evaluation of cardiac toxicity in patients includes consideration of biomarkers such as cardiac troponins and B-type natriuretic peptides, together with non-invasive imaging in the form of 2D-, 3D-, or strain-echocardiography, multiple gated radionuclide angiography, quantitative gated blood-pool SPECT, 123I-metaiodobenzylguanidine [...]

Mené sur des cohortes de 3 à 6 patients atteints d'une tumeur solide réfractaire, cet essai de phase I évalue la dose maximale tolérée du vintafolide, un conjugué injectable composé d'acide folique associé à un agent à base de vinca-alcaloïdes

Phase I Study of Folate Conjugate EC145 (Vintafolide) in Patients With Refractory Solid Tumors

LoRusso, Patricia M. ; Edelman, Martin J. ; Bever, Susan L. ; Forman, Karen M. ; Pilat, MaryJo ; Quinn, Mary F. ; Li, Jing ; Heath, Elisabeth I. ; Malburg, Lisa M. ; Klein, Patrick J. ; Leamon, Christopher P. ; Messmann, Richard A. ; Sausville, Edward A.

Purpose : EC145 (vintafolide), a conjugate of folic acid and the vinca alkaloid desacetylvinblastine hydrazide (DAVLBH), is a ligand for the folate receptor (FR), with activity against FR-positive tumor xenografts in vivo. This phase I study determined the maximum-tolerated dose (MTD) of EC145 administered as a bolus intravenous injection or 1-hour infusion in patients with refractory solid tumors. Patients and Methods : EC145 was administered as a bolus injection or 1-hour infusion on days 1, [...]

Mené sur 172 patients atteints d'un mélanome métastatique présentant une mutation Val600Glu ou Val600Lys du gène BRAF et au moins une métastase cérébrale asymptomatique, cet essai international de phase II (24 centres, 6 pays) évalue l'efficacité et la toxicité du dabrafenib

Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial

Long, Georgina V. ; Trefzer, Uwe ; Davies, Michael A. ; Kefford, Richard F. ; Ascierto, Paolo A. ; Chapman, Paul B. ; Puzanov, Igor ; Hauschild, Axel ; Robert, Caroline ; Algazi, Alain ; Mortier, Laurent ; Tawbi, Hussein ; Wilhelm, Tabea ; Zimmer, Lisa ; Switzky, Julie ; Swann, Suzanne ; Martin, Anne-Marie ; Guckert, Mary ; Goodman, Vicki ; Streit, Michael ; Kirkwood, John M. ; Schadendorf, Dirk

Background : Brain metastases are common in patients with metastatic melanoma and median overall survival from their diagnosis is typically 17-22 weeks. We assessed dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain. Methods: We undertook a multicentre, open-label, phase 2 trial in 24 centres in six countries. We enrolled patients with histologically confirmed Val600Glu or Val600Lys BRAF-mutant melanoma and at least one asymptomatic brain metastasis [...]

Mené sur 68 patients atteints d'un myélome multiple asymptomatique, cet essai de phase III évalue, du point de vue de la survie sans progression, l'ajout de thalidomide à l'acide zolédronique

A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma

Witzig, T. E. ; Laumann, K. M. ; Lacy, M. Q. ; Hayman, S. R. ; Dispenzieri, A. ; Kumar, S. ; Reeder, C. B. ; Roy, V. ; Lust, J. A. ; Gertz, M. A. ; Greipp, P. R. ; Hassoun, H. ; Mandrekar, S. J. ; Rajkumar, S. V.

Patients with asymptomatic (smoldering) multiple myeloma (AMM) have a high risk of transformation to active multiple myeloma (MM). Bisphosphonates such as zoledronic acid (ZLD) reduce skeletal events in MM and the immunomodulatory agent thalidomide (Thal) has proven effectiveness in active MM. We hypothesized that treatment with Thal and ZLD would prolong the time to progression (TTP) to MM over ZLD alone. Eligible patients had asymptomatic MM and all patients received ZLD 4 mg intravenous [...]

Mené sur 32 patients atteints d'un myélome multiple récidivant ou réfractaire, cet essai de phase I évalue l'efficacité et la toxicité d'un composé appelé IPH2101, un anticorps anti-KIR

A phase I trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma

Benson, Don M. ; Hofmeister, Craig C. ; Padmanabhan, Swaminathan ; Suvannasankha, Attaya ; Jagganath, Sundar ; Abonour, Rafat ; Bakan, Courtney ; Andre, Pascale ; Efebera, Yvonne ; Tiollier, Jérôme ; Caligiuri, Michael A. ; Farag, Sherif S.

Natural killer (NK) cells elicit cytotoxicity against multiple myeloma (MM); however, MM cells express HLA class I molecules as ligands to NK cell inhibitory killer immunoglobulin-like receptors (KIR) as a means of immunoevasion. KIR-ligand mismatch may improve outcomes in allogeneic transplantation for MM. Extrapolating on this concept, we conducted a phase I trial of IPH2101, an anti-KIR antibody, in patients with relapsed/refractory MM. IPH2101 was administered intravenously every 28 days in [...]

Cet article passe en revue les travaux récents sur l'intérêt du gefitinib, de l'erlotinib et de l'afatinib pour le traitement de patients atteints d'un cancer du poumon non à petites cellules présentant des mutations du gène EGFR

Should epidermal growth factor receptor tyrosine kinase inhibitors be considered ideal drugs for the treatment of selected advanced non-small cell lung cancer patients?

Rossi, Antonio ; Pasquale, Raffaella ; Esposito, Claudia ; Normanno, Nicola

An ideal target-based agent for the treatment of cancer patients should fulfil a number of requirements, including the availability of biomarkers to select the target population, superiority over existing treatments and specific advantages in terms of pharmacokinetics and/or metabolism. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib and afatinib, have been investigated in the treatment of non-small cell lung cancer (NSCLC), and to date a [...]

Mené sur 65 patients atteints d'un cancer colorectal métastatique sans mutations KRAS et réfractaire aux chimiothérapies de référence, cet essai du groupe GERCOR évalue un traitement de troisième ligne combinant panitumumab et irinotecan

Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study

André, T. ; Blons, H. ; Mabro, M. ; Chibaudel, B. ; Bachet, J-B. ; Tournigand, C. ; Bennamoun, M. ; Artru, P. ; Nguyen, S. ; Ebenezer, C. ; Aissat, N. ; Cayre, A. ; Penault-Llorca, F. ; Laurent-Puig, P. ; de Gramont, A.

Background The purpose of this study was to evaluate the combination of panitumumab and irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines–irinotecan and bevacizumab).Patients and methods KRAS status was first determined locally but subsequent validation of KRAS status and additional screenings (rare KRAS, NRAS, BRAF mutations and EGFR copy number) were centrally assessed. Patients received panitumumab [...]

Menée sur 30 patientes atteintes d'un carcinome lobulaire invasif traité entre 1999 et 2009, cette étude analyse les effets clinicopathologiques d'une chimiothérapie néo-adjuvante (durée médiane de suivi : 29,5 mois)

Pathologic Tumor Response of Invasive Lobular Carcinoma to Neo-adjuvant Chemotherapy

Joh, Jennifer E. ; Esposito, Nicole N. ; Kiluk, John V. ; Laronga, Christine ; Khakpour, Nazanin ; Soliman, Hatem ; Catherine Lee, M.

Abstract: Neo-adjuvant chemotherapy is used for locally advanced breast cancer patients with significant variation in tumor response. Our objective is to determine the clinicopathologic effect of neo-adjuvant chemotherapy on invasive lobular carcinoma. A review of a single-institution data base of women diagnosed with breast cancer identified 30 patients from 1999 to 2009 with operable invasive lobular carcinoma who received neo-adjuvant chemotherapy. Patient demographics and clinicopathologic [...]

A partir de données portant sur 99 patients inclus dans 5 essais cliniques de phase II évaluant le bevacizumab pour le traitement d'un glioblastome récidivant, cette étude évalue, du point de vue de la survie globale, l'intérêt de poursuivre le traitement au bevacizumab après l'observation d'une progression de la maladie

Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients

Reardon, D. A. ; Herndon, J. E., II ; Peters, K. B. ; Desjardins, A. ; Coan, A. ; Lou, E. ; Sumrall, A. L. ; Turner, S. ; Lipp, E. S. ; Sathornsumetee, S. ; Rich, J. N. ; Sampson, J. H. ; Friedman, A. H. ; Boulton, S. T. ; Bigner, D. D. ; Friedman, H. S. ; Vredenburgh, J. J.

Background: Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among recurrent glioblastoma patients as it is a common, yet unsupported practice in some countries. Methods: We analysed outcome among all patients (n=99) who received subsequent therapy after progression on one of five consecutive, single-arm, phase [...]

Cet article passe en revue les études récentes concernant l'effet des rayonnements ionisants sur l'immunité tumorale et fait le point sur les cibles thérapeutiques potentielles dans le cadre d'un traitement anticancéreux combinant radiothérapie et immunothérapie

Radiation therapy and immunotherapy: Implications for a combined cancer treatment

Levy, Antonin ; Chargari, Cyrus ; Cheminant, Morgane ; Simon, Noémie ; Bourgier, Céline ; Deutsch, Eric

Ionizing radiation (IR) is used as primary treatment for numerous localized cancers. Although it is usually described as an immunosuppressive modality, there are new preclinical evidences suggesting that IR could have also generated substantial changes in the tumor microenvironment, including triggering an inflammatory process. This finding implies that radiotherapy could both modulate tumor immunity and have out-of-field activity by recruiting biological effectors. There are numerous [...]

Menée sur 112 patientes atteintes d'un cancer du sein à risque élevé de récidive et ayant subi une mastectomie (durée médiane de suivi : 44 mois), cette étude évalue, du point de vue de la survie sans récidive locale et de la survie spécifique à 5 ans, l'efficacité et la toxicité d'une radiothérapie accélérée hypofractionnée, combinée ou non à une cytoprotection à base d'amifostine délivrée par voie sous-cutanée

Postmastectomy Hypofractionated and Accelerated Radiation Therapy With (and Without) Subcutaneous Amifostine Cytoprotection

Koukourakis, Michael I. ; Panteliadou, Marianthi ; Abatzoglou, Ioannis M. ; Sismanidou, Kyriaki ; Sivridis, Efthimios ; Giatromanolaki, Alexandra

Postmastectomy radiation therapy (PMRT) provides major local control and survival benefits. More aggressive radiation therapy schemes may, however, be necessary in specific subgroups, provided they are safely administered. We report the tolerance and efficacy of a highly accelerated and hypofractionated regimen (HypoARC). One hundred twelve high-risk patients who had undergone mastectomy received 10 consecutive fractions of 3.5 Gy in 12 days (thoracic wall and axillary/supraclavicular areas). [...]

Menée sur 72 patients atteints d'un cancer oropharyngé de stade III-IV et ayant reçu une chimiothérapie combinée à une radiothérapie avec modulation d'intensité, cette étude prospective longitudinale analyse le degré de xérostomie et de dysphagie post-traitement ainsi que la qualité de vie auto-rapportée des patients

Toxicities Affecting Quality of Life After Chemo-IMRT of Oropharyngeal Cancer: Prospective Study of Patient-Reported, Observer-Rated, and Objective Outcomes

Hunter, Klaudia U. ; Schipper, Matthew ; Feng, Felix Y. ; Lyden, Teresa ; Haxer, Mark ; Murdoch-Kinch, Carol-Anne ; Cornwall, Benjamin ; Lee, Connie S. Y. ; Chepeha, Douglas B. ; Eisbruch, Avraham

To test the hypothesis that intensity modulated radiation therapy (IMRT) aiming to spare the salivary glands and swallowing structures would reduce or eliminate the effects of xerostomia and dysphagia on quality of life (QOL). In this prospective, longitudinal study, 72 patients with stage III-IV oropharyngeal cancer were treated uniformly with definitive chemo-IMRT sparing the salivary glands and swallowing structures. Overall QOL was assessed by summary scores of the Head Neck QOL (HNQOL) and [...]