Menée in vitro et à l'aide de modèles murins, cette étude évalue l'efficacité d'une photothérapie dynamique utilisant, comme agent photosensibilisant, un complexe gadolinium-porphyrine capable de se fixer aux cellules tumorales

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

Zhang, Tao ; Lan, Rongfeng ; Chan, Chi-Fai ; Law, Ga-Lai ; Wong, Wai-Kwok ; Wong, Ka-Leung

In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. [...]

Menée sur 235 patients atteints d'un cancer du poumon non à petites cellules de stade IIIB ou IV et présentant un faible niveau de performance physique (indice de Karnofsky compris entre 40 et 30), cette étude évalue, du point de vue du taux de survie globale à 90 jours et des symptômes associés à la croissance locale de la tumeur, l'intérêt d'ajouter une radiothérapie thoracique palliative à des soins de support

Palliative thoracic radiotherapy for patients with advanced non-small cell lung cancer and poor performance status

Walasek, Tomasz ; Sas-Korczynska, Beata ; Dąbrowski, Tomasz ; Reinfuss, Marian ; Jakubowicz, Jerzy ; Blecharz, Paweł ; Łuczyńska, Elżbieta ; Darasz, Zbigniew ; Skotnicki, Piotr

Objective : The evaluation of efficacy of palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) and to compare it with efficacy of supportive care (SC) alone. Materials and Methods : Between 2000 and 2012, 235 patients with advanced NSCLC (IIIB and IV) and Karnofsky Performance Status accounted 40-30, were qualified to PTR. In fact, 125 (53.2%) out of them were treated with PTR, and 110 (46.8%)–with SC alone, in accordance with patients [...]

Menée à partir de données portant sur 55 patients présentant des métastases surrénales ayant pour origine un carcinome hépatocellulaire, cette étude chinoise évalue la sécurité d'une radiothérapie ciblant les métastases, puis identifie les facteurs prédictifs associés à la survie des patients

Radiotherapy treatment of adrenal gland metastases from hepatocellular carcinoma: clinical features and prognostic factors

Zhou, Le-Yuan ; Zeng, Zhao-Chong ; Fan, Jia ; Chen, Bing ; Rao, Sheng-xiang ; He, Jian ; Yang, Ping ; Hou, Jia-zhou ; Wu, Zhi-feng ; Zhang, Jian-ying ; Hu, Yong

Background : The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. Methods : We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were [...]

Menée à partir de données portant sur 143 patients atteints d'un lymphome hodgkinien de stade précoce (âge médian : 31 ans), cette étude met en évidence une association entre l'expression de la cyclo-oxygénase de type 2 dans les cellules de Reed-Sternberg et un pronostic défavorable, puis montre qu'une radiothérapie peut améliorer ce pronostic

Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

Mestre, Francisco ; Gutiérrez, Antonio ; Rodriguez, Jose ; Ramos, Rafael ; Garcia, Juan Fernando ; Martinez-Serra, Jordi ; Casasus, Marta ; Nicolau, Cristina ; Bento, Leyre ; Herraez, Ines ; Lopez-Perezagua, Paloma ; Daumal, Jaime ; Besalduch, Joan

Purpose : To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials : In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue [...]

Menée à partir de données portant sur 219 patients atteints d'un carcinome rhinopharyngé non métastatique de stade T1-2b traité par radiothérapie externe, cette étude compare, du point de vue du taux actuariel de survie sans récidive loco-régionale à 5 ans et du taux de survie sans maladie, l'efficacité d'une curiethérapie à haut débit de dose guidée par l'image tridimensionnelle par rapport à une curiethérapie bidimensionnelle à haut débit de dose

3D-image-guided HDR-brachytherapy versus 2D HDR - brachytherapy after external beam radiotherapy for early T-stage nasopharyngeal carcinoma

Ren, Yu ; Zhao, Quancheng ; Liu, Hui ; Huang, YingJuan ; Wang, Zhen ; Cao, Xin ; Teh, Bin ; Wen, Bi

Background : Two-dimensional high-dose-rate brachytherapy (2D-HDR-BT) is an effective method of dose escalation for local tumor control in early T-stage nasopharyngeal carcinoma (NPC). Treatment outcomes for 3D-image-guided high-dose-rate brachytherapy (3D-image-guided-HDR-BT) after external beam radiotherapy (ERT) have not been examined in early T-stage NPC patients. The current study was designed to evaluate whether addition of 3D-HDR-BT to ERT showed further improvement in treatment outcomes [...]

Menée in vitro, cette étude met en évidence des mécanismes suggérant l'intérêt d'un traitement à base d'inhibiteurs de FGFR3 pour les patients atteints d'une tumeur stromale gastro-intestinale ayant développé une résistance à l'imatinib sans mutation du gène KIT

Crosstalk between KIT and FGFR3 Promotes Gastrointestinal Stromal Tumor Cell Growth and Drug Resistance

Javidi-Sharifi, Nathalie ; Traer, Elie ; Martinez, Jacqueline ; Gupta, Anu ; Taguchi, Takehiro ; Dunlap, Jennifer ; Heinrich, Michael C ; Corless, Christopher L ; Rubin, Brian P ; Druker, Brian J. ; Tyner, Jeffrey W.

Kinase inhibitors such as imatinib have dramatically improved outcomes for GIST patients, but many patients develop resistance to these treatments. While in some patients this event corresponds with mutations in the GIST driver oncogenic kinase KIT, other patients development resistance without KIT mutations. In this study, we address this patient subset in reporting a functional dependence of GIST on the FGF receptor FGFR3 and its crosstalk with KIT in GIST cells. Addition of the FGFR3 ligand [...]

Menée sur des lignées cellulaires de cancer du poumon, du sein ou du côlon, cette étude met en évidence des mécanismes par lesquels, en inactivant les récepteurs du facteur de croissance épidermique, les bisphosphonates sont susceptibles d'exercer une activité antitumorale

Bisphosphonates inactivate human EGFRs to exert antitumor actions

Yuen, Tony ; Stachnik, Agnes ; Iqbal, Jameel ; Sgobba, Miriam ; Gupta, Yogesh ; Lu, Ping ; Colaianni, Graziana ; Ji, Yaoting ; Zhu, Ling-Ling ; Kim, Se-Min ; Li, Jianhua ; Liu, Peng ; Izadmehr, Sudeh ; Sangodkar, Jaya ; Bailey, Jack ; Latif, Yathin ; Mujtaba, Shiraz ; Epstein, Solomon ; Davies, Terry F. ; Bian, Zhuan ; Zallone, Alberta ; Aggarwal, Aneel K. ; Haider, Shozeb ; New, Maria I. ; Sun, Li ; Narla, Goutham ; Zaidi, Mone

Bisphosphonates are the most commonly prescribed medicines for osteoporosis and skeletal metastases. The drugs have also been shown to reduce cancer progression, but only in certain patient subgroups, suggesting that there is a molecular entity that mediates bisphosphonate action on tumor cells. Using connectivity mapping, we identified human epidermal growth factor receptors (human EGFR or HER) as a potential new molecular entity for bisphosphonate action. Protein thermal shift and cell-free [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude suggère l'intérêt d'un traitement à base de ruxolitinib, un inhibiteur de JAK1/2, ou d'un composé appelé PU-H71, un inhibiteur de la protéine de choc thermique Hsp90, pour les patients atteints d'une leucémie myéloïde aiguë consécutive à la transformation d'une néoplasie myéloproliférative

Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms

Rampal, Raajit ; Ahn, Jihae ; Abdel-Wahab, Omar ; Nahas, Michelle ; Wang, Kai ; Lipson, Doron ; Otto, Geoff A. ; Yelensky, Roman ; Hricik, Todd ; McKenney, Anna Sophia ; Chiosis, Gabriela ; Chung, Young Rock ; Pandey, Suveg ; van den Brink, Marcel R. M. ; Armstrong, Scott A. ; Dogan, Ahmet ; Intlekofer, Andrew ; Manshouri, Taghi ; Park, Christopher Y. ; Verstovsek, Srdan ; Rapaport, Franck ; Stephens, Philip J. ; Miller, Vincent A. ; Levine, Ross L.

Patients with myeloproliferative neoplasms (MPNs) are at significant, cumulative risk of leukemic transformation to acute myeloid leukemia (AML), which is associated with adverse clinical outcome and resistance to standard AML therapies. We performed genomic profiling of post-MPN AML samples; these studies demonstrate somatic tumor protein 53 (TP53) mutations are common in JAK2V617F-mutant, post-MPN AML but not in chronic-phase MPN and lead to clonal dominance of JAK2V617F/TP53-mutant leukemic [...]

Menée in vitro, in vivo et in silico, cette étude met notamment en évidence des mécanismes suggérant l'intérêt des bisphosphonates pour surmonter l'apparition d'une résistance à l'erlotinib chez les patients atteints d'un cancer du poumon non à petites cellules

Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer

Stachnik, Agnes ; Yuen, Tony ; Iqbal, Jameel ; Sgobba, Miriam ; Gupta, Yogesh ; Lu, Ping ; Colaianni, Graziana ; Ji, Yaoting ; Zhu, Ling-Ling ; Kim, Se-Min ; Li, Jianhua ; Liu, Peng ; Izadmehr, Sudeh ; Sangodkar, Jaya ; Scherer, Thomas ; Mujtaba, Shiraz ; Galsky, Matthew ; Gomez, Jorge ; Epstein, Solomon ; Buettner, Christoph ; Bian, Zhuan ; Zallone, Alberta ; Aggarwal, Aneel K. ; Haider, Shozeb ; New, Maria I. ; Sun, Li ; Narla, Goutham ; Zaidi, Mone

A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. Having shown that bisphosphonates, a class of drugs used widely for the therapy of osteoporosis and metastatic bone disease, reduce cancer cell viability by targeting HER1, we explored their potential utility in the prevention and therapy of HER-driven cancers. We show that bisphosphonates inhibit colony [...]

Menée in vitro et in vivo sur des modèles de cancer du sein triplement négatif, cette étude met en évidence des mécanismes suggérant l'intérêt d'ajouter un inhibiteur des facteurs induits par l'hypoxie à une chimiothérapie à base de paclitaxel ou gemcitabine

Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells

Samanta, Debangshu ; Gilkes, Daniele M. ; Chaturvedi, Pallavi ; Xiang, Lisha ; Semenza, Gregg L.

Triple negative breast cancers (TNBCs) are defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expression, and are treated with cytotoxic chemotherapy such as paclitaxel or gemcitabine, with a durable response rate of less than 20%. TNBCs are enriched for the basal subtype gene expression profile and the presence of breast cancer stem cells, which are endowed with self-renewing and tumor-initiating properties and resistance to [...]

Cet article passe en revue les travaux récents sur l'intérêt des inhibiteurs de HER2 pour le traitement des patients atteints d'un carcinome épidermoïde de la tête et du cou

HER2 as a Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Pollock, Netanya I. ; Grandis, Jennifer R.

The majority of patients with head and neck squamous cell carcinoma (HNSCC) present with advanced-stage disease. Current standard of care is surgery followed by adjuvant radiation therapy with or without chemotherapy or chemoradiation alone. The addition of cetuximab for the treatment of patients with locally advanced or recurrent/metastatic HNSCC has improved overall survival and locoregional control; however, responses are often modest, and treatment resistance is common. A variety of [...]

Menée sur 41 patients atteints d'un carcinome urothélial métastatique et inclus dans un essai de phase II évaluant le cabozantinib, cette étude analyse la fréquence et le spectre des réactions cutanées associées au traitement

Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib

Zuo, R. C. ; Apolo, A. B. ; DiGiovanna, J. J. ; et al.,

Importance  : Cabozantinib S-malate is a vascular endothelial growth factor receptor 2, c-MET, and RET multitargeted tyrosine kinase inhibitor that has antiangiogenic and antitumorigenic properties with potential efficacy for the treatment of several cancers. Cutaneous reactions, one of the most frequently observed adverse effects associated with tyrosine kinase inhibitors, can significantly affect patients’ quality of life and drug adherence and represent a major therapeutic challenge to [...]

Mené sur 65 patients atteints d'une tumeur solide (dont 58 patients atteints d'un gliome), cet essai de phase I évalue la dose maximale tolérée et l'activité clinique d'un composé appelé LY2157299, un inhibiteur de la signalisation du facteur de croissance de transformation bêta

First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma

Rodon, Jordi ; Carducci, Michael A. ; Sepulveda-Sanchez, Juan M. ; Azaro, Analia ; Calvo, Emiliano ; Seoane, Joan ; Brana, Irene ; Sicart, Elisabet ; Gueorguieva, Ivelina ; Cleverly, Ann L ; Sokalingum Pillay, N ; Desaiah, Durisala ; Estrem, Shawn T ; Paz-Ares, Luis ; Holdoff, Matthias ; Blakeley, Jaishri ; Lahn, Michael M ; Baselga, Jose

Purpose: Transforming growth factor-beta (TGF-β) signaling plays a key role in tumor progression, including malignant glioma. Small molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGF-β signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a First-in-Human Dose (FHD) study in cancer patients. Experimental Design: Sixty five patients (58 with glioma) with measurable and progressive [...]

A partir d'une revue de la littérature (52 essais identifiés, 18 282 patients au total), cette méta-analyse évalue le risque relatif d'une hépatoxicité associée à un traitement par inhibiteur du récepteur VEGFR

Hepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of randomized clinical trials

Ghatalia, Pooja ; Je, Youjin ; Mouallem, Nemer El ; Nguyen, Paul L. ; Trinh, Quoc-Dien ; Sonpavde, Guru ; Choueiri, Toni K.

A trial-level meta-analysis of randomized phase II/III controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotoxicity associated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) approved by the U.S. FDA. Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and manufacturer's package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RR of all-grade ALT, AST, [...]

Mené sur 72 patients atteints d'un cancer du poumon non à petites cellules ayant progressé après un traitement de première ligne à base de sels de platine, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout d'apricoxib à un traitement de seconde ligne à base de docétaxel ou pemetrexed, après l'observation de la diminution du niveau urinaire d'un métabolite de la prostaglandine PGE2

Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Patients With Biomarker-Selected Non–Small-Cell Lung Cancer

Edelman, Martin J. ; Tan, Ming T. ; Fidler, Mary J. ; Sanborn, Rachel E. ; Otterson, Greg ; Sequist, Lecia V. ; Evans, Tracey L. ; Schneider, Bryan J. ; Keresztes, Roger ; Rogers, John S. ; de Mayolo, Jorge Antunez ; Feliciano, Josephine ; Yang, Yang ; Medeiros, Michelle ; Zaknoen, Sara L.

Purpose : Overexpression of COX-2 correlates with advanced stage and worse outcomes in non–small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2–dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of [...]

Mené sur 168 patients atteints d'un carcinome métastatique à cellules rénales, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du nivolumab

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

Motzer, Robert J. ; Rini, Brian I. ; McDermott, David F. ; Redman, Bruce G. ; Kuzel, Timothy M. ; Harrison, Michael R. ; Vaishampayan, Ulka N. ; Drabkin, Harry A. ; George, Saby ; Logan, Theodore F. ; Margolin, Kim A. ; Plimack, Elizabeth R. ; Lambert, Alexandre M. ; Waxman, Ian M. ; Hammers, Hans J.

Purpose : Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods : Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) [...]

Mené sur 42 patients atteints d'un carcinome urothélial de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'une combinaison pemetrexed-cisplatine en traitement de première ligne

Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17)

Choi, Y. J. ; Lee, S. H. ; Lee, J. L. ; Ahn, J. H. ; Lee, K. H. ; You, D. ; Hong, B. ; Hong, J. H. ; Ahn, H.

Background: Pemetrexed has shown a favourable response rate of about 30% with minimal toxicity when used as a single agent for treatment of advanced urothelial carcinoma. This phase II study evaluated the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. Methods: This multicentre, single-arm, open-label, phase II clinical trial enrolled patients who had advanced urothelial carcinoma, ECOG PS 0–2, and measurable disease. Pemetrexed 500 mg m−2 with cisplatin [...]

Mené sur 48 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade métastatique et/ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicitié du dacomitinib

Phase II Clinical and Exploratory Biomarker Study of Dacomitinib in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck

Kim, Han Sang ; Kwon, Hyeong Ju ; Jung, Inkyung ; Yun, Mi Ran ; Ahn, Myung-Ju ; Kang, Byung Woog ; Sun, Jong-Mu ; Kim, Sung-Bae ; Yoon, Dok-Hyun ; Park, Keon Uk ; Lee, Se-Hoon ; Koh, Yoon Woo ; Kim, Se Hun ; Choi, Eun Chang ; Koo, Dong Hoe ; Sohn, Jin Hee ; Kim, Bomi ; Kwon, Nak-Jung ; Yun, Hwan Jung ; LEE, Min Goo ; Lee, Ji Hyun ; Kim, Tae-Min ; Kim, Hye Ryun ; Kim, Joo Hang ; Paik, Soonmyung ; Cho, Byoung Chul

Purpose: The goals of this study were to investigate the clinical activity, safety and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2 and HER4, in recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45mg/day. The primary endpoint was objective [...]

Menée à partir des données des registres américains des cancers et de la base Medicare portant sur 1 535 patients atteints d'un carcinome primitif du rectum de stade I à III traité par chimioradiothérapie néoadjuvante et chirurgie curative (âge : plus de 65 ans), cette étude compare, du point de vue de la survie spécifique et en fonction du stade de la maladie, l'efficacité d'une chimiothérapie adjuvante à base de 5-fluorouracile en combinaison ou non avec l'oxaliplatine

Which is the best postoperative chemotherapy regimen in patients with rectal cancer after neoadjuvant therapy?

Gao, Peng ; Song, Yong-xi ; Sun, Jing-xu ; Chen, Xiao-wan ; Xu, Ying-ying ; Zhao, Jun-hua ; Huang, Xuan-zhang ; Xu, Hui-mian ; Wang, Zhen-ning

Background : There is no general agreement about whether patients who have already received neoadjuvant chemoradiotherapy need further postoperative chemotherapy based on 5-fluorouracil(5-FU) or 5-FU plus oxaliplatin. Methods : Medicare beneficiaries from 1992 to 2008 with Union for International Cancer Control ypStages I to III primary carcinoma of the rectum who underwent 5-FU-based neoadjuvant chemoradiotherapy and surgery for curative intent were identified through the Surveillance, [...]

Menée à partir de données portant sur 101 patients pédiatriques atteints d'un rhabdomyosarcome métastatique traité entre 1998 et 2011 selon des protocoles européens (âge : de 1 à 21 ans), cette étude française évalue, du point de vue de la survie sans maladie et de la survie globale, l'intérêt d'un traitement local agressif

Does aggressive local treatment have an impact on survival in children with metastatic rhabdomyosarcoma?

Ben Arush, M. ; Minard-Colin, V. ; Mosseri, V. ; Defachelles, A. S. ; Bergeron, C. ; Algret, N. ; Fasola, S. ; André, N. ; Thebaud, E. ; Corradini, N. ; Bernier, V. ; Martelli, H. ; Ranchère, D. ; Orbach, D.

Purpose : Due to the extensive initial distant tumour spread in metastatic rhabdomyosarcoma, the importance of local treatment is sometimes underestimated. A retrospective study was conducted to identify the prognostic value of aggressive local treatment in paediatric metastatic rhabdomyosarcoma. Patients : Patients with metastatic rhabdomyosarcoma aged 1–21 years treated in France from 1998 to 2011 according to European protocols MMT-4-89, 4-91, 98 and recent national guidelines were selected. [...]

Cet article passe en revue les perspectives offertes par l'immunothérapie pour le traitement personnalisé des cancers

(R)Evolutionary Therapy: The Potential of Immunotherapy to Fulfill the Promise of Personalized Cancer Treatment

Madan, Ravi A. ; Gulley, James L.

Since the millennium, personalized medicine has been at the forefront of therapeutic endeavors in medical oncology. The latest technology has given researchers the ability to define cancer at its molecular core. This has led to the development of “targeted therapies,” designed to eliminate driver mutations while leaving healthy cells unscathed. Unfortunately, more than 10 years into the targeted molecular therapy era, successes have been infrequent, and toxicity remains largely unchanged [...]

A partir de données des registres américains des cancers et de l'assurance maladie Medicare portant sur 14 097 patients atteints d'un cancer avancé du pancréas ou du poumon (âge supérieur à 65 ans), cette étude compare la survie de ces patients, qui ont été traités selon les recommandations en vigueur, par rapport aux données de survie issues des essais cliniques ayant inclus des patients plus jeunes

Generalizability of Trial Results to Elderly Medicare Patients with Advanced Solid Tumors (Alliance 70802)

Lamont, Elizabeth B. ; Schilsky, Richard L. ; He, Yulei ; Muss, Hyman ; Cohen, Harvey Jay ; Hurria, Arti ; Meilleur, Ashley ; Kindler, Hedy L. ; Venook, Alan ; Lilenbaum, Rogerio ; Niell, Harvey ; Goldberg, Richard M. ; Joffe, Steven ; for the Alliance for Clinical Trials in Oncology

Background: In the United States, patients who enroll in chemotherapy trials seldom reflect the attributes of the general population with cancer, as they are often younger, more functional, and have less comorbidity. We compared survival following three chemotherapy regimens according to the setting in which care was delivered (ie, clinical trial vs usual care) to determine the generalizability of clinical trial results to unselected elderly Medicare patients. Methods: Using SEER-Medicare data, [...]

Cet article présente une nouvelle approche de modélisation pour évaluer les risques et les bénéfices d'une intervention thérapeutique dans le cadre de la rédaction de recommandations cliniques

Models in the Development of Clinical Practice Guidelines

Habbema, J. Dik F. ; Wilt, Timothy J. ; Etzioni, Ruth ; Nelson, Heidi D. ; Schechter, Clyde B. ; Lawrence, William F. ; Melnikow, Joy ; Kuntz, Karen M. ; Owens, Douglas K. ; Feuer, Eric J.

Clinical practice guidelines should be based on the best scientific evidence derived from systematic reviews of primary research. However, these studies often do not provide evidence needed by guideline development groups to evaluate the tradeoffs between benefits and harms. In this article, the authors identify 4 areas where models can bridge the gaps between published evidence and the information needed for guideline development applying new or updated information on disease risk, diagnostic [...]