Menée sur des lignées cellulaires cancéreuses ayant acquis une résistance aux inhibiteurs d'EGFR, cette étude suggère l'efficacité d'un composé appelé CEDC-101 pour surmonter cette résistance et inhiber la migration et l'invasion des cellules tumorales

Potential Advantages of CUDC-101, a Multi-Targeted HDAC, EGFR, and HER2 Inhibitor, in Treating Drug Resistance and Preventing Cancer Cell Migration and Invasion

Wang, Jing ; Pursell, Natalie W ; Samson, Maria Elena S. ; Atoyan, Ruzanna ; Ma, Anna W. ; Selmi, Abdelkader ; Xu, Wanlu ; Cai, Xiong ; Voi, Maurizio ; Savagner, Pierre ; Lai, Cheng-Jung

CUDC-101 is a novel, small-molecule, anti-cancer agent targeting histone deacetylases (HDACs), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2). It is currently in Phase I clinical development in patients with solid tumors. Previously, we reported that CUDC-101 has potent anti-proliferative and pro-apoptotic activity in cultured tumor cells and in vivo xenograft models. We now show that cancer cells that have acquired resistance to single-target EGFR [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en bloquant les facteurs de croissance des fibroblastes non hormonaux, un récepteur leurre, FP-1039, inhibe la croissance de divers types de cancer

Blockade of Nonhormonal Fibroblast Growth Factors by FP-1039 Inhibits Growth of Multiple Types of Cancer

Harding, Thomas C. ; Long, Li ; Palencia, Servando ; Zhang, Hongbing ; Sadra, Ali ; Hestir, Kevin ; Patil, Namrata ; Levin, Anita ; Hsu, Amy W. ; Charych, Deborah ; Brennan, Thomas ; Zanghi, James ; Halenbeck, Robert ; Marshall, Shannon A. ; Qin, Minmin ; Doberstein, Stephen K. ; Hollenbaugh, Diane ; Kavanaugh, W. Michael ; Williams, Lewis T. ; Baker, Kevin P.

The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis in many solid tumors. Although there has long been interest in FGF pathway inhibitors, development has been complicated: An effective FGF inhibitor must block the activity of multiple mitogenic FGF ligands but must spare the metabolic hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To achieve these design requirements, we engineered a soluble FGF receptor 1 Fc fusion protein, FP-1039. [...]

Cet article passe en revue les perspectives offertes par les travaux récents relatifs à des thérapies ciblant des anomalies épigénétiques pour le traitement des tumeurs solides

The future of epigenetic therapy in solid tumours - lessons from the past

Azad, Nilofer ; Zahnow, Cynthia A. ; Rudin, Charles M. ; Baylin, Stephen B.

The promise of targeting epigenetic abnormalities for cancer therapy has not been realized for solid tumours, although increasing evidence is demonstrating its worth in haematological malignancies. In fact, true clinical efficacy in haematopoietic-related neoplasms has only become evident at low doses of epigenetic-targeting drugs (namely, inhibitors of histone deacetylase and DNA methyltransferases). Describing data from preclinical studies and early clinical trial results, we hypothesize that [...]

Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes suggérant que, chez les patients traités pour une leucémie myéloïde chronique, la résistance aux inhibiteurs de tyrosine kinase est due à une instabilité génomique apparue dans des cellules souches réfractaires très primitives

Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells

Bolton-Gillespie, Elisabeth ; Schemionek, Mirle ; Klein, Hans-Ulrich ; Flis, Sylwia ; Hoser, Grazyna ; Lange, Thoralf ; Nieborowska-Skorska, Margaret ; Maier, Jacqueline ; Kerstiens, Linda ; Koptyra, Mateusz ; Müller, Martin C. ; Modi, Hardik ; Stoklosa, Tomasz ; Seferynska, Ilona ; Bhatia, Ravi ; Holyoake, Tessa L. ; Koschmieder, Steffen ; Skorski, Tomasz

Genomic instability is a hallmark of chronic myeloid leukemia in chronic phase (CML-CP) resulting in BCR-ABL1 mutations encoding resistance to tyrosine kinase inhibitors (TKIs) and/or additional chromosomal aberrations leading to disease relapse and/or malignant progression. TKI-naive and TKI-treated leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) accumulate high levels of reactive oxygen species (ROS) and oxidative DNA damage. To determine the role of TKI-refractory LSCs in [...]

Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence un mécanisme par lequel, sous l'effet du facteur de transcription FOXD3, une activation de la signalisation ERBB3 induit l'apparition d'une résistance aux inhibiteurs de RAF ou de MEK dans le traitement d'un mélanome métastatique

Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3

Abel, Ethan V. ; Basile, Kevin J. ; Kugel, Curtis H. ; Witkiewicz, Agnieszka K. ; Le, Kaitlyn ; Amaravadi, Ravi K. ; Karakousis, Giorgos C. ; Xu, Xiaowei ; Xu, Wei ; Schuchter, Lynn M. ; Lee, Jason B. ; Ertel, Adam ; Fortina, Paolo ; Aplin, Andrew E.

The mechanisms underlying adaptive resistance of melanoma to targeted therapies remain unclear. By combining ChIP sequencing with microarray-based gene profiling, we determined that ERBB3 is upregulated by FOXD3, a transcription factor that promotes resistance to RAF inhibitors in melanoma. Enhanced ERBB3 signaling promoted resistance to RAF pathway inhibitors in cultured melanoma cell lines and in mouse xenograft models. ERBB3 signaling was dependent on ERBB2; targeting ERBB2 with lapatinib in [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'un composé appelé SC144, un inhibiteur de la glycoprotéine gp130, pour le traitement d'un cancer de l'ovaire

Discovery of a Novel Orally Active Small-Molecule gp130 Inhibitor for the Treatment of Ovarian Cancer

Xu, Shili ; Grande, Fedora ; Garofalo, Antonio ; Neamati, Nouri

IL-6 and Stat3 play key roles in ovarian cancer progression. However, the role of glycoprotein 130 (gp130), the signal transducer of this signaling axis, is not well established. Currently, there are no small-molecule inhibitors of gp130 under clinical development. In this study, we demonstrate that gp130 is an attractive drug target in ovarian cancer due to its role in promoting cancer progression via the activation of its downstream Stat3 signaling. We also present preclinical studies of [...]

Menée sur des lignées cellulaires de cancer ovarien, cette étude met en évidence des mécanismes par lesquels la phosphoprotéine PEA-15 augmente la sensibilité des cellules cancéreuses au paclitaxel

Bisphosphorylated PEA-15 Sensitizes Ovarian Cancer Cells to Paclitaxel by Impairing the Microtubule-Destabilizing Effect of SCLIP

Xie, Xuemei ; Bartholomeusz, Chandra ; Ahmed, Ahmed A ; Kazansky, Anna ; Diao, Lixia ; Baggerly, Keith A ; Hortobagyi, Gabriel N. ; Ueno, Naoto T.

Paclitaxel is a standard chemotherapeutic agent for ovarian cancer. PEA-15 (phosphoprotein enriched in astrocytes-15 kDa) regulates cell proliferation, autophagy, apoptosis, and glucose metabolism and also mediates AKT-dependent chemoresistance in breast cancer. PEA-15's functions are tightly regulated by its phosphorylation status at Ser104 and Ser116. However, the effect of PEA-15 phosphorylation status on chemosensitivity of cancer cells remains unknown. Here, we tested the hypothesis that [...]

Menée sur des lignées cellulaires, cette étude met en évidence des cellules dotées de propriétés de cellules souches associées à l'apparition d'une résistance au gefitinib dans le traitement d'un cancer du poumon

Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells

Shien, Kazuhiko ; Toyooka, Shinichi ; Yamamoto, Hiromasa ; Soh, Junichi ; Jida, Masaru ; Thu, Kelsie L ; Hashida, Shinsuke ; Maki, Yuho ; Ichihara, Eiki ; Asano, Hiroaki ; Tsukuda, Kazunori ; Takigawa, Nagio ; Kiura, Katsuyuki ; Gazdar, Adi F. ; Lam, Wan L. ; Miyoshi, Shinichiro

Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a critical problem in the treatment of lung cancer. While several mechanisms have been demonstrated to be responsible for acquired resistance, all mechanisms have not been uncovered. In this study, we investigated the molecular and cellular profiles of the acquired resistant cells to EGFR-TKI in EGFR mutant lung cancers. Four EGFR-mutant cell lines were exposed to gefitinib by stepwise escalation [...]

Menée sur des lignées cellulaires de cancer du sein, cette étude met en évidence des mécanismes par lesquels des modifications épigénomiques de la chromatine favorisent l'apparition d'une résistance à une hormonothérapie

Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer

Magnani, Luca ; Stoeck, Alexander ; Zhang, Xiaoyang ; Lánczky, András ; Mirabella, Anne C. ; Wang, Tian-Li ; Gyorffy, Balázs ; Lupien, Mathieu

The estrogen receptor (ER)α drives growth in two-thirds of all breast cancers. Several targeted therapies, collectively termed endocrine therapy, impinge on estrogen-induced ERα activation to block tumor growth. However, half of ERα-positive breast cancers are tolerant or acquire resistance to endocrine therapy. We demonstrate that genome-wide reprogramming of the chromatin landscape, defined by epigenomic maps for regulatory elements or transcriptional activation and chromatin openness, [...]

Menée in vitro et à l'aide d'un modèle murin de glioblastome, cette étude suggère l'efficacité d'un traitement restaurant l'activité de la protéine p53

Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy

Shchors, Ksenya ; Persson, Anders I. ; Rostker, Fanya ; Tihan, Tarik ; Lyubynska, Natalya ; Li, Nan ; Swigart, Lamorna Brown ; Berger, Mitchel S. ; Hanahan, Douglas ; Weiss, William A. ; Evan, Gerard I.

Based on clinical presentation, glioblastoma (GBM) is stratified into primary and secondary types. The protein 53 (p53) pathway is functionally incapacitated in most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis, we used a GFAP-HRasV12 mouse model crossed into the p53ERTAM background, such that either one or both copies of endogenous p53 is replaced by a conditional p53ERTAM allele. The p53ERTAM protein can be toggled reversibly in vivo between wild-type and [...]

Menée sur deux patients pédiatriques atteints d’une leucémie lymphoblastique aiguë, cette étude évalue l'efficacité et la toxicité d'un traitement à base de lymphocytes T modifiés pour exprimer un récepteur antigénique chimérique

Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia

Grupp, Stephan A. ; Kalos, Michael ; Barrett, David ; Aplenc, Richard ; Porter, David L. ; Rheingold, Susan R. ; Teachey, David T. ; Chew, Anne ; Hauck, Bernd ; Wright, J. Fraser ; Milone, Michael C. ; Levine, Bruce L. ; June, Carl H.

Chimeric antigen receptor–modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). Two children with relapsed and refractory pre–B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×106 to [...]

Cet article passe en revue les travaux récents sur le diagnostic et la prise en charge des leucémies

Leukaemia update. Part 1: diagnosis and management

Nicholas F Grigoropoulos ; Roger Petter ; Mars B Van ‘t Veer ; Mike A Scott ; George A Follows

Chronic lymphocytic leukaemia is the most common leukaemia in adults Patients with acute leukaemia can deteriorate rapidly—urgent discussion with a haematologist is recommended if acute leukaemia is suspected Risk is best stratified according to the genetic abnormalities of the leukaemia Diagnosis of leukaemia requires a multidisciplinary approach Most chronic leukaemias are not curable but can be treated with non-intensive chemotherapy Acute leukaemias are curable if patients are fit enough [...]

Cet article passe en revue les travaux récents sur des lymphocytes T modifiés pour exprimer un récepteur antigénique chimérique anti-CD19 pour le traitement de cancers des lymphocytes B

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors

Kochenderfer, James N. ; Rosenberg, Steven A.

Most B-cell malignancies express CD19, and a majority of patients with B-cell malignancies are not cured by current standard therapies. Chimeric antigen receptors (CARs) are fusion proteins consisting of antigen recognition moieties and T-cell activation domains. T cells can be genetically modified to express CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was first reported in 2010 after a [...]

Mené sur 198 patients atteints d'un cancer colorectal métastatique, cet essai de phase IIb évalue, du point de vue de la survie sans progression, l'ajout de sorafenib à un traitement de première ligne FOLFOX6 modifié

Sorafenib in Combination with Oxaliplatin, Leucovorin, and Fluorouracil (modified FOLFOX6) as First-line Treatment of Metastatic Colorectal Cancer: The RESPECT Trial

Tabernero, Josep ; Garcia-Carbonero, Rocio ; Cassidy, James ; Sobrero, Alberto ; Van Cutsem, Eric ; Köhne, Claus-Henning ; Tejpar, Sabine ; Gladkov, Oleg ; Davidenko, Irina ; Salazar, Ramon ; Vladimirova, Liubov ; Cheporov, Sergey ; Burdaeva, Olga ; Rivera, Fernando ; Samuel, Leslie ; Bulavina, Irina ; Potter, Vanessa ; Chang, Yu-Lin ; Lokker, Nathalie A. ; O'Dwyer, Peter J.

Purpose:This randomized, double-blind, placebo-controlled, phase IIb study evaluated adding sorafenib to first-line modified FOLFOX6 (mFOLFOX6) for metastatic colorectal cancer (mCRC). Experimental Design:Patients were randomized to sorafenib (400 mg BID) or placebo, combined with mFOLFOX6 (oxaliplatin 85 mg/m2; levo-leucovorin 200 mg/m2; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 continuous infusion) every 14 days. Primary endpoint was progression-free survival (PFS). Target sample was 120 [...]

Cet article passe en revue les travaux récents sur les chimiothérapies en traitement d'induction chez les patients atteints d'un cancer avancé de la tête et du cou

Current status and future directions in induction chemotherapy for head and neck cancer

Argiris, Athanassios

As a component of multimodal therapy in locally advanced head and neck cancer, induction chemotherapy represents a strategy to reduce tumor burden and target distant metastases prior to definitive treatment. Although the addition of taxanes to the cisplatin and 5-fluorouracil induction regimen (TPF) has greatly benefitted outcomes in comparison with PF alone, recent phase III trials have not shown a survival advantage for TPF induction followed by chemoradiotherapy vs. chemoradiotherapy alone. [...]

A partir de données médicales portant sur 163 patients atteints d'un lymphome diffus à grandes cellules B de stade III-IV et traités entre 2000 et 2012 (durée médiane de suivi : 32,9 mois), cette étude évalue, du point de vue du contrôle de la maladie, de la survie sans progression et de la survie globale à 5 ans, l'intérêt d'une radiothérapie de consolidation après réponse complète à un traitement R-CHOP et identifie les facteurs d'échec associés

Patterns of Failure in Advanced Stage Diffuse Large B-cell Lymphoma Patients After Complete Response to R-CHOP Immunochemotherapy and the Emerging Role of Consolidative Radiation Therapy

Shi, Zheng ; Das, Satya ; Okwan-Duodu, Derick ; Esiashvili, Natia ; Flowers, Christopher ; Chen, Zhengjia ; Wang, Xiaojing ; Jiang, Kun ; Nastoupil, Loretta J. ; Khan, Mohammad K.

The role of consolidative radiation therapy (RT) after complete response (CR) to rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for stage III-IV diffuse large B-cell lymphoma (DLBCL) patients is unclear. We aimed to evaluate our institutional experience when consolidative RT is delivered to initial presenting sites or bulky sites in these patients. We identified 211 histologically confirmed stage III-IV DLBCL patients who received R-CHOP from January [...]

Mené sur 50 patients atteints d'un cancer métastatique de la prostate résistant à la castration, cet essai multicentrique de phase I/II évalue, du point de vue des événements indésirables, du niveau sérique de l'antigène prostatique spécifique et de la réponse complète, l'intérêt d'ajouter une radiothérapie à un traitement par ipilimumab

Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study

Slovin, S. F. ; Higano, C. S. ; Hamid, O. ; Tejwani, S. ; Harzstark, A. ; Alumkal, J. J. ; Scher, H. I. ; Chin, K. ; Gagnier, P. ; McHenry, M. B. ; Beer, T. M.

Background This phase I/II study in patients with metastatic castration-resistant prostate cancer (mCRPC) explored ipilimumab as monotherapy and in combination with radiotherapy, based on the preclinical evidence of synergistic antitumor activity between anti-CTLA-4 antibody and radiotherapy.Patients and methods In dose escalation, 33 patients (≥6/cohort) received ipilimumab every 3 weeks × 4 doses at 3, 5, or 10 mg/kg or at 3 or 10 mg/kg + radiotherapy (8 Gy/lesion). The 10-mg/kg cohorts were [...]

Mené sur 17 patients atteints d'un cancer localisé de la prostate à risque élevé de récidive, cet essai multicentrique de phase I évalue, du point de vue des événements indésirables, la faisabilité d'un protocole thérapeutique combinant sunitinib, traitement anti-androgénique et radiothérapie externe avec modulation d'intensité

Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

Corn, Paul G. ; Song, Danny Y. ; Heath, Elisabeth ; Maier, Jordan ; Meyn, Raymond ; Kuban, Deborah ; DePetrillo, Thomas A. ; Mathew, Paul

To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, [...]

Menée in vitro et à l'aide d'une xénogreffe de carcinome colorectal, cette étude évalue l'efficacité du veliparib (ABT-888), un inhibiteur oral de l'enzyme PARP, pour améliorer la réponse des cellules tumorales à une chimioradiothérapie

In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

Shelton, Joseph W. ; Waxweiler, Timothy V. ; Landry, Jerome ; Gao, Huiying ; Xu, Yanbo ; Wang, Lanfang ; El-Rayes, Bassel ; Shu, Hui-Kuo G.

Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 [...]

Menée à l'aide de modèles murins d'adénocarcinome mammaire, cette étude évalue l'activité antitumorale d'une thérapie par capture de neutrons par le bore après une injection de liposomes enrichis en bore 10

Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

Kueffer, Peter J. ; Maitz, Charles A. ; Khan, Aslam A. ; Schuster, Seth A. ; Shlyakhtina, Natalia I. ; Jalisatgi, Satish S. ; Brockman, John D. ; Nigg, David W. ; Hawthorne, M. Frederick

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2′-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected [...]

Menée sur une cohorte de 983 patientes présentant une néoplasie mammaire intra-épithéliale de type canalaire et ayant subi une résection chirurgicale (durée médiane de suivi : 7 ans), cette étude évalue, en fonction du statut ménopausique des patientes et des niveaux d'expression tumorale du récepteur des oestrogènes et du récepteur de la progestérone, l'effet d'une faible dose de tamoxifène sur le risque de récidive et le risque de cancer de l'endomètre

Effect of low-dose tamoxifen after surgical excision of ductal intraepithelial neoplasia: results of a large retrospective monoinstitutional cohort study

Guerrieri-Gonzaga, A. ; Lazzeroni, M. ; Botteri, E. ; Serrano, D. ; Rotmensz, N. ; Varricchio, M.-C. ; Cazzaniga, M. ; Bollani, G. ; Mora, S. ; Montefrancesco, C. ; Pruneri, G. ; Viale, G. ; Intra, M. ; Galimberti, V. ; Goldhirsch, A. ; Bagnardi, V. ; Bonanni, B. ; DeCensi, A.

Background Postsurgical treatment of ductal intraepithelial neoplasia (DIN) with standard doses of tamoxifen has not reached a consensus yet. Given positive results of low-dose tamoxifen on breast cancer biomarkers modulation, we analyzed a large cohort of DIN patients treated with low-dose tamoxifen or no treatment as per institutional guidelines.Patients and methods All consecutive women operated on at the European Institute of Oncology for estrogen receptor (ER)-positive DIN (474 treated [...]

Menée sur 302 patients atteints d'un carcinome épidermoïde oropharyngé avec envahissement ganglionnaire et traités entre 2002 et 2009, cette étude évalue, du point de vue du contrôle régional de la maladie et de la survie globale à 5 ans, l'efficacité d'une chimioradiothérapie concomitante définitive

Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer

Goenka, Anuj ; Morris, Luc G. T. ; Rao, Shyam S. ; Wolden, Suzanne L. ; Wong, Richard J. ; Kraus, Dennis H. ; Ohri, Nisha ; Setton, Jeremy ; Lok, Benjamin H. ; Riaz, Nadeem ; Mychalczak, Borys R. ; Schöder, Heiko ; Ganly, Ian ; Shah, Jatin P. ; Pfister, David G. ; Zelefsky, Michael J. ; Lee, Nancy Y.

Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients [...]

Cet article passe en revue les problèmes statistiques posés par l'évaluation de traitements dans de petites populations de patients et analyse l'intérêt de divers schémas d'essais cliniques non randomisés

Statistical Challenges in the Evaluation of Treatments for Small Patient Populations

Korn, Edward L. ; McShane, Lisa M. ; Freidlin, Boris

The development of a new treatment typically involves evaluation of its efficacy in a large clinical trial in which patients are randomly assigned either the new treatment or the standard of care. Results from these large randomized clinical trials allow for a definitive and unbiased assessment of the clinical benefit of the new treatment over the standard one. For rare diseases or for small patient subgroups identified within the context of a common disease, it may not be possible to conduct a [...]