Critical Reviews in Oncology / Hematology RSS feed: Current Issue. Critical Reviews in Oncology/Hematology publishes scholarly, critical reviews in all fields of oncology and hematology written by experts from the five continents. All review articles, invited or submitted spontaneously, are subject to peer review before final acceptance. CROH is the Official Journal of the European School of Oncology (ESO) as of January 2011. Journal of Geriatric Oncology , launched by the International Society of Geriatric Oncology (SIOG) and Elsevier in June 2010, has become the official publication of SIOG in place of Critical Reviews in Oncology/Hematology . Authors who wish to submit reviews to the journal are requested to submit a short synopsis of their chosen subject to the Editor, and to indicate the deadline by which they expect to submit their final manuscript. Further information regarding the submission of manuscripts and guidelines for the preparation of the manuscripts can be found in the Guide for Authors. http://www.croh-online.com/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Critical Reviews in Oncology / Hematology1040-8428823June 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.croh-online.com/article/PIIS1040842812001059/abstract?rss=yesEditorial Board10.1016/S1040-8428(12)00105-9Critical Reviews in Oncology / Hematology 82, 3 (2012)2012-06-01Critical Reviews in Oncology / Hematology2012-06-01823S1040-8428(12)X0007-6CO2CO2http://www.croh-online.com/article/PIIS1040842811001958/abstract?rss=yesHighlights: ► Necroptosis is one particular form of programmed necrosis induced by stimulating death receptors with agonists. ► Necroptosis has its own unique signaling pathway which requires the involvement of receptor interaction protein kinase 1 and 3. ► Necroptosis plays an important role in immune system regulation, tissue injury, and cancer development.Abstract: Necrosis plays an important role in multiple physiological and pathological processes. Recently, a relatively new form of necrosis has been characterized as “necroptosis”. Morphologically, necroptosis exhibits the features of necrosis; however, necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinase 1 and 3 (RIP1 and RIP3) and can be specifically inhibited by necrostatins. Necroptosis has been found to contribute to the regulation of immune system, cancer development as well as cellular responses to multiple stresses. In this review, we will summarize the signaling pathway, biological effects and pathological significance of this specific form of programmed cell death.Necroptosis: An emerging form of programmed cell deathWei Wu, Peng Liu, Jianyong Li10.1016/j.critrevonc.2011.08.004Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-10-03Critical Reviews in Oncology / Hematology2011-10-03823S1040-8428(12)X0007-6249258http://www.croh-online.com/article/PIIS1040842811001752/abstract?rss=yesHighlights: ► Rhabdomyosarcoma (RMS) mainly affects children, but also adolescents and (young) adults (AYA). ► As compared to children improvement in survival in AYA lags behind. ► AYA with RMS should be treated in studies whenever available. ► This review provides an overview of RMS at different ages. ► We propose age-independent global collaboration for treatment of RMS.Abstract: Rhabdomyosarcoma (RMS) is a rare type of soft tissue sarcoma that mainly affects children, but also occurs in adolescents and (young) adults (AYA). Despite dramatic survival improvements reported by international study groups in children over the past decades, the awareness of a dismal outcome for older patients with RMS has grown. In contrast to the world-wide organization of care for children with RMS, standard care in adults lags behind. A step forward in RMS management for patients of all ages is urgently needed. Both paediatric oncologists and medical oncologists are essential players in development of a concept of RMS care, but bringing two worlds together seems not so easy. This review provides an overview which highlights the similarities and differences in children and adults with RMS. Furthermore, it comes up with a novel concept to overcome the virtual gap between the treatment approach of children and AYA with RMS.Building the bridge between rhabdomyosarcoma in children, adolescents and young adults: The road aheadJ. Carlijn Van Gaal, Eveline S.J.M. De Bont, Suzanne E.J. Kaal, Yvonne Versleijen-Jonkers, Winette T.A. van der Graaf10.1016/j.critrevonc.2011.06.005Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-08-01Critical Reviews in Oncology / Hematology2011-08-01823S1040-8428(12)X0007-6259279http://www.croh-online.com/article/PIIS1040842811001910/abstract?rss=yesAbstract: Background: Osteosarcomas of the mandible (MOS) affect 1/10millionpersons/year, mostly the young adult. Due to lack of specific data, the treatment of MOS is extrapolated from that of extragnathic OS but varies widely between institutions.Materials and methods: We aimed at providing a focused description of MOS histologies and grades through the English literature, at determining the evidence-based role of chemotherapy, of adjuvant radiation therapy and the potential of reconstructive surgery tailored through modern pre-operative multi-modal imaging.Results: The estimated proportion of high grade MOS was 58%. However, low-grade MOS may be underestimated as they are mostly reported as case reports. The intermediate grade was hardly found in the literature. Estimated weighted-mean proportions of chondroblastic and osteoblastic MOS were 37% and 46%, respectively. Multimodal imaging modalities including MRI has a great potential for accurate pre-operative assessment of tumor extensions into bone and soft tissues. Surgery is the mainstay of treatment and margins the most important factor. The role of neoadjuvant chemotherapy in treating occult systemic metastases and in increasing the probability of clear margins is controversial, as well as the histology-dependent response to chemotherapy. The role of adjuvant radiotherapy (mostly proposed for positive margins) and/or adjuvant chemotherapy is still controversial. Crude survival is around 77% and local control around 67%. Local failure is the main cause of death in MOS compared to extragnathic sites.Osteosarcomas of the mandible: Are they different from other tumor sites?Juliette Thariat, Morbize Julieron, Anne Brouchet, Antoine Italiano, Thomas Schouman, Pierre-Yves Marcy, Guillaume Odin, Alexis Lacout, Olivier Dassonville, Isabelle Peyrottes-Birstwisles, Robert Miller, Antoine Thyss, Nicolas Isambert10.1016/j.critrevonc.2011.07.001Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-08-25Critical Reviews in Oncology / Hematology2011-08-25823S1040-8428(12)X0007-6280295http://www.croh-online.com/article/PIIS1040842811001624/abstract?rss=yesAbstract: Inconsistencies plague our understanding of the role of neutrophils in cancer and the literature provides evidence for a duality in neutrophil activity on the outcome of cancer. Here, the different effects of neutrophils during the multiple subprocesses of cancer development and progression are overviewed, in order to gain insight into the features of both antitumoral and protumoral tumor-associated neutrophils (TAN). Neutrophils can counteract the progression of malignancies through tumor cytotoxicity, tumor rejection and enhancement of antitumoral immune memory. These cells have recently been phenotypically denominated N1 neutrophils. Recent studies indicate that cytokines, such as TGF-β and IFN-β, are involved in directing neutrophil polarization by the tumor microenvironment. With the opposite polarity, N2 neutrophils may be detrimental for the host and beneficial for tumor growth, invasion and metastasis, e.g. through proteolysis of extracellullar matrix components, promotion of angiogenesis and mediation of immunosuppression.On the dual roles and polarized phenotypes of neutrophils in tumor development and progressionH. Piccard, R.J. Muschel, G. Opdenakker10.1016/j.critrevonc.2011.06.004Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-07-28Critical Reviews in Oncology / Hematology2011-07-28823S1040-8428(12)X0007-6296309http://www.croh-online.com/article/PIIS1040842811001612/abstract?rss=yesAbstract: Discovery of the over-expression of Her-2/neu or the amplification of its regulatory gene in stomach and esophageal cancer has resulted in targeted treatment directed at this protein. The fact itself and its consequences have been the topic of an abundance of studies and clinical trials. In the present report we review the current state of the art as regards diagnosis of the over-expression and amplification of Her-2/neu, its inhibition as a new therapeutic concept, treatment toxicity, and the development of resistance to Her-2/neu as a limiting factor in stomach and esophageal adenocarcinoma.Her-2/neu gene amplification and over-expression in stomach and esophageal adenocarcinoma: From pathology to treatmentJudith Maresch, Sebastian F. Schoppmann, Christiane M.R. Thallinger, Christoph C. Zielinski, Michael Hejna10.1016/j.critrevonc.2011.06.003Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-07-25Critical Reviews in Oncology / Hematology2011-07-25823S1040-8428(12)X0007-6310322http://www.croh-online.com/article/PIIS1040842811001594/abstract?rss=yesAbstract: The introduction of novel anti-angiogenic therapies has greatly improved the outcome of patients with metastatic renal cell carcinoma (mRCC). The use of these therapies in combination or sequentially is proposed to provide greater efficacy.We have reviewed completed and ongoing clinical trials in mRCC that have reported efficacy and/or safety data of novel therapies used in combination or sequentially.Bevacizumab appears to be a useful partner when combined with interferon (IFN), while controversial results have been reported when combined with temsirolimus and everolimus. Other combinations appear to have unacceptable tolerability or require dose or schedule optimization. Sequencing data provide a clear indication that multiple lines of treatment may extend survival. The ‘ideal’ sequence, however, is still unknown.In conclusion, novel therapies used in combination or sequentially have potential to provide optimised treatment and patient outcomes in mRCC. The results from ongoing/planned trials are expected to help shape future therapy.Combination or sequencing strategies to improve the outcome of metastatic renal cell carcinoma patients: A critical reviewCamillo Porta, Cezary Szczylik, Bernard Escudier10.1016/j.critrevonc.2011.06.001Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-07-06Critical Reviews in Oncology / Hematology2011-07-06823S1040-8428(12)X0007-6323337http://www.croh-online.com/article/PIIS1040842811001946/abstract?rss=yesAbstract: Systemic chemotherapy (CT) with platinum-based doublets result in modest improvements in both overall survival (OS) and quality of life in good performance status patients with advanced non-small cell lung cancer (NSCLC). However, although substantial progress has been made in the therapeutic options currently available for these patients, the overall outcome remains poor.Maintenance therapy for patients who achieved at least stable disease after first-line treatment has been an area of intense investigation in recent years as a way of improving outcomes in metastatic NSCLC. Several alternative strategies for prolongation of initial treatment have been evaluated. These include the prolongation of the initial combination CT regimen until disease progression, unacceptable toxicity or a predefined greater number of cycles, continuation with a lower intensity version of the first-line CT regimen or administration of a new active agent immediately after completion of the first-line therapy (switch-maintenance or early second-line therapy). Treatments that have been studied in randomized trials to date include CT, molecularly targeted agents, and immunotherapy approaches. Phase III trials have not revealed a survival benefit for extended first-line CT with combination regimens for more than 4–6 cycles. Nevertheless, early second-line therapy with pemetrexed in nonsquamous tumours and erlotinib have demonstrated to improve OS results, especially in select patient groups characterized by histology and/or molecular profile. This article reviews recent data with maintenance therapy in advanced NSCLC and discusses the implications for routine patient care and future drug development.Strategies for maintenance therapy in advanced non-small cell lung cancer: Current status, unanswered questions and future directionsAna Custodio, Javier de Castro10.1016/j.critrevonc.2011.08.003Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-09-12Critical Reviews in Oncology / Hematology2011-09-12823S1040-8428(12)X0007-6338360http://www.croh-online.com/article/PIIS1040842811002150/abstract?rss=yesHighlights: ► Various adjuvant breast cancer guidelines are available. ► These consensual statements can be optimized using locally available daily used technologies. ► The conjunction of the Adjuvant! Online tool with additional predictive and prognostic factors, such as the uPA/PAI-1 complex, can be used in the routine clinical decision process.Abstract: Prognosis of early breast cancer patients is significantly improved with the use of adjuvant therapies. Various guidelines have been proposed to select patients who will derive the most benefit from such treatments. However, classifications have limited usefulness in subsets of patients such as those with node negative breast cancer.The 2007 St. Paul de Vence Clinical Practice Recommendations proposed to consider adjuvant therapy in accordance with the 10-year relapse-free survival reduction estimated by Adjuvant! Online. However, many limitations remain regarding the use of Adjuvant! Online. Among them, adverse prognostic and/or predictive factors such as vascular invasion, mitotic activity, progesterone receptor negativity, and HER-2 expression are not incorporated in the routine clinical decision process. Our group has therefore issued guidelines based on the consideration of both Adjuvant! Online calculations and the prognostic and/or predictive effects of these markers. In addition, web-accessible comprehensive tables summarizing these recommendations are provided.Adjuvant early breast cancer systemic therapies according to daily used technologiesW. Jacot, M. Gutowski, D. Azria, G. Romieu10.1016/j.critrevonc.2011.09.002Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-10-24Critical Reviews in Oncology / Hematology2011-10-24823S1040-8428(12)X0007-6361369http://www.croh-online.com/article/PIIS1040842811001934/abstract?rss=yesAbstract: Nilotinib is a second generation ABL tyrosine kinase inhibitor (TKI) that exerts major anti-leukemic effects in newly diagnosed patients with chronic myeloid leukemia (CML) as well as in most patients with imatinib-resistant CML. In freshly diagnosed patients, the anti-leukemic activity of nilotinib exceeds the efficacy of imatinib, and although long-term data for nilotinib are not available yet, the drug has recently been approved for firstline treatment of chronic phase CML in various countries. Still however, several questions concerning the optimal dose, follow-up parameters, long-term safety, and patient selection remain open. Likewise, it remains uncertain whether both Sokal low-risk and high-risk patients should receive nilotinib as frontline therapy in the future. Another question is whether nilotinib can completely eradicate CML in a subset of patients. Furthermore, it remains unclear whether and what comorbidity must be regarded as relative or absolute contra-indication for this TKI. To discuss these issues, the Austrian CML Working Group organized a series of meetings in 2010. In the current article, the outcomes from these discussions are summarized and presented together with recommendations for frontline use of TKIs in various groups of patients with CML. These recommendations should assist in daily practice as well as in the preparation and conduct of clinical trials.Nilotinib as frontline and second-line therapy in chronic myeloid leukemia: Open questionsPeter Valent, Günther Gastl, Klaus Geissler, Richard Greil, Oliver Hantschel, Alois Lang, Werner Linkesch, Thomas Lion, Andreas L. Petzer, Elisabeth Pittermann, Lisa Pleyer, Josef Thaler, Dominik Wolf10.1016/j.critrevonc.2011.08.002Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-09-07Critical Reviews in Oncology / Hematology2011-09-07823S1040-8428(12)X0007-6370377http://www.croh-online.com/article/PIIS104084281100196X/abstract?rss=yesAbstract: Cutaneous adverse events commonly reported with tyrosine kinase inhibitors (TKIs) in the treatment of malignancies, represent an important clinical concern since they can limit the optimal use of these novel drugs. Although there are numerous reports in the literature of these events there are no practical guidelines on how they should be managed. The Sorafenib Working Group (SWG) was established with the objective of developing recommendations to allow the early detection, prevention and management of cutaneous adverse events in everyday clinical practice. The SWG was a multidisciplinary team made up of experts in the field who were closely involved in the sorafenib clinical development program. This review provides an overview of the nature and incidence of cutaneous adverse events which manifest with sorafenib treatment and provides recommendations for their early detection and effective management in clinical practice.Early detection, prevention and management of cutaneous adverse events due to sorafenib: Recommendations from the Sorafenib Working GroupSergio Bracarda, Enzo Maria Ruggeri, Marcello Monti, Marco Merlano, Alessandro D’Angelo, Francesco Ferraù, Enrico Cortesi, Armando Santoro10.1016/j.critrevonc.2011.08.005Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-09-26Critical Reviews in Oncology / Hematology2011-09-26823S1040-8428(12)X0007-6378386http://www.croh-online.com/article/PIIS1040842811001600/abstract?rss=yesAbstract: Evidence from a range of sources demonstrates that end-of-life (EoL) care practices and preferences vary across countries; culture is consistently one of the main explanations given for this. In order to understand how cultural factors are used to explain similarities and differences in EoL care between Spain, Italy and Portugal, database and hand searches were performed and cross-cutting core themes identified. Similarities included higher proportions of people who wished to die at home than actually died at home, a persistent trend for partial disclosure in Italy and Spain, low use of advance directives, and low incidence of all medical EoL decisions (with the exception of terminal sedation) compared to northern European countries. The role of religion and the importance of family ties were the two main cultural factors used to explain the similarities. Further research is needed in order to interpret the important differences that were also found.End-of-life care across Southern Europe: A critical review of cultural similarities and differences between Italy, Spain and PortugalArantza Meñaca, Natalie Evans, Erin V.W. Andrew, Franco Toscani, Silvia Finetti, Xavier Gómez-Batiste, Irene J. Higginson, Richard Harding, Robert Pool, Marjolein Gysels10.1016/j.critrevonc.2011.06.002Critical Reviews in Oncology / Hematology 82, 3 (2012)2011-07-11Critical Reviews in Oncology / Hematology2011-07-11823S1040-8428(12)X0007-6387401