Sarcoma Osteosarcoma: Lessons Learned and Future Avenues Guest Editors: Ajay Puri, Norman Jaffe, Peter Choong, and Hans Gelderblom Osteosarcoma: Lessons Learned and Future Avenues Sarcoma Osteosarcoma: Lessons Learned and Future Avenues Guest Editors: Ajay Puri, Norman Jaffe, Peter Choong, and Hans Gelderblom Copyright © 2013 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Sarcoma.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board A. Abudu, UK Michelle Ghert, Canada Igor Matushansky, USA Manish Agarwal, India Henk P. Giele, UK Katarzyna Miekus, Poland Irene Andrulis, Canada George Gosheger, Germany Piergiorgio Modena, Italy Carola A. S. Arndt, USA Robert Grimer, UK Farid Moinfar, Austria Shanda Blackmon, USA Alessandro Gronchi, Italy Rajaram Nagarajan, USA Frederic Blanchard, France Kenichiro Hamada, Japan S. S. Nathan, Singapore Jos Bramer, The Netherlands Bang H. Hoang, USA Ole Steen Nielsen, Denmark Bertha Brodin, Sweden Kanya Honoki, Japan Alberto Pappo, USA MarilynM.Bui,USA Shile Huang, USA Shreyaskumar Patel, USA Robert Canter, USA Antoine Italiano, France Ajay Puri, India Jose Casanova, Portugal Nora Janjan, USA R. Lor Randall, USA Justin Cates, USA Dae-Geun Jeon, Korea Chandrajit P. Raut, USA Charles Catton, Canada Lee Jeys, UK John D. Reith, USA Giovanni Cecchetto, Italy Akira Kawai, Japan Martin H. Robinson, UK Quincy Chu, Canada Akira Kido, Japan Akio Sakamoto, Japan A. Craft, UK Eugenie S. Kleinerman, USA Luca Sangiorgi, Italy Enrique de Alava, Spain E. Anders Kolb, USA Beatrice Seddon, UK Andrea T. Deyrup, USA Katsuyuki Kusuzaki, Japan Herrick J. Siegel, USA Uta Dirksen, Germany Carmela Lauria, Italy David Spooner, UK Fritz C. Eilber, USA Alexander Lazar, USA Sheri L. Spunt, USA Natia Esiashvili, USA Michael Leahy, UK S. Stacchiotti, Italy Jeffrey Farma, USA Andreas Leithner, Austria Sophie Taieb, France Noah Federman, USA Stephen L. Lessnick, USA Jeffrey Toretsky, USA Peter C. Ferguson, Canada Valerae O. Lewis, USA Clement Trovik, Norway Cyril Fisher, UK Joseph A. Ludwig, USA C. Verhoef, The Netherlands Bruno Fuchs, Switzerland Neyssa Marina, USA Qihui (Jim) Zhai, USA Contents Osteosarcoma: Lessons Learned and Future Avenues, Ajay Puri, Norman Jaffe, and Hans Gelderblom Volume 2013, Article ID 641687, 2 pages Osteosarcoma: Evolution of Treatment Paradigms, Norman Jaffe, Ajay Puri, and Hans Gelderblom Volume 2013, Article ID 203531, 7 pages Rapamycin Inhibits ALDH Activity, Resistance to Oxidative Stress, and Metastatic Potential in Murine Osteosarcoma Cells, Xiaodong Mu, Christian Isaac, Trevor Schott, Johnny Huard, and Kurt Weiss Volume 2013, Article ID 480713, 11 pages Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma, Carol H. Lin, Yi Guo, Samia Ghaffar, Peter McQueen, Jonathan Pourmorady, Alexander Christ, Kevin Rooney, Tao Ji, Ramez Eskander, Xiaolin Zi, and Bang H. Hoang Volume 2013, Article ID 147541, 11 pages Survival Trends and Long-Term Toxicity in Pediatric Patients with Osteosarcoma, MelanieM.Hagleitner,EvelineS.J.M.deBont,andD.MaroeskaW.M.teLoo Volume 2012, Article ID 636405, 5 pages Discovery of Biomarkers for Osteosarcoma by Proteomics Approaches, Yoshiyuki Suehara, Daisuke Kubota, Kazutaka Kikuta, Kazuo Kaneko, Akira Kawai, and Tadashi Kondo Volume 2012, Article ID 425636, 15 pages Genes Regulated in Metastatic Osteosarcoma: Evaluation by Microarray Analysis in Four Human and Two Mouse Cell Line Systems, Roman Muff, Ram Mohan Ram Kumar, Sander M. Botter, Walter Born, and Bruno Fuchs Volume2012,ArticleID937506,13pages -Catenin Does Not Confer Tumorigenicity When Introduced into Partially Transformed Human Mesenchymal Stem Cells, Sajida Piperdi, Lukas Austin-Page, David Geller, Manpreet Ahluwalia, Sarah Gorlick, Jonathan Gill, Amy Park, Wendong Zhang, Nan Li, So Hak Chung, and Richard Gorlick Volume 2012, Article ID 164803, 10 pages Enhanced Growth Inhibition of Osteosarcoma by Cytotoxic Polymerized Liposomal Nanoparticles Targeting the Alcam Cell Surface Receptor, Noah Federman, Jason Chan, Jon O. Nagy, Elliot M. Landaw, Katelyn McCabe, Anna M. Wu, Timothy Triche, HyungGyoo Kang, Bin Liu, James D. Marks, and Christopher T. Denny Volume 2012, Article ID 126906, 11 pages Low-Grade Central Osteosarcoma: A Difficult Condition to Diagnose,A.M.Malhas,V.P.Sumathi, S.L.James,C.Menna,S.R.Carter,R.M.Tillman,L.Jeys,andR.J.Grimer Volume 2012, Article ID 764796, 7 pages Hindawi Publishing Corporation Sarcoma Volume 2013, Article ID 641687, 2 pages http://dx.doi.org/10.1155/2013/641687 Editorial Osteosarcoma: Lessons Learned and Future Avenues Ajay Puri,1 Norman Jaffe,2 and Hans Gelderblom3 1 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai 400012, India 2 Children’s Cancer Hospital, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 3 Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands Correspondence should be addressed to Hans Gelderblom; [email protected] Received 28 July 2013; Accepted 28 July 2013 Copyright © 2013 Ajay Puri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Osteosarcoma is the most common malignant bone tumor in improved in the interferon arm, although the results may men. The incidence peaks around puberty, with a broader and have been influenced by the low randomization and high lowerpeakafter60yearsofage.Riskfactorsare(pubertal) treatment refusal rate. Definite results and results of the poor growth, genetic factors, Paget’s disease, and prior radiother- responder randomization are pending. The study has proven apy. More than 90% of tumors are of high grade, and their that a worldwide platform for potential practice changing prognosis, even without metastasis at presentation, remains rapidly accruing randomized phase III studies is feasible in dismal in up to 30–45% of cases despite great improvements this rare disease and therefore should be used in the future. due to the introduction of chemotherapy some decades ago. The Birmingham experience with low-grade conven- The contribution “Osteosarcoma: evolution of treatment tional osteosarcoma (LGCO), a rare (1.2%) and difficult to paradigms” to this osteosarcoma special issue is truly unique diagnose variant of osteosarcoma, is also part of this special as it describes the history of systemic treatment from first issue. The diagnosis of LGCO is challenging due to the hand, as the first author N. Jaffe coauthored the first studies relatively nonspecific radiological and histological findings. on the dramatic improvement of long-term survival from 10– Since treatment of LGCO is so different compared to a 15% to 55–70% due to addition of multiagent chemotherapy. benign lesion as well as to high-grade osteosarcoma, accurate This magnitude of improvement has never been observed in diagnosis is essential. The authors therefore advise that any other solid tumors, with the exception of germ cell tumors difficult or nondiagnostic biopsies of solitary bone lesions and some childhood cancers such as rhabdomyosarcoma should be referred to a specialist (bone) tumor unit for a and Ewing’s sarcoma. However, these percentages have not second opinion: a conclusion that we fully agree with and further improved over the last decades, and new therapies are should be part of all guidelines. needed urgently to cure the remaining one-third of patients N. Federman et al. describe a novel osteosarcoma-ass- and increase the chances for patients with metastatic disease. ociated cell surface antigen, ALCAM. The authors created The authors describe the design of the current EURAMOS an anti-ALCAM-hybrid polymerized liposomal nanoparti- study. Meanwhile, the first results of the PEG interferon cle immunoconjugate (-AL-HPLN) to specifically target randomization in the good responder arm were presented at osteosarcoma cells and deliver a cytotoxic agent such as dox- the 2013 annual meeting of the American Society of Clinical orubicin. If feasible in clinical practice, these -AL-HPLNs Oncology [1].Fromthe2260includedpatients,1034hada are a promising new strategy to specifically deliver cyto- good pathological response to preoperative chemotherapy. Of toxic agents in osteosarcoma. A similar approach recently these patients 715, were randomized to either PEG interferon took place in breast cancer where the antibody-drug con- or observation. Only 76% of the patients randomized to jugate trastuzumab-DM1 (T-DM1) was designed to com- interferon started treatment, mainly due to refusal. The bine the biological activity of trastuzumab with the tar- event-free survival (primary endpoint) was not statistically geted delivery of a highly potent chemotherapeutic agent to 2 Sarcoma HER2-overexpressing breast cancer cells. The success of the designed studies that can be performed rapidly in interna- approach in breast cancer underlines the promise of -AL- tional collaboration of bone centers. This osteosarcoma issue HPLN in osteosarcoma. of Sarcoma is just a tiny step in this process that will need Y. Suehara et al. focus on proteomics to provide protein perseverance. expression profiles of osteosarcoma that can be used to develop