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Cancer

Cover image for Vol. 116 Issue 22

15 November 2010

Volume 116, Issue 22

Pages 5113–5339

  1. CancerScope

    1. Top of page
    2. CancerScope
    3. Commentaries
    4. Editorials
    5. Review Articles
    6. Original Articles
    7. Communications
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  2. Commentaries

    1. Top of page
    2. CancerScope
    3. Commentaries
    4. Editorials
    5. Review Articles
    6. Original Articles
    7. Communications
    1. You have full text access to this OnlineOpen article
      Bypassing phase 1 trials in the cancer drug development paradigm: Generally unwise and potentially dangerous (pages 5116–5118)

      Maurie Markman

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25543

      Although the primary purpose of phase 1 trials is the determination of safety, these early clinical investigative efforts are also associated with several important secondary endpoints that are essential to future drug development. Unfortunately, there has been a recent trend in which some oncology investigators have suggested bypassing formal phase 1 testing of presumably theoretically attractive new/novel antineoplastic drug combinations. This commentary challenges the need for, and wisdom of, this approach and highlights the potential danger to research subjects participating in later stage trials that are not supported by rigorous phase 1 data.

  3. Editorials

    1. Top of page
    2. CancerScope
    3. Commentaries
    4. Editorials
    5. Review Articles
    6. Original Articles
    7. Communications
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      Bringing the p53 signature into focus (pages 5119–5121)

      Christopher P. Crum and Wa Xian

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25450

      The p53 signature is emerging as an important precursor to pelvic cancer. In this issue of Cancer, a report from investigators at the University of Washington School of Medicine adds important data in support of this concept in women with familial ovarian cancer.

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      Examining the association between delay in diagnosis and decreased survival in bladder cancer (pages 5122–5125)

      Michael P. Porter

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25290

      Delays in diagnosis and definitive treatment are associated with poorer survival in observational studies of patients with bladder cancer. Quality of care may be as important as tumor biology in explaining this association.

  4. Review Articles

    1. Top of page
    2. CancerScope
    3. Commentaries
    4. Editorials
    5. Review Articles
    6. Original Articles
    7. Communications
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      Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors (pages 5126–5137)

      Jean-Yves Blay, Margaret von Mehren and Martin E. Blackstein

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25267

      In this review, the authors summarized the latest recommendations provided by the 2009 European Society of Medical Oncology and National Comprehensive Cancer Network (soft tissue sarcoma) guidelines on the management of gastrointestinal stromal tumors. In addition, the 2006 Canadian guidelines and other relevant guidelines are mentioned intermittently mentioned throughout the article. The objectives of this review were to bring to light recommendations for which the guidelines reach a consensus and to identify gaps and potential nuances in the differences among them.

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      Lymphedema beyond breast cancer : A systematic review and meta-analysis of cancer-related secondary lymphedema (pages 5138–5149)

      Janice N. Cormier, Robert L. Askew, Kristi S. Mungovan, Yan Xing, Merrick I. Ross and Jane M. Armer

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25458

      This systematic review and meta-analysis of the oncology-related literature reports incidence estimates for secondary lymphedema and risk factors among various malignancies apart from breast cancer.

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      The role of kinesin family proteins in tumorigenesis and progression : Potential biomarkers and molecular targets for cancer therapy (pages 5150–5160)

      Yue Yu and Yu-Mei Feng

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25461

      The authors reviewed in detail the structure and function of kinesin family proteins, the correlation of kinesin expression with tumorigenesis, and the development of biomarkers for cancer diagnosis, prognosis, and therapy.

  5. Original Articles

    1. Top of page
    2. CancerScope
    3. Commentaries
    4. Editorials
    5. Review Articles
    6. Original Articles
    7. Communications
    1. Disease Site

      Breast Disease
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      Utility of oncotype DX risk estimates in clinically intermediate risk hormone receptor-positive, HER2-normal, grade II, lymph node-negative breast cancers (pages 5161–5167)

      Catherine M. Kelly, Savitri Krishnamurthy, Giampaolo Bianchini, Jennifer K. Litton, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi and Lajos Pusztai

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25269

      Oncotype DX yielded potentially informative risk assignments in patients considered to be at indeterminate risk by routine clinical variables. However, 40% of the time, the tests results remained intermediate risk with widely used in recurrence score thresholds. This proportion increased to 66% when revised thresholds implemented by the National Cancer Institute's Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, were used.

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      Quantitative HER2 protein levels predict outcome in fluorescence in situ hybridization-positive patients with metastatic breast cancer treated with trastuzumab (pages 5168–5178)

      Allan Lipton, Wolfgang J. Köstler, Kim Leitzel, Suhail M. Ali, Jeff Sperinde, Jodi Weidler, Agnes Paquet, Thomas Sherwood, Weidong Huang, Michael Bates and the Trastuzumab Response Biomarker Group

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25430

      By using a novel assay (HERmark) to quantify total human epidermal growth factor receptor 2 (HER2) and HER2 homodimeric protein levels in primary breast tumor tissue sections, the authors examined outcomes in 102 trastuzumab-treated metastatic breast cancer patients previously assessed as immunohistochemistry 3+ or fluorescence in situ hybridization (FISH) positive, and then retested by central FISH. A subset of patients with HER2 gene amplification by FISH expressed low levels of HER2 protein and had reduced response to trastuzumab-containing therapy, similar to FISH-negative patients.

    3. Gastrointestinal Disease
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      Expression of p16INK4A but not hypoxia markers or poly adenosine diphosphate-ribose polymerase is associated with improved survival in patients with pancreatic adenocarcinoma (pages 5179–5187)

      Daniel T. Chang, Christopher H. Chapman, Jeffrey A. Norton, Brendan Visser, George A. Fisher, Pamela Kunz, James M. Ford, Albert C. Koong and Reetesh K. Pai

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25481

      Immunohistochemical analysis was performed on tumors of 73 patients with resected pancreatic adenocarcinoma. Patients with nuclear expression of the tumor suppressor gene product p16INK4A had improved survival compared with those with no expression, which was confirmed on multivariate analysis.

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      Clinical impact of tumor-infiltrating lymphocytes for survival in stage II colon cancer (pages 5188–5199)

      Won-Suk Lee, Sanghui Park, Woo Yong Lee, Seong Hyeon Yun and Ho-Kyung Chun

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25293

      The objective of this study was to assess and compare the prognostic role of tumor-infiltrating lymphocytes (TILs) in stage II colon cancer. The results indicated that TILs may provide a novel, independent predictor of prognosis for patients with early stage colon cancer and may help to identify patients who have an unfavorable prognosis.

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      Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma (pages 5200–5206)

      Raphaël Maréchal, John R. Mackey, Raymond Lai, Pieter Demetter, Marc Peeters, Marc Polus, Carol E. Cass, Isabelle Salmon, Jacques Devière and Jean-Luc Van Laethem

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25303

      Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. In this study, the authors investigated patient outcomes according to the expression of dCK after postoperative gemcitabine-based chemoradiation. The results indicated that overall survival in patients with resected pancreatic cancer who received adjuvant gemcitabine-based radiochemotherapy depended on dCK protein expression.

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      Notch1 regulates the growth of human colon cancers (pages 5207–5218)

      Yan Zhang, Bin Li, Zong-Zheng Ji and Peng-Sheng Zheng

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25449

      The authors investigated the role of aberrant activation of Notch signaling in the pathogenesis of colon cancer. The results indicated that Notch1 signaling positively regulates the growth of colon cancers and that the modulation of Notch1-related signaling may be a promising therapy for human colon cancers.

    7. Genitourinary Disease
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      Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma (pages 5219–5225)

      Toni K. Choueiri, Zita Dubauskas Lim, Michelle S. Hirsch, Pheroze Tamboli, Eric Jonasch, David F. McDermott, Paola Dal Cin, Paul Corn, Ulka Vaishampayan, Daniel Y.C. Heng and Nizar M. Tannir

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25512

      Adult “translocation” renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized unique entity for which prognosis and therapy remain poorly understood. The results of the current study indicated that vascular endothelial growth factor-targeted therapy is active in adult translocation RCC.

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      Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer (pages 5226–5234)

      Matthew R. Cooperberg, Andrew J. Vickers, Jeanette M. Broering, Peter R. Carroll and for the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) Investigators

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25456

      In a large, prospectively accrued cohort of patients who were followed under uniform protocols regardless of initial therapy, the authors observed statistically significant, adjusted differences in cancer-specific and overall mortality among men who underwent radical prostatectomy, men who received external-beam radiation therapy, and men who received primary androgen-deprivation monotherapy. These differences were more prominent at higher levels of risk, they were robust to multiple sensitivity analyses, and they suggested that surgery should play a greater role as part of multimodal therapy for patients with high-risk prostate cancer.

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      Delays in diagnosis and bladder cancer mortality (pages 5235–5242)

      Brent K. Hollenbeck, Rodney L. Dunn, Zaojun Ye, John M. Hollingsworth, Ted A. Skolarus, Simon P. Kim, James E. Montie, Cheryl T. Lee, David P. Wood Jr. and David C. Miller

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25310

      To determine whether opportunities for improving bladder cancer outcomes may exist upstream from the diagnosis, the authors used national cancer registry data to measure the relation between a delay in diagnosis and a patient's risk of death. Among patients who had hematuria in the year before their bladder cancer diagnosis, a 9-month delay in diagnosis was associated with a nearly 30% greater risk of death from the disease, independent of cancer grade or stage, compared with patients who were diagnosed within 3 months of their first hematuria claim (adjusted hazard ratio, 1.29 [1.14-1.45]).

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      Evaluation of lymph node counts in primary retroperitoneal lymph node dissection (pages 5243–5250)

      R. Houston Thompson, Brett S. Carver, George J. Bosl, Dean Bajorin, Robert Motzer, Darren Feldman, Victor E. Reuter and Joel Sheinfeld

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25266

      In this study, the results suggested that >40 lymph nodes removed at retroperitoneal lymph node dissection (RPLND) for nonseminomatous germ cell tumors improved the diagnostic efficacy of the operation. The authors believe that these results will be useful for future trials comparing RPLNDs, especially when assessing the adequacy of lymph node dissection.

    11. Gynecologic Oncology
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      Continued chemotherapy after complete response to primary therapy among women with advanced ovarian cancer : A meta-analysis (pages 5251–5260)

      Lisa M. Hess, Nan Rong, Patrick O. Monahan, Paridha Gupta, Champ Thomaskutty and Daniela Matei

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25487

      A meta-analysis of consolidation and maintenance therapy for ovarian cancer showed a significant advantage for both progression-free and overall survival, particularly among patients with advanced stage disease who reached complete clinical or pathologic response after primary therapy.

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      The molecular pathogenesis of hereditary ovarian carcinoma : Alterations in the tubal epithelium of women with BRCA1 and BRCA2 mutations (pages 5261–5271)

      Barbara M. Norquist, Rochelle L. Garcia, Kimberly H. Allison, Chris H. Jokinen, Lauren E. Kernochan, Catherine C. Pizzi, Bethany J. Barrow, Barbara A. Goff and Elizabeth M. Swisher

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25439

      Molecular changes in fallopian tube epithelium of women with BRCA1 and BRCA2 mutations offer new insight into the pathogenesis of hereditary ovarian carcinoma.

    13. Hematologic Malignancies
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      Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia : Long-term follow-up of a phase 2 study (pages 5272–5278)

      Michael Rytting, Farhad Ravandi, Elihu Estey, Jorge Cortes, Stefan Faderl, Guillermo Garcia-Manero, Sima Jeha, Souzanne Ouzounian, Sherry Pierce and Hagop Kantarjian

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25516

      Timed sequential chemotherapy as was applied in a successful pediatric acute myeloid leukemia (AML) trial was given to adults with AML. Toxicity was significant, but was counterbalanced by improved disease-free survival.

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      Use of white blood cell growth factors and risk of acute myeloid leukemia or myelodysplastic syndrome among elderly patients with non-Hodgkin lymphoma (pages 5279–5289)

      Stephen K. Gruschkus, David Lairson, J. Kay Dunn, Jan Risser and Xianglin L. Du

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25525

      The administration of colony-stimulating factor among elderly patients with non-Hodgkin lymphoma who were receiving chemotherapy was associated with an increased risk of myelodysplastic syndromes or acute myeloid leukemia, although the absolute risk was low.

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      Does combination of lipid formulation of amphotericin B and echinocandins improve outcome of invasive aspergillosis in hematological malignancy patients? (pages 5290–5296)

      Coralia N. Mihu, Christelle Kassis, Elizabeth R. Ramos, Ying Jiang, Ray Y. Hachem and Issam I. Raad

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25312

      The authors evaluated salvage therapy with lipid formulations of amphotericin B, echinocandin, or a combination of both for refractory aspergillosis in a patient population with hematological malignancy. Our data suggest that combination therapy offered no additional benefit compared with either drug administered as a single agent in respect to clinical response and mortality.

    16. Neuro-Oncology
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      A phase 2 trial of single-agent bevacizumab given in an every-3-week schedule for patients with recurrent high-grade gliomas (pages 5297–5305)

      Jeffrey J. Raizer, Sean Grimm, Marc C. Chamberlain, M. Kelly Nicholas, James P. Chandler, Kenji Muro, Steven Dubner, Alfred W. Rademaker, Jaclyn Renfrow and Markus Bredel

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25462

      Single-agent bevacizumab given every 3 weeks was active and was comparable to a 2-week schedule. The current results indicated that the ratio of vascular endothelial growth factor (VEGF) to VEGF receptor may be predictive of activity.

    17. Discipline

      Epidemiology
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      Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies (pages 5306–5315)

      Joanne Reekie, Csaba Kosa, Frederik Engsig, Antonella d'Arminio Monforte, Alicja Wiercinska-Drapalo, Pere Domingo, Francisco Antunes, Nathan Clumeck, Ole Kirk, Jens D. Lundgren, Amanda Mocroft and for the EuroSIDA Study Group

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25311

      Low CD4 count is associated with increased risk of non–acquired immunodeficiency syndrome (AIDS)-defining malignancies. Starting human immunodeficiency virus-infected patients on combination antiretroviral therapy before immunodeficiency develops is important to decrease the risk of developing many common non–AIDS-related malignancies, especially those that are virus-related.

    18. Pediatric Oncology
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      Osteosarcoma in very young children : Experience of the Cooperative Osteosarcoma Study Group (pages 5316–5324)

      Leo Kager, Andreas Zoubek, Martin Dominkus, Susanna Lang, Nicole Bodmer, Gernot Jundt, Thomas Klingebiel, Heribert Jürgens, Helmut Gadner, Stefan Bielack and for the COSS Study Group

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25287

      The incidence of high-grade osteosarcoma varies considerably with age, and preschool children are very rarely affected, with a total of only 27 well described cases in the literature. We present detailed information on the Cooperative Osteosarcoma Study Group (COSS) experience on a total of 28 children aged younger than 5 years at diagnosis.

    19. Translational Research
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      Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer (pages 5325–5335)

      Motofumi Tanaka, Milind Javle, Xiaoqun Dong, Cathy Eng, James L. Abbruzzese and Donghui Li

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25282

      The authors demonstrated that polymorphic variants of gemcitabine metabolic and transporter genes are associated with toxicity and treatment efficacy of gemcitabine in patients with locally advanced pancreatic cancer. This information has the potential to be useful in treatment selection and dose management for individualized cancer therapy.

  6. Communications

    1. Top of page
    2. CancerScope
    3. Commentaries
    4. Editorials
    5. Review Articles
    6. Original Articles
    7. Communications
    1. You have full text access to this OnlineOpen article
      TNM seventh edition: What's new, what's changed : Communication from the International Union Against Cancer and the American Joint Committee on Cancer (pages 5336–5339)

      Leslie H Sobin and Carolyn C. Compton

      Article first published online: 3 NOV 2010 | DOI: 10.1002/cncr.25537

      The seventh edition of the TNM Classification of Malignant Tumors contains several new and modified component classifications. The purpose of this communication was to briefly summarize these changes.

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