NE Oncology Issue – September 2014

Head and Neck Cancer

Cancers of the head and neck comprise a heterogeneous group of diseases, with head and neck squamous cell carcinoma (HNSCC) representing 90% of cases worldwide. Underscoring the need for improved diagnostics, almost half of patients with HNSCC present with metastatic disease. Although there have been improvements in patient survival for other types of cancer, the 5-year survival rate for HNSCC has remained at around 50% for the past several decades.1

Increased expression of epidermal growth factor receptor (EGFR) is observed in as many as 90% of HNSCC tumours.2 EGFR pathway activation has been linked to increased tumour size, decreased radiation sensitivity, increased risk of recurrence, and decreased overall survival.3 Improved outcomes have been achieved in patients with HNSCC that have undergone EGFR-targeted therapies. However, resistance of some patients to EGFR inhibitors has presented a challenge, and the importance of therapeutic decisions based on molecular characterization of tumours has become evident. Consequently, increasing effort has been made to identify biomarkers that can assess efficacy of therapy, help predict treatment outcome, and guide selection of the therapy that is most likely to be effective.

In this article, we describe studies presented at the ASCO 2014 Annual Meeting that sought to improve clinical management of head and neck cancers by evaluating the utility of biomarkers in guiding treatment decisions, as well as by developing patient surveys that are better able to capture key symptoms:

  • Investigators outlined the rationale and design of PREDICTOR, a phase II study whose goal is to identify predictive and pharmacodynamic biomarkers to assess the efficacy of anti-EGFR treatment with afatinib in patients with untreated nonmetastatic HNSCC.
  • The nCOunter nanoString platform was used to identify a set of gene expression biomarkers that may predict outcome of treatment with inhibitors of EGFR and COX-2 in patients with premalignant head and neck cancer lesions.
  • Preliminary testing of the Vanderbilt Head and Neck Symptom Survey – Recurrent/Metastatic (VHNSS-RM), a patient-response outcome measure designed to assess symptom burden and enable improved palliation, demonstrated that the tool is feasible and helps to identify actionable problems in patients with advanced disease.

References: 1. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2011;11:9–22. 2. Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 1993;53:3579–84. 3. Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 2002;62:7350–6.

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Canadian Perspectives

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Carolyn Owen, MD

Dr. Carolyn Owen completed postgraduate training in internal medicine and hematology at the University of Ottawa and the University of British Columbia, respectively, followed by a research fellowship in molecular genetics at Barts and the London School of Medicine and Dentistry in London, UK. Her research focused on familial myelodysplasia and acute myeloid leukemia. She is currently an Assistant Professor at the Foothills Medical Centre & Tom Baker Cancer Centre, and her clinical interests are low-grade lymphoma and chronic lymphocytic leukemia. She is also the local principal investigator in Calgary for several clinical trials in these areas.

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David Macdonald, MD, FRCPC

Dr. David Macdonald is a hematologist at the QEII Health Sciences Centre in Halifax, Nova Scotia, and Assistant Professor in the Division of Hematology at Dalhousie University’s Faculty of Medicine. Dr. Macdonald chairs the Hematology Cancer Site Team for Cancer Care Nova Scotia. His interests are in hematologic malignancies and, in particular, lymphoproliferative disorders. He has done a Clinical Trials Fellowship with the National Cancer Institute of Canada – Clinical Trials Groups and is actively engaged in clinical trials research. Dr. Macdonald has also completed a clinical fellowship in the lymphoma group at the British Columbia Cancer Agency in Vancouver, and he maintains a clinical research program in lymphoma.

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Jeffrey Rothenstein, MD, FRCPC

Dr. Jeffrey Rothenstein is a medical oncologist at the R.S. McLaughlin Durham Regional Cancer Centre in Oshawa and an Adjunct Assistant Professor in the Department of Oncology at Queen’s University in Kingston, Ontario. He completed his internal medicine and medical oncology training at the University of Toronto. Dr. Rothenstein’s main clinical focus is on the management of thoracic and gastrointestinal malignancies. He is the lung cancer site group leader at the R.S. McLaughlin Durham Regional Cancer Center.

Investigator Commentaries

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Stephan Stilgenbauer, MD

Dr. Stephan Stilgenbauer is Associate Professor and Deputy Chairman at the Department of Internal Medicine III (Hematology, Oncology, Rheumatology and Infectious Diseases) at Ulm University, Germany. He received his medical training at Heidelberg Medical School and was trained in internal medicine and hematology-oncology at the Universities of Heidelberg and Ulm. He spent a postdoctoral fellowship at the German Cancer Research Center (DKFZ) in Heidelberg. His research focus is on the molecular pathogenesis of hematological malignancies and translation of this research into novel treatment strategies. Dr. Stilgenbauer has authored or co-authored numerous original articles, reviews, and book chapters in journals such as The New England Journal of Medicine, The Lancet, Nature Medicine, the Proceedings of the National Academy of Sciences of the United States of America, Journal of Clinical Oncology, Blood, Leukemia, Haematologica, among others.

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C. Tom Kouroukis, MD

Dr. C. Tom Kouroukis graduated from the University of Toronto and completed training in Internal Medicine, Hematology and MSc (Health Research Methodology) training at McGill and McMaster Universities. He was awarded a National Cancer Institute of Canada Clinical Research Fellowship. He is a hematologist at the Juravinski Cancer Centre/Hamilton Health Science, Chair of the Hematology Disease Site Team, Head of the Division of Malignant Hematology, and Associate Professor in the Department of Oncology. He is Co-chair of the Hematology Cancer Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative and Chair of the Stem Cell Committee of Cancer Care Ontario. His research interests include the care of older patients with hematological cancers, the impact and evaluation of co-morbidity in older cancer patients, clinical trials, and practice guideline development.

Expert Commentaries

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Laurie H. Sehn, MD, MPH
Dr. Laurie H. Sehn is a Clinical Assistant Professor at the BC Cancer Agency and the University of British Columbia in Vancouver. She has been a medical oncologist and clinical investigator with the Lymphoma Tumour Group since 1998. Dr. Sehn has served on the Board of Directors of Lymphoma Foundation Canada (LFC) since 2002 and is currently Director of Research Fellowships for the LFC. Dr. Sehn’s research interests include all of the lymphoid cancers, with particular interest in the biology and treatment of large-cell lymphoma, the application of new imaging techniques such as PET scanning to lymphoma management, and innovative new approaches to treatment.

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Dietger Niederwieser, MD
Dr. Dietger Niederwieser is the Head of the Department of Hematology and Oncology at the University Hospital of Leipzig in Germany. He completed his medical degree and postgraduate training in internal medicine and hemato-oncology at the University of Innsbruck in Austria. His research interests include leukemia, myelodysplastic syndrome, renal cell carcinoma, Hodgkin lymphoma, allogeneic stem cell transplantation, and graft versus host disease and he is currently involved in a variety of clinical trials in these areas. Dr. Niederwieser is President of the Worldwide Network for Blood and Marrow Transplantation, past President of the European Group for Bone and Marrow Transplantation (EBMT), and a former Chair of the EBMT Chronic Leukemia Working Party. He is a member of several scientific societies, including the European Hematology Association, the American Society of Hematology, and the American Society of Clinical Oncology and he serves as an external reviewer for universities in Europe and the United States. Dr. Niederwieser is the author or co-author of numerous articles (<390) published in international peer-reviewed journals, such as The New England Journal of Medicine, Blood, the Journal of Clinical Oncology, the Journal of the American Medical Association, Nature Clinical Practice Oncology, Annals of Oncology, Leukemia, and Bone Marrow Transplantation.

Case Study

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Barbara Melosky, MD, FRCP(C)

Dr. Barbara Melosky is a Clinical Associate Professor of Medicine at the University of British Columbia and a medical oncologist at the British Columbia Cancer Agency in Vancouver. She graduated from medical school at the University of Manitoba, and did a residency in internal medicine and an oncology fellowship at the University of British Columbia. Dr. Melosky is currently working in the fields of lung and gastrointestinal malignancies with a special interest in the side effects of targeted therapy. She sits on the Executive Committee for the Lung Disease Site NCIC Clinical Trials Group and is the annual Chair of the Canadian Lung Cancer Conference.