NE Oncology Issue – September 2014

Renfro LA et al. ASCO 2014:3537

Background

Recent retrospective analyses of clinical trials in patients with early colorectal cancer (CRC) have revealed that low and high body mass index (BMI) are associated with worse patient outcomes. However, there is limited data on the use of BMI as a prognostic measure for outcomes in metastatic colorectal cancer (mCRC). Renfro and colleagues examined pooled data in the Aide et Recherche en Cancérologie Digestive (ARCAD) trial database to investigate the influence of BMI on patient outcomes.1

Study design

  • Data from the ARCAD trial database, which included 20,078 patients with mCRC from 23 first-line trials, were pooled.
  • Cox models (stratified by treatment arm within the study) were used to assess the prognostic influence of baseline BMI on overall survival (OS) and progression-free survival (PFS).
    • Adjustments for and interactions with age, sex, and performance status (PS) were considered.
    • Possible differences in BMI effect in patients treated with anti-EGFR and anti-angiogenesis therapy were tested.
    • BMI effect was treated as possibly nonlinear.
    • Clinically relevant effects with p <0.05 were deemed significant.

Key findings

  • BMI was prognostic for OS (p <0.0001) and PFS (p <0.0001) with L-shaped risk.
  • Risk was highest for patients with BMI near 15, decreased as BMI increased to approximately 28, and then plateaued for higher BMI. (Figure 1)
    • BMI effect was significant after adjustment for age, sex, and PS.
  • Low BMI was associated with poorer OS for males than females. (Figure 2)
  • High BMI was associated with improved OS for males versus females (p < 0.001). (Figure 2)
  • Other interactions (age, PS, and therapy type) were not significant.
  • Relative to obese patients, patients with the lowest BMIs were associated with:
    • 62% increased risk of death (95% CI: 48%–77%);
    • 35% increased risk of progression or death (95% CI: 24%–46%).
  • Limitations to the analysis in this study include:
    • BMI relationships (particularly for the increased risk observed for low BMI patients) may be related to disease;
    • Although BMI is likely related to the dose received by the patient, there is no formal way to incorporate dose effect in the modeling process;
    • Investigators were unable to adjust for potential confounding factors such as affluence and nutrition.

Key conclusions

  • BMI is prognostic for both OS and PFS.
    • Low BMI, but not high BMI, is associated with increased risk of progression or death among the patients with mCRC who were studied.
  • The increased risk that is associated with low BMI is greater for males than females.
  • Further studies are warranted, including investigations into the possibility that molecular pathways are involved in the impact of BMI on disease outcome.

Reference: 1. Renfro LA, Loupakis F, Adams RA, et al. Body mass index (BMI) as prognostic in metastatic colorectal cancer (mCRC): A pooled analysis of 21 first-line trials in the ARCAD database. J Clin Oncol (ASCO Annual Meeting) 2014;32 (Suppl):abstr 3537.

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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.