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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Advanced Lung Cancer: New Strides in the Treatment of Bone Metastases


GOAL
To provide oncologists, hematologists, oncology nurse practitioners, and oncology physician assistants with up-to-date information about the management of bone health in patients with lung cancer.

TARGET AUDIENCE
This activity is designed for oncologists, hematologists, oncology nurse practitioners, and oncology physician assistants with an interest in the treatment of bone metastases in patients with lung cancer. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, the participant should be able to:

  • Describe the complications imposed by bone metastases in the clinical management of lung cancer now that patients are living longer.
  • Understand the use of radiation therapy, surgery, and radiopharmaceuticals as
     treatment for patients with bone metastases.
  • Discuss the safety and efficacy of currently available agents and next-generation
    bisphosphonates. 
  • Explain the use of intravenous therapy in the treatment armamentarium to delay and reduce skeletal complications of bone metastases in patients with lung cancer. 
  • Develop individualized treatment plans through case-based discussion to help identify and reduce the occurrence of skeletal-related events in patients with lung cancer.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The estimated time to complete this educational activity: 2 hours.

Release date: December 15, 2006. Expiration date: December 15, 2008.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Novartis Oncology.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

PROGRAM DIRECTOR

David S. Ettinger, MD, FACP, FCCP
Alex Grass Professor of Oncology
Professor of Medicine, Otolaryngology, Head & Neck Surgery, Gynecology and Obstetrics, Radiation Oncology and Molecular Radiation Sciences
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland
Dr Ettinger reports receiving grants/research support from Eli Lilly and Company, Novartis, and Sanofi-Aventis; serving as a consultant for AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck and Company, MGI Pharma, and Pfizer Inc; receiving honoraria from AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck and Company, MGI Pharma, and Pfizer Inc; serving on the speaker's bureau for AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck and Company, MGI Pharma, and Pfizer Inc.

PARTICIPATING FACULTY

James R. Berenson, MD
Chief Executive Officer
Oncotherapeutics
Medical and Scientific Director
Institute for Myeloma and Bone Cancer Research
Los Angeles, California
Dr Berenson reports receiving grant/research support from Amgen, Celgene, Cell Therapeutics, Cephalon, Chugai, Cytogen, Millennium, Novartis, Pfizer Inc, Pharmacyclics, Xcyte, and Ziopharm; serving as a consultant for Amgen, Ariad, Celgene, Cell Therapeutics, Cephalon, Chugai, Millennium, Novartis, OrthoBiotech, and Seattle Genetics; and serving on the speaker's bureau for Celgene, Cell Therapeutics, Cephalon, Chugai, Millennium, and Novartis.

Julie R. Brahmer, MD
Assistant Professor of Medical Oncology
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland
Dr Brahmer reports receiving grants/research support from AstraZeneca and Wyeth; and receiving honoraria from Sanofi-Aventis.

Walter J. Curran Jr, MD
Professor and Chairman
Department of Radiation Oncology
Jefferson Medical College
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania
Dr Curran reports receiving grants/research support from AstraZeneca, Aventis, Bristol-Myers Squibb, Millennium, Pfizer Inc, and Sanofi; and serving as a consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech, Imclone, Medimmune, and Novartis.

Jody S. Garey, PharmD
Clinical Pharmacist
Thoracic/Head and Neck Medical Oncology
Division of Pharmacy
University of Texas
MD Anderson Cancer Center
Houston, Texas
Dr Garey reports having no financial or advisory relationships with corporate organizations related to this activity.

Corey J. Langer, MD
Medical Director
Thoracic and Head & Neck Oncology
Fox Chase Cancer Center
Associate Professor of Medicine
Temple University
Philadelphia, Pennsylvania
Dr Langer reports receiving grants/research support from Active Biotech, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Cell Therapeutics Inc, Eli Lilly, Genentech, Medimmune, OrthoBiotech, OSI, Pfizer Inc, Pfizer-Pharmacia, Sanofi-Aventis, Schering-Plough Research Institute, and Vertex; serving as a scientific advisor for Abraxis, Amgen, AstraZeneca, Bayer/Onyx, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, ImClone, Intrabiotics, Novartis, Pfizer-Pharmacia, Pharmacyclics, Sanofi-Aventis, and Savient; and serving on the speaker's bureau for Bristol-Myers Squibb, Eli Lilly, Sanofi-Aventis, Genentech, and OrthoBiotech. 

Notice: The audience is advised that articles in this CME activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Berenson—arsenic trioxide, myeloma use; Celebrex, myeloma use; Quadramet, myeloma use; Revlimid, myeloma use; Thalomid, myeloma use; Velcade, myeloma use in combination with chemotherapy; Xcellerate, myeloma use; Zometa, MGUS use.

All other faculty members have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Advanced Lung Cancer: New Strides in the Treatment of Bone Metastases
David S. Ettinger, MD, FACP, FCCP*

Tremendous advances have been made in the pathophysiology and treatment of cancer. Because of these advances, today's treatment goals are different from those of the past. Oncology healthcare professionals no longer simply hope to slow tumor growth; the focus is now on quality of life, remission, and cure. However, even with early detection and more targeted chemotherapy, metastases are still an inevitability for many patients with cancer. The incidence of bone metastases is high for certain malignancies, including multiple myeloma (95%-100%), breast and prostate cancer (65%-75%), and lung cancer (30%-40%).1 Unfortunately, approximately 50% of the patients afflicted with lung cancer present for the first time already exhibiting signs and symptoms of bone metastases. 

The impact of bone metastases on survival and the quality of life of patients with cancer is well documented. Skeletal complications, such as pathologic fractures and spinal cord or nerve root compression, lead to detrimental consequences, including severe pain, impaired mobility, sleeping and eating disorders, and an overall poor prognosis. These consequences underscore the fact that, although there has been much progress in the fight against cancer, there is still much work to be done.

Skeletal complications of bone metastases result from the derangement of normal bone metabolism, which arises from interactions between factors originating in tumor cells and others originating in the microenvironment of the bone. Fortunately, there is an increasing array of treatment options that arise from breast, lung, and prostate cancer. The goals of treatment for skeletal complications are to relieve pain and reduce the risk of fracture. Traditional therapies include radiation, surgery, and chemotherapy. In recent years, bisphosphonates have become the treatment of choice because of their ability to reduce bone resorption, leading to decreases in hypercalcemia, new osteolytic lesions, and fractures.2 A better understanding of the pathophysiology of bone metastases, particularly osetolytic bone disease, has led to an abundance of promising investigational agents that slow down bone resorption. It is important for clinicians to stay abreast of all recent developments to optimize care for patients with bone metastases.  

This issue of Johns Hopkins Advanced Studies in Medicine is based on proceedings from a roundtable that was held July 12, 2006, in Baltimore, Md. The discussion focused on the latest developments in the pathophysiology of bone metastases, in addition to currently accepted treatment modalities for the prevention and treatment of skeletal-related events. The articles in this monograph are primarily focused on skeletal complications in patients with lung cancer. They also address other solid tumors and multiple myeloma because many recommendations and findings are based on research targeting these cancers.

James R. Berenson, MD, Walter J. Curran Jr, MD, and Corey J. Langer, MD, each present articles on various issues that are important in the discussion of treating bone metastases in lung cancer. Joining these experts in group discussions of their presentations and case study discussions are Julie R. Brahmer, MD, and Jody S. Garey, PharmD.

In his review article, Dr Langer provides a background and update on the mechanisms of bone metastases in lung cancer, focusing on the association between clinical events and biochemical markers. Also included in Dr Langer's article is a review of diagnosis and symptomatology of bone metastases, in addition to an extensive discussion of the incidence and impact of skeletal-related events on quality of life, healthcare costs, and survival in patients with various malignancies, including lung cancer.

Dr Curran discusses new developments associated with the available treatment modalities, including radiation therapy, radiopharmaceuticals, surgery, and bisphosphonates. He includes a review of clinical trials comparing single versus multiple fractions of external-beam radiotherapy, new and less-invasive surgical techniques, and innovative ways of mapping out surgical pathways. Also included is a primer on the pathophysiology of osteolytic bone disease and investigational therapies that reduce bone resorption by targeting osteoclasts. 

The research article by Dr Berenson reviews the available treatment modalities for bone pain, one of the most disabling symptoms of skeletal metastases. Specific options highlighted include kyphoplasty—a minimally invasive procedure used to treat vertebral compression fractures—and nitrogen-containing bisphosphonates, which have been shown to have palliative effects in metastatic bone disease. This article also offers an extensive discussion about some of the more serious side effects of bisphosphonates, including osteonecrosis of the jaw and renal dysfunction.

Led by Dr Brahmer, a roundtable discussion of 3 case studies concludes this issue. These case studies spotlight specific clinical issues in diagnosing and treating bone metastases and the difficulty in determining the appropriate course of care for individual patients. The faculty also discuss, in detail, the course of treatment for solitary and multiple metastases, with a focus on lung cancer. The case study topics include:

  • The dilemma of curative intent versus  palliative intent in treating a patient with lung cancer who has an asymptomatic solitary bone metastasis. 
  • Treatment of a patient with lung cancer who has a femoral lesion that resulted in suspected   compartment syndrome 
  • Nephrotoxicity issues in lung cancer treatment when multiple metastases are present.

The overarching goal of this monograph is to broaden the understanding of key issues and controversies surrounding the management of bone metastases related to lung cancer and other malignancies. This continuing education activity is targeted for medical and radiation oncologists, fellows in training, nurse practitioners, and other healthcare professionals caring for patients with advanced lung cancer.

REFERENCES

1. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(suppl 8):1588-1594.
2. Berenson JR, Rajdev L, Broder M. Managing bone complications of solid tumors. Cancer Biol Ther. 2006;5:[epub ahead of print].

*Alex Grass Professor of Oncology, Professor of Medicine, Otolaryngology, Head & Neck Surgery, Gynecology and Obstetrics, Radiation Oncology and Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Address correspondence to: David S. Ettinger, MD, FACP, FCCP, Alex Grass Professor of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Building, G88, 1650 Orleans Street, Baltimore, MD 21231.
E-mail: ettinda@jhmi.edu.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his/her article and all its contents.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.