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Criteria for Palliation of Bone Metastases – Clinical Applications

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Criteria for Palliation of Bone Metastases – Clinical Applications IAEA-TECDOC-1549 Criteria for Palliation of Bone Metastases – Clinical Applications April 2007 IAEA-TECDOC-1549 Criteria for Palliation of Bone Metastases – Clinical Applications April 2007 The originating Section of this publication in the IAEA was: Nuclear Medicine Section International Atomic Energy Agency Wagramer Strasse 5 P.O. Box 100 A-1400 Vienna, Austria CRITERIA FOR PALLIATION OF BONE METASTASES – CLINICAL APPLICATIONS IAEA, VIENNA, 2007 IAEA-TECDOC-1549 ISBN 92–0–104507–7 ISSN 1011–4289 © IAEA, 2007 Printed by the IAEA in Austria April 2007 FOREWORD Bone metastases are a frequent complication of cancer. It is estimated that they arise in 14–70% of all tumour patients, while it was reported that they occur in 70–85% patients in autopsy material. Although they may arise from any primary malignant tumour, certain tumours such as breast, prostate, lung, thyroid, kidney and myeloma have a predilection for a spread to bone. Bone metastases frequently cause pain, but there are also clinical situations with bone metastases causing no pain at all. The overall importance of the problem of bone metastases is well recognized by the fact that each year hundreds of thousands of cancer patients develop bone metastases. For example, more than 100 000 new patients develop this condition in the United States of America, although the prevalence is estimated to be double the number of new cases. While it is virtually unknown how many cancer patients in the developing countries develop bone metastases, it is not unrealistic to expect that these figures largely surpass those coming from the developed countries. The reason is simply that more patients in the developing countries are diagnosed as having locally advanced or metastatic cancer that will eventually widely disseminate, including bone metastasis as well. Furthermore, at least some of the cancer patients may survive prolonged periods of time. They can also develop earlier and more severe symptoms than patients harbouring other types (locations) of metastases, emphasizing the importance of the overall problem of painful bone metastases. In addition, there is a big socioeconomic problem of bone metastasis, burdening health care systems worldwide, while having continuous adverse psychological effect on both patients and their families. The management of patients with metastatic bone pain must be a multidisciplinary approach and includes the use of analgesia, radiotherapy, surgery, chemotherapy, hormone treatment, radioisotopes and bisphosphonates. Analgesia, with non-steroidal anti-inflammatory drugs, is the first option in most patients, progressing to stronger opioids as the intensity of pain rises. These drugs produce unwanted side effects such as nausea, sedation, and constipation. Local external radiotherapy or surgery can be used for localized metastatic disease and hemibody radiotherapy might be suitable for patients with disease extending to one region of the body. In patients with widespread painful bone involvement, bone-seeking radiopharmaceuticals provide a promising pain-control strategy. This TECDOC should be seen as a guide and useful resource both for researchers and practitioners alike in both radiation oncology and nuclear medicine fields. The IAEA has put special emphasis on the issue of bone metastasis in the research field of cancer. Recent coordinated research projects have shown that it is an important issue to be addressed through clinical trials setting the best need of developing countries. The IAEA officers responsible for this publication were B. Jeremic and N. Watanabe of the Division of Human Health. EDITORIAL NOTE The use of particular designations of countries or territories does not imply any judgement by the publisher, the IAEA, as to the legal status of such countries or territories, of their authorities and institutions or of the delimitation of their boundaries. The mention of names of specific companies or products (whether or not indicated as registered) does not imply any intention to infringe proprietary rights, nor should it be construed as an endorsement or recommendation on the part of the IAEA. CONTENTS CHAPTER 1. INTRODUCTION ......................................................................................... 1 1.1. Incidence ...................................................................................................................... 1 1.2. Pathophysiology of bone pain...................................................................................... 1 1.3. Clinical presentation.................................................................................................... 2 1.3.1. Pain ................................................................................................................ 2 1.3.2. Pathlogical fracture .......................................................................................... 3 1.3.3. Hypercalcemia.................................................................................................. 3 1.3.4. Spinal instability with cord compression ......................................................... 3 1.4. Diagnosis of bone metastasis ....................................................................................... 4 1.4.1. Imaging............................................................................................................. 4 1.4.2. Assessment....................................................................................................... 5 References to Chapter 1 ............................................................................................................. 8 CHAPTER 2. EXTERNAL BEAM RADIOTHERAPY...................................................... 9 2.1. Local pain from uncomplicated metastasis.................................................................. 9 2.1.1. Radiation dose................................................................................................ 10 2.1.2. Toxicity .......................................................................................................... 13 2.2. Multi-site pain from uncomplicated metastasis ......................................................... 13 2.3. Metastatic spinal cord compression (MSCC) ............................................................ 15 2.4. Pathological fracture .................................................................................................. 20 2.4.1. Impending fractures of the femur / humerus.................................................. 20 2.4.2. Actual fractures of the femur and humerus.................................................... 23 2.4.3. Vertebral body lesions.................................................................................... 23 2.5. Neuropathic pain ........................................................................................................ 24 2.6. Cost effectiveness ...................................................................................................... 25 References to Chapter 2 ........................................................................................................... 33 CHAPTER 3. RADIONUCLIDE THERAPY.................................................................... 40 3.1. Introduction................................................................................................................ 40 3.2. Radiopharmaceuticals ................................................................................................ 40 3.3. Indications and patient selection ................................................................................ 42 3.4. Procedural aspects...................................................................................................... 42 3.4.1. Preparation ..................................................................................................... 42 3.4.2. Administration and recommended administered dose ................................... 43 3.5. Efficacy ...................................................................................................................... 43 3.6. Cost aspects................................................................................................................ 44 3.7. Beyond palliation: combination of radionuclide therapy with other modalities........ 45 References to Chapter 3 ........................................................................................................... 47 CHAPTER 4. FUTURE DEVELOPMENTS: NOVEL AND TUMOUR SPECIFIC RADIOPHARMACEUTICALS ............................. 50 4.1. Short range isotopes ................................................................................................... 50 4.1.1. Sn-117m (Sn-117m-DTPA, Sn-117m-Pentetate) .......................................... 50 4.1.2. Radium-223 (Ra-223-chloride)...................................................................... 50 4.2. Radiolabelled peptides and antibodies....................................................................... 51 References to Chapter 4 ........................................................................................................... 51 CHAPTER 5. RATIONALE FOR USE OF BOTH MODALITIES.................................. 53 CONTRIBUTORS TO DRAFTING AND REVIEW ............................................................. 55 CHAPTER 1 INTRODUCTION 1.1. Incidence Metastatic bone cancer is a common and severe complication in advanced disease. It develops in up to 70% of patients with prostate cancer and breast cancer, and in up
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