Management of Bone Metastasis in Extremities

Assistant Professor Chandhanarat Chandhanayingyong, MD

Division of Orthopaedic Oncology, Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand


SYNOPSIS

Bone metastases are a common manifestation of distant relapse from many types of solid cancers, especially those arising in the lung, breast, and prostate. Bone is the third most common organ affected by metastases, after the lung and liver. Bone metastases represent a prominent source of morbidity. Skeletal-related events (SREs) that are due to bone metastases can include pain, pathologic fracture, and hypercalcemia. In some cases, the extent of bone destruction is such that a fracture is imminent but not complete (termed an impending fracture). To be considered a candidate for a surgical procedure, a patient with metastatic disease should have an expected length of survival that is longer than the expected period of recovery from the procedure. Because of the shortened expected life span of the patients with metastatic disease, one of the goals of surgical fixation should be to achieve an immediately stable construct, which will allow full weight bearing and normal function without delay. 

Classic indication of an impending pathologic fracture included a limited number of criteria- for example, fracture for the lessor trochanter, a lytic lesion involving more than 50% of the bone width, a lytic lesion involving more than 2.5 cm of bone and pain that persists after radiotherapy. Mirels’ Evaluation System has been published for prediction of lone bone fracture risk in a group of patients with predominantly metastatic breast cancer treated with radiotherapy. This system become most commonly used criteria for prediction of pathologic fractures. Four criteria are equally weighted with potential assignment of 12 points. (Table 1) The risk of fracture increased with a score of 7 points. A score of 8 points correlated with a fracture risk of 15% and warranted consideration of prophylactic fixation.

Table 1. Mirels Scoring System for Prediction of Impending Pathologic Fracture

Criteria 1 point 2 points 3 points
Site Upper extremity Lower extremity Peritrochanteric
Size <1/3 width of bone 1/3-2/3 >2/3
Type Blastic Mixed Lytic
Pain Minimal Moderate Functional

 

Three considerations must be weighted before considering prophylactic fixation: diagnosis, tumor resection and preoperative embolization. For long bone lesions that are at risk for fracture and in need for prophylactic fixation, locked intramedullary nail fixation is the preferred treatment, when feasible. The need for supplemental bone cement in prophylactic stabilization has not been well established. However, curetting and cementation larger lesions during prophylactic fixation should be considered. 


MANAGEMENT OF BONE METASTASIS IN EXTREMITIES

Chris Charoenlap, MD

Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand


SYNOPSIS

Principle of bony metastasis from cancer is palliative treatment. It aims to reduce patient suffering for the rest of their life. Holistic approach, which include body, mind, and social aspect, should be used. 

Reducing pain and severity of cancer spreading need combination of adequate pain management, radiotherapy, chemotherapy and hormonal therapy. The bone with cancer metastasis should be evaluate for potential of fracture. Fixation or reconstruction must be done in impending or already fracture case, if patient is in good status for surgery. Patient with paraneoplastic disease such as hypercalcemia may present with unspecific symptoms including depression, weakness, constipation or severe condition like seizure, coma and arrythmia. Emergency treatment with intravenous fluid and bisphosphonate should be administered to patient as quickly as possible when hypercalcemia is detected.      

The main objective of surgical treatment in bony metastasis case is to reduce pain and improve patient function. Instrument of choice should withstand daily activities and also last long enough to avoid revision surgery. Intramedullary nail gives a whole bone structure stability, but in some circumstance prosthetic reconstruction may be necessary such as extensive bony destruction.


MANAGEMENT OF BONE METASTASES IN EXTREMITIES: BONE ANTIRESORPTIVE AGENTS.

Prakrit Suwanpramote, MD

Department of Orthopaedics, Faculty of Medicine Ramathibodi hospital, Mahidol University, Bangkok, Thailand


SYNOPSIS

Skeletal system is the third common metastatic site of solid organ cancer (breast, prostate, lung, thyroid and renal cell carcinoma) and one of the most common site of myeloma. Skeletal metastasis causes unpleasant conditions that were categorized in term of “skeletal-related events” or “SREs”, such as pathologic fracture, tumor-induced osteomalacia, hypercalcemia, neural structure compression and cancer-induced bone pain. The goal of treatment in metastatic bone disease is prevention and/or treatment of SREs. 

In the past decades, treatment modality of various primary cancer has been well developed, result in satisfied long term survival of cancer patients and increase incidence of bone metastasis and SREs. Most of SREs occur via OPG/RANK/RANKL pathway create imbalance of bone formation (osteoblastic activity) and bone resorption (osteoclastic activity) lead to skeletal destruction. that has been inhibited by some antiresorptive agents, such as bisphosphonates (zoledronate) and denosumab.

Currently, zoledronate and denosumab are standard agents for prevention and reduction of SREs in patient with advanced cancer and skeletal lesions1. Nevertheless, these agents in the adjuvant of early cancer for cancer treatment-induced bone loss and/or impede metastasis still in the trials. Duration and frequency of antiresorptive agent administration are still controversy1-3.

This session will describe about usage of antiresorptive agents in metastatic bone disease in extremities and discuss about role of these agents in various situation including controversy about zoledronate and denosumab. 

References:

    1. Coleman R, Gnant M, Morgan G, Cle´zardin P. Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst 2012; 104: 1059–67

 

  • Terpos E, Confavreux CB, Clézardin P. Bone antiresorptive agents in the treatment of bone metastases associated with solid tumours or multiple myeloma. Bonekey Rep. 2015;4:744. Published 2015 Oct 7. doi:10.1038/bonekey.2015.113
  • Himelstein AL, Foster JC, Khatcheressian JL, et al. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients with Bone Metastases: A Randomized Clinical Trial. JAMA. 2017;317(1):48–58.

 


RADIATION THERAPY OF BONE METASTASIS IN EXTREMITIES

Assistant Professor Sasikarn Chamchod, MD

Faculty of Medicine and Public Health, Chulabhorn Royal Academy, Bangkok, Thailand
Radiation Oncology Department, Chulabhorn Royal Academy, Bangkok, Thailand


SYNOPSIS

Metastatic disease to the bone is a common cause of pain and other significant symptoms that are detrimental to quality of life. The ultimate prognosis for patients with bone metastases is poor, with median survival typically measured in months rather than years. Overall survival depends on the primary site and the presence or absence of visceral metastases. In the appendicular skeleton, the proximal femurs are the most common site of metastatic disease, and humeral lesions also occur frequently. The acral sites (feet and hands) are rarely involved. 

Radiation therapy has been reported to be effective in palliating painful bone metastases, with partial pain relief seen in 80% to 90% of patients and complete pain relief in 50% of patients. These data are primarily from studies using physician evaluation of pain. When patient evaluation of pain is used, pain improvement is seen in 60% to 80% of patients and complete pain relief is seen in 15% to 40% of patients. The effectiveness of the treatment also depends on the goal: palliation of pain, prevention of pathologic fracture, avoidance of future treatments, or local control of the disease. In addition to pain relief, other symptoms may be relieved by radiotherapy. Patients who have improvement in pain after radiotherapy may also have improvement in emotional functioning, decreased insomnia and decreased constipation, and overall improvement in quality-of-life scores. Radiation therapy should be an integral part of palliative treatment for bone metastases for treatment of pain and prevention of other symptoms. 

There have been multiple randomized, prospective trials in the last 30 years comparing shorter-course, lower–total-dose treatment to the more “standard” longer-course, higher–dose treatment. Several conclusions are clear from the studies: 

  1. Single-dose treatments of 8 Gy provide similar pain relief to longer-treatment regimens (30 Gy in 10 fractions or 20 to 24 Gy in five to eight treatments). 
  2. The retreatment rates are higher after short-course treatment by a factor of two to three. 
  3. Response rates are lower when scored by the patient instead of by the treating physician. 
  4. Response rates are better when the initial pain scores are lower, that is, when the patients are treated for moderate pain rather than severe pain. 
  5. There is no consistent dose–response relationship for palliation of bone metastases.

Palliative radiation therapy is of significant benefit to patients after painful bone metastasis, with most patients experiencing relief in the magnitude of pain following treatment. Response rates to palliative radiation therapy for localized sites of pain are consistently higher than response rates from palliative systemic therapy, and palliative external-beam radiation therapy remains the mainstay of treatment for clinically localized painful bone metastasis.

Event Hours(1)

  • Lotus 3-4.

    03:00 pm – 04:30 pm

    Speakers:
    1. Dr. Chandhanarat Chandhanayingyong (SI)
    2. Dr. Chris Charoenlap (CU)
    3. Dr. Prakrit Suwanpramote (Rama)
    4. Asst. Prof. Sasikarn Chamchod (CRA)
    5. Dr.Siravich Suvithayasir (CRA)
    6. Dr.Tippamas Taechawiwat (CRA)

    Moderator:
    Dr. Thanapon Chobpenthai (CRA)