This document discusses the general approach and therapeutic options for managing bone metastases. The goals of management are to control pain and symptoms, preserve function, minimize risks of skeletal-related events, and enhance local tumor control. Therapeutic options include analgesics, osteoclast inhibitors, systemic therapies, radiation therapies, surgery, and ablation. Radiation therapies like EBRT and SBRT provide pain relief in many cases. Systemic therapies and osteoclast inhibitors can also help control pain by reducing tumor bulk. Surgery is generally reserved for impending fractures while ablation is used for localized recurrent pain.

1. Bone Metastasis-Part 2
By Dr Prabhat Ranjan
Department of medical oncology
SRMC

2. GENERAL APPROACH TO THE PATIENT
• The goals of management for patients with bone metastases include
1. Maximizing pain or symptom control
2. Preserving and restoring function
3. Minimizing the risk for SREs
4. Stabilizing the skeleton (if needed)
5. Enhancing local tumor control

3. • Therapeutic options include
1. Pain management/analgesia, which may be administered in parallel with osteoclast
inhibitors (bone modifying agents)
2. Systemic anticancer therapy
3. Radiation therapy (EBRT or SBRT)
4. Bone-targeting radiopharmaceuticals
5. Surgery (which is generally reserved for patients with a complete or impending pathologic
fracture)
6. Image-guided thermal ablation

4. Analgesia
• Initially, nonopioid analgesic drugs, such as acetaminophen and nonsteroidal
anti-inflammatory drugs (NSAIDs), may be used alone for mild to moderate
pain
• When pain is not adequately relieved, these nonopioid analgesic drugs may
be used in combination with an opioid
• For moderate or severe cancer pain, opioids are the most common medical
therapy because they are effective for all types of cancer pain

5. WHO PAIN LADDER

6. • Glucocorticoids may be helpful for patients with somatic pain from bone
metastases whose pain is incompletely resolved with opioids with or without
NSAIDs
• Other adjuncts include antidepressants and antiepileptics such as gabapentin,
which may be effective for tingling and burning pain
• Consultation with an anesthesia pain specialist can be considered for
integration of interventional procedures (eg, nerve block, spinal cord
stimulator, epidural port-a-cath, or implanted pain pump)

8. Osteoclast inhibitors
• Osteoclast inhibitors slow or reverse the progression of skeletal metastases
and reduce the likelihood of SREs
• In addition, they also have some analgesic benefit, although it is modest
• Denosumab has proven modestly superior to bisphosphonates for
prevention of SREs and in analgesic efficacy although it is costlier
• Zoledronic acid is the preferred agent for breast,castrate resistant prostate
cancer and multiple myeloma

9. • Bisphosphonates and denosumab are associated with side effects such as jaw
osteonecrosis, hypocalcemia [especially in vitamin D-deficient patients]
• Risks specific to bisphosphonates in patients with malignancy include
1. impaired renal function
2. a temporary flu-like syndrome with fever and body aches
3. significantly increased risk of atrial fibrillation/flutter and stroke
• Risks specific to denosumab include an increased risk of infection

10. • Dosage Modifications in case of Renal impairment (Zoledronic acid)
1. CrCl >60 mL/min: 4 mg
2. CrCl 50-60 mL/min: 3.5 mg
3. CrCl 40-49 mL/min: 3.3 mg
4. CrCl 30-39 mL/min: 3 mg
5. CrCl <30 mL/min: Not recommended

11. Systemic anticancer therapy
• Chemotherapy, targeted therapies, and hormone therapy may contribute to pain
relief by reducing tumor bulk and/or by modulating pain signaling pathways
• However, primary tumor type, disease extent, and treatment-related toxicity are
important considerations:
1. For patients with breast cancer, limited disease bulk, and more favorable features
(such as a HR +ve metastasis) initiation of HT may be sufficient for pain relief
and disease control
2. Systemic therapy plays a major role in treatment in the setting of CRPC with
symptomatic bone metastases

12. • Limitations
1. Pain relief is usually not swiftly achieved, and patients may not have a sufficient
performance status to tolerate chemotherapy
2. Chemotherapy may also cause painful side effects or be complicated by side
effects that limit the effective dose that can be administered, such as neuropathy
(eg, platinum, taxanes, vinca alkaloids)
3. Newer biologic or molecularly targeted agents have fewer side effects and may be
more tolerable. However, like chemotherapy, they are not associated with
immediate pain relief.

14. Local treatment options

15. RADIATION THERAPY
• External beam radiation therapy (EBRT)
1. Standard approach for symptomatic skeletal metastases
2. Achieving pain reduction in 50 to 80 percent cases
3. A single fraction of 8 Gy to the involved area provides equivalent pain palliation
and is more cost-effective and convenient than fractionated regimens
4. Although approx 20 percent of patients may require retreatment after a single
fraction of 8 Gy, compared with 8 percent for those who received a fractionated
regimen

16. • Stereotactic body radiation therapy
• SBRT should be reserved mostly for patients who have a
1. Reasonable (>6 months) life expectancy
2. Persistent or recurrent bone pain after a standard course of EBRT
3. Require reirradiation

17. • Settings in which SBRT may be preferred over EBRT is
1. In the definitive treatment of patients with symptomatic bone metastases
from relatively radioresistant neoplasms (eg, RCC, melanoma, sarcoma), esp
in the setting of vertebral mets with epidural extension but no high-grade
epidural spinal cord compression
2. Patients with oligometastatic disease who have a relatively long life
expectancy

18. Diffuse bone pain
• There are two options in such circumstances:
1. Bone-targeted radiopharmaceutical therapy
2. Hemibody irradiation
• Hemibody irradiation can provide rapid pain relief when multiple sites of
symptomatic bone metastases are present
• But its use has largely been replaced, at least for advanced prostate cancer, by the
administration of bone-targeted radiopharmaceuticals, which offer a similar degree
of pain relief and may be associated with less toxicity

19. Bone-targeted radiopharmaceutical therapy
• Samarium-153(153Sm) and strontium-89 (89Sr) emit beta particles and are
effective for palliation of pain, with response rates between 40 and 95 percent
• However, the onset of pain relief is slower than with EBRT, taking up to two to
four weeks
• Also patients can have prolonged hematologic toxicity (more prominent with 89Sr
than 153Sm)
• They do not improve survival.
• Both agents are generally reserved for individuals with persistent or recurrent
multifocal bone pain after EBRT and/or other forms of therapy.

20. • Radium-223 is a new class of i.v injected bone-targeted radioisotopes
• Advantage of these alpha emitters is that they deposit high-energy radiation
over a much shorter distance than the beta particles emitted by 153Sm or
89Sr
• Radium-223 has been approved by the FDA for treatment of men with
castration-resistant prostate cancer, multifocal symptomatic bone metastases,
and no known visceral metastatic disease.

21. • Indications for bone-targeted radiopharmaceutical therapy include
1. positive bone scan
2. refractory bone pain despite analgesic
3. life expectancy >3 months
4. no chemotherapy or bisphosphonate six weeks prior to treatment

22. • Contraindications of bone-targeted radiopharmaceutical therapy include
1. Acute or chronic renal failure
2. Acute spinal cord compression
3. Pregnancy
4. Breastfeeding
5. Myelosuppression.

23. INDICATIONS FOR SURGICAL
CONSULTATION
• Surgical management of bone metastases is typically reserved for lesions
with a complete or impending pathologic fracture
• Surgery may also be needed for spine metastases that are causing mechanical
instability or epidural spinal cord compression
• For patients with long bone or spinal metastases, postop RT is generally
given after surgical stabilization to promote remineralization and bone
healing, alleviate pain, improve functional status, and reduce the risk for
subsequent fracture or loss of fixation by treating residual metastatic disease.

24. Nonvertebral bones
• Impending or complete fractures
 If a pathologic fracture of a long bone is present, it is often best treated
with internal fixation and instrumentation
 Prophylactic fixation of an impending pathologic fracture may be
considered for patients with a high risk for pathologic fracture as assessed by
Mirels criteria

25. • No impending or complete fracture
 Do not require surgery for bone metastasis
 However, for highly selected patients with advanced cancer who present with
or develop a bone lesion as the only focus of cancer beyond the primary site,
en bloc resection of the metastasis may optimize local tumor control,
provide durable pain relief, and possibly prolong patient survival
 In general, curative resection is rare for bone metastasis, except for selected
patients with isolated spine or sternal involvement.

26. Vertebral bones
• Surgical consultation should be sought for patients with spine metastases
with associated ESCC or vertebral column instability
• Consultation with a surgeon skilled in spine surgery (orthopedic spine
surgeon or a neurosurgeon) is recommended for patients with SINS scores
greater than 7

29. VERTEBROPLASTY AND
KYPHOPLASTY
• Another option for patients with painful vertebral bone metastases with a
compression fracture is percutaneous vertebral augmentation, with vertebroplasty or
kyphoplasty
• Percutaneous vertebral augmentation has been used to improve the mechanical
stability of the vertebrae as well as pain from a vertebral compression fracture
• When it is performed, vertebroplasty/kyphoplasty is generally reserved for patients
with symptomatic osteolytic spinal metastases, with intact bone cortex and without
epidural disease, spinal cord compression, or retropulsion of bone fragments into
the spinal cord

30. LOCAL ABLATION
• For patients who have persistent or recurrent pain attributed to 1 or a few skeletal
sites with small volume disease after pall RT and who are not candidates for surgery
or reirradiation with stereotactic techniques, local thermal ablation is an important
therapeutic option
• Radiofrequency ablation, cryoablation, and focused ultrasound are all effective
ablative treatments
• Patients should have at least moderate pain levels, pain referable to a limited
number of metastases that are visible on imaging, and target lesions that are
remote (or separable) from normal critical structures

31. • Absolute contraindications include
1. uncorrectable bleeding diatheses
2. inability of the patient to tolerate the level of anesthesia required to
perform the procedure
3. inaccessibility of the target lesion from a percutaneous approach

32. • Relative contraindications include
1. widespread skeletal metastases
2. the presence of active infection
3. tumor location adjacent to a critical normal structure that cannot be
displaced or monitored adequately to allow safe ablation