Palliative Radiation Therapy For Bone Metastases

Anatomy and Physiology

Healthy bone is in a constant state of turnover. Bone is deposited by osteoblasts, with absorption occurring via osteoclasts. Osteoclasts function under the influence of parathyroid hormone and calcitonin in response to calcium levels. Osteoclasts secrete enzymes and acids to mediate bone deposition and formation. Bone metastasis occurs due to growth at the primary tumor site, leading to tumor neovascularization. Tumor cells then detach from the primary tumor bed and invade nearby tissues with invasion into the blood. The tumor cells that survive in circulation then enter the bone marrow. In the bone marrow, the cells evade host defenses and further growth with stimulation of osteoclasts, leading to further bone resorption.[11] Cancer cells can release a whole host of growth factors that propagate osteoclasts. In addition, bone metastasis produces an increased inflammatory cell response, resulting in pain. The other mechanisms of bone pain relate to infiltration of the nerve root, microfractures, stretching of the periosteum, increased pressure in the bone, muscle spasms, and nerve compression.[12]

Indications

The primary goal of palliative radiation therapy is to alleviate pain. After treatment, most patients will expect to experience pain relief in 2 to 3 weeks in 60% of patients.[13][14] The indications for palliative radiotherapy to bone metastasis include:

• Pain from bone metastases that is difficult to control with oral regimens
• Malignant spinal cord compression
• Prevention of pathologic fractures

Contraindications

Contraindications to radiotherapy include patients with a history of inflammatory bowel disease, collagen vascular disease, pregnancy, and those with inherited cancer predisposition syndromes (eg, Down syndrome, Fanconi anemia, Gorlin syndrome, Cockayne syndrome, Gardner syndrome, Usher syndrome, Ataxia-telangiectasia, and Nijmegen breakage syndrome).[15] In addition, patients must be able to tolerate laying still for short periods. Patients must be able to provide informed consent for the procedure. Patients must be able to abide by verbal commands from radiation technicians in the adjacent room. The patient should have reasonable follow-up to monitor the effectiveness of pain control and adverse effects.[16]

Personnel

To design radiotherapy treatment, the radiation oncology team includes:

• Radiation oncologists: Board-certified clinicians in radiology oncology evaluate patients with various cancers for radiation therapy.
• Dosimetrists: Licensed health professionals who design the most potent radiation dosing possible for the area of interest with the fewest adverse effects of radiation.
• Medical physicists: Certified in therapeutic medical physics, these individuals work with dosimetrists to create effective treatment plans based on tumor location to deliver potent radiation with minimal healthy tissue involvement. Physicists ensure that the treatment plan is the actual plan delivered with the machine through a series of quality assurance checks before the patient is treated.
• Radiation therapists: These licensed therapists operate the machinery required to deliver treatment.
• Radiation oncology nurses and support staff: Specialized team members responsible for aiding in simulation setup, scheduling, and patient management.

Technique or Treatment

Radiotherapy Administration

A dedicated center uses a linear accelerator to deliver high-energy x-rays to the target lesion. Before receiving treatment, patients are examined in a consultation session termed simulation. During simulation, the patient is placed in an optimal position to treat the target lesion. The position must balance patient comfort, tolerance, and reproducibility at future appointments. The patient is expected to be in nearly the same position for all treatment appointments. Typically, patients must be able to lie still for roughly 15 to 30 minutes to complete a single treatment. A patient may need to wear a tight-fitting mask or garment when treating upper neck, head, and chest lesions. These high-energy beams delivered during treatment cause DNA damage and lead to cell death. Most patients undergoing curative treatment are scheduled to receive small daily doses called fractions. The fragmentation of radiotherapy treatment into smaller fractions reduces harm to healthy tissue near the target lesion and aids in avoiding permanent adverse effects. Patients undergoing palliative treatments typically receive a lower total dose, shifting the focus to symptom management of pain. The result for a patient receiving palliative radiotherapy is a shorter duration of a larger fraction.[16]

Radiotherapy Techniques

The primary radiotherapy techniques utilized are three-dimensional conformal radiation therapy (3-DCRT) and stereotactic body radiation (SBRT). The 3-DCRT external beam technique first requires a computed tomography (CT) scan of the target lesion and surrounding anatomy. In the case of spine metastasis to a vertebral body, the desired dose to the target volume is delivered to the site of the bone metastasis, including the vertebral body, often including a vertebral level above and below the lesion. Using 3-DCRT spares neighboring critical organs at risk.[17] However, SBRT delivers high doses of radiation to the target lesion with greater accuracy. This treatment modality allows minimal dose to surrounding structures in the treatment field and involves only the tumor.[18][19] SBRT is used less often than external beam radiation therapy (EBRT), but SBRT is useful for bone metastasis that is highly radioresistant (eg, sarcoma, renal cell carcinoma, and melanoma) or in the case of oligometastatic disease.

As of July 2023, a new study evaluated SBRT with EBRT for patients with painful spine metastases. The trial included 339 randomized patients with 1 to 3 spinal metastases where a pain response was measured on an 11-point scale. The results showed that EBRT elicited a complete or partial pain response more commonly than SBRT (61% versus 41%). EBRT continues to be used for most patients with a finite number of spinal bone metastases.[20]

Recommended Treatment Course

The American Society for Radiation Oncology (ASTRO) recommends single-fraction EBRT with 8 Gy for palliative pain relief of bone metastases. Fractionation schedules lead to higher costs and patient inconvenience than a single-fraction treatment plan.[21] An updated review of high-quality data shows pain relief equivalency following a single 8 Gy fraction, 20 Gy in 5 fractions, 24 Gy in 6 fractions, and 30 Gy in 10 fractions for patients with previously unirradiated painful bone metastases. Patients should be aware that single-fraction radiotherapy is associated with a higher incidence of retreatment to the same painful site compared to fractionated treatment.[22]

At times, surgery may be required before beginning radiation in patients who experience pathologic fracture of the long bones. Surgery may also be performed prophylactically to prevent pathologic fracture occurrence. Should a patient undergo surgical stabilization, radiotherapy is often administered postoperatively to provide local control of disease and alleviate associated pain. Several scoring systems have been developed to provide a more objective way of predicting patients' fracture risk with metastatic disease to long bones and vertebral lesions, including:

• Mirels scoring system: This scoring system considers the patient's level of cortex involvement, site of bone metastasis, radiographic nature, and pain level to attribute a score. The system is used to evaluate long bones with metastatic disease. Scoring <7 leads to a <10% fracture risk. A score of 8 has a 15% chance of fracture, and fixation should be considered. Scores ≥9 have more than a 33% chance of fracture and should be seen by an orthopedist. Generally, scores ≥8 should have an orthopedic consultation to assess prophylactic fixation.[23]

• Spinal instability neoplastic score: A scoring system developed to assess vertebral metastases. This score takes into account the clinical and radiographic findings of the lesion. Points are assigned to the spinal location, with the junctional occiput scoring the highest, pain relief with lying down, bone lesion quality (lytic versus blastic), radiographic spinal alignment, percent of vertebral body collapse, and amount of posterolateral spinal involvement. When all 6 components are combined, a score of 13 to 18 designates instability and should prompt a surgical consultation; scores between 7 and 12 are indeterminate and should involve a surgical consultation. Scores of ≤6 are considered a stable spine.[24]

Interventional Radiology Techniques

The following interventional radiology techniques may also be utilized in patients with bone metastases:

• Embolization: This technique acts by decreasing the vascularization of bone lesions. Embolic agents (nano-particles) are injected after peripheral artery access to the desired arterial location.[25]
• Thermal ablation: Radiofrequency, cryoablation, laser, or thermal ablation are various forms of this technique, which uses a variety of agents to induce a rapid temperature change in cells, leading to damage and necrosis.[26]
• Radiofrequency ablation: Computed tomography guidance is utilized to place ablation probes in the center of the tumor.[27] The downside to this technique is potential pain, and patients typically need sedation or analgesia.
• Microwave ablation: This technique typically provides faster coagulation and is less time-consuming than other techniques. Like radiofrequency ablation, an ablation probe is placed in the center of the tumor, and a set energy and time is used to complete the ablation.[28]
• Nonpercutaneous thermal ablation-high-intensity focused ultrasound ablation: This technique uses focused ultrasound beams backed by energy to burn the lesion that can be combined with magnetic resonance imaging-guided intensity-focused ultrasound as a noninvasive way of ablation to achieve coagulative necrosis.[29]
• Cementoplasty: Polymethyl methacrylate is injected into the bone portion weakened by metastasis. The compound acts to strengthen the bone to reduce pain.[30][31]

Complications

Most adverse effects relate to the anatomic location treated and fraction used. The most common adverse effect after treatment is fatigue. Up to 35% of patients may experience a pain flare within the first week of treatment, which typically resolves in 3 days.[32] Oral dexamethasone 8 mg daily before treatment and for 4 days after can be used to limit pain flare.[33] Other adverse effects due to radiation of the spine include bowel-related symptoms (eg, nausea, diarrhea, or abdominal discomfort). The typical treatment regimen to alleviate nausea symptoms is prescribing 5-HT3 antagonists (ie, seratonin antagonists) before, during, and after treatment. Loperamide and hyoscine butylbromide may be used to treat diarrhea. Adverse effects generally resolve in 4 to 6 weeks after completion of therapy. Long-term complications are not common.[16]

At times, repeated irradiation to the target lesion is required when the patient does not experience a response, pain recurs, or only a partial response is achieved. Up to 40% of patients do not obtain pain relief after initial therapy, and pain relapse is seen in 50% within 1 year of treatment.[34] No defined recommendation exists for reirradiation. A radiation oncologist should follow patients who have undergone repeated irradiation at their discretion.

Clinical Significance

The use of palliative radiotherapy has increased as the population with cancer has been able to reach a higher life expectancy. A well-organized, interprofessional team approach is required to utilize radiotherapy effectively. Understanding the appropriate indication and patient selection for treatment is critical in limiting complications and damage to surrounding structures and improving overall patient quality of life. Clinicians taking care of cancer patients should fully comprehend the utility of palliative radiotherapy when discussing care plans with patients who are no longer systemic therapy or surgical candidates. Educating patients on the role of palliative therapy is of high importance. Patients must understand the intent of treatment is to improve quality of life, not necessarily improve survival. Though adverse effects occur in any treatment in medicine, palliative radiotherapy is often well-tolerated and individualized such that most patients can complete their proposed treatment plans.

Enhancing Healthcare Team Outcomes

An interprofessional approach involving various healthcare professionals is vital for optimizing patient-centered care and outcomes related to palliative radiation therapy for bone metastases, consisting of medical oncologists, radiation oncologists, surgeons, pain management specialists, interventional radiologists, and palliative care clinicians. Effective communication and collaboration among these professionals are crucial for timely referral and patient selection, especially considering clinicians' challenges in identifying suitable candidates and involving radiation oncologists promptly. This collaborative effort aims to bridge the practice gap by effectively addressing variable referral patterns, disseminating guidelines, and rectifying misconceptions about treatment efficacy and adverse effects. By understanding the patient's primary cancer diagnosis, medical comorbidities, and life expectancy, healthcare professionals can tailor treatment plans to prevent further skeletal injury, alleviate symptoms, and enhance overall patient quality of life. Additionally, patient education regarding the role of palliative therapy is essential to align expectations and improve treatment adherence. Through interprofessional collaboration, healthcare professionals can optimize patient-centered care, improve outcomes, ensure patient safety, and effectively enhance team performance in managing bone metastases.

Nursing, Allied Health, and Interprofessional Team Monitoring

Patients should be followed after palliative radiotherapy treatments to monitor for adverse effects and to evaluate treatment effectiveness. Generally, patients should be seen by their medical oncologist, radiation oncologist, and other interprofessional team members to ensure patient safety and satisfaction.