2. Indications and optimal doses for bone metastases RT

External beam RT (EBRT) continues to be the mainstay treatment for painful, uncomplicated, bone metastases. EBRT can provide rapid successful palliation of painful bone metastasis in 50–80% of patients, is associated with very few adverse effects and leads to complete pain relief at the treated site in up to one-third of patients. Although various fractionation schemes can provide good palliation rates, numerous prospective randomized trials have shown that 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction provide excellent pain control with minimal side effects (Table 1) [2–7]. Longer fractionated courses have the advantage of a lower incidence of repeat irradiation to the same site, whereas single fractions have proved more convenient for patients and caregivers. In addition, repeat irradiation with EBRT might be safe, effective and less commonly necessary in patients with a short life expectancy.


BPTWP, Bone Pain Trial Working Party; NA, not assessed; Fx, fraction(s).

Table 1. Outcomes of single fraction or multifraction external beam radiotherapy for painful bone metastases.

For metastatic spinal cord compression (MSCC), EBRT is the standard of care. Although a total of 30 Gy in 10 fractions is the most frequently employed fractionation schedule, multiple fractionation schemes have been reported, which undoubtedly reflect the heterogeneity in patient populations and tumor histologies (Table 2) [8–11]. In a retrospective study, Rades et al. [11] suggested that dose escalation beyond 30 Gy in 10 fractions did not improve motor function and local control in patients with MSCC who had radioresistant tumors such as renal cell carcinomas, colorectal cancers and malignant melanomas. However, in patients with breast cancer, prostate cancer, myeloma or lymphoma and others who had a favorable prognosis, dose escalation beyond 30 Gy provided better local control and extended overall survival [10]. Therefore, the use of 30 Gy in 10 fractions could be regarded as the standard therapeutic dose for MSCC, although the available evidence is limited. In patients with a favorable survival prognosis, dose escalation beyond 30 Gy might improve local control and overall survival, but it might not improve functional outcome and dose escalation to 40 Gy in 20 fractions might be insufficient against radioresistant tumors.


RCT, randomized controlled trial; Fx, fraction(s); NA, not assessed.

fractures. Proper care of patients with bone metastasis requires interdisciplinary treatments delivered by orthopedic surgeons, radiation oncologists, rehabilitation specialists, medical oncologists, pain medicine specialists, radiologists and palliative care professionals. Radiotherapy (RT) has played a central role for palliation of painful bone metastasis, leading to complete pain relief at the treated site in up to one-third of patients [1]. The role of RT and radiotherapeutic techniques using a multidisciplinary approach for the treatment of bone metasta-

External beam RT (EBRT) continues to be the mainstay treatment for painful, uncomplicated, bone metastases. EBRT can provide rapid successful palliation of painful bone metastasis in 50–80% of patients, is associated with very few adverse effects and leads to complete pain relief at the treated site in up to one-third of patients. Although various fractionation schemes can provide good palliation rates, numerous prospective randomized trials have shown that 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction provide excellent pain control with minimal side effects (Table 1) [2–7]. Longer fractionated courses have the advantage of a lower incidence of repeat irradiation to the same site, whereas single fractions have proved more convenient for patients and caregivers. In addition, repeat irradiation with EBRT might be safe,

2. Indications and optimal doses for bone metastases RT

effective and less commonly necessary in patients with a short life expectancy.

relief (%)

BPTWP [2] 775 8 Gy in 1 Fx 78 57 30 2 23

Foro [3] 160 8 Gy in 1 Fx 75 15 13 NA 28

Nielsen [5] 241 8 Gy in 1 Fx 62 15 35 5 21

Roos [6] 272 8 Gy in 1 Fx 53 26 5 5 29

Steenland [7] 1171 8 Gy in 1 Fx 72 37 Equivalent 4 25

Table 1. Outcomes of single fraction or multifraction external beam radiotherapy for painful bone metastases.

Complete response (%)

30 Gy in 10 Fx 86 13 18 NA 2

20 Gy in 4 Fx 71 15 35 5 12

20 Gy in 5 Fx 61 27 11 4 24

24 Gy in 6 Fx 69 33 Equivalent 2 7

Acute toxicity (%)

78 58 32 1 10

66 15 10 4 18

Late toxicity (%) Repeat treatment rate (%)

Dose and fractions Overall pain

20 Gy in 5 Fx/30 Gy

BPTWP, Bone Pain Trial Working Party; NA, not assessed; Fx, fraction(s).

in 10 Fx

Hartsell [4] 898 8 Gy in 1 Fx/30 Gy in 10 Fx

ses have been discussed recently.

4 Radiotherapy

Author Patients (n)

Table 2. External beam radiotherapy outcomes for metastatic spinal cord compression.

#### 3. Intensity-modulated RT or stereotactic body RT for bone metastases

Recently, intensity-modulated RT (IMRT) or stereotactic body RT (SBRT) has been applied for spinal bone metastases and the development of systemic treatments has improved survival in patients with bone metastasis. However, in such cases, the standard regimens for bone metastases including 30 Gy in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction were insufficient for long-term pain management. Therefore, to increase the duration of pain control, it might be necessary to consider more intense RT or treatment regimens.

IMRT delivers high doses to tumor targets while decreasing the dose to organs-at-risk and, therefore, presents a major dosimetric advantage over three-dimensional conformal RT. IMRT took radiation treatment planning and delivery to a higher level by combining technologies. It utilizes movement of the multileaf collimator (MLC) during the actual beam-on time to modulate, or alter, the radiation beam as it leaves the radiation treatment unit. Such beam modulation allows the application of concave dose distributions. The computer system calculates an IMRT plan incorporating several beams, or, alternatively, a moving arc arrangement with the movement of the MLC to create a plan that achieves the radiation-dosing goals (Figure 1). On the other hand, SBRT is emerging as an alternative RT technique to deliver dose-escalated radiation to tumor targets. Due to the application of several nonisocentric beams, SBRT delivers highly conformal large radiation dose fractions to target volumes with precision (<1 mm) and steep dose gradients. This allows for planning target volume reductions, thereby minimizing exposure to critical adjacent organs, which produces a toxicity profile comparable with that of conventionally fractionated RT, despite the use of higher doses per fraction (Figure 2).

Figure 1. Comparison of radiation dose distributions between conventional radiotherapy and intensity-modulated radiotherapy (IMRT). (A) The osteolytic change in the lumbar vertebral body and infiltration into the spinal canal. (B) The dose distribution of conventional radiotherapy (two-directional anteroposterior-posteroanterior opposed irradiation at 30 Gy in 10 fractions). (C) The distribution of IMRT using volumetric modulated arc therapy (50 Gy in 10 fractions).

survival in patients with bone metastasis. However, in such cases, the standard regimens for bone metastases including 30 Gy in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction were insufficient for long-term pain management. Therefore, to increase the duration of pain control, it might be necessary to consider more intense RT or treatment

IMRT delivers high doses to tumor targets while decreasing the dose to organs-at-risk and, therefore, presents a major dosimetric advantage over three-dimensional conformal RT. IMRT took radiation treatment planning and delivery to a higher level by combining technologies. It utilizes movement of the multileaf collimator (MLC) during the actual beam-on time to modulate, or alter, the radiation beam as it leaves the radiation treatment unit. Such beam modulation allows the application of concave dose distributions. The computer system calculates an IMRT plan incorporating several beams, or, alternatively, a moving arc arrangement with the movement of the MLC to create a plan that achieves the radiation-dosing goals (Figure 1). On the other hand, SBRT is emerging as an alternative RT technique to deliver dose-escalated radiation to tumor targets. Due to the application of several nonisocentric beams, SBRT delivers highly conformal large radiation dose fractions to target volumes with precision (<1 mm) and steep dose gradients. This allows for planning target volume reductions, thereby minimizing exposure to critical adjacent organs, which produces a toxicity profile comparable with that of conventionally fractionated RT, despite the use of higher doses per fraction

Figure 1. Comparison of radiation dose distributions between conventional radiotherapy and intensity-modulated radiotherapy (IMRT). (A) The osteolytic change in the lumbar vertebral body and infiltration into the spinal canal. (B) The dose distribution of conventional radiotherapy (two-directional anteroposterior-posteroanterior opposed irradiation at 30 Gy

in 10 fractions). (C) The distribution of IMRT using volumetric modulated arc therapy (50 Gy in 10 fractions).

regimens.

6 Radiotherapy

(Figure 2).

Figure 2. A 70-year-old male patient suffering from lung cancer with cervical vertebral bone metastasis. The schema and dose distribution of SBRT for bone metastasis using CyberKnife treatment system. (A) The blue line indicates the beam directions. (B) Representative dose distribution.

Three important factors should be considered for the decision to utilize IMRT or SBRT. First, IMRT or SBRT must be adapted for the treatment of oligometastasis in the bone. Long-term survival has been noted in patients diagnosed with isolated bone metastasis [12–15]. Therefore, successful control of oligometastasis of the bone due to the delivery of higher doses might contribute to improved treatment outcomes and quality of life (QOL). Second, IMRT or SBRT can be performed for reirradiation of the same site. It is technically difficult to reirradiate the same site using conventional RT. However, with IMRT or SBRT the dose to the spinal cord or adjacent organs can be reduced to within the tolerable range, facilitating reirradiation. Third, IMRT or SBRT can be applied for radioresistant bone metastases. Therefore, when indicating IMRT or SBRT for metastatic bone tumors, oncologists should consider the disease behavior and estimated life expectancy of the patient.

The treatment outcomes of previous studies that utilized IMRT or SBRT for bone metastases [16–19] are compared in Table 3. Each study performed IMRT or SBRT using various dose or fractionation protocols because standard regimens have not yet been proposed. The majority of studies demonstrated excellent local control without serious harmful phenomenon such as myelopathy. However, because most previous studies were retrospective and sufficient evidence has not yet been accumulated, any adaptation of IMRT or SBRT to deliver higher doses must be carefully discussed for individual patients. A multidisciplinary team comprising radiation oncologists, orthopedists, medical oncologists, radiologists, rehabilitation physicians and palliative care medicine doctors would be ideal for discussing and deciding treatment options including the application of higher dose RT.


IMRT, intensity modulated radiotherapy; SBRT, stereotactic body radiotherapy; LCR, local control rate.

Table 3. Outcomes of IMRT or SBRT in bone metastasis.
