Treatment/Prognosis

Question 1

Name 6 Tx for bone mets.

Answer 1

Bone met Tx:

Chemo
Radionuclides
Local EBRT
Endocrine therapy
NSAIDs
Narcotics

Question 2

What supportive measures can be used for pts with painful bone mets?

Answer 2

Supportive care for bone mets may include orthopedic braces such as thoracolumbosacral orthosis, canes, walkers, and wheelchairs.

Question 3

What interventional procedures can decrease pain from cancer-associated vertebral body collapse (i.e., compression fracture)?

Answer 3

Kyphoplasty and vertebroplasty are procedures performed by interventional radiologists that can address pain from vertebral body collapse. They are often performed in conjunction with EBRT.

Question 4

What is the difference b/t kyphoplasty and vertebroplasty?

Answer 4

Vertebroplasty utilizes fluoroscopic guidance to inject bone cement (methyl methacrylate) into the collapsed vertebral body. In kyphoplasty, an inflatable bone tamp is inserted to restore the height of the vertebral body, creating a cavity that can be filled with bone cement.

Question 5

According to the ASTRO Guidelines for Palliative RT for bone mets, what factors favor the inclusion of surgical decompression in addition to EBRT for SC compression?

Answer 5

Solitary site of tumor progression
Absence of visceral or brain mets
Spinal instability
Age <65 yrs
KPS ≥70
Projected survival >3 mos
Slow progression of neurologic Sx
Maintained ambulation
Nonambulatory for <48 hrs
Relatively radioresistant tumor (i.e., melanoma)
Site of origin suggesting relatively indolent course (i.e., prostate, breast, kidney)
Previous EBRT failed
(Lutz S et al., PRO 2017)

Question 6

In what cancers may chemo eradicate bone mets?

Answer 6

Chemo can cure bone mets from lymphomas and germ cell tumors.

Question 7

What is the chief action of bisphosphonates? Name 2 common ones.

Answer 7

Bisphosphonates inhibit osteoclast activity. Pamidronate and zoledronic acid are 2 common bisphosphonates.

Question 8

What is denosumab (XGEVA)?

Answer 8

Denosumab is a fully human monoclonal antibody that targets receptor activator of nuclear factor-kappa beta ligand (RANKL), thereby inhibiting maturation of osteoclasts.

Question 9

What are the American Society for Clinical Oncology (ASCO) 2017 guidelines for bone-modifying agents (BMAs) in the Tx of bone mets from breast cancer?

Answer 9

ASCO 2017 guidelines state that either zoledronic acid (IV, q6mos) or clodronate (PO, daily) should be given to postmenopausal women deemed candidates for adj therapy. Data for denosumab are promising, however not included in the current guidelines due to insufficient evidence. BMAs are adjunctive therapy, not recommended for 1st-line therapy and should be used concurrently for pain relief with analgesics, chemo, RT, and/or hormonal therapy. (Dhesy-Thind S et al., JCO 2017)

Question 10

Name 4 radionuclides used to treat bone mets.

Answer 10

Radionuclides available in the United States for Tx of bone mets:

Strontium-89
Samarium-153
Phosphorus-32
Radium-223 (currently for prostate cancer only)

Question 11

Describe the clinical implications of the differences in physical properties between strontium-89, samarium-153, phosphorus-32, and radium-223.

Answer 11

Both strontium-89 and phosphorus-32 emit β particles with higher energy than those of samarium-153, causing deeper tissue penetration. Though these higher-energy β particles may have a therapeutic benefit, they can also cause greater marrow toxicity.

The half-life of samarium-153 is much shorter than that of strontium-89. Thus, the planned RT dose from samarium-153 is delivered more quickly, leading to faster time to pain relief in many published trials.

Radium-223 emits high-energy α particles, which have high linear energy transfer inducing double-stranded DNA breaks, but a short range resulting in very limited toxic effects on adjacent healthy tissues.

Question 12

Why is phosphorus-32 seldom used for bone mets?

Answer 12

Phosphorus-32 was the 1st radionuclide to be used for bone mets, but it has greater hematologic toxicity compared with the other radionuclides available in the United States.

Question 13

When should radionuclides be considered?

Answer 13

Radionuclides should be considered in pts with adequate blood counts and multifocal painful bone mets imaged on bone scan.

Question 14

What are some contraindications to radionuclides for bone pain?

Answer 14

Contraindications for using radionuclides for bone pain:

Myelosuppression
Impaired renal function
Pregnancy
Cord compression
Nerve root compression
Impending pathologic fracture
Extensive ST component

Question 15

What randomized data support the use of samarium-153?

Answer 15

A double-blind placebo controlled study of samarium-153 supports its use. 118 pts with symptomatic bone mets were randomized to low-dose samarium-153 (0.5 mCi/kg), high-dose samarium-153 (1 mCi/kg), or placebo. Pts receiving high-dose samarium-153 had significant improvement in pain during the 1st 4 wks per pt and medical evaluation. Relief persisted until at least wk 16 in 43% of pts. There was a significant reduction in the pain score and analgesic use only in pts receiving the high dose. (Serafini A et al., JCO 1998)

Question 16

What randomized data supports the use of radium-223?

Answer 16

ALSYMPCA is a multi-institution double-blind placebo controlled study of radium-223 that showed an OS benefit for pts with castrate-resistant metastatic prostate cancer (14.9 mos vs. 11.3 mos, p < 0.001). 901 pts completing Tx were randomized 2:1 to 6 IV injections of radium-223 (dose 50 kBq/kg) q4wks vs. placebo injections on the same schedule. The trial was stopped early due to OS benefit on planned interim analysis. (Parker C et al., NEJM 2013)

Question 17

What RTOG study originally reported no difference in bone pain relief b/t different fractionation schemes?

Answer 17

RTOG 7402 randomized 759 pts. Those with solitary bone mets were randomized to 40.5 Gy (2.7 Gy × 15) vs. 20 Gy (4 Gy × 5). Pts with multiple mets were randomized to 30 Gy (3 Gy × 10), 15 Gy (3 Gy × 5), 20 Gy (4 Gy × 5), or 25 Gy (5 Gy × 5). The initial report revealed that 90% of pts had some pain relief, and 54% had eventual CR of pain. There was no difference b/t regimens. (Tong D et al., Cancer 1982) Reanalysis showed that a higher # of fx correlated with CR of pain, suggesting that a more protracted course was more effective. The analysis was based only on physician assessment of pain. (Blitzer P et al., Cancer 1985)

Question 18

Which pts are generally excluded from RCTs of different fractionations for bone-met RT?

Answer 18

RCTs assessing different fractionation schemes for the Tx of bone mets have generally excluded pts with cord compression and pathologic fracture.

Question 19

Did the study by the Bone Pain Trial Working Party support single- or multi-fx Tx of bone mets?

Answer 19

The Bone Pain Trial Working Party supported single-fx Tx. The study (UK/NZ) randomized 765 pts with painful bone mets to 8 Gy × 1 vs. a protracted regimen (2 Gy × 5 or 3 Gy × 10). Pain relief was evaluated for up to 1 yr post-Tx by the use of a validated pt questionnaire. There was no difference in pain control b/t the arms. Re-Tx was twice as common with single-fx Tx (23% vs. 10%), though this may have been due to a greater willingness to re-treat pts who rcvd only 8 Gy × 1. (No author, Radiother Oncol 1999)

Question 20

Did the Dutch Bone Metastasis Study support single- or multi-fx Tx of bone mets?

Answer 20

The Dutch Bone Metastasis Study supported single-fx Tx. 1,171 pts were randomized to 8 Gy × 1 fx vs. 4 Gy × 6 fx. Pain relief was evaluated for up to 2 yrs post-Tx by the use of a validated pt questionnaire. No difference was seen with respect to pain relief. However, re-Tx was more common in the single-fx arm (25% vs. 7%). (Steenland E et al., Radiother Oncol 1999) Reanalysis suggested that the higher rate of re-Tx in the single-fx arm may be related to a greater willingness to re-Tx pts who rcvd only 8 Gy × 1 fx. (Van der Linden YM et al., IJROBP 2004)

Question 21

Did RTOG 9714 support single- or multi-fx Tx of bone mets?

Answer 21

RTOG 9714 supported single-fx Tx. The study randomized 898 pts with breast or prostate cancer to 8 Gy × 1 fx vs. 3 Gy × 10 fx. There was no difference in complete pain relief (15% vs. 18%) or partial pain relief (50% vs. 48%), but there was increased acute toxicity in the 3 Gy × 10 arm (10% vs. 17%). The re-Tx rate was significantly greater in the 8 Gy × 1 arm. (Hartsell W et al., JNCI 2005)

Question 22

What were the results of the Chow et al. meta-analysis of trials comparing single- vs. multi-fx Tx of bone mets?

Answer 22

In this meta-analysis of trials comparing single- vs. multi-fx Tx of bone mets, no significant differences b/t fractionation schemes with respect to pain control were shown. However, re-Tx was more common with single-fx Tx. (Chow et al., JCO 2007)

Question 23

What study supported use of hemibody irradiation (HBI) after focal RT for bone mets?

Answer 23

RTOG 8206 randomized pts treated with focal RT to HBI (8 Gy) vs. no further Tx. HBI increased the time to progression as well as the time to re-Tx. (Poulter C et al., IJROBP 1992) This continues to be studied.

Question 24

What are the published response rates of RT for palliation of symptomatic bone mets irrespective of the fractionation scheme?

Answer 24

The published response rates of RT for palliation of symptomatic bone mets are 60%–80%.

Question 25

What is the benefit of PORT after orthopedic stabilization?

Answer 25

PORT following orthopedic stabilization of impending or pathologic fracture decreases the need for 2nd Sg (2% vs. 15%) and increases the rate of regaining normal function (53% vs. 11.5%) as c/w Sg alone. (Townsend P et al., JCO 1994)

Question 26

What data support the use of SBRT/SRS for spinal mets?

Answer 26

Prospective nonrandomized data from the University of Pittsburgh support the use of SRS for spinal mets. 500 cases were treated with CyberKnife to a median dose of 20 Gy. SRS improved pain in 86% of cases (defined as a 3-point improvement on a 10-point pain scale). The majority of pts had prior Tx; however, in the 65 cases treated with SRS as the primary modality, the LC was 90%. (Gerstzen P et al., Spine 2007)

The current ASTRO 2017 Bone Mets Guidelines recommend that pts be part of ongoing clinical trials or registries if being treated with SBRT to mets, in order to collect toxicity and effectiveness data, of which solid and comparative data are lacking.

Question 27

When should re-Tx of previously treated painful bone mets be considered?

Answer 27

ASTRO 2017 consensus statement on bone mets recommends re-Tx of met sites if they are still painful after or pain recurs >1 mo post-Tx, including both spine and peripheral sites of pain recurrence.