Unanswered Questions About SBRT in Bone Metastases

The goal of palliative radiotherapy is to treat symptoms as rapidly and efficiently as possible, with the fewest side effects.[1] For many years, pain medication, radiotherapy, and surgery were the only tools available for the treatment of bone metastases. This has changed significantly over the past 15 years. New systemic agents, including bisphosphonates such as zoledronic acid (Reclast, Zometa), are available to prevent the development of new lesions, strengthen the bone, and improve symptoms. In addition, targeted treatments directed at achieving tumor ablation now include radiofrequency ablation and stereotactic body radiation therapy (SBRT).

Radiation therapy continues to be frequently used for palliation of bone metastases because it is so effective at relieving pain. Multiple studies have shown that a single larger dose of treatment provides as effective pain relief as a longer course of 10 or more treatments.[2] The use of SBRT takes this a step further, by giving a much higher dose of treatment to a smaller volume of tissue.

Jhaveri and colleagues have provided an excellent review of the current status of SBRT for the treatment of painful bone metastases. They have addressed many questions regarding SBRT, including the feasibility, safety, and efficacy of the technique. However, several important questions were not addressed-for example, should we use SBRT to treat bone metastases; and, if so, to whom should this treatment be given?

Precision vs Accuracy

The promise of SBRT compared to conventional treatment is that it provides the precise delivery of an ablative dose of radiation to a tumor. The hypothesis stated by Jhaveri et al is that this will provide better local control and relief of pain. This rationale assumes that tumor control is the primary reason for pain relief. However, the causes of pain may be structural (weakening of the bone) or may be related to the tumor microenvironment. Treatments that re-establish the normal osteoblast-osteoclast cycle may provide relief of pain even with minimal tumor cell kill. This is one reason that bisphosphonates such as zoledronic acid are effective in treating painful bone metastases, but with an added benefit of preventing the appearance of new bone metastases.

Is our ability to hit a small target better than our ability to define the appropriate target volume? Although the treatment is very precise, it is not clear that it is always accurate. Current imaging modalities may underestimate the extent of disease. Chang et al found local tumor progression in 16% of patients at 1 year after SBRT for spinal metastases.[3] These investigators determined that the primary patterns of failure were locally in the bone (primarily into the pedicles or posterior processes) or into the epidural space, and advocated treatment with a wider margin to the bone and epidural space. This study thus underscores the fundamental question of whether the high degree of precision found with SBRT is indicated in patients where the primary treatment goal is palliation of symptoms, not target accuracy.

Patient Selection

Jhaveri and colleagues list potential candidates for SBRT, based on a report by Gerszten et al.[4] The criteria listed are based primarily on surgical considerations (inoperable lesions, recurrent lesions after surgery, minimal cord compression, no need for spinal stabilization), with two other conditions that apply directly to radiation therapy (well-circumscribed lesions and those that have been previously irradiated). Multiple other considerations are used to determine whether a patient is an appropriate candidate for SBRT. Jhaveri et al discuss many important considerations for patient selection in their sections on advantages and disadvantages of SBRT, including the extent of disease elsewhere (solitary or oligometastasis), and the presence of certain histologic types that may respond better to large doses per treatment (such as melanoma, renal cell carcinoma, or sarcoma).

Several other considerations are important in determining whether a patient is an appropriate candidate for SBRT, especially performance status and expected longevity. Van der Linden et al prospectively evaluated 342 patients with painful spinal metastases without neurologic impairment.[5] The overall survival was 7 months, and the best predictors for survival were Karnofsky performance status (KPS), primary tumor site, and absence of visceral metastases. Their patients with breast primaries, no visceral metastases, and a KPS of 80 to 100 had a median survival of 18 months. This favorable group comprised only 18% of their patients with spinal metastases. Survival in the other groups of patients was only 3 to 9 months. SBRT would not be appropriate for patients with an expected survival of only a few months.

One of the primary disadvantages of SBRT is economic cost. The cost of a course of SBRT with one to five fractions is many times greater than a single fraction of standard palliative irradiation. There may be additional costs, including the need to implant fiducial markers and the potential need for general anesthesia.

Conclusions

Many additional questions remain to be answered regarding SBRT for bone metastases. For example, how is bone stability affected by SBRT? Will more patients require surgical fixation or stabilization of the bone with higher doses? It is likely that determining which patients with bone metastasis stand to receive the greatest benefit from SBRT will require a multidisciplinary approach. This is one of the advantages of SBRT: It requires a multidisciplinary evaluation of patients, which will likely lead to better overall care.[1]

We agree with Jhaveri et al that there is a need for well-designed prospective trials to answer these questions, and these trials should be designed to answer not only questions about clinical efficacy and safety, but also those about quality-of-life and cost-utility outcomes.

-William F. Hartsell, MD
-Patrick J. Sweeney, MD

References:

References

1. Janjan N: Palliation and supportive care in radiation medicine. Hematol Oncol Clin North Am 20:187-211, 2006.

2. Wu JS, Wong R, Johnston M, et al: Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 55:594-605, 2003.

3. Chang EL, Shiu AS, Medel E, et al: Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine 7:151-160, 2007.

4. Gerszten PC, Ozhasoglu C, Burton SA, et al: CyberKnife frameless stereotactic radiosurgery for spinal lesions: Clinical experience in 125 cases. Neurosurgery 55:89-99 (incl discussion), 2004.

5. van der Linden, Dijkstra SP, Vonk EJ, et al: Prediction of survival in patients with metastases in the spinal column: Results based on a randomized trial of radiotherapy. Cancer 103:320-328, 2005.