The August 2021 #radonc #JC begins Saturday, August 21st 8am CST and continues through Sunday, August 22nd to the Live Hour on Sunday at 4pm CST.
Cancer in the spine is common. Bone is the 3rd most common site for cancer spread (metastases) with up to 80% of patients developing bone metastases1. The spine accounts for 70% of bone metastases due to its abundant marrow and adjacent paravertebral venous plexus system2. Many patients will experience back pain as a result of the disease spread to the spine.
Effective pain relief from spine metastases is a challenge. Surgery and medications may help but are not always indicated. Over the past couple decades, multiple randomized controlled trials (RCTs) have shown radiation treatment (RT) to be effective, although many questions have remained.
Conventional Fractionation (cEBRT): Multiple (MFRT) vs. Single Fraction (SFRT)
Conventional external beam radiation treatment to the spine is delivered using a 3D conformal technique with 1-2 beams. Historically people used multiple fractions (commonly 10) until data emerged demonstrating efficacy of a single fraction 3.
RTOG 9714 compared 30 Gy in 10 fractions to a single fraction of 8 Gy.4 Uncomplicated spinal metastases (no evidence of spinal cord involvement) made up 51% (n=460) of patients. Results suggested a single 8 Gy was an option for painful bony metastases – compelling for its convenience and cost. However, one fraction is associated with a higher retreatment rate (~2.5x) 4. Also, although two-thirds of patients experienced partial pain relief, complete relief with cEBRT is lower (10-30%) 4.
Single Fractionations: Stereotactic (SBRT) vs. Conventional (cEBRT)
Stereotactic radiation treatment (SBRT) is a newer technique that delivers a higher dose of RT more precisely and with fewer treatments compared to conventional EBRT 3. This allows potential for better local control. The tradeoff is a higher risk of side effects in the treated region – for the spine this can be serious (compression fractures or spinal cord injury). For this reason, total SBRT doses around the spine tend to be less than for other (non-CNS) regions.
RTOG 0631 compared single-fraction SBRT (16 Gy or 18 Gy) to a single 8Gy of conventional RT (8 Gy) for patients with limited spine metastases (1-3 separate sites, each site involving up to 2 contiguous spine segments) 5. Pain control at 3 months was similar in both arms (40.3% vs. 57.9%). However, other studies suggested higher doses may be required 6.
What about multi-fraction SBRT?
As discussed in a recent #RadOnc #JC7, spreading out radiation dose over multiple treatments (fractionation) can take advantage of differences in biology to maximize destruction of cancer cells while minimizing side effects.8
CCTG SC.24/TROG 17.06 compared multi-fraction SBRT at a higher total dose (24 Gy in 2 fractions) to conventional EBRT (20 Gy in 5 fractions) with a different conclusion. Even with more inclusive patient selection criteria, the 24 Gy in 2 fraction arm was superior to cEBRT in its complete response to pain at 3 months . These findings are fascinating and have potentially wide implications for clinical practice.
This weekend we’re excited to discuss….
Sahgal A et al. SBRT vs conventional EBRT in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. The Lancet Oncology. 2021.
Thank you to The Lancet Oncology for making the article free to access here.
We’re pleased to be joined by study author Dr. Shankar Siva (@_ShankarSiva) and lead discussants Drs. Kristin Redmond, Simon Lo (@SimonLo21054188), Matthias Guckenberger (@Mat_Guc) and more!
Guiding Topics for this month’s #radonc #JC:
T1. Background: What is your current practice for managing painful spine metastases? Which criteria do you use for determining whether a patient should receive treatment with SBRT versus conventional fractionation?
T2. Methods: In terms of clinical methodology, how was radiotherapy performed in terms of target volumes? What metrics were used to determine treatment response? In terms of research methodology, was this a superiority trial or a non-inferiority trial?
T3. Results: How did 3-month response rate compare for treatment with 24 Gy in 2 fractions versus 20 Gy in 5 fractions? What was the incidence of grade 3-4 adverse events in each group?
T4. Discussion: Are the findings of this study expected? Would we expect different findings if comparing single-fraction SBRT to multi-fraction conventional radiotherapy?
T5. #PatientsIncluded: What do patients want when treating painful spine metastases?T6. Next Steps: For which patients would you consider treating with SBRT, following results of this study?
Tips to Participate:
Suggestions? Leave a comment or tweet us at @Rad_Nation. And please join us this weekend!
Open Access & #PatientsIncluded
1. Targeting Cancer. External Beam Radiation Therapy (EBRT: Conventional EBRT, SRS/SBRT, Protons). Accessed Aug 16, 2021. https://www.targetingcancer.com.au/radiation-therapy/ebrt/
2. Katz MS. HyTEC – Guidance for Stereotactic and Hypofractionated Radiation Treatment Planning. Radiation Nation. Accessed Aug 17, 2021. http://radonc.radiationnation.com/high-dose-hytec-guidance-for-stereotactic-radiation-treatment-planning/
3. Radiopaedia. Fractionation (radiation therapy). Radiopaedia. Accessed August 17, 2021. https://radiopaedia.org/articles/fractionation-radiation-therapy
4. Kenan S et al. Skeletal Metastases. Holland-Frei Cancer Med. 6th ed. Hamilton (ON); 2003. Accessed Aug 17 2021: https://www.ncbi.nlm.nih.gov/books/NBK12348/
1. Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. Jun 2001;27(3):165-76. doi:10.1053/ctrv.2000.0210
2. Sahgal A, Myrehaug SD, Siva S, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. The Lancet Oncology. 2021;22(7):1023-1033. doi:10.1016/S1470-2045(21)00196-0
4. Chow R, Hoskin P, Schild SE, et al. Single vs multiple fraction palliative radiation therapy for bone metastases: Cumulative meta-analysis. Radiotherapy and Oncology. 2019;141:56-61. doi:10.1016/j.radonc.2019.06.037
5. Ryu S, Deshmukh S, Timmerman RD, et al. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631. International Journal of Radiation Oncology, Biology, Physics. 2019;105(1):S2-S3. doi:10.1016/j.ijrobp.2019.06.382
6. Sprave T, Verma V, Förster R, et al. Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy. Radiother Oncol. Aug 2018;128(2):274-282. doi:10.1016/j.radonc.2018.04.030