# Radiation Oncology/Palliation/Bone metastases

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
Palliation of Spine and Bone Metastases
* For spinal cord compression, please see: spinal cord compression
* For specific tumor types, see also: Renal cell
* For spinal cord tolerance, please see Spine NTCP

## Guidelines

* ASTRO; 2011 PMID 21277118 -- "Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline." (Lutz S, Int J Radiat Oncol Biol Phys. 2011 Jan 27. [Epub ahead of print])
* Society of Nuclear Medicine; 2003 PDF Guidelines link -- "Palliative Treatment for Painful Bone Metastases" (version 3.0)
* International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. PMID 22608954-- (Cox BW Int J Radiat Oncol Biol Phys. 2012 Aug 1. [Epub ahead of print])
** Describes target delineation of the CTV and created the "SSS" (Spratt Six Segmentation) to unify communication regarding the location of involvement of spinal tumors/metastases.

## Open Reduction Internal Fixation (ORIF)

* Mayo Clinic; 2004 PMID 15289695 -- "Management of pathologic fractures of the proximal femur: state of the art." (Jacofsky DJ, J Orthop Trauma. 2004 Aug;18(7):459-69.)
** Review of surgical techniques
** Radiation therapy recommendation: RT should follow ORIF, typically 2-4 weeks later. Typical schedule 30/10 though British Association of Surgical Oncologists guideline recommends 20/5

## Prophylactic Fixation
### Long Bones

* Mirels Criteria
** 1989 PMID 2684463 -- "Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathologic fractures" (Mirels H, Clin Orthop Relat Res. 1989;249:256–264.)
** PMID Article
** Score >8 suggests benefit from pinning
| Mirels Criteria |
| Score | 1 | 2 | 3 |
| Site | upper limb | lower limb | peritrochanteric |
| Pain | mild | moderate | functional |
| Lesion | blastic | mixed | lytic |
| Size (cortical involvement) | < 1/3 | <2/3 | >2/3 |
* Harrington's criteria
** 1986 PMID 3819423 -- "Impending pathologic fractures from metastatic malignancy: evaluation and management." (Harrington KD, Instr Course Lect. 1986;35:357-81.)
* Harrington's Criteria
* >50% destruction of diaphyseal cortices
* >2.5 cm in any dimension
* Destruction of subtrochanteric femoral region
* Persistent pain following radiation

### Vertebral body

* Spinal Instability Neoplastic Score (SINS)
** 2010 PMID 20562730 -- "A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group." (Fisher CG, Spine (Phila Pa 1976). 2010 Oct 15;35(22):E1221-9. doi: 10.1097/BRS.0b013e3181e16ae2)
*** Potentially unstable lesions ≥ 7; unstable lesions ≥ 13
*** Surgical consultation recommended for lesions ≥ 7
| Variable | 0 | 1 | 2 | 3 | 4 |
| Location | Rigid (S2-S5) | Semirigid (T3-T10) | Mobile (C3-C6, L2-L4) | Junctional (Occiput-C2, C7-T2, T11-L1, L5-S1) | - |
| Pain | None | Occasional | - | Yes | - |
| Bone lesion | Blastic | Mixed | Lytic | - | - |
| Radiographic alignment | Normal | - | De novo kyphosis/scoliosis | - | Subluxation/translation |
| Vertebral body collapse | None, <50% VB involved | None, >50% VB involved | <50% | >50% | - |
| Posterior involvement | None | Unilateral | - | Bilateral | - |
** 2014 PMID 24594004 -- "Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases." (Fisher CG, Radiat Oncol. 2014 Mar 4;9:69. doi: 10.1186/1748-717X-9-69.)
*** Survey. 33 radiation oncologists, 10 sites, 30 cases.
*** Outcome: Interobserver variability 0.76, intra-observer variability 0.80. All unstable cases were rated as appropriately
*** Conclusion: Among radiation oncologists, SINS is highly reliable, reproducible and valid assessment tool
* CT-based algorithm
** Harvard; 2009 PMID 19996215 -- "Noninvasive Prediction of Fracture Risk in Patients with Metastatic Cancer to the Spine." (Snyder BD, Clin Cancer Res. 2009 Dec 15;15(24):7676-7683.)
*** Retrospective. 94 women, CT scans. Load-bearing capacity, axial rigidity, bending rigidity calculated, and normalized by BMI. Vertebral fracture risk calculated
*** Outcome: 11 fractures occurred in 10 patients. Structural parameters 100% sensitive; 55-70% specific to predict fracture risk
*** Conclusion: CTRA is as sensitive and more specific than current radiographic criteria

## Palliative RT Endpoints

* Bone Metastases Consensus Working Party; 2002 PMID 12242115 -- "International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases." (Chow E, Radiother Oncol. 2002 Sep;64(3):275-80.)
** Pain assessment: 11 point scale (0-10), should relate to worst and average pain over prior 3 days
** Narcotic use: should be converted to daily oral morphine equivalent
** Endpoints:
*** Partial response: reduction of 2 or more points (0-10 point scale) without analgesic increase OR analgesic reduction of 25% in daily morphine equivalent without increase in pain
*** Pain progression: increase in pain score 2 or more points with stable analgesic use OR increase of 25% in daily morphine equivalent with pain stable or 1 point above baseline

## External Beam Asymptomatic

* Memorial Sloan Kettering (2018 - 2021) -- RT to asymptomatic high risk sites vs standard of care
** Outcome 2024 PMID -- "Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial" (Gillespie EF, J Clin Oncol. 2024 Jan 1;42(1):38-46. doi: 10.1200/JCO.23.00753. Epub 2023 Sep 25.)
*** Multicenter Phase II. 73 patients. Adult, widely metastatic solid tumors. Arm 1) standard of care (systemic therapy or observation) vs Arm 2) prophylactic RT. Lung 27%, breast 24%, prostate 22%
*** Outcome: Skeletal events RT 2% vs OBS 29% (SS). Fewer hospitalizations (SS). Improved overall survival HR 0.49, SS.
*** Conclusion: Prophylactic radiation lowered skeletal events, hospitalization, and improved survival

## External Beam Painful
### Overview

* A UK trial reported in 1986 was the first to randomize patients to RT 8/1 vs. 30/10. While there was no difference in pain relief at 12 weeks, the trial was criticized for low compliance and short follow-up
* A follow-on UK trial revealed that RT 8/1 has higher rate of clinical response than RT 4/1
* Several other trials have confirmed equivalent safety and efficacy of 8 Gy x1 compared with multi-fraction regimens, including RTOG 97-14
* All trials show a higher re-treatment rate for 8/1 fractionation (~25% vs. ~10% for multifraction regimens), but some of this may be for other reasons than pain level prior to re-irradiation
* Cochrane review (2004) found overall pain response ~60%, complete pain response ~33%, with no difference between single fraction and multifraction regimens. The composite retreatment rate was higher for single fraction 21% vs. 7%. Conclusion was that single fraction is effective
* Based on the Dutch Bone Metastasis Study, patient who live <12 weeks do particularly poorly after RT. Only half respond (and that means their pain score decreases from 7 to 5 on 11 point scale), and most die in pain even in the presence of analgesics. Patients who live >12 weeks do better, with 78% responders

### Meta-analyses

* University of Toronto, 2007 - PMID 17416863 — "Palliative Radiotherapy Trials for Bone Metastases: A Systematic Review." Chow E et al. J Clin Oncol. 2007 Apr 10;25(11):1423-1436.
** Single-fraction vs multiple fraction RT. Updates previous meta-analysis. Literature review.
** Conclusion: Overall response and complete response same in single fraction (8/1) and multi-fraction treatments. Retreatment rate higher with single fraction
* Cochrane Review, 2004 PMID 15106258 -- "Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials." (Wai MS, Cochrane Database Syst Rev. 2004;(2):CD004721.)
** Pooled meta-analysis. 11 trials, 3435 patients. Any primary site, but mainly prostate, breast, and lung
** Pain response: single fraction 60% vs. multifraction 59% (NS). Complete response 34% vs. 32% (NS). Single fraction higher re-treatment 21% vs. 7% (SS)
** Pathologic fracture: single fraction 3% vs. 1.5%
** Conclusion: Single fraction as effective as multiple fractions at relieving pain. Higher re-treatment and higher rate of pathologic fracture in the single fraction arm
* McMaster University, 2003 PMID 12573746 -- "Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases." (Wu JS, Int J Radiat Oncol Biol Phys. 2003 Mar 1;55(3):594-605.)
** 16 trials,
** Conclusion: No significant difference in complete and overall pain relief between single and multifraction palliative RT for bone metastases. More frequent re-irradiation rate in the lower dose arms.

### Randomized

* RTOG 97-14 (1998-2002) -- RT short (8/1) vs. RT long (30/10)
** Randomized. 898 patients. Prostate or breast cancer. Weight-bearing 56%, C-spine 5%, T-spine 19%, L-spine 27%, cord compression not allowed. Life expectancy >3 months, KPS >=40 Arm 1) RT 8/1 vs. Arm 2) 30/10. Primary outcome pain relief at 3 months
** Outcome; 2005 PMID 15928300 -- "Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases." (Hartsell WF, J Natl Cancer Inst. 2005 Jun 1;97(11):798-804.)
*** Outcome: 3-month complete pain relief 8/1 15% vs. 30/10 18% (NS); partial 50% vs. 48% (NS); stable 26% vs 24%; progressive 9% vs 10%. Comparable narcotic relief. Retreatment rate 18% vs. 9% (p<.001)
*** Toxicity: acute 8/1 10% vs. 30/10 17% (SS); late toxicity rare
*** Conclusion: Both regimens equivalent for pain control and narcotic relief at 3 months. 8/1 less acute toxicity but higher retreatment
** Single males; 2006 PMID 16814950 — "Continuing evidence for poorer treatment outcomes for single male patients: retreatment data from RTOG 97-14." Konski A et al. Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):229-33.
*** Retreatment (within the original RT portal) at 36 months: 8/1 18% vs 30/10 9% (SS) No difference in retreatment rate between arms for unmarried males, but difference was seen in all other groups.
*** Conclusion: Patients receiving 8 Gy in a single fraction had significantly higher retreatment rates compared with patients receiving 30 Gy in 10 fractions.
** Economic analysis; 2009 PMID 19546803 -- "Economic analysis of radiation therapy oncology group 97-14: multiple versus single fraction radiation treatment of patients with bone metastases." (Konski A, Am J Clin Oncol. 2009 Aug;32(4):423-8.)
*** Markov model using information from the trial. Cost modeled using Medicare RVU rates
*** Outcome: Mean cost 8 Gy group $998 vs 30 Gy group $2316. QALY survival 7.3 months vs 9.5 months. ICER $6973/QALY
*** Conclusion: Single fraction was the less expensive and more cost-effective treatment
* Norway/Sweden (1998-2000) -- short RT (8/1) vs. long RT (30/10)
** Randomized. Stopped early due to comparable outcomes on interim analysis. 376/1000 patients. Bone metastases (spine 38%, pelvis 35%, extremity 20%) resulting in clinically important pain, KPS >40, life expectancy >6 weeks. Spinal cord compression excluded. Arm 1) RT 8/1 vs. 30/10. Target known mets with 2-3 cm margin, for spinal lesions 1 VB above/below. Prophylactic corticosteroids not used. Primary outcome pain relief over 28 weeks (82% questionnaire compliance)
** 2006 PMID 16793154 -- "Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy x 1) versus multiple fractions (3 Gy x 10) in the treatment of painful bone metastases." (Kaasa S, Radiother Oncol. 2006 Jun;79(3):278-84.) F/U 18 months
*** Outcome: No difference in pain intensity, global QoL, fatigue, or opioid/non-opioid analgesics. (NS). Median O/S 8 Gy 9.6 months vs. 30 Gy 7.9 months (NS)
*** Conclusion: Similar benefit. Recommend single fraction 8 Gy as standard
* TROG 96.05 PMID 15878101 -- "Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05)." (Roos DE, Radiother Oncol. 2005 Apr;75(1):54-63. Epub 2004 Oct 28.)
** Phase III. 272 patients. Bone mets, known primary, no change in therapy x6 weeks, no cord compression. Lung 31%, prostate 29%, breast 8%
** Randomized to 8 Gy/1 fx vs. 20 Gy/5 fxs in 15 centers
** Response rate: 53% vs. 61% (p=NS); TTF 2.4 mo vs. 3.7 mo (p=0.056)
** Conclusion: "8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small."
* Dutch Bone Metastasis Study (1996-1998) -- short RT (8/1) vs long RT (24/6)
** Randomized. 1171 patients. Painful bone metastases, spinal cord compression excluded, C-spine excluded (T/L-spine 37%, pelvis 29%, femur 16%, other 18%). Primary endpoint pain. Median F/U 4 months
** 1999 PMID 10577695 -- "The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study." (Steenland E, Radiother Oncol. 1999 Aug;52(2):101-9.)
*** Outcome: Response 71% (breast 76%, prostate 78%, NSCLC 60%), complete response 35%. No difference in pain relief at 3 months, 12 months. No difference in time-to-progression. Median OS 7 months (NS); breast CA 16 months vs. NSCLC 3 months.
*** Retreatment: overall 16%; 8/1 25% vs. 24/6 7% (SS), on further analysis higher recurrence pain score in 24/6 group before retreatment
*** Toxicity: No difference in acute toxicity; double the rate of subsequent pathologic fractures in the single fraction arm
*** Conclusion: Equality of 8/1 vs 24/6, provided 4x more retreatments accepted. Equality holds in long-term survivors
** Last 12 weeks; 2010 PMID 20225326 -- "Efficacy of radiotherapy for painful bone metastases during the last 12 weeks of life: results from the Dutch Bone Metastasis Study." (Meeuse JJ, Cancer. 2010 Mar 11. [Epub ahead of print])
*** Subset analysis. 274 patients who died within 12 weeks after randomization. Patient classified as responders (decrease in initial pain intensity score by 2 of 11 points without analgesic increase, or decrease in analgesics without increase in pain. Used )
*** Outcome: Response 8/1 53% vs 24/6 56% (NS); median time-to-response 2 weeks (1-9) in both groups. In responders, pain score decreased from 7/11 to 5/11 by death. In non-responders, no change. 60% of patients never reached below pain score 5 until death (regardless of RT and medication use). Compared with patients who lived >12 weeks, response percentage for patients who lived <12 weeks was poor 45% vs 78% (SS)
*** Conclusion: Pain responded in ~50% of patients with short survival, regardless of fractional schema. Single fraction should be preferred, and additional palliative measure remain essential
* UK/NZ (1992-1997) -- short RT (8/1) vs. long RT (20/5 or 30/10)
** Randomized. 761 patients. Painful skeletal metastases (pelvis/hip 28%, L-spine 20%, ribs 11%, T-spine 9%, femur 6%, C-spine 3%, other 22%). Arm 1) RT 8/1 vs. Arm 2) RT 20/5 or 30/10. Primary endpoint pain relief.
** 1999 PMID 10577696 -- "8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party." ([No authors listed], Radiother Oncol. 1999 Aug;52(2):111-21.) Full 12 month follow-up available in 30%.
*** Outcome: No difference in time-to-improvement, time-to-complete pain relief, or class of analgesics (NS). Complete response (no pain, no increase in pain meds) 58%. Retreatment 8/1 23% vs. long-RT 10% (SS) but on further analysis likely due to greater readiness to reatreat rather than need due to pain outcome
*** Toxicity: No difference in nausea (56% vs. 65%), vomiting (30% vs. 32%), spinal cord compression, or pathological fracture
*** Conclusion: No difference in safety or efficacy; pain relief durable over 12-month follow up. 8 Gy single fraction is the treatment of choice
* Germany, 1996 - PMID 8985030, — "Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases." Niewald M et al. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1085-9.
** Randomized to 20 Gy / 5 fractions vs 30 Gy / 15 fractions
** Slight trend favoring 30 Gy in frequency of pain relief and recalcification. No significant differences in frequency, duration of pain relief, pathologic fractures, or survival.
* UK -- short RT (4/1) vs short RT (8/1)
** Randomized. 270 patients. Painful bone metastases. Arm 1) RT 4/1 vs. Arm 2) RT 8/1. Compliance with questionnaire 72% at 4 weeks
** 1992 PMID 1372126 -- "A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain." (Hoskin PJ, Radiother Oncol. 1992 Feb;23(2):74-8.)
*** Outcome: 4-week response 4 Gy 44% vs. 8 Gy 69% (SS); but no difference in complete response or duration of response
*** Conclusion: 8 Gy higher probability of pain relief, but 4 Gy can be effective
* UK -- short RT (8/1) vs long RT (30/10)
** Randomized. 288 patients with metastatic bone pain. Arm 1) RT 8/1 vs. Arm 2) RT 30/10. Questionnaire compliance 31% beyond 12 weeks
** 1986 PMID 3775071 -- "Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases." (Price P, Radiother Oncol. 1986 Aug;6(4):247-55.)
*** Outcome: No difference in speed of onset, duration of pain relief at 12 weeks. Pain relief independent of histology. Reirradiation more likely with 8/1 schedule but increased analgesic use in 30/10
* RTOG 74-02 -- Solitary 40.5/15 vs. 20/5; Multiple 30/10 vs. 15/5 vs. 20/5 vs. 25/5
** Randomized. Pts with solitary lesions randomized to 270 cGy x 15 (40.5 Gy) or 400 x 5 (20 Gy). Pts with multiple lesions randomized to 300 x 10 (30 Gy), 300 x 5 (15 Gy), 400 x 5 (20 Gy), or 500 x 5 (25 Gy, blocking cord after 20 Gy).
** 1982 PMID 6178497 — "The palliation of symptomatic osseous metastases: final results of the Study by the Radiation Therapy Oncology Group." Tong D et al. Cancer. 1982 Sep 1;50(5):893-9.
*** Outcome: 90% with some relief of pain. 54% had eventual complete pain relief. No difference between radiotherapy regimens in pain relief. No difference among regimens in promptness of pain relief, except there was an association between the dose and the promptness to complete pain relief (fastest in 15 Gy, slowest in 25 Gy group); no difference in the duration of pain relief.
*** Conclusion: No difference between regimens
** 1985 PMID 2579716, 1985 — "Reanalysis of the RTOG study of the palliation of symptomatic osseous metastasis." Blitzer PH et al. Cancer. 1985 Apr 1;55(7):1468-72.
*** Higher number of fractions (40.5/15 and 30/10) found related to complete relief of pain.

### Kyphoplasty + RT

* Pittsburgh, 2005 PMID 15771398 -- Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures. (Gerszten PC, Neurosurg Focus. 2005 Mar 15;18(3):e8.)
** 26 patients with pathologic fractures secondary to tumor treated with Kyphoplasty followed by single fraction (16-20 Gy) RT
** Conclusion: "A combined kyphoplasty and spinal radiosurgery treatment paradigm was found to be safe and clinically effective for patients with pathological fractures without significant spinal canal compromise. This technique combines two minimally invasive surgical procedures, thereby avoiding the morbidity associated with open surgery while providing immediate fracture fixation as well as a single-fraction tumoricidal radiation dose."

### Hemibody radiation

Fractionated hemibody RT:
* RTOG 88-22 (1989-93) - PMID 8823257, 1996 — "A phase I/II study to evaluate the effect of fractionated hemibody irradiation in the treatment of osseous metastases--RTOG 88-22." Scarantino CW et al. Int J Radiat Oncol Biol Phys. 1996 Aug 1;36(1):37-48.
** 142 pts. Phase I/II, dose escalation. Pts w/ painful bone mets (single or multiple) confined to one hemibody (upper/mid/lower) from breast or prostate ca.
*** Treatment of local painful site (local RT) followed by hemibody. Escalation of hemibody RT dose, 2.5 Gy/fx to 4-8 fx (10 - 20 Gy). Hemibody began within 3 days of local RT, and the local RT portal was shielded during hemibody RT. Lung shielding to keep lung dose to 6 Gy. Liver and kidney limited to 15 Gy.
*** Dose-limiting toxicity at 17.5 Gy (hematologic toxicity). Time to new disease in the hemibody field: 19% at 1 yr, no difference between arms; no difference in retreatment rates.
** Conclusion: Comparing this study to single fraction study (RTOG 82-06), there was a reduction of 36% of new disease with the fractionated technique. No difference in survival.
Single-fraction hemibody RT:
* RTOG 82-06 - 8 Gy
** 499 pts. Received 300x10 local radiation to the painful site, then randomized to hemibody RT (8 Gy/1) or observation.
** PMID 1374061, 1992 — "A report of RTOG 8206: a phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases." Poulter CA et al. Int J Radiat Oncol Biol Phys. 1992;23(1):207-14.
*** Disease progression at 1 yr: 35% (local+HBI) vs 46% (local only); new disease in hemibody: 50% vs 68%; median time to new disease in hemibody: 12.6 m vs 6.3 m.
* RTOG 78-10 (1978-81)
** 168 pts (129 evaluable). Doses: 600-800 rad (upper half body), 800-1000 rad (lower and middle). Dose rate 15-45 rad/min. Used comprehensive premedication program (IV hydration, antiemetics, steroids) for pts receiving upper half RT; antiemetics only for mid or lower half. 10 pts received treatment to both body halves (sequentially).
*** PMID 2423225, 1986 — "Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report." Salazar OM et al. Cancer. 1986 Jul 1;58(1):29-36.
**** Pain relief in 73%; 20% with complete relief. No dose response seen: optimum response at the lower doses tested (600 for UHBI, 800 for LHBI and MBI). Time to pain relief - 50% within 48 hrs, 80% within 1 week, 95% in 2 wks.
*** PMID 6169699 (No abstract), 1981 — "Single-dose half-body irradiation for the palliation of multiple bone metastases from solid tumors: a preliminary report." Salazar OM et al. Int J Radiat Oncol Biol Phys. 1981 Jun;7(6):773-81.
** Conclusion: rapid pain relief. Safest dose appears to be 600 (upper) and 800 (lower/mid). Compared with conventional RT (a la RTOG 74-02), overall pain relief and duration of pain relief are similar, but HBI achieved pain relief much sooner (complete pain relief within 2 weeks vs many months), 4 times lower recurrence of pain in the radiated fields (54% vs 13%)
Reviews:
* PMID 2579726, 1985 — "Systemic hemibody irradiation for overt and occult metastases." Rubin P et al. Cancer. 1985 May 1;55(9 Suppl):2210-21.

## SBRT

* University of Toronto; 2023 PMID 36309076 -- "Dose-Escalated 2-Fraction Spine Stereotactic Body Radiation Therapy: 28 Gy Versus 24 Gy in 2 Daily Fractions" (Zeng KL, Int J Radiat Oncol Biol Phys. 2023 Mar 1;115(3):686-695. doi: 10.1016/j.ijrobp.2022.09.076. Epub 2022 Oct 26.)
** Retrospective. 947 vertebral body segments, 482 patients. Comparison of 28 Gy (301 segments) vs 24 Gy (646 segments) in 2 fractions SBRT. Median f/u 24 months.
** Outcome: 28 Gy - 6-mo LF 3%, 1-year LF 5%, 2-year LF 11% vs 24 Gy 6%, 12%, 18% (SS). Higher risk of failure in 24 Gy group, paraspinal extension, epidural extension
** Toxicity: Vertebral compression fracture 5%, 8%, and 11%, and similar between cohorts. Higher risk in spinal malalignment, pre-existing VCF, junctional spine location, and higher V90 dose
** Conclusion: Dose escalation to 28 Gy in 2 fractions improved local control, similar risk of vertebral fracture.
* Pittsburgh; 2007 PMID 17224814 -- "Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution." (Gerszten PC, Spine. 2007 Jan 15;32(2):193-9.)
** Prospective cohort study. 500 cases of spinal metastases (cervical 15%, thoracic 42%, lumbar 22%, sacral 20%), treated with radiosurgery. Maximum dose 12.5-25 Gy (mean 20 Gy). Prior EBRT 69% (typically 30/10 or 35/14)
** Outcome: Long-term pain control 86%; at least some improvement in neurologic function in 85% (30/35)
** conclusion: Radiosurgery has potential to improve long-term palliation
* MD Anderson
** Phase I/II study. 63 patients with 74 spinal mets. SBRT 30 Gy in 5 fractions @ 6 Gy/fraction. Spinal cord max dose 10 Gy.
** 2007 PMID 17688054 "Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure." (Chang EL, J Neurosurg Spine. 2007 Aug;7(2):151-60.). Median F/U 1.8 years
*** Outcome: Actuarial 1-year PFS 84%. Failure mostly 1) recurrence in adjacent bone, or 2) recurrence in epidural space
*** Toxicity: no neuropathy or myelopathy; Grade 3 GI (n=1), Grade 3 dysphagia (n=1), Grade 3 chest pain (n=1). No late Grade 3-4 toxicity
*** Conclusion: Safe and effective
** 2004 PMID 15275711 -- "Phase I clinical evaluation of near-simultaneous computed tomographic image-guided stereotactic body radiotherapy for spinal metastases." (Chang EL, Int J Radiat Oncol Biol Phys. 2004 Aug 1;59(5):1288-94.)
*** Phase I. 15 patients. Median F/U 9 months
*** Toxicity: none
*** Conclusion: Technically feasible
** 2003 PMID 14529763 -- "Near simultaneous computed tomography image-guided stereotactic spinal radiotherapy: an emerging paradigm for achieving true stereotaxy." (Shiu AS, Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):605-13.)
*** Description of treatment technique
* Memorial Sloan Kettering; 2005 PMID 15850902 -- "Multifractionated image-guided and stereotactic intensity-modulated radiotherapy of paraspinal tumors: a preliminary report." (Yamada Y, Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):53-61.)
** Retrospective. 35 patients (21 metastases, 20 previously irradiated). Treated with paraspinal IMRT. Prior median dose 30/10. Retreatment dose median 20/5 (20-30 Gy). If no prior RT, median dose 70 Gy. Median F/U 11 months
** Outcome: Palliation 90%; LC for primary tumors 81% vs. mets 75%
** Toxicity: No radiation-induced myelopathy or radiculopathy
** Conclusion: Stereotactic IGRT allows delivery of high doses to close proximity of spinal cord
* Heidelberg; 2003 (1997-2001) PMID 12504049 -- "Clinical results of retreatment of vertebral bone metastases by stereotactic conformal radiotherapy and intensity-modulated radiotherapy." (Milker-Zabel S, Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):162-7.)
** Retrospective. 18 patients, 19 recurrent spinal metastases. Treated with 3D-CRT (n=5) or IMRT (n=14). Prior conventional RT (median 38 Gy). Median time-to-recurrence 18 months. Median retreatment 39.6 Gy (spinal cord dose limited to ~60-65% of Rx dose) @2 Gy/fraction. Median F/U 12 months.
** Outcome: LC 95%, significant pain relief 81%, neurologic improvement 42%. Tumor size unchanged 84%, 1 local progression 9 months after RT.
** Toxicity: No significant late toxicity
** Conclusion: Fractionated 3DCRT and IMRT safe and effective for re-treatment
Review
* MD Anderson; 2008 PMID 18514775 -- "Stereotactic body radiosurgery for spinal metastases: a critical review." (Sahgal A, Int J Radiat Oncol Biol Phys. 2008 Jul 1;71(3):652-65.)
* MSKCC, 2007 PMID 17762734 -- "A Review of Image-Guided Intensity-Modulated Radiotherapy for Spinal Tumors." (Yamada Y, Neurosurgery. 61(2):226-235, August 2007.)
** Review of IGRT for spinal tumors, including hypofractionated and SBRT approaches

## Unsealed Sources

* Please see the Unsealed sources page for more information

## Kyphoplasty

* Cancer Patient Fracture Evaluation (CAFE) (2005-2008) -- kyphoplasty vs non-surgical management
** Randomized. 134 patients, 1-3 painful vertebral compression fractures. Arm 1) kyphoplasty vs Arm 2) non-surgical management. Primary endpoint Roland-Morris disability questionnaire (RDQ) at 1 month
** 2010 PMID not yet available -- "Using DOIBalloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial" (Berenson J, The Lancet Oncology, Early Online Publication, 17 February 2011doi:10.1016/S1470-2045(11)70008-0)
*** Outcome: RDQ disability score pre-treatment to post-treatment change: vertebroplasty 17.6 to 9.1 (-8.3 points) vs non-surgical management 18.2 to 18.0 (-0.1 points) (SS)
*** Conclusion: Kyphoplasty effective and safe for painful vertebral compression fractures

## Re-treatment

    See also: Radiation_Oncology/Palliation/Spinal_Cord_Compression#Re-treatment for re-treatment of spinal metastases.
Meta-analysis:
* Netherlands; 2012 (1985-2000) PMID 22300568 -- "Effectiveness of Reirradiation for Painful Bone Metastases: A Systematic Review and Meta-Analysis." (Huisman M, Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):8-14.)
** 7 articles included in the meta-analysis. 527 pts treated with reirradiation. Initial dose 4-8 Gy x 1. Most patients retreated with single fraction again. Pain response was achieved after reirradiation in 58%. Location: spine in 36%.
** Conclusion: "Reirradiation of painful bone metastases is effective in terms of pain relief for a small majority of patients; approximately 40% of patients do not benefit from reirradiation. Although the validity of results is limited, this meta-analysis provides a comprehensive overview and the most quantitative estimate of reirradiation effectiveness to date."