Single Fraction and Multifraction Arc-Based Radiotherapy for Painful Bone Metastases (SMART)

The SMART Trial: A Randomised Feasibility Study Comparing Single Fraction and Multifraction Arc-Based Radiotherapy for Painful Bone Metastases

This prospective randomised pilot feasibility study will compare single-fraction radiotherapy (8 Gy × 1) with multifraction radiotherapy (20 Gy in 5 fractions) for the palliation of painful bone metastases. The study will evaluate pain response at 4 weeks following radiotherapy, together with feasibility, treatment compliance, toxicity, pain flare, retreatment, patient convenience and resource utilisation. The study will generate preliminary data to inform the design of a future definitive randomised trial.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer Pain; Bone Metastases of a Malignant Tumor
• Intervention / Treatment: Radiation: Single-Fraction Radiotherapy (8Gy x 1#); Radiation: Multifraction Radiotherapy (20 Gy in 5 #)

Detailed Description

Single-fraction radiotherapy (SFRT) is an established standard treatment for palliation of painful bone metastases. However, multifraction radiotherapy (MFRT) continues to be widely used in clinical practice because of concerns regarding durability of pain control and retreatment. With the increasing use of modern arc-based radiotherapy techniques such as volumetric modulated arc therapy (VMAT), there is a need to evaluate whether single-fraction radiotherapy can provide effective pain palliation while reducing treatment burden and improving resource utilisation.

The SMART trial is a prospective, single-centre, randomised, open-label, parallel-group pilot feasibility study comparing VMAT-based SFRT (8 Gy in 1 fraction) with VMAT-based MFRT (20 Gy in 5 fractions) in patients with painful bone metastases, including spinal metastases.

Approximately 70 participants will be randomised in a 1:1 ratio to receive either SFRT or MFRT. Both treatment schedules will be delivered using VMAT with daily image-guided radiotherapy using cone-beam computed tomography (CBCT)-based image guidance.

Stratified block randomisation will be used according to the site of metastasis (spine versus non-spine) to maintain balance between the two treatment groups. Within each stratum, computer-generated variable block randomisation using block sizes of 4 and 6 will be used. Allocation will be concealed using sequentially numbered, opaque, sealed envelopes.

Pain will be assessed using the Numeric Rating Scale (NRS-11) and Wong-Baker FACES Pain Scale at baseline and during follow-up. Participants will be assessed at 2 weeks, 4 weeks and 12 weeks after radiotherapy.

The primary aim of this pilot study is to assess the feasibility of conducting a randomised controlled trial at the participating tertiary oncology centre. Feasibility will include recruitment, treatment completion, follow-up completion and completeness of study data.

The primary efficacy outcome will be overall pain response at 4 weeks following radiotherapy. Secondary outcomes will include pain response at other follow-up time points, retreatment rates, pain flare, treatment-related toxicity, patient convenience and resource utilisation.

The study is not powered to provide a definitive non-inferiority conclusion. A non-inferiority margin of 15% has been prespecified to guide estimation of the treatment effect and inform the design and sample size of a future definitive randomised trial. The primary efficacy analysis will compare overall pain response between the two treatment groups using the intention-to-treat population.

The study will generate preliminary feasibility and clinical outcome data to inform the design of a future definitive randomised controlled trial evaluating single-fraction versus multifraction radiotherapy for painful bone metastases.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Balaji Subramanian Sitaraman, MBBS, DNB; Phone Number: +96871926769; Email: balaji.radonc@gmail.com

Study Locations

• Oman
  • Muḩāfaz̧at Masqaţ
    • Muscat, Muḩāfaz̧at Masqaţ, Oman, 100
      • Royal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Histologically proven malignancy
• Radiological evidence of bone or spine metastases
• Pain score ≥4 on Numeric Rating Scale (NRS-11)
• ECOG Performance Status 0-3
• Life expectancy ≥3 months.
• Ability to provide written informed consent

Exclusion Criteria:

• Spinal cord compression requiring emergency therapy
• Previous radiotherapy to same site
• Unstable pathological fracture requiring surgery
• Pregnancy
• Inability to provide consent
• Oligometastatic bone metastases requiring Stereotactic Body Radiotherapy (SBRT)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-Fraction Radiotherapy (SFRT); Participants will receive VMAT-basd radiotherapy to painful none metastasis, a total dose of 8 Gy delivered in a single fraction using CBCT based imaging guidance.	Radiation: Single-Fraction Radiotherapy (8Gy x 1#); VMAT-based external beam radiotherapy planned to deliver 8 Gy in a single fraction with CBCT-based image guidance for the palliation of painful bone metastasis
Active Comparator: Multifraction Radiotherapy (MFRT); Participants will receive VMAT-basd radiotherapy to painful none metastasis, a total dose of 20Gy delivered in Five fractions using daily CBCT based imaging guidance.	Radiation: Multifraction Radiotherapy (20 Gy in 5 #); VMAT-based external beam radiotherapy planned to deliver 20 Gy in Five fractions of 4 Gy each with daily CBCT-based image guidance for the palliation of painful bone metastasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of target sample recruited	The percentage of the planned target sample successfully recruited during the recruitment period. Recruitment feasibility will be interpreted using predefined traffic-light criteria: Green ≥80% (feasibility achieved), Amber 70-79% (borderline feasibility requiring review), and Red <70% (feasibility not achieved and requiring review).	From study initiation through completion of the recruitment period.
Percentage of participants completing assigned radiotherapy	The percentage of randomised participants who complete the assigned radiotherapy treatment according to the study protocol. Treatment completion feasibility will be interpreted using predefined traffic-light criteria: Green ≥90% (feasibility achieved), Amber 80-89% (borderline feasibility requiring review), and Red <80% (feasibility not achieved and requiring review).	From randomisation through completion of assigned radiotherapy.
Percentage of participants completing 3-month follow-up	The percentage of randomised participants who complete the required study follow-up through 3 months after radiotherapy. Follow-up feasibility will be interpreted using predefined traffic-light criteria: Green ≥80% (feasibility achieved), Amber 70-79% (borderline feasibility requiring review), and Red <70% (feasibility not achieved and requiring review).	From randomisation through 3 months after radiotherapy.
Percentage of participants with complete required study data	The percentage of participants with complete required study data according to the study data collection requirements. Data completeness will be interpreted using predefined traffic-light criteria: Green ≥90% (feasibility achieved), Amber 80-89% (borderline feasibility requiring review), and Red <80% (feasibility not achieved and requiring review).	From study initiation through 3 months after radiotherapy.
Percentage of participants with major protocol deviations	The percentage of participants with major protocol deviations during the study. A major protocol deviation is a significant departure from the study protocol that may affect participant safety, treatment allocation, assessment of the primary outcome, or validity of the study results. Protocol adherence will be interpreted using predefined traffic-light criteria: Green <10% major protocol deviations (feasibility achieved), Amber 10-20% (borderline feasibility requiring review), and Red >20% (feasibility not achieved and requiring review).	From randomisation through 3 months after radiotherapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving overall pain response at 4 weeks.	Overall pain response will be assessed using the NRS-11 and analgesic use. Pain response is defined as a reduction of at least 2 points in pain from baseline with no escalation in analgesic use. The percentage of participants achieving pain response will be compared between the SFRT and MFRT groups.	4 weeks after radiotherapy
Percentage of participants requiring retreatment	The percentage of participants requiring repeat radiotherapy to the treated sitefor persisten or recurrence of pain will be recorded and compared between the SFRT and MFRT groups.	From completion of radiotherapy through 3 months after radiotherapy
Percentage of participants experiencing pain flare	Pain flare following radiotherapy will be recorded and compared between the SFRT and MFRT groups. Pain flare is defined as increase in NRS pain score by ≥2 points without reduction in analgesic use, or Increase in analgesic requirement by ≥25% without improvement in pain score, followed by return to the baseline pain level or analgesic requirement within 10 days after radiotherapy.	From completion of radiotherapy through 10 days after radiotherapy.
Percentage of participants achieving overall pain response at 2 weeks and 3 months	Overall pain response will be assessed using the NRS-11 and analgesic use. Pain response is defined as a reduction of at least 2 points in pain from baseline with no escalation in analgesic use. The percentage of participants achieving pain response will be recorded at 2 weeks and 3 months after radiotherapy and compared between the SFRT and MFRT groups.	2 weeks and 3 months after radiotherapy
Change in analgesic requirement from baseline	Change in analgesic requirement from baseline will be assessed using the patient's analgesic consumption and expressed as oral morphine equivalent dose (OMED). The change in analgesic requirement will be recorded and compared between the SFRT and MFRT groups.	At 2 weeks, 4 weeks, and 3 months after radiotherapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants receiving radiotherapy to new painful metastatic sites	The number of participants who receive radiotherapy to new painful metastatic sites during the 3-month follow-up period will be recorded descriptively. This outcome reflects the occurrence of new painful metastatic disease during follow-up and is not intended to assess the efficacy of SFRT versus MFRT.	From completion of radiotherapy through 3 months after radiotherapy

Collaborators and Investigators

• Sponsor: Oman Ministry of Health
• Collaborators: Royal Hospital, Oman
• Investigators: Principal Investigator: Balaji Subramanian Sitaraman, MBBS, DNB, Royal Hospital, Ministry of Health, Oman

Publications and helpful links

General Publications

• Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M 3rd, Suh JH, Demas WF, Movsas B, Petersen IA, Konski AA, Cleeland CS, Janjan NA, DeSilvio M. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005 Jun 1;97(11):798-804. doi: 10.1093/jnci/dji139.
• Sahgal A, Myrehaug SD, Siva S, Masucci GL, Maralani PJ, Brundage M, Butler J, Chow E, Fehlings MG, Foote M, Gabos Z, Greenspoon J, Kerba M, Lee Y, Liu M, Liu SK, Thibault I, Wong RK, Hum M, Ding K, Parulekar WR; trial investigators. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021 Jul;22(7):1023-1033. doi: 10.1016/S1470-2045(21)00196-0. Epub 2021 Jun 11.
• McDonald R, Chow E, Lam H, Rowbottom L, Soliman H. International patterns of practice in radiotherapy for bone metastases: A review of the literature. J Bone Oncol. 2014 Nov 7;3(3-4):96-102. doi: 10.1016/j.jbo.2014.10.003. eCollection 2014 Nov.
• Hird A, Chow E, Zhang L, Wong R, Wu J, Sinclair E, Danjoux C, Tsao M, Barnes E, Loblaw A. Determining the incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: results from three canadian cancer centers. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):193-7. doi: 10.1016/j.ijrobp.2008.10.044. Epub 2009 Jan 23.
• Westhoff PG, de Graeff A, Monninkhof EM, Pomp J, van Vulpen M, Leer JW, Marijnen CA, van der Linden YM; Dutch Bone Metastasis Study Group. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases. Int J Radiat Oncol Biol Phys. 2015 Nov 1;93(3):694-701. doi: 10.1016/j.ijrobp.2015.06.024. Epub 2015 Jun 20.
• BalajiSubramanian S, Sathiya K, Balaji K, Thirunavukarasu M, Phanikiran S, Rela M. Re-irradiation after stereotactic body radiotherapy for spine metastases from hepatocellular carcinoma: a case report. Rep Pract Oncol Radiother. 2021 Dec 30;26(6):1060-1065. doi: 10.5603/RPOR.a2021.0098. eCollection 2021.
• Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol). 2012 Mar;24(2):112-24. doi: 10.1016/j.clon.2011.11.004. Epub 2011 Nov 29.
• Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, de Haes H, Martijn H, Oei B, Vonk E, van der Steen-Banasik E, Wiggenraad RG, Hoogenhout J, Warlam-Rodenhuis C, van Tienhoven G, Wanders R, Pomp J, van Reijn M, van Mierlo I, Rutten E. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999 Aug;52(2):101-9. doi: 10.1016/s0167-8140(99)00110-3.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: August 8, 2026
• First Submitted That Met QC Criteria: August 14, 2026
• First Posted (Actual): August 19, 2026

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 14, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Feasibility; Bone Metastases; Single fraction radiotherapy; Multifraction radiotherapy; Pain response,
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cancer Pain
• Other Study ID Numbers: MoH/CSR/26/32133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be routinely shared with other researchers. The study is a single-center feasibility study, and the collected data will be used for the approved study objectives and institutional research purposes. Any data sharing, if required in the future, will be considered in accordance with institutional policies, ethical approval, participant confidentiality, and applicable regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No