Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer (SABR-COMET-3)

Phase III Randomized Controlled Trial and Economic Evaluation of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer (SABR-COMET-3)

Stereotactic Ablative Radiotherapy (SABR) is a modern RT technique that delivers high doses of radiation to small tumor targets using highly conformal techniques. SABR is non-invasive and delivered on an outpatient basis. The purpose of this study is to compare the effect of SABR, relative to standard of care (SOC) alone, on overall survival, progression-free survival, toxicity, and quality of life. An integrated economic evaluation will determine the cost per quality of life year gained using SABR (vs. SOC) and a translational component will enable identification of predictive/prognostic biomarkers of the oligometastatic state.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Tumors
• Intervention / Treatment: Radiation: palliative radiotherapy; Radiation: Stereotactic ablative radiotherapy

Detailed Description

TREATMENT PLAN

5.1.1 Standard Arm (Arm 1)

Radiotherapy for patients in the standard arm should follow the principles of palliative radiotherapy as per the individual institution, with the goal of alleviating symptoms or preventing imminent complications. Patients in this arm should not receive stereotactic doses or radiotherapy boosts. Recommended dose fractionations in this arm will include 8 Gy in 1 fractions, 20 Gy in 5 fractions, and 30 Gy in 10 fractions.

Systemic therapy will be pre-specified based on the standard of care approach for that patient, and it may include systemic therapy (cytotoxic, targeted, hormonal, or immunotherapy) or observation.

5.1.2 Experimental Arm (Arm 2)

Dose/Fractionation

Treatment recommendations are as follows:

Lung: Tumors 5 cm or less surrounded by lung parenchyma: 48 Gy in 4 fractions (12 Gy/#), 54 Gy in 3 fractions (18 Gy/#), daily or every second day

Lung: Within 2 cm of mediastinum or brachial plexus 60 Gy in 8 fractions (7.5 Gy/#) daily

Bone: Any bone 35 Gy in 5 fractions (7 Gy/#), 24 Gy in 2 fractions (12 Gy/#), daily

Brain: Stereotactic lesions (no whole brain RT):

<2cm 20-24 Gy in 1 fraction (20-24 Gy/#) Once

2-3 cm 18 Gy in 1 fraction (18 Gy/#) Once

3-4cm 15 Gy in 1 fraction (15 Gy/#) Once

Metastases only: 35Gy 5 7 Gy to PTV Daily, Whole brain + Mets: 35Gy to metastases 5 7 Gy to PTV Daily, 20 Gy whole brain 4 Gy WBRT Daily,

Liver: 54 Gy in 3 fractions (18 Gy/#), every second day

Adrenal/Pancreas: 40 Gy in 5 fractions (8 Gy/#)/ 35Gy in 5 fractions (7 Gy/#), daily

Lymph Node: 40 Gy in 5 fractions (8 Gy/#), daily

5.1.2.1 Immobilization Treatment will be setup using reproducible positioning and verified using an on-line protocol for all patients in this study. Immobilization may include a custom immobilization device, such as thermoplastic shell or vacuum bag, as per individual institutional practice when delivering SABR. Some centers do not use immobilization devices and have demonstrated high degrees of accuracy; this is acceptable in this study.

5.1.2.2 Imaging/Localization/Registration All patients in Arm 2 will undergo planning CT simulation. 4-dimensional CT will be used for tumors in the lungs, liver, or adrenals. Axial CT images will be obtained throughout the region of interest. For centres using stereotactic radiosurgery platforms, real-time tumor tracking and orthogonal imaging systems are permitted.

5.1.2.3 4D-CT Procedures

For patients undergoing 4D-CT, physics will review the 4D-CT images and will perform the following quality assurance procedures indicated on the 4D-CT template designed specifically for SABR:

i) Ensure all end inspiration (0%) tags exist and are in the right place. This ensures image integrity.

ii) If the quality of the 4D-CT images is not sufficient (determined by Physics), then standard 3D-CT will be performed on the fast helical CT or Untagged Average CT.

iii) Motion measurements in all 3 directions are performed:

1. If the motion is less than or equal to 7 mm and the good quality images exist, then treatment planning may be performed on the Untagged Average CT with the 50% or 60% phase (End Expiration) and the 0% phase being fused to it. This will define the IGTV.
2. If the motion is greater than 7 mm in any one direction, then respiratory-gated radiotherapy can be considered. In this case, treatment planning will be performed on a subset average CT dataset (usually labeled either 30%-60% Avg CT or 40%-70% Avg CT) generated by Physics. This is an average CT over the intended gated interval. Therefore, the GTV that is delineated on this scan will incorporate residual motion in the intended gated interval. The 0% phase will also be fused to this dataset. The PTV for planning will include the GTV delineated on the subset average CT plus margins for microscopic extension (Physician's discretion) and setup uncertainty. The GTV_0% should also be delineated and combined with the GTV delineated on the subset average CT to define an additional volume labeled IGTV_CBCT. This contour may be used for image registration with CBCT only.

5.1.2.4 Volume Definitions (Arm 2) For all lesions, the gross tumor volume (GTV) will be defined as the visible tumor on CT and/or MRI imaging +/- PET. No additional margin will be added for microscopic spread of disease (i.e. Clinical Target Volume [CTV]=GTV). For bone lesions, CTV of 3-5mm will be allowed. For vertebral lesions, anatomic approach will be taken as per International Spinal consortium guideline (Cox 2012)

An anatomic approach is taken to the CTV based on where the disease within the spinal segment is located. The rules for CTV are as follows:

1. If the vertebral body is involved with GTV then the entire vertebral body is taken as CTV.
2. If the ipsilateral pedicle and/or transverse process has GTV then the entire ipsilateral posterior segment (pedicle, lamina and transverse process) ±the spinous process is taken into the CTV. The inclusion of the spinous process is per the discretion of the radiation oncologist.
3. If the ipsilateral pedicle, lamina, and/or transverse process has GTV, then the entire ipsilateral posterior segment (pedicle, lamina, and transverse process) plus the spinous process is taken into the CTV
4. If bilateral involvement of the pedicle and/or transverse process with GTV, then the posterior segment anatomy ± the spinous process is taken into the CTV. The inclusion of the spinous process is per the discretion of the radiation oncologist.
5. If bilateral involvement of the pedicles and lamina, and/or transverse process with GTV, then the entire posterior segment anatomy is taken into the CTV, including the spinous process.
6. If the spinous process is involved with GTV alone then the bilateral lamina ± pedicles are to be taken into the CTV.

The International Spinal Consortium Guideline is a reference for CTV delineation (Cox 2012) and can be adhered to as described.

In the case of epidural disease, a 5 mm anatomic margin (excluding the spinal cord) beyond the GTV may be used within the epidural compartment including in the cranio-caudal direction. A circumferential CTV as per a donut based CTV is allowed and encouraged in the case of epidural disease at the discretion of the treating radiation oncologist. If paraspinal disease present, a minimum 5 mm CTV margin may be applied beyond the GTV.

A Planning Target Volume (PTV) margin of 2-5 mm will be added depending on site of disease, immobilization, and institutional set-up accuracy: 2-3 mm margins should be used for spinal stereotactic treatments, 0-2 mm for brain tumors, and 5 mm for other sites.

Targets should be named based on the organ involved, and numbered from cranially to caudally. For example, in a patient with 3 lung lesions, there would be: GTV_lung_1, GTV_lung_2, and GTV_lung_3, and corresponding PTV_lung_1, PTV_lung_2_, and PTV_lung_3, representing the lesions from superior to inferior.

For spinal lesions, a pre-treatment MRI is required to assess the extent of disease and position of the cord. This must be fused with the planning CT scan. A Planning Organ at Risk Volume (PRV) expansion of 2 mm will be added to the spinal cord, and dose constraints for the spinal cord apply to this PRV. Alternatively, the thecal sac may be used as the PRV. For radiosurgery platforms, a PRV margin of 1 mm is permitted for the spinal cord.

Organ At Risk (OAR) Doses OAR doses are listed in Appendix 1 of protocol. OAR doses may not be exceeded except in the case of chestwall / ribs. In cases where the PTV coverage cannot be achieved without exceeding OAR doses, the PTV coverage is to be compromised. All serial organised OARs within 5 cm of the PTV must be contoured (partial organ contours allowed); for parallel organised organs (liver, lung, etc.) within 5cm of PTV, the whole organs need to be contoured. This should be tested for each PTV by creating a 5 cm expansion to examine which OARs lie within that expansion.

Treatment Planning Treatment can be delivered using static beams (either 3D-conformal radiotherapy or intensity-modulated) or rotational therapy (volumetric modulated arc therapy, or tomotherapy).

Dose constraints may not be exceeded (except chestwall/ribs). If a dose constraint cannot be achieved due to overlap of the target with an organ at risk, the fractionation can be increased or the target coverage compromised in order to meet the constraint. In cases where the target coverage or dose must be reduced, the priority for dose coverage is the GTV (e.g. attempt to cover as much of the GTV as possible with the prescription dose). All such cases of dose reduction or target coverage compromise must be approved by the local PI prior to treatment. For vertebral tumors, note that the spinal cord constraints apply to the PRV (see section 6.2.5).

For all targets, doses should be prescribed to 60-90% isodose line surrounding the PTV, and all hotspots should fall within the GTV. 95% of the PTV should be covered by the prescription dose, and 99% of the PTV should be covered by 90% of the prescription dose.

Doses must be corrected for tissue inhomogeneities. Several non-overlapping 6/10 MV beams (on the order of 7-11 beams) or 1-2 VMAT arcs combined possibly with a few non-coplanar beams should be utilized. Non-coplanar beams can be used to reduce 50% isodose volume.

The number of isocentres is at the discretion of the treating physician, physicists, and dosimetrists. Generally, metastases can be treated with separate isocenters if they are well-separated.

The scheduling and sequence of treating each metastasis is at the discretion of individual physicians, but in general should begin with the brain, due to risks associated with progression. All SABR must be completed within 2 weeks.

5.1.2.5 Quality Assurance (Arm 2)

In order to ensure patient safety and effective treatment delivery, a robust quality assurance protocol is incorporated. The following requirements must be completed for each patient:

• Prior to treatment, each patient must be discussed at quality assurance (QA) rounds or be peer reviewed by a radiation oncologist with SABR expertise.
• All radiotherapy plans must meet target dose levels for organs at risk (except chestwall/ribs) (Appendix 1). Prior to plan approval, the dose to each organ at risk must be verified by the physicist or treating physician.
• All dose delivery for intensity-modulated plans (including arc-based treatments) will be confirmed before treatment by physics staff.

5.1.2.6 Systemic Therapy Patients treated with prior systemic therapy are eligible for this study, however, no chemotherapy agents (cytotoxic, or molecularly targeted agents) are allowed within the period of time commencing 2 weeks prior to radiation lasting until 1 week after the last fraction. Hormonal therapy is allowed. Use of chemotherapy schemes containing potent enhancers of radiation damage (e.g. gemcitabine, adriamycin/doxorubicin, bevacizumab) are discouraged within the first month after radiation.

5.1.2.7 Further radiotherapy for progressive disease at new metastatic sites Patients in Arm 1 who develop new, untreated metastatic deposits should be treated with standard-of-care approaches. SABR to those sites is not permitted, except for unique scenarios where it would be considered standard of care (e.g. all disease controlled on systemic therapy with a newly developed brain metastasis). Apart from brain metastases, treatment of 'oligo-progression' with SABR is not permitted.

Patients in Arm 2 who develop new, untreated metastatic deposits should be considered for SABR at those sites, if such deposits can be treated safely with SABR, and if the treating institution offers SABR for that body site. If SABR is not possible, then palliative RT can be delivered if indicated.

5.1.2.8 Quality Assurance for Centres Joining Study Prior to opening the study, each participating research centre will be required to send to one of the Principal Investigators a mock treatment plan for the anatomic sites that will be treated (e.g. Lung, brain, liver, adrenal), to ensure that the treatment plans are designed in compliance with the protocol. The principal investigators will provide pertinent CT datasets. Each participating research centre can choose which tumor sites will be treated at their individual centre (i.e. some centres may only choose to treat a subset of the eligible metastatic sites). Sites that have prior accreditation for SABR through a clinical trial (e.g. SABR-COMET, or organ-specific SABR trials) are exempt from this requirement for the organ sites that have been accredited in those trials.

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robert Olson, MD, MSC, FRCPC; Phone Number: 250-645-7300; Email: rolson2@bccancer.bc.ca
• Study Contact Backup: Name: Hadassah Abraham, MSc; Phone Number: 687247 250-675-7300; Email: hadassah.abraham@bccancer.bc.ca

Study Locations

• Australia
  • New South Wales
    • Wagga Wagga, New South Wales, Australia, 2650
      • Recruiting
      • Riverina Cancer Care Centre
      • Contact: Noel Aherne, MD; Phone Number: +61 2 6932 1000; Email: noel.aherne@health.nsw.gov.au
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Hospital
      • Contact: Sashendra Senthi, MD; Phone Number: +61 3 9076 2000; Email: S.Senthi@alfred.org.au
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Tom Baker Cancer Centre
      • Contact: Rishi Sinha, MD, FRCPC; Phone Number: 403-521-3095; Email: rishi.sinha@albertahealthservices.ca
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Recruiting
      • BC Cancer
      • Contact: Benjamin Mou, MD; Phone Number: 250-712-3900; Email: benjamin.mou@bccancer.bc.ca
    • Prince George, British Columbia, Canada, V2M 7E9
      • Recruiting
      • BC Cancer - Prince George
      • Contact: Hadassah Abraham; Phone Number: 250-645-7300; Email: hadassah.abraham@bccancer.bc.ca
      • Contact: Robert Olson, MD MSc FRCPC; Phone Number: 250-645-7300; Email: rolson2@bccancer.bc.ca
    • Surrey, British Columbia, Canada
      • Recruiting
      • BC Cancer
      • Contact: Devin Schellenberg, MD; Phone Number: 604-930-4085; Email: dschellenberg@bccancer.bc.ca
    • Vancouver, British Columbia, Canada
      • Recruiting
      • BC Cancer
      • Contact: Mitchell Liu, MD; Phone Number: 604-877-6000; Email: mliu@bccancer.bc.ca
    • Victoria, British Columbia, Canada
      • Recruiting
      • BC Cancer
      • Contact: Tanya Berrang, MD; Phone Number: 250-519-5577; Email: TBerrang@bccancer.bc.ca
  • Ontario
    • London, Ontario, Canada
      • Recruiting
      • London Health Sciences Centre
      • Contact: David Palma, MD, PhD; Phone Number: 519-685-8600; Email: david.palma@lhsc.on.ca
    • Saint Catharines, Ontario, Canada, L2S 0A9
      • Recruiting
      • Walker Family Cancer Centre
      • Contact: Adrian Ishkanian; Email: Adrian.Ishkanian@niagarahealth.on.ca
• Ireland
  • Cork, Ireland
    • Recruiting
    • Bon Secours Radiotherapy Cork in partnership with UPMC Hillman Cancer Centre
    • Contact: Paul Kelly, MD, FRCPI; Phone Number: +353 21 486 1100; Email: kellyp6@upmc.ie
  • Dublin
    • Rathgar, Dublin, Ireland, 6
      • Recruiting
      • St. Luke's Radiation Oncology Network
      • Contact: John Armstrong, MD, FRCPI, DABR, FFRRCSI; Phone Number: +353 01 704 5500; Email: john.armstrong@beaconhospital.ie
  • Sandyford
    • Dublin, Sandyford, Ireland, D18 AK68
      • Recruiting
      • Beacon Hospital
      • Contact: Alina Mihai, MD, FRCPI; Phone Number: .+353 1 293 7556; Email: alina.mihaelamihai@beaconhospital.ie
• United Kingdom
  • Glasgow, United Kingdom
    • Recruiting
    • Beatson West of Scotland Cancer Centre
    • Contact: Sean O'Cathail, MD; Phone Number: +44-141-301-7000; Email: sean.ocathail@glasgow.ac.uk
  • Scotland
    • Aberdeen, Scotland, United Kingdom
      • Recruiting
      • Aberdeen Royal Infirmary
      • Contact: Adnan Shaukat, MD; Phone Number: +44 345 456 6000; Email: adnan.shaukat@nhs.scot
    • Edinburgh, Scotland, United Kingdom
      • Recruiting
      • Edinburgh Cancer Centre
      • Contact: Iain Phillips, MD; Phone Number: +44 131 537 1000; Email: iain.phillips1@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Total number of 1-3 current metastases, and a maximum 8 lifetime metastases
• Age 18 or older
• Willing to provide informed consent
• ECOG score 0-2
• Life expectancy >6 months
• Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.

• Controlled primary tumor

  • defined as: at least 3 months since original tumor treated definitively, with no progression at primary site (can be considered controlled if no evidence of the primary tumour on imaging)
• A history and physical exam, including ECOG performance status, performed within 6 weeks prior to trial enrollment
• Not suitable for resection at all sites or decline surgery
• Patient has had a CT chest, abdomen and pelvis or PET-CT within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR). CT neck as clinically indicated.
• Patient has had a nuclear bone scan (if no PET-CT) within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR)
• If solitary lung nodule for which biopsy is unsuccessful or not possible, patient has had an FDG PET scan or CT (chest, abdomen, pelvis) and bone scan within 8 weeks prior to enrollment, and with 12 weeks prior to treatment (if randomized to SABR). CT neck as clinically indicated.
• If colorectal primary with rising CEA, but equivocal imaging, patient has had an FDG PET scan within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR)
• Patient has had CT or MRI brain imaging if primary has a propensity for CNS metastasis within 8 weeks prior to enrollment, and within 12 weeks prior to treatment(if randomized to SABR)
• Patient is judged able to:
• Maintain a stable position during therapy
• Tolerate immobilization device(s) that may be required to deliver SABR safely
• Negative pregnancy test for Women of Child-Bearing potential (WOCBP) within 4 weeks of RT start date
• Patient is able and willing to complete the quality of life questionnaires, and other assessments that are a part of this study, via paper or online using REDCap (if email address is provided by participant on the informed consent)

Waivers to the inclusion criteria will NOT be allowed.

Exclusion Criteria:

• Lesion in femoral bone requiring surgical fixation
• Chemotherapy agents (cytotoxic, or molecularly targeted agents) used within the period of time commencing 2 weeks prior to radiation, lasting until 1 week after the last fraction for patients randomized to SABR
• Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Crohn's disease in patients where the GI tract will receive radiotherapy, and connective tissue disorders such as lupus or scleroderma.
• Substantial overlap with a previously treated radiation volume. Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints herein. For patients treated with conventional radiation previously, biological effective dose calculations should be used to equate previous doses to the tolerance doses listed below. All such cases should be discussed with one of the study PIs.
• Concurrent malignant cancer, or history of malignant cancers within the past 5 years
• Malignant pleural effusion
• History of poor lung function (if treating near lung)
• History of poor liver function (if treating near liver)
• Inability to treat all sites of disease

• Maximum size of 5 cm for lesions outside the brain, except:

  • Bone metastases over 5 cm may be included, if in the opinion of the local PI it can be treated safely (e.g. rib, scapula, pelvis)
  • Any brain metastasis >3 cm in size or a total volume of brain metastases greater than 30 cc.
• Clinical or radiologic evidence of spinal cord compression, or epidural tumor within <2 mm of the spinal cord. Patients can be eligible if surgical resection has been performed, but the surgical site counts toward the total of up to 8 lifetime metastases.
• Dominant brain metastasis requiring surgical decompression
• Pregnant or breastfeeding women

Waivers to exclusion criteria will NOT be allowed.

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
Active Comparator: Standard of Care Treatment (Arm 1); Standard of care, palliative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist	Radiation: palliative radiotherapy; Radiotherapy for patients in the standard arm should follow the principles of palliative radiotherapy as per the individual institution, with the goal of alleviating symptoms or preventing imminent complications. Patients in this arm should not receive stereotactic doses or radiotherapy boosts. Recommended dose fractionations in this arm will include 8 Gy in 1 fractions, 20 Gy in 5 fractions, and 30 Gy in 10 fractions.
Experimental: Stereotactic Arm (Arm 2); Stereotactic ablative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist	Radiation: Stereotactic ablative radiotherapy; Lung: Tumors 5 cm or less surrounded by lung parenchyma 48 Gy/4#, or 54 Gy/3#, daily or every second day Within 2 cm of mediastinum or brachial plexus 60 Gy/8#, daily Bone: Any bone 35 Gy/5#, or 24 Gy/2#, daily Brain: Stereotactic lesions (no whole brain RT) <2cm 20-24 Gy/1#, once 2-3 cm 18 Gy/1#, once Metastases only: 35Gy/5# to PTV, daily Whole brain + Mets: 35Gy to metastases, daily 20 Gy whole brain, daily Liver: 54 Gy/3#, every second day Adrenal/Pancreas: 40 Gy/5# / 35Gy/7#, daily Lymph Node: 40 Gy/5#, daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to death from any cause	At approximately end of year 5 (study completion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects	Occurrences of grade 2 or higher adverse events	At 6 weeks, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Progression-free survival (PFS)	Time from randomization to disease progression at any site or death.	At 6 weeks, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Patient-reported quality of life (QoL)	Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire	At baseline, 6 weeks, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Health-related quality of life (HRQoL) questionnaire	EuroQOL Group EQ-5D-5L	At baseline, 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Resource Utilization (Patient and Provider Reported)	Number of hospital admissions, ER visits, systemic or radiation therapy	At 3 months, 6 months, and every 6 months post treatment for years 1 and 2. At approximately end of years 3, 4, and 5.
Correlation between candidate biomarkers of oligometastatic disease (blood-derived) and oncologic outcomes	CTC and ctDNA Enumeration	At baseline, 3 months, and disease progression or study completion (Year 5)

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Collaborators: The Alfred; London Regional Cancer Program, Canada; Tom Baker Cancer Centre; Cancer Trials Ireland; Beatson West of Scotland Cancer Centre; Cancer Research UK Edinburgh Centre; Beacon Hospital, Ireland; Bon Secours Cork Cancer Centre; UPMC Hillman Cancer Centre; Walker Family Cancer Centre; Riverina Cancer Care Centre
• Investigators: Principal Investigator: Robert A Olson, MD, MSc, FRCPC, BC Cancer Prince George

Publications and helpful links

General Publications

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• Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr; International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg. 1997 Jan;113(1):37-49. doi: 10.1016/s0022-5223(97)70397-0.
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• Hong JC, Ayala-Peacock DN, Lee J, Blackstock AW, Okunieff P, Sung MW, Weichselbaum RR, Kao J, Urbanic JJ, Milano MT, Chmura SJ, Salama JK. Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis. PLoS One. 2018 Apr 12;13(4):e0195149. doi: 10.1371/journal.pone.0195149. eCollection 2018.
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• Palma DA, Salama JK, Lo SS, Senan S, Treasure T, Govindan R, Weichselbaum R. The oligometastatic state - separating truth from wishful thinking. Nat Rev Clin Oncol. 2014 Sep;11(9):549-57. doi: 10.1038/nrclinonc.2014.96. Epub 2014 Jun 24.
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• Ruers T, Punt C, Van Coevorden F, Pierie JPEN, Borel-Rinkes I, Ledermann JA, Poston G, Bechstein W, Lentz MA, Mauer M, Van Cutsem E, Lutz MP, Nordlinger B; EORTC Gastro-Intestinal Tract Cancer Group; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO) and the National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012 Oct;23(10):2619-2626. doi: 10.1093/annonc/mds053. Epub 2012 Mar 19.
• Cheruvu P, Metcalfe SK, Metcalfe J, Chen Y, Okunieff P, Milano MT. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer. Radiat Oncol. 2011 Jun 30;6:80. doi: 10.1186/1748-717X-6-80.
• Rava P, Leonard K, Sioshansi S, Curran B, Wazer DE, Cosgrove GR, Noren G, Hepel JT. Survival among patients with 10 or more brain metastases treated with stereotactic radiosurgery. J Neurosurg. 2013 Aug;119(2):457-62. doi: 10.3171/2013.4.JNS121751. Epub 2013 May 10.
• Ritter TA, Matuszak M, Chetty IJ, Mayo CS, Wu J, Iyengar P, Weldon M, Robinson C, Xiao Y, Timmerman RD. Application of Critical Volume-Dose Constraints for Stereotactic Body Radiation Therapy in NRG Radiation Therapy Trials. Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):34-36. doi: 10.1016/j.ijrobp.2017.01.204. No abstract available.
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• Devlin NJ, Krabbe PF. The development of new research methods for the valuation of EQ-5D-5L. Eur J Health Econ. 2013 Jul;14 Suppl 1(Suppl 1):S1-3. doi: 10.1007/s10198-013-0502-3. No abstract available.
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• Olson R, Mathews L, Liu M, Schellenberg D, Mou B, Berrang T, Harrow S, Correa RJM, Bhat V, Pai H, Mohamed I, Miller S, Schneiders F, Laba J, Wilke D, Senthi S, Louie AV, Swaminath A, Chalmers A, Gaede S, Warner A, de Gruijl TD, Allan A, Palma DA. Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial. BMC Cancer. 2020 May 5;20(1):380. doi: 10.1186/s12885-020-06876-4.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 8, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: SABR-COMET-3

Drug and device information, study documents

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