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

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.

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 o Покажи пълното описание...

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.