None listed
Conditions
Brief summary
The purpose of this study is to investigate whether improved radiation planning technology that conforms to the shape and size of the cancer, can be used to treat multiple sites of cancer within the brain, and at the same time protect and preserve brain (memory and cognitive) function. This study is for patients who are are aged 18 years or above and have been diagnosed with 3-10 cerebral metastases, i.e. the cancer has spread to three or more spots on the brain. All participants in this study will receive a new treatment called Hypofractionated Stereotactic Radiotherapy. This is highly focused radiation given in one to five treatments. Robotic targeting is used to avoid important parts of the normal brain. Whereas previous treatment for multiple sites of cancer within the brain has involved giving radiation to the whole brain, this treatment will allow for targeted treatment of just the affected areas. In this way, the dose of radiation delivered to key areas of the brain involved with memory function can be minimised. All participants will be monitored throughout treatment for safety. At the beginning of the study, and then at 3 and 6 months following treatment, patients will be asked to undergo MRI scans to assess disease control, have assessments of neurocognitive function by a trained neuropsychologist, and complete quality of life questionnaires. We estimate that this study will contribute further to the research into using radiotherapy to control cancers that have spread to the brain, while minimising the effects on brain function.
Interventions
Prescription Dose Per Site
Stereotactic radiotherapy over 5-6 days or stereotactic radiosurgery over 1-2 days will be performed using planning software which allows for the planning and treatment of multiple (3-10) cerebral metastases. Dose prescription and fractionation schedules will be based on metastases’ size, location and previous surgery. For each metastatic site identified, 98.5% of the defined PTV volume must be covered by the appropriate dose. All prescribed doses per lesion classifica
Prescription Dose Per Site Stereotactic radiotherapy over 5-6 days or stereotactic radiosurgery over 1-2 days will be performed using planning software which allows for the planning and treatment of multiple (3-10) cerebral metastases. Dose prescription and fractionation schedules will be based on metastases’ size, location and previous surgery. For each metastatic site identified, 98.5% of the defined PTV volume must be covered by the appropriate dose. All prescribed doses per lesion classification are outlined below: PTV* (total) -Total Dose (Gy) to 80% IDL* - Fractions 0.5-15 cubic cm will receive 20 Gy in 1 fraction 6.0-15 cubic cm will receive 27 Gy in 3 fractions *PTV = Planning target volume; IDL = Isodose level Dose prescriptions All fractionation is based on the prescription dose covering >98.5% of the PTV. Dose-fractionation has been designed to provide similar efficacy in terms of tumour control with increasing fractionation based on volume (PTV), and to provide maximum safety in terms of late reactions such as tumour necrosis and symptomatic cerebral oedema. For participants prescribed hypofractionated dose regimes, it is expected that treatments will be delivered daily totalling up to 5 fractions per week according to departmental policies, except where interruptions to treatment schedule are unavoidable due to public holidays or any other reason. If an interruption in treatment is needed due to an adverse event, the cause and nature shall be documented and scored using the per-protocol CTCAE v4.03, with treatment to resume as soon as is clinically feasible. Any other alternative events that result in treatment interruptions should also be documented. Beam Arrangement and Technique Selection (i) Treatment Modality BrainLab Elements™ and Varians HyperArc TM are both novel radiotherapy planning software designed solely for the planning of multiple brain metastases simultaneously. Internal algorithms within the software analyse predefined target and critical structure proximity and dose constraints, structure priority, size and shape, and work to construct a plan that best achieves the dosimetry that matches all the input parameters. BrainLab Elements™ and Varians HyperArc TM Planning software both employ dynamic high definition multi-leaf collimators (HD-MLC) to create tight margins around identified targets. This creates dose distributions with steep dose gradients, greatly minimising dose to the normal healthy surrounding tissues and structures. At the discretion of the investigator and as per local policy, BrainLab iPlan™ RT Dose and Varian Eclipse may be utilised in planning of isolated metastases using single isocentre per target and non-coplanar dynamic arcs techniques if required to achieve optimal plan and OAR constraints. (ii) Number of treatment arcs and arrangement To facilitate treatment efficiency and to meet predefined dose constraints, TPS software automatically places a single virtual isocentre and utilises multiple dynamic arcs at multiple (non-coplanar) table angles (maximum 10 arcs at 5 table positions). Arcs will rotate backward and forward at the same couch position to ensure adequate coverage of metastases that may be occluding one another.
Sponsors
Icon Cancer Foundation
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Pathological evidence of a known non-haematological malignancy within 5 years of enrolment. • Three to ten metastatic brain lesions or surgical cavities which correlate with the confirmed non-haematological malignancy. • Total Planning Target Volume <15cc for single or three fraction treatment and <35cc for fractionated treatment (five fractions). • Largest single Planning Target Volume of unresected disease <10cc • Largest single Planning Target Volume of a resection cavity <15 cc • Age >18years • Participants 60 years of age or older must nominate a friend or relative whom will participate in the cognitive decline questionnaire sub-study. • Must be sufficiently proficient in English to complete neuropsychology tests
Exclusion criteria
• Cognitive impairment which may interfere with ability to participate in the neurocognitive assessments • Untreated clinically significant hydrocephalus • Haematological, Small cell, Germ Cell malignancy or unknown primary tumour • Leptomeningeal disease • Multiple new cranial nerve deficits in the absence of overt intracranial disease • Prior cranial irradiation which would compromise safety if overlapped with protocol treatment • Contra-indication for MRI and gadolinium contrast use: o Participants with a known risk of poor renal function must have an estimated Glomerular Filtration Rate >50 millilitres per minute o Known hypersensitivity to Gadolinium contrast o Non-MRI compatible VP shunt/surgical apparatus o Pacemaker/cardiac defibrillator not MRI compatible • Contra-indications to steroid support (e.g. active peptic ulceration or previous steroid psychosis)
Outcome results
None listed