Background
Methods
Objectives
Study design
Study population
Initial inclusion criteria
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Patient age ≥ 18 years.
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1–3 painful bone metastasis(-es) requiring treatment in the ribs, clavicles, scapulae, or sternum; if more than 1 metastasis can be treated within the same treatment field, it will be counted as 1 metastatic site for the purpose of trial treatment.
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Bone metastases that can be treated within a field size up to 7.5 cm x 30 cm without overlap of other radiation fields.
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Life expectancy > 6 months (in the judgment of the investigator).
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Patients who are able to comply with the protocol.
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Provision of signed and dated informed consent form.
Final inclusion criteria
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A clinically acceptable FLASH treatment plan.
Exclusion criteria
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> 3 painful bone metastases of the thorax requiring palliative RT. If > 1 metastasis can be treated within the same treatment field, it will be counted as one metastatic site for the purpose of trial treatment; patients with > 3 painful bone metastases in the thorax requiring treatment are more likely to have generalized thoracic pain that may confound measurement of pain relief response to treatment.
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Overlap of FLASH radiation fields with any previous or planned radiation fields to the same site.
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Patients with pathologic bone fractures in the treatment field.
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Patients with metal implants in the treatment field (proton range and dosimetry are less certain in the presence of metal).
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Patients with symptomatic pneumonitis at the time of screening, or a history of symptomatic radiation pneumonitis.
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Patients with known contraindications to thoracic radiation.
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Patients who received or will receive cytotoxic chemotherapy and/or any prescribed systemic therapy known to impact tissue response to radiation within 2 weeks prior or 1 week following their planned radiation treatment (concurrent therapies may affect the tissue response to radiation).
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Prior local therapy modality to the treatment site(s) within 2 weeks of study enrollment that, in the judgment of the investigator, might compromise interpretation of pain response.
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Patients with persistent toxicity ( except for alopecia and peripheral neuropathy) grade > 1 from prior systemic therapy that is within the proposed treatment field.
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Patients with pacemakers or other implanted devices at risk of malfunction during RT.
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Patients with any other medical condition or laboratory value that would, at the discretion of the investigator, preclude the patient from participating in this clinical investigation.
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Patients at known risk of enhanced normal tissue sensitivity to RT due to inherited predisposition or documented comorbidity that might lead to hypersensitivity to ionizing radiation.
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Patients enrolled in any other clinical studies that the investigator believes to conflict with this clinical investigation.
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Patients who are pregnant or nursing.
Intervention
CT simulation and planning target volume (PTV)
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If the maximum target excursion is > 10 mm, an abdominal compression approach will be used to reduce the extent of motion. An additional 4DCT scan of the subject with abdominal compression will then be acquired and used for treatment planning in combination with an Internal Target Volume (ITV) approach due to residual target motion.
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If the subject’s motion cannot be reduced to less than 10 mm, the subject will be withdrawn from the study and replaced.
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If the maximum target excursion is ≤ 10 mm, the existing 4DCT scan will be used for treatment planning (using an ITV approach). No additional motion mitigation strategies (beyond the ITV approach used in planning) are required.
Treatment planning
Tissue | Volume | Volume Max (Gy) | Max point dose (Gy) | Potential Adverse Outcome (≥ Grade 3) per TG101 |
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Spinal Cord | < 1.2 cc | 7 | 14 | Myelitis |
Lung (Right and Left) | 1500 cc | 7 | NA-Parallel tissue | Basic Lung Function |
Lung (Right and Left) | 1000 cc | 7.4 | NA-Parallel tissue | Pneumonitis |
Lung (Right and Left) | 37% | 8 | NA-Parallel tissue | Pneumonitis |
Heart/pericardium | 15 cc | 16 | 22 | Pericarditis |
Esophagus | 5 cc | 11.9 | 15.4 | Stenosis/fistula |
Radiotherapy quality assurance (QA)
FLASH therapy
Follow-up
Treatment Simulation to Treatment Delivery (≤ 10 business days) | Post Treatment Follow-up | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Event | Enrollment, baseline (1–2 weeks) | Prep for treat-ment | Prior to treatment delivery (Day 1) | Treatment delivery (Day 1) | After treatment delivery (Day 1) | Day 2 - Day 11 (daily)1 | Day 2 (± 1 calendar day) | Day 7 (± 2 business days) | Day 15 (± 2 business days) | Month 1 (± 5 business days) | Months 2, 3, 6, 9, 12, then every 6 months |
Patient screening (initial inclusion/ exclusion criteria) | X | ||||||||||
Informed consent | X | ||||||||||
Demographics | X | ||||||||||
Disease information | X | ||||||||||
CT-based simulation | X | ||||||||||
Treatment planning | X | ||||||||||
Treatment plan QA | X | ||||||||||
FLASH treatment delivery | X | ||||||||||
Questionnaire for pain flare assessment | X | X | |||||||||
Questionnaire for overall pain assessment | X | X | X | X | X | ||||||
Questionnaire for pain assessment at treated sites | X | X | X | X | X | ||||||
Subject evaluation2 | X | X | X | X | X | X | |||||
Review of pain medication (including steroid medications) | X | X | X | X | X | X | |||||
AE evaluation3 | X | X4 | X | X | X | X |
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Subject characteristics: date of birth, sex, ethnicity, race, history of medical comorbidities or genetic or autoimmune disorders, diagnosis date, and prior cancer-directed treatments.
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Tumor characteristics: histology, anatomic location of the original primary tumor and the anatomic location of treatment site(s), target lesion size, and radiographic appearance of the target (e.g., lytic, sclerotic).
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Baseline data specific to outcome assessments: performance status, photographs of skin and any physical findings on examination involving the skin or other normal tissue in the planned treatment site(s), and information about treatment for other bone metastases not treated as part of this study.
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Pain medications (including narcotics, gabapentin class drugs, other non-narcotic analgesics, and steroid medications).
Outcomes
Toxicity
Efficacy
Clinical workflow
Stopping rules
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2 out of 6 study participants, or if 3 or more study participants, experience grade 3 or higher toxicity that is possibly, probably, or definitely related to study treatment;
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1 subject experiences a grade 5 AE, unless probably or definitely related to the underlying disease, complications of subsequent cancer therapies, or extraneous causes;
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A major device malfunction in dose delivery occurs (as indicated by the dose monitoring system). This includes potential recordable or reportable medical events under the Ohio Department of Health classification.