This purpose of this study is to assess the feasibility of FLASH radiotherapy for the palliative treatment of painful bone metastases. FLASH radiotherapy is radiation treatment delivered at ultra-high dose rates compared to conventional radiation treatment.

This clinical investigation is designed to assess the workflow feasibility of FLASH radiotherapy treatment in a clinical setting, as well as the toxicities, and pain relief when used to treat bone metastasis(-es) in the extremities (excluding feet, hands, wrists). FLASH radiotherapy has been shown in preclinical studies to cause less injury to surrounding normal tissues during radiation treatment, while still having similar tumor cell killing. Patients at least 18 years of age with painful bone metastases located in the limbs will be considered for the study. These patients represent an ideal population for a feasibility study of FLASH radiotherapy as they are known to benefit from the palliative effects of radiotherapy using single dose radiation regimens of 8Gy which is what is being used in this investigation. After treatment, patients will be assessed for pain response as well as any adverse side-effects of radiation. The workflow feasibility of the treatment will also be evaluated.

Inclusion Criteria:

• Patient age at least 18 years
• Up to 3 painful bone metastasis(-es) in the extremities
• Bone metastases that can be treated using pre-defined treatment field sizes (7.5 cm x 7.5 cm; 7.5 cm x 10 cm; 7.5 cm x 12 cm; 7.5 cm x 14 cm; 7.5 cm x 16 cm; 7.5 cm x 18 cm; 7.5 cm x 20 cm), without overlap of radiation fields
• Life expectancy of >2 months (in the judgement of the investigator)
• Patients who are able to comply with the protocol
• Provision of signed and dated informed consent form

Exclusion Criteria:

• Prior radiotherapy to the treatment site(s)
• Lesions of the feet, hands, wrists are not eligible treatment sites for FLASH
• More than 3 painful bone metastases of the limbs requiring palliative radiotherapy
• Tumor lysis of >50% of the circumferential bone cortex, or other factors considered to place the subject at significant risk of pathologic fracture
• Patients with bone fractures and/or metal implants in the treatment field
• Patients who will receive cytotoxic chemotherapy within 1 week prior to or 1 week following their planned radiation treatment
• Prior local therapy modality to the treatment site(s) within 2 weeks of study enrollment
• Patients with pacemakers or other implanted devices at risk of malfunction during radiotherapy
• Patients with any other medical condition or laboratory value that would, at the discretion of the investigator, preclude the patient from participation in this clinical investigation
• Patients at known risk of enhanced normal tissue sensitivity to radiotherapy due to inherited predisposition or documented comorbidity that might lead to hypersensitivity to ionizing radiation
• Patients enrolled in any other clinical studies the investigator believes to be in conflict with this clinical investigation.
• Patients who are pregnant or nursing

Adverse event data was collected at Day 2, 15, Months 1, 2, 3, long term, or subject death/lost to follow up, up to 17.8 months (for the longest follow up). Length of follow up for each subject is as follows: #1: 2.3 months, #2: 16.5 months, #3: 17.8 months, #4: 9.3 months, #5: 3 months, #6: 4.5 months, #7: 8.5 months, #8: 16 months, #9: 12 months, #10: 17.8 months.

All AEs were collected and classified per CTCAE version 5.0. However, only those AEs and SAEs that were attributed by the investigators to be possibly, probably, or definitely related to FLASH radiotherapy were used for the assessment of toxicity of the FLASH treatment. There were no SAEs attributed to FLASH treatment, and the 7 AEs attributed to FLASH treatment were listed in the table as "Treatment Related". The remaining AEs in the table were unrelated to FLASH.