Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

All of:

* No VCF
* Predominantly sclerotic lesion (as determined by the Investigator based on MRI)
* Normal spinal alignment
* \<50% vertebral body involvement

Any of:

* Pre-existing VCF
* Predominantly lytic lesion (as determined by the Investigator based on MRI)
* Spinal deformity
* ≥50% vertebral body involvement

Treatment will consist of image guided dose escalated SABR using a simultaneous integrated boost (SIB) delivered in two fractions adhering to organ at risk dose-volume histogram constraints. There will be three dose levels delivered to the Planning Target Volume_1 (PTV_1) in each treatment arm as follows: 28 Gy (14 Gy per fraction), 30 Gy (15 Gy per fraction) and 32 Gy (16 Gy per fraction). A lower dose of 20 Gy (10 Gy per fraction) will be delivered to the PTV_2 which will be defined according to international consensus guidelines (Cox et al., 2012). The dose to PTV_2 will remain the same through all dose levels. All doses are prescribed to the target volume.

Radiation: image guided dose escalated SABR using a simultaneous integrated boost (SIB)

Clare Faul, MBBS

This study will look at treatment for patients that have already been diagnosed with cancer, but develop a new tumor(s) in the spine. Patients who are not recommended for surgery are usually treated with 5-10 sessions of radiotherapy to manage symptoms. For patients with a longer life expectancy (\>6 months), it is better to give a higher dose of treatment to potentially improve the duration of pain relief, cancer control and potentially survival. Higher doses of radiotherapy, however, may also cause worse toxicity and side effects. This study will look at delivering higher doses of radiation in 2 sessions rather than 5-10, using a more modern, targeted technique called image-guided Stereotactic Ablative Body Radiotherapy (SABR). This method requires special equipment and expertise compared to the traditional radiotherapy and this has limited availability in Ireland. This study aims to find out the highest dose that is safe to be given to patients and carefully examine the side effects. These results will help create national and international guidelines to benefit all cancer patients. Patients will be monitored closely during treatment and for 2 years afterwards. Patients have been involved in developing the treatment protocol and the patient information leaflet. Patients will also be asked to fill in quality of life (QOL) questionnaires at certain timepoints during the study. It is anticipated that this study will support the delivery of high quality SABR to all cancer patients in Ireland, resulting in potentially better quality of life, symptom and tumor control.

Spine SABR - Dose-escalated Stereotactic Ablative Body Radiotherapy (SABR) for Solid Tumour Spine Metastases

Time-to-event analyses will be conducted for time to onset of ≥ Grade 2 VCF. Kaplan-Meier curves will be presented and median point estimates (with 95% Cis) will be reported. Patients free of an event at the time of analysis will be censored at last available assessment.

Cox proportional hazards regression will be used to assess baseline demographic or clinical variables as risk factors for post-SABR VCF and to develop a nomogram to estimate risk of VCF for future studies.

The mean and standard deviation (SD) of the overall and domain- and symptom-specific QoL outcomes at 6-months and 1-year post SABR (compared to baseline) using EORTC QLQ-BM22 scores at baseline and 6 months' post treatment will be reported. Scoring will be performed in accordance with the published guidelines.

DLT rate will be calculated as the proportion of evaluable patients (along with the 95% CI) experiencing a DLT, among the total evaluable patients.

All evaluable patients will be used in the DLT analysis which will be performed after they have been potentially followed for the 6-months observation period. Patients not evaluable will be reported separately. For each such patient, the reason for exclusion, protocol treatment received, and toxicities reported during the first year will be listed.

Post treatment response and outcomes using MRI at 3, 6, 9, 12, 15, 18, and 24 months post-RT will be evaluated.

The same patients used for DLT analysis will be used in these analyses. Radiation site (treated per study protocol) PFS (i.e. local PFS) at 1 year will be considered the key efficacy endpoint.

Local progression is progression within the radiation site treated per study protocol, as identified on serial imaging. When local progression is suspected, two or three MRI scans 6-8 weeks apart are recommended per Investigator discretion (in line with international consortium (SPINO guidelines) (Thibault et al., 2015)).

* Local control may be defined as the absence of progression within the radiation site treated per study protocol on serial imaging (MRI).
* Any new or progressive tumor within the epidural space
* Neurological deterioration attributable to pre-existing epidural disease with equivocal increased epidural disease dimensions on MRI

The Kaplan-Meier method will be used to estimate overall survival at each dose level. Cox proportional hazards regression will be used to characterise overall survival rate as a function of dose. Overall survival will be measured from the date of study registration until the date of death due to any cause or censoring.

Pain score (including acute pain flare) at the radiation site treated per study protocol (assessed by numerical pain rating score, 0-10) (time frame: 1 week post treatment). \[with secondary endpoint 4:\] The changes in raw scores and percent change will be assessed over time using the Wilcoxon Signed rank test.

Pain score (including acute pain flare) at the radiation site treated per study protocol (assessed by numerical pain rating score, 0-10) (time frame: 1 week post treatment). The changes in raw scores and percent change will be assessed over time using the Wilcoxon Signed rank test.

Counts and frequencies will be provided for the worst grade toxicity experienced by the patient. Acute toxicity profiles of ≥Grade 2 toxicities and their relatedness to study RT will be calculated, summarised and presented in tabular format with proportions, plus 95% confidence intervals where appropriate, at 1 and 4 weeks post treatment and at 3 months post-treatment using NCI CTCAE V5.

Counts and frequencies will be provided for the worst grade toxicity experienced by the patient. Late toxicity profiles of ≥Grade 2 toxicities at 6, 9, 12, 15, 18 and 24 months post treatment completion, will be calculated, summarised and presented in tabular format with proportions, plus 95% confidence intervals where appropriate, using NCI CTCAE V5.

Time-to-event analyses will be conducted for time to onset of the worst grade ≥2 and grade ≥3 acute toxicities separately. Kaplan-Meier curves will be presented and median point estimates (with 95% Cis) will be reported. Patients free of an event at the time of analysis will be censored at last available toxicity assessment. Time to toxicity will be measured from treatment start date. Patients alive and free of event at the time of analysis and patients lost to follow-up will be censored at the last available assessment.

Cancer Trials Ireland

All participants received SBRT at 600 cGy x 5 fractions

Post-operative, Stereotactic Body Radiation Therapy (SBRT)

Kristin Redmond, M.D.

Although it is being increasingly used off protocol, there is minimal data regarding the efficacy of stereotactic radiosurgery to the tumor bed following surgical resection of metastatic lesions to the spine. The primary objective of this study is to evaluate radiographic local recurrence in the tumor bed following stereotactic radiosurgery compared to the expected rate following conventional radiation therapy.

This is a phase II trial evaluating the rate radiographic local recurrence following post-operative stereotactic radiosurgery boost in patients with metastatic solid malignancies with spine metastases status post resection. Patients will be treated with 600 cGy x 5 fractions to the tumor bed and then followed both clinically and radiographically to determine if local recurrence following this treatment is better than might be expected for conventional radiation therapy.

Radiotherapy for Solid Tumor Spine Metastases

Phase II Study of Post-Operative Stereotactic Radiosurgery for Solid Tumor Spine Metastases

To estimate the rate of radiographic local recurrence at 12 months in patients treated with a post-operative stereotactic radiosurgery boost for resected spine metastases.

To estimate the time (in months) to radiographic local recurrence in patients treated with a post-operative stereotactic radiosurgery boost for resected spine metastases.

To estimate the rate of re-treatment at 12 months in patients treated with a post-operative stereotactic radiosurgery boost for resected spine metastases

To estimate the rate of symptomatic local recurrence at 12 months in patients treated with a post-operative stereotactic radiosurgery boost for resected spine metastases

Number of participants experiencing radiation myelopathy in patients treated with a post-operative stereotactic radiosurgery boost for resected spine metastases

Number of participants treated with a post-operative stereotactic radiosurgery boost for resected spine metastases, experiencing wound dehiscence.

Time in months to return to chemotherapy in patients treated with a post-operative stereotactic radiosurgery boost for resected spine metastases.

To evaluate the post-treatment symptomatic local recurrence in patients with radio-sensitive tumors.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Adverse Events were defined by Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC) criteria.

Post-operative, Stereotactic Body Radiation Therapy (SBRT): All participants received SBRT at 600 cGy x 5 fractions

Treatment

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

35 participants were enrolled and baseline data was collected on all 35. However, only 33 participants actually started treatment.

Terrence Caldwell

Number of Participants With Radiographic Recurrence at 12 Months

Time to Local Recurrence

Post-Operative Stereotactic Radiosurgery

Post-operative, Stereotactic Body Radiation Therapy (SBRT): All participants received SBRT at 600 cGy x 5 fractions

Number of Participants Receiving Re-treatment

Number of Participants With Symptomatic Recurrence

Number of Participants Experiencing Radiation Myelopathy

Number of Participants Experiencing Wound Dehiscence

Time to Return to Chemotherapy

Only 3 participants had radio-sensitive tumors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Spine SABR - Dose-escalated Stereotactic Ablative Body Radiotherapy (SABR) for Solid Tumour Spine Metastases	NCT06078813	Solid Tumor Spi...	Radiation: imag...	18 Years -	Cancer Trials Ireland
Radiotherapy for Solid Tumor Spine Metastases	NCT01752036	Solid Tumor Spi...	Post-operative,...	12 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Spine SABR - Dose-escalated Stereotactic Ablative Body Radiotherapy (SABR) for Solid Tumour Spine Metastases	NCT06078813	Solid Tumor Spi...	Radiation: imag...	18 Years -	Cancer Trials Ireland
Radiotherapy for Solid Tumor Spine Metastases	NCT01752036	Solid Tumor Spi...	Post-operative,...	12 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for solid tumor spine metastases