Neoplasms

Nervous System Diseases

All Conditions

Musculoskeletal Diseases

Spinal Cord Neoplasms

Spinal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Spinal Cord Diseases

Central Nervous System Diseases

Bone Neoplasms

Bone Diseases

Spinal Diseases

Hypofractionated stereotactic radiosurgery

Cyberknife stereotactic radiosurgery

Yongye Chen, MS

This study aims to explore the reliability of the combination of functional magnetic resonance imaging and radiomics for evaluation of the therapeutic efficacy of CyberKnife stereotactic radiosurgery for spinal tumors. Accurate imaging assessment can help clinicians plan personalized therapeutic schedules for patients with spinal tumors .

Spinal tumors may be metastases or primary tumors; the former are more common. About 40% of cancer patients will have spinal metastasis. Primary spinal tumor is relatively rare, accounting for only about 8% of spinal tumors. For both metastasis and primary tumor, the aim of treatment is to reduce pain, maintain or improve neurological function, and maintain or restore spinal stability.

In patients who cannot undergo surgery or need additional treatment after surgery, radiation therapy can relieve pain, prolong survival, improve the success rate of surgery, and reduce risk of metastasis and recurrence. However, the complex anatomy of the spine, and the numerous important organs around it, makes radiation treatment challenging. High-dose radiation therapy is necessary for long-term control of the tumor and for prevention of spinal column instability; however, this is impossible with traditional radiotherapy due to the presence of the radiosensitive spinal cord. Outcomes therefore tend to be poor for large and complex lesions. The CyberKnife-a stereotactic body radiation therapy (SBRT) platform that combines a lightweight linear accelerator, a robotic arm, an imaging system, and a respiratory tracking system-offers a feasible approach. It can achieve submillimeter level-precision treatment under imaging guidance.

Currently, the effectiveness of CyberKnife radiosurgery for spinal tumors is decided by assessing imaging changes, relief of clinical symptoms, and needle biopsy, but all of these methods have limitations. On imaging, for example, change in lesion volume is used to assess tumor regression, but the size of a spinal tumor is not easy to measure and, moreover, decrease in tumor volume after treatment may take time . Post-treatment signal intensity changes in conventional magnetic resonance imaging (MRI) T1-weighted and T2-weighted sequences are difficult to interpret, and their relationship with treatment efficacy is also not clear.

Generally speaking, alterations in microscopic structure and biological activity of the tumor occur much earlier than changes in gross morphology . Functional magnetic resonance imaging (fMRI) can therefore be more useful than conventional MRI for assessing treatment response. In fMRI, sequences such as diffusion-weighted imaging (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and diffusion kurtosis imaging (DKI) reflect functional information of tissues from different perspectives.

Application of artificial intelligence technology for analysis of medical imaging data is now an area of intense research. This new method, which is called radiomics, can help in solving many difficult clinical problems. By extracting a large number of highly representative quantitative imaging features from high-throughput medical image data, radiomics can help in evaluating treatment efficacy and predicting prognosis of spinal tumors.

Investigators intend to explore the use of the combination of fMRI and radiomics for evaluating the effectiveness of CyberKnife radiosurgery for spinal tumors. The method will be able to evaluate both volume and functional changes in the tumor, and thus provide important information for planning of individualized therapeutic schedules for patients with spinal tumors.

Evaluation of Effectiveness of CyberKnife Stereotactic Radiosurgery for Spinal Tumors

Functional Magnetic Resonance Imaging Combined With Radiomics for Evaluation of Effectiveness of CyberKnife Stereotactic Radiosurgery for Spinal Tumors

The time from the start of treatment to the date of death or last follow-up

The time from the start of treatment to the date of diagnosis of tumor progression or death. Tumor progression is defined as increase in lesion volume on MRI compared to baseline, or identification of new metastasis on imaging or histological examination.

A 11 point scale where the end points are the extremes of no pain and pain as bad as it could be, or worst pain.

The QLQ-C30 is a cancer-specific, self-administered, structured questionnaire designed for use in clinical trials, which contains 30 questions (items),

Peking University Third Hospital

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

36.25 Gy delivered in 5 fractions of 7.25 Gy per fraction in patients with low and intermediate risk prostate cancer.

36.25 Gy delivered in 5 fractions of 7.25 Gy per fraction

CyberKnife Stereotactic Radiosurgery

Robert Meier, MD

Irving Kaplan, MD

Martin Sanda, MD

The purpose of this study is to determine the effects of CyberKnife radiosurgery in patients with early stage organ-confined prostate cancer.

The CyberKnife Robotic Radiosurgery System is a unique radiosurgical system capable of treating tumors anywhere in the body noninvasively and with sub-millimeter accuracy. The CyberKnife System delivers radiation using a precise targeting methodology allowing a focal treatment margin around the target, thus limiting the volume of adjacent tissue receiving high doses radiation. This in turn allows the delivery of high doses of radiation to the prostate over a short series of treatments.

CyberKnife Radiosurgery for Organ-Confined Prostate Cancer: Homogenous Dose Distribution

Prospective Evaluation of CyberKnife Stereotactic Radiosurgery for Low and Intermediate Risk Prostate Cancer: Homogenous Dose Distribution

To estimate the rates of acute and late Grade 3-5 gastrointestinal and genitourinary toxicities (adverse events \[AE\]) observed during the 5 years following CyberKnife (CK) treatment for prostate cancer. Kaplan Meier estimates for 5-yr and 10-yr are reported.

Adverse events occurring within 3 months of treatment were categorized as acute toxicities, and those developing after 3 months were considered late toxicities.

The rates were determined using the first Grade 3 or higher adverse event per patient, reported as possibly, probably, or definitely related to CK treatment.

The Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 was used to determine the Grade or severity of adverse events in this study, with Grade 3 being severe or medically significant but not immediately life-threatening, Grade 4 being life-threatening and Grade 5 being death related to the adverse event.

To determine the rate of biochemical Disease-Free Survival (bDFS), using the Phoenix definition, following CyberKnife treatment. Kaplan Meier estimates for 5-yr and 10-yr are reported.

The Phoenix definition uses a Prostate Specific Antigen (PSA) value exceeding the patient's lowest PSA value (nadir) + 2 ng/mL as an indicator of disease recurrence. The percentage of patients who did not have such a PSA rise or receive any interventional therapy to treat prostate cancer are reported below.

To determine the rates of local failure, distant failure, disease-free survival, disease-specific survival, and overall survival following CyberKnife treatment in prostate cancer patients. Kaplan Meier estimates for 5-yr and 10-yr are reported.

AUA-SI is a 7-item self-report measure used to assess urinary urgency, frequency, and voiding symptoms with scores ranging from 0 (no symptom) to 5 (symptom occurs almost always).

Total score: 0-7 mild symptoms; 8-19 moderate symptoms; 20-35 severe symptoms

EPIC-26 is a short form version of the Expanded Prostate Cancer Index Composite, and is a validated comprehensive instrument developed to measure the health-related quality of life among men with prostate cancer. EPIC-26 consists of 26 items under 5 domains of urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal.

Answers qualitatively measure patient's bother for each symptom and are then normalized on a scale of 0 (worst) to 100 (best) to calculate domain scores if sufficient input is provided.

Accuray Incorporated

All adverse events were collected. Serious Adverse Events reported in clinicaltrials.gov are all events meeting serious criteria regardless of causality.

Low and intermediate risk patients received 36.25 Gy delivered in 5 fractions of 7.25 Gy per fraction

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black/African American

Hispanic/Latino

Native Hawaiian or Other Pacific Islander

White

Unknown

Race/Ethnicity, Customized

United States

Region of Enrollment

T1b = Tumor incidental histological finding in >5% of tissue resected

T1c = Tumor identified by needle biopsy found in one or both sides, but not palpable

T2a = Tumor involves ½ of one side or less

T2b = Tumor involves >½ of one side but not both sides

Clinical T category of prostate cancer, estimated by investigator at the time of patient screening.

Clinical Stage (Tumor)

Gleason 2 - 6

Gleason 7

The Gleason score is calculated by adding together the two grades of cancer cells that make up the largest areas of the biopsied tissue sample. The Gleason score usually ranges from 6 to 10. Cancer cells that look similar to healthy cells receive a low score. Cancer cells that look less like healthy cells or look more aggressive receive a higher score.

Patients with Gleason scores 2-6 are in the Low Risk Group. Patients with Gleason scores of 7 are in the Intermediate Risk Group.

Total Gleason Score

Prostate Specific Antigen (PSA)

0 = Fully active, able to carry on all pre-disease performance without restriction

1 = Restricted in physically strenuous activity

2 = Capable of all selfcare but unable to carry out any work activities

3 = Capable of only limited selfcare

Unreported

The ECOG Performance Status Scale describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.).

It was developed by the ECOG and published in 1982.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Low: Clinical Stage (CS) T1b-T2a, Gleason 2-6, Prostate Specific Antigen (PSA) ≤ 10 ng/ml

Intermediate: CS T2b, Gleason 2-6, PSA ≤ 10 ng/ml

Intermediate: CS T1b-T2b, and Gleason 2-6, PSA ≤ 20 ng/ml

Intermediate: CS T1b-T2b and Gleason 7, PSA ≤ 10 ng/ml

American Joint Committee on Cancer (AJCC) 6th Edition Risk Group

A limitation of this study is that of the 21 sites originally enrolling eligible patients, only 14 opted to continue beyond year 5. While 189 patients were followed through year 5, only 135 of these consented to continued follow-up. We also note that several patients were due for their 10-year follow-up during Coronavirus Disease (COVID) lockdowns, hampering study activities such as monitoring visits as well as patient compliance with protocol-required visit windows.

Director of Clinical Affairs

Probability of experiencing Acute GI Grade 3+ event(s)

Probability of experiencing Acute GU Grade 3+ event(s)

Probability of experiencing Late GI Grade 3+ events 5 years post treatment

Probability of experiencing Late GU Grade 3+ events 5 years post treatment

Probability of experiencing Late GI Grade 3+ event(s) at 10 years post CK treatment

Probability of experiencing Late GU Grade 3+ event(s) at 10 years post CK treatment

Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity

Probability of remaining disease-free at 5 years post-CyberKnife treatment

Probability of remaining disease-free at 10 years post-CyberKnife treatment

Biochemical Disease-Free Survival (bDFS)

Probability of remaining free from Local Failure at 5 years post-CyberKnife treatment

Probability of remaining free from Local Failure at 10 years post-CyberKnife treatment

Probability of remaining free from Distant Failure at 5 years post-CyberKnife treatment

Probability of remaining free from Distant Failure at 10 years post-CyberKnife treatment

Probability of remaining free from disease at 5 years post-CyberKnife treatment

Probability of remaining free from disease at 10 years post-CyberKnife treatment

Probability of remaining free from prostate cancer at 5 years post-CyberKnife treatment

Probability of remaining free from prostate cancer at 10 years post-CyberKnife treatment

Probability of Overall survival at 5 years post-CyberKnife treatment

Probability of Overall survival at 10 years post-CyberKnife treatment

Disease Control and Survival Outcomes

Baseline

Last Day of Treatment

1 Week Post Treatment

1 Month Post Treatment

3 Months Post Treatment

6 Months Post Treatment

12 Months Post Treatment

18 Months Post Treatment

24 Months Post Treatment

36 Months Post Treatment

48 Months Post Treatment

60 Months Post Treatment

72 Months Post Treatment

84 Months Post Treatment

96 Months Post Treatment

108 Months Post Treatment

120 Months Post Treatment

AUA questionnaires were completed by patients for milestone follow-up visits, with 306/310 patients completing a baseline questionnaire. All questions needed to be completed in order to calculate the score. Scores obtained per instructions (if possible) and analyzed even if questionnaires were received/dated outside protocol specified visit window.

Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI)

EPIC questionnaires were completed by patients at follow-up visits, with 300/310 patients completing a baseline questionnaire. A minimum number of questions needed to be completed within each domain in order to calculate a domain score. Domain scores obtained per instructions (if possible) and analyzed even if questionnaires were received/dated outside protocol specified visit window.

Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence

Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive

Quality of Life Assessments: EPIC-26 Bowel

Quality of Life Assessments: EPIC-26 Sexual

Overall Study

This treatment concentrates large doses of radiation onto the tumor so that injury from radiation to the nearby normal tissue will be minimal. CyberKnife Stereotactic Radiosurgery is not investigational and is considered standard of care.

Five treatments given over about one week.

Mary Monahan

The purpose of this study is to find out the effects (good and bad) of highly focused radiation on you and your prostate cancer. The purpose of this evaluation is to see if this treatment causes fewer side effects that other standard treatment approaches, and to evaluate the effect of this treatment on your prostate tumor and your quality of life over time.

Stereotactic Body Radiotherapy for Stage I-III Prostate Cancer

Function-Preserving Stereotactic Body Radiotherapy for Clinical State I-III Prostate Cancer

Measure quality of life after five years following cyberknife stereotactic radiosurgery.

In the low- and intermediate-risk prostate cancer groups, to determine whether study treatment improves patient-reported quality of life outcomes compared to the approach used in a previous multi-center cyberknife stereotactic radiosurgery trial.

In the high-risk group, to estimate rates of acute and late grade 3-5 gastrointestinal and genitourinary toxicities following cyberknife stereotactic radiosurgery.

After five years following cyberknife stereotactic radiosurgery, estimate rates of toxicities related to treatment.

Measure disease free survival after five years following cyberknife stereotactic radiosurgery.

Measure overall survival after five years following cyberknife stereotactic radiosurgery.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Effectiveness of CyberKnife Stereotactic Radiosurgery for Spinal Tumors	NCT04192383	Spinal Neoplasm...	Cyberknife ster...	-	Peking University Third Hospital
CyberKnife Radiosurgery for Organ-Confined Prostate Cancer: Homogenous Dose Distribution	NCT00643994	Prostate Cancer Prostatic Cance... Prostate Neopla... Prostatic Neopl... Cancer of the P...	CyberKnife Ster...	18 Years -	Accuray Incorporated
Evaluation of Effectiveness of CyberKnife Stereotactic Radiosurgery for Spinal Tumors	NCT04192383	Spinal Neoplasm...	Cyberknife ster...	-	Peking University Third Hospital
Stereotactic Body Radiotherapy for Stage I-III Prostate Cancer	NCT02334579	Prostate Cancer Prostatic Cance... Prostate Neopla... Prostatic Neopl... Cancer of the P...	CyberKnife Ster...	18 Years -	Swedish Medical Center

Spots Global Cancer Trial Database for cyberknife stereotactic radiosurgery