Clinical trial NCT03963713: Stereotactic Radiotherapy and Image-guided Intensity Modulated Radiotherapy for Spinal Metastatic Tumors
Official title: Stereotactic Radiotherapy and Conventionally-fractionated-image-guided Intensity Modulated Radiotherapy for Spinal Metastatic Tumors：A Prospective Multicenter Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Radiotherapy
Spine Metastases
Radiosurgery
Keywords: Stereotactic radiotherapy
Intensity modulated radiotherapy
spinal metastatic tumors
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Mianyang Central Hospital
name: Second Hospital of Shanxi Medical University
name: Qingdao chengyang hospital
name: Qingdao Hiser Medical Group
name: Beijing 302 Hospital
name: Guangxi Ruikang Hospital
name: Third Affiliated Hospital of Guizhou Medical University
name: Panjin Liaohe Oilfield Gem Flower Hospital
name: Tang-Du Hospital
First posted: 2019-05-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: non-randomized trial
Primary purpose: TREATMENT

Brief summary: Data of 100 patients with spinal metastatic tumor who received stereotactic radiotherapy or conventionally-fractionated image-guided intensity-modulated radiotherapy in the multi-center of the research group from July 2019 to June 2021 will be collected, as well as their follow-up data.Previous treatment and follow-up data will be analyzed to evaluate the clinical efficacy comparison of stereotactic radiotherapy and conventionally-fractionated image-guided intensity-modulated radiotherapy for spinal metastatic tumors, local control rate and side effects, and to clarify the effectiveness and safety of different doses of radiotherapy.

Detailed description: In this study, Data of 100 patients with spinal metastatic tumor who received stereotactic radiotherapy or conventionally-fractionated image-guided intensity-modulated radiotherapy in the multi-center of the research group from July 2019 to June 2021 will be collected, as well as their follow-up data.The metastases were treated with SBRT.Using multimodal image fusion to outline the target area.PTV = GTV + 0-10mm Target volume radiation dose: The range of BED value of radiotherapy was 60-72 when the distance between the tumor and gastrointestinal tract or spinal cord was more than 5 mm (alpha/beta=10) and 51.3-59.5 when the distance between the tumor and gastrointestinal tract or spinal cord was less than 5 mm (alpha/beta=10).The metastases were treated with Conventionally-fractionated image- guided Intensity modulated radiotherapy.Using multimodal image fusion to outline the target area.The dose of the target volume radiotherapy dose is 30 Gy/10f or 40Gy/20f.Previous treatment and follow-up data will be analyzed to evaluate the clinical efficacy comparison of stereotactic radiotherapy and conventionally-fractionated image-guided intensity-modulated radiotherapy for spinal metastatic tumors, local control rate and side effects, and to clarify the effectiveness and safety of different doses of radiotherapy.

Eligibility criteria: Inclusion Criteria:

* 18-80 years old;
* Spine metastatic tumor patients confirmed by pathology and imaging; Number 3; Surgical treatment is not possible due to iatrogenic or (and) personal factors;
* Spinal metastasis after previous systemic treatment or progression after previous treatment of spinal metastasis;
* The anatomy of the spinal metastases form Tomita parting Ⅰ type - Ⅲ type; Without systemic metastasis or metastasis, the lesion was controlled.
* ECOG physical condition score: 0-1, Karnofsky score 60, able to withstand puncture;
* Expected survival 3 months;
* Main organ function is good, without serious hypertension, diabetes and heart disease.
* Has signed informed consent;
* The compliance was good and the family members agreed to follow up for survival.

Exclusion Criteria:

* Of the anatomy of the spinal metastases form Tomita classification: Ⅳ, Ⅴ Ⅵ, Ⅶ.
* Participated in other drug clinical trials within four weeks; There was a history of bleeding, and any bleeding event with severe grade of CTCAE5.0 or above occurred within 4 weeks before screening;
* Screening of patients with known central nervous system metastasis or a history of central nervous system metastasis. For patients with clinical suspected central nervous system metastasis, CT or MRI examination must be performed within 14 days before randomization to exclude central nervous system metastasis.
* Patients with hypertension who cannot obtain good control by single antihypertensive drug treatment (systolic blood pressure \>140mmHg, diastolic blood pressure \>90mmHg); Having a history of unstable angina pectoris; Patients newly diagnosed with angina within 3 months before screening or myocardial infarction within 6 months before screening; Arrhythmia (including QTcF: 450ms in male and 470ms in female) requires long-term use of anti-arrhythmia drugs and New York heart association grade II cardiac dysfunction;
* Long-term unhealed wounds or incomplete fracture healing;
* Imaging showed that the tumor had invaded important blood vessels or the researchers judged that the patient's tumor had a very high possibility to invade important blood vessels during the treatment and cause fatal bleeding;
* Coagulation function is unusual, have haemorrhage tendency person (before random 14 days must satisfy: below the circumstance that does not use anticoagulant INR is in normal value range); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; The use of low-dose warfarin (1mg oral, once daily) or low-dose aspirin (no more than 100mg daily) for preventive purposes is permitted on the premise that the international standardized ratio of prothrombin time (INR) is 1.5;
* Screening for the occurrence of hyperactive/venous thrombosis events in the first 6 months, such as cerebrovascular accidents (including temporary ischemic attack), deep vein thrombosis (except for venous thrombosis caused by intravenous catheterization in the early stage of chemotherapy, which was determined by the researchers to have recovered) and pulmonary embolism, etc.
* Thyroid function was abnormal in the past and could not be kept within the normal range even in the case of drug treatment.

  (10) Attending has a history of psychotropic drug abuse, and can't attend or has mental disorder;
* Always half a year after spinal tumors or other close to the spine tumor lesion lesions radiation;
* Immunodeficiency disease, or has other acquired, congenital immunodeficiency disease, or has a history of organ transplantation;
* Judgment according to the researchers, there is serious to endanger the safety of patients or patients completed the research associated with disease.

Primary outcomes:
measure: Cancer pain score
timeFrame: 1 year after the treatment
measure: Muscle strength and muscle tension grading
timeFrame: 1 year after the treatment
measure: JOA score of cervical and lumbar vertebrae
timeFrame: 2 years after the treatment
measure: Quality of Life Score of Tumor Patients(0-60)
timeFrame: 2 years after the treatment
Secondary outcomes:
measure: Duration of pain response
timeFrame: 1 years after the treatment
measure: Overall survival
timeFrame: 3 years after the treatment
measure: Local control rate
timeFrame: 3 years after the treatment
measure: Adverse reactions
timeFrame: 6 months after the treatment
measure: Progression-free survival
timeFrame: 3 years after the treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: BeiJing
country: China
facility: The fifth medical center of PLA general hospital
state: Beijing
city: NanNing
country: China
facility: Guangxi ruikang hospital
state: Guangxi
city: GuiYang
country: China
facility: Third Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Panjin
country: China
facility: GEM flower hospital of Liaohe oil field Tang-Du Hospital
state: Liaoning
city: Qingdao
country: China
facility: Hiser Medical Center of Qingdao
state: Shandong
city: Qingdao
country: China
facility: Qingdao chengyang people's hospital
state: Shandong
city: TaiYuan
country: China
facility: Second hospital of Shanxi Medical University
state: Shanxi
city: Xian
country: China
facility: Tangdu hospital
state: Shanxi
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
Study officials:
affiliation: Peking University Third Hospital
name: Junjie Wang, MD
role: STUDY_CHAIR
affiliation: Peking University Third Hospital
name: Fei Xu, M Med
role: STUDY_DIRECTOR
affiliation: Peking University Third Hospital
name: Hongqing Zhuang, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Mianyang Central Hospital
name: Xiaobo Du, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mianyang Central Hospital
name: Jie Li, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Hospital of Shanxi Medical University
name: Xiang Song, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Hospital of Shanxi Medical University
name: Lei Zhang, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Qingdao chengyang people's hospital
name: Jianguo Zhang, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Qingdao Hiser Medical Group
name: Peng Liu, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing 302 Hospital
name: Xuezhang Duan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangxi Ruikang Hospital
name: Zuping Lian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Third Affiliated Hospital of Guizhou Medical University
name: Liang Liu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Panjin Liaohe Oilfield Gem Flower Hospital
name: Longhai Shen, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Tang-Du Hospital
name: Dongjie He, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Third Hospital
name: Xuemin Li, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Third Hospital
name: Yi Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Massicotte E, Foote M, Reddy R, Sahgal A. Minimal access spine surgery (MASS) for decompression and stabilization performed as an out-patient procedure for metastatic spinal tumours followed by spine stereotactic body radiotherapy (SBRT): first report of technique and preliminary outcomes. Technol Cancer Res Treat. 2012 Feb;11(1):15-25. doi: 10.7785/tcrt.2012.500230.
citation: Sahgal A, Whyne CM, Ma L, Larson DA, Fehlings MG. Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases. Lancet Oncol. 2013 Jul;14(8):e310-20. doi: 10.1016/S1470-2045(13)70101-3.
citation: Rades D, Stalpers LJ, Veninga T, Schulte R, Hoskin PJ, Obralic N, Bajrovic A, Rudat V, Schwarz R, Hulshof MC, Poortmans P, Schild SE. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. J Clin Oncol. 2005 May 20;23(15):3366-75. doi: 10.1200/JCO.2005.04.754.
citation: Gong Y, Wang J, Bai S, Jiang X, Xu F. Conventionally-fractionated image-guided intensity modulated radiotherapy (IG-IMRT): a safe and effective treatment for cancer spinal metastasis. Radiat Oncol. 2008 Apr 22;3:11. doi: 10.1186/1748-717X-3-11.
citation: Guckenberger M, Goebel J, Wilbert J, Baier K, Richter A, Sweeney RA, Bratengeier K, Flentje M. Clinical outcome of dose-escalated image-guided radiotherapy for spinal metastases. Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):828-35. doi: 10.1016/j.ijrobp.2008.11.017. Epub 2009 Feb 26.
citation: Zhang M, Chen YR, Chang SD, Veeravagu A. CyberKnife stereotactic radiosurgery for the treatment of symptomatic vertebral hemangiomas: a single-institution experience. Neurosurg Focus. 2017 Jan;42(1):E13. doi: 10.3171/2016.9.FOCUS16372.
citation: Gandhidasan S, Ball D, Kron T, Bressel M, Shaw M, Chu J, Chander S, Wheeler G, Plumridge N, Chesson B, David S, Siva S. Single Fraction Stereotactic Ablative Body Radiotherapy for Oligometastasis: Outcomes from 132 Consecutive Patients. Clin Oncol (R Coll Radiol). 2018 Mar;30(3):178-184. doi: 10.1016/j.clon.2017.11.010. Epub 2017 Dec 8.
citation: Ryu S, Rock J, Rosenblum M, Kim JH. Patterns of failure after single-dose radiosurgery for spinal metastasis. J Neurosurg. 2004 Nov;101 Suppl 3:402-5.
citation: Chang EL, Shiu AS, Mendel E, Mathews LA, Mahajan A, Allen PK, Weinberg JS, Brown BW, Wang XS, Woo SY, Cleeland C, Maor MH, Rhines LD. Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine. 2007 Aug;7(2):151-60. doi: 10.3171/SPI-07/08/151.
citation: Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine (Phila Pa 1976). 2007 Jan 15;32(2):193-9. doi: 10.1097/01.brs.0000251863.76595.a2.
citation: Wowra B, Zausinger S, Drexler C, Kufeld M, Muacevic A, Staehler M, Tonn JC. CyberKnife radiosurgery for malignant spinal tumors: characterization of well-suited patients. Spine (Phila Pa 1976). 2008 Dec 15;33(26):2929-34. doi: 10.1097/BRS.0b013e31818c680a.
citation: Expert Panel on Radiation Oncology-Bone Metastases; Lo SS, Lutz ST, Chang EL, Galanopoulos N, Howell DD, Kim EY, Konski AA, Pandit-Taskar ND, Rose PS, Ryu S, Silverman LN, Sloan AE, Van Poznak C. ACR Appropriateness Criteria (R) spinal bone metastases. J Palliat Med. 2013 Jan;16(1):9-19. doi: 10.1089/jpm.2012.0376. Epub 2012 Nov 20.