Intraoperative Radiotherapy in Treating Spinal Metastases

Официальное название

The Efficacy and Safety of Intraoperative Radiotherapy Vesus Stereotactic Body Radiotherapy in Managing Spinal Metastases: A Prospective, Single-center, Open-label, Non-inferior, Randomized Controlled Trial

Обзор

In order to provide theoretical evidence for the comprehensive and standardized treatment of spinal metastases with pathological fractures and/or spinal cord compression, the investigators conduct this trial to investigate the efficacy and safety of IORT and postoperative SBRT in adjuvant treatment of metastatic spinal tumors after posterior decompression surgery by recruiting patients with spinal metastases who met the inclusion criteria, and randomly divided them into the following treatment cohorts: 1) decompression surgery + IORT (15-20 Gy, 20-50min）; 2) decompression surgery and postoperative SBRT(30Gy, 5 fractions, 3 weeks).

Подробное описание

Spine is the most common metastatic site for advanced malignancies, accounting for about 70% of all patients with bone metastasis. Approximately 40% -70% of patients with advanced cancer eventually develop spinal metastases.

Spinal metastases require multidisciplinary treatments, and surgical decompression surgery is the preferred treatment in managing spinal metastases with bone related events, especially those with spinal cord compression. The purpose of decompression surgery is to directly relieve nerve compression, alleviate pain, rebuild spinal stability, and reduce tumor burden, which improves the quality of life, and extend the life span indirectly.

At the same time, radiotherapy is also an indispensable treatment for spinal metastases after surgical decompression. The purpose of radiotherapy is to remove residual tumor lesions, alleviate pain, and prevent further pathological fractures. Recent years have witnessed the rapid development of stereotactic bone radiotherapy (SBRT). As reported, SBRT can not only increase the radiation dose at the tumor site, but also reduce radiation damage to the spinal cord and surrounding normal tissues, which is the preferred adjuvant treatment for patients with metastatic spinal tumors. However, SBRT has the several risks, including radiation myelitis, delayed vertebral pathological fractures, local skin allergies, radiotherapy side effects in the esophagus and lungs, and duodenal perforation. Moreover, stereotactic radiotherapy technology has higher costs compared to traditional external beam radiotherapy.

Recently, the application of intraoperative radiotherapy (IORT) can effectively reduce the direct radiation for surrounding normal tissues and maximally eliminate the residual tumor cells. The advantages of IORT include: ① immediate reduction of the possibility of tumor cell expansion after surgery; ② Safe direct radiation and effective protection of normal tissues beyond the radiation depth; ③ To effectively protect adjacent normal tissues, light-limiting tubes with different diameters can be selected based on the size and range of tumor; ④ Shortening treatment course with lower costs and better compliance; ⑤ Slight systemic side effects and bone marrow suppression.

To the knowledge, no research focuses on the efficacy of IORT and SBRT in the adjuvant treatment of spinal metastases. Therefore, in order to provide theoretical evidence for the comprehensive and standardized treatment of spinal metastases with pathological fractures and/or spinal cord compression, the investigators conduct this trial to investigate the efficacy and safety of IORT and postoperative SBRT in adjuvant treatment of metastatic spinal tumors after posterior decompression surgery by recruiting patients with spinal metastases who met the inclusion criteria, and randomly divided them into the following treatment cohorts: 1) decompression surgery + IORT (15-20 Gy, 20-50min）; 2) decompression surgery and postoperative SBRT(30Gy, 5 fractions, 3 weeks).

Вмешательства

• Лучевая терапия Intraoperative radiotherapy (IORT)
  Intraoperative radiotherapy (IORT, 15-20 Gy, 20-50min)
• Лучевая терапия Stereotactic body radiotherapy (SBRT)
  postoperative stereotactic body radiotherapy (SBRT, 30Gy, 5 fractions, 3 weeks)

Первичные конечные точки

• Local control rate [Срок оценки: 2 years]

Вторичные конечные точки (4)

• Health-related quality of life [Срок оценки: 2 years]
• Progression-free survival [Срок оценки: 2 years]
• Overall survival [Срок оценки: 2 years]
• Radiation-related complications [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Clinical diagnosis of spinal metastases;
• Estimated survival time more than 3 months;
• The spinal instability neoplastic score (SINS) >12;
• The general condition allows to recieve surgery;
• Single or multiple metastatic lesions with only one site presenting epidural spinal cord compression;
• signed informed consent.

Критерии исключения

• Clinical diagnosis of primary spinal tumors;
• Presence of metastases in central nerve system;
• Isolated lesion undergoing en bloc resection;
• Mental disorder and/or intellectual dificiency;
• Refusing to accept follow-up;
• without signing informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Changzheng Hospital — Шанхай

Публикации

• Barzilai O, Laufer I, Yamada Y, Higginson DS, Schmitt AM, Lis E, Bilsky MH. Integrating Evidence-Based Medicine for Treatment of Spinal Metastases Into a Decision Framework: Neurologic, Oncologic, Mechanicals Stability, and Systemic Disease. J Clin Oncol. 2017 Jul 20;35(21):2419-2427. doi: 10.1200/JCO.2017.72.7362. Epub 2017 Jun 22. PMID 28640703
• Laufer I, Rubin DG, Lis E, Cox BW, Stubblefield MD, Yamada Y, Bilsky MH. The NOMS framework: approach to the treatment of spinal metastatic tumors. Oncologist. 2013 Jun;18(6):744-51. doi: 10.1634/theoncologist.2012-0293. Epub 2013 May 24. PMID 23709750
• Calvo FA. Intraoperative irradiation: precision medicine for quality cancer control promotion. Radiat Oncol. 2017 Feb 2;12(1):36. doi: 10.1186/s13014-017-0764-5. PMID 28148287
• Vaidya JS, Bulsara M, Baum M, Alvarado M, Bernstein M, Massarut S, Saunders C, Sperk E, Wenz F, Tobias JS; TARGIT-A investigators. Intraoperative radiotherapy for breast cancer: powerful evidence to change practice. Nat Rev Clin Oncol. 2021 Mar;18(3):187-188. doi: 10.1038/s41571-021-00471-7. No abstract available. PMID 33495552
• Barzilai O, McLaughlin L, Amato MK, Reiner AS, Ogilvie SQ, Lis E, Yamada Y, Bilsky MH, Laufer I. Predictors of quality of life improvement after surgery for metastatic tumors of the spine: prospective cohort study. Spine J. 2018 Jul;18(7):1109-1115. doi: 10.1016/j.spinee.2017.10.070. Epub 2017 Nov 6. PMID 29122701
• Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, Mohiuddin M, Young B. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005 Aug 20-26;366(9486):643-8. doi: 10.1016/S0140-6736(05)66954-1. PMID 16112300
• Correia D, Moullet B, Cullmann J, Heiss R, Ermis E, Aebersold DM, Hemmatazad H. Response assessment after stereotactic body radiation therapy for spine and non-spine bone metastases: results from a single institutional study. Radiat Oncol. 2022 Feb 21;17(1):37. doi: 10.1186/s13014-022-02004-7. PMID 35189919
• Thibault I, Chang EL, Sheehan J, Ahluwalia MS, Guckenberger M, Sohn MJ, Ryu S, Foote M, Lo SS, Muacevic A, Soltys SG, Chao S, Gerszten P, Lis E, Yu E, Bilsky M, Fisher C, Schiff D, Fehlings MG, Ma L, Chang S, Chow E, Parelukar WR, Vogelbaum MA, Sahgal A. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SP PMID 26678212

Идентификаторы

NCT: NCT06093854 · 2022SL052

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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