Ablative Radiosurgery vs Stereotactic RT in 5 Fractions With SIB for Oligometastatic Bone Lesions

Официальное название

A Randomised, Prospective, Monoinstitutional Study of Ablative Radiosurgery vs Stereotactic Radiotherapy in 5 Fractions, With Simultaneous Integrated Boost, for the Treatment of Bone Lesions in Oligometastatic Disease

Обзор

This is a randomised prospective monoinstitutional study comparing radiosurgery at a total dose up to 24 Gy to five fraction stereotactic radiotherapy with simultaneous integrated boost (SIB) up to 50 Gy for the treatment of bone metastases in oligometastatic cancer treated with radical intent. At the end of the first 12 months from the start of the study an interim analysis will be performed taking into account all major endpoints for an initial evaluation of the study , with only an observational purpose, without subsequent protocol changes.

Подробное описание

The study is interventional, homogeneous (performed in a single institution). Patient recruitment Patients who meet the inclusion criteria will be enrolled during the initial Radiation Oncology examination in our institution or during the multidisciplinary meeting.

Recruitment and selection The patients will be informed of the possibility to participate in the study. I pazienti verranno informati ella possibilità di accedere allo studio. After a careful verification of the inclusion and exclusion criteria, and precise description of the benefits, risks and procedure of the current study, the patient will be asked to sign the informed consent and subsequently randomised.

The following information will be collected for each patient, as is standard practice in our department: demographic data, clinical history, concomitant medical treatments, physical exam, blood exam, tumoral markers, diagnoses CT / Bone scintigraphy/ MRI/ PET and any other staging exam or post tumoral treatment re-evaluation performed.

Randomisation A centralized randomization, with closed envelopes, will be performed by a secretary not involved in the study.

Pre-treatment phase Each patient will undergo the simulation CT, in line with routine clinical practice, with immobilisation devices within 15 (+/- 5) days from the randomisation. The simulation CT will be performed in the Radiotherapy department, the MRI in the Radiology department.

Treatment phase The protocol treatment uses two radiotherapy regimens with ablative doses, which are already included in the daily clinical practice at San Raffaele Scientific Institute and many other national centers equipped with High Technology. The treatment machine will be randomly assigned, depending on the availability of slots for the timing required by the protocol.

The patients will be randomized at a 1:1 ratio between:

* Arm A: radiosurgery ( in one fraction) to the bone metastases ( 21-24 Gy in 1 fraction) * Arm B: Multifractionated ablative stereotactic radiotherapy (5 fractions, one fraction per day, 5 consecutive weekdays) with SIB to the bone metastases (up to 40-50 Gy).

The treatment should be completed within 1 month from the CT simulation and within 45 (+/- 5) days from randomization (first visit).

Post-treatment phase:

Patients will be evaluated according to departmental clinical practice: at the first visit, at the end of the treatment and at follow-up visits at 3, 6, 12, 18, 24, 36 months from the end of radiotherapy with CT and/or Bone Scan and/or MRI and/or PET/CT based on the treated sites, on the histology of primary tumor, and by means of laboratory exams. Subsequent radiological images of laboratory analyses will be performed at the discretion of the radiation oncologist, based on symptoms or clinical findings. At every visit the anamnesis, physical examination, the CTCAE(Common Terminology Criteria for Adverse Events) toxicity evaluation will be performed and registered, together with any skeletal events, re-irradiation, other systemic therapy lines, or palliative treatment. The patient will fill in the Pain Diary and the quality of life questionnaires (EORTC QLQ-C30, QLQBM22, and EQ-5D-3L). The follow-up visits will be performed in the dedicated rooms of the Radiation Oncology department.

Вмешательства

• Лучевая терапия radiosurgery and stereotactic ablative radiotherapy with simultaneous integrated boost, respectively
  Two protocols of stereotactic ablative radiotherapy, in one vs five fractions ( the later with SIB) are compared

Первичные конечные точки

• Local recurrence-free surival [Срок оценки: 3 years from the end of treatment]

Вторичные конечные точки (9)

• Acute and late local toxicity [Срок оценки: Changes form baseline at 3 years from the end of treatment]
• Pain control [Срок оценки: Changes form baseline at 3 years from the end of treatment]
• Overall survival [Срок оценки: 3 years from the end of treatment]
• Cancer Specific Survival [Срок оценки: 3 years from the end of treatment]
• Progression to polymetastatic disease [Срок оценки: 3 years from the end of treatment]
• Adjusted disease-free survival [Срок оценки: 3 years from the end of treatment]
• Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-C30 [Срок оценки: Changes from baseline at 3 years after the treatment]
• Incidence of Treatment-Emergent Adverse Events as assessed by EORTC-QLQ-BM22 [Срок оценки: Changes from baseline at 3 years after the treatment]
• Satisfaction assessed by EQ-5D-3L [Срок оценки: Changes from baseline at 3 years after the treatment]

Критерии участия

Критерии включения

• Performance status ECOG ≤2
• Life expectancy > 6 months according to Mizumoto criteria\*
• Oligometastatic disease (Total number of metastases from 1 to 5: both synchronous and metachronous with maximum involvement of three organs in total - lymph nodes, bones, lungs, liver, adrenal gland, brain- with known histology
• At least one bone metastasis treatable with SABR or SRS
• Each secondary localization (synchronous, metachronous or oligoprogressive) must be treated with radical intent.
• Patients may have received other anticancer treatments (surgery for initial site of disease or other metastases, chemotherapy, radiotherapy for other metastatic sites)

Критерии исключения

• Sites of disease not eligible for stereotactic radiotherapy
• Serious medical comorbidities that preclude RT
• Overlap with a previously treated volume of radiotherapy
• Dimension greater than 5 cm for extra-cranial lesions.
• Size greater than 3 cm for brain lesions
• More than 1 brain metastases
• Clinical or radiological evidence of spinal cord compression or epidural tumor within 2mm of the spinal cord
• Radiological evidence of vertebral body fracture or involvement of more than 40% of the vertebral body
• Radiological evidence of cortical involvement in long bones
• Pregnant or breastfeeding women

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

Италия · 1 центр

• San Raffaele Scientific Institute — Milan

Публикации

• Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10. doi: 10.1200/JCO.1995.13.1.8. No abstract available. PMID 7799047
• Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr; International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg. 1997 Jan;113(1):37-49. doi: 10.1016/s0022-5223(97)70397-0. PMID 9011700
• Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, Mendez Romero A, Nevens D, Palma D, Park C, Ricardi U, Scorsetti M, Yu J, Woodward WA. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiother Oncol. 2020 Jul;148:157-166. doi: 10.1016/j.radonc.2020.04.003. Epub 2020 Apr 22. PMID 32388150
• Lehrer EJ, Singh R, Wang M, Chinchilli VM, Trifiletti DM, Ost P, Siva S, Meng MB, Tchelebi L, Zaorsky NG. Safety and Survival Rates Associated With Ablative Stereotactic Radiotherapy for Patients With Oligometastatic Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2021 Jan 1;7(1):92-106. doi: 10.1001/jamaoncol.2020.6146. PMID 33237270
• Zelefsky MJ, Yamada Y, Greco C, Lis E, Schoder H, Lobaugh S, Zhang Z, Braunstein S, Bilsky MH, Powell SN, Kolesnick R, Fuks Z. Phase 3 Multi-Center, Prospective, Randomized Trial Comparing Single-Dose 24 Gy Radiation Therapy to a 3-Fraction SBRT Regimen in the Treatment of Oligometastatic Cancer. Int J Radiat Oncol Biol Phys. 2021 Jul 1;110(3):672-679. doi: 10.1016/j.ijrobp.2021.01.004. Epub 2021 PMID 33422612
• Ryu S, Jin R, Jin JY, Chen Q, Rock J, Anderson J, Movsas B. Pain control by image-guided radiosurgery for solitary spinal metastasis. J Pain Symptom Manage. 2008 Mar;35(3):292-8. doi: 10.1016/j.jpainsymman.2007.04.020. Epub 2008 Jan 22. PMID 18215498
• Ryu S, Jin JY, Jin R, Rock J, Ajlouni M, Movsas B, Rosenblum M, Kim JH. Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery. Cancer. 2007 Feb 1;109(3):628-36. doi: 10.1002/cncr.22442. PMID 17167762
• Zeng KL, Tseng CL, Soliman H, Weiss Y, Sahgal A, Myrehaug S. Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Spine Metastases: An Overview. Front Oncol. 2019 May 1;9:337. doi: 10.3389/fonc.2019.00337. eCollection 2019. PMID 31119099

Идентификаторы

NCT: NCT05679427 · ONES Trial

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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