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Bone metastases occur frequently during the evolution of solid tumors, either isolated or associated with visceral metastases. The incidence varies between 20 and 85% depending on the primary cancer. Breast, prostate, and lung cancers are responsible for 70% of bone metastases. Cancer with bone metastases compared to other metastatic sites is considered as associated with a better prognosis, particularly for breast and prostate cancer. Bone metastases may be present at diagnosis (synchronous metastasis) or appear at a later time (metachronous metastasis).
The concept of "oligometastases" was proposed in patients with about 3 up to 5 metastases (without restriction on the primary site) and associated with an intermediate prognosis. It was hypothesized that local treatment with curative intent, aiming at the few metastatic sites, would yield long-term survival probabilities, along with systemic therapies.
Long-term survivors have been reported after curative-intent treatment of metastasis in sarcoma and colorectal cancers with liver or lung metastasis. We chose to focus on bone metastasis because of their high incidence, their impact on the patient's quality of life and autonomy, and their accessibility to potentially curative radiotherapy.
The systemic treatment of metastatic cancer includes hormonal therapy (breast and prostate cancer), biologically-targeted drugs and chemotherapy (all cancers).
Stereotactic radiotherapy is a highly accurate technique was initially developed for performing the radiosurgery of brain tumors in patients for whom it was deemed be too difficult to proceed to classical excision surgery. In this process, a high total dose of radiation is delivered in a single fraction to a well-defined intra-cranial target. The concept of radiotherapy in stereotactic conditions was extended to one or several fractions delivered to small volumes primary tumors/ metastases in extra-cranial sites (Stereotactic Body RadioTherapy [SBRT]). At present, high control rates have been achieved for lung metastases. Similarly, very high local control rates have been reported in bone metastases after stereotactic radiotherapy.
In this protocol, our purpose is to demonstrate, via a randomized phase III trial, that high doses of radiotherapy, delivered in stereotactic conditions to the bone metastases (between 1 and 5 metastases) in solid tumor patients is able to improve the survival without progression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Systemic treatment + SBRT | Experimental | Systemic treatment and SBRT to the bone metastases. Two SBRT schemes are allowed: 9 Gy x 3 fractions or 7 Gy x 5 fractions for axial and appendicular bones metastases. The choice is at the discretion of the investigator. |
|
| Systemic treatment | No Intervention | Palliative radiotherapy on bone metastases is allowed if necessary (pain, fracture, spinal cord compression…) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SBRT | Radiation | SBRT will be added to systemic (standard) treatment of bone metastases. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival | To evaluate the impact of SBRT on Progression-Free Survival (PFS) at 1 year according to RECIST 1.1 and PERCIST 1.0 Criteria | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| PFS at 2 and 3 years | Progression-Free Survival (PFS) at 2 and 3 years will be evaluated according to RECIST 1.1 and PERCIST | 2 years and 3 years after treatment |
| Bone progression free survival at 1, 2 and 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sebastien Thureau, MD | Centre Henri Becquerel | Principal Investigator |
| Jean-Christophe Faivre, MD | Institut de Cancérologie de Lorraine - Alexis Vautrin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ICO - Site Paul Papin | Angers | France | ||||
| Centre Marie Curie |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33541288 | Derived | Thureau S, Marchesi V, Vieillard MH, Perrier L, Lisbona A, Leheurteur M, Tredaniel J, Culine S, Dubray B, Bonnet N, Asselain B, Salleron J, Faivre JC. Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS). BMC Cancer. 2021 Feb 4;21(1):117. doi: 10.1186/s12885-021-07828-2. |
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Distant bone progression at 2 and 3 years will be evaluated according to RECIST Criteria 1.1 and at 1 year according to RECIST Criteria 1.1 and PERCIST
| 1, 2 and 3 years after treatment |
| Local control at 1, 2 and 3 years | Local control will be evaluated at 1, 2 and 3 years according to RECIST Criteria 1.1 and PERCIST | 1, 2 and 3 years after treatment |
| Cancer-specific survival | The length of time from the start of treatment for the disease until the death identified as being due to the specified cancer. | 1, 2 and 3 years after treatment |
| Overall survival | The length of time from the start of treatment for the disease until patients are still alive. | 1, 2 and 3 years after treatment |
| SBRT toxicities | according CTCAE 4.0 scale | 1, 2 and 3 years after treatment |
| Patient's Quality of life | self-administered questionnaire | at baseline, 6 weeks after randomization, and 3 months, 6 months and 1, 2 and 3 years after treatment |
| Pain score | according to Numeric Scale related to pain medication | at baseline, once a week during 2 weeks and 6 weeks after randomization, and at 3 months, 6 months and 1, 2 and 3 years after treatment |
| Cost utility | QALYs (Quality-Adjusted Life Years) and ICERs (Incremental Cost-Effectiveness Ratios) calculation based on EQ-5D-3L questionnaire. | 6 weeks after randomization |
| Arras |
| France |
| Hôpital Privé Les Bonnettes | Arras | France |
| Institut Sainte Catherine | Avignon | France |
| Centre Pierre Curie | Beuvry | France |
| Clinique Ambroise Pare | Beuvry | France |
| Clinique Tivoli Ducos | Bordeaux | France |
| Institut Bergonié | Bordeaux | France |
| Hôpital Métropole Savoie | Chambéry | France |
| Pôle Leonard de Vinci | Chambray-lès-Tours | France |
| Centre Amethyst CROM | Creil | France |
| Hôpital Henri Mondor | Créteil | France |
| Centre Léonard de Vinci | Dechy | France |
| Institut de Cancérologie de Bourgogne | Dijon | France |
| Chu Grenoble | Grenoble | France |
| Centre Oscar Lambret | Lille | France |
| Hôpital Privé Le Bois | Lille | France |
| Centre Léon Bérard | Lyon | France |
| Institut Paoli Calmettes | Marseille | France |
| Centre de Cancérologie du Grand Montpellier | Montpellier | France |
| Institut de Cancérologie de Lorraine | Nancy | France |
| Institut de Cancérologie de l'Ouest | Nantes | France |
| Centre Catalan D'Oncologie | Perpignan | France |
| Institut Jean Godinot | Reims | France |
| Centre Henri Becquerel | Rouen | France |
| Centre d'oncologie et radiothérapie Saint-Jean | Saint-Doulchard | France |
| GCS RISSA - Institut de cancérologie Paris Nord | Sarcelles | France |
| Clinique des dentellières | Valenciennes | France |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D008175 | Lung Neoplasms |
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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