A Dose-escalation Trial of Stereotactic Ablative Body Radiotherapy for Non-spine Bone & Lymph Node Oligometastates

Stereotactic ablative body radiotherapy (SABR) can be considered for patients with so-called "oligometastatic" disease. However, since this is a relatively new technique, information on the optimal scheduling is lacking. Even prospective randomized trials on SABR for oligometastases typically allow different fractionation schedules to be used. This is especially true for non-spine bone and lymph node metastases, where the literature is scarce to non-existent. There is also emerging evidence that SABR can stimulate the immune response, by a variety of mechanisms such as increasing TLR4 expression on dendritic cells, increasing priming of T cells in draining lymph nodes, and increasing tumor cell antigen presentation by dendritic cells. Again, it is not clear which fractionation schedule elicits the most robust immune response. Therefore, it is opportune to compare the most commonly used stereotactic regimens regarding toxicity, efficacy, and immune priming. This trial is a non-randomized prospective phase I trial determining a regimen of choice for patients with non-spine bone and lymph node oligometastases (≤ 3 lesions). The metastatic lesion(s) must be visible on CT and \< 5 cm in largest diameter. A total of ninety patients will be consecutively included in three different fractionation regimens. They will be offered stereotactic ablative radiotherapy to all metastatic lesions in 5, 3 or 1 fractions. Dose-limiting toxicity (DLT), defined as any acute grade 3 or 4 toxicity, will be recorded as the primary endpoint. Overall acute and late toxicity, quality of life, local control, and progression-free survival are secondary endpoints. Liquid biopsies will be collected throughout the course of this trial, i.e. at simulation, after each fraction and at 6 months after the end of the radiotherapy. Translational research will focus on assessment of circulating cytokines and flow cytometry analysis of immune cells.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Patients ≥ 18 years old with histologically confirmed malignancy.
* Patients with radiosensitive malignancy (e.g. breast, prostate,…) and oligometastases (i.e. ≤ 3 metastases) OR patients with radioresistant malignancy (e.g. renal cell carcinoma, melanoma,…) and an unlimited number of metastases.
* Metastatic lesion must be visible on CT and \< 5 cm in largest diameter.
* Patients with ECOG performance status ≤ 1.
* Patients who have received the information sheet and signed the informed consent form.
* Patients must be willing to comply with scheduled visits, treatment plan, and other study procedures.
* Patients with a public health insurance coverage.

Exclusion Criteria:

* Patients with life expectancy \< 6 months.
* Patients with previous radiotherapy to the metastatic area excluding stereotactic re-irradiation to the required dose level.
* Patients with significantly altered mental status or with psychological, familial, sociological or geographical condition potential hampering compliance with the study.
* Individual deprived of liberty or placed under guardianship.

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