SBRT-based PArtial Tumor Irradiation of HYpoxic Segment

Inclusion Criteria:

* Metastatic biopsy proven malignant cancer with at least one "bulky" (diameter of at least 6 cm or greater) lesion, or in the case of a biopsy missing for any reason-progression of the suspicious lesion evaluated on at least 2 consecutive radiological examinations,
* Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluation,
* Ineligibility for systemic therapy or being in progression under systemic therapy,
* A minimum time interval of four weeks from the last dose of systemic therapy before radiotherapy,
* Median life expectancy of \>3 months,
* Age \> 18 years at the time of study entry,
* Adequate bone marrow function: Haemoglobin ≥ 9.0 g/dL, absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3), platelet count ≥ 100 x 109/L (\>100,000 per mm3),
* Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry,
* Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.

Exclusion Criteria:

* Patients without metastatic cancer (regional metastatic lymph nodes considered as metastatic),
* Patients without bulky lesions,
* Median life expectancy of less than three months,
* Patients with prior radiation therapy to the same site,
* Contraindication to IV iodine contrast medium administration, particularly estimated glomerular filtration rate (GFR) less than 45 mL/min/1.73 m2,
* History of autoimmune disease,
* Current or prior use of immunosuppressive medication within 28 days before enrollment with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid,
* History of primary immunodeficiency,
* History of allogeneic organ transplant,
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent,
* Known history of previous clinical diagnosis of tuberculosis,
* History of leptomeningeal carcinomatosis,
* Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control,
* Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results,
* Subjects with uncontrolled seizures.