Particle-based Partial Tumor Irradiation of Unresectable Bulky Tumors

Inclusion Criteria:

1. Written informed consent obtained from the patient prior to performing anytreatment-related procedures.
2. Biopsy proven malignant unresectable solid bulky primary or recurrent tumor (diameterof at least 6 cm or greater, except for the Central Nervous System (CNS) tumors), orin a case of lack of recent biopsy progression on at least two consecutiveradiological examinations, with biopsy proof in the past. Presence of locally advanced (cN+) and/or metastatic disease will be accepted in order to allow for assessment ofthe abscopal effects.
3. Ineligibility for standard treatments including surgery, conventional (whole tumor)radiotherapy and systemic therapy, or being in progression or stable (with no responseto systemic treatment) under systemic therapy.
4. A minimum time interval from last dose of systemic therapy before radiotherapy of twoweeks; Systemic therapy may be resumed 4 weeks following radiotherapy in order topermit assessment of the treatment efficacy.
5. Median life expectancy of >2 months.
6. Age > 18 years.
7. Adequate bone marrow function as follows below: Haemoglobin ≥ 8.0 g/d; Absoluteneutrophil count (ANC) ≥ 1.5 x 10ꝰ/L (> 1500 per mm3); Platelet count ≥ 100 x 10ꝰ/L (>100,000 per mm3).
8. Female patients must either be of non-reproductive potential (i.e. post-menopausal byhistory: ≥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 ofbilateral oophorectomy) OR women of fertile age must have adequate conceptionprevention measures and must have a negative serum pregnancy test upon study entry.
9. Patient is willing and able to comply with the follow up including scheduled visitsand examinations.

Exclusion Criteria:

1. Patients without bulky lesions.
2. Tumors suitable for the standard therapies including surgery, conventional (wholetumor) irradiation and systemic therapies.
3. Median life expectancy of less than 2 months.
4. Contraindication to i.v. Computer Tomography and Magnetic Resonance Tomographycontrast medium administration, particularly estimated glomerular filtration rate (GFR) less than 45 mL/min/1.73 m2.
5. History of autoimmune disease.
6. Current or prior use of immunosuppressive medication within 14 days before enrollmentwith the exceptions of intranasal and inhaled corticosteroids or systemiccorticosteroids at physiological doses, which are not to exceed 10 mg/day ofprednisone, or an equivalent corticosteroid.
7. History of primary immunodeficiency.
8. History of allogeneic organ transplant.
9. Uncontrolled intercurrent comorbidity including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, uncontrolled hypertension, unstableangina pectoris, active bleeding diatheses including any patient known to haveevidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with studyrequirements or compromise the ability of the patient to give written informedconsent.
10. Female patients who are pregnant, breast-feeding or male or female patients ofreproductive potential who are not employing an effective method of birth control.
11. Any condition that, in the opinion of the investigator, would interfere withevaluation of study treatment or interpretation of patient safety or study results. (Note: criterion will be evaluated on the four eyes principle, evaluated by bothPrinciple Investigator and Sub-Investigators.)
12. Patients with uncontrolled seizures.