Pulmonary Resectable Osteosarcoma Treated by Metastasectomy and Pre-operative Immunotherapy and Stereotactic Body Radiotherapy (PROMIS): a Prospective Clinical Trial

Inclusion Criteria:

1. Written informed consent signed before any trial-related procedures are carried out.
2. Histologically confirmed osteosarcoma, with a diagnosis of pulmonary metastaseswithout the existence of local recurrence (previous re-resection of local recurrencewith wide margin is allowed).
3. Resectable pulmonary nodule(s), defined as nodule(s) that are removable by wedgeresection/ segmentectomy/lobectomy without necessitating a total pneumonectomy (e.g.,nodules immediately adjacent to the main stem bronchus or main pulmonary vessels), andno evidences of malignant pleural effusion.
4. Participants have received at least one standardized systemic treatment regimen at thetime of enrollment, and have not received gemcitabine in the past.
5. Patient has adequate pulmonary function eligible for one-staged or two-staged thoracicsurgery.
6. Aged no less than 10 years old and no more than 65 years old;
7. For patients ≥16 years old, ECOG score is between 0 and 2 (for patients withamputations, if they can basically take care of themselves and can move freely formore than 50% of their waking hours with the assistance of stretchers, walkers,wheelchairs, etc.) still included);
8. For patients under 16 years old, Lansky score is at least 70 or above (for patientswith amputations who are unable to participate in active recreational activities dueto amputation, if they can participate in most active recreational activities with theassistance of walkers, wheelchairs, etc., they are still eligible included).
9. The expected survival time is greater than 24 weeks;
10. The majority of the recurrent lesions with an established radiological diagnosis couldreceive SBRT;
11. Major organ functions meet basic safety standards within 7-14 days before treatment.
12. Women of childbearing age should agree that they must use contraceptive measures (suchas intrauterine devices, birth control pills or condoms) during the study and within 6months after the end of the study; if in doubt, serum or urine tests within 7 daysbefore study enrollment The pregnancy test is negative and the patient must benon-lactating; the male should agree that contraceptive measures must be used duringthe study period and within 6 months after the end of the study period;
13. If there are recurrent lesions previously treated by surgery, radiofrequency ablationor radiotherapy:
14. If the image of the metastatic lesion is stable, enrollment is allowed and SBRTis not required for that lesion;
15. If the metastatic lesion has image progression, if it was previously treated withsurgery and SBRT can be performed, enrollment is allowed; if it was previouslytreated with radiofrequency ablation or radiotherapy, if repeat SBRT can beconsidered, enrollment is still allowed.

Exclusion Criteria:

1. Diagnosed with malignant diseases other than tumors within 5 years before the firstdose;
2. Currently participating in interventional clinical research treatment, or havereceived other research drugs or used research equipment within 4 weeks before thefirst dose;
3. Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2drugs or drugs targeting another stimulating or synergistic inhibition of T cellreceptors (e.g., CTLA-4, OX-40, CD137) drug and secondary resistance to the drug (i.e., the best efficacy evaluation is CR, PR or SD lasting more than 4 months, butsecondary tumor resistance develops after treatment).
4. Received systemic systemic treatment with Chinese patent medicines with anti-tumorindications or drugs with immunomodulatory effects (including thymosin, interferon,interleukin, except local use to control pleural effusion) within 2 weeks before thefirst dose;
5. Active autoimmune disease requiring systemic treatment (such as use ofdisease-modifying drugs, glucocorticoids, or immunosuppressants) within 2 years beforethe first dose. Replacement therapies (such as thyroxine, insulin, or physiologicalglucocorticoids for adrenal or pituitary insufficiency, etc.) are not consideredsystemic treatments;
6. Are receiving systemic glucocorticoid treatment (excluding nasal spray, inhaled orother route of topical glucocorticoids) or any other form of immunosuppressive therapywithin 7 days before the first dose of the study;
7. Known allogeneic organ transplantation (except corneal transplantation) or allogeneichematopoietic stem cell transplantation;
8. Known to be allergic to any components of monoclonal antibody preparations (haveexperienced grade 3 or above allergic reactions);
9. Have not fully recovered from toxicity and/or complications caused by any interventionbefore initiating treatment (i.e., ≤Grade 1 or reaching baseline, excluding fatigue oralopecia);
10. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV1/2 antibodypositive);
11. Get live vaccine within 30 days before the first dose (cycle 1, day 1);
12. Pregnant or lactating women;
13. Any serious or uncontrollable systemic disease