Spatially targeted radiation followed by shorter or standard radiotherapy with iparomlimab and tuvonralimab for relapsed bulky solid tumors

Inclusion Criteria:

1. Age 18-75 years, male or female.
2. Histologically confirmed malignant tumor in the past.
3. Disease recurrence after treatment, including local regional relapsed and distant metastasis.
4. At least one measurable lesion with a maximum diameter greater than 6 cm, unsuitable for conventional surgery, ablation, or other treatments.
5. ECOG: 0-2 points.
6. Expected survival ≥3 months.
7. Washout period of previous anti-tumor treatment \>4 weeks.
8. The patient agrees and signs the informed consent form.
9. The function of vital organs meets the following requirements (no use of any blood components, cell growth factors, leukocyte boosters, platelet boosters, or anemia correction drugs within 14 days prior to the first use of the study drug):

   1. Absolute neutrophil count (ANC) ≥1.5×10\^9/L;
   2. Platelets ≥90×10\^9/L;
   3. Hemoglobin ≥8g/dL;
   4. Serum albumin ≥2.8g/dL;
   5. Total bilirubin ≤1.5×ULN, ALT, AST, and/or AKP ≤2.5×ULN; if liver metastasis is present, ALT and/or AST ≤5×ULN; if liver or bone metastasis is present, AKP ≤5×ULN;
   6. Serum creatinine ≤1.5×ULN or creatinine clearance rate greater than 60 mL/min;
   7. Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5×ULN (patients on stable doses of anticoagulation therapy such as low molecular weight heparin or warfarin with INR within the expected therapeutic range can be screened).
10. Negative pregnancy test for female subjects (for female patients of childbearing potential);
11. The subject voluntarily joins the study, signs the informed consent form, has good compliance, and cooperates with follow-up;
12. The investigator believes that the patient may benefit.

Exclusion Criteria:

1. History of severe immediate hypersensitivity reaction to any of the drugs used in this study.
2. Any of the following conditions within 6 months prior to screening: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. Patients known to have coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \<50% must be on an optimized stable medical regimen as determined by the treating physician; consultation with a cardiologist may be appropriate if necessary.
3. History of receiving anti-tumor vaccines or live vaccines within 4 weeks prior to the first dose of the investigational drug.
4. Active autoimmune diseases or history of autoimmune diseases that may recur. However, patients with the following conditions are not excluded and can proceed to further screening:

   1. Controlled Type 1 diabetes
   2. Hypothyroidism (if it can be controlled with hormone replacement therapy alone)
   3. Skin conditions that do not require systemic therapy (e.g., vitiligo, psoriasis, alopecia)
   4. Any other condition not expected to recur without external triggering factors
5. Lack of civil capacity or limited civil capacity.
6. Physical or mental conditions that impair the patient's ability to fully or adequately understand the potential complications of this study, as judged by the investigator.
7. Patients with an expected survival of less than 3 months.
8. Patients with significantly diminished cardiac, hepatic, pulmonary, renal, and bone marrow function.
9. Drug abuse or alcohol addiction.
10. Tumor lesions invading major blood vessels such as the internal carotid artery and vein and their major branches, posing a high risk of bleeding.
11. Subjects requiring systemic treatment with corticosteroids (more than 10mg/day prednisone equivalent dose) or other immunosuppressive agents within 2 weeks prior to the first use of the investigational drug, except for the use of corticosteroids for local esophageal inflammation and prevention of allergies and nausea/vomiting. Special cases need to be discussed with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal corticosteroid replacements at doses \>10mg/day prednisone equivalent are allowed.
12. History of immunodeficiency, including HIV-positive status, or other acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation.
13. Pregnant or breastfeeding female patients, male or female patients of childbearing potential who are unwilling or unable to use contraception for at least 1 year after the end of the treatment protocol throughout the study period.
14. The investigator deems the patient unsuitable for inclusion.