Immunotherapy Combined With Carbon Ion Radiotherapy for Locally Advanced Cervical Cancer

Prior treatment

• Presence of severe concomitant complications (e.g., uncontrolled cardiovascular disease, hypertension, diabetes mellitus, refractory infection, active peptic ulcer, uncontrolled psychiatric disorders, etc.)
• Concurrent active second primary malignancy.
• Prior receipt of immunotherapy agents (including anti-PD-1, anti-PD-L1, anti-CTLA-4, etc.).
• Prior radical surgery, radiotherapy, or systemic therapy (including investigational agents) for cervical cancer. Note: Conisation of the cervix is permitted.
• Administration of any investigational drug within 4 weeks before the initiation of immunotherapy.
• Confirmed immunodeficiency or receipt of chronic systemic corticosteroid therapy (prednisone equivalent dose \>10 mg/day) or other immunosuppressive therapy within 7 days prior to immunotherapy.
• Prior history of non-infectious pneumonitis/interstitial lung disease requiring steroid treatment, or current active pneumonitis/interstitial lung disease.
• Previous allogeneic tissue or solid organ transplantation.
• Metallic implants within the radiation field path that may compromise the accuracy of radiotherapy dose calculation.

Other illness

• History of grade ≥3 severe hypersensitivity reactions to immunotherapeutic agents.
• Active autoimmune disease requiring systemic therapy within the past 2 years (replacement therapies such as thyroxine, insulin and physiological glucocorticoids are excluded).
• Active infection requiring systemic treatment.
• History of active hepatitis B (HBsAg positive) or active hepatitis C (detectable HCV RNA).
• Known psychiatric illness or substance abuse that may impair subject compliance; pregnant or breastfeeding females, or those planning conception/pregnancy during the study period (from screening to 120 days after the last study treatment).
• History of HIV infection.

Lab values

• Any disease, treatment, laboratory abnormality or other condition that, in the investigator's judgement, may confound study results, hinder full study participation or pose additional risks to the subject.

Other

• Tumour invasion of the rectum (Stage IVA) or peritoneal metastasis (M1).
• Subject requests withdrawal from the study.

• Female patients aged ≥ 18 years at the time of signing the informed consent form.
• Histopathologically confirmed diagnosis of cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma).
• Stage IIB-IVA disease per the 2018 FIGO staging system.
• Presence of measurable lesions as defined by RECIST version 1.1.
• Patients reviewed by the carbon ion radiotherapy multidisciplinary team (MDT) with an indication for carbon ion radiotherapy.
• Patients voluntarily receiving carbon ion radiotherapy at Zhejiang Cancer Hospital and bearing all relevant treatment expenses.
• Complete clinical and imaging data available.
• Patients willing to participate in the trial and complete questionnaire surveys.
• Patients willing to participate in the trial and provide biospecimens, including cervical tissue, various body fluid specimens and tissue samples.
• Patients willing to attend regular standardised outpatient follow-up visits at our hospital.
• Eastern Cooperative 11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-2.
• No prior history of surgery, radiotherapy or chemotherapy for cervical cancer.
• Adequate function of major vital organs (bone marrow, liver, kidney, etc.), with laboratory values meeting the following criteria within 1 week prior to treatment: Absolute neutrophil count (ANC) ≥ 1500/μL; Platelet count ≥ 100,000/μL; Haemoglobin ≥ 9.0 g/dL (or ≥ 5.6 mmol/L); Creatinine clearance ≥ 50 mL/min; Total bilirubin ≤ 1.5 × upper limit of normal (ULN); if total bilirubin \> 1.5 × ULN, direct bilirubin shall be ≤ ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; International Normalised Ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (excluding patients receiving anticoagulant therapy within the therapeutic range).
• Estimated overall survival ≥ 6 months.