Immunotherapy Combined With Carbon Ion Radiotherapy for Locally Advanced Cervical Cancer

The primary objective of this study is to explore whether carbon ion radiotherapy combined with immunotherapy and chemotherapy can improve the 2-year progression-free survival (PFS) of patients with locally advanced cervical cancer (Stage IIB-IVA). The secondary objectives are to investigate whether this regimen can improve the 2-year overall survival (OS) of patients with locally advanced cervical cancer, and to evaluate the adverse events associated with carbon ion radiotherapy combined with immunotherapy and chemotherapy based on RTOG and CTCAE criteria.

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Tumour invasion of the rectum (Stage IVA) or peritoneal metastasis (M1).
• 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.
• 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).
• Prior history of non-infectious pneumonitis/interstitial lung disease requiring steroid treatment, or current active pneumonitis/interstitial lung disease.
• Active infection requiring systemic treatment.
• History of active hepatitis B (HBsAg positive) or active hepatitis C (detectable HCV RNA).
• 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.
• 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).
• Previous allogeneic tissue or solid organ transplantation.
• History of HIV infection.
• Metallic implants within the radiation field path that may compromise the accuracy of radiotherapy dose calculation.
• Subject requests withdrawal from the study.