Toripalimab for High-risk Locally Advanced Cervical Cancer

Inclusion Criteria:

1. Patients with histologically confirmed cervical squamous cell carcinoma,adenocarcinoma, or adenosquamous carcinoma.

2. FIGO 2018 staging criteria classifying the disease as stages III-IVA.

3. Age range from 18 to 70 years inclusive.

4. No prior receipt of surgery, radiotherapy, or systemic anticancer therapy for thetreatment of cervical cancer.

5. No previous exposure to the study drug.

6. Presence of at least one measurable or evaluable lesion as per RECIST version 1.1,with the measurable lesion exhibiting a longest diameter of ≥10 mm on spiral CT scanor a shortest diameter of ≥15 mm for enlarged lymph nodes, which has not beenpreviously irradiated.

7. Absence of central nervous system diseases, both primary and metastatic.

8. WHO/ECOG performance status score of 0-1.

9. Anticipated survival duration of at least 12 weeks.

10. Adequate organ function within the following parameters (without the use of anyblood components, cytokines, or growth factors within 14 days prior torandomization):

11. Absolute neutrophil count (ANC) ≥1.5×10^9/L

12. Platelet count ≥90×10^9/L

13. Hemoglobin level ≥90 g/L

14. Serum albumin level ≥30 g/L

15. Bilirubin level ≤1.5 times the upper limit of normal (ULN)

16. Alanine transaminase (ALT) and aspartate transaminase (AST) levels ≤3×ULN

17. Serum creatinine level ≤1.5×ULN

18. Thyroid-stimulating hormone (TSH) level ≤1×ULN (with eligibility also extendedto patients with free triiodothyronine [FT3] or free thyroxine [FT4] levels ≤1×ULN).

19. For women of childbearing potential not undergoing surgical sterilization, anegative serum pregnancy test (hCG) within 72 hours prior to study randomization isrequired; breastfeeding must be absent. Additionally, the use of a medicallyapproved contraceptive method is mandatory from the time of informed consent throughthe study treatment period and for 120 days following the final administration ofthe trial medication or 180 days after the last chemotherapy/radiotherapy session.Participants must also agree not to donate eggs for reproductive purposes or tofreeze/preserve eggs for this use during the aforementioned period.

20. Provision of a tumor tissue biopsy specimen is mandatory.

21. Informed consent must be obtained with documentation.

22. Availability for follow-up assessments.

Exclusion Criteria:

1. Known hypersensitivity to any component of the study medication. 2.Participation in other clinical trials, with a washout period of less than 4weeks following completion.

2. Prior treatment with immune checkpoint inhibitors, including but not limited toother anti-PD-1 and anti-PD-L1 monoclonal antibodies.

3. Patients requiring immunosuppressive pharmacotherapy. 5. Individuals requiringsystemic or absorbable topical corticosteroids at immunosuppressive doses. Useof prednisone at a dosage greater than 10mg/day or equivalent is prohibitedwithin two weeks of study drug administration.

4. Presence of active autoimmune diseases or a history thereof, excludingvitiligo, resolved childhood asthma, or resolved atopic diseases. Patients withasthma requiring intermittent bronchodilator therapy or other interventions arealso excluded.

5. Active infectious processes necessitating antimicrobial therapy, including theuse of antibacterial, antiviral, or antifungal agents.

6. History of immunodeficiency, including HIV seropositivity or other acquired andcongenital immunodeficiency disorders.

7. Uncontrolled cardiac symptoms or diseases, such as NYHA class II or higherheart failure, unstable angina, myocardial infarction within the past year,atrial fibrillation, clinically significant supraventricular or ventriculararrhythmias requiring treatment or intervention, PR interval greater than 250ms, or QTc interval ≥470 ms.

8. A history of arterial or venous thromboembolic events within the past 6 months.

9. Poorly controlled hypertension despite antihypertensive therapy (systolic bloodpressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg).

10. Proteinuria of 2+ or higher and a 24-hour urinary protein excretion exceeding 1.0 g.

11. Coagulopathy (INR >2.0, PT >16 seconds), a bleeding diathesis, or concurrentanticoagulation or thrombolytic therapy.

12. Bilateral hydronephrosis, unless resolved by unilateral stent placement orpercutaneous nephrostomy, or deemed mild and without clinical significance bythe investigator.

13. Contraindications to chemotherapy administration. 16. Contraindications toreceiving brachytherapy. 17. History of other malignancies within the past 5years, except for basal cell carcinoma and squamous cell carcinoma of the skin.

14. Administration of live vaccines within 4 weeks preceding the first dose of thetrial medication. Inactivated seasonal influenza vaccines are permissible.

15. History of substance abuse that has not been successfully managed or presenceof psychiatric disorders that may interfere with study participation.

16. Any medical, psychiatric, or social conditions deemed by the investigator topotentially impact the subject's ability to provide informed consent,participate fully in the study, or affect the interpretability of the studyresults.