Neoadjuvant Immunotherapy And Chemotherapy Followed By Concurrent Chemoradiation Or Organ Preservation Surgery In Locally Advanced Laryngeal Cancer And Hypopharyngeal Cancer
In the global landscape of cancer, head and neck malignancies are highly prevalent, with 878,000 new cases and 444,000 deaths recorded in 2020. Notably, laryngeal and hypopharyngeal cancers contribute to around 30% of these instances. More than 50% of patients are diagnosed with locally advanced disease, necessitating intensive treatments that significantly impact their quality of life. Despite these efforts, the prognosis for laryngeal and hypopharyngeal cancers remains grim, with a 5-year survival rate of 30% to 50%. Past approaches focused on preserving laryngeal function and patient well-being, including minimally invasive surgery, advanced radiotherapy, and induction chemotherapy. Our prior research highlighted the effectiveness of combining toripalimab-based induction therapy and chemotherapy, followed by concurrent chemoradiotherapy or surgery. Positive short-term outcomes and manageable side effects were observed, with encouraging larynx preservation rates after one year. Against this backdrop, the current study aims to explore neoadjuvant immunotherapy combined with chemotherapy for patients with locally advanced laryngeal and hypopharyngeal cancer. It seeks to compare the therapeutic efficacy and quality of life impacts of concurrent radiochemotherapy and organ-preserving surgery. The ultimate goal is to identify optimal strategies for future interventions.
• Signing of the informed consent form and willingness to comply with the study protocol.
• Age ≥18 and ≤75 years.
• Histologically confirmed laryngeal or hypopharyngeal squamous cell carcinoma.
• Locally advanced laryngeal/hypopharyngeal cancer patients eligible for surgical resection (AJCC 8th edition stage: T2N+M0, T3-T4aN0-3M0).
• Presence of at least one measurable lesion before treatment, in accordance with RECIST 1.1 criteria for measurable lesions.
• Patients who have received neoadjuvant immunotherapy combined with chemotherapy and have achieved a partial response (PR) in the primary lesion according to RECIST 1.1 criteria and are suitable candidates for organ preservation surgery.
• Expected survival of more than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Good organ function, meeting the following criteria:
∙ Absolute neutrophil count (ANC) ≥1.5×10\^9/L.
‣ Platelet count ≥100×10\^9/L.
‣ Hemoglobin ≥9 g/dL.
‣ Serum albumin ≥2.8 g/dL.
‣ Total bilirubin ≤1.5× upper limit of normal (ULN), ALT, AST, and/or ALP ≤3× ULN.
‣ Serum creatinine ≤1.5× ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault formula, see Appendix III).
‣ Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5× ULN (patients on stable doses of anticoagulation with agents like low molecular weight heparin or warfarin, and INR within the expected therapeutic range, may be included).
⁃ Patients with hepatitis B virus (HBV) infection, inactive/asymptomatic HBV carriers, or patients with chronic or active HBV infection with HBV DNA \<500 IU/mL (or 2500 copies/mL) at screening will be allowed to participate. Patients positive for hepatitis C antibodies, if HCV-RNA is negative at screening, will be allowed to participate.
⁃ Females of childbearing potential must have a negative pregnancy test result in urine or serum ≤7 days before treatment initiation. They must use a medically accepted contraceptive measure (such as intrauterine device, oral contraceptives, or condoms) during the study treatment period, for at least 3 months after the last dose of toripalimab, and for at least 6 months after the last dose of chemotherapy.
⁃ Non-sterilized male participants must be willing to use a medically accepted contraceptive measure (such as intrauterine device, oral contraceptives, or condoms) during the study treatment period, for at least 3 months after the last dose of toripalimab, and for at least 6 months after the last dose of chemotherapy.