This was a phase II clinical study. Patients with histologically confirmed, resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) without distant metastasis were enrolled. Enrolled patients received three cycles of neoadjuvant immunotherapy combined with chemotherapy. Radical surgery was performed 3-5 weeks after completion of the third neoadjuvant cycle, with the requirement of achieving negative surgical margins (R0 resection). Adjuvant radiotherapy was administered based on postoperative pathological findings.
Inclusion Criteria:
1. Patients who have signed the informed consent form and are willing to complete the study according to the protocol;
2. Age ≥18 years and ≤75 years;
3. Histologically confirmed squamous cell carcinoma of the head and neck (SCCHN), with the primary tumorlocated in the oropharynx, oral cavity, larynx, or hypopharynx;
4. Resectable, locally advanced squamous cell carcinoma of the head and neck without distant metastasis (AJCC8th edition: HPV-negative SCCHN: Stage III-IVB; HPV-positive oropharyngeal cancer: T1-4N1-3M0 or T3-4N0M0);
5. At least one measurable lesion prior to treatment that meets the criteria for "measurable disease" according toRECIST version 1.1;
6. Expected survival \>3 months;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
8. Adequate organ function, meeting the following requirements: a. Absolute neutrophil count (ANC) ≥1.5×10⁹/L; b. Platelet count ≥100×10⁹/L; c. Hemoglobin ≥9 g/dL; d. Serum albumin ≥2.8 g/dL; e. Total bilirubin ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or alkalinephosphatase (ALP) ≤3×ULN; f. Serum creatinine ≤1.5×ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault formula); g. Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5×ULN (patients receiving stable-dose anticoagulant therapy such as low-molecular-weight heparin or warfarin with an INR within the expected therapeutic range of the anticoagulant may be screened);
9. Patients with hepatitis B virus (HBV) infection, including inactive/asymptomatic HBV carriers or those withchronic or active HBV, are eligible for enrollment if HBV DNA \<500 IU/mL (or 2,500 copies/mL) at screening.Patients with positive hepatitis C antibody are eligible for enrollment if HCV-RNA is negative at screening;
10. Women of childbearing potential must have a negative urine or serum pregnancy test within ≤7 days prior totreatment. They must also use a medically acceptable method of contraception (e.g., intrauterine device, oralcontraceptive, or condom) during study treatment and for at least 3 months after the last dose of PD-1 inhibitorand at least 6 months after the last dose of chemotherapy;
11. Non-sterilized male subjects must be willing to use a medically acceptable method of contraception (e.g.,intrauterine device, oral contraceptive, or condom) during study treatment and for at least 3 months after the last dose of PD-1 inhibitor and at least 6 months after the last dose of chemotherapy.
Exclusion Criteria:
1. Prior or concurrent malignancy (except for malignancies cured with disease-free survival \>5 years, such as basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid carcinoma);
2. Receipt of any of the following treatments: a. Any investigational drug within 4 weeks prior to the first dose of study drug. b. Concurrent enrollment in another clinical study, except for observational (non-interventional) clinical studies. c. Requirement for systemic corticosteroids at a dose \>10 mg/day prednisone equivalent or other immunosuppressive agents within 2 weeks prior to the first dose of study drug, except for corticosteroids used for local inflammation or for prophylaxis of allergy, nausea, and vomiting. Other special circumstances require discussion with the investigator. In the absence of active autoimmune disease, inhaled or topical corticosteroidsand adrenal corticosteroid replacement at doses \>10 mg/day prednisone equivalent are permitted. d. Receipt ofantitumor vaccines or live vaccines within 4 weeks prior to the first dose of study drug (for COVID-19 vaccination,an interval of \>2 weeks between vaccination and treatment is required). e. Major surgery or severe trauma within 4weeks prior to the first dose of study drug.
3. Prior radiotherapy to the head and neck region;
4. Uncontrolled cardiac symptoms or diseases, such as: a. New York Heart Association (NYHA) Class II or higher heart failure; b. Unstable angina; c. Myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
5. Severe infection (Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>2) within 4 weeks prior tothe first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, or complicated infections; active pulmonary inflammation indicated by baseline chest imaging; or presence of signs and symptoms of infection within 4 weeks prior to the first dose of study drug, or requirement for oral or intravenous antibiotic therapy;
6. Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); excluding autoimmune-mediated hypothyroidism managed with a stable dose of thyroid replacement hormone, Type 1 diabetes mellitus managed with a stable dose of insulin, vitiligo, or childhood asthma/allergy that has resolved and requires no intervention in adulthood;
7. History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation;
8. History of interstitial lung disease (excluding radiation pneumonitis not treated with corticosteroids) or historyof non-infectious pneumonitis;
9. Active tuberculosis infection identified by medical history or CT examination, or history of active tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection \>1 year prior without formal treatment;
10. Active hepatitis B (HBV DNA ≥500 IU/mL or 2,500 copies/mL) or hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay);
11. Known history of psychoactive substance abuse, alcoholism, or drug addiction;
12. Pregnant or breastfeeding women;
13. Any other condition that, in the opinion of the investigator, may result in premature discontinuation from the study, such as other severe diseases (including psychiatric disorders) requiring concomitant treatment, severely abnormal laboratory values, or family or social factors that may affect subject safety or data collection.
Locations (2)
Hunan Cancer Hospital
Changsha, Hunan, China
Fudan University Shanghai Cancer Center
Shanghai, China
Outcomes
Primary Outcomes
Rate of cervical nodal recurrence
defined as the probability of neck nodal recurrence occurring before local recurrence or distant metastasis, analyzed using a competing risk model.
Time frame: 2 year
Secondary Outcomes
Progression-free survival rate
Progression-free survival, defined as the time from enrollment to the date of first documented objective tumor progression or death from any cause, whichever occurs first. Patients without documented progression or death at the data cutoff date will be censored.
Time frame: 2 year
Overall survival rate
Overall survival, defined as the time from enrollment to death from any cause. Data for patients who are alive at the time of analysis will be censored at the date last known to be alive.
Time frame: 2 year
Major pathologic response
Major pathologic response, defined as residual viable tumor cells ≤10% within the surgical tumor bed.
Time frame: 6 month
Adverse events
An adverse event is any untoward medical occurrence in a clinical trial subject following administration of a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE may be any unfavourable and unintended sign (including abnormal laboratory findings), symptom, or disease.
Time frame: 2 year
Swallowing function
Swallowing function will be assessed using the MD Anderson Dysphagia Inventory (MDADI) and the Eating Assessment Tool-10 (EAT-10).