The Efficacy and Safety of De-escalated Postoperative Radiotherapy in Locally Advanced HNSCC With pCR/MPR

Study Overview
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Brief Summary
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This is an open-label, single-arm, phase II clinical trial to explore the efficacy and safety of de-escalation of postoperative radiotherapy in locally advanced head and neck squamous cell carcinoma with pathological complete response/major pathological response to neoadjuvant therapy. The eligible patients are scheduled to administered postoperative radiotherapy, PTV 50Gy/25F, instead of the standard dose of 60Gy. The overall primary study hypothesis is that reducing the dose of postoperative radiotherapy in the specific population does not affect DFS but significantly reduces treatment related adverse events.

Official Title
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De-escalation of Postoperative Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma With Pathological Complete Response/Major Pathological Response: A Single-arm, Prospective Phase II Clinical Study

Conditions
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Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: dose-reduced radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated, histologically confirmed head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx or larynx), staging T3-4N0M0 or T1-4N1-3M0, III-IVB, according to the eighth edition of the AJCC staging system; within 6 weeks after receiving neoadjuvant therapy and radical surgery. Pathological evaluation of surgical specimens was pCR (pathologic complete response, no viable tumor cells) or MPR (Major pathologic response, residual viable tumor cells≤10%). Negative surgical margin. No extranodal extension. Aged ≥ 18 years and ≤ 70 years. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Life expectancy of more than 6 months. Adequate organ function, based on meeting all of the following criteria (no blood components and cytologic growth factors were received within 14 days prior to the test): Hemoglobin ≥ 75 g/L; absolute neutrophil count ≥ 1.5 × 10^9/L; and platelet count ≥ 100 × 10^9/L; Serum albumin ≥ 25 g/L; Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN; Activated partial clotting enzyme time and international standardized ratio (INR) ≤ 1.5 × ULN (Patients on stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin with INR within the expected treatment range of anticoagulants can be screened ). Women of childbearing age should agree to the use of contraception (e.g., intrauterine devices, birth control pills, or condoms) during treatment and for 3 months thereafter. The regimen of neoadjuvant therapy can be determined by the clinician. Subjects voluntarily join the study and sign an informed consent form, with good compliance. Exclusion Criteria: Pregnant or lactating women. A history of other malignant tumors within the previous 5 years or at the time of enrollment, except for cured skin basal cell carcinoma and cervical in situ cancer, as well as thyroid papilloma. Neoadjuvant therapy or radical surgery was not completed. Recurrence or distant metastasis occurred before postoperative radiotherapy. There are contraindications for radiotherapy, chemotherapy, immunotherapy and targeted therapy. Uncontrolled cardiac clinical symptoms or diseases. Serious infections. A history of immunodeficiency, including HIV-positive status or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and bone marrow transplantation. Patients with active tuberculosis infection found by history or CT examination, or patients with active tuberculosis infection history within 1 year prior to enrollment, or patients with active tuberculosis infection history before 1 year without formal treatment. Active hepatitis B (HBV DNA ≥ 2,000 IU/mL or 10,000 copies/mL) or hepatitis C (positive HCV antibody test and HCV RNA above the lower limit of detection). Known history of psychotropic drug abuse, alcoholism and drug use. Not suitable for inclusion, as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: de-escalation radiotherapy<br>Postoperative radiotherapy alone | Radiation: dose-reduced radiotherapy<br>* Patients receive 50Gy/25F, 2Gy/F QD, five days a week for 5 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (DFS) | 2-year disease free survival rate | from the first day of treatment to the follow up of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | 2-year overall survival rate | from the first day of treatment to the follow up of 2 years | 
| Local Relapse Free Survival (LRFS) | 2-year local relapse free survival rate | from the first day of treatment to the follow up of 2 years | 
| Distant Metastasis Free Survival (DMFS) | 2-year distant metastasis free survival rate | from the first day of treatment to the follow up of 2 years | 
| EORTC QLQ-C30 | Quality of life evaluation | from 1 week before treatment to the follow up of 2 years | 
| EORTC HN35 | Quality of life evaluation | from 1 week before treatment to the follow up of 2 years | 
| RTOG/EORTC late radiation morbidity scoring scheme | Toxicity criteria of RTOG/EORTC | from 1 week before treatment to the follow up of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pathological complete response, major pathological response