Hypofractionated Radiotherapy for Postoperative Intermediate-Risk Head and Neck Squamous Cell Carcinoma

Hypofractionated Radiotherapy for Postoperative Intermediate-Risk Head and Neck Squamous Cell Carcinoma: A Prospective Phase II Clinical Trial

This study aims to evaluate the safety and efficacy of hypofractionated radiotherapy in patients with postoperative intermediate-risk head and neck squamous cell carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: Hypofractionated Radiotherapy

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo a screening period of up to 28 days to determine eligibility for study entry. Eligible patients will then receive hypofractionated radiotherapy (PGTVtb/PGTVnd-tb: 45 Gy in 15 fractions of 3.0 Gy; PTV1: 40.5 Gy in 15 fractions of 2.7 Gy, once daily, 5 days per week for 3 weeks.).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pinfei Pan; Phone Number: 15607421631; Email: PPF0521@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Histologically or cytologically confirmed stage II-IVA head and neck squamous cell carcinoma (AJCC 8th edition), including oral cavity, oropharynx, hypopharynx, larynx, or cervical lymph node metastasis from unknown primary
• R0 resection and standard neck dissection per surgical evaluation
• Negative surgical margins and no extranodal extension in metastatic lymph nodes on postoperative pathology
• Presence of at least one intermediate-risk factor: close margins (<5 mm), pT3-4, pN2, lymphovascular invasion, perineural invasion, poor differentiation, or for oral cavity cancer T2 with depth of invasion >5 mm
• Adequate organ function (without blood transfusion or growth factors within 14 days):
• White blood cell count ≥ 2.0 × 10^9/L
• Absolute neutrophil count ≥ 1.0 × 10^9/L
• Platelet count ≥ 80 × 10^9/L
• Hemoglobin ≥ 90 g/L
• Willing and able to comply with study and follow-up procedures
• Voluntary participation with written informed consent

Exclusion Criteria:

• Prior radiotherapy or surgery to the head and neck region
• Primary head and neck cancer arising from other sites such as paranasal sinuses, nasopharynx, glottic larynx, skin, or salivary glands
• Concurrent other anti-tumor therapy
• Prior neoadjuvant drug therapy
• Evidence of tumor progression on imaging within 28 days before enrollment
• History of severe infection within 1 month before enrollment, including but not limited to infection complications requiring hospitalization, bacteremia, severe pneumonia; any active infection, or unexplained fever >38.5°C during screening or before first dose
• Severe cardiovascular disease: grade II or higher myocardial ischemia or infarction, uncontrolled arrhythmia (including QTc interval ≥450 ms for males or ≥470 ms for females); New York Heart Association (NYHA) class III-IV heart failure, or left ventricular ejection fraction (LVEF) ≤50% on echocardiography
• History of other malignancy within 5 years (except adequately treated in situ cervical cancer or basal cell/squamous cell carcinoma of the skin)
• History of psychoactive substance abuse that cannot be abstained from, or mental disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Hypofractionated Radiotherapy; Patients receive hypofractionated radiotherapy: PGTVtb/PGTVnd-tb 45 Gy in 15 fractions of 3.0 Gy, and PTV1 40.5 Gy in 15 fractions of 2.7 Gy, once daily, 5 days per week for 3 weeks.	Radiation: Hypofractionated Radiotherapy; Hypofractionated radiotherapy: 45 Gy in 15 fractions (3.0 Gy/fraction) to PGTVtb/PGTVnd-tb and 40.5 Gy in 15 fractions (2.7 Gy/fraction) to PTV1, once daily, 5 days per week for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade ≥3 Late Toxicity at 2 Years	Proportion of participants with grade 3 or higher late adverse events related to radiotherapy, assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Late toxicity is defined as adverse events occurring more than 90 days after completion of radiotherapy.	Up to 2 years after completion of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-Year Disease-Free Survival (DFS)	Disease-free survival defined as time from enrollment to first occurrence of disease progression (locoregional recurrence or distant metastasis) or death from any cause, whichever occurs first. Disease progression is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	From enrollment to 2 years
2-Year Locoregional Control (LRC)	Locoregional control defined as time from enrollment to locoregional recurrence (recurrence at the primary tumor site or regional lymph nodes), assessed according to RECIST version 1.1.	From enrollment to 2 years
2-Year Overall Survival (OS)	Overall survival defined as time from enrollment to death from any cause.	From enrollment to 2 years
Incidence and Severity of Acute Adverse Events	Number of participants experiencing adverse events during or within 90 days after completion of radiotherapy, graded according to NCI-CTCAE version 5.0. All adverse events, regardless of relationship to radiotherapy, will be recorded and summarized by type, frequency, and severity.	From start of radiotherapy to 90 days post-treatment
Change in EORTC Head and Neck Cancer Module (QLQ-H&N35) Score	Change from baseline in head and neck cancer-specific symptoms and quality of life assessed by the European Organization for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-H&N35). Scores are transformed to a 0-100 scale. According to the study protocol scoring method, higher scores indicate better quality of life.	Baseline, end of radiotherapy, and at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment
Change in M.D. Anderson Dysphagia Inventory (MDADI) Score	Change from baseline in swallowing-related quality of life assessed by the M.D. Anderson Dysphagia Inventory (MDADI). The total score ranges from 20 to 100, with higher scores indicating better swallowing function and quality of life. The scale includes Global (1 item), Emotional (6 items), Functional (5 items), and Physical (8 items) subscales.	Baseline, end of radiotherapy, and at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment
Change in EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) Score	Change from baseline in quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 V3.0). Scores are transformed to a 0-100 scale according to the EORTC scoring manual. For global health status and functional scales, higher scores indicate better quality of life/function. For symptom scales, higher scores indicate worse symptoms.	Baseline, end of radiotherapy, and at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment
Change in Body Weight	Change in body weight assessed in kilograms (kg) from baseline to each follow-up time point.	Baseline, weekly during radiotherapy, and at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment
Change in Serum Albumin Level	Change in serum albumin levels assessed in grams per liter (g/L) from baseline to each follow-up time point.	Baseline, weekly during radiotherapy, and at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment
Change in Patient-Generated Subjective Global Assessment (PG-SGA) Score	Change in nutritional status assessed by the Patient-Generated Subjective Global Assessment (PG-SGA) score. The PG-SGA consists of two sections: a patient-completed medical history (weight, food intake, symptoms, activities and function) and a professional-completed physical examination and metabolic stress score. Scores range from 0 to 35 or higher, with higher scores indicating worse nutritional status (higher symptom burden and greater need for nutrition intervention). A score ≥9 typically indicates critical need for nutrition intervention.	Baseline, weekly during radiotherapy, and at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment
Rate of Radiotherapy Interruption or Discontinuation	Proportion of participants who require temporary interruption or permanent discontinuation of radiotherapy due to adverse events or other reasons.	During the 3-week radiotherapy treatment period

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Ye Zhang, MD, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 15, 2026
• First Submitted That Met QC Criteria: March 29, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HNSCC; Hypofractionated Radiotherapy; Postoperative Radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Therapeutics; Radiotherapy; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiation Dose Hypofractionation
• Other Study ID Numbers: 25/173-0173

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) will be shared with other researchers upon reasonable request. The data to be shared include de-identified participant data related to the study outcomes, including demographic data, efficacy outcomes (DFS, LRC, OS), safety data (adverse events), and quality of life assessments (EORTC QLQ-C30, QLQ-H&N35, MDADI).
• IPD Sharing Time Frame: Data will become available within 6 months after publication of the primary results and will be available for up to 5 years following publication.
• IPD Sharing Access Criteria: Access to IPD will be granted to qualified researchers who submit a methodologically sound research proposal. Requests should be sent to the Principal Investigator (drzye1983@163.com). A data use agreement must be signed before data are released. Data will be provided in a de-identified format to protect participant privacy.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No