This prospective study investigates the dynamic changes in plasma calcitonin gene-related peptide (CGRP) levels during radiotherapy and their association with radiotherapy-related pain in patients with head and neck malignancies.

Radiotherapy-related pain is a major clinical challenge that significantly affects the long-term quality of life and treatment adherence of patients with head and neck cancer. Current analgesic strategies offer limited efficacy, and reliable biomarkers for predicting pain risk are lacking. In recent years, calcitonin gene-related peptide (CGRP) has drawn increasing attention for its critical role in chronic pain regulation, as demonstrated in various pain models. However, no systematic studies have yet investigated the expression patterns and clinical relevance of CGRP in radiotherapy-induced pain among patients with head and neck malignancies. This single-center, prospective observational study aims to enroll patients with head and neck cancer receiving either definitive or postoperative adjuvant radiotherapy. Plasma samples will be collected before, during, and after radiotherapy for measurement of CGRP levels. Pain intensity will be simultaneously assessed using the Numeric Rating Scale (NRS) and the Brief Pain Inventory-Short Form (BPI-SF). The study seeks to explore the dynamic changes in plasma CGRP levels throughout the radiotherapy course and to analyze their correlation with patient-reported pain, thereby providing potential insights into biomarker-based pain prediction and management strategies in this patient population.

Inclusion Criteria:

• Age ≥ 18 years

Histologically confirmed head and neck malignancy

Planned to receive definitive or postoperative adjuvant radiotherapy

Radiotherapy duration ≥ 4 weeks, with irradiation field involving the oral cavity, pharynx, or neck region

Able and willing to provide written informed consent

Able to complete pain assessments and blood sample collection

Exclusion Criteria:

• History of significant chronic pain prior to radiotherapy (e.g., postherpetic neuralgia, rheumatoid arthritis)

Presence of uncontrolled hypertension, diabetes, or migraines

Presence of other active malignancies or major systemic diseases (e.g., severe hepatic or renal dysfunction)

Currently receiving or recently received treatments that may significantly affect pain perception (e.g., opioids, antidepressants)

Pregnant or breastfeeding

Inability to complete follow-up or poor treatment compliance

Adult patients (≥18 years) with histologically confirmed head and neck malignancies scheduled to receive definitive or postoperative adjuvant radiotherapy (≥4 weeks) involving the oral cavity, pharynx, or neck will be enrolled. Exclusion criteria include pre-existing significant chronic pain (e.g., postherpetic neuralgia, rheumatoid arthritis), uncontrolled hypertension, diabetes, or migraines, other active malignancies or major systemic diseases (e.g., severe hepatic/renal dysfunction), recent or current use of medications affecting pain perception (e.g., opioids, antidepressants), pregnancy or breastfeeding, and inability to complete follow-up or poor treatment compliance.