Prospective Immuno-Radiomic Profiling in Nasopharyngeal Carcinoma Treated With Proton or Photon Chemoradiotherapy (IMPRINT)

Integrated Prospective Analysis of Radiomic and Immunologic Signatures in Nasopharyngeal Carcinoma Treated With Proton or Photon Radiotherapy

To prospectively investigate and integrate radiomic and immunologic signatures in patients with nasopharyngeal carcinoma (NPC) treated with either proton or photon radiotherapy, with the aim of identifying biomarkers associated with treatment response, toxicity, and long-term outcomes.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC); NPC Patients
• Intervention / Treatment: Radiation: Proton chemoradiotherapy; Radiation: Photon chemoradiotherapy

Detailed Description

This is a non-randomized, single-center, phase II prospective trial enrolling patients with stage I-III NPC undergoing definitive proton or photon chemoradiotherapy. Participants will be followed for ≥2 years after treatment completion to evaluate clinical outcomes and longitudinal biomarker dynamics, including radiomic and immunologic signatures.

Radiotherapy target delineation was performed according to established consensus guidelines. The gross tumor volume (GTV) included all radiologically visible primary tumors and involved lymph nodes. The clinical target volume receiving 69.96 Gy encompassed the GTV with a 0-5 mm margin and may also include the entire nasopharynx. The clinical target volume receiving 59.4 Gy was optionally delineated at the discretion of the treating physician to encompass regions at high risk for microscopic disease spread, including the nasopharynx, nasal cavity, maxillary sinuses, pterygoid plates, parapharyngeal space, retropharyngeal lymph nodes, clivus, skull base, sphenoid sinus, and bilateral upper cervical lymph nodes. The elective neck volumes, receiving 50-54.12 Gy , encompassed the bilateral cervical lymphatic drainage regions. The detailed contour definitions followed the International Consensus Guidelines on Delineation of Clinical Target Volumes at Different Dose Levels for Nasopharyngeal Carcinoma.

Concurrent Chemotherapy Regimens:

1. Cisplatin Based Regimens

   o Dosage: Cisplatin 100 mg/m² IV on Day 1 every 3 weeks during radiotherapy (total 2-3 cycles); Cisplatin 50 mg/m² IV on Day 1 every 2 weeks during radiotherapy (typically 6-8 weeks); Cisplatin 40 mg/m² IV weekly during radiotherapy (typically 6-7 weeks)

2. Carboplatin-Based Regimens o Dosage: Carboplatin AUC 5-6 IV every 3 weeks

The use of induction chemotherapy is allowed in locally advanced NPC

1. TPF Regimen (Docetaxel + Cisplatin + 5-Fluorouracil)

   • Docetaxel: 75 mg/m² IV on Day 1
   • Cisplatin: 75 mg/m² IV on Day 1
   • 5-FU: 750-1000 mg/m²/day continuous IV infusion on Days 1-5
   • Cycle: Every 3 weeks × 2-3 cycles

2. GP Regimen (Gemcitabine + Cisplatin)

   • Gemcitabine: 1000 mg/m² IV on Days 1 and 8
   • Cisplatin: 80 mg/m² IV on Day 1
   • Cycle: Every 3 weeks × 2-3 cycles

3. TP Regimen (Docetaxel + Cisplatin)

   • Docetaxel: 75 mg/m² IV on Day 1
   • Cisplatin: 75 mg/m² IV on Day 1
   • Cycle: Every 3 weeks × 2-3 cycles

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Rodney Cheng-En Hsieh, MD, PhD; Phone Number: 7000 +886-3-328-1200; Email: rodney445@gmail.com

Study Locations

• Taiwan
  • Taiwan
    • Taoyuan, Taiwan, Taiwan, 333
      • Recruiting
      • Chang Gung Memorial Hospital at Linkou
      • Contact: Cheng-En Hsieh, MD, PhD; Phone Number: 7000 +886-3-328-1200; Email: rodney445@gmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients with AJCC 9th edition stage I-III nasopharyngeal carcinoma undergoing definitive chemoradiotherapy using either proton or photon radiotherapy.

Description

Inclusion Criteria:

1. Willingness to provide written informed consent.
2. Pathologically confirmed diagnosis of nasopharyngeal carcinoma
3. Age ≥18 years
4. ECOG performance status 0-1
5. Patients with AJCC v.9 stage I-III disease who undergo chemoradiotherapy

6. Adequate bone marrow, liver, and renal function within 4 weeks before study registration

   • Hemoglobin ≥ 9.0 g/dL
   • Absolute neutrophil count (ANC) ≥ 1,000/mm3
   • Platelet count ≥ 50,000/μL
   • Total bilirubin < 2.5 mg/dL
   • Serum albumin >2.8 g/dL
   • Serum creatinine ≤ 1.5 mg/dL

Exclusion Criteria:

1. Presence of distant metastasis
2. Patients with AJCC v.9 cT1N0M0 disease who undergo radiotherapy alone.
3. Synchronous or prior invasive malignancy, unless disease-free for at least 2 years.
4. Prior radiotherapy to the head and neck region
5. Presence of severe major organ dysfunction
6. Pregnant women or women of childbearing potential who are unwilling to use medically acceptable contraception.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Proton chemoradiotherapy; Proton chemoradiotherapy: 69.96 cobalt Gray equivalent (CGE) in 33 fractions	Radiation: Proton chemoradiotherapy; Concurrent chemoradiotherapy will be delivered using intensity modulated proton therapy, with a total dose of 69.96 CGE administered in 33 fractions.
Photon chemoradiotherapy; Photon chemoradiotherapy: 69.96 Gy in 33 fractions	Radiation: Photon chemoradiotherapy; Concurrent chemoradiotherapy will be delivered using photon-based volumetric modulated arc therapy, with a total dose of 69.96 Gy administered in 33 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is defined as the time from signing the informed consent to death from any cause.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival is defined as the time from signing the informed consent to the first occurrence of disease progression or death from any cause (whichever occurs first) according to RECIST1.1	2 years
Time to progression	Time to progression is defined as the time from signing the informed consent to the first occurrence of disease progression according to RECIST1.1.	2 years
Incidence and severity of adverse events	Acute and late adverse events will be graded using CTCAE v5	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of myeloid-derived suppressor cell levels	The levels of myeloid-derived suppressor cells (MDSCs) in peripheral blood will be analyzed at baseline, 6-8 weeks, and 3-4 months following the initiation of radiotherapy.	4 months
Changes in MRI radiomic parameters	Radiomic features will be extracted from MRI obtained pre-treatment and at 3-4 months post-chemoradiotherapy; feature changes will be computed as absolute (Δf = fpost - fpre) and percent change (Δ% = 100 × (fpost - fpre) / fpre)	4 months

Collaborators and Investigators

• Sponsor: Cheng-En Hsieh
• Investigators: Principal Investigator: Rodney Cheng En Hsieh, MD, PhD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2025
• Primary Completion (Estimated): August 15, 2031
• Study Completion (Estimated): August 15, 2034

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Estimated): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: IMRT; chemoradiation; NPC; Immune response; Radiomics; proton radiotherapy; photon radiotherapy; proton beam therapy; IMPT; IMAT
• Other Study ID Numbers: 202501031A3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The sharing of individual participant data (IPD) will be conducted only after obtaining approval from the Institutional Review Board (IRB) and in accordance with applicable ethical and data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No