Overview
This prospective observational cohort study will evaluate different radiotherapy target volume delineation patterns in patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy combined with immunotherapy.
In routine clinical practice, physicians may use different margins around the primary tumor and different approaches to regional lymph node irradiation. The study will not assign participants to a specific radiotherapy strategy. Instead, participants will receive treatment according to routine clinical practice, and the actual radiotherapy plans will be recorded and analyzed.
The study will compare locoregional tumor control, recurrence patterns, survival, treatment-related toxicity, lymphocyte reduction, and completion of immunotherapy among patients receiving different target volume strategies. The main objective is to evaluate 2-year locoregional recurrence-free survival and to identify radiotherapy approaches that may achieve effective tumor control while reducing unnecessary radiation exposure and treatment-related toxicity.
Description
This is a prospective, non-interventional observational cohort study of patients with locally advanced esophageal squamous cell carcinoma treated with radiotherapy in combination with immunotherapy in routine clinical practice. Treatment decisions, including radiotherapy target volume delineation and systemic therapy, will be made by the treating physicians according to the patient's clinical condition and routine clinical practice and will not be assigned by the study protocol.
Eligible participants will be prospectively followed, and clinical, imaging, pathological, radiotherapy planning, systemic treatment, laboratory, toxicity, and follow-up data will be collected. Participants will be classified according to the radiotherapy strategy actually received, particularly the longitudinal gross tumor volume-to-clinical target volume (GTV-CTV) margin and the extent of regional lymph node irradiation, including involved-field irradiation and approaches incorporating partial elective nodal irradiation.
The primary objective is to compare 2-year locoregional recurrence-free survival among patients receiving different target volume delineation strategies. Additional outcomes include marginal and regional recurrence patterns, overall survival, treatment-related toxicity, lymphocyte reduction, immunotherapy completion, and other treatment outcomes.
The study will also evaluate whether clinical and biological factors, including tumor location and length, T and N stage, lymph node burden, PET/CT metabolic parameters, PD-L1 combined positive score, circulating tumor DNA status, and radiotherapy dosimetric parameters, are associated with the effectiveness and safety of different target volume strategies. Target trial emulation, propensity score methods, and multivariable models will be used where appropriate to reduce confounding and to explore factors associated with recurrence and toxicity.
Eligibility
Inclusion Criteria:
- Age 18 to 80 years, regardless of sex.
- Histologically confirmed esophageal squamous cell carcinoma.
- Clinical stage cT2-4aN0-3M0, or considered by a multidisciplinary team to be suitable for definitive immunotherapy combined with radiotherapy or preoperative immunotherapy combined with radiotherapy.
- Planned to receive one of the following modern precision radiotherapy techniques: IMRT, VMAT, TOMO, proton therapy, or heavy-ion radiotherapy.
- Contrast-enhanced CT completed before radiotherapy; endoscopy, EUS, PET/CT, or MRI is recommended when clinically appropriate to assist target volume delineation.
- ECOG performance status of 0-2.
- Expected survival of at least 6 months.
- Able to understand the study and provide written informed consent.
Exclusion Criteria:
- Presence of distant metastasis or malignant pleural or peritoneal effusion.
- Previous thoracic radiotherapy that may affect the current target volume design or dose constraints.
- Pre-existing esophagotracheal fistula, esophagoaortic fistula, or a high risk of perforation considered unsuitable for radiotherapy.
- Active interstitial lung disease, severe infection, or uncontrolled autoimmune disease considered unsuitable for immunotherapy.
- Severe missing data that prevent determination of the actual CTV margin, lymph node irradiation extent, or major study outcomes.
- Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.
