Trial Title: Postoperative radiotherapy followed by immunotherapy for locally advanced
esophageal squamous cell carcinoma: A pilot study Trial Objective: To explore the safety
and efficacy of combining postoperative radiotherapy and immunotherapy for patients with
locally advanced esophageal squamous cell carcinoma after esophagectomy.
Trial Design: To enroll 70 patients with locally advanced esophageal squamous cell
carcinoma who would be randomly assigned to experimental arm (esophagectomy followed by
postoperative radiotherapy with immunotherapy) and controlled arm (esophagectomy followed
by postoperative radiotherapy).
Inclusion Criteria: a. 18-75 years old. b. after esophagectomy. c. confirmation of
squamous cell carcinoma by pathological examination. d. pathological staging of pIIb-IVa.
e. over 12 lymph nodes dissected during surgery. f. ECOG 0-1. g. signature of inform
consent by patients Exclusion Criteria: a. younger than 18 years old or older than 75
years old. b. without esophagectomy. c. non-squamous cell carcinoma. d. pathological
staging of pI, IIa, IVb. e. less than 12 lymph nodes dissected during surgery. f. ECOG
2-3 g. no signature of inform consent.
Esophagectomy: Mckeown or Ivor-Lewis surgery
Staging Examination before Postoperative Radiotherapy: a. ECOG scoring. b. PET-CT
(preferred), or chest contrast CT, abdominal ultrasonography and bone scan. c. PD-L1
expression level of surgical specimen. d. NRS2002 and PG-SGS scoring.
Postoperative radiotherapy Radiotherapy CT simulation: Intravenous contrast is
recommended for CT simulation. Scan thickness should be less than 5 mm. Thermal mask or
vacuum bag is recommended.
Delineation of Clinical Tumor Volume (CTV): CTV should involve relative lymphatic
drainage area for primary lesion at different site. For cervical and upper-thoracic
esophageal squamous cell carcinoma, CTV should involve bilateral supraclavicular (1R),
upper and lower paratracheal (2R and 4R), upper and middle paraesophageal (8U and 8M),
subcarinal lymphatic drainage area. For middle esophageal squamous cell carcinoma, CTV
should involve bilateral supraclavicular (1R), upper and lower paratracheal (2R and 4R),
upper, middle and lower paraesophageal (8U, 8M and 8L), subcarinal lymphatic drainage
area. For lower esophageal squamous cell carcinoma, CTV should involve middle and lower
paraesophageal (8M and 8L), subcarinal lymphatic drainage area.
Production of Planning Tumor Volume (PTV): PTV is produced by a margin of 5 mm added to
CTV.
Prescription Dose: 50.4Gy/28f was prescribed to 95% PTV. Dosimetric Limitation: 95%
prescription dose should cover 100% PTV and 95% PTV should receive 100% prescription
dose. Total Lung: V20<25%, Dmean<13Gy, V5<50%. Spinal Cord: Dmax<45Gy. Heart: V30<40%,
Dmean<25Gy. Treatment Implementation: Radiotherapy is implemented every day. Conebeam CT
should be utilized per week to confirm set-up error.
Randomization All participants enrolled after postoperative radiotherapy would be
randomly assigned to the experimented arm and controlled arm.
Experimental Arm (Immunotherapy Maintenance) Participants enrolled into experimental arm
were prescribed to receive immunotherapy maintenance for one year.
Controlled Arm Participants enrolled into controlled arm began to be followed-up after
postoperative radiotherapy.
Follow-up: Participants should be follow-up every three months right after the completion
of radiotherapy or immunotherapy to 3 years after radiotherapy or immunotherapy. Then
follow-up every half year is allowed to 5 years after radiotherapy or immunotherapy.
After 5 years, follow-up every year is appropriate. In follow-up, chest CT and abdominal
ultrasonography should be implemented.
Primary endpoint: 1-year disease-free survival (RECIST V1.1) Secondary endpoint: Rate of
irradiation-induced or immune-induced pneumonitis, 3-year disease-free survival and
3-year overall survival.