The goal of this randomized clinical trial is to learn about if carbon ion radiotherapy dose boost in hypoxia lesions detected by 18F-Misonidazole PET/CT could improve clinical outcomes in locally advanced non-small cell lung cancer patients compared with standard treatment protocol in our center. The patients will be randomly divided into two arms: standard treatment arm and hypoxic lesions dose boost arm. The standard treatment arm will receive carbon ion beam radiotherapy of 77Gy (RBE equivalent) per 22 fractions for gross tumor volume. The hypoxic lesions dose boost arm will receive 77Gy (RBE equivalent) per 22 fractions for gross tumor volume and a simultaneously dose boost of 83.6Gy (RBE equivalent) per 22 fractions for hypoxic lesions detected by 18F-Misonidazole PET/CT. Researchers will compare the local progression-free survival of two groups (primary endpoint), progression-free survival (secondary endpoint), overall survival (secondary endpoint), response rate (secondary endpoint), factional hypoxia volume (FHV) reduction rate (secondary endpoint) and toxicities (secondary endpoint).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
77
The standard treatment arm will receive carbon ion beam radiotherapy of 77Gy (RBE equivalent) per 22 fractions for gross tumor volume.
The hypoxic lesions dose boost arm will receive 77Gy (RBE equivalent) per 22 fractions for gross tumor volume and a simultaneously dose boost of 83.6Gy (RBE equivalent) per 22 fractions for hypoxic lesions detected by 18F-Misonidazole PET/CT.
Shanghai Proton and Heavy Ion Center
Shanghai, Shanghai Municipality, China
RECRUITINGLocal progression-free survival
Local progression-free survival was defined from the start of carbon ion radiotherapy till the date of local progression or the last follow-up
Time frame: From date of radiotherapy started until the date of first documented local disease progression, assessed up to 100 months
Disease progression-free survival rate
Disease progression-free survival rate was defined from the start of carbon ion radiotherapy till the date of disease progression at any site or death, or the last follow up
Time frame: From date of radiotherapy started until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall survival rate
Overall survival rate was defined from the start of carbon ion radiotherapy till the date of death or the last follow-up
Time frame: From date of radiotherapy started until the date of death from any cause, assessed up to 100 months
Overall response rate
Proportion of complete response and partial response in all patients
Time frame: From date of radiotherapy started until 6 months after first radiotherapy
Change of fractional hypoxia volume
The hypoxia volume of the hypoxia-positive region of interested was defined as the sum of pixels with a tumor muscle rate ≥1.4. The FHV, defined as the HV-to-gross tumour volume ratio. The FHV before and after carbon ion radiotherapy within 1 month will be recorded.
Time frame: From date of radiotherapy started until 1 month after first radiotherapy
Incidence of Treatment-induced Adverse Events
Treatment-induced toxicities were scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and EORTC/RTOG criteria, for events observed after the first dose of irradiation. Toxicities occurred 90 or more days after the completion of CIRT were defined as late toxicities.
Time frame: From date of radiotherapy started, every 3-4 months within the first 2 years, every 6 months between years 3 and 5, and annually thereafter, assessed up to 100 months
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