Radiotherapy to All Residual Lesions After Chemoimmunotherapy

Trial design: To enroll 150 patients diagnosed with extensive-stage small-cell lung cancer to receive first-line chemoimmunotherapy with or without radiotherapy to all residual lesions.

Primary endpoint: Progression-free Survival Secondary endpoint: Overall Survival, Objective Response Rate, Duration of Response, Disease Control Rate.

Randomization: All the enrolled patients would be randomly assigned to chemoimmunotherapy group and chemoimmunotherapy with radiotherapy group using random table method.

All enrolled patients with accordance to the inclusion criteria would first receive 4 to 6 cycles of chemoimmunotherapy (etoposide and cisplatin & carboplatin with Adebrelimab). Then patients who were evaluated as partial response or stable disease would be assigned randomly to receive radiotherapy to all residual lesions followed by Adebrelimab maintenance or only Adebrelimab maintenance up to 2 years.

Chemoimmunotherapy: Etoposide 80-100mg/m2 day 1, 2, 3 and cisplatin 75-80mg/m2 day 1 & carboplatin AUC 5 day 1 and Adebrelimab 1200mg day 1 q3w totally 4 to 6 cycles.

Immunotherapy maintenance: Adebrelimab 1200mg q3w to 2 year or disease progression & untolerated toxicity.

Response evaluation: After 4 to 6 cycles of chemoimmunotherapy, patients would undertake response evaluation according to RECIST criteria. These patients who were evaluated as partial response and stable disease could be included into the study and receive randomization.

Radiotherapy to residual lesions: Patients assigned to chemoimmunotherapy with radiotherapy group would first receive PET-CT and cranial contrasted MRI to ascertain residual lesions. All residual lesions would be irradiated in a hypofractionated manner. Radiotherapy should be completed in two weeks. The suggested dose fraction for different lesion was as follows:

Thoracic lesion: 40Gy/10f Cranial lesion: Hippocamps-sparing whole brain irradiation of 30Gy/10f with or without simultaneous integrated lesion boost of 40Gy/10f Hepatic or adrenal lesion: 40Gy/10f Osseous lesion: 30Gy/10f or 40Gy/10f Dose constraint to organs at risk could be referred to QUANTEC criteria (30Gy/10f) and Timmerman's sheet (40Gy/10f) Follow-up: Patients should be follow-up every three months right after the completion of the final cycle of immunotherapy to 3 years after that. Then follow-up every half year is allowed to 5 years. After 5 years, follow-up every year is appropriate. In follow-up, chest CT and abdominal ultrasonography should be implemented. Cranial MRI should be performed every half year. Bone scan should be undertaken every year for all patients.

Inclusion criteria

• 18-70 years old;
• ECOG 0-1;
• Adequate organ function to tolerate chemotherapy, immunotherapy and radiotherapy;
• Small-cell lung cancer;
• Extensive stage confirmed by cranial MRI, chest CT, abdominal ultrasonograph, bone scan or cranial MRI and PET-CT;
• Signature of inform consent.

Exclusion criteria

Younger than 18 years old or older than 70 years old;

• ECOG>1;
• Inadequate organ function to tolerate chemotherapy, immunotherapy and radiotherapy;
• Non-small cell lung cancer and other neuroendocrine carcinoma including typical or atypical carcinoid, large-cell neuroendocrine carcinoma;
• Limited stage confirmed by cranial MRI, chest CT, abdominal ultrasonograph, bone scan or cranial MRI and PET-CT;
• No signature of inform consent.