Hypofractionated Radiotherapy Combined with Immunotherapy for Limited-stage Small-cell Lung Cancer

Trial design: To enroll 45 patients diagnosed with limited stage small-cell lung cancer to receive concurrent chemoradiotherapy with consolidative Adebrelimab maintenance.

Primary endpoint: Progression-free Survival Secondary endpoint: 2-year progression-free survival, 2-year overall survival rate.

All enrolled patients are proposed to receive concurrent chemoradiotherapy and consolidative Adebrelimab maintenance up to 2 years. After concurrent chemoradiotherapy, hippocampus-sparing prophylactic cranial irradiation or MRI surveillance are both allowed.

Chemotherapy: Etoposide 80-100mg/m2 day 1, 2, 3 and cisplatin 75-80mg/m2 day 1 \& carboplatin AUC 5 day 1 q3w for totally 6 cycles.

Radiotherapy began at the second cycle of chemotherapy followed by hippocampus-sparing prophylactic cranial irradiation or MRI surveillance.

Immunotherapy consolidation began at the third cycle of chemotherapy: Adebrelimab 1200mg q3w to 2 year or disease progression \& untolerated toxicity.

Radiotherapy details:

Radiotherapy CT simulation: 4-Dimensional CT (4D-CT) with intravenous contrast is recommended for simulation. Scan thickness should be less than 5 mm. Thermal mask or vacuum bag is recommended.

Target Delineation: Considering hypofraction and involved field irradiation (IFI), only Internal Tumor Volume (ITV) should be delineated without the need to delineate Clinical Tumor Volume (CTV).

Delineation of ITV: ITV should include pulmonary gross tumor and metastatic mediastinal lymph nodes. PET-CT registration with simulation CT is recommended for patients with obstructive atelectasis. For patients with suspected mediastinal lymph nodes, Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) is recommended.

Production of Planning Tumor Volume (PTV): PTV is produced by a margin of 5 mm added to ITV. Modification of PTV is suggested to respect anatomic boundary.

Dosimetric Limitation: 95% prescription dose should cover 100% PTV and 95% PTV should receive 100% prescription dose. Total Lung: V20\<23%, Dmean\<13Gy, V5\<50%. Spinal Cord: Dmax\<40Gy. Heart: V30\<40%, Dmean\<25Gy. Esophagus: V40\<5cc.

Treatment Implementation: Radiotherapy is implemented every day. Cone-beam CT should be utilized every day to minimize set-up error.

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:

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

Exclusion Criteria:

1. Younger than 18 years old or older than 70 years old;
2. ECOG\>1;
3. Inadequate organ function to tolerate chemotherapy, immunotherapy and radiotherapy;
4. Non-small cell lung cancer and other neuroendocrine carcinoma including typical or atypical carcinoid, large-cell neuroendocrine carcinoma;
5. Extensive stage confirmed by cranial MRI, chest CT, abdominal ultrasonograph, bone scan or cranial MRI and PET-CT;
6. No signature of inform consent.