Trial Design: To enroll 36 patients diagnosed with limited stage small cell lung cancer to receive hypofraction radiotherapy (18 patients receiving high dose of 60Gy/15f and 18 patients receiving low dose of 48Gy/12f).
Primary Endpoint: Rate of radiation-induced penumonitis, esophagitis, myelosuppression (CTCAE V4.0).
Secondary Endpoint: 1-year local-regional control rate, 1-year progression-free survival rate, 1-year overall survival rate (RECIST v1.1).
Randomization: Patients would be randomly assigned to high dose group and low dose group using random number table method.
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 metastaticmediastinal 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): Low Dose Hypofraction Arm (48Gy/12f) PTV: PTV is produced by a margin of 5 mm added to ITV. Modification of PTV is suggested to respect anatomic boundary.
High Dose Hypofraction Arm (60Gy/15f) PTV: Planning Tumor Volume (PTV) is produced by a margin of 5 mm added to ITV. Modification of PTV is suggested to respect anatomic boundary. For patients with ITV abutting esophagus, the technique of Esophagus-Sparing Simultaneous Integrated Boost (ES-SIB) should be utilized. PTV should be modified not to cover esophagus to ensure that the maximum dose to esophagus should be ≤ 45Gy.
The dose to PTV in adjacent to esophagus could be compromised (D99% of PTV should be ≥ 51Gy).
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\<40Gy. Heart: V30\<40%, Dmean\<25Gy.
Treatment Implementation: Radiotherapy is implemented every day. Cone-beam CT should utilized every day to minimize set-up error.
Concurrent Chemotherapy: Chemotherapy etoposide with cisplatin for 4-6 cycles was recommended.
Prophylactic Cranial Irradiation (PCI): Patients evaluated as partial response or complete response after chemoradiotherapy were recommended to receive hippocampus-sparing prophylactic cranial irradiation.
Follow-up: Patients should be follow-up every three months right after the completion of prophylactic cranial irradiation 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.
