Hypofraction Radiotherapy for Limited-Stage Small Cell Lung Cancer

Hypofraction Radiotherapy for Limited-Stage Small Cell Lung Cancer: A Pilot Trial

Concurrent chemoradiotherapy is the standard modality for locally advanced small-cell lung cancer, which could achieve median overall survival of 25 mos. Conventional fractionation of 66Gy/33f and hyperfractionation of 45Gy/30f twice daily have been acknowledged as the two standard radiotherapy modalities according to CONVERT study. In 2021, a phase II trial demonstrated that 60Gy/40f twice daily was superior to the standard 45Gy/30f twice daily in light of overall survival (2y OS 74.2% vs. 39% p=0.0005), which to some extent implied that higher dose may confer better survival. Hypofractionated radiotherapy was another useful modality to increase biological effective dose with the advantage of short course and convenience. The effectiveness and safety of 60Gy/15f has been demonstrated in the treatment of locally advanced non-small cell lung cancer. Therefore, this trial is designed to explore the safety and primary efficacy of hypofraction radiotherapy for stage III locally advanced small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Safety Issues; Efficacy, Self
• Intervention / Treatment: Radiation: Low-dose hypofraction Arm (Standard BED); Radiation: High-dose hypofraction Arm

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provicial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-75 years old;
• ECOG 0-1;
• Small cell lung cancer;
• Limited stage confirmed by cranial MRI, chest CT, abdominal ultrasonagraph, bone scan or cranial MRI and PET-CT;
• Signature of inform consent.

Exclusion Criteria:

• Younger than 18 years old or older than 75 years old;
• ECOG>1;
• Non-small cell lung cancer and other neuroendocrine carcinoma including typical or atypical carcinoid, large-cell neuroendocrine carcinoma;
• Extensive stage confirmed by cranial MRI, chest CT, abdominal ultrasonagraph, bone scan or cranial MRI and PET-CT;
• No signature of inform consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose hypofraction Arm (Standard BED); Patients in this arm (Low-dose hypofraction Arm) would receive high-dose fractionated radiotherapy with 48Gy/12f.	Radiation: Low-dose hypofraction Arm (Standard BED); Patients in this arm would receive low-dose fractionated radiotherapy with 48Gy/12f
Experimental: High-dose hypofraction Arm; Patients in this arm (High-dose hypofraction Arm) would receive high-dose fractionated radiotherapy with 60Gy/15f.	Radiation: High-dose hypofraction Arm; Patients in this arm would receive high-dose fractionated radiotherapy with 60Gy/15f

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of radiation-induced pneumonitis (CTCAE V4.0)	Rate of radiation-induced pneumonitis (CTCAE V4.0)	1 to 2 years
Rate of radiation-induced esophagitis (CTCAE V4.0)	Rate of radiation-induced esophagitis (CTCAE V4.0)	1 to 2 years
Rate of myelosuppression (CTCAE V4.0)	Rate of myelosuppression (CTCAE V4.0)	1 to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 year locoregional control rate (RECIST 1.1)	2 year locoregional control rate (RECIST 1.1)	2 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 year progression-free rate (RECIST 1.1)	2 year progression-free rate (RECIST 1.1)	2 year
2 year overall survival rate (RECIST 1.1)	2 year overall survival rate (RECIST 1.1)	2 year

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Dong P Qian, M.D., The First Affiliated hospital of USTC

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Hypofraction RT, Limited-Stage SCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: 2022ky454

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No