Functional Lung Avoidance Planning Guided by Lung Perfusion PET/CT Versus Anatomical Planning for Lung Stereotactic Body Radiotherapy (Pegasus 2)

Stereotactic body radiotherapy (SBRT) has an increasing role in the treatment of both primary and secondary lung tumors. However, lung SBRT remains associated with significant radiation induced lung injury (RILI). Indeed, the reported incidence of symptomatic radiation induced lung injury (grade≥2) in the published literature is up to 20%. A current challenge of lung SBRT is therefore to better preserve lung function and to reduce pulmonary toxicity.

During standard lung SBRT planning, dose constraints are defined on the anatomical lung volume. This planning considers the lung as functionally uniform and does not take into account the variability of regional lung function distribution. Functional lung avoidance is an emerging concept in lung radiotherapy (RT). The technique aims at personalizing RT treatment planning to individuals' lung functional distribution, by sparing functional pulmonary areas while prioritizing delivery of high doses to non-functional regions.

68Ga-MAA lung perfusion PET/CT is a novel imaging modality for regional lung function assessment. As compared with conventional lung scintigraphy, lung perfusion PET/CT is inherently a vastly superior technology for image acquisition (higher sensitivity and spatial resolution, greater access to respiratory gated acquisition). A more accurate lung functional mapping improves the possibility of functional lung avoidance planning for SBRT.

The hypothesis is that functional lung avoidance planning guided by 68Ga-MAA perfusion PET/CT, while delivering an optimal dose to the tumor, will reduce the frequency of RILI in patients treated with lung SBRT.

Study Overview

• Status: Not yet recruiting
• Conditions: Stereotactic Body Radiotherapy; Lung Cancer (Diagnosis); 68Ga-MAA
• Intervention / Treatment: Radiation: Conventional anatomical planning radiotherapy; Radiation: Functional Lung avoidance planning

• Study Type: Interventional
• Enrollment (Estimated): 418
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pierre-Yves Le roux, Professeur; Phone Number: +33 2 98 22 31 17; Email: Pierre-yves.leroux@chu-brest.fr

Study Locations

• France
  • Lyon, France, 69000
    • Centre de Lutte Contre le Cancer Leon Bérard Lyon
    • Contact: Vanina Isnardi; Phone Number: +33 478 78 26 83; Email: Vanina.isnardi@lyon.unicancer.fr
  • Finistère
    • Brest, Finistère, France, 29200
      • CHU Brest
      • Contact: Pierre-Yves Le roux, Professeur; Phone Number: +33 2 98 22 31 17; Email: Pierre-yves.leroux@chu-brest.fr
      • Principal Investigator: Pierrre-Yves Le roux, Professeur

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged > 18 years planned to be treated in the radiotherapy department of the participating centers with SBRT for primary or secondary lung tumors will be eligible to participate into the study

Exclusion Criteria:

• Inability to give informed consent
• Patientsunder guardianship or curatorship
• Pregnant or breastfeeding women.
• Contraindications to the radiolabeled product infused for lung perfusion PET/CT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group: A conventional anatomical planning will be performed.	Radiation: Conventional anatomical planning radiotherapy; Conventional anatomical planning will be performed
Experimental: Experimental group; functional planning will be carried out, respecting the standard constraints especially to the tumor and the anatomical lung volume, but also incorporating "lung functional volume" constraints defined by regional lung function mapping.	Radiation: Functional Lung avoidance planning; Functional Lung Avoidance guided by lung perfusion PET/CT imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine whether a functional planning guided by lung perfusion PET/CT imaging is superior to a conventional anatomical planning with regards to the occurrence of grade 2 or higher lung toxicity during the year following lung SBRT.	Occurrence of symptomatic RILI (grade≥2 lung toxicity as assessed using the CTCAE 5.0) during the year following lung SBRT. This evaluation will be performed by a medical oncologist blinded from the allocated arm.	At year after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
quality of life assessment	Quality of life as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), with scores ranging from 0 to 100; higher scores indicate better quality of life for the global health status and functional scales, and worse symptoms for the symptom scales.	Measured at 3, 6, 9, and 12 months after baseline
quality of life assessment	Quality of life as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC29), with scores ranging from 0 to 100; higher scores indicate worse symptom burden.	Measured at 3, 6, 9 and 12 months after baseline
quality of life assessment	Quality of life as assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, with index values ranging from -0.594 to 1.0, where higher scores indicate better health-related quality of life.	Measured at 3, 6, 9, and 12 months after baseline
Grade 3 or higher RILI	Lung toxicity as assessed using the CTCAE 5.0, RTOG and Late effects in normal tissue-subjective objective management analysis (LENT-SOMA) scales	Measured at 3, 6, 9, and 12 months after baseline
Local tumor control;	Local tumor control;	Measured at 3, 6, 9, and 12 months after baseline
Progression-free survival;	Progression-free survival	Measured at 3, 6, 9, and 12 months after baseline
Overall survival.	Overall survival	at 12 months after baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease of lung perfusion	Lung perfusion PET/CT imaging	at 3 months after baseline
Overall survival	Grade≥2 lung toxicity during the year following lung SBRT	at 12 months after baseline

Collaborators and Investigators

• Sponsor: University Hospital, Brest

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): May 15, 2029

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Estimated): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: PET/CT; Stereotactic body radiotherapy; 68Ga-MAA lung perfusion; lung radiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pathological Conditions, Signs and Symptoms; Lung Neoplasms; Disease
• Other Study ID Numbers: 29BRC23.0220

Drug and device information, study documents

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