What are the definitions of peripheral, central, and ultracentral lung tumors in the context of Stereotactic Body Radiation Therapy (SBRT) for lung cancer?

Definitions of Peripheral, Central, and Ultracentral Lung Tumors for SBRT

Central tumors are defined by the IASLC as tumors located within 2 cm in all directions of any mediastinal critical structure (including the bronchial tree, esophagus, heart, brachial plexus, major vessels, spinal cord, phrenic nerve, and recurrent laryngeal nerve), while ultracentral tumors are those where the planning target volume (PTV) directly overlaps or touches the trachea or main bronchi, and peripheral tumors are those located 2 cm or more away from these central structures. 1

Peripheral Tumors

Definition:

• Peripheral lung tumors are lesions that lie 2 cm or more from the mediastinum and proximal bronchial tree 2
• These tumors are located away from critical mediastinal structures and major airways 1

Clinical Significance:

• SBRT for peripheral tumors is associated with low toxicity, even in patients with COPD and the elderly 1
• The standard SBRT approach with biologically equivalent tumor doses of 100 Gy can be safely delivered to peripheral lesions 1
• Chest wall toxicity is the most common side effect but usually resolves with conservative management 2

Central Tumors

Definition:

• Central tumors are defined by the IASLC as tumors located within 2 cm in all directions of any mediastinal critical structure 1
• Critical structures include: bronchial tree, esophagus, heart, brachial plexus, major vessels, spinal cord, phrenic nerve, and recurrent laryngeal nerve 1
• This definition encompasses tumors in the hilar region 1

Clinical Significance:

• Central tumors require "risk-adapted" fractionation schemes rather than standard peripheral dosing 1, 3
• The recommended dose is 50 Gy in 5 fractions for central tumors, which provides optimal tumor control while minimizing toxicity 3
• Early studies using higher doses (60-66 Gy in 3 fractions) for central tumors reported serious and even lethal toxicity 3
• With appropriate dose modifications, SBRT can achieve high local control rates with limited toxicity for central tumors 1

Ultracentral Tumors

Definition:

• Ultracentral tumors are those where the planning target volume (PTV) overlaps or directly touches the trachea or main bronchi 1
• Some definitions also include tumors where the PTV contacts the esophagus, pulmonary vein, or pulmonary artery 4
• This represents a distinct subset of central tumors with the highest risk profile 1

Critical Clinical Distinction:

• SBRT is not appropriate for ultracentral tumors using standard stereotactic doses due to significantly increased toxicity risk 1, 3
• Ultracentral tumors have demonstrated increased rates of grade 2+ toxicity (57.6% at 2 years) compared to other central (14.2%) and paramediastinal tumors (7.1%) 5
• Grade 5 (fatal) respiratory failure has been reported in ultracentral tumor treatment 5
• Until prospective data from RTOG studies become available, radical RT using hypofractionated or more conventional schedules is recommended instead of SBRT for ultracentral lesions 1

Treatment Algorithm Based on Location

For Peripheral Tumors (≥2 cm from central structures):

• Standard SBRT with biologically equivalent dose of 100 Gy 1
• Low toxicity profile expected 1, 2

For Central Tumors (within 2 cm of critical structures, but PTV does not overlap trachea/main bronchi):

• Risk-adapted SBRT with 50 Gy in 5 fractions 3
• Careful dose constraints to critical structures 3

For Ultracentral Tumors (PTV overlaps trachea/main bronchi):

• Avoid standard SBRT 1
• Use radical RT with hypofractionated or conventional schedules 1
• For tumors >5 cm and/or moderately central location in medically inoperable patients, conventional or accelerated RT schedules are recommended 1, 3

Common Pitfalls to Avoid

• Do not use peripheral SBRT dosing for central tumors - this significantly increases toxicity risk 3, 6
• Carefully distinguish between central and ultracentral tumors on planning CT scans, as the treatment approach differs fundamentally 1
• Do not assume all tumors within 2 cm of the bronchial tree can receive SBRT - those with PTV overlap of trachea/main bronchi require alternative approaches 1
• Early studies that failed to make this distinction reported bronchial stricture, secondary loss of lung volume, and grade 3-5 pulmonary toxicities in 33% of central tumor patients 6