For a medically inoperable patient with early‑stage (T1‑T2a) non‑small‑cell lung cancer, what are the recommended stereotactic body radiation therapy (SBRT) dose regimens for peripheral versus central lesions and the corresponding organ dose constraints?

SBRT Dose Regimens for Early-Stage NSCLC

For medically inoperable patients with early-stage (T1-T2a) non-small cell lung cancer, SBRT should deliver a biological equivalent dose (BED10) of at least 100 Gy, with peripheral tumors treated using 48-60 Gy in 3-5 fractions, while central tumors require risk-adapted fractionation of 50 Gy in 5 fractions to minimize toxicity to critical mediastinal structures. 1, 2

Peripheral Tumor Dose Regimens

Standard peripheral tumor dosing:

• 48 Gy in 4 fractions (most commonly used, BED10 = 105.6 Gy) 3
• 54 Gy in 3 fractions (BED10 = 151.2 Gy) 1
• 60 Gy in 3 fractions (BED10 = 180 Gy) 1
• All regimens must achieve BED10 ≥ 100 Gy for optimal local control 1

Critical dosing boundaries:

• Avoid BED10 > 146 Gy, as doses above this threshold significantly increase toxicity without improving outcomes 1, 4
• The median BED10 across successful studies is 100 Gy, with a range of 83.2-106 Gy showing excellent results 1

Central Tumor Dose Regimens

Mandatory dose reduction for central lesions:

• 50 Gy in 5 fractions is the recommended standard for central tumors (BED10 = 100 Gy) 2
• Central tumors are defined as those within 2 cm in all directions of the proximal bronchial tree, esophagus, heart, brachial plexus, major vessels, spinal cord, phrenic nerve, or recurrent laryngeal nerve 2

Critical distinction - ultracentral tumors:

• When the planning target volume (PTV) directly overlaps the trachea or main bronchi, SBRT is contraindicated due to prohibitive toxicity risk 2
• Early studies using 60-66 Gy in 3 fractions for central tumors reported serious and lethal toxicities, mandating the lower dose-per-fraction approach 2

Risk-Adapted Fractionation Algorithm

Use extended fractionation when:

• Tumor size > 5 cm 1
• Large planning target volume (PTV) 1
• Severe pulmonary comorbidity (COPD, limited pulmonary reserve) 1
• Central or moderately central location 1, 2

For these high-risk scenarios:

• Consider conventional or accelerated radiotherapy schedules instead of SBRT 1
• If SBRT is used, increase fractions to 8-10 while maintaining BED10 ≥ 100 Gy 1

Essential Organ-at-Risk Dose Constraints

For central tumors, critical structure constraints include:

• Advanced dose calculation algorithms (type B models) are mandatory 2
• Planning organ at risk volume (PRV) margins must be applied to all serial organs 2
• 4-dimensional analysis of tumor and critical structure motion during simulation is essential 4

Specific constraints to prevent major toxicity:

• Limit lung parenchyma exposure to prevent radiation pneumonitis (maximum 3-3.5 cm of lung in treatment field) 5
• Minimize esophageal, tracheal, and major vessel doses for central lesions 2, 6
• Protect brachial plexus, vagus nerve, and recurrent laryngeal nerve to prevent radiation-induced neuropathies 6

Treatment Planning Requirements

Mandatory technical specifications:

• Use intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) over 3D conformal techniques 5
• Consistent patient positioning with immobilization devices 4
• PTV must account for respiratory motion using 4D-CT simulation 2, 4
• Dose homogeneity verification is required 5

Clinical Outcomes by Location

Peripheral tumors:

• 3-year local control: 86-98% 1, 7
• 3-year overall survival: 53-95% 7, 3
• Grade 3-4 toxicity: 10-30% 7

Central tumors:

• Comparable local control when appropriate dose reduction is used 2
• Significantly higher toxicity risk if standard peripheral doses are applied 2

Common Pitfalls to Avoid

Do not:

• Use peripheral tumor doses (60-66 Gy in 3 fractions) for central lesions—this causes life-threatening toxicity 2
• Exceed BED10 of 146 Gy, as this increases toxicity without benefit 1, 4
• Treat ultracentral tumors (PTV overlapping trachea/main bronchi) with SBRT 2
• Offer SBRT to patients with very limited life expectancy from comorbidities 1

Always:

• Discuss treatment selection in multidisciplinary tumor boards 1
• Verify medically inoperable status through thoracic surgery evaluation 1
• Use risk-adapted fractionation for large tumors, central location, or severe pulmonary disease 1