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Abstract
BackgroundLung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, however there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed ‘ultra-central’ tumors. As there is no consensus regarding the optimal radiotherapy treatment regimen for these tumors, we performed a modeling study to evaluate the trade-offs between predicted toxicity and local control for commonly used high-precision dose-fractionation regimens.MethodsTen patients with ultra-central lung tumors were identified from our institutional database. New plans were generated for 3 different hypofractionated schemes: 50 Gy in 5 fractions, 60 Gy in 8 fractions and 60 Gy in 15 fractions. For each regimen, one plan was created that prioritized planning target volume (PTV) coverage, potentially at the expense of organ at risk (OAR) tolerance, and a second that compromised PTV coverage to respect OAR dose constraints. Published radiobiological models were employed to evaluate competing treatment plans based on estimates for local control and the likelihood for toxicity to OAR.ResultsThe risk of esophageal or pulmonary toxicity was low (< 5%) in all scenarios. When PTV coverage was prioritized, tumor control probabilities were 92.9% for 50 Gy in 5 fractions, 92.4% for 60 Gy in 8 fractions, and 52.0% for 60 Gy in 15 fractions; however the estimated risk of grade ≥ 4 toxicity to the proximal bronchial tree was 68%, 44% and 2% respectively. When dose to OAR was prioritized, the risk of major pulmonary toxicity was reduced to < 1% in all schemes, but this compromise reduced tumor control probability to 60.3% for 50 Gy in 5 fractions, 65.7% for 60 Gy in 8 fractions and 47.8% for 60 Gy in 15 fractions.ConclusionsThe tradeoff between local control and central airway toxicity are considerable in the use of 3 commonly used hypofractionated radiotherapy regimens for ultra-central lung cancer. The results of this planning study predict that the best balance may be achieved with 60 Gy in 8 fractions compromising PTV coverage as required to maintain acceptable doses to OAR. A prospective phase I trial (SUNSET) is planned to further evaluate this challenging clinical scenario.
Highlights
Lung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed ‘ultra-central’ tumors
When dose to the organs at risk was prioritized, planning target volume (PTV) coverage by the 100% isodose line for the 50 Gy in 5 fraction regimen was reduced from 96.0% (95.0–100) to 67.8% (19.6–89.2); for 60 Gy in 8, from 96.0% (95.0–99.9) to 68.5% (18.8–89.5); and for 60 Gy in 15 fractions, coverage by the 95% isodose line was reduced from 97.3% (95.5–100) to 91.6% (82.0– 97.8)
A comparison of the OARprioritized with PTV-prioritized plans illustrates an appreciable difference in dose to the proximal bronchial tree and esophagus for all fractionation regimens, whereas dose to the lung was similar regardless of plan or prioritization
Summary
Lung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed ‘ultra-central’ tumors. Morbidity is low when SABR is employed for tumors that are peripherally located, and risk-adapted schemes can be employed when the lesion is near critical mediastinal structures at increased risk for treatment-related toxicity. The magnitude of such risk has been the subject of debate and the optimal SABR dose-fractionation regimen for central tumors is an active area of research [1, 2]. Tumors directly abutting or invading the proximal bronchial tree – defined as ‘ultracentral’ lung tumors – were not addressed in the RTOG 0813 or LungTech trials and represent what is likely to be a higher-risk subgroup
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