Stereotactic ablative radiotherapy for ultra-central lung tumors: prioritize target coverage or organs at risk?

Abstract

Background: Lung 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.

Methods: Ten 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.

Results: The 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.

Conclusions: The 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.

Keywords: Normal tissue complication probability; Stereotactic ablative radiotherapy; Ultra-central lung tumor.

Fig. 1

An illustrative example of a contoured ultra-central lung tumor case. The relative locations of tumor and OAR are indicated; IGTV (red), PTV (blue), proximal bronchial tree (yellow), esophagus (green), heart (maroon), and healthy lung (cyan). Here, the PTV volume is 83.1 cm³ and 2.2 cm³ overlap with the proximal bronchial tree

Fig. 2

Dose-volume relationships in 2 Gy per fraction for competing dose-fractionation regimens, based on α/β =3 for OAR and α/β = 10 for tumor. Data are graphed at 50 cGy resolution and are expressed as the median (PTV) or average (OAR) fractional volumes to illustrate the relative differences in PTV coverage and OAR sparing between the treatment plans

Fig. 3

Relationship between likelihood of proximal bronchial tree injury and the tumor overlap volume. The risk of grade 4 or 5 toxicity to the proximal bronchial tree based on D_1cc vs. PTV overlap volume with the proximal bronchial tree for plans that prioritize PTV coverage