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

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.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1001-6) contains supplementary material, which is available to authorized users.

Stereotactic ablative radiotherapy of 60 Gy in eight fractions is safe for ultracentral non‐small cell lung cancer

“…The rate of grade 2 or 3 toxicity was 7.9% and no grade 4 or 5 toxicities were observed. Murrell et al 19 suggested that 60 Gy in eight fractions was practical. Table 5 summarizes several other studies on SBRT for ultracentral lung cancer.…”

Risk‐adapted stereotactic body radiation therapy for central and ultra‐central early‐stage inoperable non‐small cell lung cancer

“…Organs at risk contouring was adopted from RTOG 0813, EORTC LungTech, SUNSET, and RTOG 1106 contouring atlas, and normal tissue constraints were adopted from RTOG 0813 and previous HILUS studies . Meanwhile, maximum point dose and volumetric maximum dose analyses were evaluated for OAR including esophagus, heart, pulmonary artery, pulmonary vein, spinal cord, ipsilateral lung, contralateral lung, lung total, trachea, mainstem bronchi, lobe bronchi, and proximal bronchial tree.…”

“…Organs at risk contouring was adopted from RTOG 0813, 35 EORTC LungTech, 36 SUNSET, 18 and RTOG 1106 contouring atlas, 37 and normal tissue constraints were adopted from RTOG 0813 and previous HILUS studies. 6,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Meanwhile, maximum point dose and volumetric maximum dose analyses were evaluated for OAR including esophagus, heart, pulmonary artery, pulmonary vein, spinal cord, ipsilateral lung, contralateral lung, lung total, trachea, mainstem bronchi, lobe bronchi, and proximal bronchial tree. Treated doses were converted to biologically effective doses (BED) based on the formula: nd [1 + d/(α/β)], where n is number of fractions, and d is dose/fraction (Gy); assuming α/β value of 10 for NSCLC (ie BED 10 ) and α/β value of 3 for normal tissues (ie BED 3 ).…”

“…In the 2010s, a new subgroup within the cohort of patients with central tumors was designated as “high‐risk” or “ultra‐central” tumors, or those that abut the PBT . Ultra‐central tumors have increased grade 4+ toxicity, even with conservative radiotherapy fractionation .…”

“…11,12 In the 2010s, a new subgroup within the cohort of patients with central tumors was designated as "high-risk" or "ultra-central" tumors, or those that abut the PBT. 7,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Ultra-central tumors have increased grade 4+ toxicity, even with conservative radiotherapy fractionation. 25 Of concern, Haseltine et al reported that in patients with PBT-abutting tumors who received conservative dose-fractionation SBRT plus bevacizumab, two patients experienced grade 5 pulmonary hemorrhages.…”