Dataset Information

Analysis of pneumonitis and esophageal injury after stereotactic body radiation therapy for ultra-central lung tumors.

ABSTRACT:

Objectives

SBRT has been associated with serious toxicity in ultra-central lung tumors, but little is known about the incidence and dosimetric correlates of pulmonary and esophageal complications in this setting.

Materials and methods

We retrospectively reviewed SBRT patients whose lung tumor abutted proximal airways, or whose planning target volume overlapped esophagus. All patients received 5-15 fractions of high-dose, image-guided radiation. The primary endpoint was SBRT-related toxicity, with local control and survival as secondary endpoints.

Results

We included 88 patients. Nineteen patients (22 %) experienced grade ≥3 (G3+) toxicity, including 6 cases of G3+ radiation pneumonitis and 4 cases of G3+ esophageal injury. Two patients developed trachea-esophageal fistula. Overall incidence of radiation pneumonitis was 23 %. Ten patients (11.4 %) succumbed to SBRT-related complications. Multiple dosimetric parameters for lung (including mean lung dose and V20_Gy) and esophagus (including maximum point dose) correlated with radiation pneumonitis and esophageal toxicity, respectively. No impact of fractionation on toxicity was seen.

Conclusion

This analysis indicates that high rate and multiple manifestations of pulmonary and esophageal toxicity occur after SBRT for ultra-central tumors. In particular, severe radiation pneumonitis and tracheoesophageal fistula are possible. Dosimetric parameters such as mean lung dose and maximum esophageal dose are significantly correlated with toxicity. Further study is needed to optimize the safe delivery of SBRT in these patients.

SUBMITTER: Wang C

PROVIDER: S-EPMC7484437 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRadiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT).MethodsAmong consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ≥6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis.ResultsFive hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ≥ grade 2 and ≥ grade 3 were significantly lower in CAM-era (grade ≥2, 16% vs. 9.6%, P=0.047; grade ≥3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ≥ grade 3 was significantly lower, and that of grade ≥2 had a lower tendency (grade ≥3, 7.2% vs. 0%, P=0.011; grade ≥2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ≥ grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ≥ grade 2 and ≥ grade 3.ConclusionsCAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be conﬁrmed in prospective studies.

Project description:PurposeStereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters.Methods and materialsWe identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity.ResultsOne hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT ("no-fly-zone" [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum.ConclusionsUsing moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.