Relationship between radiation doses to heart substructures and radiation pneumonitis in patients with thymic epithelial tumors

Abstract

Radiation doses to the heart are potentially high in patients undergoing radiotherapy for thymoma or thymic carcinoma because of their origin site and propensity for pericardial invasion. We investigated potential relationships between radiation pneumonitis (Rp) and the dosimetric parameters of lung and heart substructures in patients with thymic epithelial tumors. this retrospective study included 70 consecutive patients who received definitive or postoperative radiotherapy at a median dose of 58.3 Gy. Heart substructures were delineated according to a published atlas. The primary end point of ≥ grade 2 RP was observed in 13 patients (19%) despite a low lung dose; median lung V20 (i.e. percentage of the volume receiving at least 20 Gy) was only 16.6%. In a univariate analysis, four lung parameters, heart V35, three pulmonary artery (PA) parameters, two left ventricle parameters, and left atrium V35 were associated with the development of RP. In a multivariate analysis, only PA V35 remained significant (hazard ratio 1.04; 95% CI 1.01-1.07, p = 0.007). PA V35 of the RP versus non-RP groups were 84.2% versus 60.0% (p = 0.003). The moderate dose sparing of PA could be a candidate as a planning constraint for reducing the risk of Rp in thoracic radiotherapy. Thymic epithelial tumors (TET) generally originate within the thymus of the anterior mediastinal region, and these advanced tumors are more likely to invade the pericardial space. When patients with advanced thymoma or thymic carcinoma receive radiotherapy (RT), doses to the heart may be markedly higher than in those with locally advanced (LA) non-small-cell lung cancer (NSCLC). The RTOG 0617 study recently reported a relationship between heart doses and overall survival (OS) in LANSCLC patients treated with chemoradiotherapy (CRT) 1. Thus, heart V5 and V30 (i.e. the percentage of the normal structure volume receiving more than the indicated dose) were both identified as important predictors of OS 1. Similar findings were reported by Speirs et al. 2 ; the heart dose was associated with both OS and cardiac toxicity in LANSCLC patients treated with CRT. Potential relationships between doses to heart substructures and non-cancer death have also been investigated in early-stage NSCLC patients treated with stereotactic body radiation therapy (SBRT) 3. However, these studies left one shared question unanswered: the uncertainty of the cause of death. Difficulties are often associated with distinguishing among death due to RT-associated cardiac toxicity, other treatment-related death, and death due to comorbidities, particularly in retrospective studies 2,3. Several types of RT-associated cardiac toxicities have been identified: e.g. ischemic, pericardial, valvular, and arrhythmic 4,5. Each type of RT-associated cardiac toxicity has a different underlying mechanism 4,5 ; however, tissue fibrosis is a common mediator. For example, patients with breast cancer and lymphoma are at risk of ischemic

Predictors of Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Definitive Chemoradiation Followed by Consolidative Durvalumab

“…Although heart dose may potentially be a surrogate for lung dose, previous studies have suggested a role for heart dose in the development of pneumonitis. 26 , 32 , 33 , 34 Our study detected a role for heart dosimetric parameters including MHD with a cut point of 10 Gy similar to a similar recently published case series which identified an MHD cut point of 5 Gy. 26 Similarly, we also found that increased cardiac dose metrics including MHD and V40 were correlated with increased risk of death corresponding to a Mayo Clinic case series, which showed worse OS with higher cardiac dose, as well as a secondary analysis of Radiation Therapy Oncology Group (RTOG) 0617, which showed certain cardiac dosimetry metrics corresponded with worse OS.…”

Radiation Pneumonitis in Thoracic Cancer Patients: Multi-Center Voxel-Based Analysis

“…In addition to the straightforward boost of statistical power granted by the increasing number of analyzed patients, which permitted us to obtain by the present study an unparalleled accuracy of the dose-response findings associated with RP of any grade. In particular, it is noteworthy that, despite the valuable independence of the dose values observed in the different substructures in the whole cohort (Figure 9), previously claimed interactions between the heart and the lungs in the RP development [38][39][40][41][42][43] are hereby confirmed. Indeed, we found, in the whole cohort, extended lung and heart regions in which the dose appears significantly correlated with the development of any-grade RP.…”

“…One hundred and six patients were treated at the Memorial Sloan Kettering Cancer Center of New York with stereotactic body RT (SBRT) for NSCLC. Patients received a median total dose of 50 Gy (range: [40,54] Gy) in median 4 fractions (range: [3,5]). Plans were designed in Eclipse v.13 (Varian Medical Systems, Palo Alto, CA, USA) using the AAA dose calculation engine.…”

Modulators of radiation-induced cardiopulmonary toxicities for non-small cell lung cancer: Integrated cytokines, single nucleotide variants, and HBP systems imaging

“…Some, but not all, of these reports suggested that minimizing the dose to the heart (“dose sparing”), particularly the upper regions of the heart, could improve RT-induced pneumonitis. One example involved evaluating the relationship between radiation doses to the heart and its substructures and pneumonitis during treatment for thymic epithelial tumors, because these tumors generally originate within the anterior mediastinal region and can spread into the pericardial space ( 25 ). This retrospective analysis indicated that RT-induced pneumonitis appeared despite the mean lung dose and lung V20 being lower than those used for locally advanced NSCLC, and that this seemed to be related to the dose (V35) to the pulmonary artery; the authors proposed that minimizing the dose to the pulmonary artery might reduce the incidence of pneumonitis in patients undergoing mediastinal RT.…”