Heart Dose Is an Independent Dosimetric Predictor of Overall Survival in Locally Advanced Non–Small Cell Lung Cancer

Abstract

Introduction: In the randomized trial of standard-versus high-dose chemoradiotherapy for locally advanced (LA) NSCLC (Radiation Therapy Oncology Group 0617), overall survival (OS) was worse in the high-dose arm. Although heart dose was suggested as a contributing factor, actionable parameters have not been established. We present an analysis of clinical and dosimetric parameters affecting OS in this patient population, focusing on heart dose. Methods: Clinical data were collected on 416 patients with LA NSCLC treated at a single institution, with a subset of 333 available treatment plans recontoured using Radiation Therapy Oncology Group 0617 normal tissue guidelines. Toxicity and dosimetry data were analyzed for 322 patients; multivariate analysis was performed on 251 patients. Dosimetric parameters of radiation to tumor and organs at risk were analyzed with clinical data pertaining to OS, disease-free survival, and toxicity. Results: Patients were treated with radiation therapy to prescribed doses of 50.0 to 84.9 Gy (median 66.0 Gy). Median follow-up was 14.5 months. Median OS was 16.8 months. The 1-and 2-year OS rates were 61.4% and 38.8%, respectively. On multivariate analysis, factors independently associated with worse OS were increasing heart V 50 (volume receiving 50 Gy), heart volume, lung V 5 (proportion of the lung structure [excluding the target volume]) receiving at least 5 Gy), bilateral mediastinal lymph node involvement, and lack of concurrent chemotherapy. When stratified by heart V 50 less than 25% versus 25% or greater, the 1-year OS rates were 70.2% versus 46.8% and the 2-year OS rates were 45.9% versus 26.7% (p < 0.0001). Median heart V 50 was significantly higher (20.8% versus 13.9%, p < 0.0001) for patients with cardiac toxicity with a Common Terminology Criteria for Adverse Events grade of 1 or higher. Conclusions: Heart dose is associated with OS and cardiac toxicity for patients with LA NSCLC treated with chemoradiotherapy.

Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy

“…It is especially important for patients with upper gastrointestinal tumors, given its impact on organs in the mediastinum and abdomen. Dose and volume to critical organs, including the heart, lungs, kidneys, liver, small bowel, and spinal cord, have been linked to morbidity, and in some cases survival . The dosimetric superiority of more conformal techniques such as intensity‐modulated RT (IMRT) over 3‐dimensional conformal RT (3DCRT) has been well documented.…”

“…Dose and volume to critical organs, including the heart, lungs, kidneys, liver, small bowel, and spinal cord, have been linked to morbidity, and in some cases survival. [12][13][14]22 The dosimetric superiority of more conformal techniques such as intensitymodulated RT (IMRT) over 3-dimensional conformal RT (3DCRT) has been well documented. Series have shown significant reductions in doses to the lungs (mean volume of the lung receiving a dose of at least 10 Gy [V10] and V20) and heart (mean, V30 [right coronary]) in patients with esophageal and GEJ adenocarcinomas.…”

Heart dosimetric analysis of three types of cardiac toxicity in patients treated on dose-escalation trials for Stage III non-small-cell lung cancer

“…5 On the other hand, studies with a larger number of patients including RTOG 0617 and analyses by Stam et al (which analyzed patients with early stage lung cancer) and Speirs et al were able to find an association between heart dose and decreased survival. 4,8,43 …”

The Role of Mitochondrial Dysfunction in Radiation-Induced Heart Disease: From Bench to Bedside

“…Other studies have also examined the association between mean heart dose and cardiac events/disease, finding an ∼4-16% increased risk per Gy of mean heart dose (7)(8)(9). Studies have also suggested RIHD can occur in non-small cell lung cancer patients within 2 years post-radiation exposure (8)(9)(10)(11). In a number of lung cancer studies, mortality rates were cardiac dose-dependent, either based on mean heart dose (12) or with the percent of heart receiving 5 Gy (13), 30 Gy (13), or 50 Gy (10).…”

“…Studies have also suggested RIHD can occur in non-small cell lung cancer patients within 2 years post-radiation exposure (8)(9)(10)(11). In a number of lung cancer studies, mortality rates were cardiac dose-dependent, either based on mean heart dose (12) or with the percent of heart receiving 5 Gy (13), 30 Gy (13), or 50 Gy (10). In pediatric and young adult cancer patients who received cardiac radiation, there is over a 6-fold relative risk of RIHD, defined as congestive heart failure, myocardial infarction, pericardial disease, and/or valvular abnormalities (14).…”