ABSTRACT

PURPOSE/OBJECTIVE(S): Cardiotoxicity is a significant late effect of esophageal radiotherapy (RT). Mean heart dose has been implicated with major adverse cardiac events (MACE) and emerging evidence increases MACE association with left anterior descending (LAD) coronary artery specific dose. This retrospective planning study investigates the dosimetric impact of including the LAD as an OAR-sparing objective for VMAT-based plan optimization in patients previously treated for esophageal cancers.

MATERIALS/METHODS: A retrospective cohort was identified of patients who underwent neoadjuvant RT for esophageal cancers between 2017-2020 without intentional LAD sparing. Treatment planning was performed using Eclipse™ treatment planning system. Doses were calculated using Acuros® XB algorithm or anisotropic analytical algorithm with a 2-2.5mm calculation grid. For each patient, the LAD was delineated and the treated VMAT plan was re-optimized to reduce the dose to the LAD receiving 15 Gy to less than 10%, when possible. Re-plans were performed such that 95% of the PTV received the prescription dose. Institutional constraints were used to minimize the dose to the heart, lung, and spinal cord (Table 1). A paired t-test was used to compare the dose between the original VMAT plan used for treatment (Esophagus Original) against those re-optimized (Esophagus + LAD), with significance of p

RESULTS: A total of 19 patients were identified. Of those treated, 12 of 19 original plans (63%) exceeded the LAD constraint (V15<10%)

CONCLUSION: Accounting for LAD dose in treatment planning may help reduce future MACE risks. LAD dose can be significantly reduced without compromising PTV coverage or having significant effects on other OAR dose sparing.

PMID:37786067 | DOI:10.1016/j.ijrobp.2023.06.2197

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PubMed articles on: Cardio-Oncology

Simulation CT Features and Radiation Cardiotoxicity in Non-Small Cell Lung Cancer

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e69. doi: 10.1016/j.ijrobp.2023.06.799.

ABSTRACT

PURPOSE/OBJECTIVE(S): Radiation cardiotoxicity is a significant clinical dilemma in non-small cell lung cancer (NSCLC) radiation therapy (RT). Baseline cardiovascular (CV) status may influence the risk of cardiotoxicity, and may be ascertainable from the appearance of the heart on simulation computed tomography (CT). We examined the association of CT features with incidental heart dose and risk of cardiac events in NSCLC.

MATERIALS/METHODS: Patients treated with curative-intent RT between 2015 and 2020 at a regional center were identified. Clinical notes were interrogated for baseline patient and CV health details, and follow-up CV events. Cardiac events were verified by a cardiologist. A deep learning-based auto-segmentation tool was applied, allowing extraction of a pre-specified list of volume parameters in a programming environment. CAC was graded as none, mild, moderate and severe in patients with a non-contrast scan. The craniocaudal relationship of the PTV and heart (Feng atlas) were annotated.

RESULTS: A total of 478 patients were included, with a median age of 70 and Charlson Index of 5. The median mean heart dose was 6.3 Gy (IQR 2.7-11.4). The median lung V20 was 20.0% (IQR 14.8-27.1). Cardiovascular risk factors were common, with most patients having 2 (39%) or 3 (31%). A history of previous cardiac events was common, including myocardial infarction (14%), arrhythmia (11%) or heart failure (9%). A total of 6.9% and 7.1% patients developed a new atrial arrhythmia (AA) or heart failure (HF) after completing RT. The volume metrics with the highest AUC for AA and HF events were the left atrium (LA) (AUC 0.67, p = 0.0002) and left ventricle:right ventricle (LV:RV) ratio (AUC 0.66, p = 0.0021). Kaplan-Meier analysis for cardiac events dichotomizing at the optimal cut-point for maximum sensitivity and specificity demonstrated significantly different rates for both AA (LA 109cc, HR 3.35, 95% CI 1.64-6.83, p = 0.0009) and HF (LV:RV ratio 1.61, HR 2.37, 95% CI 1.19-4.74, p = 0.0143). Only 2 patients with non-contrast scans developed a myocardial infarction, both had mild CAC. The incidence of pooled cardiac events was not significantly different between patients with no (n = 2/21, 9.5%), mild (n = 10/38, 26.3%), moderate (n = 8/53, 15.1%) and severe (n = 7/24, 29.2%) CAC (p = 0.3916). Where the inferior border of the PTV was above the superior border of the heart, mean heart dose was significantly lower than compared with overlap of levels (1.9 Gy v 9.7 Gy, p<0.0001),<0.001),<0.001)<0.001)

CONCLUSION: LA volume and LV:RV volume ratio are predictive for the development of AA and HF respectively. CAC grade did not differentiate patients by risk of cardiac events. Where the craniocaudal level of the PTV doesn't overlap with the level of the heart, the cardiac dose is likely to be very low. Several simulation CT features are associated with cardiac events following treatment for NSCLC and prospective evidence of cardiac risk could enable medical optimization prior to RT.

PMID:37786027 | DOI:10.1016/j.ijrobp.2023.06.799

12:52

PubMed articles on: Cardio-Oncology

Patient-Level and Endpoint-Specific Clinico-Dosimetric Analysis of the Cardiac Base as a Mediator of Radiation Cardiotoxicity in Non-Small Cell Lung Cancer

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e69-e70. doi: 10.1016/j.ijrobp.2023.06.800.

ABSTRACT

PURPOSE/OBJECTIVE(S): Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer (NSCLC) radiation therapy. Radiation dose to the cardiac base is associated with poor overall survival in several clinical studies, but has not been validated in a non-dose escalated cohort, or with individual patient delineations. In this study we examined the impact of cardiac base dose on overall survival (OS) and cardiac events (CEs), and interrogated the relationships of the substructures comprising the heart base with OS and CEs.

MATERIALS/METHODS: Patients with stage I-III NSCLC treated with curative-intent radiation therapy between 2015 and 2020 at a regional cancer center were identified. Clinical notes were examined for baseline patient, tumor and cardiac details, and both cancer and cardiac outcomes. Three cardiologists verified CEs. Cardiac delineations were completed using a validated deep learning-based autosegmentation tool. Cox and Fine and Gray regressions were undertaken for the risk of death and CEs respectively, accounting for pre-specified evidence-based dose metrics and clinically relevant cardiac covariates.

RESULTS: Most patients received 55 Gy/20# (n = 461/478, 96%) without chemotherapy (58%), planned with VMAT (51%) or IMRT (20%). Pre-existing cardiovascular morbidity was common, with 78% having ≥2 risk factors, and 46% having >1 established cardiac disease. The median follow-up was 21.1 months. Dichotomized at the median, higher heart base Dmax was associated with poorer survival on Kaplan-Meier analysis (21.6 months (95% CI 19.3-24.9) versus 29.4 months (95% CI 21.6-36.6), p = 0.021), and remained significant when statistically compared in published multivariate models. In a multivariate analysis for pooled acute CEs, heart base Dmax was associated with CEs (HR 1.75, 95% CI 1.01-1.06, p = 0.04), but this was not the case for individual CEs. Using Fine and Gray models to account for the competing risk of death, left main coronary maximum dose was associated with atrial fibrillation (p = 0.024), proximal right coronary artery V15 (p = 0.023) and mean dose (p = 0.032), and the right atrium mean dose (p = 0.029) were associated with heart failure. No dose-volume metrics were significantly associated with acute coronary syndrome. None of the constituent base substructures dose were significantly associated with death.

CONCLUSION: Dose to the heart base was associated with increased mortality and an increased pooled cardiac event rate. Accounting for endpoint-specific clinical covariates, only select constituent substructures of the heart base were associated with CEs and no substructures were independently associated with survival. Together, these findings are suggestive of possible interplay between the constituent base substructures in their mediation of radiation cardiotoxicity.

PMID:37786026 | DOI:10.1016/j.ijrobp.2023.06.800

12:52

PubMed articles on: Cardio-Oncology

Planning Considerations for the Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Radiotherapy for Locally-Advanced Non-Small Cell Lung Cancer

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e48-e49. doi: 10.1016/j.ijrobp.2023.06.754.

ABSTRACT

PURPOSE/OBJECTIVE(S): Phase III prospective randomized trial of primary lung tumor stereotactic body radiation therapy followed by concurrent mediastinal chemoradiation for locally-advanced non-small cell lung cancer (NRG LU-008), designed to lower the rates of radiation pneumonitis and improve the progression-free survival, is expected to become active nationally in July 2023. Due to the specific nature of the cases selected for this trial, a new approach to treatment planning had to be developed to satisfy the conditions of the trial. Levice Cancer Institute (Atrium Health, North Carolina) ran the initial Phase II trial and investigated several approaches, providing recommendations for the future dosimetry planning approach.

MATERIALS/METHODS: A total of 60 patients were selected for the initial trial and treated with a combination of SBRT treatment to the primary tumor (50-54 Gy in 3-5 fractions) and conventional IMRT treatment to 60 Gy to the involved lymph nodes for patients with stage 3 or unresectable stage II NSCLC, combined with chemotherapy. Depending on the location of the primary tumor, all cases could be subdivided into no overlap between the SBRT and IMRT targets, adjacent targets, and overlapping targets. All SBRT plans were done with a 6X-FFF beam, advanced dose calculation algorithm, and 0.1 cm grid size. IMRT targets were primarily treated with VMAT plans, though a minority of cases were planned with the DMLC technique, with a 6X beam, advanced dose calculation algorithm, and 0.25 cm grid size. Various approaches to the planning included target cropping, avoidance via adjusting optimization objectives and utilizing the base dose of the SBRT plan to optimize the dose for the IMRT nodal plan. Various geometries utilized in the plan included a variation in the number of arcs, covered arc angles, and the number of beams.

RESULTS: A significant reduction in the side effects was achieved throughout the trial, with only three patients experiencing grade 3 or higher pneumonitis, 3 patients experiencing grade 3 or higher cardiotoxicity, and 1 patient experiencing grade 3 esophagitis. For targets with no significant overlap between the primary tumor and nodal target, standard planning techniques proved to be sufficient. For the overlapping targets, the planning approach of utilizing 2 arcs, >180-degree coverage, for the SBRT plan, and using ¼ of the base SBRT dose to plan the IMRT nodal plan provided the best target coverage while achieving sufficient OAR sparing.

CONCLUSION: Planning the joint SBRT-IMRT plan in the cases of a significant target overlap requires a careful approach, but is feasible with the proposed guideline and should be achievable for any center electing to participate in the NRG LU-008 trial.

PMID:37785520 | DOI:10.1016/j.ijrobp.2023.06.754

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PubMed articles on: Cardio-Oncology

Tracking Changes in Global Longitudinal Strain in Lung Cancer Patients Receiving Thoracic Radiation

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e252-e253. doi: 10.1016/j.ijrobp.2023.06.1196.

ABSTRACT

PURPOSE/OBJECTIVE(S): Thoracic radiation improves survival in many lung cancer patients. However, radiation-induced cardiotoxicity is a major source of morbidity and mortality in such patients. Global longitudinal strain (GLS), a novel echocardiography (ECHO) method of assessing left ventricular function, has been shown to predict long-term adverse cardiovascular risk in diverse patient populations. We hypothesized that receipt of thoracic radiation is associated with GLS changes in lung cancer patients.

MATERIALS/METHODS: We retrospectively identified patients with lung cancer treated at our institution between 2005-2020 who had ECHOs performed both before and after RT, and in whom GLS was extractable. ECHO Board-Certified cardio-oncologists measured GLS and left ventricular ejection fraction (LVEF) from these ECHOs.

RESULTS: A total of 40 patients met inclusion criteria. Median time to ECHO was 78 days prior and 172 days after RT. Two chamber (2C), 3C, 4C, and average GLS were significantly decreased after RT on paired t-test [mean difference (SD) 2.23 (3.29), 2.99 (2.78), 2.25 (3.63), 2.51 (2.66) respectively, all p < 0.001]. Thirteen patients (32.5%) had abnormal GLS (<18%)<50%)

CONCLUSION: This cohort exhibited a significant decrease in 2C, 3C, 4C, and average GLS after RT. ∼1/3 of patients had abnormal GLS at baseline (suggesting a high-risk group for cardiac complications) and 67.5% of patients had clinically significant decrease in GLS after RT. Among the patients with normal GLS before RT, although 51.9% of patients demonstrated a clinically significant drop in GLS after RT, only 3.7% of patients developed abnormal LVEF, suggesting that this is a late occurrence. GLS changes may serve as a valuable tool for early identification of patients who are at high risk for future cardiac complications after receiving thoracic radiation.

PMID:37784979 | DOI:10.1016/j.ijrobp.2023.06.1196

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PubMed articles on: Cardio-Oncology

The Predictive Value of Changes in Basal Myocardial F-18 Fluorodeoxyglucose Uptake for Cardiotoxicity in Locally Advanced Esophageal Cancer Patients Receiving Definitive Radiotherapy

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e285. doi: 10.1016/j.ijrobp.2023.06.1272.