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      Enhanced cardiac substructure sparing through knowledge-based treatment planning for non-small cell lung cancer radiotherapy

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          Abstract

          Radiotherapy (RT) doses to cardiac substructures from the definitive treatment of locally advanced non-small cell lung cancers (NSCLC) have been linked to post-RT cardiac toxicities. With modern treatment delivery techniques, it is possible to focus radiation doses to the planning target volume while reducing cardiac substructure doses. However, it is often challenging to design such treatment plans due to complex tradeoffs involving numerous cardiac substructures. Here, we built a cardiac-substructure-based knowledge-based planning (CS-KBP) model and retrospectively evaluated its performance against a cardiac-based KBP (C-KBP) model and manually optimized patient treatment plans. CS-KBP/C-KBP models were built with 27 previously-treated plans that preferentially spare the heart. While the C-KBP training plans were created with whole heart structures, the CS-KBP model training plans each have 15 cardiac substructures (coronary arteries, valves, great vessels, and chambers of the heart). CS-KBP training plans reflect cardiac-substructure sparing preferences. We evaluated both models on 28 additional patients. Three sets of treatment plans were compared: (1) manually optimized, (2) C-KBP model-generated, and (3) CS-KBP model-generated. Plans were normalized to receive the prescribed dose to at least 95% of the PTV. A two-tailed paired-sample t-test was performed for clinically relevant dose-volume metrics to evaluate the performance of the CS-KBP model against the C-KBP model and clinical plans, respectively. Overall results show significantly improved cardiac substructure sparing by CS-KBP in comparison to C-KBP and the clinical plans. For instance, the average left anterior descending artery volume receiving 15 Gy (V15 Gy) was significantly lower (p < 0.01) for CS-KBP (0.69 ± 1.57 cc) compared to the clinical plans (1.23 ± 1.76 cc) and C-KBP plans (1.05 ± 1.68 cc). In conclusion, the CS-KBP model significantly improved cardiac-substructure sparing without exceeding the tolerances of other OARs or compromising PTV coverage.

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          Most cited references40

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          Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study

          The Lancet Oncology, 16(2), 187-199
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            Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures

            Purpose A relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD. Patients and Methods The cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data. Results The median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91). Conclusion A significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.
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              Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer.

              Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                02 December 2022
                2022
                : 12
                : 1055428
                Affiliations
                [1] Department of Radiation Oncology and Winship Cancer Institute, Emory University , Atlanta, GA, United States
                Author notes

                Edited by: James Chow, University of Toronto, Canada

                Reviewed by: Joshua Niedzielski, University of Texas MD Anderson Cancer Center, United States; Ahmed I. Ghanem, Henry Ford Health System, United States

                *Correspondence: Shadab Momin, shadab.momin@ 123456emory.edu

                This article was submitted to Radiation Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.1055428
                9755869
                36531046
                bf59d3de-5b32-487d-bb71-6e7fcf4746a0
                Copyright © 2022 Momin, Wolf, Roper, Lei, Liu, Bradley, Higgins, Yang and Zhang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 September 2022
                : 10 November 2022
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 40, Pages: 10, Words: 4817
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                knowledge based treatment planning,cardiac substructures,non-small cell lung cancer radiotherapy,machine learning,cardiac toxicities

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