Sparing Cardiac Substructures With Optimized Volumetric Modulated Arc Therapy and Intensity Modulated Proton Therapy in Thoracic Radiation for Locally Advanced Non-small Cell Lung Cancer

Ferris, Matthew J.; Martin, Katherine S.; Switchenko, Jeffrey M.; Kayode, Oluwatosin; Wolf, Jonathan; Dang, Quang; Press, Robert H.; Curran, Walter J.; Higgins, Kristin

doi:10.1016/j.prro.2019.04.013

Cited by 25 publications

(19 citation statements)

References 20 publications

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“…Concerning the sparing of lungs and cardiac structures with VMAT and IMPT, many studies addressed the issue also in different thoracic treatments. Ferris [29], for locally advanced non-small cell lung cancer and Scorsetti [30] and Baues [31] for Hodgkin's lymphoma patients, demonstrated that both techniques could achieve significant sparing of these structures with a clear benefit when protons are considered.…”

Section: Introductionmentioning

confidence: 99%

Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer

et al. 2020

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Background: To investigate the role of intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT), realised with RapidArc and RapidPlan methods (RA_RP) for neoadjuvant radiotherapy in locally advanced oesophagal cancer. Methods: Twenty patients were retrospectively planned for IMPT (with two fields, (IMPT_2F) or with three fields (IMPT_3F)) and RA_RP and the results were compared according to dose-volume metrics. Estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the lungs. For the cardiac structures, the relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated. Results: Both the RA_RP and IMPT approached allowed to achieve the required coverage for the gross tumour volume, (GTV) and the clinical and the planning target volumes, CTV and PTV (V 98% > 98 for CTV and GTV and V 95% > 95 for the PTV)). The conformity index resulted in 0.88 ± 0.01, 0.89 ± 0.02 and 0.89 ± 0.02 for RA_RP, IMPT_2F and IMPT_3F respectively. With the same order, the homogeneity index for the PTV resulted in 5.6 ± 0.6%, 4.4 ± 0.9% and 4.5 ± 0.8%. Concerning the organs at risk, the IMPT plans showed a systematic and statistically significant incremental sparing when compared to RA_RP, especially for the heart. The mean dose to the combined lungs was 8.6 ± 2.9 Gy for RA_RP, 3.2 ± 1.5 Gy and 2.9 ± 1.2 Gy for IMPT_2F and IMPT_3F. The mean dose to the whole heart resulted to 9.9 ± 1.9 Gy for RA_RP compared to 3.7 ± 1.3 Gy or 4.0 ± 1.4 Gy for IMPT_2F or IMPT_3F; the mean dose to the left ventricle resulted to 6.5 ± 1.6 Gy, 1.9 ± 1.5 Gy, 1.9 ± 1.6 Gy respectively. Similar sparing effects were observed for the liver, the kidneys, the stomach, the spleen and the bowels. The EAR per 10,000 patients-years of secondary cancer induction resulted in 19.2 ± 5.7 for RA_RP and 6.1 ± 2.7 for IMPT_2F or 5.7 ± 2.4 for IMPT_3F. The RR for the left ventricle resulted in 1.5 ± 0.1 for RA_RP and 1.1 ± 0.1 for both IMPT sets. For the coronaries, the RR resulted in 1.6 ± 0.4 for RA_RP and 1.2 ± 0.3 for protons.

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Section: Introductionmentioning

confidence: 99%

Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer

et al. 2020

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“…Our previous work found that integrating cardiac substructures into the re-optimization of retrospective thoracic RT plans drastically reduced dose to sensitive substructures with a negligible increase in plan complexity while maintaining other clinical dosimetric endpoints [29]. Cardiac substructure sparing via volumetric modulated arc therapy was shown by Ferris et al who achieved significant improvements in mean dose to the chambers, great vessels, and coronary arteries [30]. These studies underscore the importance in considering cardiac substructures in planning which will also require adequate setup and motion margin consideration.…”

Section: Discussionmentioning

confidence: 99%

Quantifying inter-fraction cardiac substructure displacement during radiotherapy via magnetic resonance imaging guidance

Morris

Ghanem

Zhu³

et al. 2021

Physics and Imaging in Radiation Oncology

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Emerging evidence suggests cardiac substructures are highly radiosensitive during radiation therapy for cancer treatment. However, variability in substructure position after tumor localization has not been well characterized. This study quantifies inter-fraction displacement and planning organ at risk volumes (PRVs) of substructures by leveraging the excellent soft tissue contrast of magnetic resonance imaging (MRI).Eighteen retrospectively evaluated patients underwent radiotherapy for intrathoracic tumors with a 0.35 T MRI-guided linear accelerator. Imaging was acquired at a 17-25 s breath-hold (resolution 1.5 × 1.5 × 3 mm 3 ). Three to four daily MRIs per patient (n = 71) were rigidly registered to the planning MRI-simulation based on tumor matching. Deep learning or atlas-based segmentation propagated 13 substructures (e.g., chambers, coronary arteries, great vessels) to daily MRIs and were verified by two radiation oncologists. Daily centroid displacements from MRI-simulation were quantified and PRVs were calculated.Across substructures, inter-fraction displacements for 14% in the left-right, 18% in the anterior-posterior, and 21% of fractions in the superior-inferior were > 5 mm. Due to lack of breath-hold compliance, ~4% of all structures shifted > 10 mm in any axis. For the chambers, median displacements were 1.8, 1.9, and 2.2 mm in the left-right, anterior-posterior, and superior-inferior axis, respectively. Great vessels demonstrated larger displacements (> 3 mm) in the superior-inferior axis (43% of shifts) and were only 25% (left-right) and 29% (anterior-posterior) elsewhere. PRVs from 3 to 5 mm were determined as anisotropic substructure-specific margins.This exploratory work derived substructure-specific safety margins to ensure highly effective cardiac sparing. Findings require validation in a larger cohort for robust margin derivation and for applications in prospective clinical trials.

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“…Some studies have aimed to investigate the dosimetric impact of different types of therapy on cardiac substructure sparing. A study by Ferris et al 35 evaluated cardiac substructure sparing for optimized volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) and found that cardiac‐optimized plans led to statistically significant improvements in mean dose to the chambers, great vessels, and coronary arteries. Our findings agree with Ferris et al with respect to significant reductions in the maximum dose to the LADA and RV (>4 Gy on average) while maintaining or improving clinical OAR (e.g., lung, esophagus, and spinal cord) constraints and PTV coverage.…”

Section: Discussionmentioning

confidence: 99%

“…At present, few studies have integrated cardiac substructures into treatment planning optimization. Ferris et al evaluated cardiac spared plans using VMAT and IMPT with CT for locally advanced non‐small lung cancer patients with a conventional fractionation to 60 Gy under free‐breathing conditions 35 . Lester et al focused on cardiac spared planning for mediastinal lymphomas by incorporating ECG‐gated CT and coronary angiography acquired at deep inspiration breath hold 36 .…”

Section: Discussionmentioning

confidence: 99%

Incorporating sensitive cardiac substructure sparing into radiation therapy planning

Morris

Aldridge²,

Ghanem

et al. 2020

J Applied Clin Med Phys

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Purpose: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low-field MRIs acquired on an MR-linac via image registration to further enable cardiac substructure sparing on TPCTs. Methods: Sixteen upper thoracic patients treated at various breathing states (7 end-exhalation, 7 end-inhalation, 2 free-breathing) on a 0.35T MR-linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three-dimensional (3D) U-Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re-optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV-V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches. Results: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re-optimized plans reduced left anterior descending artery (LADA) mean and LADA 0.03cc (0.0-63.9% and 0.0-17.3 Gy, respectively). LV 0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV-V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D 0.03cc. One patient exhibited >10 Gy reduction in D 0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re-optimization. Four patients benefited from new beam arrangements, leading to further dose reductions. Conclusions: By introducing 0.35T MRIs acquired on an MR-linac to verify cardiac substructure segmentations for CT-based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation-related cardiotoxicities.

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Sparing Cardiac Substructures With Optimized Volumetric Modulated Arc Therapy and Intensity Modulated Proton Therapy in Thoracic Radiation for Locally Advanced Non-small Cell Lung Cancer

Cited by 25 publications

References 20 publications

Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer

Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer

Quantifying inter-fraction cardiac substructure displacement during radiotherapy via magnetic resonance imaging guidance

Incorporating sensitive cardiac substructure sparing into radiation therapy planning

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