The Limits of the Linear Quadratic (LQ) Model for Late Cardiotoxicity Prediction: Example of Hypofractionated Rotational Intensity Modulated Radiation Therapy (IMRT) for Breast Cancer

Loap, Pierre; Kirova, Youlia

doi:10.1016/j.ijrobp.2019.12.006

Cited by 19 publications

(10 citation statements)

References 9 publications

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“…In the present study, as a consequence of using the 40/15 regimen instead of the 50/25 regimen, albeit not statistically signi cant, the MHD decreased by 1.5 Gy and 0.71 Gy under FB and CPAP conditions, respectively. The maximum LAD dose showed a signi cant reduction of 9.3 Gy and 8.4 Gy with an HF schedule in FB and CPAP conditions, respectively; this nding is similar to that reported by Pierre et al [10]. In addition, the 40/15 HF schedule can help reduce the lung dose to a greater extent than the 50/25 schedule, a result consistent with that of a previous study [25].…”

Section: Discussionsupporting

confidence: 91%

“…In light of the accumulating evidence regarding the safety and effectiveness of hypofractionated radiotherapy (HF-RT), the 3-week schedule of 40 Gy in 15 fractions is being increasingly selected in the treatment of breast cancer, especially during the current coronavirus disease (COVID-19) pandemic [9]. Rotational IMRT such as VMAT has been suggested to reduce the dose to cardiac substructures in the hypofractionated (HF) group [10]. However, how they (cardiac sparing techniques, IMRT/PBT, and HF-RT) affect dose avoidance to the organs-at-risk (OARs) individually or in any combination is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study

Chang

Moon

et al. 2020

Preprint

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Background: Radiotherapy (RT) target volumes in breast cancer treatment increasingly include the internal mammary nodes, potentially increasing doses delivered to the heart and lung. The aim of this study was to compare cardiac and pulmonary doses in three-dimensional conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), and proton beam therapy (PBT) with and without continuous positive airway pressure (CPAP), delivered in conventional fractionation (CF) or in hypofractionated (HF) schedules.Methods: In a dataset of 15 patients with left-sided breast cancer, partial wide tangential 3DCRT delivered in CF (50/25) and in HF (40/15) schedules as well as PBT delivered in CF and two-partial arc VMAT delivered in a HF schedule, each under CPAP and free breathing (FB) conditions were extensively examined. Target volume coverage and doses to organs-at-risk (OARs) were calculated for each technique. Outcomes were compared with one-way analysis of variance and the Bonferroni test, with P-values <0.05 considered significant. Results: Target volume coverage was within acceptable levels in all interventions, except for internal mammary lymph nodes D90 (99% in PBT, 90% in VMAT-CPAP, 84% in VMAT-FB, and 74% in 3DCRT). Mean heart dose (MHD) was the lowest and highest in PBT (<1 Gy) and 3DCRT with CF/FB (7.8 Gy), respectively. In photon-based techniques, the use of VMAT in HF schedules with CPAP resulted in an MHD of 2.2 Gy. Lung V20 and mean lung dose (MLD) were the highest in 3DCRT-CF-FB (44% and 20 Gy, respectively) and lowest in both VMAT-HF-CPAP and PBT (7–9% and approximately 5–6 Gy, respectively). VMAT-HF-CPAP and PBT delivered a comparable maximum dose to the left ascending artery (7.2 Gy and 6.70 Gy, respectively, with the highest dose delivered by 3DCRT [47.6 Gy]). The average doses to the contralateral breast were 0.004, 1, and 2.1 Gy in PBT, 3DCRT, and VMAT, respectively.Conclusions: PBT delivered the lowest doses to most OARs in RT for left-sided breast cancer with regional nodal irradiation. However, the dosimetric gap between proton and photon RT has narrowed substantially with modern techniques such as VMAT and CPAP; the clinical relevance of these differences is yet to be elucidated.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study

Chang

Moon

et al. 2020

Preprint

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“…In the present study, as a consequence of using the 40/15 regimen instead of the 50/25 regimen, albeit not statistically significant, the MHD decreased by 1.5 Gy and 0.71 Gy under FB and CPAP conditions, respectively. The maximum LAD dose showed a significant reduction of 9.3 Gy and 8.4 Gy with an HF schedule in FB and CPAP conditions, respectively; this finding is similar to that reported by Pierre et al (13). In addition, the 40/15 HF schedule can help reduce the lung dose to a greater extent than the 50/25 schedule, a result consistent with that of a previous study (28).…”

Section: Vmat With Cpap In Hf: An Encouraging Choicesupporting

confidence: 91%

“…In light of the accumulating evidence regarding the safety and effectiveness of hypofractionated radiotherapy (HF-RT), a 3-week schedule of 40 Gy in 15 fractions is being increasingly selected in the treatment of breast cancer, especially during the current coronavirus disease (COVID-19) pandemic (12). Rotational IMRT, such as VMAT, has been suggested to reduce the dose to cardiac substructures in the hypofractionated (HF) group (13). However, how cardiac sparing techniques, IMRT/PBT, and HF-RT affect dose avoidance to the organs-at-risk (OARs) individually or in any combination is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study

Chang

Moon

et al. 2021

Front. Oncol.

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PurposeHow modern cardiac sparing techniques and beam delivery systems using advanced x-ray and proton beam therapy (PBT) can reduce incidental radiation exposure doses to cardiac and pulmonary organs individually or in any combination is poorly investigated.MethodsAmong 15 patients with left-sided breast cancer, partial wide tangential 3D-conformal radiotherapy (3DCRT) delivered in conventional fractionation (CF) or hypofractionated (HF) schedules; PBT delivered in a CF schedule; and volumetric modulated arc therapy (VMAT) delivered in an HF schedule, each under continuous positive airway pressure (CPAP) and free-breathing (FB) conditions, were examined. Target volume coverage and doses to organs-at-risk (OARs) were calculated for each technique. Outcomes were compared with one-way analysis of variance and the Bonferroni test, with p-values <0.05 considered significant.ResultsTarget volume coverage was within acceptable levels in all interventions, except for the internal mammary lymph node D95 (99% in PBT, 90% in VMAT-CPAP, 84% in VMAT-FB, and 74% in 3DCRT). The mean heart dose (MHD) was the lowest in PBT (<1 Gy) and VMAT-CPAP (2.2 Gy) and the highest in 3DCRT with CF/FB (7.8 Gy), respectively. The mean lung dose (MLD) was the highest in 3DCRT-CF-FB (20 Gy) and the lowest in both VMAT-HF-CPAP and PBT (approximately 5–6 Gy). VMAT-HF-CPAP and PBT delivered a comparable maximum dose to the left ascending artery (7.2 and 6.13 Gy, respectively).ConclusionsBoth proton and VMAT in combination with CPAP can minimize the radiation exposure to heart and lung with optimal target coverage in regional RT for left-sided breast cancer. The clinical relevance of these differences is yet to be elucidated. Continued efforts are needed to minimize radiation exposures during RT treatment to maximize its therapeutic index.

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“…Using the 9 Gy × 5 regimen, the IL2RG −/− rats had slightly decreased sensitivity to RT, resulting in improved cardiac parameters such as EF and FS at three months post-RT, when compared to the immune-competent SS WT rats (Figure 7). Using a linear quadratic model to approximate equivalent doses, with an estimated α/β ratio of 3 for the heart (although it is difficult to model cardiac equivalent doses using this model due to the complexity of the structure of the heart) [60], the 9 Gy × 5 regimen yields an equivalent dose at 2 Gy fractions of approximately 108 Gy, while the 24 Gy × 1 regimen yields an equivalent dose at 2 Gy fractions of approximately 130 Gy. While it is also difficult to model equivalent doses for large fraction sizes and with single-fraction regimens, our previous results indicated that the 24 Gy × 1 regimen yields cardiotoxicity that is either equivalent to or worse than that sustained in rats receiving 9 Gy × 5 [26].…”

Section: Discussionmentioning

confidence: 99%

Acquired Immunity Is Not Essential for Radiation-Induced Heart Dysfunction but Exerts a Complex Impact on Injury

Schlaak

Frei

Fish

et al. 2020

Cancers

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While radiation therapy (RT) can improve cancer outcomes, it can lead to radiation-induced heart dysfunction (RIHD) in patients with thoracic tumors. This study examines the role of adaptive immune cells in RIHD. In Salt-Sensitive (SS) rats, image-guided whole-heart RT increased cardiac T-cell infiltration. We analyzed the functional requirement for these cells in RIHD using a genetic model of T-and B-cell deficiency (interleukin-2 receptor gamma chain knockout (IL2RG −/− )) and observed a complex role for these cells. Surprisingly, while IL2RG deficiency conferred protection from cardiac hypertrophy, it worsened heart function via echocardiogram three months after a large single RT dose, including increased end-systolic volume (ESV) and reduced ejection fraction (EF) and fractional shortening (FS) (p < 0.05). Fractionated RT, however, did not yield similarly increased injury. Our results indicate that T cells are not uniformly required for RIHD in this model, nor do they account for our previously reported differences in cardiac RT sensitivity between SS and SS.BN3 rats. The increasing use of immunotherapies in conjunction with traditional cancer treatments demands better models to study the interactions between immunity and RT for effective therapy. We present a model that reveals complex roles for adaptive immune cells in cardiac injury that vary depending on clinically relevant factors, including RT dose/fractionation, sex, and genetic background.

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The Limits of the Linear Quadratic (LQ) Model for Late Cardiotoxicity Prediction: Example of Hypofractionated Rotational Intensity Modulated Radiation Therapy (IMRT) for Breast Cancer

Cited by 19 publications

References 9 publications

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study

Acquired Immunity Is Not Essential for Radiation-Induced Heart Dysfunction but Exerts a Complex Impact on Injury

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