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Garcia AV, Strangas Y. Cardiovascular Health in Women. Prim Care 2025; 52:317-328. [PMID: 40412909 DOI: 10.1016/j.pop.2025.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the developed world. Although women generally have a lower prevalence, they have unique factors placing them at risk for CVD compared to their male counterparts. Studies show that prevention, early detection, and treatment can reduce downstream sequelae of CVD. However, sex and gender-specific recommendations are lagging and not always optimally disseminated to patients and providers. This article will explore sex and gender-based differences in cardiovascular burden of disease, risk factors, presentation, and natural history to aid in early identification and intervention.
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Affiliation(s)
- Aury V Garcia
- Department of Internal Medicine, Center for Family and Community Medicine; Columbia University Irving Medical Center/New York Presbyterian Hospital, 610 West 158th Street, New York, NY 10032, USA.
| | - Yorgos Strangas
- Department of Internal Medicine, Center for Family and Community Medicine; Columbia University Irving Medical Center/New York Presbyterian Hospital, 720 West 173rd Street Apartment 42, New York, NY 10032, USA
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2
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Shin S, Bae GH, Han JH, Shin HE, Park JD, Ko S, Koh EY, Han J, Han SC, Lee JJB, Kim DH, Nam H, Park W. Dual-Functional Hafnium Oxide Nanoplatform Combining High-Z Radiosensitization With Bcl-2 Gene Silencing for Enhanced Cancer Radiotherapy. Adv Healthc Mater 2025; 14:e2404819. [PMID: 40025923 DOI: 10.1002/adhm.202404819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 02/08/2025] [Indexed: 03/04/2025]
Abstract
The efficacy of radiotherapy is often limited by insufficient radiosensitization and tumor radioresistance. This study reports a dual-functional hafnium oxide nanoplatform that combines high-Z radiosensitization with Bcl-2 gene silencing for enhanced cancer radiotherapy. The nanoplatform is developed by surface modification of hafnium oxide nanoparticles with polyethyleneimine, enabling efficient siRNA delivery while maintaining inherent high-Z radiosensitizing properties. Comprehensive physicochemical characterization confirmed the successful surface modification and stable siRNA complexation. Upon radiation exposure, the nanoplatform enhanced reactive oxygen species generation and DNA damage while simultaneously delivering Bcl-2 siRNA to suppress radioresistance mechanisms. In vitro studies revealed significant enhancement of radiation-induced cell death through synergistic effects of high-Z radiosensitization and Bcl-2 silencing, evidenced by increased γ-H2AX expression and apoptotic cell population. In a murine colon cancer model, the nanoplatform achieved remarkable tumor growth inhibition (80%) when combined with radiotherapy while exhibiting favorable biocompatibility in major organs. Mechanistic studies confirmed effective Bcl-2 downregulation and enhanced DNA damage in tumor tissues, validating this dual-functional therapeutic approach. This study presents a promising strategy for improving radiotherapy outcomes through the simultaneous enhancement of radiosensitization and suppression of radioresistance, potentially advancing the field of cancer radiotherapy.
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Affiliation(s)
- Seungyong Shin
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Ga-Hyun Bae
- Department of MetaBioHealth, Institute for Cross-disciplinary Studies (ICS), SKKU, Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Jun-Hyeok Han
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Ha Eun Shin
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Joo Dong Park
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Seunghyo Ko
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Eun-Young Koh
- Department of MetaBioHealth, Institute for Cross-disciplinary Studies (ICS), SKKU, Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Jieun Han
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
| | - Su Chul Han
- Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Saemunan-ro 29, Seoul, 03181, Republic of Korea
| | - Jason Joon Bock Lee
- Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Saemunan-ro 29, Seoul, 03181, Republic of Korea
| | - Dong-Hyun Kim
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, 60611, USA
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, 60208, USA
- Department of Biomedical Engineering, University of Illinois, Chicago, IL, 60607, USA
| | - Heerim Nam
- Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Saemunan-ro 29, Seoul, 03181, Republic of Korea
| | - Wooram Park
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
- Department of MetaBioHealth, Institute for Cross-disciplinary Studies (ICS), SKKU, Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea
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3
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Loap P, Monteil R, Kirova Y, Vu-Bezin J. Automated contouring for breast cancer radiotherapy in the isocentric lateral decubitus position: a neural network-based solution for enhanced precision and efficiency. Strahlenther Onkol 2025; 201:601-605. [PMID: 39900818 DOI: 10.1007/s00066-024-02364-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 12/18/2024] [Indexed: 02/05/2025]
Abstract
BACKGROUND Adjuvant radiotherapy is essential for reducing local recurrence and improving survival in breast cancer patients, but it carries a risk of ischemic cardiac toxicity, which increases with heart exposure. The isocentric lateral decubitus position, where the breast rests flat on a support, reduces heart exposure and leads to delivery of a more uniform dose. This position is particularly beneficial for patients with unique anatomies, such as those with pectus excavatum or larger breast sizes. While artificial intelligence (AI) algorithms for autocontouring have shown promise, they have not been tailored to this specific position. This study aimed to develop and evaluate a neural network-based autocontouring algorithm for patients treated in the isocentric lateral decubitus position. MATERIALS AND METHODS In this single-center study, 1189 breast cancer patients treated after breast-conserving surgery were included. Their simulation CT scans (1209 scans) were used to train and validate a neural network-based autocontouring algorithm (nnU-Net). Of these, 1087 scans were used for training, and 122 scans were reserved for validation. The algorithm's performance was assessed using the Dice similarity coefficient (DSC) to compare the automatically delineated volumes with manual contours. A clinical evaluation of the algorithm was performed on 30 additional patients, with contours rated by two expert radiation oncologists. RESULTS The neural network-based algorithm achieved a segmentation time of approximately 4 min, compared to 20 min for manual segmentation. The DSC values for the validation cohort were 0.88 for the treated breast, 0.90 for the heart, 0.98 for the right lung, and 0.97 for the left lung. In the clinical evaluation, 90% of the automatically contoured breast volumes were rated as acceptable without corrections, while the remaining 10% required minor adjustments. All lung contours were accepted without corrections, and heart contours were rated as acceptable in 93.3% of cases, with minor corrections needed in 6.6% of cases. CONCLUSION This neural network-based autocontouring algorithm offers a practical, time-saving solution for breast cancer radiotherapy planning in the isocentric lateral decubitus position. Its strong geometric performance, clinical acceptability, and significant time efficiency make it a valuable tool for modern radiotherapy practices, particularly in high-volume centers.
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Affiliation(s)
- Pierre Loap
- Department of radiation oncology, Institut Curie, Paris, France.
- Laboratoire d'imagerie translationnelle en oncologie, Institut Curie, Orsay, France.
| | - Rémi Monteil
- Department of radiation oncology, Institut Curie, Paris, France
| | - Youlia Kirova
- Department of radiation oncology, Institut Curie, Paris, France
| | - Jérémi Vu-Bezin
- Department of radiation oncology, Institut Curie, Paris, France
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Zhao Y, Tan F, Zhao J, Zhou S, Luo Y, Gong C. Targeting the Enhanced Sensitivity of Radiotherapy in Cancer: Mechanisms, Applications, and Challenges. MedComm (Beijing) 2025; 6:e70202. [PMID: 40384989 PMCID: PMC12079026 DOI: 10.1002/mco2.70202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 04/10/2025] [Accepted: 04/10/2025] [Indexed: 06/04/2025] Open
Abstract
Cancer is a major public health, societal, and economic challenge worldwide. According to Global Cancer Statistics 2022, it is estimated that by 2050, there will be 35 million new cancer cases globally. Although patient survival rates have improved through various therapeutic approaches, including surgery, chemotherapy, and radiotherapy, treatment efficacy remains limited once tumor metastasis occurs. Among various cancer treatment strategies, radiotherapy plays a crucial role. Along with surgery and chemotherapy, radiotherapy is a cost-effective single-modality treatment, accounting for approximately 5% of total cancer care costs. The use of radiosensitizing agents such as histone deacetylase inhibitors, 2-deoxy-d-glucose, enterolactone, and squalene epoxidase can enhance radiotherapy effectiveness. Recent radiosensitization methods involve physical stimuli and chemical radiosensitizers. However, improving their efficacy, durability, and overcoming radioresistance remain significant challenges. This review first introduces current applications of radiotherapy in cancer treatment, the molecular mechanisms underlying its anticancer effects, and its side effects. Second, it discusses the main types of radiosensitizers, their latest applications, and recent challenges in cancer treatment. Finally, it emphasizes on clinical trials of radiosensitizing agents and explores potential biomarkers for radiotherapy response in cancer. Multifunctional nanoparticles have shown greater clinical applicability than single-functional nanoparticles. Future research will focus on enhancing the drug-carrying capacity of nanomaterials to further improve radiotherapy outcomes.
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Affiliation(s)
- Yuanyuan Zhao
- Department of OncologyDepartment of RadiologyInstitute of Organ TransplantationTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Key Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesOrgan Transplantation Clinical Medical Research Center of Hubei Province WuhanWuhanChina
| | - Fangqin Tan
- Department of OncologyDepartment of RadiologyInstitute of Organ TransplantationTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Jiajia Zhao
- Department of StomatologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Shuchang Zhou
- Department of OncologyDepartment of RadiologyInstitute of Organ TransplantationTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yao Luo
- Department of Laboratory MedicineSichuan Clinical Research Center for Laboratory MedicineWest China HospitalSichuan UniversityChengduChina
| | - Chen Gong
- Department of OncologyDepartment of RadiologyInstitute of Organ TransplantationTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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Parvej M, Cappelletto C, Caroli A, Vinante L, Drigo A, Chiovati P. Comparative analysis of radiotherapy modalities and techniques for left breast cancer: dose coverage, setup accuracy, with patient-specific selection criteria for applying deep inspiration breath hold. Radiol Phys Technol 2025; 18:417-424. [PMID: 40032813 DOI: 10.1007/s12194-025-00891-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 02/08/2025] [Accepted: 02/12/2025] [Indexed: 03/05/2025]
Abstract
To compare dosimetric outcomes between Free Breath (FB) and Deep Inspiration Breath Hold (DIBH) across different radiotherapy modalities, establish patient selection criteria for DIBH, and optimizing the setup margin (SM) in left breast cancer treatment. 26 patients with left breast cancer were studied at CRO, Aviano in Italy. FB and DIBH simulations were done using CT with a real-time position management system. 3DCRT and IMRT plans were prepared for both simulations of each patient. The setup margin was measured by Van Herk's formula and compared with residual uncertainties. The dose coverage of PTV and spare OARs were better with DIBH. The distance of more than 1.6 cm between (Left Anterior Descending artery) LAD and PTV was no significantly different for FB and DIBH. The setup margin by Van Herk's formula was calculated as 0.9 cm for DIBH_IMRT. The average duration of DIBH per respiration was 19 ± 4 s. So, holding one breath at least 19 s would be the criteria for choosing a patient to apply DIBH. DIBH enhances PTV dose coverage and OAR sparing in both 3DCRT and IMRT. When the distance between the LAD and PTV exceeds 1.6 cm, the application of DIBH depends on the availability of a LINAC with RPM and the patient's breathholding ability.
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Affiliation(s)
- Masud Parvej
- Department of Physics, Oakland University, Rochester, MI, USA.
| | - Cristina Cappelletto
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081, Aviano, Italy
| | - Angela Caroli
- Radiation Oncology Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081, Aviano, Italy
| | - Lorenzo Vinante
- Radiation Oncology Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081, Aviano, Italy
| | - Annalisa Drigo
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081, Aviano, Italy
| | - Paola Chiovati
- Medical Physics Department, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini 2, 33081, Aviano, Italy
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Kim JP, Cunningham JM, Moats E, Ghanem AI, Movsas B, Levin K, Feldman AM, Thind K. Optimizing Dose Reduction to the Left Anterior Descending Artery in Patients With Locally Advanced Lung Cancer Treated With Definitive Radiation Therapy: A Feasibility Study of Coplanar Treatments Using Double-Stacked Multileaf Collimator. Adv Radiat Oncol 2025; 10:101779. [PMID: 40371385 PMCID: PMC12076829 DOI: 10.1016/j.adro.2025.101779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 02/27/2025] [Indexed: 05/16/2025] Open
Abstract
Purpose Recent studies have shown that cardiac substructures and particularly left anterior descending artery (LAD) dose strongly correlates with the incidence of late adverse cardiac events. We evaluated whether greater cardiac and, importantly, LAD dose sparing could be achieved using a newly introduced closed bore (O-ring gantry) linac with a double-stacked multileaf collimator (Varian Ethos) relative to conventional linacs. Methods and Materials Twenty patients with locally advanced non-small cell lung cancer previously treated with definitive chemoradiotherapy were retrospectively evaluated. Volumetric modulated arc therapy plans were retrospectively generated for the Ethos system using optimization criteria focused on reducing overall heart and LAD doses (Heart_Ethos). Plans were also reoptimized using the same optimization criteria on a conventional C-arm linac (Heart_TB). Investigational plans were compared with the original plans and with each other using standard dose-volume histogram metrics such as percentage (V) volume receiving a specific dose (x) in Gy (Vx) or mean dose (Dmean) in Gy. Results Statistically significant decreases existed between the Heart_Ethos and original plans for mean heart dose (11.3 vs 14.8 Gy; P < .001) and V5, V30, and V50 (63.6% vs 75.2%; P < .001, 7.1% vs 12.3%; P < .001, 2.1% vs 2.9%; P = .03, respectively) and also for LAD mean dose (4.8 Gy vs 12.0 Gy [P < .001]) and V15 (4.9% vs 21.5%; P < .001). Compared with Heart_TB, Heart_Ethos plans had significantly less mean heart dose (11.6 vs 12.2 Gy; P = .006), and less heart V5 (64.4% vs 67.2%; P = .049) and V30 (7.7% vs 8.8%; P = .03), whereas other parameters were not significant. Optimal target coverage and other organs at risk constraints were maintained for all generated plans. Conclusions Heart_Ethos plans showed significant reduction in cardiac and LAD doses in comparison to the original plans while maintaining target and organ at risk goals. Our findings suggest that Ethos technology has the potential for better cardiac toxicity safety because Heart_Ethos plans were still able to reduce cardiac dose compared with Heart_TB plans.
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Affiliation(s)
- Joshua P. Kim
- Department of Radiation Oncology, Henry Ford Health, Detroit, MI
| | | | - Emily Moats
- Department of Radiation Oncology, Henry Ford Health, Detroit, MI
| | - Ahmed I. Ghanem
- Department of Radiation Oncology, Henry Ford Health, Detroit, MI
- Department of Clinical Oncology, Alexandria University, Alexandria, Egypt
| | - Benjamin Movsas
- Department of Radiation Oncology, Henry Ford Health, Detroit, MI
| | - Kenneth Levin
- Department of Radiation Oncology, Henry Ford Health, Detroit, MI
| | | | - Kundan Thind
- Department of Radiation Oncology, Henry Ford Health, Detroit, MI
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7
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Romera-Martínez I, Cancio IO, Buxó M, Martínez J, Fuentes-Raspall R, Urién AE, Vilanova JC. Heart substructure exposure during left breast cancer radiotherapy: a dosimetric comparison between hybrid VMAT and 3DCRT in free breathing and deep inspiration breath hold (DIBH). Clin Transl Oncol 2025:10.1007/s12094-025-03943-9. [PMID: 40413717 DOI: 10.1007/s12094-025-03943-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 04/24/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND AND PURPOSE Radiotherapy plays a pivotal role in breast cancer treatment. Incidental irradiation of the heart can cause cardiac toxicity. We conducted a dosimetric comparison between Hybrid VMAT (H-VMAT) and 3D Conformal Radiotherapy (3DCRT) in both Free Breathing (FB) and Deep inspiration breath hold (DIBH) techniques for left-sided breast cancer patients. MATERIALS AND METHODS Thirty-seven patients underwent CT scans in both FB and DIBH positions. Heart substructures were delineated following established guidelines. Subsequently, 3DCRT and H-VMAT plans were generated for each patient in both breath techniques. The dosimetric parameters of heart and its cavities were analysed: Dmean(Gy) and V5Gy(%) for heart substructures, Dmean(Gy), V25Gy(%) and V30Gy(cm3) for heart and D98%(%), D2%(%), D50%(%) and V95%(%) or V90%(%) for PTVs. Statistical analyses were performed. RESULTS The analysis revealed statistically significant differences for the heart, and its cavities. The 3DCRT plans generated in DIBH offered a statistically significant lower dose for the heart and its substructures compared to the other techniques. When comparing PTV dosimetry, the H-VMAT plans showed an increase D98%(%) and a decrease D2%(%) relative to the 3DCRT plans, for both breathing techniques employed. CONCLUSION Our study demonstrates significant differences in the dosimetric outcomes for the heart substructures among the four evaluated techniques, with 3DCRT in DIBH yielding the lowest parameters for most substructures. Although H-VMAT provided superior target coverage, it resulted in greater low doses incidental exposure of the heart substructures. Notably, 3DCRT plans in the DIBH setting exhibited lower doses compared to H-VMAT in FB, supporting its preferential use for minimising cardiac exposure.
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Affiliation(s)
- Ingrid Romera-Martínez
- Medical Physics and Radiation Protection Department, Catalan Institute of Oncology, Girona, Spain.
- Radiation Oncology and Medical Physics of Girona Research Group (ONCORFIM), Girona, Spain.
| | | | - Maria Buxó
- Girona Biomedical Research Institute (IDIBGI-CERCA), Girona, Spain
| | - Joan Martínez
- Girona Biomedical Research Institute (IDIBGI-CERCA), Girona, Spain
| | - Rafael Fuentes-Raspall
- Radiation Oncology and Medical Physics of Girona Research Group (ONCORFIM), Girona, Spain
- Radiation Oncology Department, Catalan Institute of Oncology, Girona, Spain
- Department of Medical Sciences, University of Girona, Girona, Spain
| | - Arantxa Eraso Urién
- Radiation Oncology and Medical Physics of Girona Research Group (ONCORFIM), Girona, Spain
- Radiation Oncology Department, Catalan Institute of Oncology, Hospitalet de Llobregat, Spain
| | - Joan Carles Vilanova
- Department of Medical Sciences, University of Girona, Girona, Spain
- Department of Radiology, Clínica Girona, Girona, Spain
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Wallisch E, Tomita-Mitchell A, Liang HL, Szabo A, Lenarczyk M, Kwitek A, Smith JR, Tutaj M, Baker JE. Advancing cell-free DNA as a biomarker of damage to heart caused by ionizing radiation. JOURNAL OF RADIATION RESEARCH 2025; 66:329-340. [PMID: 40304705 PMCID: PMC12100473 DOI: 10.1093/jrr/rraf022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/17/2025] [Indexed: 05/02/2025]
Abstract
Exposure to diagnostic and therapeutic radiation introduces risks for development of diseases later in life by causing DNA damage in cells. Currently, there is no clinical method for determining exposure risk caused by radiation toxicity to DNA. Cell-free DNA (cfDNA), a marker of DNA damage, is currently used to assess risk for long-term effects following organ transplantation, surgery and inflammation. The goal of our proposed study is to develop cfDNA as an early biomarker for assessing risk for cardiovascular disease and cancer from radiation exposure so that strategies to mitigate the damaging effects of medical radiation can be assessed. Hearts from male and female WAG/RijCmcr rats (n = 6-10/group) were exposed to increasing doses of X-radiation (50 mGy and 3.5 Gy). Blood was collected prior to and after (15 minutes-96 hours) irradiation, and cell-free plasma was prepared. Primers and probes were designed for quantitative analysis of sequences of mitochondria (12S rRNA) and nuclear (Gapdh) cfDNA present in rat plasma using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Exposure of hearts to radiation increased nuclear and mitochondrial cfDNA in a dose-dependent manner. Three point five grays from X-radiation increase cfDNA for Gapdh in plasma after 1 hour with a 15.8-fold increase (P < 0.001) after 6 hours. The earliest time nuclear and mitochondrial cfDNA increases were detected in plasma was at 60 minutes following exposure to 3.5 Gy. cfDNA has potential to advance as a biomarker of exposure to medical doses of radiation in patients.
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Affiliation(s)
- Erin Wallisch
- Division of Congenital Heart Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Aoy Tomita-Mitchell
- Division of Congenital Heart Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Huan-Ling Liang
- Division of Congenital Heart Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Aniko Szabo
- Data Science Institute, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Marek Lenarczyk
- Division of Congenital Heart Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
- Radiation Biosciences Laboratory, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Anne Kwitek
- Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Jennifer R Smith
- Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Monika Tutaj
- Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - John E Baker
- Division of Congenital Heart Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
- Radiation Biosciences Laboratory, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
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9
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Loap P, Uakkas A, Bouziane J, Fourquet A, Kirova Y. Long-term cardiac outcomes in breast cancer patients treated with helical tomotherapy: Evaluating the applicability of 3D-based dose constraints for intensity modulated radiation therapy. Int J Cancer 2025. [PMID: 40405829 DOI: 10.1002/ijc.35474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/19/2025] [Accepted: 04/28/2025] [Indexed: 05/24/2025]
Abstract
Adjuvant breast radiotherapy has been associated with cardiac toxicity due to older 2D and 3D techniques, with a linear relationship between mean heart dose (MHD) and ischemic cardiac events. Cardiac dose distribution differs with modern techniques like intensity-modulated radiotherapy (IMRT), potentially affecting this relationship. This study evaluates long-term cardiac toxicity in breast cancer patients treated with tomotherapy to reassess 3D-derived dose constraints. Breast cancer patients treated with tomotherapy at Institut Curie from August 2010 to December 2015 were included. Patients had undergone breast-conserving surgery or mastectomy, with some receiving chemotherapy or trastuzumab. Tomotherapy was used for anatomically challenging cases. The primary endpoint was cardiac toxicity correlated with MHD; secondary endpoints were overall and disease-specific survival. Statistical analyses included logistic regression and Cox models. Among 179 patients, the median MHD was 7.04 Gy, with 95.6% having an MHD above 5 Gy. Sixty-six patients had cardiovascular risk factors, and 28.5% were obese. Over a median follow-up of 9.1 years, eight patients (4.5%) experienced cardiovascular events-all with pre-existing risks or obesity. No significant correlation was found between MHD and major coronary events (p = 0.607) or heart failure (p = 0.800). Cardiac mortality was absent, and 10-year overall and disease-specific survival were 88.0% and 94.3%, respectively. Cardiac events in patients treated with tomotherapy were rare and driven by pre-existing risk factors. The linear MHD-toxicity relationship observed in 3D radiotherapy may not apply to IMRT, potentially leading to overestimated risks. Long-term studies are needed to refine IMRT dose constraints.
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Affiliation(s)
- Pierre Loap
- Department of Radiation Oncology, Institut Curie, Paris, France
- Laboratoire d'Imagerie Translationnelle en Oncologie (LITO), Institut Curie, Orsay, France
| | | | - Jihane Bouziane
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Alain Fourquet
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Youlia Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
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10
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Waldrip BR, Malik M, Paez P, Lenards N, Hunzeker A, Park J. Relative biological effectiveness-weighted dose sparing utilizing a linear energy transfer optimization function for organs-at-risk in left breast proton treatment plans. Med Dosim 2025:S0958-3947(25)00026-3. [PMID: 40410073 DOI: 10.1016/j.meddos.2025.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 04/04/2025] [Accepted: 04/11/2025] [Indexed: 05/25/2025]
Abstract
Current proton treatment plans employ a constant relative biological effectiveness (RBE) of 1.1, which may underestimate organs-at-risk (OAR) doses due to high linear energy transfer (LET) at the distal end of the proton beam. When 2 anterior fields are used for left breast treatment using pencil beam scanning (PBS), the ipsilateral lung and heart are susceptible to high LET. Although studies have indicated a potential increase in OAR toxicity linked to LET effects, the strategy of optimizing LET to RBE-weighted doses (D_vRBE) to spare OAR is still underexplored in treatment planning research. Addressing this gap is crucial for improving treatment outcomes and minimizing toxicities. To evaluate the effectiveness of LET optimization in reducing doses to OAR, we aimed to achieve more than a 10% reduction in the mean or maximum D_vRBE for the heart, ipsilateral lung, and humeral joint, while ensuring adequate target coverage. In this study, 12 cases of left-sided breast cancer with locally advanced invasive carcinoma were randomly selected to assess the dose reduction of OAR using LET optimization. The OAR doses were compared to those of clinically accepted PBS plans that did not incorporate LET optimization. To validate the hypothesis, a statistical analysis was implemented using the Wilcoxon-Signed Rank test. The results demonstrated a significant reduction in mean D_vRBE for both the heart and ipsilateral lung, as well as the maximum D_vRBE for humeral joint (p < 0.05). A decrease in both maximum and mean LET was observed in the ipsilateral lung (p < 0.05). These findings indicate that optimizing LET has the potential to effectively reduce D_vRBE for OAR, which can lead to minimizing organ toxicity.
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Affiliation(s)
- Bobby R Waldrip
- Medical Dosimetry Program, University of Wisconsin, La Crosse, WI, USA; University of Florida Health Proton Therapy Institute, Jacksonville, FL, USA.
| | - Mahnoor Malik
- Medical Dosimetry Program, University of Wisconsin, La Crosse, WI, USA
| | - Paula Paez
- Medical Dosimetry Program, University of Wisconsin, La Crosse, WI, USA
| | - Nishele Lenards
- Medical Dosimetry Program, University of Wisconsin, La Crosse, WI, USA
| | - Ashley Hunzeker
- Medical Dosimetry Program, University of Wisconsin, La Crosse, WI, USA
| | - Jiyeon Park
- University of Florida Health Proton Therapy Institute, Jacksonville, FL, USA
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11
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Zhao C, Xu S, Yang Y, Shen X, Wang J, Xing S, Yu Z. Intersection of Cardio-Oncology: An Overview of Radiation-Induced Heart Disease in the Context of Tumors. J Am Heart Assoc 2025; 14:e040937. [PMID: 40357679 DOI: 10.1161/jaha.124.040937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Radiation-induced heart disease (RIHD) is a prevalent cardiovascular complication of radiation therapy, with coronary heart disease being the most common manifestation. Clinical presentations of RIHD vary and may include conduction abnormalities, ischemic heart disease, cardiomyopathy, heart failure, and valvular damage. Even low doses of radiation significantly increase the risk of cardiovascular disease, often associated with severe stenosis detected via angiography. Radiation-induced damage to the cardiac endothelium triggers inflammatory responses and oxidative stress, which contribute to the progression of atherosclerosis. This study explores how radiation activates multiple signaling pathways through the generation of reactive oxygen species, resulting in vascular endothelial damage, cellular senescence, inflammatory responses, and DNA damage. It further examines the impact of radiation on vascular integrity and tight junction proteins, leading to increased vascular permeability and infiltration by inflammatory cells. From a clinical perspective, we emphasize the challenges posed by the coexistence of tumors in many patients with RIHD, as tumors complicate the microenvironment and may have mutually reinforcing interactions with radiation-induced damage. We also discuss various therapeutic strategies, including novel approaches targeting cellular senescence and immune responses, with a focus on the potential use of navitoclax and IL-6 (interleukin-6) inhibitors to prevent irreversible cardiomyocyte fibrosis and ongoing vascular damage. In conclusion, RIHD is a multifaceted disease involving complex biological processes and signaling pathways. Early intervention and targeted therapies are crucial for improving patient outcomes. Future research should prioritize uncovering the molecular mechanisms of RIHD and developing more effective therapeutic strategies.
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Affiliation(s)
- Chunan Zhao
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing China
| | - Shuai Xu
- Department of Cardiology Chinese PLA General Hospital Beijing China
| | - Yanru Yang
- Department of Cardiology Chinese PLA General Hospital Beijing China
| | - Xing Shen
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing China
| | - Jingjing Wang
- Department of Cardiology Chinese PLA General Hospital Beijing China
| | - Shuang Xing
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing China
| | - Zuyin Yu
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing China
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12
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Guo HL, Lu ZH, Zhong JH, Zhang HW. Effect of physical parameter differences on the performance of a knowledge-based partial arc VMAT RapidPlan model for left breast cancer. Front Oncol 2025; 15:1589270. [PMID: 40432918 PMCID: PMC12106513 DOI: 10.3389/fonc.2025.1589270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Accepted: 04/22/2025] [Indexed: 05/29/2025] Open
Abstract
Objective To optimize the protection of organs at risk (OARs) in left breast cancer radiotherapy, this study investigated how physical parameter adjustments affect the performance of a Rapidplan-based dose-volume histogram (DVH) prediction model. Methods Twenty patients who underwent left breast-conserving surgery were enrolled. Partial arc volumetric modulated arc therapy (VMAT) plans were designed per patient, with X-direction field width set to half-beam and right breast (Breast-R) contoured as an avoidance structure to generate Rapidplan model. The model was used to predict and generate three plans: AP_partial arc (avoidance structure prioritized), RP_partial arc (no avoidance structure), and FP_partial arc (expanded field width). Dosimetric comparisons against the original plan evaluated the impact of parameter selection. Results AP_partial arc reduced mean doses of Breast-R, Heart, Lung-L, and Lung-R by 7.7 cGy, 9.8 cGy, 16.7 cGy, and 1.1 cGy, respectively (p < 0.05). Conversely, RP_partial arc increased mean dose of Breast-R by 66.3 cGy (p < 0.05). FP_partial arc raised V5 of Lung-L, V5 of Heart, and mean dose of Lung-L by 4.01%, 2.25%, and 36 cGy (p < 0.05). Conclusion The knowledge-based partial arc model for rapid planning of left breast cancer accurately predicts the DVH of OARs. However, before performing dose prediction, physical parameters such as radiation field width and planned avoidance structures should be considered to reduce the risk of low-dose exposure volume to OARs and secondary cancer.
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Affiliation(s)
- Hai-liang Guo
- Department of Oncology, the First Affiliated Hospital of Gannan Medical University, Jiangxi Clinical Research Center for Cancer, First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Zeng-hong Lu
- Department of Oncology, the First Affiliated Hospital of Gannan Medical University, Jiangxi Clinical Research Center for Cancer, First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Jing-hua Zhong
- Department of Oncology, the First Affiliated Hospital of Gannan Medical University, Jiangxi Clinical Research Center for Cancer, First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Huai-wen Zhang
- Department of Radiation Oncology, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China
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Park KU, Somerfield MR, Anne N, Brackstone M, Conlin AK, Couto HL, Dengel LT, Eisen A, Harvey BE, Hawley J, Kim JN, Lasebikan N, McDonald ES, Pradhan D, Shams S, Vega RM, Thompson AM, Torres MA. Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update. J Clin Oncol 2025; 43:1720-1741. [PMID: 40209128 DOI: 10.1200/jco-25-00099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 01/22/2025] [Indexed: 04/12/2025] Open
Abstract
PURPOSE To update the ASCO evidence-based recommendations on the use of sentinel lymph node biopsy (SLNB) in patients with early-stage breast cancer treated with initial surgery. METHODS ASCO convened an Expert Panel to develop updated recommendations based on a systematic literature review (January 2016-May 2024). RESULTS Eleven randomized clinical trials (14 publications), eight meta-analyses and/or systematic reviews, and one prospective cohort study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop practice recommendations. RECOMMENDATIONS Clinicians should not recommend routine SLNB in select patients who are postmenopausal and ≥50 years of age and with negative findings on preoperative axillary ultrasound for grade 1-2, small (≤2 cm), hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer and who undergo breast-conserving therapy. Clinicians may offer postmastectomy radiation (RT) with regional nodal irradiation (RNI) and omit axillary lymph node dissection (ALND) in patients with clinically node-negative invasive breast cancer ≤5 cm who receive mastectomy and have one to two positive sentinel nodes. Clinicians may offer SLNB in patients who have cT3-T4c or multicentric tumors (clinically node-negative) or ductal carcinoma in situ treated with mastectomy, and in patients who are obese, male, or pregnant, or who have had prior breast or axillary surgery. Clinicians should not recommend ALND for patients with early-stage breast cancer who do not have nodal metastases, and clinicians should not recommend ALND for patients with early-stage breast cancer who have one or two sentinel lymph node metastases and will receive breast-conserving surgery and whole-breast RT with or without RNI.Additional information is available at www.asco.org/breast-cancer-guidelines.This guideline has been endorsed by the American Society for Radiation Oncology (ASTRO).
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Affiliation(s)
- Ko Un Park
- Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA
| | | | - Nirupama Anne
- Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Muriel Brackstone
- Department of Surgery, University of Western Ontario, London, ON, Canada
| | | | | | - Lynn T Dengel
- Emily Couric Clinical Cancer Center, Charlottesville, VA
| | - Andrea Eisen
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | - Jeffrey Hawley
- Stephanie Spielman Comprehensive Breast Center, The Ohio State University Medical Center, Columbus, OH
| | - Janice N Kim
- University of Washington School of Medicine, Seattle, WA
| | | | | | | | | | | | | | - Mylin A Torres
- Glenn Family Breast Center at Winship Cancer Institute, Atlanta, GA
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14
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Pan H, Chen M, Yan Y, Cao L, Cai G, Chen J, Shan S, Zhang Y. Plan comparison of left-sided breast postmastectomy radiotherapy: Halcyon IMRT and VMAT plan versus TrueBeam IMRT plan. Med Dosim 2025:S0958-3947(25)00022-6. [PMID: 40348722 DOI: 10.1016/j.meddos.2025.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 02/03/2025] [Accepted: 03/26/2025] [Indexed: 05/14/2025]
Abstract
The goal of this work is to compare the Varian TrueBeam plan quality and delivery verification with two Halcyon plans in order to give a Varian Halcyon planning solution for left-sided breast postmastectomy radiotherapy (PMRT). Twenty-five patients who previously received left-sided breast postmastectomy intensity-modulated radiotherapy (IMRT) on TrueBeam were retrospectively selected and replanned using Halcyon. The planning target volume (PTV) included the chest wall, the supra/infra-clavicular region, and the internal mammary region, with a prescribed dose of 50 Gy in 25 fractions (2 Gy/F). For each patient, a Halcyon IMRT (HA-IMRT) plan and a Halcyon volumetric-modulated arc treatment (HA-VMAT) plan were created in addition to the initial TrueBeam fixed-jaws IMRT (TB-IMRT) plan. The conformity index (CI) and homogeneity index (HI) of the PTVs, the dose of organs at risk (OARs), the delivery MUs and time, and the verification passing rate were calculated and compared. Statistical significance was determined with a significance level of 0.05 using the Wilcoxon signed-rank test. HA-IMRT and TB-IMRT made generally clinical equivalence and have tiny differences for target coverage and OAR sparing. HA-IMRT lowered the V10, V20, V30, and Dmean of the ipsilateral lung, the V5, V10, V20, V30, and Dmean of the heart compared to TB-IMRT (p < 0.05). On the other hand, it increased V5 of the ipsilateral lung, Dmean of the contralateral lung, V10 of the contralateral breast, left humeral head, and thyroid, and HI of the target (p < 0.05). No significant differences were found in CI, V5 and V10 of the contralateral lung, V5 and Dmean of the contralateral breast, V30 and Dmax of thyroid, Dmean and Dmax of esophagus, or Dmax of spinal cord (p > 0.05). HA-VMAT showed a better CI but increased most OAR metrics mentioned above than TB-IMRT and/or HA-IMRT (p < 0.05). Both HA-IMRT and HA-VMAT decreased delivery time compared to TB-IMRT (2.96 ± 0.61 min, 0.77 ± 0.11 min, and 3.52 ± 0.92 min, respectively, p < 0.05). The mean gamma passing rates of HA-IMRT and HA-VMAT were also significantly raised compared to TB-IMRT.
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Affiliation(s)
- Hailun Pan
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Mei Chen
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Yuanlin Yan
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Lu Cao
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Gang Cai
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Jiayi Chen
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Shucan Shan
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Yibin Zhang
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Proton-Therapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China.
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15
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Zeng C, Gao Y, Lan B, Wang J, Ma F. Metabolic reprogramming in cancer therapy-related cardiovascular toxicity: Mechanisms and intervention strategies. Semin Cancer Biol 2025; 113:39-58. [PMID: 40349808 DOI: 10.1016/j.semcancer.2025.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 04/20/2025] [Accepted: 05/07/2025] [Indexed: 05/14/2025]
Abstract
Cancer therapy-related cardiovascular toxicity (CTR-CVT) poses a major challenge in managing cancer patients, contributing significantly to morbidity and mortality among survivors. CTR-CVT includes various cardiovascular issues, such as cardiomyopathy, myocardial ischemia, arrhythmias, and vascular dysfunction, which significantly impact patient prognosis and quality of life. Metabolic reprogramming, characterized by disruptions in glucose, lipid, and amino acid metabolism, represents a shared pathophysiological feature of cancer and cardiovascular diseases; however, the precise mechanisms underlying CTR-CVT remain inadequately understood. In recent years, strategies targeting metabolic pathways have shown promise in reducing cardiovascular risks while optimizing cancer treatment efficacy. This review systematically summarizes metabolic reprogramming characteristics in both cancer and cardiovascular diseases, analyzes how anticancer therapies induce cardiovascular toxicity through metabolic alterations, and explores emerging therapeutic strategies targeting metabolic dysregulation. By integrating current research advancements, this review aims to enhance the understanding of CTR-CVT and provide groundwork for the development of safer and more effective cancer approaches.
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Affiliation(s)
- Cheng Zeng
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
| | - Ying Gao
- Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
| | - Bo Lan
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
| | - Jiani Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
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Kang NK, Choi KH, Jeong JU, Ahn SJ, Yu M, Kim JH, Jeong BK, Kang HB, Lee HC, Lee JH. Long-term risk of major cardiac events in breast cancer patients treated with intensity-modulated and 3-dimensional conformal radiotherapy: Secondary analysis of a randomized clinical trial. Int J Cancer 2025. [PMID: 40345828 DOI: 10.1002/ijc.35476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 04/10/2025] [Accepted: 04/28/2025] [Indexed: 05/11/2025]
Abstract
We assess the relationship between radiation dose to the heart and cardiac disease within the context of modern radiotherapy techniques of 3-dimensional and intensity-modulated radiotherapy (IMRT). The KROG 15-03 study was a multicenter phase III trial involving 693 breast cancer patients who underwent breast-conserving surgery (BCS). Patients were randomly assigned to receive either IMRT or 3D-CRT following BCS. Major cardiac event (MCE), defined as the occurrence of angina pectoris or myocardial infarction requiring coronary angiography, and admission for cardiac arrhythmia related to the irradiation of the heart. The primary outcome of the study was to investigate the incidence of MCE and factors associated with MCEs. At a median follow-up of 6.5 years, the incidence of MCEs at 6.5 years was 1.8%. The mean heart dose (MHD) for the entire cohort of 647 patients was 2.1 (±2.3) Gy. The cumulative incidence of MCEs at 6.5 years was 1.1% for the subgroup of MHD <2.9 Gy and 3.3% for the subgroup of MHD >2.9 Gy (p = 0.010), and 0.9% for the subgroup of age ≤55 years and 3.3% for the subgroup of age >55 years (p = 0.006), respectively. Multivariate analyses confirmed that MHD (p = 0.044; hazard ratio [HR], 1.21 per 1 Gy; 95% confidence interval [CI], 1.09-1.46) and age (p = 0.034; HR, 1.07 per 1 year; 95% CI, 1.03-1.14) were significant factors of MCEs. The incidence of MCE increased by 21% per 1-Gy increase in MHD within 6.5 years after radiotherapy.
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Affiliation(s)
- Nam Kyu Kang
- Department of Radiation Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyu Hye Choi
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae Uk Jeong
- Department of Radiation Oncology, Chonnam National University Hospital, Chonnam National University School of Medicine, Gwangju, Republic of Korea
| | - Sung Ja Ahn
- Department of Radiation Oncology, Chonnam National University Hospital, Chonnam National University School of Medicine, Gwangju, Republic of Korea
| | - Mina Yu
- Department of Radiation Oncology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Bae Kwon Jeong
- Department of Radiation Oncology, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Han Byul Kang
- Department of Radiation Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyo Chun Lee
- Department of Radiation Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Hoon Lee
- Department of Radiation Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Guo HL, Huan Y, Zhong JH, Pang HW, Zhang HW. Effect of jaw width in jaw tracking mode on the radiotherapy dose of partial arc VMAT in patients undergoing left breast-conserving surgery. Sci Rep 2025; 15:16195. [PMID: 40346123 PMCID: PMC12064805 DOI: 10.1038/s41598-025-01267-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Accepted: 05/05/2025] [Indexed: 05/11/2025] Open
Abstract
To analyze the effect of jaw width in jaw tracking mode on the dose of radiotherapy partial arc VMAT (P-VMAT) for patients undergoing left breast-conserving surgery and to explore the best jaw width as the initial inverse optimization parameter. Twenty patients who underwent left breast-conserving surgery were randomly selected. Six groups of P-VMAT plans were designed (named Plan0, Plan0.3, Plan0.6, Plan0.9, Plan-0.3, and Plan-0.6). The width of the jaw of each plan was changed in 0.3 cm steps along the X direction (from - 0.6 to 0.9 cm) according to the beginning of the half beam (Plan0). The PTV coverage, conformity index (CI), homogeneity index (HI), monitor units (MU) and organs at risk (OARs) dose were evaluated by repeated measurement data analysis of variance between plan0 and the other plans. Additionally, the correlations between CI, HI, MU and OARs to change in jaw width were analyzed using Spearman's bivariate correlation analysis. The PTV dose distributions of Plan-0.3 and Plan-0.6, which have smaller jaw widths than those of Plan0, did not meet the clinical requirements. CI, HI and MU were correlated with jaw width (r = 0.554, -0.501, -0.641, p < 0.05, respectively). The V5, V10, V20, V40, Dmean and Dmax of the heart were correlated with jaw width (r = 0.288, 0.284, 0.191, -0.27, 0.186, -0.245, p < 0.05, respectively). The V2.5, V5, V10, V20, V40 and Dmean of the left lung (Lung-L) were correlated with jaw width (0.298, 0.421, 0.516, 0.391, -0.241, 0.356, p < 0.05, respectively). Among all the plans to ensure PTV target coverage, Plan0 had the lowest clinical indicators for the heart and Lung-L (p < 0.05, respectively). The internal boundary of the jaw set as 0 cm (Plan0) represents the optimal jaw width for the initial optimization of the plan design. This method is the simplest and most effective for radiotherapy treatment planning for breast-conserving surgery for breast cancer as well as allows ideal dose distribution.
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Affiliation(s)
- Hai-Liang Guo
- Department of Oncology, Jiangxi Clinical Research Center for Cancer, the First Affiliated Hospital of Gannan Medical University, First Clinical Medical College, Gannan Medical University, Ganzhou, 341000, China
| | - Yan Huan
- Department of Oncology, People's Hospital of Qianxinan Buyi and Miao Minority Autonomous Prefecture, Qian xinan, Xingyi, 562400, China
| | - Jing-Hua Zhong
- Department of Oncology, Jiangxi Clinical Research Center for Cancer, the First Affiliated Hospital of Gannan Medical University, First Clinical Medical College, Gannan Medical University, Ganzhou, 341000, China.
| | - Hao-Wen Pang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
| | - Huai-Wen Zhang
- Department of Radiotherapy, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital & Institute, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, 330029, China.
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Cheptea C, Kirova Y, Baude J, Laki F, Fourquet A, Loap P. Survival determinants and toxicity of second-course radiotherapy for isolated nodal recurrences in breast cancer. Strahlenther Onkol 2025:10.1007/s00066-025-02409-9. [PMID: 40327108 DOI: 10.1007/s00066-025-02409-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 04/13/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Isolated nodal recurrence (INR) after localized breast cancer is rare, with an incidence of less than 1%. Curative management typically includes surgical resection, often with axillary lymph node dissection (ALND), followed by regional nodal radiotherapy. However, evidence-based guidelines remain limited due to the rarity of this clinical scenario. The aim of this study was to evaluate survival determinants and the acute and long-term toxicities associated with second-course regional nodal irradiation as part of curative strategies for INR after localized breast cancer. MATERIALS AND METHODS This retrospective study included 11 patients with localized breast cancer who developed ipsilateral, nonmetastatic INR between 2003 and 2019. All patients were treated with curative intent, including regional nodal irradiation. Overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), local control, and treatment toxicities were analyzed. Survival probabilities were calculated using the Kaplan-Meier method, and Cox regression was used to assess prognostic factors. RESULTS The 5‑year OS and CSS were 71.6%, while MFS was 62.3%. Inclusion of internal mammary chain (IMC) irradiation significantly improved OS, CSS, and MFS (p < 0.01). Triple-negative breast cancer (TNBC) INRs were associated with worse survival outcomes. Acute grade 2 toxicities included radiodermatitis (36.4%), and late grade 2 toxicities were limited to fibrosis (18.2%). No cardiac, pulmonary, or grade 3 or higher toxicities were reported. CONCLUSION This study highlights the favorable survival outcomes and safety profile of contemporary curative strategies for INRs following localized breast cancer, with a 5-year OS rate exceeding historical benchmarks. Internal mammary chain irradiation appears to improve survival without increased toxicity. However, the poor prognosis associated with TNBC INR underscores the need for effective systemic therapies. Prospective multicenter trials are essential to validate these findings and optimize treatment protocols.
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Affiliation(s)
- Cezara Cheptea
- Department of Radiation Oncology, Institut Curie, Paris, France
- Proton therapy center, Institut Curie, Orsay, France
| | - Youlia Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Jeremy Baude
- Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon, France
| | - Fatima Laki
- Department of Surgery, Institut Curie, Paris, France
| | - Alain Fourquet
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Pierre Loap
- Department of Radiation Oncology, Institut Curie, Paris, France.
- Proton therapy center, Institut Curie, Orsay, France.
- Laboratoire d'Imagerie Translationnelle en Oncologie (LITO), Institut Curie, Orsay, France.
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Gregucci F, Bonzano E, Ng J, Talebi F, Patel M, Trick D, Chandrasekhar S, Zhou XK, Fenton-Kerimian M, Pennell R, Formenti SC. Heart and Left Anterior Descending Coronary Artery (LAD) Exposure from Hypo-Fractionated Whole Breast Radiotherapy with a Prone Setup. Cancers (Basel) 2025; 17:1562. [PMID: 40361488 PMCID: PMC12071539 DOI: 10.3390/cancers17091562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/11/2025] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Prone breast radiotherapy has been shown to optimally spare the dose to the heart and lungs; we report on the heart and left anterior descending coronary artery (LAD) dosimetry and their implications for current care. Aims: (I) To measure the mean heart dose (MHD) and LAD mean and maximum doses (Dmean and Dmax) in patients with left-side breast cancer who have undergone hypo-fractionated whole breast radiotherapy (WBRT) with a concomitant boost to the post-operative cavity (40.50 Gy to the breast and 48 Gy to the cavity in 15 fractions) in the prone position; (II) to compare the dosimetry results to those reported in the literature for other techniques. Materials and Methods: In a consecutive series of 524 irradiated left-side breast cancer patients, heart and LAD dosimetry data were collected and correlated to breast volume and the volume of the radiation boost to the tumor cavity. A descriptive statistical analysis was performed to compare the same dosimetry data with those reported in the literature from supine techniques. To account for dosimetry differences in hypo-fractionation and conventional fractionated regimens (50-60 Gy in 25-30 fractions) reported in the literature, the cardiac doses were converted to the equivalent dose in 2 Gy fractions (EQD2). As previously reported, the prone setup protocol placed the medial edges of the tangential radiation fields at least 2.5 mm from the contoured LAD. Results: In all patients' plans, the target coverage was successfully achieved. The mean values (±SD) were as follows: MHD = 0.69 Gy (±0.19) (EQD2 0.35 Gy ± 0.1); LAD Dmean = 2.20 Gy (±0.68) (EQD2 1.18 Gy ± 0.35); LAD Dmax = 4.44 Gy (±1.82) (EQD2 2.55 Gy ± 0.97). The values were consistently lower compared with those achieved by the multiple supine techniques reported in the literature. Spearman's correlation analysis revealed a strong positive correlation between LAD and heart dosimetry variables. In contrast, no strong correlation was observed between the cardiac dose metrics and breast volume, boost volume, or their ratio index. A linear correlation was detected between LAD Dmean and LAD D2% (R2 0.64); LAD D2% and heart D2% (R2 0.60); LAD Dmax and heart D2% (R2 0.41). Conclusions: The prone position protocol minimizes heart and LAD exposure. This approach results in a dosimetry advantage when compared with more complex and expensive WBRT techniques in the supine position.
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Affiliation(s)
- Fabiana Gregucci
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Elisabetta Bonzano
- Department of Radiation Oncology, IRCCS San Matteo Polyclinic Foundation, 27100 Pavia, Italy;
| | - John Ng
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Fereshteh Talebi
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Maahi Patel
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Dakota Trick
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Sharanya Chandrasekhar
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Xi Kathy Zhou
- Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, NY 10065, USA;
| | - Maria Fenton-Kerimian
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Ryan Pennell
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
| | - Silvia C. Formenti
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA; (F.G.); (J.N.); (F.T.); (M.P.); (D.T.); (S.C.); (M.F.-K.); (R.P.)
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Retif P, Djibo Sidikou A, Gribelbauer J, Al Salah A, Pfletschinger E, Michel X. Automated Deep Inspiration Breath-Hold (DIBH) in breast radiotherapy: A comprehensive assessment of the VitalHold system on the Radixact platform. Phys Med 2025; 133:104977. [PMID: 40209547 DOI: 10.1016/j.ejmp.2025.104977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 03/01/2025] [Accepted: 04/04/2025] [Indexed: 04/12/2025] Open
Abstract
PURPOSE To evaluate the performance of the VitalHold module for automated Deep Inspiration Breath-Hold (DIBH) treatment on the Radixact platform, focusing on its dosimetric accuracy, responsiveness to respiratory motion and system latency. MATERIALS AND METHODS A Delta4 Phantom+ system with customized 3D-printed breast add-ons was used to simulate a clinically relevant setup for DIBH. A treatment plan was created with 40 Gy in 15 fractions using TomoDirect. The Phantom was coupled with the HexaMotion motion platform to to simulate simple (tested with various amplitude, periods and gating thresholds) and complex respiratory patterns, including irregular breathing, patient-specific motion, and baseline shifts. Respiratory motion was analyzed, and dose distributions were measured using gamma analysis with varying criteria. System latency was evaluated following TG-147 guidelines. RESULTS The measured simple respiratory curve closely matched the simulated motion, with amplitude differences under 0.1 mm and cycle variations of 0.1 s. Gamma pass rates for 2-5 mm gating tolerances were ≥95 %, indicating high system accuracy. Complex motion scenarios showed average measured amplitude deviations below 0.1 mm. The system exhibited a mean latency of 4.3 ms. CONCLUSIONS The VitalHold module on the Radixact platform demonstrates strong potential for automated DIBH treatment, providing precise and reliable beam control across both simple and complex respiratory patterns and exhibiting minimal latency. This study supports the integration of automated breath-hold techniques in clinical practice.
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Affiliation(s)
- Paul Retif
- Medical Physics Unit, CHR Metz-Thionville, Metz, France; Université de Lorraine, CNRS, CRAN, F-54000 Nancy, France.
| | | | | | | | | | - Xavier Michel
- Radiation Therapy Department, CHR Metz-Thionville, Metz, France
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Wang Y, Zhang Y, Chen SY, Lv T, Liu Y, Fang H, Jing H, Lu NN, Zhai YR, Song YW, Liu YP, Zhang WW, Qi SN, Tang Y, Chen B, Li YX, Men K, Chen X, Zhao W, Wang SL. An upfront patient selection strategy based on personalized data-driven computed tomography generation for deep inspiration breath-hold in breast radiotherapy. Phys Med 2025; 133:104964. [PMID: 40288024 DOI: 10.1016/j.ejmp.2025.104964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/15/2024] [Accepted: 03/23/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Currently there is no widely used upfront selection method to determine whether patients are suitable for deep inspiration breath-hold (DIBH) in left-sided breast radiotherapy. PURPOSE To establish an upfront patient selection strategy to improve the decision-making efficiency of DIBH and avoid extra computed tomography (CT) exposure to patients. METHODS A total of 174 patients who underwent both free-breathing (FB) and DIBH scans were enrolled. A general principal component analysis model for DIBH-CT synthesis was trained and consists of principal component feature vectors extracted from paired FB-CT and DIBH-CT in training set. The coefficients of the vectors were optimized to minimize the difference between synthetic CT and breath-hold scout image of each patient in test set, leading to personalized DIBH-CT synthesis. An upfront patient selection strategy was established based on cardiac dose in synthetic DIBH-CT plan. The performance of DIBH-CT synthesis was analyzed in terms of geometric and dosimetric consistency between synthetic and scanned DIBH-CTs. The accuracy of the patient selection strategy was evaluated. Time assumption of the patient selection workflow was analyzed. RESULTS Synthetic DIBH-CTs had average Dice similarity coefficients of 0.84 for the heart and 0.91 for the lungs compared with scanned DIBH-CTs. Synthetic DIBH-CT plans revealed an average mean heart dose reduction of 1.46 Gy, which was not significantly different from 1.51 Gy in scanned DIBH-CT plans (p = 0.878). The patient selection strategy yielded the correct benefit results with accuracy of 86.7 %. The average time assumption for patient selection was 11.9 ± 3.6 min. CONCLUSIONS The proposed patient selection strategy can accurately identify patients benefiting from DIBH and provides a more efficient workflow for DIBH.
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Affiliation(s)
- Yunxiang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yihang Zhang
- School of Physics, Beihang University, Beijing 102206, China
| | - Si-Ye Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Tie Lv
- School of Physics, Beihang University, Beijing 102206, China
| | - Yuxiang Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hui Fang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hao Jing
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ning-Ning Lu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yi-Rui Zhai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yong-Wen Song
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yue-Ping Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wen-Wen Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shu-Nan Qi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yuan Tang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Kuo Men
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xinyuan Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
| | - Wei Zhao
- School of Physics, Beihang University, Beijing 102206, China; Hangzhou International Innovation Institute, Beihang University, Hangzhou 310056, China; Tianmushan Laboratory, Hangzhou 311115, China.
| | - Shu-Lian Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
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Loap P, Vu Bezin J, Fourquet A, Kirova Y. Heart and lung sparing with isocentric lateral decubitus positioning compared with dorsal decubitus positioning during adjuvant localized breast cancer radiotherapy. Br J Radiol 2025; 98:679-685. [PMID: 40059328 DOI: 10.1093/bjr/tqaf049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 02/07/2025] [Accepted: 02/25/2025] [Indexed: 04/23/2025] Open
Abstract
OBJECTIVES The cardiac and pulmonary dosimetric benefit of alternative positioning in isocentric lateral decubitus compared with dorsal decubitus during adjuvant breast irradiation has yet to be proven, in spite of the relative long-standing use of isocentric lateral decubitus. METHODS Eight consecutive patients with an indication for adjuvant breast irradiation without boost or lymph node irradiation were scanned in both isocentric lateral and dorsal decubitus positions. For each patient, a plan delivering 40.05 Gy in 15 fractions in isocentric lateral decubitus and in dorsal decubitus using a field-in-field technique was calculated. Doses to the heart, to various cardiac substructures, and to the lungs were compared. RESULTS Mean dose to the heart, to various cardiac structures (left ventricle, left coronary, right coronary), to the homolateral lung, and to the contralateral lung were significantly lower in isocentric lateral decubitus than in dorsal decubitus. Average absolute mean dose reductions were -40 cGy for the heart, -27.5 cGy for the left ventricle, -56.5 cGy for the right coronary artery, -64.5 cGy for the left coronary artery, -45.5 cGy for the sinoatrial node, -74 cGy for the homolateral lung, and -4.5 cGy for the contralateral lung. For all organs at risk, median dose-volume histograms in isocentric lateral decubitus showed lower relative volumes than in dorsal decubitus. CONCLUSION Lateral decubitus positioning significantly reduces dose to the heart, to various cardiac substructures, to the homolateral lung, and to the contralateral lung, compared with dorsal decubitus. This technique is easily implemented and can be widely recommended to reduce heart and lung doses to a minimum. ADVANCES IN KNOWLEDGE Lateral decubitus positioning significantly reduces dose to the heart, to various cardiac substructures, to the homolateral lung, and to the contralateral lung, compared with dorsal decubitus. This technique is easily implemented and can be widely recommended to reduce heart and lung doses to a minimum.
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Affiliation(s)
- Pierre Loap
- Department of Radiation Oncology, Institut Curie, Paris 75005, France
- Laboratoire d'Imagerie Translationnelle en Oncologie, Institut Curie, Paris 75005, France
| | - Jeremi Vu Bezin
- Department of Radiation Oncology, Institut Curie, Paris 75005, France
| | - Alain Fourquet
- Department of Radiation Oncology, Institut Curie, Paris 75005, France
| | - Youlia Kirova
- Department of Radiation Oncology, Institut Curie, Paris 75005, France
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Ansari F, Neshasteh-Riz A, Paydar R, Mohagheghi F, Felegari S, Beigi M, Cheraghi S. Radiomics Analysis on Computed Tomography Images for Prediction of Chemoradiation-induced Heart Failure in Breast Cancer by Machine Learning Models. JOURNAL OF MEDICAL SIGNALS & SENSORS 2025; 15:14. [PMID: 40421235 PMCID: PMC12105806 DOI: 10.4103/jmss.jmss_51_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 10/01/2024] [Accepted: 10/29/2024] [Indexed: 05/28/2025]
Abstract
Background This study aimed to evaluate the effectiveness of clinical, dosimetric, and radiomic features from computed tomography (CT) scans in predicting the probability of heart failure in breast cancer patients undergoing chemoradiation treatment. Materials and Methods We selected 54 breast cancer patients who received left-sided chemoradiation therapy and had a low risk of natural heart failure according to the Framingham score. We compared echocardiographic patterns and ejection fraction (EF) measurements before and 3 years after radiotherapy for each patient. Based on these comparisons, we evaluated the incidence of heart failure 3 years postchemoradiation therapy. For machine learning (ML) modeling, we first segmented the heart as the region of interest in CT images using a deep learning technique. We then extracted radiomic features from this region. We employed three widely used classifiers - decision tree, K-nearest neighbor, and random forest (RF) - using a combination of radiomic, dosimetric, and clinical features to predict chemoradiation-induced heart failure. The evaluation criteria included accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (area under the curve [AUC]). Results In this study, 46% of the patients experienced heart failure, as indicated by EF. A total of 873 radiomic features were extracted from the segmented area. Out of 890 combined radiomic, dosimetric, and clinical features, 15 were selected. The RF model demonstrated the best performance, with an accuracy of 0.85 and an AUC of 0.98. Patient age and V5 irradiated heart volume were identified as key predictors of chemoradiation-induced heart failure. Conclusion Our quantitative findings indicate that employing ML methods and combining radiomic, dosimetric, and clinical features to identify breast cancer patients at risk of cardiotoxicity is feasible.
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Affiliation(s)
- Farzaneh Ansari
- Department of Radiation Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Neshasteh-Riz
- Department of Radiation Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Paydar
- Department of Radiation Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Sahar Felegari
- Department of Information Technology, K. N. Toosi University of Technology, Tehran, Iran
| | - Manijeh Beigi
- Department of Radiation Oncology, Shohadaye Haftome Tir Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Susan Cheraghi
- Department of Radiation Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
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Zhang Z, Tang Z, Yang M, Moraros J, Li X, Zhang X, Li Y, Chen G, Wang S, Liu Y. Multiphases dose analysis of cardiac substructures using coronary CT angiography in postmastectomy radiotherapy. Med Dosim 2025:S0958-3947(25)00020-2. [PMID: 40312190 DOI: 10.1016/j.meddos.2025.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 03/01/2025] [Accepted: 03/20/2025] [Indexed: 05/03/2025]
Abstract
This study used coronary computed tomography angiography (CCTA) in left breast cancer patients. It assessed real-time dose delivery of postmastectomy radiotherapy (PMRT) with internal lymph node irradiation (IMNIs) and normal tissue complications probability (NTCP) to the heart and subcardiac structures using tangential volumetric modulated arc therapy (T-VMAT). This research and its findings are critical in refining PMRT strategies to safeguard patient health and promote the overall efficacy of cancer management protocols. In this study, CCTA images from 16 patients were analyzed. These images were reconstructed at multiple phases (0%-90%) of the cardiac cycle for each patient. Substructures including the left ventricle (LV), right ventricle (RV), right atrium (RA), left atrium (LA), right coronary artery (RCA), and left anterior descending artery (LAD) were delineated using the RTOG 1106 OAR atlas guidelines. A rigid registration process aligned the CCTA images with planning chest CT scans. The heart's CT values were adjusted to ensure accuracy in electron density representation. The PTV was simulated, and a T-VMAT plan was created. The radiation fields were then applied to the 10 different cardiac phase images, and an accumulated plan was generated and compared with a conventional radiotherapy plan. Comparing the accumulated plan with the conventional plan, the absolute Dmean difference to the heart was 73.2 (cGy), and demonstrated a significant change of 14%. Among cardiac substructures, the largest differences in Dmean were observed in the LAD, RCA and LV-V25 with a variation of 387.5 cGy (22.5%), 195.8 cGy (34.7%) and 1.53% (52%), respectively. NTCP was slightly higher in the accumulated plan (0.44±1.57%) than in the conventional plan (0.17±0.47%). The results of this study underscore the critical role of real-time cardiac imaging in refining the delivery of PMRT with IMNIs. By leveraging CCTA and T-VMAT, we have achieved a more precise assessment of the cardiac dose, leading to a potential reduction in radiation-related cardiovascular risks without compromising cancer treatment efficacy. This research highlights the importance of integrating advanced imaging and radiation planning techniques to ensure the highest standards of patient care in the context of left breast cancer treatment.
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Affiliation(s)
- Zhe Zhang
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Hong Kong University of Science and Technology Medical Center, Shenzhen 518048, China; Department of Biosciences and bioinformatics, Suzhou Municipal key Lab AI4Health, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China; Department of Computer Sciences, University of Liverpool, Liverpool L69 7ZX, UK
| | - Zhaohui Tang
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Hong Kong University of Science and Technology Medical Center, Shenzhen 518048, China
| | - Mengqi Yang
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Hong Kong University of Science and Technology Medical Center, Shenzhen 518048, China
| | - John Moraros
- Department of Biosciences and bioinformatics, Suzhou Municipal key Lab AI4Health, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China; Department of Computer Sciences, University of Liverpool, Liverpool L69 7ZX, UK
| | - Xin Li
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Hong Kong University of Science and Technology Medical Center, Shenzhen 518048, China
| | - Xiaomin Zhang
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Hong Kong University of Science and Technology Medical Center, Shenzhen 518048, China
| | - Ying Li
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Hong Kong University of Science and Technology Medical Center, Shenzhen 518048, China
| | - Gaoxiang Chen
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing 100039, China
| | - Shuihua Wang
- Department of Biosciences and bioinformatics, Suzhou Municipal key Lab AI4Health, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China; Department of Computer Sciences, University of Liverpool, Liverpool L69 7ZX, UK
| | - Yajie Liu
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Hong Kong University of Science and Technology Medical Center, Shenzhen 518048, China.
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Nuruddeen MG, A Karim NK, A/L Appalanaido GK, Mohd Zin MH, Sayuti KA, Mad Naser MN. Cardiac substructure dose distributions in node-positive and node-negative breast cancer patients undergoing 3D-CRT: comparing the predictive accuracy of mean heart dose and mean left ventricular dose. Radiat Oncol 2025; 20:65. [PMID: 40301974 PMCID: PMC12039179 DOI: 10.1186/s13014-025-02607-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 02/20/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND AND PURPOSE Cardiotoxicity is a concern, especially in left breast cancer (BC) radiotherapy (RT), and accurate dosimetry is essential for minimizing cardiac exposure. This study evaluated the radiation exposure of cardiac substructures in node-positive and node-negative BC patients who underwent three-dimensional conformal therapy (3D-CRT) and compared the predictive accuracy of mean heart dose (MHD) and mean left ventricular dose (MLVD) in estimating dose distribution to cardiac substructures. MATERIALS AND METHODS This study included 55 patients with left-sided breast cancer, comprising 39 with node-positive and 16 with node-negative disease. All underwent adjuvant whole-breast irradiation using 3D-CRT. The heart, ventricles, atria, right coronary (RC), left anterior descending coronary (LADCA), and left circumflex (LCx) arteries were contoured. Dosimetric distributions were evaluated, and Pearson's correlation and linear regression analyses were used to assess the relationship between cardiac substructures. RESULTS The distribution of doses to cardiac substructures was heterogeneous, with LADCA receiving the highest doses: 15.6 Gy in node-positive and 13.2 Gy in node-negative breast cancer patients. Linear regression analysis revealed a weak to moderate predictive ability of MHD/MLVD to predict doses received by the cardiac substructure in both groups, with MLVD demonstrating marginally better results. For node-positive patients, the analysis revealed an R² of 0.40 (p < 0.001) for the association between MHD and LADCA and an R² of 0.45 (p < 0.001) for MLVD and LADCA. In node-negative patients, the R² values were 0.27 (p < 0.001) for MHD versus LADCA and 0.30 (p < 0.03) for MLVD versus LADCA. Pearson's correlation analysis for node-positive patients indicated r = 0.63 (p < 0.001) for MHD versus LADCA and r = 0.67 (p < 0.001) for MLVD versus LADCA. For node-negative patients, the correlation coefficients were r = 0.52 (p < 0.001) for MHD versus LADCA and r = 0.54 (p < 0.001) for MLVD versus LADCA. CONCLUSION Radiation exposure to cardiac substructures during 3D-CRT for left breast cancer was heterogeneous, with the LADCA receiving the highest mean dose, followed by the LV. MLVD demonstrated superior predictive accuracy over mean heart dose (MHD) for estimating doses to critical substructures, particularly in node-positive patients.
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Affiliation(s)
- Mohammad Gunda Nuruddeen
- Department of Biomedical Imaging, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, 13200, Malaysia
- Department of Medical Radiography, Faculty of Allied Health Sciences, College of Medical Sciences, University of Maiduguri, Bama Road, Maiduguri, 1069, Nigeria
| | - Noor Khairiah A Karim
- Department of Biomedical Imaging, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, 13200, Malaysia.
- Breast Cancer Translational Research Programme (BCTRP), Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, 13200, Malaysia.
- Heart Failure Research Initiative, Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, 13200, Malaysia.
| | - Gokula Kumar A/L Appalanaido
- Department of Biomedical Imaging, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, 13200, Malaysia
| | - Mohd Hafiz Mohd Zin
- Department of Biomedical Imaging, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, 13200, Malaysia
- Breast Cancer Translational Research Programme (BCTRP), Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, 13200, Malaysia
| | - Khairil Amir Sayuti
- Department of Radiology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, 16150, Malaysia
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Kotanidis CP, Halborg T, Tomlins P, Chan K, Fry S, Jimenez G, Lapeyre M, Sabharwal N, Channon KM, Neubauer S, Jacob S, Antoniades C. Coronary inflammation and cardiovascular risk in breast cancer after radiotherapy. Eur Heart J 2025:ehaf260. [PMID: 40256882 DOI: 10.1093/eurheartj/ehaf260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/14/2025] [Accepted: 03/30/2025] [Indexed: 04/22/2025] Open
Affiliation(s)
- Christos P Kotanidis
- Acute Multidisciplinary Imaging and Interventional Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
- Division of Cardiovascular Medicine, Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Thomas Halborg
- Acute Multidisciplinary Imaging and Interventional Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
| | | | - Kenneth Chan
- Acute Multidisciplinary Imaging and Interventional Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
| | - Sam Fry
- Caristo Diagnostics Ltd, Oxford, UK
| | - Gaëlle Jimenez
- Department of Radiation Oncology, Clinique Pasteur, Toulouse 31076, France
| | - Matthieu Lapeyre
- Department of Radiology, Clinique Pasteur, Toulouse 31076, France
| | - Nikant Sabharwal
- Department of Cardiology, NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
| | - Keith M Channon
- Acute Multidisciplinary Imaging and Interventional Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
- Department of Cardiology, NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
| | - Stefan Neubauer
- Acute Multidisciplinary Imaging and Interventional Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
- Department of Cardiology, NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
| | - Sophie Jacob
- Laboratory of Epidemiology, Institute for Radiation Protection and Nuclear Safety (IRSN), Fontenay-Aux-Roses 92260, France
| | - Charalambos Antoniades
- Acute Multidisciplinary Imaging and Interventional Centre, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
- Department of Cardiology, NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU Oxford, UK
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Luo Y, Liu J, Qu P, Han S, Li X, Wang Y, Su X, Zeng J, Li J, Deng S, Liang Q, Hou L, Cheng P. The crosstalk of breast cancer and ischemic heart disease. Cell Death Discov 2025; 11:185. [PMID: 40251177 PMCID: PMC12008236 DOI: 10.1038/s41420-025-02428-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 03/07/2025] [Accepted: 03/21/2025] [Indexed: 04/20/2025] Open
Abstract
In recent years, the continuous optimization of anti-tumor therapy has greatly improved the cancer-specific survival rate for patients with breast cancer (BC). The prevention and treatment of breast cancer-related heart diseases have become a new breakthrough in improving the long-term survival for BC patient. The cardiac damages caused by BC treatment are increasingly prominent among BC patients, of which ischemic heart disease (IHD) is the most prominent. Besides, the systemic inflammatory response activated by tumor microenvironment c an induce and exacerbate IHD and increase the risk of myocardial infarction (MI). Conversely, IHD can also exert detrimental effects on tumors. MI not only increases the risk of BC, but also induces specialized immune cell to BC and accelerates the progression of BC. Meanwhile, the treatment of IHD can also promote BC metastasis and transition to more aggressive phenotypes. Although BC and IHD are diseases of two independent systems, their crosstalk increases the difficulty of anti-cancer treatment and IHD management, which reduces the survival for both diseases. Therefore, this review mainly explores the mutual influence and underlying mechanisms between BC and IHD, aiming to provide insights for improving the long-term survival for patients with BC or IHD.
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Affiliation(s)
- Yunbo Luo
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Jun Liu
- Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P.R. China
| | - Peng Qu
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
| | - Shiqi Han
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Xue Li
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
| | - Yali Wang
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Xiaohan Su
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Jiao Zeng
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Jinsui Li
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Shishan Deng
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Qi Liang
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China.
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China.
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China.
| | - Lingmi Hou
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
| | - Panke Cheng
- Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P.R. China.
- Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Chengdu, 610072, P.R. China.
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Kefeli AU, Diremsizoglu U, Erdogan S, Karabey AU, Konuk AO, Tirpanci B, Aksu MG, Sarper EB. Patient coaching for deep inspiration breath hold decreases set-up duration and left anterior descending artery dose for left-sided breast cancer radiotherapy. Support Care Cancer 2025; 33:387. [PMID: 40240656 PMCID: PMC12003517 DOI: 10.1007/s00520-025-09446-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Accepted: 04/09/2025] [Indexed: 04/18/2025]
Abstract
PURPOSE The purpose is to show the impact of patient coaching and home practice using the deep inspiration breath hold (DIBH) technique on radiation treatment set-up times and cardiac at-risk doses. METHODS The study involved patients who received tangential field radiotherapy using the DIBH technique for treating left breast cancer. Patients were divided into two groups: the first group consisted of those who received coaching from an oncology nurse and were given an instruction sheet at least 1 week before the computed tomography (CT) simulation. The second group consisted of those who were only taught how to hold their breath by the radiation technician on the simulation day and without further education. During treatment, the patients were monitored using the Varian RPM™ respiratory gating system, and 2D kV orthogonal imaging was performed daily. The setup duration of each patient was noted and compared between treatment groups. For each patient, the dose-volume histograms (DVHs) of the heart, LAD (left anterior descending artery), were calculated and compared for both coached DIBH (cDIBH) and non-coached DIBH (ncDIBH). RESULTS Thirty-six coached and 28 non-coached patients were identified. Compared with ncDIBH, coached patients were older (55.5 versus 46.5, p = 0.003) and had a significantly higher BMI (body mass index) (29.95 versus 26.32 kg/m2, p = 0.006). Nevertheless, in more than half of the treatment fractions, the set-up duration was detected to be statistically longer in the ncDIBH group than in the cDIBH group. Additionally, the LAD max dose was significantly lower in the cDIBH group (36.5 versus 29.5, p = 0.02). CONCLUSION Coaching at least 1 week before the simulation with an instruction sheet decreased the set-up duration, and the cardiac LAD max dose should be further decreased by this method.
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Affiliation(s)
- Aysegul Ucuncu Kefeli
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey.
| | - Umut Diremsizoglu
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey
| | - Sevda Erdogan
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey
| | - Aysegul Unal Karabey
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey
| | - Aykut Oguz Konuk
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey
| | - Berna Tirpanci
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey
| | - Maksut Gorkem Aksu
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey
| | - Emine Binnaz Sarper
- Department of Radiation Oncology, Kocaeli University School of Medicine, Kabaoglu Mahallesi, Baki Komsuoglu bulvarı No:515, Umuttepe, 41001 İzmit, Turkey
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Ryan TD, Bates JE, Kinahan KE, Leger KJ, Mulrooney DA, Narayan HK, Ness K, Okwuosa TM, Rainusso NC, Steinberger J, Armenian SH. Cardiovascular Toxicity in Patients Treated for Childhood Cancer: A Scientific Statement From the American Heart Association. Circulation 2025; 151:e926-e943. [PMID: 40104841 DOI: 10.1161/cir.0000000000001308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/20/2025]
Abstract
The field of cardio-oncology has expanded over the past 2 decades to address the ever-increasing issues related to cardiovascular disease in patients with cancer and survivors. There is increasing recognition that nearly all cancer treatments pose some short- or long-term risk for development of cardiovascular disease and that pediatric patients with cancer may be especially vulnerable to cardiovascular disease because of young age at treatment and expected long life span afterward. Anthracycline chemotherapy and chest-directed radiotherapy are the most well-studied cardiotoxic therapies, and dose reduction, use of cardioprotection for anthracyclines, and modern radiotherapy approaches have contributed to improved cardiovascular outcomes for survivors. Newer treatments such as small-molecule inhibitors, antibody-based cytotoxic therapy, and immunotherapy have expanded options for previously difficult-to-treat cancers but have also revealed new cardiotoxic profiles. Application of effective surveillance strategies in patients with cancer and survivors has been a focus of practitioners and researchers, whereas the prevention and treatment of extant cardiovascular disease is still developing. Incorporation of new strategies in an equitable manner and appropriate transition from pediatric to adult care will greatly influence long-term health-related outcomes in the growing population of childhood cancer survivors at risk for cardiovascular disease.
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Morris AD, Hanes DA, Kaplan HG. Long-Term Outcomes of Radiation Monotherapy Versus Combined Radiation Monotherapy + Hormone Therapy in Low-Risk Early-Stage Breast Cancer Patients 70 Years or Older After Breast-Conserving Surgery. Int J Radiat Oncol Biol Phys 2025; 121:1134-1144. [PMID: 39864014 DOI: 10.1016/j.ijrobp.2024.11.098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 10/16/2024] [Accepted: 11/03/2024] [Indexed: 01/27/2025]
Abstract
PURPOSE Standard therapy for breast cancer after breast-conserving surgery is radiation therapy (RT) plus hormone therapy (HT). For patients with a low-risk of recurrence, there is an interest in deescalating therapy. METHODS AND MATERIALS A retrospective study was carried out for patients treated at the Swedish Cancer Institute from 2000 to 2015, aged 70 years or older, with pT1N0 or pT1NX estrogen receptor-positive and ERBB2-negative unifocal breast cancer without positive surgical margins, high nuclear grade, or lymphovascular invasion. RESULTS Patient numbers were sufficient to carry out analyses for RT + HT (n = 307) and RT alone (n = 148). The median follow-up was 9.6 years. There were no statistically significant differences in adjusted overall survival (OS), disease-specific death, progression-free survival (PFS), distant recurrence, and second primary cancers with RT monotherapy compared with RT + HT. Cumulative rates of all of these outcomes were <5%, even at 15 years of follow-up, regardless of treatment, greatly outweighed by the incidence of death from other causes in this elderly population. In matched analysis, we calculated a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for OS and a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for PFS. CONCLUSIONS Our data suggest that elderly, low-risk breast cancer patients have similarly high OS and PFS with low rates of local recurrence, distant recurrence, and death from breast cancer with much higher rates of death from competing causes, whether treated with RT or HT + RT. These patients are likely to die of other causes without disease recurrence, regardless of which of these treatments is used. Thus, they may benefit from the administration of more modern forms of breast irradiation without the need for adjuvant systemic hormone therapy. A detailed analysis of which clinical, pathologic, genomic, and comorbidity variables are needed to select these patients.
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Affiliation(s)
| | | | - Henry G Kaplan
- Providence Swedish Cancer Institute, Seattle, Washington
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31
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Meillan N, Rivera S, Ederhy S, Gueiderikh A, Lamrani-Ghaouti A, De Vathaire F, Allodji RS. Early Breast Cancer Treatment and Cardiac Events: A Systematic Review. Clin Breast Cancer 2025:S1526-8209(25)00085-0. [PMID: 40288934 DOI: 10.1016/j.clbc.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 03/07/2025] [Accepted: 03/23/2025] [Indexed: 04/29/2025]
Abstract
Cancer-treatment induced cardiovascular diseases are a concern in early breast cancer, especially when radiation is involved and systemic treatments may contribute. Our primary objective was to estimate the frequency of cardiac adverse events after early breast cancer treatment. We performed a systematic review on cardiac events after early breast cancer treatment, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, by searching PubMed, Scopus and Web of Science and cross-checking references from international guidelines on breast cancer treatment and cardio-oncology. Eighty-one studies were selected. Reporting of cardiac events and dose parameters was heterogeneous among studies due to the variability of the events being considered, follow-up duration and patient's age (most reported less than 5% with some as high as 34% at a maximum follow-up of 28 years). The most frequent are ischemic and valvular heart disease. Radiation modalities (hypofractionation, boost, partial or nodal irradiation) do not seem to change the risk of cardiac events. Anthracycline and aromatase inhibitors increase long-term cardiac risk, whereas anti-HER2-related effects are mostly transient. Myocardites with immunotherapy are rare (<1%) but follow-up is short. Other chemotherapy agents and poly(adenosine-diphosphate-ribose)-polymerase inhibitors have not been shown to increase cardiac risks which is reduced with more recent treatments, and increased by young age at diagnosis and previous cardiac risk factors. Advances in treatment seem to lower cardiac events. Prospective studies with exhaustive reporting of toxicity and radiotherapy features are warranted as well as the help of a cardio-oncologist to manage risk factors.
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Affiliation(s)
- Nicolas Meillan
- Oncology-radiation therapy department, Victor Dupouy Hospital, Argenteuil, France; Gustave Roussy, Comprehensive Cancer Research Center, Villejuif, France; Centre for Research in Epidemiology and Population Health, U1018 Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France; Paris-Saclay University, Unité Mixte de Recherche (UMR), 1018, Villejuif, France.
| | - Sofia Rivera
- Gustave Roussy, Comprehensive Cancer Research Center, Villejuif, France; Gustave Roussy, Radiation Therapy Department, Villejuif, France; Paris-Saclay University, Gustave Roussy, Institut National de la Santé et de la Recherche Médicale (INSERM) 1030, Villejuif, France
| | - Stéphane Ederhy
- Department of Cardiology, UNICO Cardio-Oncology Program, Saint-Antoine Hospital, AP-HP, Paris, France; Inserm U 856, 75013 Paris, France
| | - Anna Gueiderikh
- Gustave Roussy, Radiation Therapy Department, Villejuif, France
| | | | - Florent De Vathaire
- Gustave Roussy, Comprehensive Cancer Research Center, Villejuif, France; Centre for Research in Epidemiology and Population Health, U1018 Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France; Paris-Saclay University, Unité Mixte de Recherche (UMR), 1018, Villejuif, France
| | - Rodrigue Setcheou Allodji
- Gustave Roussy, Comprehensive Cancer Research Center, Villejuif, France; Centre for Research in Epidemiology and Population Health, U1018 Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France; Paris-Saclay University, Unité Mixte de Recherche (UMR), 1018, Villejuif, France
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Wilson F, Gupta P, Halvorsen H, Anandadas C, Lines D, Aznar M. A Systematic Review of Deep Inspiration Breath Hold and Free Breathing in Proton Beam Therapy Plans for Breast Cancer Radiotherapy. Clin Oncol (R Coll Radiol) 2025; 40:103782. [PMID: 39999640 DOI: 10.1016/j.clon.2025.103782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 12/24/2024] [Accepted: 01/30/2025] [Indexed: 02/27/2025]
Abstract
AIMS To conduct a systematic review of breast cancer radiotherapy studies reporting a comparison of proton beam therapy (PBT) in deep inspiration breath hold (DIBH) and in free breathing (FB). METHODS AND MATERIALS Studies comparing DIBH and FB proton beam therapy plans, in the same patient, published between 2015 and 2023 were included. Doses to organs at risk were compared between DIBH and FB plans. RESULTS Nine papers were identified for inclusion, reporting on 97 patients in total. All plans were for left-sided treatment. Average weighted mean heart dose was 0.31 Gy for DIBH and 0.48 Gy for FB. Average weighted mean left lung dose was 5.27 Gy for DIBH and 4.80 Gy for FB. Average weighted mean near maximum/maximum left anterior descending artery dose was 6.49 Gy for DIBH and 8.74 Gy for FB. CONCLUSION Based on the current literature, it does not appear that DIBH offers a marked dosimetric benefit to most breast cancer patients treated with PBT. However, the benefits of combining PBT and DIBH for individual breast RT patients cannot be excluded.
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Affiliation(s)
- F Wilson
- Radiotherapy Related Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Patterson Building, Wilmslow Road, Manchester, M20 4BX, UK; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
| | - P Gupta
- Radiotherapy Related Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Patterson Building, Wilmslow Road, Manchester, M20 4BX, UK.
| | - H Halvorsen
- Radiotherapy Related Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Patterson Building, Wilmslow Road, Manchester, M20 4BX, UK.
| | - C Anandadas
- The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
| | - D Lines
- The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
| | - M Aznar
- Radiotherapy Related Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Patterson Building, Wilmslow Road, Manchester, M20 4BX, UK; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
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33
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Van der Vorst A, Lambrecht M, Van Aelst L, Verhoeven J, Jacobs J, Baten A, Weltens C. Radiation-induced heart disease in breast cancer patients: a narrative review of epidemiology, risk factors, radiotherapy parameters, and prevention. Strahlenther Onkol 2025; 201:368-382. [PMID: 39976674 DOI: 10.1007/s00066-024-02362-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/23/2024] [Indexed: 03/22/2025]
Abstract
BACKGROUND Breast cancer is the most prevalent cancer in women worldwide; nevertheless, the prognosis is good, with a 5-year overall survival of 80-90%. Therefore, it becomes crucial to strive for high quality of life after cure by minimizing treatment-related toxicity. One such concern is radiation-induced heart disease, which remains a significant focus of ongoing investigations. PURPOSE The aim of this review is to summarize current knowledge on radiation-induced heart disease in breast cancer patients by giving an overview of its epidemiology, risk factors, radiation parameters related to its development, solutions in radiation practice, and prevention. The goal is to raise awareness and maximize prevention of radiation-induced heart disease. METHODS The PubMed database was screened for articles published between January 2013 and November 2023 related to the keywords , , , and . Moreover, by screening the literature lists of these publications, additional articles were added. RESULTS Ninety-four relevant papers remained for final review. CONCLUSION Radiation-induced heart disease is a rare complication after breast cancer radiotherapy and represents a clinical spectrum of various cardiovascular conditions. Several heart-sparing techniques have been developed, and more attention has been paid to early diagnosis and prevention of radiation-induced heart disease. However, further research remains important to refine radiotherapy techniques and deepen our understanding for improved prevention and treatment of this condition in the future. This clinical review summarizes the existing evidence and literature on radiation-induced heart disease following modern breast cancer radiotherapy, offering clinical guidance for physicians.
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Affiliation(s)
- Aline Van der Vorst
- Laboratory of Experimental Radiotherapy, UZ Leuven, Leuven, Belgium.
- Department of Radiation-Oncology, UZ Leuven, Leuven, Belgium.
| | - Maarten Lambrecht
- Laboratory of Experimental Radiotherapy, UZ Leuven, Leuven, Belgium
- Department of Radiation-Oncology, UZ Leuven, Leuven, Belgium
| | - Lucas Van Aelst
- Laboratory of Clinical Cardiology, UZ Leuven, Leuven, Belgium
- Department of Cardiology, UZ Leuven, Leuven, Belgium
| | - Jelle Verhoeven
- Department of Radiation-Oncology, UZ Leuven, Leuven, Belgium
| | - Johanna Jacobs
- Laboratory of Clinical Cardiology, UZ Leuven, Leuven, Belgium
- Department of Cardiology, UZ Leuven, Leuven, Belgium
| | - Adinda Baten
- Department of Radiation-Oncology, UZ Leuven, Leuven, Belgium
| | - Caroline Weltens
- Laboratory of Experimental Radiotherapy, UZ Leuven, Leuven, Belgium
- Department of Radiation-Oncology, UZ Leuven, Leuven, Belgium
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34
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Jacob S, Kirova Y, Marijon E. Beyond Mean Heart Dose: Rethinking Cardiac Dysfunction and Risk Assessment in Breast Radiation Therapy. JACC CardioOncol 2025; 7:231-233. [PMID: 40136253 PMCID: PMC12046804 DOI: 10.1016/j.jaccao.2025.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/04/2025] [Accepted: 03/05/2025] [Indexed: 03/27/2025] Open
Affiliation(s)
- Sophie Jacob
- Authority for Nuclear Safety and Radiation Protection (ASNR), PSE-SANTE, SESANE, LEPID, Fontenay-aux-Roses, France.
| | - Youlia Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Eloi Marijon
- Division of Cardiology, European Georges Pompidou Hospital, Paris, France
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35
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Long M, Alnoury M, Udupa JK, Tong Y, Wu C, Poole N, Mannikeri S, Ky B, Feigenberg SJ, Zou JW, O'Reilly S, Torigian DA. Prediction of Radiation Therapy Induced Cardiovascular Toxicity from Pretreatment CT Images in Patients with Thoracic Malignancy via an Optimal Biomarker Approach. Acad Radiol 2025; 32:1895-1905. [PMID: 39870564 PMCID: PMC11981848 DOI: 10.1016/j.acra.2025.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 01/06/2025] [Accepted: 01/12/2025] [Indexed: 01/29/2025]
Abstract
RATIONALE AND OBJECTIVES Cardiovascular toxicity is a well-known complication of thoracic radiation therapy (RT), leading to increased morbidity and mortality, but existing techniques to predict cardiovascular toxicity have limitations. Predictive biomarkers of cardiovascular toxicity may help to maximize patient outcomes. METHODS The machine learning optimal biomarker (OBM) method was employed to predict development of cardiotoxicity (based on serial echocardiographic measurements of left ventricular ejection fraction and longitudinal strain) from computed tomography (CT) images in patients with thoracic malignancy undergoing RT. Manual segmentations of 10 cardiovascular objects of interest were performed on pre-treatment non-contrast-enhanced CT simulation images in 125 patients with thoracic malignancy (41 who developed cardiotoxicity and 84 who did not after RT). 1078 features describing morphology, image intensity, and texture for each of these objects were extracted and the top 5 features among them that were most uncorrelated and showed the best ability to discriminate between cardiotoxicity/ no cardiotoxicity were determined. The best combination among all possible combinations among these 5 features that yielded the highest accuracy of prediction on a training data set was selected, an SVM classifier was then trained on this combination, and tested for prediction accuracy on an independent data set. Prediction accuracy was quantified for the optimal features derived from each object. RESULTS The best feature combination based on 5 CT-based features derived from the left ventricle had the highest testing prediction accuracy of 0.88 among all objects. Prediction accuracies over all objects ranged from 0.76-0.88. Heart, Left Atrium, Aortic Arch, Thoracic Aorta, and Descending Thoracic Aorta showed the next best accuracy of 0.84. Most optimal features were texture properties based on the co-occurrence matrix. CONCLUSION It is feasible to predict future cardiotoxicity following RT with high accuracy in individual patients with thoracic malignancy from available pre-treatment CT images via machine learning techniques.
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Affiliation(s)
- Mujun Long
- College of Materials Science and Engineering, Chongqing University, Chongqing 400044, PR China (M.L.); Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.)
| | - Mostafa Alnoury
- Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.)
| | - Jayaram K Udupa
- Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.)
| | - Yubing Tong
- Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.)
| | - Caiyun Wu
- Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.)
| | - Nicholas Poole
- Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.)
| | - Sutirth Mannikeri
- Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.)
| | - Bonnie Ky
- Department of Medicine, Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA 19104 (B.K.)
| | - Steven J Feigenberg
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104 (S.J.F., J.W.Z., S.O.)
| | - Jennifer W Zou
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104 (S.J.F., J.W.Z., S.O.)
| | - Shannon O'Reilly
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104 (S.J.F., J.W.Z., S.O.)
| | - Drew A Torigian
- Medical Image Processing Group, 602 Goddard building, 3710 Hamilton Walk, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (M.L., M.A., J.K.U., Y.T., C.W., N.P., S.M., D.A.T.).
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Bachmann N, Loebner HA, Althaus A, Hemmatazad H. Stereotactic Re-irradiation of Sternal Metastases Using Skin Surface Fiducial Markers and Real-Time Motion Synchronization. Cureus 2025; 17:e82239. [PMID: 40370907 PMCID: PMC12077580 DOI: 10.7759/cureus.82239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2025] [Indexed: 05/16/2025] Open
Abstract
Due to respiratory motion, treating sternal metastases with stereotactic body radiotherapy (SBRT) is challenging, often requiring large irradiation volumes to account for target movement. To address this, we implemented a straightforward approach by placing skin fiducial markers near the sternal metastasis, enabling real-time motion synchronization with the CyberKnife® System (Accuray Inc., Sunnyvale, CA). Advances in anti-cancer therapies have significantly extended survival in metastatic patients, increasing their likelihood of requiring re-irradiation and experiencing late toxicities. We present the outcomes of two patients, one with metastatic hepatocellular carcinoma (mHCC) and one with metastatic breast cancer (mBC), who underwent two courses of SBRT for sternal metastases using the CyberKnife® and skin fiducial markers for motion management. Both patients tolerated the treatment well, achieving complete pain relief and durable local control. No late toxicity was observed in the mHCC case, while the mBC patient developed significant left anterior descending artery (LAD) stenosis, which may have been linked to cumulative radiation exposure. Given the known risk of cardiac toxicity associated with radiation therapy, these findings underscore the importance of minimizing cardiac dose to reduce long-term toxicity, particularly in re-irradiation cases.
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Affiliation(s)
- Nicolas Bachmann
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, CHE
| | - Hannes A Loebner
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, CHE
| | - Alexander Althaus
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, CHE
| | - Hossein Hemmatazad
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, CHE
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Polomski EAS, Heemelaar JC, de Ronde MES, Al Jaff AAM, Mertens BJA, van Dijkman PRM, Jukema JW, Antoni ML. Increased prevalence of coronary atherosclerosis in cancer survivors: A retrospective matched cross-sectional study with coronary CT angiography. Am Heart J 2025; 282:134-145. [PMID: 39793723 DOI: 10.1016/j.ahj.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 12/16/2024] [Accepted: 01/06/2025] [Indexed: 01/13/2025]
Abstract
BACKGROUND Cancer and cancer treatment may accelerate the development of cardiovascular disease. With the improved prognosis of cancer survivors, cardiovascular events are increasing in this patient group. However, it is unknown whether the prevalence of coronary atherosclerosis is increased in patients with a history of cancer. This study aims to evaluate the prevalence and severity of coronary atherosclerosis in different age groups of cancer survivors compared to matched controls. METHODS Consecutive cancer survivors aged > 30 years who underwent evaluation for stable coronary artery disease with coronary computed tomography angiography (CCTA) were included in this retrospective study. Propensity score matching was performed and cancer survivors were matched 1:2 to a control population without oncological history. The presence of coronary atherosclerosis was assessed in both groups. RESULTS The study population consisted of 312 cancer survivors and 624 matched controls. Median age at CCTA scan was 59.2 [50.3-67.5] years and 66.0% was female. Coronary atherosclerosis was observed in 257 (82.4%) cancer survivors compared to 459 (73.6%) control patients with an Odds Ratio (OR) of 1.68 [95% CI: 1.19-2.36], P = .003. Mainly younger cancer survivors aged between 30 and 59 years had an increased prevalence of coronary atherosclerosis with an OR of 2.21 [95% CI: 1.40-3.49] compared to control patients (P = .001). In addition, thoracic radiotherapy showed a significant association with increased prevalence of atherosclerosis in the younger population with an OR of 3.29 ([95% CI: 1.70-6.38], P < .001). CONCLUSIONS Patients with a history cancer have an increased prevalence of coronary atherosclerosis on CCTA compared to matched patients without cancer. This effect was most pronounced in younger patients aged 30 to 59 years.
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Affiliation(s)
- Elissa A S Polomski
- Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Julius C Heemelaar
- Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Mian E S de Ronde
- Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Ahmed A M Al Jaff
- Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, The Netherlands
| | - B J A Mertens
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Paul R M van Dijkman
- Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, The Netherlands
| | - J Wouter Jukema
- Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Heart Institute, Utrecht, The Netherlands
| | - M Louisa Antoni
- Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, The Netherlands.
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Lamy J, Spoor DS, Langendijk JA, Vliegenthart R, Eraso A, Ventura M, Constantino Rosa Santos S, Fiúza M, Kachenoura N, Crijns APG, Mousseaux E. Cardiac MRI-based Subclinical Cardiac Dysfunction during 2 Years after Breast Cancer Irradiation: The MEDIRAD EARLY-HEART Study. Radiol Cardiothorac Imaging 2025; 7:e240231. [PMID: 40178396 DOI: 10.1148/ryct.240231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2025]
Abstract
Purpose To evaluate the relationship between cardiac radiation doses and subclinical changes in cardiac function using cardiac MRI during 2 years of follow-up in patients with breast cancer treated with radiation therapy without chemotherapy after lumpectomy. Materials and Methods This prospective multicenter study (NCT03297346) enrolled female individuals with breast cancer treated with radiation therapy between December 2017 and September 2019. Participants underwent cardiac MRI at baseline, 6 months, and 24 months. Cardiac radiation doses were assessed for the whole heart (WH) and right and left ventricles (LV). A persistent decrease in LV global longitudinal strain (GLS) from baseline to the other two measurement points over the 2-year follow-up was considered an adverse subclinical change in cardiac function. Statistical analysis included Wilcoxon tests for continuous variables and odds ratios for risk assessment. Results The study included 138 female participants (mean age, 58.4 years ± 8.0 [SD]). Mean WH and LV doses were 1.42 Gy (IQR, 1.03-2.01) and 1.46 Gy (IQR, 0.64-2.34). At the 2-year follow-up, all participants had reduced LV end-diastolic volume (EDV) (-4.0% ± 13.2; P < .001) and stroke volume (-3.4% ± 15.2; P < .001), preserved LV ejection fraction, and increased LV remodeling (LV mass/EDV ratio) (4.2% ± 18.1; P < .04) without associated symptoms. Twenty-three (16.6%) participants showed a persistent decrease in LV GLS and received higher mean WH and LV doses compared with participants without persistent decrease in LV GLS (WH: 2.09 Gy [IQR, 1.50-2.45] vs 1.36 Gy [IQR, 1.01-1.87], P < .001; LV: 2.40 Gy [IQR, 1.09-2.88] vs 1.34 Gy [IQR, 0.63-2.02], P = .002). The relative changes in LV EDV and LV mass/EDV were -12.7% ± 9.0 versus -2.2% ± 13.3 (P < .001) and 14.2% ± 15.5 versus 2.2% ± 18.1 (P = .002), respectively, in participants with and without a persistent decrease in LV GLS. A higher WH cardiac radiation dose was associated with a higher risk of a persistent decrease in LV GLS (odds ratio, 1.09 [95% CI: 1.02, 1.16]). Conclusion In participants with recent breast cancer radiation therapy, a modest but persistent reduction in LV GLS over a 2-year follow-up period was associated with the cardiac radiation dose. Keywords: Radiotherapy, Magnetic Resonance Imaging, Cardiotoxicity, Strain Clinical trial registration no. NCT03297346 Supplemental material is available for this article. © RSNA, 2025.
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Affiliation(s)
- Jérôme Lamy
- AP-HP, Service de Radiologie, Hôpital Européen Georges-Pompidou, Université de Paris-Cité, 20-40 rue Leblanc, 75015 Paris, France
- Institut National de la Santé et de la Recherche Médicale, PARCC, Paris, France
| | - Daan S Spoor
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Johannes A Langendijk
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Rozemarijn Vliegenthart
- Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Arantxa Eraso
- Department of Radiation Oncology, Institut Català d'Oncologia, Barcelona, Spain
| | - Montserrat Ventura
- Department of Radiation Oncology, Institut Català d'Oncologia, Barcelona, Spain
| | - Susana Constantino Rosa Santos
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Manuela Fiúza
- Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
- Santa Maria University Hospital (CHULN), Lisbon, Portugal
| | - Nadjia Kachenoura
- Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, Paris, France
| | - Anne P G Crijns
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Elie Mousseaux
- AP-HP, Service de Radiologie, Hôpital Européen Georges-Pompidou, Université de Paris-Cité, 20-40 rue Leblanc, 75015 Paris, France
- Institut National de la Santé et de la Recherche Médicale, PARCC, Paris, France
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Feng X, Deng Z, McCullough MS, May BJ, Selznick E, Sheng JY, Connor AE, Armstrong DK, Visvanathan K. The impact of cardiovascular risk factors on cancer progression: a prospective study in female breast cancer survivors. Breast Cancer Res Treat 2025; 210:737-748. [PMID: 39928264 DOI: 10.1007/s10549-025-07611-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 01/05/2025] [Indexed: 02/11/2025]
Abstract
PURPOSE To examine the effect of selected cardiovascular disease (CVD) risk factors over time on early cancer outcomes in breast cancer (BC) survivors. METHODS A prospective study was conducted among women aged 20-65 years with an incident invasive BC enrolled in the Breast and Ovarian Surveillance Service (BOSS) Cohort between 2005 and 2013. CVD risk based on selected risk factors was assessed at baseline and two follow-ups. Participants were categorized into low, medium, and high-risk groups. The primary outcome was BC recurrence (distant or local) or second primary cancer (SPC). Kaplan-Meier failure curves and multivariable Cox proportional hazard models were performed to compare the hazards across CVD risk score groups. RESULTS A total of 212 women with invasive BC contributed to 2211 person-years (median follow-up 11.7 years), 103 had low, 73 medium, and 36 high CVD risk scores at baseline. In multivariable analyses, BC survivors with medium CVD risk score had 2.09 times higher risk (95%CI = 1.09-4.02; p = 0.027) of recurrence/SPC compared to survivors with low CVD risk score. This association was particularly pronounced in postmenopausal women, those with estrogen receptor-positive BC, regional disease, or newly diagnosed BC. After excluding women taking cardiac medications, a higher risk of recurrence/SPC was also observed among those in the high-CVD-risk-score group, although not significant. CONCLUSION Higher CVD risk score based on selected risk factors was significantly associated with BC recurrence or SPC, particularly in certain subgroups. Monitoring and treating a combination of CVD risk factors in BC survivors may help reduce BC progression.
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Affiliation(s)
- Xinyi Feng
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Room E6142, Baltimore, MD, 21205, USA
- The Johns Hopkins School of Medicine, Baltimore, MD, USA
| | | | - Michelle S McCullough
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Room E6142, Baltimore, MD, 21205, USA
| | - Betty J May
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Room E6142, Baltimore, MD, 21205, USA
| | - Erica Selznick
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Room E6142, Baltimore, MD, 21205, USA
| | | | - Avonne E Connor
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Room E6142, Baltimore, MD, 21205, USA
- The Johns Hopkins School of Medicine, Baltimore, MD, USA
- Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA
| | | | - Kala Visvanathan
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Room E6142, Baltimore, MD, 21205, USA.
- The Johns Hopkins School of Medicine, Baltimore, MD, USA.
- Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA.
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Patel D, Parikh C, Gharavi D, Patil S, Werner T, Simone CB, Alavi A. Radiation-Induced Coronary Artery Disease in Lung and Breast Cancer Patients: Insights from PET Imaging and Long-Term Risk Assessment. PET Clin 2025; 20:231-241. [PMID: 39955159 DOI: 10.1016/j.cpet.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2025]
Abstract
Radiation-induced coronary artery disease (RI-CAD) is a significant cardiovascular complication for cancer survivors treated with thoracic radiation therapy (RT). Despite advances in RT techniques, exposure to the heart during treatment remains a critical factor influencing long-term cardiac outcomes, particularly in patients with breast and lung cancer. RI-CAD develops due to radiation-induced endothelial injury, inflammation, and accelerated atherosclerosis, presenting a unique and aggressive disease profile. This review explores the pathophysiology, risk factors, and diagnostic advancements for RI-CAD, emphasizing the role of PET in improving patient outcomes.
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Affiliation(s)
- Dev Patel
- Department of Radiology, Hospital of the University of Pennsylvania, PA, USA; Sidney Kimmel Medical College, Philadelphia, PA, USA
| | - Chitra Parikh
- Department of Radiology, Hospital of the University of Pennsylvania, PA, USA; Sidney Kimmel Medical College, Philadelphia, PA, USA
| | - Daniel Gharavi
- Department of Radiology, Hospital of the University of Pennsylvania, PA, USA; Virginia Commonwealth University, Richmond, VA, USA
| | - Shiv Patil
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
| | - Thomas Werner
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Charles B Simone
- New York Proton Center, 225 East 126th Street, New York, NY 10035, USA; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Abass Alavi
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Chufal KS, Ahmad I, Miller AA, Bajpai R, Dwivedi A, Dwivedi A, Umesh P, Bhatia K, Gairola M. Machine learning model for predicting DIBH non-eligibility in left-sided breast cancer radiotherapy: Development, validation and clinical impact analysis. Radiother Oncol 2025; 205:110764. [PMID: 39894262 DOI: 10.1016/j.radonc.2025.110764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/15/2025] [Accepted: 01/24/2025] [Indexed: 02/04/2025]
Abstract
OBJECTIVE Multi-day assessments accurately identify patients with left-sided breast cancer who are ineligible for irradiation in Deep Inspiration Breath Hold (DIBH) and minimise on-couch treatment time in those who are eligible. The challenge of implementing multi-day assessments in resource-constrained settings motivated the development of a machine learning (ML) model using data only from the 1st day of assessment to predict DIBH ineligibility. METHODS This prospective cohort study used data from 202 patients collected between January and December 2023 for model development. Patient-related and DIBH assessment-related variables (upper, lower, and average breath-hold amplitude; average breath-hold duration; breath-hold consistency) were included. Nine ML algorithms (and three modelling strategies) were evaluated, and a decision curve analysis was used to select the best model. The best model was temporally validated on a prospective dataset of 47 patients (January to March 2024). Further, a clinical impact study on another prospective cohort of 64 patients (April to August 2024) was performed, to assess its practical utility by comparing its predictions with the clinical team's decision to treat a patient in DIBH or not. RESULTS The uncalibrated gradient-boosting ensemble model demonstrated the highest performance [AUC (95 % CI) = 0.803 (0.686-0.941); Recall = 0.526] and net benefit in decision curve analysis. Key predictors included average breath-hold duration and lower breath-hold amplitude levels. The clinical impact study suggests that the model reduces the need for additional DIBH assessments by up to 20 % without misclassifying eligible patients. CONCLUSION The developed ML model accurately predicts DIBH ineligibility using only first-day DIBH assessment data and could be a decision aid for patient selection in resource-constrained or busy departments. External validation is necessary to confirm its generalizability.
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Affiliation(s)
- Kundan Singh Chufal
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India.
| | - Irfan Ahmad
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India.
| | - Alexis Andrew Miller
- Department of Radiation Oncology, Illawarra Cancer Care Centre, Wollongong, New South Wales, Australia
| | - Ram Bajpai
- School of Medicine, Keele University, Staffordshire, United Kingdom.
| | - Avani Dwivedi
- Department of Computer Science, Royal Holloway University of London, United Kingdom
| | - Alok Dwivedi
- Discover Financial Services, Reading, United Kingdom
| | - Preetha Umesh
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Kratika Bhatia
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| | - Munish Gairola
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
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Berlin E, Ko K, Ma L, Messing I, Hollawell C, Smith AM, Taunk NK, Narayan V, Upshaw JN, Clark AS, Shah PD, Knollman H, Bhattacharya S, Koropeckyj-Cox D, Wang J, Yegya-Raman N, Han IS, Lefebvre B, Li T, Wilcox NS, Jung W, Chen J, Freedman GM, Ky B. Cardiac Effects of Modern Breast Radiation Therapy in Patients Receiving Systemic Cancer Therapy. JACC CardioOncol 2025; 7:219-230. [PMID: 40044512 PMCID: PMC12046838 DOI: 10.1016/j.jaccao.2025.01.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 01/15/2025] [Accepted: 01/15/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Radiation therapy (RT) improves breast cancer outcomes, but cardiac morbidity remains a concern. OBJECTIVES This study sought to evaluate changes in cardiac function after RT and the relationship between cardiac dose metrics and echocardiography-derived measures of function. METHODS In a longitudinal cohort study of women with breast cancer, radiation cardiac dose metrics and core lab quantitated echocardiographic measures of cardiac function were evaluated. Dose metrics included the whole heart, left ventricle, right ventricle, and left anterior descending artery (LAD). Echocardiographic measures included left ventricular ejection fraction (LVEF), longitudinal strain, circumferential strain, E/e' (ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity), Ea/Es (ventricular arterial coupling; ratio of effective arterial elastance to end systolic elastance), and right ventricular fractional area change. The mean change in echocardiographic measures over time and the association between cardiac dose metrics and echocardiographic measures were estimated by repeated-measures multivariable linear regression via generalized estimating equations. RESULTS The cohort included 303 participants (median age 52 years, 33.3% African American) who received adjuvant RT (2010-2019) with a median mean heart dose of 1.19 Gy (Q1-Q3: 0.75-2.61 Gy), were followed over a median of 5.1 years (Q1-Q3: 3.2-7.1 years). Across all participants, there was a modest increase in LVEF (52.1% pre-RT to 54.3% at 5 years; P < 0.001) but a worsening in sensitive measures of function, such as circumferential strain (-23.7% pre-RT to -21.0% at 5 years; P = 0.003). Among left-sided/bilateral breast cancer participants, changes in cardiac function were observed across all parameters (P < 0.05). The maximum LAD dose was associated with a modest worsening in LVEF, longitudinal strain, circumferential strain, and E/e'. CONCLUSIONS Over a median of 5.1 years, modest changes in cardiac function were observed with RT. Maximum LAD dose was associated with a worsening in systolic and diastolic function parameters.
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Affiliation(s)
- Eva Berlin
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kyunga Ko
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Lin Ma
- Department of Radiation Oncology, Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA
| | - Ian Messing
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Casey Hollawell
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Amanda M Smith
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Neil K Taunk
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Vivek Narayan
- Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jenica N Upshaw
- Division of Cardiology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA
| | - Amy S Clark
- Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Payal D Shah
- Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Hayley Knollman
- Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Saveri Bhattacharya
- Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Daniel Koropeckyj-Cox
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jessica Wang
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nikhil Yegya-Raman
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ivy S Han
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Benedicte Lefebvre
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Tang Li
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nicholas S Wilcox
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Wonyoung Jung
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jinbo Chen
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Gary M Freedman
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Bonnie Ky
- Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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Montalvo SK, Lue B, Kakadiaris E, Ahn C, Zhang-Velten E, Aliru M, Lu W, Westover KD, Iyengar P, Timmerman RD, Zaha VG, Vallabhaneni S, Zhang K, Chandra A, Alluri PG. Global Longitudinal Strain: A Potential Noninvasive Tool for Early Detection of Radiation-Induced Cardiac Dysfunction in Patients With Lung Cancer Receiving Thoracic Radiation Therapy. Int J Radiat Oncol Biol Phys 2025:S0360-3016(25)00257-3. [PMID: 40174646 DOI: 10.1016/j.ijrobp.2025.03.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 03/11/2025] [Accepted: 03/19/2025] [Indexed: 04/04/2025]
Abstract
PURPOSE Radiation-induced cardiac dysfunction (RICD) is a competing cause of morbidity and mortality in patients receiving thoracic radiation therapy (RT). Currently, there are no clinically-validated approaches for early detection of RICD at a time point that affords the potential for mitigation. The goal of this study was to evaluate the potential of global longitudinal strain (GLS) derived from standard-of-care echocardiogram (ECHO) for the early detection of RICD and to assess the association between adverse GLS changes and survival in patients receiving thoracic RT. METHODS AND MATERIALS A retrospective review of changes in GLS was carried out in patients with primary or secondary lung cancer who received standard-of-care thoracic RT with a mean heart dose of ≥5 Gy and had measurable GLS on ECHOs performed before and after RT. Changes in 2-chamber (2C), 3-chamber (3C), and 4-chamber (4C) GLS and peak average GLS after RT (relative to pre-RT baseline) were quantified. Survival probabilities were estimated in patients with normal versus abnormal GLS. RESULTS Thirty-eight patients had measurable GLS before and after RT. Abnormal GLS (defined as <18% or >15% relative decline in GLS after RT from a normal baseline value) was present in 31.6% of patients before RT and 57.9% of patients after RT (P = .012). On paired comparisons, the absolute median reduction (IQR) in 2-chamber, 3-chamber, 4-chamber, and average GLS after RT relative to pre-RT baseline was 1.90 (4.43), 3.00 (3.83), 2.50 (3.63), and 2.25 (3.53), respectively, all P < .001. No statistically significant change in left ventricular ejection fraction was noted after RT. Patients with abnormal GLS after RT had significantly worse survival than those with normal GLS on univariable analysis (P = .049). Despite the small sample size of the study, the survival detriment in patients with abnormal GLS after RT strongly trended toward significance on multivariable analysis (P = .063). CONCLUSIONS Adverse changes in GLS are detectable on standard-of-care ECHOs and precede significant changes in left ventricular ejection fraction in this cohort of high-risk patients with primary and secondary lung cancer receiving thoracic RT. Thus, ECHO-derived GLS has the potential to serve as an early and noninvasive marker of RICD in this patient population and may enable early adoption of GLS-guided cardioprotective therapy, which has been shown to mitigate cardiac dysfunction in patients with cancer receiving cardiotoxic treatments.
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Affiliation(s)
- Steven K Montalvo
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Brian Lue
- University of Texas Southwestern Medical School, Dallas, Texas
| | | | - Chul Ahn
- O'Donnell School of Public Health, University of Texas Southwestern Medical School, Dallas, Texas
| | - Elizabeth Zhang-Velten
- Department of Radiation Oncology, University of Southern California, Los Angeles, California
| | - Maureen Aliru
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Weiguo Lu
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas
| | - Kenneth D Westover
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas
| | - Puneeth Iyengar
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Robert D Timmerman
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas
| | - Vlad G Zaha
- Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas; Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Srilakshmi Vallabhaneni
- Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas; Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Kathleen Zhang
- Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas; Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Alvin Chandra
- Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas; Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
| | - Prasanna G Alluri
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas.
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Kayalı Fİ, Habiboğlu R, Aral İP, Çevik V, Tezcan Y. Breast cancer radiotherapy: analysis of unintended internal mammary node doses and influencing factors. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2025; 71:e20241325. [PMID: 40172395 PMCID: PMC11964305 DOI: 10.1590/1806-9282.20241325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 11/03/2024] [Indexed: 04/04/2025]
Abstract
OBJECTIVE Breast cancer is a prevalent malignancy requiring ongoing treatment advancements. Radiotherapy is vital for reducing recurrence and improving survival. This study evaluates unintended doses to internal mammary lymph nodes and influencing factors in patients at Ankara Bilkent City Hospital's Radiation Oncology Clinic. METHODS We analyzed 44 right-sided breast cancer patients treated with radiotherapy between November 2019 and April 2023. Data on demographics, treatment, and dose-volume histograms were reviewed using various statistical tests. RESULTS Median age was 54 years; 88.6% had invasive ductal carcinoma, and 11.4% had ductal carcinoma in situ. Patients received conventional (54.5%) or hypofractionated radiotherapy (45.5%) using intensity-modulated radiotherapy or three-dimensional conformal radiotherapy. Median internal mammary lymph node volume was 7.3 cc with dose variability. Internal mammary lymph nodes V45 dose showed no correlation with internal mammary lymph nodes volume, radiotherapy field, pT stage, or pN stage. However, the nodal stage significantly impacted the internal mammary lymph nodes D95 dose, with higher doses in N1 patients. Wider radiotherapy fields led to increased D95 doses. DISCUSSION The findings highlight the variability in internal mammary lymph nodes doses and the impact of nodal stage and radiotherapy field on dose distribution. Advanced techniques like intensity-modulated radiotherapy can reduce risks, but careful planning is essential. CONCLUSION Understanding internal mammary lymph nodes dose factors can enhance treatment planning and outcomes. Future research should focus on refining guidelines and leveraging technology to improve radiotherapy efficacy.
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Affiliation(s)
| | - Rahşan Habiboğlu
- Ankara Bilkent City Hospital, Department of Radiation Oncology – Ankara, Turkey
| | - İpek Pınar Aral
- Ankara Yıldırım Beyazıt University, Ankara Bilkent City Hospital, Radiation Oncology Clinic, Department of Radiation Oncology – Ankara, Turkey
| | - Volkan Çevik
- Ankara Bilkent City Hospital, Department of Radiation Oncology – Ankara, Turkey
| | - Yılmaz Tezcan
- Ankara Yıldırım Beyazıt University, Ankara Bilkent City Hospital, Radiation Oncology Clinic, Department of Radiation Oncology – Ankara, Turkey
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Mukherjee T, Elliott S, Manikandan N, Higgins TJ, Zhong Y, Montalvo SK, Saha D, Wansapura J, Avazmohammadi R, Alluri PG. Principal Strain Analysis for Early Detection of Radiation-Induced Cardiotoxicity in a Mouse Model. Int J Radiat Oncol Biol Phys 2025:S0360-3016(25)00256-1. [PMID: 40174647 DOI: 10.1016/j.ijrobp.2025.03.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 03/04/2025] [Accepted: 03/10/2025] [Indexed: 04/04/2025]
Abstract
PURPOSE Radiation-induced cardiotoxicity (RIC) is common in patients receiving thoracic radiation and is a major risk factor for morbidity and mortality. The development of novel approaches for early detection and mitigation of RIC remains an acute unmet need. The objective of this study is to develop a mouse model of RIC that recapitulates the progression of cardiac dysfunction seen in patients receiving thoracic radiation and to develop novel cardiac strain markers that exhibit higher sensitivity in detecting subclinical RIC over existing approaches. METHODS AND MATERIALS We developed a mouse model of RIC through image guided whole heart irradiation of male C57BL/6J mice using 2 radiation regimens (8 Gy × 5 and 24 Gy × 1). We developed a pipeline for analyzing anatomic and principal strains derived from cardiac magnetic resonance (CMR) imaging obtained at baseline, 3 months, and 6 months following radiation. RESULTS Both radiation regimens used for whole heart irradiation caused a progressive decline in both anatomic and principal cardiac strains over time. The minimum principal cardiac strain detected a subclinical decline in cardiac contractility at an earlier time point than the traditional anatomic cardiac strains. We also observed asymmetric changes in contractility at the epicardium and endocardium relative to averaged cardiac strain across the full thickness of the left ventricle following cardiac irradiation, further reinforcing the limitations of existing methods, which do not capture the heterogeneity in cardiac strain changes along the transmural axis. CONCLUSIONS We have developed a mouse model of RIC that recapitulates time-dependent deterioration in myocardial contractility noted in patients receiving thoracic radiation. We also developed CMR imaging-derived novel principal strain cardiac markers that detect subclinical deterioration in cardiac contractile function earlier than traditional anatomic cardiac strain markers. If successfully translated into patients, our novel approach of measuring CMR imaging-derived cardiac principal strain analysis may enhance the detection of subclinical RIC in patients receiving thoracic radiation.
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Affiliation(s)
- Tanmay Mukherjee
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas
| | - Sarah Elliott
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Nandhini Manikandan
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas
| | - Taylor-Jade Higgins
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Yuncheng Zhong
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Steven K Montalvo
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Debabrata Saha
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Janaka Wansapura
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Reza Avazmohammadi
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas; J. Mike Walker '66 Department of Mechanical Engineering, Texas A&M University, College Station, Texas; Department of Cardiovascular Sciences, Houston Methodist Academic Institute, Houston, Texas.
| | - Prasanna G Alluri
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas; Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas.
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Yang M, Wang Z, Xue J, Dai J, Zhu C, Qin X. Subsequent primary cancer risk and mortality among premenopausal breast cancer survivors. Sci Rep 2025; 15:10829. [PMID: 40155641 PMCID: PMC11953267 DOI: 10.1038/s41598-024-84606-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 12/24/2024] [Indexed: 04/01/2025] Open
Abstract
Patients with premenopausal breast cancer (preBC) usually have long-term survivorship. However, less is known about the risk pattern of subsequent primary cancer (SPC) and noncancer diseases among them. Here, this study aimed to evaluate the risk of developing SPCs and mortality among preBC survivors. In this population-based, retrospective cohort study, 5-year preBC survivors diagnosed at age 20-59 years during 1992-2014, in the 11 Surveillance, Epidemiology and End Result registries were included. Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) were estimated for SPCs and mortality by cause, respectively. Among 181,947 survivors (mean age at diagnosis, 49.1 years; 65.9% White), there were 12,503 SPC cases, 4,280 SPC-related deaths, and 10,591 noncancer-related deaths. SPC risk was increased compared with the general population (SIR 1.06, [95% CI, 1.04-1.08]). The elevated risk was primarily associated with soft tissue cancer, bones/joints cancer, and acute non-lymphocytic leukemia (SIRs 2.01 [95% CI, 1.73-2.33], 1.78 [95% CI, 1.21-2.53], and 1.68 [95% CI, 1.46-1.93], respectively). Young-onset, Asian survivors, those with hormone receptor-negative BC, and initially treated with chemo-radiotherapy were at high-risk. The risk of dying from SPCs was also increased (SMR 1.07, [95% CI, 1.04-1.10]) and featured with similarly vulnerable subpopulations. Survivors of non-White ethnicity had a higher risk of dying from noncancer diseases. This study highlighted the excess risk of developing and dying from SPCs among preBC survivors, suggesting that targeted healthcare is warranted. Strategies for SPCs and noncancer comorbidity management are in great demand to achieve better long-term survivorship among preBC patients.
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Affiliation(s)
- Mei Yang
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No. 219 Xinglong Lane, Changzhou City, Jiangsu, China
| | - Zhihuai Wang
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No. 219 Xinglong Lane, Changzhou City, Jiangsu, China
| | - Jiao Xue
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No. 219 Xinglong Lane, Changzhou City, Jiangsu, China
| | - Jianbo Dai
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No. 219 Xinglong Lane, Changzhou City, Jiangsu, China
| | - Chunfu Zhu
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No. 219 Xinglong Lane, Changzhou City, Jiangsu, China
| | - Xihu Qin
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, No. 219 Xinglong Lane, Changzhou City, Jiangsu, China.
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Nardone V, Ruggiero D, Chini MG, Bruno I, Lauro G, Terracciano S, Nebbioso A, Bifulco G, Cappabianca S, Reginelli A. From Bench to Bedside: Translational Approaches to Cardiotoxicity in Breast Cancer, Lung Cancer, and Lymphoma Therapies. Cancers (Basel) 2025; 17:1059. [PMID: 40227572 PMCID: PMC11987928 DOI: 10.3390/cancers17071059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 03/10/2025] [Accepted: 03/19/2025] [Indexed: 04/15/2025] Open
Abstract
Cardiotoxicity represents a critical challenge in cancer therapy, particularly in the treatment of thoracic tumors, such as lung cancer and lymphomas, as well as breast cancer. These malignancies stand out for their high prevalence and the widespread use of cardiotoxic treatments, such as chemotherapy, radiotherapy, and immunotherapy. This work underscores the importance of preclinical models in uncovering the mechanisms of cardiotoxicity and developing targeted prevention and mitigation strategies. In vitro models provide valuable insights into cellular processes, enabling the observation of changes in cell viability and function following exposure to various drugs or ionizing radiation. Complementarily, in vivo animal models offer a broader perspective, allowing for evaluating of both short- and long-term effects and a better understanding of chronic toxicity and cardiac diseases. By integrating these approaches, researchers can identify potential mechanisms of cardiotoxicity and devise effective prevention strategies. This analysis highlights the central role of preclinical models in advancing knowledge of cardiotoxic effects associated with common therapeutic regimens for thoracic and breast cancers.
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Affiliation(s)
- Valerio Nardone
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (V.N.); (D.R.); (A.N.); (S.C.); (A.R.)
| | - Dafne Ruggiero
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (V.N.); (D.R.); (A.N.); (S.C.); (A.R.)
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy; (I.B.); (G.L.); (S.T.); (G.B.)
| | - Maria Giovanna Chini
- Department of Biosciences and Territory, University of Molise, Contrada Fonte Lappone, Pesche, 86090 Isernia, Italy
| | - Ines Bruno
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy; (I.B.); (G.L.); (S.T.); (G.B.)
| | - Gianluigi Lauro
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy; (I.B.); (G.L.); (S.T.); (G.B.)
| | - Stefania Terracciano
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy; (I.B.); (G.L.); (S.T.); (G.B.)
| | - Angela Nebbioso
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (V.N.); (D.R.); (A.N.); (S.C.); (A.R.)
| | - Giuseppe Bifulco
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy; (I.B.); (G.L.); (S.T.); (G.B.)
| | - Salvatore Cappabianca
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (V.N.); (D.R.); (A.N.); (S.C.); (A.R.)
| | - Alfonso Reginelli
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (V.N.); (D.R.); (A.N.); (S.C.); (A.R.)
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Oyeniyi JF, Loving BA, Almahariq MF, Jawad MS, Dilworth JT. Leveraging technology and standardized institutional practices to mitigate disparities in breast cancer radiation therapy. Cancer Causes Control 2025:10.1007/s10552-025-01978-5. [PMID: 40108095 DOI: 10.1007/s10552-025-01978-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025]
Abstract
OBJECTIVES Disparities in various dimensions, including racial, in breast cancer treatment and outcomes are well established. A recent multi-institutional study reported a higher mean heart dose (MHD) in Black and minority women compared to White women who underwent left-sided breast/chest wall irradiation which translated into excess cardiac events and mortality. We evaluated the MHD of women treated in our institution and investigated whether institution-wide measures including the use of readily available but inconsistently adopted technologies can mitigate this disparity. METHODS We identified 509 female patients treated with left-sided breast/chest wall irradiation with/without regional nodal irradiation (RNI). Details regarding cardiac dosimetry, deep-inspiratory breath-hold (DIBH) such as active breathing coordinator (ABC) use, breast size, internal mammary nodal (IMN) irradiation, and whether the treatment plan met boarding pass requirements and was peer reviewed were noted. MHD differences across racial groups were analyzed using Kruskal-Wallis test, while UVA and MVA linear regression analyses assessed influence of various factors on MHD. RESULTS MHD(Gy) was similar across racial groups; 1.38, 1.35, and 1.39 (p = 0.6) in Black, White, and other racial groups, respectively. Utilization of hypofractionation, cavity boosts, RNI, IMN irradiation, meeting boarding pass requirements, and peer review were similar. ABC usage (%) was 83/75/62 (p = 0.005), while median breast size(cc) was 1504/1904/1331 (p = 0.001) in White/Black/other women, respectively. On UVA and MVA, MHD differed with IMN treatment, boost and ABC use but not racial groups and varying breast sizes. CONCLUSION Despite anatomical differences such as breast size, achieving similar cardiac dose is feasible across racial groups by uniformly utilizing appropriate technology such as ABC, with standardized boarding pass constraints, and peer review of all cases. Further studies to identify factors that may cause varied cardiac morbidity rates despite similar cardiac dosimetry among racial groups are warranted.
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Affiliation(s)
- Jacob F Oyeniyi
- Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Bailey A Loving
- Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Muayad F Almahariq
- Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Maha Saada Jawad
- Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Joshua T Dilworth
- Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA.
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Cao L, Ou D, Qi W, Xu C, Ye M, Fang Y, Shi M, Huang X, Lin Q, Liu T, Cai G, Cai R, Chen M, Zhang Y, Su X, Qian X, Shen K, Chen J. A randomized trial of early cardiotoxicity in breast cancer patients receiving postoperative IMRT with or without serial cardiac dose constraints. Int J Cancer 2025; 156:1213-1224. [PMID: 39499199 PMCID: PMC11737017 DOI: 10.1002/ijc.35245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/11/2024] [Accepted: 10/16/2024] [Indexed: 11/07/2024]
Abstract
Optimal cardiac dose constraints in breast cancer (BC) patients undergoing postoperative intensity-modulated radiation therapy (IMRT) are unclear, although as low as possible is recommended. This trial proposes serial cardiac dose constraint to optimize cardiac safety. Postoperative BC patients eligible for anthracycline/taxanes-based chemotherapy or HER2-targeted therapy were randomized to cardiac safety arm with prespecified mean heart dose (MHD) (≤6 Gy), V30 (≤20%), and V10 (≤50%) constraints, or to a control arm with in-house protocol (mainly MHD ≤8 Gy). The primary endpoint was cumulative incidence of newly onset cardiac events within 1-year post-RT. An exploratory analysis examined the relationship between whole heart dose metrics and those of substructures. Of 199 participants, 93 were in the cardiac safety and 106 in the control arm. The cardiac safety group showed lower MHD, V10, and V30. The 1-year cardiac event incidence was slightly lower in the cardiac safety group (19.4%) compared to controls (24.9%). The LVEF and diastolic dysfunction rates were 0% and 5.4% in the study arm, and 1.9% and 8.8% in the control arm, respectively. The LAD, LV, and RV received the highest doses for left-sided patients. For right-sided patients, RA, RCA, and RV were most irradiated. The MHD, V10, and Dmax of heart significantly correlated with all substructure doses in either laterality. Our study supports the early cardiac safety profile using IMRT in BC patients receiving cardiac-toxic systemic therapy, with serial cardiac dose constraints. Combined constraints on MHD and dose-volume parameters are representative of the cardiac substructure dose.
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Affiliation(s)
- Lu Cao
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Dan Ou
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Wei‐Xiang Qi
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Cheng Xu
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Ming Ye
- Department of Radiation Oncology, Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Yue‐Hua Fang
- Department of Cardiology, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Mei Shi
- Department of Radiation OncologyXijing Hospital, Air Force Medical UniversityXi'anChina
| | - Xiao‐Bo Huang
- Department of Radiation Oncology, Sun Yat‐Sen Memorial HospitalSun Yat‐Sen UniversityGuangzhouChina
| | - Qing Lin
- Department of Radiation OncologyTenth People's Hospital Affliated to Tongji UniversityShanghaiChina
| | - Tong Liu
- Tianjin Key Laboratory of Ionic‐Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjinChina
| | - Gang Cai
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Rong Cai
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Mei Chen
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Yi‐Bin Zhang
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Xiu‐Xiu Su
- Department of Cardiology, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Xiao‐Fang Qian
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
| | - Kun‐Wei Shen
- Comprehensive Breast Health Center, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Jia‐Yi Chen
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
- Shanghai Key Laboratory of Proton‐therapyShanghaiChina
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Agolli L, Exeli AK, Schneider U, Ihne-Schubert SM, Lurtz A, Habermehl D. Development of heart-sparing VMAT radiotherapy technique incorporating heart substructures for advanced NSCLC patients. Radiat Oncol 2025; 20:40. [PMID: 40087770 PMCID: PMC11908025 DOI: 10.1186/s13014-025-02597-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 02/04/2025] [Indexed: 03/17/2025] Open
Abstract
OBJECTIVE To investigate the feasibility of active heart sparing (AHS) planning in patients with locally advanced and centrally located NSCLC receiving standard definitive radiotherapy (RT), while maintaining or improving appropriate lung, esophagus, and spinal cord constraints and planning target volume (PTV) coverage intent. METHODS AND MATERIALS A total of 27 patients with stage IIIA/B NSCLC treated with curative intent RT were selected for this analysis. All existing radiation plans were revised and 27 further new equivalent plans were calculated using AHS for the same cohort of patients. Primary end-point was feasibility of AHS using constraints for heart substructures. The secondary end point was to calculate the difference in terms of dosimetric parameters of heart substructures and principal OARs as well as PTV-coverage parameters within the current patient group. RESULTS AHS was feasible in the entire group of patients. An optimal coverage of the target volume was obtained and all mandatory constraints for OARs have been met. The median value of the mean heart dose (MHD) was 8.18 Gy and 6.71 Gy in the standard planning group and AHS-group, respectively (p = 0.000). Other heart parameters such as V5Gy (40.57% vs. 27.7%; p = 0.000) and V30Gy (5.39% vs. 3.86%; p = 0.000) were significantly worse in the standard planning group. The following relevant dosimetric parameters regarding heart substructures were found to be significantly worse in the standard planning group compared to the AHS-group: median dose to heart base (16.97 Gy vs. 6.37 Gy, p = 0.000), maximum dose (18.64 Gy vs. 6.05 Gy, p = 0.000) and V15Gy (11.11% vs. 0% p = 0.000) to LAD; mean dose; V5Gy (9.55% vs. 0.94%, p = 0.000) and V23Gy (0.00% vs. 0.00% maximum 45.68% vs. 6.57%, p = 0.002 to the left ventricle. CONCLUSION Our analysis showed an improvement of dosimetric parameters of the heart and heart substructures in patients affected by locally advanced and centrally located NSCLC treated with curative RT using AHS optimization. This approach could lead to a possible reduction of heart events and a prolonged survival. New clinical studies regarding RT in advanced NSCLC should include cardiologic evaluations and biomarkers as well as the contouring of cardiac substructures.
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Affiliation(s)
- Linda Agolli
- Department of Radiation Oncology, Justus-Liebig-University Giessen, Giessen-Marburg University Hospital, Giessen, Klinikstraße, Germany.
| | - Ann-Katrin Exeli
- Department of Radiation Oncology, Justus-Liebig-University Giessen, Giessen-Marburg University Hospital, Giessen, Klinikstraße, Germany
| | - Uwe Schneider
- Department of Radiation Oncology, Justus-Liebig-University Giessen, Giessen-Marburg University Hospital, Giessen, Klinikstraße, Germany
| | - Sandra Michaela Ihne-Schubert
- Department of Internal Medicine IV, University Hospital Gießen and Marburg, Giessen, Germany
- Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
- CIRCLE - Centre of Innovation Research, Lund University, Lund, Sweden
| | - Andreas Lurtz
- Department of Radiation Oncology, Justus-Liebig-University Giessen, Giessen-Marburg University Hospital, Giessen, Klinikstraße, Germany
| | - Daniel Habermehl
- Department of Radiation Oncology, Justus-Liebig-University Giessen, Giessen-Marburg University Hospital, Giessen, Klinikstraße, Germany
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