Detection of Early Myocardial Dysfunction by Imaging Biomarkers in Cancer Patients Undergoing Photon Beam Vs. Proton Beam Radiotherapy: A Prospective Study

Overview

Journal J Cardiovasc Dev Dis

Specialty Cardiology & Vascular Diseases

Date 2023 Oct 27

PMID 37887865

Authors

Muhannad Aboud Abbasi

Giulia Bruno

Cristina Di Stefano

Laura Garcia Bello

Nadia N Laack

Kimberly S Corbin

Thomas J Whitaker

Patricia A Pellikka

Robert W Mutter

Hector R Villarraga

Affiliations

Soon will be listed here.

Abstract

We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27-79] vs. 217 [120-596] cGy, respectively; < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment ( = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up ( = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up ( = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [ = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up ( = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up ( = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.

Citing Articles

Subclinical cardiac damage monitoring in breast cancer patients treated with an anthracycline-based chemotherapy receiving left-sided breast radiation therapy: subgroup analysis from a phase 3 trial.

Marrazzo L, Meattini I, Becherini C, Salvestrini V, Visani L, Barletta G Radiol Med. 2024; 129(12):1926-1935.

PMID: 39436588 DOI: 10.1007/s11547-024-01897-6.

Pilot study to assess the early cardiac safety of carbon ion radiotherapy for intra- and para-cardiac tumours.

Barcellini A, Rordorf R, Dusi V, Fontana G, Pepe A, Vai A Strahlenther Onkol. 2024; 200(12):1080-1087.

PMID: 39212688 DOI: 10.1007/s00066-024-02270-2.

References

Firstenberg M, Greenberg N, Garcia M, Thomas J . Relationship between ventricular contractility and early diastolic intraventricular pressure gradients: a diastolic link to systolic function. J Am Soc Echocardiogr. 2007; 21(5):501-6. DOI: 10.1016/j.echo.2007.08.023. View

Mutter R, Choi J, Jimenez R, Kirova Y, Fagundes M, Haffty B . Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee. Int J Radiat Oncol Biol Phys. 2021; 111(2):337-359. PMC: 8416711. DOI: 10.1016/j.ijrobp.2021.05.110. View

Stoodley P, Richards D, Boyd A, Hui R, Harnett P, Meikle S . Altered left ventricular longitudinal diastolic function correlates with reduced systolic function immediately after anthracycline chemotherapy. Eur Heart J Cardiovasc Imaging. 2012; 14(3):228-34. DOI: 10.1093/ehjci/jes139. View

Ishizu T, Seo Y, Enomoto Y, Sugimori H, Yamamoto M, Machino T . Experimental validation of left ventricular transmural strain gradient with echocardiographic two-dimensional speckle tracking imaging. Eur J Echocardiogr. 2010; 11(4):377-85. DOI: 10.1093/ejechocard/jep221. View

Darby S, Cutter D, Boerma M, Constine L, Fajardo L, Kodama K . Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010; 76(3):656-65. PMC: 3910096. DOI: 10.1016/j.ijrobp.2009.09.064. View

Voigt J, Pedrizzetti G, Lysyansky P, Marwick T, Houle H, Baumann R . Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging. 2014; 16(1):1-11. DOI: 10.1093/ehjci/jeu184. View

Paganetti H, Niemierko A, Ancukiewicz M, Gerweck L, Goitein M, Loeffler J . Relative biological effectiveness (RBE) values for proton beam therapy. Int J Radiat Oncol Biol Phys. 2002; 53(2):407-21. DOI: 10.1016/s0360-3016(02)02754-2. View

Mutter R, Remmes N, Kahila M, Hoeft K, Pafundi D, Zhang Y . Initial clinical experience of postmastectomy intensity modulated proton therapy in patients with breast expanders with metallic ports. Pract Radiat Oncol. 2017; 7(4):e243-e252. DOI: 10.1016/j.prro.2016.12.002. View

Ersboll M, Andersen M, Valeur N, Mogensen U, Fakhri Y, Fahkri Y . Early diastolic strain rate in relation to systolic and diastolic function and prognosis in acute myocardial infarction: a two-dimensional speckle-tracking study. Eur Heart J. 2013; 35(10):648-56. DOI: 10.1093/eurheartj/eht179. View

10.

Citrin D . Recent Developments in Radiotherapy. N Engl J Med. 2017; 377(22):2200-2201. DOI: 10.1056/NEJMc1713349. View

11.

Darby S, Ewertz M, McGale P, Bennet A, Blom-Goldman U, Bronnum D . Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013; 368(11):987-98. DOI: 10.1056/NEJMoa1209825. View

12.

Lancellotti P, Nkomo V, Badano L, Bergler-Klein J, Bergler J, Bogaert J . Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr. 2013; 26(9):1013-32. DOI: 10.1016/j.echo.2013.07.005. View

13.

Dahl J, Barros-Gomes S, Videbaek L, Poulsen M, Issa I, Carter-Storch R . Early Diastolic Strain Rate in Relation to Systolic and Diastolic Function and Prognosis in Aortic Stenosis. JACC Cardiovasc Imaging. 2016; 9(5):519-28. DOI: 10.1016/j.jcmg.2015.06.029. View

14.

Lo Q, Hee L, Batumalai V, Allman C, Macdonald P, Delaney G . Subclinical cardiac dysfunction detected by strain imaging during breast irradiation with persistent changes 6 weeks after treatment. Int J Radiat Oncol Biol Phys. 2015; 92(2):268-76. DOI: 10.1016/j.ijrobp.2014.11.016. View

15.

Gao R, Mullikin T, Aziz K, Afzal A, Smith N, Routman D . Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes. Int J Radiat Oncol Biol Phys. 2023; 117(4):846-856. DOI: 10.1016/j.ijrobp.2023.05.036. View

16.

Bradley J, Dagan R, Wei Ho M, Rutenberg M, Morris C, Li Z . Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons. Int J Radiat Oncol Biol Phys. 2015; 95(1):411-421. DOI: 10.1016/j.ijrobp.2015.09.018. View

17.

Taylor C, Correa C, Duane F, Aznar M, Anderson S, Bergh J . Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials. J Clin Oncol. 2017; 35(15):1641-1649. PMC: 5548226. DOI: 10.1200/JCO.2016.72.0722. View

18.

Remouchamps V, Vicini F, Sharpe M, Kestin L, Martinez A, Wong J . Significant reductions in heart and lung doses using deep inspiration breath hold with active breathing control and intensity-modulated radiation therapy for patients treated with locoregional breast irradiation. Int J Radiat Oncol Biol Phys. 2003; 55(2):392-406. DOI: 10.1016/s0360-3016(02)04143-3. View

19.

Underwood T, Grassberger C, Bass R, MacDonald S, Meyersohn N, Yeap B . Asymptomatic Late-phase Radiographic Changes Among Chest-Wall Patients Are Associated With a Proton RBE Exceeding 1.1. Int J Radiat Oncol Biol Phys. 2018; 101(4):809-819. DOI: 10.1016/j.ijrobp.2018.03.037. View

20.

Chang J, Jabbour S, De Ruysscher D, Schild S, Simone 2nd C, Rengan R . Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2016; 95(1):505-516. PMC: 10868643. DOI: 10.1016/j.ijrobp.2016.01.036. View