Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation

Witt, Jacob S.; Jagodinsky, Justin C.; Liu, Yifei; Yadav, Poonam; Kuczmarska-Haas, Aleksandra; Yu, Menggang; Maloney, James D.; Ritter, Mark A.; Bassetti, M.; Baschnagel, Andrew M.

doi:10.1097/coc.0000000000000573

Cited by 16 publications

(14 citation statements)

References 18 publications

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“…Thoracic radiotherapy is an important cancer treatment for patients diagnosed with malignant tumors, such as breast cancer, lung cancer, Hodgkin's lymphoma and esophageal cancer (1)(2)(3)(4). radiotherapy improves overall survival (oS) in patients with thoracic cancer, but it can result in some inevitable complications, particularly radiation-induced heart damage (riHd), which has gradually become an increasing concern of oncologists and cardiologists (5,6).…”

Section: Introductionmentioning

confidence: 99%

Radiation‑induced dysfunction of energy metabolism in the heart results in the fibrosis of cardiac tissues

Luo

et al. 2021

Mol Med Rep

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Thoracic radiotherapy increases the risk of radiation-induced heart damage (riHd); however, the molecular mechanisms underlying these changes are not fully understood. The aim of the present study was to investigate the effects of radiation on the mouse heart using high-throughput proteomics. Male c57Bl/6J mice were used to establish a model of riHd by exposing the entire heart to 16 Gy high-energy X-rays, and cardiac injuries were verified using a cardiac echocardiogram, as well as by measuring serum brain natriuretic peptide levels and conducting H&e and Masson staining 5 months after irradiation. Proteomics experiments were performed using the heart apex of 5-month irradiated mice and control mice that underwent sham-irradiation. The most significantly differentially expressed proteins were enriched in 'cardiac fibrosis' and 'energy metabolism'. Next, the cardiac fibrosis and changes to energy metabolism were confirmed using immunohistochemistry staining and western blotting. extracellular matrix proteins, such as collagen type 1 α 1 chain, collagen type iii α 1 chain, vimentin and cccTc-binding factor, along with metabolism-related proteins, such as fatty acid synthase and solute carrier family 25 member 1, exhibited upregulated expression following exposure to ionizing radiation. additionally, the myocardial mitochondria inner membranes were injured, along with a decrease in aTP levels and the accumulation of lactic acid in the irradiated heart tissues. These results suggest that the high doses of ionizing radiation used lead to structural remodeling, functional injury and fibrotic alterations in the mouse heart. Radiation-induced mitochondrial damage and metabolic alterations of the cardiac tissue may thus be a pathogenic mechanism of riHd.

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Section: Introductionmentioning

confidence: 99%

Radiation‑induced dysfunction of energy metabolism in the heart results in the fibrosis of cardiac tissues

Luo

et al. 2021

Mol Med Rep

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“…A series of single institution studies with sample sizes ranging from 15 to 123 have described a similar association between radiation in esophageal cancer and a variety of cardiovascular endpoints. This includes studies identifying a link between radiation and increased myocardial perfusion defects 7 , decreased ejection fraction 8,9 , and clinically significant cardiac toxicity 10,11 . Similarly, a study evaluating patients within SEER found a 2.8% absolute increased risk of death from cardiovascular disease among esophageal cancer patients treated with radiation 12 .…”

Section: Discussionmentioning

confidence: 99%

“…With other cancer types, including breast cancer, lung cancer, and Hodgkin's lymphoma, large clinical studies demonstrate a clear link between thoracic radiation and adverse cardiovascular outcomes [4][5][6] . Multiple small institutional studies have demonstrated a potential link between radiation and cardiovascular disease in esophageal cancer patients treated with radiotherapy [7][8][9][10][11] . Additionally, a study evaluating patients within the Surveillance Epidemiology and End Results (SEER) cancer registry found increased cardiovascular mortality among esophageal cancer patients receiving radiation 12 .…”

Section: Introductionmentioning

confidence: 99%

Impact of Radiation on Cardiovascular Outcomes in Patients with Resectable Esophageal Cancer

Sarkar

Hatamipour

Panjwani

et al. 2019

Preprint

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Purpose: Preoperative radiation therapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiation therapy and different radiation techniques on cardiovascular morbidity among a large cohort of esophageal cancer patients. Methods: We identified 1,125 Medicare beneficiaries diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation. We used Medicare claims to identify severe adverse cardiovascular events in the perioperative and postoperative periods. Multivariable logistic regression and Fine-Gray models were used to determine the effect of pre-surgery treatment on the risk of perioperative and postoperative cardiovascular disease. Results: Preoperative chemotherapy or preoperative chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared to surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a postoperative cardiovascular event compared to patients treated with surgery alone (subdistribution hazard ratio [SDHR] 1.36; p=0.035). There was no significant increase in cardiovascular events among patients treated with preoperative chemotherapy (SDHR 1.18; p=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy (IMRT) had a 68% decreased risk of having a cardiovascular event compared to patients receiving conventional radiation (SDHR 0.32; p=0.007). Conclusions: This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as IMRT.

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“…In patients undergoing CRT for esophageal cancer, up to 10.8% develop symptomatic cardiac toxicity (44). Institutional retrospective and database analyses show that compared to patients who undergo esophagectomy alone, those who undergo nCRT have a significantly increased risk of grade 3 or higher cardiac events and that higher radiation doses to the heart correlates with a higher incidence of cardiac events (45)(46)(47). In a prospective phase II trial by Lin et al, 145 patients with esophageal cancer were randomized to definitive treatment with proton beam therapy or photon-based intensity-modulated radiation therapy.…”

Section: Reducing Treatment-related Toxicitymentioning

confidence: 99%

Review of MR-Guided Radiotherapy for Esophageal Cancer

et al. 2021

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In this review, we outline the potential benefits and the future role of MRI and MR-guided radiotherapy (MRgRT) in the management of esophageal cancer. Although not currently used in most clinical practice settings, MRI is a useful non-invasive imaging modality that provides excellent soft tissue contrast and the ability to visualize cancer physiology. Chemoradiation therapy with or without surgery is essential for the management of locally advanced esophageal cancer. MRI can help stage esophageal cancer, delineate the gross tumor volume (GTV), and assess the response to chemoradiotherapy. Integrated MRgRT systems can help overcome the challenge of esophageal motion due to respiratory motion by using real-time imaging and tumor tracking with respiratory gating. With daily on-table MRI, shifts in tumor position and tumor regression can be taken into account for online-adaptation. The combination of accurate GTV visualization, respiratory gating, and online adaptive planning, allows for tighter treatment volumes and improved sparing of the surrounding normal organs. This could lead to a reduction in radiotherapy induced cardiac toxicity, pneumonitis and post-operative complications. Tumor physiology as seen on diffusion weighted imaging or dynamic contrast enhancement can help individualize treatments based on the response to chemoradiotherapy. Patients with a complete response on MRI can be considered for organ preservation while patients with no response can be offered an earlier resection. In patients with a partial response to chemoradiotherapy, areas of residual cancer can be targeted for dose escalation. The tighter and more accurate targeting enabled with MRgRT may enable hypofractionated treatment schedules.

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Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation

Cited by 16 publications

References 18 publications

Radiation‑induced dysfunction of energy metabolism in the heart results in the fibrosis of cardiac tissues

Radiation‑induced dysfunction of energy metabolism in the heart results in the fibrosis of cardiac tissues

Impact of Radiation on Cardiovascular Outcomes in Patients with Resectable Esophageal Cancer

Review of MR-Guided Radiotherapy for Esophageal Cancer

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