Heart and lung doses are independent predictors of overall survival in esophageal cancer after chemoradiotherapy

Cai, Xu; Guo, Lanwei; Liao, Zhongxing; Wang, Yifan; Liu, Xiyou; Zhao, Shuangtao; Wang, Jun; Yuan, Zhigang; Wang, Ping; Lin, Steven H.

doi:10.1016/j.ctro.2019.04.016

Cited by 33 publications

(52 citation statements)

References 34 publications

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“…In line with the large comprehensive research evaluating the association of cardiac dosimetric factors and the outcomes in esophageal cancer after CCRT with or without surgery [8], heart V20 was shown to in uence the survival of ESCC treated with de nitive CCRT in the present study. However, heart V5 and V10 which acted as independent prognostic factors in the current cohort were not found to independently in uence OS in the previously published report.…”

Section: Discussionsupporting

confidence: 81%

“…However, heart V5 and V10 which acted as independent prognostic factors in the current cohort were not found to independently in uence OS in the previously published report. These discrepant results were possibly derived from the different cancer histologies and treatments between studies as the current cohort only reviewed ESCC patients receiving de nitive CCRT without surgery while the previous research included patients with adenocarcinoma and ESCC treated by CCRT with or without operation [8]. In addition, heart V30, V40, and V50 were not reported as independent predictors of OS in the present study because the statistical signi cance was not achieved in multivariate analytic models in which lung V5 was included.…”

Section: Discussionmentioning

confidence: 74%

“…Radiation dose to the heart was a prognostic factor of non-small cell lung cancer treated with de nitive CCRT [5,6,7]. Similarly, cardiac radiation dose was shown to correlate with overall survival (OS) in a large group of esophageal cancer patients undergoing CCRT with or without surgery [8]. However, the prognostic signi cance of cardiac radiation dose remains to be elucidated speci cally in esophageal cancer after de nitive CCRT without surgery.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac radiation dose predicts survival in esophageal squamous cell carcinoma treated by definitive concurrent chemotherapy and intensity modulated radiotherapy

Pao

Chang

Chiang

et al. 2020

Preprint

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Background: The prognostic significance of cardiac radiation dose in esophageal cancer after definitive concurrent chemoradiotherapy (CCRT) remains largely unknown. We aimed to investigate the association between cardiac dose-volume parameters and overall survival (OS) in esophageal squamous cell carcinoma (ESCC) after definitive CCRT. Methods: One hundred and twenty-one ESCC patients undergoing definitive CCRT with intensity modulated radiotherapy technique between 2008 and 2018 were reviewed. Cardiac dose-volume parameters were calculated. Survival of patients and cumulative incidence of adverse events were estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The prognostic significance of cardiac dose-volume parameters was determined with multivariate Cox proportional hazards regression analysis. Results: Median follow-up was 16.2 months (range, 4.3-109.3). Median OS was 18.4 months. Heart V5, V10, and V20 were independent prognostic factors of OS. Median OS was longer for patients with heart V5 ≤ 94.3% (24.7 vs. 16.3 months, p = 0.0025), heart V10 ≤ 86.4% (24.8 vs. 16.9 months, p = 0.0041), and heart V20 ≤ 76.9% (20.0 vs. 17.2 months, p = 0.047). Lower cumulative incidence of symptomatic cardiac adverse events was observed among patients with heart V5 ≤ 94.3% (p = 0.017), heart V10 ≤ 86.4% (p = 0.02), and heart V20 ≤ 76.9% (p = 0.0057). Patients without symptomatic cardiac adverse events had a higher 3-year OS rate (33.8% vs. 0%, p = 0.03). Conclusions: Cardiac radiation dose inversely correlated with survival in ESCC after definitive CCRT. Radiation dose to the heart should be minimized.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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Cardiac radiation dose predicts survival in esophageal squamous cell carcinoma treated by definitive concurrent chemotherapy and intensity modulated radiotherapy

Pao

Chang

Chiang

et al. 2020

Preprint

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“…Research evaluating radiation dosimetry demonstrates that the more conformal radiation dose distributions with IMRT have the potential to reduce radiation doses to the heart compared to conventional forms of radiation 14,[25][26][27][28] . Similarly, other retrospective analyses have found potential reductions in cardiovascular toxicity associated with IMRT compared to older radiation techniques 29,30 . Furthermore, a cancer registry study found that IMRT was associated with a decreased risk of cardiac mortality compared to conventional radiation 31 .…”

Section: Resultsmentioning

confidence: 90%

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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“…Radiotherapy remains a cornerstone of treatment for many cancers. Lung, esophageal, breast, and proximal gastric cancers still receive incidental radiation to the heart as part of curative intent or palliative care [1][2][3][4]. Contemporary and more sophisticated administration of thoracic radiotherapy and systemic immunotherapy have been effective in reducing cancer-related mortality and limiting exposure to the heart.…”

Section: Introductionmentioning

confidence: 99%

Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

et al. 2020

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Background: Irradiation of the heart during cancer radiotherapy is associated with a dose-dependent risk of heart failure. Animal studies have demonstrated that irradiation leads to an inflammatory response within the heart as well as a reduction in cardiac reserve. In the current study we aimed to evaluate whether inflammatory biomarkers correlated with changes in cardiac function and reserve after radiotherapy for breast or lung cancer. Methods and results: We studied 25 subjects with a history of breast or lung cancer without a prior diagnosis of cardiovascular disease or heart failure, 1.8 years [0.4-3.6] post-radiotherapy involving at least 5 Gray (Gy) to at least 10% of the heart. High-sensitivity C-reactive protein (CRP) was abnormal (≥2 mg/L) in 16 (64%) subjects. Cardiac function and reserve was measured with Doppler echocardiography before and after exercise and defined as leftventricular ejection fraction (LVEF), early diastolic mitral annulus velocity (e'), and increase in LV outflow tract velocity time integral cardiac output (cardiac reserve) with exercise. Subjects with abnormal CRP had significantly lower LVEF (51 [44-59] % vs 61 [52-64] %, P = 0.039), lower e' (7.4 [6.6-7.9] cm/sec vs 9.9 [8.3-12.0] cm/sec, P = 0.010), and smaller cardiac reserve (+ 1.5 [1.2-1.7] L/min vs + 1.9 [1.7-2.2] L/min, P = 0.024). Conclusion: Elevated systemic inflammation is associated with impaired left-ventricular systolic and diastolic function both at rest and during exercise in subjects who have received radiotherapy with significant incidental heart dose for the treatment of cancer.

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Heart and lung doses are independent predictors of overall survival in esophageal cancer after chemoradiotherapy

Cited by 33 publications

References 34 publications

Cardiac radiation dose predicts survival in esophageal squamous cell carcinoma treated by definitive concurrent chemotherapy and intensity modulated radiotherapy

Cardiac radiation dose predicts survival in esophageal squamous cell carcinoma treated by definitive concurrent chemotherapy and intensity modulated radiotherapy

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

Increased C-reactive protein is associated with the severity of thoracic radiotherapy-induced cardiomyopathy

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