Clinical Investigation
Risk Factors for Pericardial Effusion in Inoperable Esophageal Cancer Patients Treated With Definitive Chemoradiation Therapy

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Purpose

To identify clinical and dosimetric factors influencing the risk of pericardial effusion (PCE) in patients with inoperable esophageal cancer treated with definitive concurrent chemotherapy and radiation therapy (RT).

Methods and Materials

Data for 101 patients with inoperable esophageal cancer treated with concurrent chemotherapy and RT from 2000 to 2003 at our institution were analyzed. The PCE was confirmed from follow-up chest computed tomography scans and radiologic reports, with freedom from PCE computed from the end of RT. Log-rank tests were used to identify clinical and dosimetric factors influencing freedom from PCE. Dosimetric factors were calculated from the dose–volume histogram for the whole heart and pericardium.

Results

The crude rate of PCE was 27.7% (28 of 101). Median time to onset of PCE was 5.3 months (range, 1.0–16.7 months) after RT. None of the clinical factors investigated was found to significantly influence the risk of PCE. In univariate analysis, a wide range of dose–volume histogram parameters of the pericardium and heart were associated with risk of PCE, including mean dose to the pericardium, volume of pericardium receiving a dose greater than 3 Gy (V3) to greater than 50 Gy (V50), and heart volume treated to greater than 32–38 Gy. Multivariate analysis selected V30 as the only parameter significantly associated with risk of PCE.

Conclusions

High-dose radiation to the pericardium may strongly increase the risk of PCE. Such a risk may be reduced by minimizing the dose–volume of the irradiated pericardium and heart.

Introduction

Many malignant tumors occurring in the thoracic region are treated routinely by means of radiotherapy (RT), often in combination with chemotherapy. Although advances in multiagent chemotherapy and RT have led to increased survival, this was made at the expense of increased toxicities 1, 2, 3. Reducing the risk of radiation injury to adjacent healthy organs could have a significant impact on patient outcome in clinical RT. In the treatment of patients with esophageal cancer, a significant portion of the heart may be unavoidably included in the planning target volume (PTV), especially in patients with distal esophageal cancer. Therefore, radiation-induced cardiac toxicities have been observed post-therapy. Cardiac toxicities include pericardial effusion (PCE), pericarditis, coronary artery disease, cardiomyopathy, valvular dysfunction, conduction abnormalities, and autonomic dysfunction (4). Previous reviews showed an incidence of PCE after RT in the range of 20–40%, and asymptomatic PCE is the most common cardiac side effect from radiation 5, 6.

Effects of RT on the heart were well documented in patients with breast cancer 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and lymphoma 17, 18, 19, 20, 21, 22, 23, 24. However, results varied considerably across different institutions about which dosimetric factors were more important than the others 8, 11, 16, 20, 23, 24. Cardiac dose may be alarmingly high in patients with distal esophageal cancer; but with few published studies available 25, 26, radiation injury to the heart is not well understood in this cohort of patients. In particular, PCE in patients with esophageal cancer treated with definitive concurrent chemotherapy (CCT) and RT was not investigated to date.

The present study was undertaken to determine clinical and dosimetric risk factors influencing the risk of PCE in patients with esophageal cancer. Findings from this study may lead to better understanding of PCE and prevention of this toxicity in RT for patients with esophageal cancer.

Section snippets

Patient selection

This study was approved by an institutional review board, abiding regulations of the Health Insurance Portability and Accountability Act. We retrospectively reviewed medical and radiation records of all patients with inoperable esophageal cancer treated with definitive concurrent chemoradiation therapy without surgery from January 2000 to December 2003 in the Department of Radiation Oncology at the University of Texas M.D. Anderson Cancer Center, Houston, TX. The following criteria were used to

Results

A total of 101 patients met criteria for inclusion in this study. Patient characteristics are listed in Table 1. Median follow-up for the present cohort of patients was 8.4 months (range, 0.4–48.6 months). A total of 40.6% of patients (41 of 101 patients) had follow-up less than 6 months; 16.8% (17 of 101 patients), 6–12 months; 26.7% (27 of 101 patients), 13–24 months; and 15.9% (16 of 101 patients), longer than 24 months. Of this patient cohort, 25 patients underwent induction chemotherapy

Discussion

In this study, we investigated the pattern of onset for PCE and important factors that may influence its risk in patients with inoperable esophageal cancer treated with concurrent chemoradiation therapy. Inflammation of the pericardium and PCE are some of the most common acute cardiac toxicities in patients treated with chest irradiation. Table 4 lists previous studies of PCE, pericarditis, and other cardiac toxicities, especially in patients with esophageal cancer. Radiation dosage 5, 24, 25,

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    Presented at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), Philadelphia, PA, November 5–9, 2006.

    Supported in part by the Radiological Society of North America Education and Research Foundation, a grant to “Teach the Teachers in Emerging Nations,” and a research grant from the National Cancer Institute (NCI-R01-CA074043-08A2).

    Conflict of interest: none.

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