Clinical Investigation
Dose–Volume Histogram Parameters and Clinical Factors Associated With Pleural Effusion After Chemoradiotherapy in Esophageal Cancer Patients

Presented at the 50th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), Boston, MA, Sept 21–25, 2008.
https://doi.org/10.1016/j.ijrobp.2010.03.046Get rights and content

Purpose

To investigate the dose–volume histogram parameters and clinical factors as predictors of pleural effusion in esophageal cancer patients treated with concurrent chemoradiotherapy (CRT).

Methods and Materials

Forty-three esophageal cancer patients treated with definitive CRT from January 2001 to March 2007 were reviewed retrospectively on the basis of the following criteria: pathologically confirmed esophageal cancer, available computed tomography scan for treatment planning, 6-month follow-up after CRT, and radiation dose ≥50 Gy. Exclusion criteria were lung metastasis, malignant pleural effusion, and surgery. Mean heart dose, mean total lung dose, and percentages of heart or total lung volume receiving ≥10–60 Gy (Heart-V10 to V60 and Lung-V10 to V60, respectively) were analyzed in relation to pleural effusion.

Results

The median follow-up time was 26.9 months (range, 6.7–70.2) after CRT. Of the 43 patients, 15 (35%) developed pleural effusion. By univariate analysis, mean heart dose, Heart-V10 to V60, and Lung-V50 to V60 were significantly associated with pleural effusion. Poor performance status, primary tumor of the distal esophagus, and age ≥65 years were significantly related with pleural effusion. Multivariate analysis identified Heart-V50 as the strongest predictive factor for pleural effusion (p = 0.01). Patients with Heart-V50 <20%, 20%≤ Heart-V50 <40%, and Heart-V50 ≥40% had 6%, 44%, and 64% of pleural effusion, respectively (p < 0.01).

Conclusion

Heart-V50 is a useful parameter for assessing the risk of pleural effusion and should be reduced to avoid pleural effusion.

Introduction

The prognosis in patients with esophageal cancer has been poor. Surgical resection is a potentially curative treatment for esophageal cancer. However, the mortality is high, and patients are often inoperable because of advanced tumor presentation at diagnosis, cardiopulmonary complications, or poor performance status (1). Radiotherapy (RT) alone was performed for inoperable esophageal cancer, but the 5-year survival rate was less than 10% (2). During the past decade, definitive chemoradiotherapy (CRT) has been considered a curative treatment option and has improved the prognosis for esophageal cancer, with 5-year survival of 26–46% 3, 4, 5, 6.

Chemoradiotherapy has been considered a tolerable treatment as compared to surgical resection, even for patients who had poor performance status or cardiopulmonary complications. As the number of long-term survivors treated with CRT is increasing, treatment-related toxicities have recently been reported, such as radiation pneumonitis, heart failure, pericardial effusion, myocardial infarction, and pleural effusion (7). These late toxicities significantly impair patients' quality of life. Radiation pneumonitis and pericardial effusion have been analyzed to identify risk factors using dose–volume histogram (DVH) parameters in esophageal cancer 8, 9. Pleural effusion often occurs in esophageal cancer after CRT. Most pleural effusion is asymptomatic, whereas a few patients develop symptomatic pleural effusion that requires medical treatment, such as diuretics, thoracentesis, and pleurodesis. However, little has been known about the effect of CRT on pleural effusion in esophageal cancer. Furthermore, to our knowledge there have been no reports to investigate the relationship between DVH parameters and pleural effusion.

Therefore, in this study, we evaluated pleural effusion in esophageal cancer patients treated with concurrent CRT. The DVH parameters and clinical factors were analyzed in relation to pleural effusion.

Section snippets

Patient population

The institutional review board of our hospital approved this analysis. Esophageal cancer patients treated with definitive CRT between January 2001 and March 2007 at Gunma Prefectural Cancer Center were reviewed retrospectively on the basis of the following criteria: pathologically confirmed esophageal cancer, available computed tomography (CT) scan for treatment planning, 6-month follow-up after CRT, and radiation dose ≥50 Gy. Exclusion criteria were lung metastasis, malignant pleural effusion,

Results

Forty-three patients (39 males and 4 females) were enrolled with median follow-up of 27 months after CRT (range, 6–70 months). The median age was 64 years (range, 40–80 years). The Eastern Cooperative Oncology Group performance status of 0, 1, and 2 were 6, 32, and 5 patients, respectively. Squamous cell carcinoma was observed in 40 patients, adenocarcinoma in 2, and basaloid carcinoma in 1. The numbers of patients with Stage I, II, III, IVa, and IVb disease were 9, 7, 16, 3, and 8,

Discussion

We showed the incidence of pleural effusion and the risk factors in esophageal cancer patients treated with concurrent CRT. Although this was a retrospective study, patients were treated with a homogeneous CRT regimen involving nedaplatin and 5-fluorouracil, with a median follow-up of 27 months. Table 3 shows the rate of pleural effusion by several studies of esophageal cancer patients treated with definitive CRT 7, 13, 14. In these studies, Grade 2 or worse pleural effusion was 9–19%, and

Conclusions

Our results suggest that Heart-V50 is a useful DVH parameter as a risk factor for pleural effusion in esophageal cancer patients treated with CRT. The heart should be delineated and be reduced to avoid pleural effusion during radiation treatment planning.

References (27)

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    The V5 (0.50 vs. 0.55, P = 0.006) and V10 (0.34 vs. 0.41, P < 0.001) of the lung were significantly lower for the IMRT group than those for 3DCRT group but no differences were seen for V15 and V20 (Supplementary Table 5). IMRT has been shown to reduce radiation dose to adjacent organs compared to 3DCRT in numerous dosimetric studies [7,8,11,12,18], but how this translates to clinical benefit for esophageal cancer patients, especially the risk of developing PCE and PE, has been largely unknown. In the present study, our results showed that IMRT decreased the incidence and postponed the median onset times of PCE and PE, and increased the survival probability of PCE or death and PE or death compared to 3DCRT.

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    The strongest prognostic factor was a V30 pericardium of >46%. Shirai et al. retrospectively analyzed 43 esophageal cancer patients [7]. In total, 35% of the patients developed non-malignant PE, including 4 patients (13%) with grade ⩾2, which required medical intervention.

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Conflict of interest: none.

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