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1
Department of Radiology, MC 2026, The University of Chicago, 5841 S. Maryland
Ave., Chicago, IL 60637.
2
Present address: Department of Radiology, Brigham and Women's Hospital, 75
Francis St., Boston, MA 02115.
3
Present address: 1606 E. 50th Pl., Apt. 13B, Chicago, IL 60615.
4
Present address: Anusha Apartments, Apt. 204, Chikoti Gardens, Begumpet,
Hyderabad-16, India.
5
Department of Obstetrics and Gynecology, MC 2050, The University of Chicago,
Chicago, IL 60637.
Received June 13, 2000;
accepted after revision August 30, 2000.
Address correspondence to A. H. Dachman.
Abstract
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MATERIALS AND METHODS. Retrospective review of our tumor registry yielded 96 patients with ovarian adenocarcinoma who had only a single primary malignancy and at least one CT scan of the chest, abdomen, and pelvis. CT scans were reviewed to assess the presence of metastatic chest disease in relation to disease activity in the abdomen and pelvis. Chest CT findings were correlated with the physical examination findings and CA-125 levels and were reviewed in consultation with a gynecologic oncologist to select only those patients with chest abnormalities attributable to metastatic disease.
RESULTS. A total of 266 CT scans were obtained. Forty (41.7%) of the 96 patients had abnormalities attributable to metastatic chest disease on one or more scans. In the absence of disease progression in the abdomen and pelvis, chest disease progression was seen in only six (2.7%) of the 226 follow-up CT scans. Five of the six patients had rising CA-125 levels.
CONCLUSION. Correlation of the findings of abdominal and pelvic CT with the physical findings and the CA-125 levels serves as effective follow-up in patients with ovarian adenocarcinoma. The contribution of additional chest CT in these patients is small.
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The aim of this study was twofold. The first was to assess the prevalence of metastatic chest disease as perceived on CT. The second was to determine whether routine chest CT added any pertinent information beyond that obtained by routine follow-up (physical examination, CA-125 levels, and abdominopelvic CT) that would potentially change the clinical management.
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Physical findings (decreased breath sounds, dullness to percussion, and crackles) and CA-125 levels (normal range, 0-35 U/mL) were collected from the patient's medical records for the patients with evidence of metastatic chest abnormalities. Clinical findings and the CA-125 levels obtained within 2 weeks of CT were correlated with the chest CT findings. The cause of the chest abnormality was evaluated in consultation with the gynecologic oncologist to select only patients with chest abnormalities attributable to metastatic disease. Evaluation of disease in the chest, abdomen, and pelvis on each CT scan was compared with the prior CT scan to assess progression versus stability or regression of the disease. The total number of patients who had disease progression in the chest in the absence of disease progression in the abdomen or pelvis was determined from this analysis.
An analysis was also performed to separate the chest abnormalities into those that were detectable on CT at the level of the lung bases and those that were not. This was done to determine the percentage of chest abnormalities that could be detected on the uppermost images of an abdominal CT scan.
CT was performed using the oral and IV contrast medium iohexol (120-150 mL of Omnipaque 300; Nycomed Amersham, Princeton, NJ). Helical scanning was performed on the 9800 or CTi scanners (General Electric Medical Systems, Milwaukee, WI) using 10-mm collimation in the chest, 7-mm collimation through the liver, and 10-mm collimation in the abdomen and pelvis below the liver, with a pitch of 1:1-1.6:1. Soft-tissue, lung, and liver windows were routinely photographed. CT scans were reinterpreted by an experienced radiologist who was unaware of the patient's clinical staging or CA-125 level.
Our criteria for the CT features of metastatic chest disease included pleural effusions, mediastinal and cardiophrenic lymphadenopathy with a short axis greater than 1 cm in diameter, pleural soft-tissue masses, and noncalcified parenchymal masses greater than 5 mm in diameter.
Transient or stable small pleural effusions of another cause, parenchymal nodules less than or equal to 5 mm in diameter that did not progress on follow-up CT, mediastinal lymph nodes less than or equal to 1 cm diameter in short axis that did not progress on follow-up, and chest CT findings suggestive of pneumonia were deemed benign.
Of the 96 patients, 29 (30.2%) had normal findings on chest CT. Of the 67 cases (69.8%) with abnormal findings on chest CT, 27 (40.3%) were the result of unrelated causes and 40 (59.7%) resulted from metastatic ovarian adenocarcinoma. Thirty-four (85%) of these 40 patients had abnormal CT findings in the abdomen or pelvis. Six (15%) of the 40 had stable disease in the abdomen or pelvis, and of these six, five had a rising CA-125 level. Note that metastatic disease was considered the cause of the chest abnormality in 40 (59.7%) of the 67 patients with an abnormal finding on chest CT. These 40 patients comprised the study group. A comparison of the patient's stage at diagnosis with age, follow-up, and the histology of the ovarian adenocarcinoma is summarized in Table 1. The average age at diagnosis of ovarian cancer in the 40 study patients was 58.3 years (range, 20-79 years). Most patients (n = 35, 87.5%) presented at initial diagnosis with advanced disease (stage III or IV). These patients were followed up for 0-96.5 months (average, 23.1 months) using CT and for 1-99 months (average, 31.9 months) by clinical examination.
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Chest disease progressed in conjunction with the progression of disease in the abdomen and pelvis in 54 (23.9%) of the 226 CT scans (266 minus 40 baseline CT scans). Chest disease was stable despite disease progression in the abdomen or pelvis in 85 (37.6%) of the 226 CT scans. Chest disease was stable in conjunction with stable disease in the abdomen and pelvis in 81 (35.8%) of the 226 CT scans. Chest disease progression in the absence of disease progression in the abdomen or pelvis was noted in only six (2.7%) of the total of 226 CT scans. These six scans were all from different patients. The findings of the CT scans of the abdomen and pelvis were correlated with the CA-125 levels in these six patients. Despite stable disease in the abdomen and pelvis, in five of the six patients the CA-125 levels increased (from a minimum of 38% to 108% above the previous value) corresponding to disease progression as seen on the chest CT scans. In the remaining instance, the CA-125 level was abnormal (CA-125 = 5943 U/mL) but falling; however, CT in this patient showed a marked increase in the size of the pleural effusion.
In the 54 instances of chest disease progression in conjunction with disease progression in the abdomen and pelvis, physical examination findings suggested chest disease progression in only 12 instances. The physical findings were false-negative in 38 instances. There was no mention of chest physical findings in four instances. In the six instances of chest disease progression in the absence of disease progression in the abdomen and pelvis, physical findings suggested chest disease progression in only two instances. In the remaining four of six instances, physical findings were false-negative.
The 40 patients had a total of 54 chest CT abnormalities (each number representing either pleural effusion, mediastinal lymphadenopathy, pulmonary parenchymal nodule, or pleural soft-tissue mass). Forty-two (77.8%) of these 54 abnormalities were at the level of the lung bases and could have been detected on abdominal CT scans (Fig. 1). Twelve abnormalities (22.2%) were superior to the level of the lung bases and hence could not have been detected on an abdominal CT scan.
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A detailed explanation of the chest CT abnormalities with presumed benign causes in the 27 (40.3%) of the 67 patients is provided in the following text. Of the 27 patients, five (18.5%) had small transient pleural effusions; 10 (37%) had transient or stable pulmonary parenchymal nodules less than or equal to 5 mm in diameter; four (14.8%) had both small transient effusions and parenchymal nodules that were less than or equal to 5 mm; and seven (25.9%) had history, physical examination findings, and chest CT findings consistent with pneumonia. Mediastinal lymphadenopathy less than or equal to 1 cm in diameter was present in four of the seven patients with pneumonia, and it regressed or resolved on follow-up CT scans. Only one (3.7%) of the 27 patients had large bilateral pleural effusions. However, the CT scan in this patient was obtained in the immediate postoperative period; the cytology of the pleural effusions was negative for malignancy. The pleural effusions in this patient were attributed to postoperative volume expansion. The effusions were not present on the subsequent CT scan obtained 2 months after the initial scan.
The transient small pleural effusions were thought to be related to congestive heart failure and pulmonary edema in two patients, to anemia in two patients, to atrial fibrillation and ascites, ascites, thrombus in the superior vena cava plus the brachiocephalic veins, and the postoperative state in one patient each.
The 14 patients with transient or stable pulmonary nodules less than or equal to 5 mm in diameter showed no evidence of nodule progression on CT for an average follow-up period of 14.2 months (range, 1.5-26 months). We also saw no evidence of progression of the concomitant small pleural effusions in the four patients with both pleural effusions and parenchymal nodules. At the initial diagnosis of the pulmonary nodules, the CA-125 levels were decreasing in nine patients (64.3%) and increasing in three patients (21.4%); two (14.3%) of the 14 patients had no prior levels for comparison. In all three patients with rising CA-125 levels, an increase in the abdominal or pelvic disease seen on CT might explain the rising CA-125 levels.
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Data regarding metastatic chest disease in epithelial ovarian cancer are based primarily on autopsy series [20,21,22,23,24,25]. The role of chest radiography in the detection of metastatic chest disease has been addressed in a few articles [26,27,28,29]. Description of metastatic chest disease on CT is limited to case reports [30,31,32,33].
The criterion for the presence of metastatic chest disease at autopsy was pathologic proof [20,21,22,23,24,25]. Either pathologic proof or radiologic findings were used as criteria for the presence of metastatic chest disease in other series [26, 27, 30]. Kerr and Cadman [27], in the second largest series, considered the presence of pleural effusions; parenchymal metastases; lymphangitic metastatic disease; hilar or nodal metastases; solid pleural metastases; and rib, pericardial, and pulmonary intravascular metastases to be criteria for metastatic involvement of the chest. These inclusion criteria were obtained from the findings of the chest radiographs, biopsy results, and autopsy data.
The reported prevalence of metastatic chest disease in ovarian cancer varies from 0% to 52% [20,21,22,23,24,25,26,27]. Rose et al. [22] separated the prevalence of metastatic lung disease (25-35%) and metastatic pleural disease (0-28%). Chest abnormalities attributable to metastatic disease were present in 59.7% (n = 40) of the patients in our study. This number was comparable to that reported by Kerr and Cadman (44%) [27] and by Julian et al. (44%) [23].
The most common reported manifestation of metastatic chest disease is pleural effusion, variably reported to be between 25% and 52% [20, 21, 26, 27]. Rose et al. [22] reported a higher incidence of pulmonary parenchymal metastases (25-35%) when compared with pleural effusions (0-28%). Determining the cause of a pleural effusion is often difficult because of the low yield of positive cytology in pleural effusions; the true nature of pleural effusions cannot always be determined on cytology. However, Kerr and Cadman [27] have shown that there is statistically no significant difference in patient survival, whether the pleural effusion was benign or was malignant.
The most frequent manifestation of chest abnormality on CT in our series was also pleural effusion, seen in 27 (28%) of the 96 patients with ovarian adenocarcinoma. This finding was comparable to the numbers reported in other articles [22, 26, 27].
The prevalence of malignant pleural effusion in this study was lower than that reported by Dvoretsky et al. (48%) [21] and Reed et al. (52%) [20]. The differences in the prevalence of the pleural effusions can be explained in part by the differences in timing of the studies in relation to the disease course of epithelial ovarian cancer. The research by Dvoretsky et al. and Reed et al. involved autopsy series, and those groups' research likely evaluated epithelial ovarian cancer at a later stage, whereas in our study we followed up living patients.
In our study, progression of chest lesions typically occurred in conjunction with disease progression in the abdomen and pelvis. In the absence of disease progression in the abdomen and pelvis, chest disease progression was seen in only six (2.7%) of the 226 (266 minus 40 baseline scans) CT scans each of the chest, abdomen, and pelvis. This observation—seldom having pulmonary metastases in the absence of abdominal or pelvic metastases—has been reported by other groups of researchers [24, 25, 27] and correlates with our findings. Even in these six instances, correlation of the CT findings of the abdomen and pelvis with the rising CA-125 levels indicated disease progression in five of the six patients. In the 226 instances, routine chest CT added pertinent information in only one patient beyond that obtained by correlating the CT findings in the abdomen and pelvis with the physical findings and CA-125 levels.
The lung bases are imaged during acquisition of the uppermost abdominal images during abdominal CT. Thus, metastatic chest disease, such as pleural effusion or cardiophrenic lymphadenopathy, in the lung bases can be detected as part of the abdominal CT examination. In our study, 77.8% of the chest abnormalities were at the level of the lung bases and could be detected on abdominal CT scans. This finding diminishes the role of routine chest CT in the detection of metastatic chest disease.
Our study has several limitations. The study is retrospective, and pathologic proof of suspicious lesions on chest CT or cytologic proof of pleural effusions was not always present. However, our method is consistent with accepted clinical practice, in which an elevated or rising CA-125 level is sufficient to justify therapy. In addition, the results of this study were comparable to those of other studies [22, 23, 26, 27]; the effect of not always having pathologic proof was minimized by using precise inclusion criteria and by performing follow-up CT of lesions that did meet the criteria. Another limitation of this study is that the CT features of metastatic chest disease occur along a continuum, and the strict criteria used in this study are somewhat arbitrary. However, follow-up of all lesions seen on CT was performed in addition to these criteria. Incorporating these results with the inclusion criteria further helped separate the patients with benign lesions and those with malignant lesions.
A future prospective study comparing chest radiographs with chest CT scans in the follow-up examination of patients with ovarian adenocarcinoma will be interesting. Few patients with epithelial ovarian cancer have metastatic chest disease progression in the absence of disease progression in the abdomen and pelvis. Most of these patients have elevated or rising CA-125 levels. Furthermore, most chest abnormalities (77.8% of 54 abnormalities found in the 40 study patients) are detectable on the upper slices of the abdominal CT scans. We conclude that the correlation of the findings of abdominal and pelvic CT with the physical examination and CA-125 level serves as an effective follow-up examination in patients with ovarian adenocarcinoma. The contribution of additional chest CT in the follow-up of these patients is small.
Acknowledgments
We thank Peter MacEneaney for his review of and suggestions for this
manuscript and Theodore Karrison for review of statistical issues.
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