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DOI:10.2214/AJR.04.1973
AJR 2006; 187:1260-1265
© American Roentgen Ray Society

Clinical Observations

Ventilation-Perfusion Scintigraphy to Predict Postoperative Pulmonary Function in Lung Cancer Patients Undergoing Pneumonectomy

Thida Win1, Angela D. Tasker2, Ashley M. Groves3, Carol White2, Andrew J. Ritchie4, Francis C. Wells4 and Clare M. Laroche1

1 Department of Thoracic Oncology, Papworth Hospital, Papworth Everard, Cambridge, CB3 8RE, United Kingdom.
2 Department of Radiology, Papworth Hospital, Cambridge, United Kingdom.
3 Institute of Nuclear Medicine, University College London, London, United Kingdom.
4 Department of Cardiothoracic Surgery, Papworth Hospital, Cambridge, United Kingdom.

Received December 28, 2004; accepted after revision June 13, 2005.

 
The study received funding from a National Health Service Research and Development Grant.

Address correspondence to T. Win (drthidawin{at}hotmail.com).


Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The American College of Chest Physicians (ACCP) recommends using quantitative perfusion scintigraphy to predict postoperative lung function in lung cancer patients with borderline pulmonary function tests who will undergo pneumonectomy. However, previous scintigraphic data were gathered on small cohorts more than a decade ago, when surgical populations were significantly different with respect to age and sex compared with typical lung cancer patients undergoing pneumonectomy in 2005. We therefore revisited the use of V/Q scintigraphy in pneumonectomy patients in predicting postoperative pulmonary function and the appropriateness of current clinical guidelines.

CONCLUSION. Contrary to ACCP guidelines, we found that ventilation scintigraphy alone provided the best correlation between the predicted and actual postoperative values and recommend its use to predict postoperative lung function. However, scintigraphic techniques may underestimate postoperative lung function, so caution is required before unnecessarily preventing a patient from undergoing surgery that offers a potential cure.

Keywords: bronchogenic carcinoma • cancer • lung disease • nuclear medicine • pneumonectomy • scintigraphy • ventilation-perfusion


Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Patients with bronchogenic carcinoma frequently have impaired pulmonary function, usually secondary to chronic airway obstruction [1]. If these patients are referred for possible curative surgery, they are at increased risk of developing postoperative complications, and some have such poor respiratory reserve that a pneumonectomy may result in an unacceptable quality of life. Numerous techniques have been used to evaluate the postsurgical risk. These include pulmonary function tests (PFTs), exercise tests, and quantitative ventilation-perfusion (V/Q) scintigraphy.

Recent American College of Chest Physicians (ACCP) guidelines [2], as well as those from equivalent European organizations such as the British Thoracic Society (BTS) [3], recommend using quantitative Q scintigraphy in patients with borderline lung function (forced expiratory volume at 1 second [FEV1] < 2.0 L) to predict the postoperative lung function in lung cancer patients who are considering undergoing pneumonectomy. The evidence base for the ACCP and others' guidelines comes from previous V/Q scintigraphy data, much of which were obtained between 10 and 30 years ago from studies that used small numbers of participants (usually fewer than 20), with populations significantly younger and with a male predominance compared with the patients who presented for curative surgery in 2005.

The correlation between the actual and predicted postoperative FEV1 using quantitative V/Q scintigraphy has been variable, with correlative figures quoted between r = 0.67 and r = 0.9 [4-11]. Many of these investigators, however, found that the scintigraphically predicted postoperative FEV1 was lower than the actual postoperative FEV1 [4, 8, 9]. Also in the literature, we found inconsistencies in terminology and in the choice of the most useful postoperative measurement. Some investigators use scintigraphy to predict the FEV1 after pneumonectomy [8, 9], whereas others quote the predicted percentage of FEV1 (the FEV1 value predicted for a patient of a given height, sex, and age) [12-16]. Moreover, we found no clear evidence as to whether it is better to use a V scan or a Q scan alone or in combination. We therefore revisited the use of V/Q scintigraphy in pneumonectomy patients for predicting postoperative pulmonary function and the appropriateness of present clinical guidelines.


Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Over 24 months, we prospectively performed pre- and postsurgical PFTs and quantitative planar V/Q scintigraphy on 32 patients (21 men and 11 women; mean age, 68.4 years; range, 42-85 years) who were undergoing pneumonectomy for non-small cell lung cancer. All patients were former smokers and had preoperative peak oxygen consumption (VO2 peak) greater than 10 mL/kg/min. Twelve out of 32 had FEV1 less than 2.0 L, connoting borderline lung function. Twenty-one patients underwent left pneumonectomy, and 11 underwent right pneumonectomy. All pneumonectomies were performed using a standard posterolateral thoracotomy technique by one of three designated cardiothoracic surgeons. All patients gave written consent, and the study had local ethical committee approval.


Figure 1
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  		Fig. 1 —Anterior and posterior images from perfusion scintigram. Three equally sized regions of interest over lungs are shown. Counts in each zone were measured. Geometric means of anterior and posterior images were then used to calculate relative perfusion and ventilation for each zone for each lung. By this method, percentages were obtained for upper, middle, and lower zones of right and left lungs for both perfusion and ventilation.

 
Spirometry
The FEV1 measurements were made before surgery and repeated, in the same manner, 1 month after surgery for all patients. The FEV1 was calculated from a record of forced vital capacity (FVC) performed on a wedge bellows, 12-second spirometer (Vitalograph). At least three recordings were made until the results were reproducible, and the best of three reproducible attempts was adopted.

Quantitative Planar V/Q Studies
Quantitative planar V/Q studies were performed using an Apex SP4 single-headed camera (Elscint) with a low-energy all-purpose collimator. Patients were imaged while erect, with four views obtained (anterior, posterior, and right and left posterior oblique at 30°). Qualified nuclear medicine technicians supervised all studies. Images were reported by specialists in cardiothoracic imaging.

Ventilation studies were performed using 1,200 MBq of technetium-99m (99mTc) diethylenetriamine pentaacetic acid (DTPA), which was nebulized through a Venticis II aerosol delivery system (CIS bio international) until an activity of 40 MBq could be detected in the lungs. Perfusion imaging was then performed 4 hours later by IV infusion of 75 MBq 99mTc macroaggregated albumin (MAA), with deep respiration. Images were obtained from four routine views (anterior, posterior, and right and left posterior oblique at 30°) for both the ventilation and the perfusion studies. Only the anterior and posterior views were analyzed as part of this study.

Relative perfusion and ventilation analyses were performed by obtaining three equally sized regions of interest over the lungs (Fig. 1) and by performing a geometric mean of the anterior and posterior images, thus giving relative perfusion and ventilation for the three zones in each lung. Percentage results were thereby obtained for the upper, middle, and lower zones of the right and left lungs for both the perfusion and ventilation studies.

To estimate the predicted postoperative FEV1, the following equations, described by Wernly et al.[17], were used:

Formula(1)

Formula(2)

Formula(3)

Statistical Analysis
Pearson's correlation coefficient was used for all the comparisons. Bland-Altman plots were used to establish the bias and reliability of the different scintigrams.


Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The mean preoperative FEV1 was 2.13 L (SD, 0.38 L; range, 1.2-3.3 L), and the mean actual postoperative FEV1 was 1.36 L (SD, 0.36 L; range, 0.8-2.5 L). The mean preoperative percentage of predicted FEV1 was 85% (SD, 16%; range, 42-119%), and the mean actual postoperative percentage of predicted FEV1 was 53% (SD, 13%; range, 28-90%).

One death (secondary to tumor reoccurrence) occurred 6 months after surgery. None of the 31 surviving patients suffered from respiratory insufficiency during this period.

Predicted Postoperative FEV1
The mean predicted postoperative FEV1 using V scintigraphy, Q scintigraphy, and combined V/Q scintigraphy was 1.22 L (SD, 0.36 L; range, 0.55-1.79 L). 1.31 L (SD, 0.37 L; range, 0.62-2.4 L), and 1.26 L (SD, 0.32 L; range, 0.59-1.74 L), respectively (Tables 1 and 2).


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  		TABLE 1: Measured and Predicted Postoperative FEV1 Using Ventilation-Perfusion Scintigraphy Scan

 

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  		TABLE 2: Percentage of Predicted Postoperative FEV1 Using Ventilation-Perfusion Scintigraphy Scan

 

The correlation (r) between actual and predicted postoperative values for FEV1 was 0.7, 0.58, and 0.54 for V scintigraphy, Q scintigraphy, and combined V/Q scintigraphy, respectively (Table 3 and Fig. 2).


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  		TABLE 3: Correlation Between Actual and Predicted Postoperative FEV1

 

Figure 2
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  		Fig. 2 —Histogram shows relationship and correlation (r) between predicted FEV1 and actual measured postoperative FEV1 using ventilation (V) scintigraphy, perfusion (Q) scintigraphy, and combined V/Q scintigraphy.

 

The Bland-Altman analysis shows the differences between V scintigraphy, Q scintigraphy, and combined V/Q scintigraphy in predicting postoperative FEV1 (Table 4). Figures 3 and 4 provide examples and further explanation.


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  		TABLE 4: Bland-Altman Analysis of Different Methods to Predict Postoperative FEV1

 

Figure 3
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  		Fig. 3 —Bland-Altman plot of actual postoperative FEV1 (in liters) and predicted postoperative FEV1 (in liters) using ventilation scintigraphy. If this relationship were perfect (no bias), all points would lie close to zero line on x-axis. Most points lie beneath this line, indicating that ventilation scintigraphy underestimates actual postoperative lung function.

 

Figure 4
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  		Fig. 4 —Bland-Altman plot of measured FEV1 (in liters) and predicted postoperative FEV1 (in liters) using perfusion scintigraphy. Equal points lie above and beneath zero line, indicating that perfusion scintigraphy underestimates actual postoperative lung function less than ventilation scintigraphy (as seen in Fig. 3).

 

Predicted Postoperative Percentage of FEV1
The mean percentage of predicted postoperative FEV1 using V scintigraphy, Q scintigraphy, and combined V/Q scintigraphy was 49% (SD, 14%; range, 19-71%), 52% (SD, 15%, range; 22-81%), and 50% (SD, 14%; range, 21-78%), respectively (Table 1 and Fig. 5).


Figure 5
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  		Fig. 5 —Histogram shows relationship and correlation (r) between predicted percentage FEV1 and actual measured postoperative percentage of predicted FEV1 using ventilation (V) scintigraphy, perfusion (Q) scintigraphy, and combined V/Q scintigraphy.

 
The correlation (r) between the actual and the predicted percentage of FEV1 was 0.73,0.6, and 0.62, respectively, for the V scintigraphy, the Q scintigraphy, and combined V/Q scintigraphy (Table 3 and Figs. 6 and 7).


Figure 6
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  		Fig. 6 —Correlation between measured postoperative and predicted postoperative percentage of FEV1 using ventilation scintigraphy scan; r = 0.73.

 

Figure 7
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  		Fig. 7 —Correlation between measured postoperative and predicted postoperative percentage of FEV1 using perfusion scintigraphy scan; r = 0.60.

 
The Bland-Altman analysis shows the differences among V scintigraphy, Q scintigraphy, and combined V/Q scintigraphy in predicting the postoperative percentage of predicted FEV1 (Table 4).


Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The presence of bronchogenic carcinoma causes a decrease in both ventilation and perfusion of the involved lung, especially if the lesions are in the hilar region. The lung function will further diminish with loss of lung parenchyma after a pneumonectomy procedure. Radionuclide lung quantification offers a simple method of predicting the loss in lung air capacity with quantitative measurement of differential ventilation or perfusion [13, 18]. Our study contained an older population with more female patients compared with previously reported studies and, therefore, reflects current practice. Our study population was considerably larger than that used in most previous studies [4-9] (Table 5) and also contained patients with lower FEV1 values than has been investigated previously, reflecting the impact of modern surgical techniques.


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  		TABLE 5: Comparison of Analyses of Ventilation-Perfusion Scanning for Predicting Postoperative FEV1

 

The correlation between actual and predicted values was significant for both FEV1 and percentage of predicted FEV1 values. The correlation was not as good as that previously reported [4-9] (Table 5). The highest reported correlation was obtained from V/Q SPECT quantification [10]. Although the American College of Chest Physicians [2] and the British Thoracic Society [3] recommend using perfusion scintigraphy only, we found that the ventilation scan offered the best correlation, a finding that has been previously reported [17]. Most likely the guidelines favor perfusion scintigraphy because more reports have been published on perfusion scintigraphy [6, 7, 9, 19, 20] than on ventilation scintigraphy. The use of ventilation scintigraphy alone has the advantages of requiring a lower radiation dose and avoiding the use of needles. We also found that no added predictive advantage was gained from combining both ventilation and perfusion studies, a finding that also has been previously noted [17]. Although ventilation scintigraphy offered better correlation than perfusion scintigraphy (r = 0.7 vs 0.58), a statistically significant difference between the two tests was not seen. Therefore, it would still be acceptable to perform perfusion scintigraphy alone as is done in traditional practice.

In keeping with previous findings, we showed that scintigraphy usually predicted lower postoperative FEV1 values than what actually occurred. This tendency also has been reported by other investigators [4, 8]. This finding has potentially serious implications in deciding patients' fitness for lung cancer surgery, because underestimating patients' postoperative lung function may unnecessarily preclude them from curative surgery. Our experience suggests that this underestimation occurs both when scintigraphy is used to predict the postoperative FEV1 and when it is used to determine the percentage of predicted FEV1, although we found the latter marginally more accurate.

Improvements in the correlation between scintigraphy and pulmonary function tests may have been found by using more sophisticated techniques such as SPECT. This is a tomographic technique (similar to the principles of CT) where the gamma camera rotates around the patient's body, acquiring images in different positions. SPECT gives better target-to-nontarget ratios than do planar images. This, in turn, affords improved resolution in any given plane, better definition of shape, and accurate quantification. However, because multiple camera projections are required, imaging time is much longer than for a single planar image. Unfortunately, many institutions do not have enough camera time capacity to perform this on all such patients.

Our technique could have been further enhanced by the use of ventilation gases (e.g., 99mTc gas) rather than aerosol. Aerosols, being larger and heavier particles than gases, are more likely to undergo central airway clumping. This is especially so in patients with obstructive airway disease. Technetium-99m aerosol is used because it is a cheap and readily available tracer and does not require complicated delivery systems. It is reassuring to note that in our series, only six patients had criteria for airway obstruction and only one had evidence of clumping. Technetium-99m gas is not only more expensive, but also requires more sophisticated delivery systems because very high concentrations of tracers are needed in tiny volumes. For these reasons, our institution has greater expertise in and prefers to use aerosols. Nonetheless, our use of aerosols may, in part, have explained why our correlation figures were not as high as previously reported (Table 5). Probably the best ventilation agent would have been krypton-81m (81mKr) [10], but the availability of this agent remains limited.

In conclusion, in certain lung cancer patients being considered for pneumonectomy, and in contradiction to current American College of Chest Physician and British Thoracic Society guidelines, we recommend the use of ventilation scintigraphy alone to predict postoperative FEV1. However, it is important to note that ventilation scintigraphy tends to underestimate actual postoperative lung function and, if this underestimation is not fully appreciated, some patients may unnecessarily be deprived of curative surgery.


Acknowledgments
 
We thank Linda Sharples, PhD, Cambridge MRC, for her invaluable statistical input and Prof. Adrian Dixon, Radiology Department, University of Cambridge, for his input.


References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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