| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA.
Correspondence to: Josephine Lee, MD, 7224 Beacon Terrace, Bethesda, MD 20817; e-mail: josilee1{at}home.com
 |
Abstract |
|---|
 TOP Abstract IntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
Design: A retrospective review of the PET database of our hospital from April 29, 1997, to March 20, 1999, identified 196 patients referred for the evaluation of new lung findings, either as an incidental finding or following definitive treatment of a primary carcinoma. The diagnosis of either malignancy or a benign condition was established in 71 patients. This was determined by either histopathology from biopsy, or by subsequent imaging demonstrating disease progression, resolution, or stability of the initial lung findings.
Results: In patients presenting with new lung findings without a history of carcinoma (n = 37), the sensitivity and specificity of PET was 95% and 82%, respectively. In this population, the negative predictive value was 93% and the positive predictive value was 86%. PET was less sensitive and specific for evaluating metastatic or recurrent disease in patients previously treated for carcinoma. In patients presenting with a previously treated primary lung cancer (n = 13), the sensitivity of PET was 70%, with a specificity of 67%. The negative predictive value was only 40% and the positive predictive value was 88% in this subset of patients. In patients with an extrapulmonary primary carcinoma presenting with new lung nodules (n = 21), the sensitivity and specificity of PET was 92% and 63%, respectively. In this population, the negative predictive value was 83% while the positive predictive value was 80%. Of the 71 total cases for which follow-up data were available, there were 5 false-negative cases and 7 false-positive cases, for an overall sensitivity of 88%, specificity of 75%, negative predictive value of 81%, and positive predictive value of 84%.
Conclusions: The sensitivity of PET is highest for the evaluation of new malignancy in patients without a known primary carcinoma. PET is less sensitive for evaluating metastatic or recurrent disease.
Key Words: positron emission tomography • pulmonary nodule • malignancy • metastasis
|
Introduction |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
1.2 cm. Another study2
suggested an equal sensitivity
and specificity for lesions as small as 7 mm. Many of these studies
were designed to specifically address the performance of PET scanning
in the evaluation of solitary pulmonary nodules in patients without a
history of carcinoma.3
4
5
6
7
A few studies8
9
have evaluated the performance of PET scanning in diagnosing metastatic
cancer or recurrent lung cancer in patients with a previously treated
carcinoma, presenting with new lung nodules. Given the high sensitivity
and negative predictive value reported in these studies, some authors
have suggested that PET evaluation demonstrating hypermetabolic
activity in the location of the lesion in question, with an SUR of
< 2.5, is adequate to diagnose a benign nodule. According to this
approach, these patients could be managed with follow-up imaging and
biopsy of the nodule could thus be avoided.10
11
12 Anecdotal experience in our institution suggested a higher false-negative and false-positive rate than has been published in the literature. We therefore decided to test the accuracy of PET scanning in a tertiary-care hospital with an active PET referral center.
|
Materials and Methods |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
One hundred ninety-six patients referred for PET met criteria for inclusion in the study. The patients were classified into one of three categories: (1) patients without a history of carcinoma presenting with new lung nodule or mass (n = 94); (2) patients with prior resection/treatment of lung carcinoma with new or changing lung findings worrisome for recurrent or metastatic disease (n = 51); and (3) patients with a known extrapulmonary primary carcinoma presenting with new lung nodules (n = 51).
PET Imaging
All subjects fasted at least 4 h prior to the examination
and had a documented normal serum glucose level prior to injection of
FDG. PET imaging was performed approximately 60 to 90 min after IV
administration of a dose of 4.218 megabecquerel/kg of FDG, according to
department protocol, which is similar to the protocol used by other
investigators for tumor studies.13
Multiple partially
overlapping scans of 12.8 cm were obtained from the lung apices through
the pelvis using a scanner (PENN-PET 240H; UGM Medical Systems;
Philadelphia, PA). The scanner has an intrinsic resolution of 5.5 mm in
all three planes at the center of the field of view and operates
without septa. Transmissions scans were obtained at the conclusion of
the study for nonuniform attenuation correction over the chest (Fig 1
).
|
In the majority of cases, CT examination demonstrating the lesion in question was available at the time of study interpretation and the PET scan was interpreted in conjunction with the CT. Visual analysis, as well as calculation of the SUR for the dominant lesion identified by PET and/or lesion seen on CT, was performed by two experienced readers as part of the clinical interpretation. Lesions demonstrating increased uptake with respect to the mediastinum were considered abnormal. A cutoff SUR value of 2.5 was used to establish benignity.1 A focus of high FDG activity (SUR > 2.5) was considered positive for malignancy. If the patient presented with multiple nodules, visual analysis and SUR, if possible, were performed for the dominant lesion identified on CT, as well as for any lesion demonstrating abnormal increased metabolic activity on visual inspection.
Attenuation-corrected scans were available in all cases. Attenuated and nonattenuated PET images, as well as the SUR were taken into account for the final interpretation.
Follow-up
Follow-up was obtained primarily via a questionnaire that was
sent to all referring physicians. Specifically, we asked if
histopathology or follow-up imaging was obtained, and if treatment with
surgery, radiation, and/or chemotherapy was initiated. In addition, a
review of the pathology reports and charts of the patients referred
from within our own hospital was performed. Only patients in whom the
diagnosis of malignancy or benignancy was established were included in
our final analysis. Malignancy or benignancy was established if
patients had definitive pathology of the lesion in question. If
histopathology was not obtained, the diagnosis of malignancy was
established if follow-up imaging demonstrated interval disease
progression (range, 3 months to 3.5 years) A benign condition was
established if follow-up imaging demonstrated lesion regression with a
minimum 6-month interval or lesion stability for a minimum of 1 year.
Statistical Analysis
Sensitivity and specificity of PET were determined by comparing
the results from PET scan with the histologic findings, if available,
or with patient survival and follow-up imaging demonstrating disease
progression, regression, or stability.
|
Results |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
20). Overall, of the 71 patients with definitive diagnosis, there were five false-negative cases and seven false-positive cases, for an overall sensitivity of 88% and a specificity of 75%. The overall negative predictive value for all patients presenting with an abnormality in the lungs is 81% (Table 1 ). The breakdown of histologic subtypes for false-positive and false-negative results is included in Table 2 .
|
|
There was one false-negative result in a patient who presented with a 1.5-cm nodule in the right lower lobe noted on CT, in which both visual qualitative inspection and semiquantitative analysis of PET scan demonstrated no metabolically active process within the chest. The lesion was resected because of high clinical suspicion; histology demonstrated adenocarcinoma of the lung. No lymph nodes were positive for malignancy (Table 3 ).
|
|
|
There were three false-positive results in this population. In all three cases, the patients presented with a single lung nodule/mass. PET scan demonstrated abnormal increased glucose uptake (SUR > 2.5) in all three cases, suggesting a metastatic process. In all three cases, the lesion in question was resected. In two cases, histology demonstrated nonspecific inflammatory change (one patient had primary squamous cell carcinoma of the penis; the other patient had primary adenocarcinoma of the colon). In the third case, histology was consistent with a hamartoma in a patient with a primary liver hepatoma.
Overall, PET scan had a sensitivity of 92% and a specificity of 63% in evaluating potential metastasis in patients with a known extrapulmonary primary carcinoma. The negative predictive value of PET scan in this population is 83% (Table 6 ).
|
|
There was a single false-positive result in this patient population. The patient had been treated with radiation approximately 6 months prior, and was now being evaluated for an enlarging pulmonary soft-tissue mass suggesting possible recurrence vs radiation change. The PET scan demonstrated hypermetabolic uptake in the region of CT abnormality (SUR > 2.5), suggesting recurrent tumor. Subsequent follow-up imaging with CT every 6 months for 1.5 years demonstrated stability and eventual decrease in size of the abnormal soft tissue, compatible with benign radiation changes.
In this population, PET demonstrated a sensitivity of 70%, with a specificity of 67% and a negative predictive value of only 40% (Table 8 ). Follow-up data were not available in 124 patients because the primary referring physician did not respond to the questionnaire, could not be located, or did not provide adequate information in response to the questionnaire.
|
|
Discussion |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
Our study is in contradiction to the findings of Knight et al,8 who found a similar sensitivity of 100% in patients with or without a history of malignancy. Like Patz et al,1 Knight et al8 demonstrated no false-negative results for lesions > 1.0 cm in either patient population group using a cutoff level of SUR > 2.5 for malignancy. In our study, however, patients with a treated extrapulmonary primary carcinoma or primary lung carcinoma demonstrated a lower sensitivity (92% and 70%, respectively) and specificity (63% and 67%, respectively) for evaluating metastatic and/or recurrent disease. Furthermore, in our population, false-negative results occurred in patients in whom visual analysis failed to even demonstrate a region of increased FDG uptake at the site of the lesion in question, so a region of interest or SUR could not be calculated.
In addition, Knight et al8 demonstrated a higher accuracy for evaluation of malignancy in patients with a history of malignancy (95%) than in patients with new lung nodules (81%). This is opposite to what we observed in our study. Our study appears to confirm the findings of Hubner et al,7 who demonstrated a lower sensitivity (83 to 87%) of PET in evaluating lung recurrence or metastatic disease when compared to solitary pulmonary nodules (sensitivity, 100%). However, unlike Hubner et al,7 who reported a similar specificity of 80 to 83% in patients with a history of any carcinoma when compared to those without a history of carcinoma, we noted a lower specificity (63 to 67%) of PET in patients with a history of carcinoma.
In the literature, false-negative results have been documented14 15 for bronchoalveolar lung cancer, which are typically slow growing tumors and may not demonstrate a hypermetabolic state. Therefore, it is notable that in our study, false-negative lesions occurred in cases where the histology confirmed adenocarcinoma (three cases) and squamous cell carcinoma (one case), which typically are hypermetabolic tumors. In all four cases, the tumor was approximately 1.5 cm in size. In one case, the patient had no known primary carcinoma; the lesion was believed to represent a new lung primary. In the other three cases, the patients had been previously treated for a primary lung tumor and were presenting with new pulmonary nodules after treatment.
Frequently, small lesion size (< 1.2 cm) is cited as a reason for a lower sensitivity of PET. The use of SUR > 2.5 as a cutoff for benign lesions was established using lesions that were at least 1.2 cm in size.1 Subsequent studies4 6 12 have reported a high sensitivity and specificity for lesions as small as 7 mm in size when combined qualitative visual analysis and semiquantitative SUR values are implemented. Furthermore, a recent study by Lowe and Naunheim12 found that the sensitivity and specificity of PET was not statistically different when comparing nodules 7 mm to 1.5 cm in size with nodules > 1.5 cm, when lesions were analyzed with both qualitative visual inspection and a SUR cutoff of 2.5. However, in our study, the five false-negative cases occurred when the lesion in question was at least 1.2 to 1.5 cm in size, which is within the resolution of our PET camera. In all five false-negative cases, PET failed to show any hypermetabolic uptake, so an SUR value could not be calculated. This was seen in four cases of metastatic disease (primary breast [n = 1], squamous cell of the lung [n = 1], and adenocarcinoma of the lung [n = 2]), and one case of newly diagnosed primary adenocarcinoma of the lung (Table 3) . We speculate that this may be related in part to a slower metabolic rate in metastatic lesions when compared with a primary carcinoma.
A recent study from our institution using dual time point FDG-PET imaging has shown promising results in differentiating between malignant and benign nodules (A. Matthies, MD; unpublished data; June 2000). We are currently reviewing our data to determine whether the use of dual time point imaging may improve both sensitivity and specificity in evaluating patients presenting with pulmonary nodules worrisome for metastatic or recurrent disease after treatment with chemotherapy and/or radiation.
A potential criticism of our study was the relatively short interval follow-up in several cases. Ideally, an imaging follow-up interval of 2 years is considered definitive for benignity. However, in all cases with short interval (< 1 year) follow-up, the lesion in question had either regressed or resolved and was therefore considered benign, or had demonstrated significant growth and subsequent progression in lesion size or number of nodules, and thus considered malignant.
A second potential criticism of our study is the relatively small number of cases; follow-up data were available in only 71 cases. However, to our knowledge, this is still the largest study to date and represents the largest number of cases.
|
Conclusion |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
|
Footnotes |
|---|
Received for publication December 6, 2000. Accepted for publication June 28, 2001.
|
References |
|---|
|
TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  L. K. Shankar and D. C. Sullivan Functional Imaging in Lung Cancer J. Clin. Oncol., May 10, 2005; 23(14): 3203 - 3211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Rohren, T. G. Turkington, and R. E. Coleman Clinical Applications of PET in Oncology Radiology, May 1, 2004; 231(2): 305 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Pfister, D. H. Johnson, C. G. Azzoli, W. Sause, T. J. Smith, S. Baker Jr, J. Olak, D. Stover, J. R. Strawn, A. T. Turrisi, et al. American Society of Clinical Oncology Treatment of Unresectable Non-Small-Cell Lung Cancer Guideline: Update 2003 J. Clin. Oncol., January 15, 2004; 22(2): 330 - 353. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
