Factors causing inaccurate staging of mediastinal nodal involvement in non-small cell lung cancer patients staged by positron emission tomography

Despite documented superiority of positron emission tomography over other investigative modalities in the preoperative staging of non-small cell lung cancer, a proportion of patients will have an inaccurate staging of their mediastinal nodes. The aim of this retrospective review is to analyse the clinicopathological factors responsible for inaccurate nodal staging by integrated PET-CT. A total of 100 consecutive patients with histologically proven non-small cell lung cancer underwent staging with PET-CT prior to lung resection. Thirty-three patients, inaccurately staged by PET-CT, were analysed. Univariate analysis identified the following as significant in causing inaccurate nodal staging: history of tuberculosis (P=0.039) and non-insulin dependant diabetes (P=0.014). In multivariate analysis, we have identified the following as independent factors in causing inaccurate staging of mediastinal lymph nodes: rheumatoid arthritis, non-insulin dependent diabetes, history of tuberculosis, presence of atypical adenomatous hyperplasia and pneumonia (P<0.05). The highest rate of inaccuracy in mediastinal nodal staging was in nodal station 4 (11%, P=0.01) followed by station 7 (10%, P=0.02) and station 9 (3.5%, P=0.01). Interpretation of PET-CT staging of the mediastinum in patients with a history of the above should be with caution, as the incidence of false upstaging and down staging in these subgroups is high. Vigilance of such factors may improve the accuracy of PET-CT in staging mediastinal lymph nodes. Histological confirmation should always be sought.     

The size of metastatic foci and lymph nodes yielding false-negative and false-positive lymph node staging with positron emission tomography in patients with lung cancer

BACKGROUND: We examined the sizes of lymph nodes and metastatic foci within the lymph nodes that affect false-positive and false-negative lymph node staging by positron emission tomography in lung cancer. METHODS: Preoperative positron emission tomography and computed tomography scans were performed for 564 lymph node stations in 80 patients with peripheral-type lung cancer. The sizes of both the lymph nodes and the metastatic foci within the lymph nodes were measured, and these measurements were compared with those obtained with positron emission tomography scanning. To establish general sizes of metastatic foci within the lymph nodes, 277 metastatic lymph nodes in operative specimens previously resected from another 111 patients with lung cancer were examined as a control. RESULTS: The sensitivity was significantly higher for positron emission tomography than for computed tomographic scanning (P =.026). The sizes of metastatic foci within lymph nodes that showed false-negative (n = 8) and true-positive (n = 28) with positron emission tomography ranged from 0.5 to 9 mm (3 +/- 1 mm) and from 4 to 18 mm (10 +/- 3 mm), respectively (P <.001). None of the metastatic foci smaller than 4 mm could be detected with positron emission tomography scanning. The review of the 277 previously resected metastatic lymph nodes showed that 89 (32%) had metastatic foci smaller than 4 mm. The sizes of true-positive (n = 28) and false-positive (n = 10) lymph nodes ranged from 6 to 15 mm (10 +/- 2 mm) and from 9 to 16 mm (12 +/- 2 mm), respectively (P <.01). None of the false-positive lymph nodes was smaller than 9 mm. CONCLUSIONS: Although positron emission tomography was superior to computed tomography scanning in lymph node staging in lung cancer, positron emission tomography was unable to distinguish metastatic foci smaller than 4 mm, which were not unusual sizes for lymph node metastases in lung cancer. Positive lymph nodes with positron emission tomography smaller than 9 mm are likely to be true-positive rather than false-positive.     

Advantages of positron emission tomography over computed tomography in mediastinal staging of non-small cell lung cancer

BACKGROUND: New treatment algorithms in early stage non-small cell lung cancer (NSCLC) involving preoperative chemotherapy require accurate clinical staging of the mediastinum. This study compares the accuracy of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) scanning with that of computed tomography (CT) scanning in the clinical staging of non-small cell lung cancer. MATERIALS AND METHODS: A retrospective review was performed on 52 patients with NSCLC who were evaluated with both CT and PET scans. All patients had their mediastinal lymph nodes sampled by mediastinoscopy or at the time of thoracotomy for pulmonary resection. Each imaging study was evaluated separately and correlated with histopathologic results. RESULTS: For detecting mediastinal metastases the sensitivities of PET and CT scans were 67 and 50%, respectively; specificities were 91 and 65%, respectively; accuracies were 88 and 63%, respectively; positive predictive values were 50 and 16%, respectively; negative predictive values were 95 and 88%, respectively. PET scans were significantly better than CT scans at detecting mediastinal metastases (PET, 4/8; CT, 3/19) (P = 0.01). CONCLUSIONS: PET scanning is superior to CT scanning for clinical staging of the mediastinum in NSCLC. A more confident decision regarding stratification of patients into current treatment algorithms can be made when the decision is based on PET scanning rather than the current "gold standard" of CT scanning.     

Fluorodeoxyglucose positron emission tomography improves preoperative staging of resectable lung metastasis

OBJECTIVE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is now a procedure of proven clinical value in the staging of primary lung cancer. This study evaluated the role of PET in the preoperative assessment of resectable lung metastases. METHODS: Eighty-six patients with previously treated malignancy and proven or suspected lung metastases, deemed resectable at computed tomography scan, were investigated with 89 preoperative PET procedures. Primary tumor sites were: gastrointestinal in 32 cases, sarcoma in 13, urologic in 14, breast in 8, head and neck in 7, gynecologic in 5, thymus in 5, other in 5. Seventy lung resections were performed in 68 patients of whom only 54 proved to be lung metastasis, 7 were primary lung tumors, and 9 were benign lesions. RESULTS: In 19 cases (21%) lung surgery was excluded on the basis of PET scan results due to extrapulmonary metastases (11 cases), primary site recurrence (2), mediastinal adenopathy (2), or benign disease (4). All mediastinal node metastases (7 cases) were detected by PET with a sensitivity, accuracy, and negative predictive value for mediastinal staging of 100%, 96%, and 100%, respectively, versus 71%, 92%, and 95% of the computed tomography scan. In the group of patients who underwent lung resection, PET sensitivity for detection of lung metastasis was 87%. CONCLUSIONS: PET scan proved to be a valuable staging procedure in patients with clinically resectable lung metastasis and changed the therapeutic management in a high proportion of cases.     

Role of positron emission tomography in mediastinal lymphatic staging of non-small cell lung cancer.

OBJECTIVE: Positron emission tomography (PET) is used increasingly in staging of non-small cell lung cancer (NSCLC) as a non-invasive tool. The role of the PET in mediastinal lymphatic staging of NSCLC is not clear. We aimed to demonstrate the efficacy of PET in determining mediastinal lymphatic metastasis by comparing the results of PET with mediastinoscopy. PATIENTS AND METHODS: We performed PET preoperatively in 170 patients with clinically operable NSCLC between 2004 and 2006. Stations defined as metastasis by PET (SUV(max) >2.5) were recorded. Mediastinoscopy was performed initially in all patients and a total of 687 stations which can be reached with mediastinoscope were sampled (mean 4.04). Forty-three patients with mediastinal metastasis were referred to the oncology clinic for chemotherapy while lung resection and complete mediastinal lymphatic dissection through thoracotomy was performed in the remaining 127 patients. Involvement of mediastinal lymph nodes was verified to compare the sensitivity and specificity of mediastinoscopy and the related PET results. RESULTS: Histopathologic classification of the tumors revealed 79 squamous carcinomas and 58 adenocarcinomas. False positivity rate of PET was 26% (95% CI: 14-38), false negativity was 25% (95% CI: 18-33), sensitivity was 74% (95% CI: 63-86), specificity was 73% (95% CI: 66-82) and accuracy was 74% in mediastinal staging. Negative predictive value of mediastinoscopy was 94% (95% CI: 89-98), positive predictive value 100%, sensitivity 84% (95% CI: 74-94), specificity 100% and accuracy was 95%. CONCLUSION: PET results do not provide acceptable accuracy rates. Mediastinoscopy still remains the gold standard for mediastinal staging of NSCLC, although it cannot reach to all the mediastinal stations.     

Pulmonary suture abscess with false-positive 18F-fluorodeoxyglucose positron emission scan mimicking lung cancer recurrence

We present the case of a 57-year-old woman with pulmonary suture abscess. She had undergone right S3 segmentectomy for early lung adenocarcinoma 7 years before and right breast-conserving surgery for invasive ductal carcinoma 5 months previously, followed by irradiation plus endocrine therapy. Chest radiography and computed tomography revealed an irregular mass (3.5?cm in diameter) between the residual S1 segment and the middle lobe, neighboring the staple line of the segmentectomy. ¹⁸F-fluorodeoxyglucose uptake into the mass increased, seen by positron emission scans. Therefore, we could not rule out the possibility of local recurrence of lung cancer and resected it. Pathologically and microbiologically, the mass was a suture abscess arising around the nylon suture of the previous segmentectomy. This lesion was the result of a foreign-body reaction, as confirmed by polarized microscopy. Moreover, titanium staples at the segmentectomy and breast-conserving surgery may also have contributed to this condition.     

The role of integrated positron emission tomography-computerized tomography in evaluating and staging patients with non-small cell lung cancer

The stage of non-small cell lung cancer (NSCLC) determines that the treatment strategy and proper staging lead to improved survival. Integrated positron emission tomography/computerized tomography (CT) scan provides more accurate staging and better targets for biopsy than traditional methods such as CT scans of the chest and upper abdomen, bone scans, and magnetic resonance imaging scans. Integrated positron emission tomography/CT is the best initial test for an indeterminate pulmonary nodule that is 8 mm or greater; for the noninvasive staging of patients with NSCLC, it is the only test that produces a quantitative assessment of an NSCLC's virulence or biologic aggressiveness in a particular patient and is the best tool for restaging patients after radiation and and/or chemotherapy. Finally, its use as a tool for postoperative surveillance is under study.     

Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography

Objective: To evaluate the accuracy of integrated positron emission tomography with ¹⁸F-fluoro-2-deoxy-d-glucose (FDG) and computed tomography (PET/CT) in preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer (NSCLC) and to ascertain the role of invasive staging in verifying positron emission tomography (PET)/computed tomography (CT) results. Methods: Retrospective, single institution study of consecutive patients with suspected or pathologically proven, potentially resectable NSCLC undergoing integrated PET/CT scanning in the same PET centre. Lymph node staging was pathologically confirmed on tissue specimens obtained at mediastinoscopy and/or thoracotomy. Statistical evaluation of PET/CT results was performed on a per-patient and per-nodal-station bases. Results: A total of 1001 nodal stations (723 mediastinal, 148 hilar and 130 intrapulmonary) were evaluated in 159 patients. Nodes were positive for malignancy in 48 (30.2%) out of 159 patients (N1 = 17; N2 = 30; N3 = 1) and 71 (7.1%) out of 1001 nodal stations (N1 = 24; N2 = 46; N3 = 1). At univariate analysis, lymph node involvement was significantly associated (p < 0.05) with the following primary tumour characteristics: increasing diameter, maximum standardised uptake value >9, central location and presence of vascular invasion. PET/CT staged the disease correctly in 128 out of 159 patients (80.5%), overstaging occurred in nine patients (5.7%) and understaging in 22 patients (13.8%). The overall sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT for detecting metastatic lymph nodes were 54.2%, 91.9%, 74.3%, 82.3% and 80.5% on a per-patient basis, and 57.7%, 98.5%, 74.5%, 96.8% and 95.6% on per-nodal-station basis. With regard to N2/N3 disease, PET/CT accuracy was 84.9% and 95.3% on a per-patient basis and on per-nodal-station basis, respectively. Referring to nodal size, PET/CT sensitivity to detect malignant involvement was 32.4% (12/37) in nodes <10 mm, and 85.3% (29/34) in nodes ≥10 mm. Conclusion: Our data show that integrated PET/CT provides high specificity but low sensitivity and accuracy in intrathoracic nodal staging of NSCLC patients and underscore the continued need for surgical staging.     

Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer

BACKGROUND: Surgical resection of lung cancer remains the treatment of choice in appropriately staged disease, but conventional imaging techniques have limitations. Positron emission tomography (PET) may improve staging accuracy. METHODS: We studied whole body and localized thoracic PET in staging lung cancer. Standardized uptake value was calculated for the primary lesion. Ninety-seven patients under consideration for surgical resection were included. PET, computed tomography, and clinical staging were compared to stage at operation, biopsy, or final outcome. Mean follow up was 17.5 months. RESULTS: PET detected all primary lung cancers with two false-positive primary sites. Sensitivity and specificity for N2 and N3 mediastinal disease was 20% and 89.9% for computed tomography and 70.6% and 97% for PET. PET correctly altered stage in 26.8%, nodal stage in 13.4%, and detected distant metastases in 16.5%. PET missed 7 of 10 cerebral metastases. PET altered management in 37% of patients. PET staging (p<0.0001) and standardized uptake value (p<0.001) were the best predictors of time to death apart from operative staging. CONCLUSIONS: PET provides significant staging and prognostic information in lung cancer patients considered operable by standard criteria. Routine use of PET will prevent unnecessary operation and may be cost effective.     

11C-choline positron emission tomography in prostate cancer: primary staging and recurrent site staging

OBJECTIVES: To evaluate the usefulness of 11C-choline positron emission tomography (PET) for primary staging and re-staging of prostate cancer. PATIENTS AND METHODS:11C-choline PET, a total of 22 scans, was performed on 13 patients with histologically proven prostate cancer in primary staging (n = 6) and recurrent site staging; following radical prostatectomy (n = 5) and following radiation therapy (n = 3). In 1 patient, 11C-choline PET was performed in both primary staging and re-staging. Also, 3 patients histologically proven to have no malignant prostate were included. RESULTS: Because urinary 11C-choline activity was low, it did not interfere with the visualization of pelvic structures. 11C-choline PET visualized normal prostate with a mean SUV of 2.99 (range 2.27-3.68) and primary prostate cancer as a hot spot in 5/6 scans with a mean SUV of 4.21 (range 2.99-6.2). In re-staging, 11C-choline PET was true positive in 9/16 scans and true negative in 2/16 scans. 5/16 scans in 2 patients were false negative with negative conventional imaging. CONCLUSIONS: In primary staging, 11C-choline PET may not be of use because of no reliable differential 11C-choline uptake of BPH and prostate cancer. On the other hand, 11C-choline PET may be of value in recurrent site staging and monitoring for the prostate cancer.     

Comparative efficacy of positron emission tomography with FDG and computed tomographic scanning in preoperative staging of non-small cell lung cancer

OBJECTIVE: To determine the sensitivity, specificity, and accuracy of positron emission tomography with 2-fluorine-18-fluorodeoxyglucose (PET-FDG) in the preoperative staging (N and M staging) of patients with lung cancer. The authors wanted to compare the efficacy of PET scanning with currently used computed tomography (CT) scanning. MATERIALS AND METHODS: Results of whole-body PET-FDG imaging and CT scans were compared with histologic findings for the presence or absence of lymph node disease or metastatic sites. Sampling of mediastinal lymph nodes was performed using mediastinoscopy or thoracotomy. RESULTS: PET-FDG imaging was significantly more sensitive, specific, and accurate for detecting N disease than CT. PET changed N staging in 35% and M staging in 11% of patients. CT scans helped in accurate anatomic localization of 6/57 PET lymph node abnormalities. CONCLUSION: PET-FDG is a reliable method for preoperative staging of patients with lung cancer and would help to optimize management of these patients. Accurate lymph node staging of lung cancer may be ideally performed by simultaneous review of PET and CT scans.     

A novel approach to positron emission tomography in lung cancer

18F-fluorodeoxyglucose positron emission tomography-computed tomography is integral to the staging of lung cancer. We describe the combined use of diagnostic preoperative 18F-fluorodeoxyglucose positron emission tomography-computed tomography, intraoperative 18F-fluorodeoxyglucose handheld gamma probe detection, and immediate postoperative 18F-fluorodeoxyglucose positron emission tomography-computed tomography patient and specimen imaging for improved staging and determination of adequacy of mediastinal lymph node dissection.