Cancer cell liver small

Study objectives: Correct detection of bone metastases in patients with non-small cell lung cancer (NSCLC) is crucial for prognosis and selection of an appropriate treatment regimen. The aim of this study was to investigate the role of whole-body bone scanning (WBBS) and clinical factors in detecting bone metastases in NSCLC.

Design and patients: One hundred twenty-five patients with a diagnosis made between 1998 and 2002 were recruited (squamous cell carcinoma, 54.4%; adenocarcinoma, 32.8%; non-small cell carcinoma, 8.8%; large cell carcinoma, 4%). Clinical factors suggesting bone metastasis (skeletal pain, elevated alkaline phosphatase, hypercalcemia) were evaluated. WBBS was performed in all patients, and additional MRI was ordered in 10 patients because of discordance between clinical factors and WBBS findings.

Measurements and results: Bone metastases were detected in 53% (n = 21) of 39 clinical factor-positive patients, 5.8% (n = 5) of 86 clinical factor-negative patients, and 20.8% of total patients. The existence of bone-specific clinical factors as indicators of metastasis presented 53.8% positive predictive value (PPV), 94.2% negative predictive value (NPV), and 81.6% accuracy. However, the findings of WBBS showed 73.5% PPV, 97.8% NPV, and 91.2% accuracy. Adenocarcinoma was the most common cell type found in patients with bone metastasis (39%). The routine bone scanning prevented two futile thoracotomies (8%) in 25 patients with apparently operable lung cancer.

Conclusions: In spite of the high NPV of the bone-specific clinical factors and the high value obtained in the false-positive findings in the bone scan, the present study indicates that in patients for whom surgical therapy is an option, preoperative staging using WBBS can be helpful to avoid misstaging due to asymptomatic bone metastases.

Key words: imaging; non-small cell lung cancer; skeletal metastases; staging

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Abbreviations: ACCP = American College of Chest Physicians; CWU = conventional workup; FDG = F-18 fluorodeoxyglucose; NPV = negative predictive value; NSCLC = non-small cell lung cancer; PET = positron emission tomography; PPV = positive predictive value; WBBS = whole-body bone scanning

Lung cancer is the most common cause of cancer-related deaths in both men and women. (1) Surgical resection of the lung mass with mediastinal lymph node sampling is the best treatment modality for non-small cell lung cancer (NSCLC) in patients without preoperative evidence of mediastinal invasion or distant metastasis. However, recurrence rates after curative surgical procedures are high. (2) Many patients have undetected disseminated disease at the time of thoracotomy, and this is the most likely cause of treatment failure and ultimate death.

If history, physical examination, and initial laboratory screening results are negative, the likelihood of finding metastatic disease on subsequent staging procedures is low. (3) The joint statement of the American Thoracic Society and the European Respiratory Society (4) on pretreatment evaluation of NSCLC advocates no preoperative imaging of the distant metastases in patients who have no symptoms or other evidence of distant metastases. According to American College of Chest Physicians (ACCP) evidence-based guidelines, (5) patients with clinical stage I and II lung cancer and normal results of a clinical evaluation require no further imaging for detection of extrathoracic disease. However, patients with stage IIIA and IIIB disease should undergo routine imaging studies. Some authors (6,7) suggest a more aggressive approach to rule out clinically occult, but detectable metastases.

METHODS AND MATERIALS

In our clinic, Cerrahpasa Medical Faculty, Department of Pulmonology, between January 1998 and September 2002, 125 patients who had histologically proven NSCLC received treatment according to cancer stage. They were then retrospectively subjected to evaluation for bone metastases. The patients with radiographic evidence of extrathoracic metastases demonstrated prior to discovery and staging of the primary bronchogenic carcinoma were excluded from the study. These patients had either CNS abnormalities with a cranial CT showing metastases, or plain radiographic abnormalities considered malignant bone metastases.

Of the patients, 111 were men and 14 were women. The mean ([+ or -] SD) age was 61 [+ or -] 10 years (range, 34 to 79 years). Histologic diagnosis were as follows: squamous cell carcinoma, n = 68 (54.4%); adenocarcinoma, n = 41 (32.8%); large-cell carcinoma, n = 5 (4.0%); and non-small cell carcinoma, n = 11 (8.8%).

All patients included in the study had undergone the routine extrathoracic metastasis screening procedures of our clinic. All of them underwent a CT scan of the thorax including the liver and the adrenal glands. Staging factors T and N were performed by CT and fiberoptic bronchoscopy according to the International System for Staging Lung Cancer adopted by the American Joint Committee on Cancer and the International Union Against Cancer in 1997. (2) Lymph nodes measuring < 1 cm in the short axis were considered normal. The retrospective evaluation of the patients was made alter the last ACCP evidence-based guidelines were published. (8) The patients were classified into two main groups. The first group was considered operable and consisted of T1-2-3 and radiologic N0-1 patients. Patients with radiologic N2-3,T4 made up the second, unfavorable group. The separate tumor nodule(s) in the ipsilateral nonprimary-tumor lobe(s) of the lung or contralateral lung and intra-abdominal metastases were classified as M1.

The medical records of patients were reviewed to determine the bone-specific clinical factors suggestive of bone metastases. These factors include bone pain or tenderness, and elevated serum alkaline phosphatase and serum calcium levels.

All patients underwent whole-body bone scanning (WBBS) using [sup.99m]Tc. If the abnormal findings were multiple and asymmetric, they were considered positive for metastatic disease. Study findings were classified as normal if there was no scintigraphic abnormality or if there was a definite benign explanation for the scintigraphic findings (osteoarthritis, osteolnalacia, etc). The remaining study findings were classified as "probable."

Additional MRI was ordered due to disagreement between WBBS and bone-specific clinical factors (n = 10). Interpretation of WBBS and bone-specific clinical factors were assessed for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and accuracy.

RESULTS

In 26 of 125 patients (20.8%), bone metastases were detected with the use of clinical factors, by bone scan and/or MRI. Besides bone metastases, 12 patients (9.6%) also had metastatic disease in the liver (n = 4), the lung (n = 3), the brain (n = 3), the adrenal glands (n = 1), and the liver plus the adrenal glands (n = 1). Thirty-nine of the 125 patients (31.2%) presented at least one bone-specific clinical factor suspicious of metastasis. In 21 of them (53.8%), bone metastases were confirmed. There were no bone-specific clinical factors in five patients (5.8%) with metastases (Fig 1, Table 1). Therefore, the existence of bone-specific clinical factors as indicators of metastasis presented 80.8% sensitivity, 81.8% specificity, 53.8% PPV, 94.2% NPV, and 81.6% accuracy. Proportions were furnished with their 95% confidence intervals (Table 2).

[FIGURE 1 OMITTED]

Abnormal WBBS results were obtained in 34 of the 125 patients (27.2%). WBBS and bone-specific clinical factors were in agreement in 98 of 125 patients (Table 3). MRI was ordered in 10 of 27 patients with disagreement (Table 4). Fifteen of the 27 patients were inoperable due to chest CT scan results (T4, N2, N3, or M1); 1 patient was 78 years of age and refused any proposed treatment. The last patient of the 17 who was inoperable due to chest CT scan results and positive WBBS findings was followed up for 14 months without clinical or radiographic evidence of neoplastic bone involvement, and this patient's WBBS result was considered false-positive. In these 17 patients, radiologic confirmation of bone metastases via MRI or pathologic confirmation via bone biopsy were considered unnecessary, as the results would not change the treatment modality.

Any scans with positive and probable results were listed as true-positive, and scans with negative results were true-negative. Of the six abnormal WBBS results in patients free of clinical evidence of metastases, two were true-positive and the remaining four were false-positive according to MRI (Table 4).