Differences in clinical presentation of non-small cell lung cancer in never-smokers versus smokers.

OBJECTIVES: This study was conducted to evaluate whether or not tumor spread and the diagnostic process in non-small cell lung cancer (NSCLC) is different based on smoking history. METHODS: Associations between smoking status and clinical presentation were evaluated controlling for the effect of histology. Lung cancer with delayed diagnosis (LCDD) and incidental detection (LCID) were determined based on medical records. RESULTS: Of 914 patients, frequency of distant metastases was more common in never-smokers than in smokers (59% and 36%, respectively; P<0.001). Although never-smokers were more likely to have LCDD than smokers (18% and 11%, respectively; P=0.038), LCDD were not significantly associated with frequency of distant metastases [49% (LCDD) vs. 42% (non-LCDD); P=0.189] as well as tumor [29% (T3-4) vs. 24% (T1-2); P=0.134] and node [43% (N2-3) vs. 44% (N0-1); P=0.838] stage. Interestingly, never-smokers are more likely to have LCID than smokers (31% and 19%, respectively; P=0.010). In survival analysis, LCID (P=0.001; HR, 0.63) remained a prognostic factor, while LCDD did not. CONCLUSIONS: This study suggests distinct metastatic pattern and diagnostic processes of never-smokers. The link between survival and incidental detection was also indicated.

Epidermal growth factor receptor mutations in female patients with postoperative recurrent non-small-cell lung cancer.

PURPOSE: We did this retrospective study to explore the association between epidermal growth factor receptor (EGFR) mutation and clinical features in postoperative recurrent female non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We reviewed clinical data on 86 female patients who had postoperative recurrent disease between December 1992 and July 2007. The start of tyrosine kinase inhibitor therapy was treated as a censoring event. Corresponding surgical specimens of primary tumors were used to test for EGFR mutations. RESULTS: Thirty patients presented with local recurrence and distant recurrence was identified in 56. Thirty-four of the 86 patients (40%) harbored EGFR mutations. Patients with distant recurrence were more likely to have EGFR mutations than patients with local recurrence (48% versus 23%; P = 0.024). On multivariate analysis, distant recurrence was associated with a high frequency of EGFR mutations (OR, 3.3; P = 0.028). Survival analysis showed poor survival of patients with mutated EGFR (HR, 2.3; P = 0.017) or with non-adenocarcinoma histology (HR, 3.3; P = 0.001). CONCLUSION: The association between recurrence pattern and EGFR mutation status was suggested in recurrent female NSCLC patients. In addition, our data indicate unfavorable disease process of EGFR mutated tumors. Further studies need to be conducted to validate these findings.

CT findings in non-small-cell lung cancer patients treated with gefitinib or erlotinib.

PURPOSE: We performed this study to explore the association of computed tomography (CT) findings with outcomes of patients with non-small-cell lung cancer (NSCLC) treated with tyrosin kinase inhibitor (TKI) such as gefitinib or erlotinib. MATERIALS AND METHODS: We analyzed outcomes for 240 patients according to primary tumor (T), regional nodal (N) staging and diffuse small pulmonary metastases (DSPM) at the initial presentation. Tests for epidermal growth factor receptor (EGFR) mutation were performed in 92 patients. RESULTS: On multivariate analysis for tumor response, the N3 stage was predictive of a poor response (P < 0.001), whereas DSPM was a favorable factor (P = 0.007). Multivariate analysis for progression-free survival showed that the T3-4 stage (hazard ratio [HR]: 2.5, P < 0.001), in addition to the N3 stage (HR: 2.1, P < 0.001), was predictive of a poor outcome, whereas DSPM (HR: 0.6, P = 0.006) was a favorable factor. Notably, the multivariate model that included the EGFR mutational status revealed that the T3-4 stage predicted poor progression-free survival (HR: 2.2, P = 0.017) and poor overall survival (HR: 4.1, P < 0.001). CONCLUSION: Our data suggest that, in addition to EGFR mutational status, T-stage based on CT is predictive of outcomes of TKI-treated NSCLC patients.

Association of epidermal growth factor receptor mutations with metastatic presentations in non-small cell lung cancer.

We performed this retrospective study to assess the association of epidermal growth factor receptor (EGFR) with metastatic presentations in advanced non-small cell lung cancer (NSCLC). The data from 125 patients with stage III or IV NSCLC were analyzed. We detected EGFR mutations in 36 NSCLC patients. EGFR mutations were predominant in never-smokers (P < .001), patients with adenocarcinomas (P < .001), and female patients (P < .001). When the metastatic sites were analyzed, pleural metastases were associated with a high incidence of EGFR mutations (P = .028). Particularly, pleural metastases with minimal effusion (PMME) were associated with EGFR mutational status (P = .001). Patients with N3 lesions were less likely to harbor EGFR mutations (P = .033). On multivariate analysis, N3 lesions (P = .017) and PMME (P < .001) remained significant factors for EGFR mutations. EGFR mutations may be associated with different presentations of pleural and N3 nodal metastases.

Evaluation of Adrenal Masses in Lung Cancer Patients Using F-18 FDG PET/CT.

PURPOSE: The aim of this study was to assess the diagnostic efficacy of PET/CT using various parameters for the characterization of adrenal nodules in lung cancer patients. METHODS: Sixty-one adrenal nodules in 51 lung cancer patients were evaluated. The final diagnosis was based on histology (n = 2) or imaging follow-up (n = 59, range of follow-up: 7-57 months, median 27 months). Each adrenal nodule was analyzed using four parameters of PET/CT: the maximum standardized uptake value (SUVmax), the adrenal nodule/liver ratio of the SUV (SUV ratio), Hounsfield units (HU) and size. The optimal cutoff of each parameter for the identification of metastatic nodule was determined by ROC analysis and then the diagnostic efficacy was compared among the parameters. RESULTS: Of the 61 adrenal nodules, 45 (73%) were considered metastasis. The optimal cutoff values of the parameters were SUVmax >2.7, SUV ratio >1.3, HU >18 and size >20 mm, respectively. The sensitivity, specificity and accuracy by SUVmax >2.7 were 88.9%, 87.5% and 88.5%, and those by SUV ratio >1.3 were 84.4%, 100% and 88.5%, respectively. The combination of SUV ratio >1.3 and HU >18 had sensitivity of 97.7%, specificity of 81.2% and accuracy of 93.4% to predict adrenal metastasis in patients with lung cancer. CONCLUSION: SUV ratio from F-18 FDG PET/CT could identify the adrenal metastasis in lung cancer patients. The combination of SUV ratio and HU can improve the accuracy of differentiating benign and metastatic adrenal lesions in lung cancer patients.

Age at diagnosis predicts outcomes in gefitinib-treated female patients with non-small-cell lung cancer.

We performed this retrospective study to evaluate the association between age at diagnosis and outcome in female patients with non-small-cell lung cancer, who were treated with gefitinib. We analyzed the outcomes for 162 female patients who had received gefitinib monotherapy. Receiver operating characteristic curve analysis was performed to select a cutoff value for age with respect to tumor response. Patients were categorized as older and younger, with a value of 55 years. Most of the study population comprised never-smokers (89%) and patients with adenocarcinoma (82%). The mean age was 58 years and the response rate was 47% (76 patients). Older female patients showed higher response rates than younger patients (57% and 27%, respectively; P<0.001), whereas there were no differences between never-smokers and smokers (P=0.824). Patients with adenocarcinoma had better response rates than those with nonadenocarinoma but this difference was not significant (50% and 34%, respectively; P=0.139). In terms of progression-free survival, older age (P=0.005) and adenocarcinoma histology (P=0.008) were favorable factors but never-smoking was not (P=0.316). Multivariate analysis confirmed that age predicted progression-free survival (hazard ratio, 0.60; P=0.008) and overall survival (hazard ratio, 0.60; P=0.014). Our data indicate that age at diagnosis may predict outcomes after gefitinib treatment in female patients with non-small-cell lung cancer. When molecular tests are not feasible, our results might help physician to select a beneficial subgroup in female patients.

18F-FDG uptake and EGFR mutations in patients with non-small cell lung cancer: a single-institution retrospective analysis.

This retrospective study was performed to evaluate a possible association between the presence of epidermal growth factor receptor (EGFR) mutations and the standardized uptake value (SUV) of (18)F-fluoro-2-deoxy-glucose ((18)F-FDG) uptake in patients with non-small cell lung cancer (NSCLC). We included 100 patients who were tested for EGFR mutations by direct sequencing of resected tissues and who underwent preoperative positron emission tomography/computed tomography at the time of diagnosis. The maximum SUV by the primary tumor was chosen for further analysis. EGFR mutations in exons 19 and 21 were detected in 21 NSCLC patients (21%). EGFR mutations were more frequent in never-smokers than ever-smokers (35% versus 11%; P=0.003), in adenocarcinomas than non-adenocarcinomas (34% versus 6%; P=0.001), and in females than males (41% versus 12%; P=0.001). The SUV ranged from 1.3 to 33.0 (median 10.6). Area under receiver operating characteristic curve for SUVs in respect to the presence of EGFR mutations was 0.74 (95% CI: 0.62-0.85). When a cut off value was used, patients with low SUVs were more likely to have EGFR mutations than those with high SUVs (40% versus 11%; P=0.001). On multivariate analysis, a low SUV remained a significant predictors for EGFR mutations (P=0.025). (18)F-FDG uptake was associated with the presence of EGFR mutation. These results extrapolate that (18)F-FDG uptake might be helpful to discriminate patients who harbor EGFR mutations, especially when a genetic test is not feasible.

Sonographic changes after removing all benign breast masses with sonographically guided vacuum-assisted biopsy.

BACKGROUND: Total removal of benign breast masses by vacuum-assisted biopsy (VAB) is now increasingly accepted as a treatment option. However, little is known about whether this procedure produces early changes on follow-up sonography and, if so, how often and what factors might influence them. PURPOSE: To evaluate sonographic changes after total removal of benign breast masses using sonographically guided VAB and to determine the influencing factors. MATERIAL AND METHODS: We evaluated sonographic changes prospectively 1 week, 1 month, and 6 months after biopsying 32 benign masses from which all sonographic evidence had been removed during sonographically guided directional VAB performed with 8- or 11-gauge needles. Procedural factors were documented and compared with sonographic findings. RESULTS: At 1-week follow-up, hematomas were observed in 84% (27/32) of the lesions. After 1 month, while the hematomas had resolved in all but five lesions, focal new architectural distortion had developed in 26 (90%) lesions; 11 lesions were graded as severe, mimicking malignancy. After 6 months, 23 lesions with various degrees of architectural distortion were observed. Six of the 32 lesions (19%) contained a residual lesion. No statistically significant association between sonographic findings and procedural variables was identified, except between the degree of hematoma and lesion size. CONCLUSION: The total removal of benign breast masses using sonographically guided VAB frequently produces changes on follow-up sonography after 6 months. Although these changes failed to show statistical significance with procedural factors, a larger dedicated study is needed.

Noncalcified ductal carcinoma in situ: imaging and histologic findings in 36 tumors.

OBJECTIVE: The purpose of this study was to evaluate imaging findings in noncalcified ductal carcinoma in situ (DCIS) and to compare histologic findings between noncalcified and calcified DCIS. METHODS: From January 2005 to May 2008, 195 patients with pathologically confirmed DCIS were recruited. Among these, 36 patients (18%) had noncalcified DCIS. We retrospectively reviewed their imaging findings according to the American College of Radiology Breast Imaging Reporting and Data System. We also reviewed pathologic reports for all patients with DCIS to obtain information on the histologic type, nuclear grade, and biological markers. RESULTS: Among the 36 patients with noncalcified DCIS, 21 (58%) were symptomatic. On mammography, 25 patients (69%) showed abnormal findings, and 11 patients showed false-negative findings. On sonography, 29 of 36 patients (81%) showed a mass, whereas the remaining 7 patients (19%) showed nonmass lesions. The sonographic findings for the masses were variable: 25 of 29 masses (86%) were irregular in shape; 14 of 29 (48%) showed indistinct margins; and 9 (31%) were angular or spiculated. The orientation of the mass was not parallel in 6 of 29 cases (21%). Two of 29 masses (7%) showed an echogenic halo at the lesion boundary. Noncalcified DCIS tended to have a nonhigh nuclear grade and was frequently the noncomedo type. In addition, c-erb-B2 was more commonly expressed in calcified DCIS. CONCLUSIONS: Imaging findings for noncalcified DCIS are relatively nonspecific and are frequently similar to those of invasive malignancy. This knowledge may be useful for detecting noncalcified DCIS, planning treatment, and predicting the prognosis.

Therapeutic embolization of systemic arterial supply to normal basal segments of the left lower lobe of the lung.

Systemic arterialization of normal lung without sequestration is a rare congenital abnormality. The basal segments of the left lower lobe are most frequently involved. The involved lung has no structural abnormalities of the tracheobronchial tree that distinguish this abnormality from bronchopulmonary sequestration. Haemoptysis and exertional dyspnoea are common presenting symptoms. We report the case of a 26-year-old man who presented with recurrent haemoptysis due to systemic arterialization of basal segments of the left lower lobe of the lung, without sequestration. Therapeutic embolization using metallic coils was successfully performed without any complications. There was no further haemoptysis during a 6-month follow up. Therapeutic embolization is a safe and effective method of managing the haemoptysis associated with aberrant systemic arterial supply to the normal lung.

A diagnostic model to detect silent brain metastases in patients with non-small cell lung cancer.

We aimed to discriminate subgroups according to the risk of brain metastases in patients with non-small cell lung cancer (NSCLC) lacking neurological symptoms. We performed a retrospective review of 433 patients with NSCLC who underwent chest computed tomography (CT), brain magnetic resonance imaging (MRI) and bone scans at an initial staging work-up between April 2003 and April 2007. Brain metastases were determined by MRI. Patients were stratified into groups according to the number of risk factors (0-3) identified by multivariate analysis. In multivariate analysis, histopathology with non-squamous cell carcinoma, nodal stage 2 on CT and presence of bone metastases were three risk factors for brain metastases. Patients were divided into four groups according to the number (0-3) of these predictive factors. The proportions of patients with brain metastases in the four groups were 2%, 3%, 17% and 35%, respectively, and these differences were significant (P<0.001). When analysis was performed in patients with localised disease, the number of risk factors was correlated with the prevalence of brain metastases (P=0.013) but stage was not (P=0.153). Although this diagnostic model should be validated through further studies, our data suggest that the number of risk factors might be a useful tool to identify silent brain metastases in patients with NSCLC.

18F-fluoro-2-deoxy-glucose uptake predicts clinical outcome in patients with gefitinib-treated non-small cell lung cancer.

PURPOSE: To evaluate response and survival according to (18)F-fluoro-2-deoxy-glucose uptake at presentation in patients with gefitinib-treated non-small cell lung cancer. EXPERIMENTAL DESIGN: We retrospectively analyzed 84 positron emission tomography/computed tomography findings. Patient characteristics, response rates, and survivals were evaluated according to the maximum standardized uptake value (SUV) of primary tumor. The cutoff value of SUVs was obtained from receiver operating characteristic analysis. RESULTS: The response rate (RR) was higher for never-smokers (41%) than ever-smokers (9%; P=0.001). Patients with adenocarcinoma showed higher RR than those with other tumor histopathology (35% versus 9%; P=0.009). The SUV was significantly lower in patients who were never-smokers (P=0.005), patients with adenocarcinoma (P<0.001), and female patients (P=0.017). Patients with a low SUV showed higher RR compared with those with a high SUV (53% versus 18%; P=0.003). Prolonged progression-free survival was observed in patients with low SUVs compared with those with high SUVs (median, 33.1 weeks versus 8.6 weeks; P=0.003). While controlling for performance status, smoking history, and pathology, the high SUV conferred unfavorable outcome (hazard ratio, 2.3; P=0.012). In terms of overall survival, a low SUV was associated with favorable outcome in univariate analysis (P=0.011). Patients with a low SUV showed prolonged survival in multivariate analysis (P=0.043). CONCLUSIONS: These results suggest that low SUVs at presentation can predict favorable response and survival in gefitinib-treated non-small cell lung cancer patients.

Clinical significance of (18)F-FDG uptake by N2 lymph nodes in patients with resected stage IIIA N2 non-small-cell lung cancer: a retrospective study.

This study evaluated the potential role of (18)F-fluoro-2-deoxy-glucose (FDG) uptake by primary tumors and N2 nodes on positron emission tomography (PET) in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC). We retrospectively analyzed PET scans of 57 NSCLC patients who received surgical resection and proved pathologically to have stage IIIA N2 disease between January 2000 and April 2005. On each patient's PET scan, FDG uptake by the primary tumor and N2 nodes was evaluated using the maximum standardized uptake value (SUV). The SUV of the primary tumor (SUVt) and the highest value of the N2 nodes (SUVn) in each patient were treated as continuous variables for initial analysis. The SUVn and T stage (T1-2 vs. T3) were significant prognostic factors in univariate analysis (P=0.004 and 0.017, respectively), but the SUVt was not. Adjusted for the size of the N2 node (1cm), SUVt, and T stage (T1-2 vs. T3), the SUVn was associated with survival (P=0.019). Patients were divided into those with a low and high SUVn using a cutoff value. Controlling for the size of N2 nodes and T stages, patients with a low SUVn showed a tendency for prolonged survival (P=0.053). These results suggest that FDG uptake by the N2 node may predict survival of patients with stage IIIA N2 NSCLC.

Mammographic and sonographic findings of primary breast lymphoma.

The objective of this study was to describe the mammographic and sonographic appearances of primary lymphoma of the breast. We retrospectively reviewed the mammographic and ultrasonographic images of 12 patients with primary lymphoma of the breast. Descriptions of imaging findings were made according to the Breast Imaging Reporting and Data System lexicon by two radiologists. Mammography was performed on 11 patients. Most of the lesions were shown to be oval-shaped (72.7%) and high-density (90.9%) masses on mammography. Ultrasound examination was performed on 8 patients. The lymphomas were commonly single (75%), circumscribed (50%) or microlobulated (37.5%), and oval (50%) masses on sonography. The echo pattern of the mass was hypoechoic in 7 patients (87.5%) but hyperechoic in 1 patient (12.5%). No mass had spiculated margins or calcifications. Ipsilateral axillary lymph node involvement was noted in 1 patient. In conclusion, most primary lymphomas of the breast present as oval-shaped and high-density masses on mammography and as single and hypoechoic masses with circumscribed or microlobulated margins on sonography.

Incidental pulmonary emboli in oncology patients: prevalence, CT evaluation, and natural history.

PURPOSE: To retrospectively determine the prevalence and natural history of incidental pulmonary emboli in oncology patients, the number of such cases reported at initial thoracic computed tomographic (CT) image interpretation, and the factors that contribute to underdiagnosis. MATERIALS AND METHODS: Institutional review board approval, which included HIPAA-compliant access to protected health information and waived patient consent requirements, was obtained for this retrospective study. Four hundred three consecutive oncology patients (199 male, 204 female; age range, 14-87 years; mean age, 55 years) in whom adequate-quality multidetector thoracic CT was performed within a 10-day period for indications other than pulmonary emboli assessment were identified. There were 31 (7.7%) inpatients at the time of imaging. Each imaging case was reviewed by two independent radiologists, and all pulmonary emboli were confirmed by a panel of three thoracic radiologists. Clinical charts were reviewed for demographic data, embolus detection, and outcomes up to 2 years after the initial examination. Patient groups were compared by using chi2 and one-sided binomial tests. RESULTS: Sixteen (4.0%) of the 403 patients had pulmonary emboli. The highest prevalences were in patients with gynecologic malignancies (two of 13, 15%) and in those with melanoma (four of 41, 10%). Four (25%) of the 16 patients with emboli were identified at initial clinical CT image interpretation, and all had multiple emboli involving at least the lobar arteries. Missed emboli typically were solitary and involved smaller arteries; no other confounding factors were identified. Six (60%) of 10 patients with emboli who underwent any lower extremity imaging had deep vein thrombosis. With the exception of one patient, who was transferred back to the referring physician and lost to follow-up, all patients with reported pulmonary emboli were treated. Two patients had subsequent embolic events: one death despite treatment and one recurrent embolus in a nontreated patient. CONCLUSION: Incidental pulmonary emboli were seen in 16 (4%) oncology patients but were initially reported in only four of them. The small size of involved arteries contributes to the failed detection at initial CT image interpretation, and patients with emboli in these small vessels may have deep vein thrombosis or recurrent emboli.

Volume-expanding complications after pneumonectomy: comparison of CT findings.

The purpose of this study was to assess and characterize the computed tomographic (CT) findings of various volume-expanding complications occurring in the postpneumonectomy space. Chest CT scans, obtained in 17 patients in whom plain chest radiographs had revealed shift of the mediastinum away from the surgical side after pneumonectomy for lung cancer, were retrospectively reviewed. Recurrent neoplasm (n=6) appeared as soft-tissue mass projecting into the postpneumonectomy space and/or enlarged mediastinal lymph nodes. Empyema (n=4) was manifested by smooth thickening of the residual pleura with or without thickening of the extrapleural tissues. Hemothorax (n=4) was characterized by amorphous material of high attenuation contained within the postpneumonectomy space. Chylothorax (n=2) presented no abnormal finding except for expansion of the postpneumonectomy space. The remaining one case showed only expansion of the postpneumonectomy space and it was normalized without any treatment, which was supposed to be transient pleural fluid collection of uncertain cause. When mediastinal shift away from the surgical side occurs on plain chest radiography following pneumonectomy, CT can be helpful in differentiating various volume-expanding complications providing characteristic features.

Tumor cavitation in stage I non-small cell lung cancer: epidermal growth factor receptor expression and prediction of poor outcome.

PURPOSE: To retrospectively identify radiographic characteristics of stage I non-small cell lung cancer (NSCLC) that may correlate with epidermal growth factor receptor (EGFR) or HER2 expression or with prognosis. MATERIALS AND METHODS: This study was approved by the institutional review board, with waiver of informed consent, and was in compliance with HIPAA regulations. Findings of chest computed tomography (CT) were retrospectively evaluated in 72 patients who underwent resection of pathologic stage I NSCLC; tumor diameter, presence of calcifications, type of contour, type of margins, attenuation of the nodule, presence of a halo, presence of cavitation, and tumor location were documented. Immunohistochemical studies were performed in surgical specimens. Imaging and molecular data were correlated with patient outcome. Cox proportional hazards regression models were used to correlate biologic and radiographic variates with clinical outcome. RESULTS: There were 38 men (53%) and 34 women (47%) (median age, 65.5 years). Median follow-up was 56.3 months; median overall survival, 76.3 months. A strong correlation was found between tumor diameter measured by radiologists and that measured by pathologists (P < .001; Pearson correlation coefficient, 0.81). EGFR overexpression was found in 48 (67%) tumors; significantly more was found in squamous cell carcinomas than was found in adenocarcinomas (P = .028), and more was found in T2 tumors than was found in T1 tumors (P = .001). HER2 overexpression was found in 13 (18%) tumors; cavitation, in 16 (22%) tumors. Cavitary lesions were significantly more common in squamous cell carcinomas than were in adenocarcinomas (P = .013) and in EGFR-overexpressing tumors (P = .012) than in tumors that did not overexpress EGFR. Cavitary lesions were significantly associated with shorter disease-free survival time (P = .01) and shorter overall survival time (P < .007). CONCLUSION: Patients who have stage I NSCLC with cavitary lesions have an adverse prognosis and are likely to have tumor EGFR overexpression.