High efficacy of erlotinib in Taiwanese NSCLC patients in an expanded access program study previously treated with chemotherapy.

PURPOSE: Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which has demonstrated a survival benefit in non-small-cell lung cancer (NSCLC) patients. An open label phase II study was conducted in Taiwanese patients with NSCLC to evaluate its efficacy. METHODS: Patients with proven stage IIIB/IV NSCLC who had received at least one line of standard chemotherapy or radiotherapy were enrolled into this study. All patients were given oral erlotinib, 150mg/day till disease progression. RESULTS: From May 2005 to July 2006, 300 patients were entered from 14 hospitals in Taiwan. This analysis was based on 299 patients who received at least one dose of erlotinib. The best response rates were a 29% partial response and 44% stable disease in 273 patients who had response data available. Non-smoking (p=0.033), adenocarcinoma/BAC (p=0.0027), female (p=0.0013), aged less than 65 years (p=0.0115), stage IV (p=0.0492), patients with skin rash (p=0.0216), and a higher grade of skin rash (p=0.003) were significantly correlated with response to treatment. Skin rash was a common adverse event (any grade: 84%, Gr 3-4: 16%). The median time to disease progression was 5.6 months. Cox regression model for progression free survival showed patients most at risk of early progression were males of low performance status having squamous cell carcinoma. CONCLUSIONS: This was the largest multicenter prospective clinical study of NSCLC in Taiwan. The results demonstrated the excellent response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese NSCLC patients who had been previously treated with chemotherapy or radiotherapy.

Squamous cell lung carcinoma metastatic to the breast.

Secondary malignancy metastatic to the breast is uncommon with an incidence of 0.5% to 3% of patients with extramammary malignancy. Here, an intriguing, rare case with metastasis to the breast from squamous cell lung carcinoma is reported. A 48-year-old women suffered from chronic cough with sputum for two months. The histological diagnosis, a achieved by bionchoscopic biopsy was squamous cell lung carcinoma. Concurrent chemoradiation therapy was given. Unfortunately, a left breast lump was noted eight months later and metastatic squamous cell lung carcinoma to the breast was diagnosed by surgical biopsy. Secondary malignancy metastatic to the breast is uncommon, yet this entity does exist. In view of the therapeutic implication, a metastatic breast lesion should not be mistaken for a primary breast carcinoma. Only with the awareness of such a possibility can prompt diagnosis and optimal treatment be achieved.

Endobronchial ultrasonography with distance for peripheral pulmonary lesions.

BACKGROUND: We assessed the effectiveness of applying the distance from the orifice of the bronchus to visualized peripheral pulmonary lesion (PPL) under endobronchial ultrasonography (EBUS) to transbronchial biopsy (TBB), as an alternative to EBUS with a guide sheath (GS) and fluoroscopy. PATIENTS AND METHODS: From October 2004 to July 2005, a total of 158 consecutive patients with solitary PPLs, which were not visualized under flexible video bronchoscopy, were received EBUS for advanced localization subsequently. One hundred and thirteen of 158 patients with solitary PPLs which were visualized on EBUS image were included in this prospective study and randomly divided into two groups for TBB using different methods. In group EBUS-D (57 patients) the distance from the bronchial orifice to pulmonary lesion was measured, then the biopsy forceps were advanced to this measured distance and biopsy followed. In group EBUS (56 patients) the biopsy forceps were advanced regardless of distance. The diagnostic yields were then compared. RESULTS: TBBs in group EBUS-D patients had a significantly higher diagnostic yield (45/57, 78.9%) than group EBUS patients (32/56, 57.1%) [P=0.013]. Size and location of lesion, duration of EBUS, diagnosis of malignancy, and whether the probe was located within the lesion on EBUS image did not differ between these two groups. Mild bleeding occurred in three patients in group EBUS-D and two in group EBUS. One group EBUS patient had a self-limited pneumothorax. CONCLUSIONS: Measuring and applying the distance between the orifice of bronchus and the lesion could increase the diagnostic yield of EBUS-guided TBBs for PPLs.

Differentiating peripheral pulmonary lesions based on images of endobronchial ultrasonography.

PURPOSE: To attempt to develop a simple method to discriminate between neoplasm and nonneoplasm peripheral pulmonary lesions based on images of endobronchial ultrasonography (EBUS). METHODS: Between June 2004 and June 2005, 151 patients with bronchoscopic peripheral lesions that could not be detected via a conventional bronchoscope underwent EBUS for advanced localization with a 20-MHz miniature radial probe in a tertiary-referral teaching hospital. The image characteristics were applied subsequently to correlate definite histopathologic results in studied patients. RESULTS: Based on an initial 20 consecutive patients with a definite diagnosis, four image characteristics were issued: (1) continuous hyperechoic margin outside the lesion, (2) homogeneous, or heterogeneous internal echoes, (3) hyperechoic dots in the lesion, and (4) concentric circles along the echo probe. In the following 131 patients, excluding five cases due to inconsistent typing, 93 patients (73.8%) established a diagnosis later. Most cases involving the image characteristics of homogenous internal echoes and concentric circles had nonneoplasm lesions (18 of 19 cases, 94.7%, and 14 of 16 cases, 87.5%, respectively). The difference shown in these two respects with neoplasm lesions was significant by univariate analysis (p < 0.001), although only concentric circles had a significant p value after multivariate analysis. Another two image patterns (continuous hyperechoic margins and hyperechoic dots) did not yield a significant difference (p = 0.090 and p = 0.079, respectively). The average additional time for EBUS was 3.94 min (1.5 to 10 min). CONCLUSION: EBUS can provide characteristic information to differentiate the nature of a peripheral pulmonary lesion from the image characteristics of concentric circles.

First- or second-line gefitinib therapy in unknown epidermal growth factor receptor mutants of non-small-cell lung cancer patients treated in Taiwan.

Gefitinib is effective in treating patients with non-small-cell lung cancer (NSCLC). The response rate and improvement in survival are related to several aspects, including race, gender, smoking status, and histology; however, little is known about the relationship between survival and length of gefitinib treatment. We conducted this retrospective study to examine this relationship and identify the predictive factors influencing survival and tumor response in chemonaive and chemotherapy patients who had stage IIIb or IV NSCLC with unknown epidermal growth factor receptor mutants. This analysis was aimed to clarify the difference between first- and second-line gefitinib therapy. Among the 918 newly diagnosed, inoperable NSCLC patients from March 2003 to December 2006, 437 (47.6%) had ever received gefitinib therapy. One hundred forty-nine patients (34.0%) who selected gefitinib as first- or second-line therapy were included in the analysis. The overall survival rates of first- and second-line gefitinib therapy were 12.8 months and 20.7 months, respectively (P = .110). The shorter overall survival may be caused by the omission of platinum-based doublet chemotherapy in 37 patients from the first-line group (39.4%). There was also no significant difference in progression-free survival (6.8 months versus 4.9 months; P = .415), and the objective tumor response and disease control rates were similar. Better prognosis and tumor response was associated with female gender, adenocarcinoma, nonsmokers, and good performance status. The difference in overall survival between patients undergoing second-line treatment compared with those undergoing first-line treatment preceding chemotherapy was significant (P = .041). The overall survival, progression-free survival, and tumor response rates were similar in the patients who received gefitinib as initial therapy or after conventional chemotherapy.

Endobronchial ultrasonography-guided transbronchial needle aspiration increases the diagnostic yield of peripheral pulmonary lesions: a randomized trial.

BACKGROUND: The diagnostic yield of endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs) has not been evaluated. The diagnostic impact of TBNA when the EBUS probe is adjacent to lesions remains to be determined. DESIGN: A prospective, randomized trial. METHODS: Two hundred two patients with PPLs and positive EBUS findings were enrolled. They were randomly classified into two groups. In the EBUS conventional diagnostic procedures (CDPs) group (103 patients), both transbronchial biopsy (TBB) and bronchial washing (BW) were performed. In the EBUS-TBNA plus CDPs group (99 patients), TBNA, TBB, and BW were performed. The diagnostic yield in each group was compared. RESULTS: A total of 182 patients (94 in the EBUS CDPs group and 88 in the EBUS-TBNA plus CDPs group) were analyzed. The yield in the EBUS-TBNA plus CDPs group (78.4%) was significantly higher than the EBUS CDPs group (60.6%, p = 0.015). Cases in which the EBUS probe was located within the lesions had a significantly higher diagnostic yield (78.3%) than when the EBUS probe was adjacent to them (47.2%, p < 0.001). Concerning the three different techniques, TBNA showed the highest diagnostic yield (62.5%) in comparison to TBB (48.9%) and to BW (19.8%). The diagnostic yield of TBNA remained unchanged even when the EBUS probe was adjacent to the lesions (p = 0.89). No additional adverse effects were observed in the EBUS-TBNA plus CDPs group. CONCLUSIONS: Applying TBNA to EBUS-guided CDPs further increased the diagnostic yield of PPLs without additional risk. The diagnostic advantage of TBNA became more obvious if the EBUS probe was adjacent to the lesions. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00626587.

New image characteristics in endobronchial ultrasonography for differentiating peripheral pulmonary lesions.

Endobronchial ultrasonography (EBUS) rapidly and accurately localizes peripheral pulmonary lesions. It can aid differential diagnosis by characterizing lesions and discriminating between neoplastic and non-neoplastic disease. From July 2005 through December 2006, patients with peripheral lesions underwent EBUS examination in a tertiary-referral teaching hospital. Image characteristics were subsequently correlated with definite histopathologic diagnosis. Three current-issued image patterns of EBUS were assayed from 40 initial patients, including (a) hypoechoic areas, (b) anechoic areas and (c) luminant areas around the probe. Excluding 22 cases because of inconsistent typing, 193 patients possessing definite diagnoses were enrolled in the investigation, of which 107 cases (55.4%) were neoplastic diseases. Hypoechoic areas appeared to be unrelated to the nature of the lesions (p = 0.288). Most lesions with anechoic areas were neoplasms (18 of 21 cases, 85.7%) and lesions without luminant areas suggested non-neoplastic disease (19 of 24 cases, 79.2%). Anechoic and luminant areas were significantly different between neoplasm and non-neoplasm groups (p = 0.003 and p < 0.001, respectively). The average additional time for EBUS required was 3.85 +/- 2.36 min (range 1 to 13 min). In conclusion, this uncomplicated and time-saving method of using EBUS image patterns could provide additional information to facilitate differential diagnoses.

Lung cancer at a medical center in Southern Taiwan.

BACKGROUND: In Taiwan, lung cancer is the second most common cause of cancer death and its incidence has been rising for the last 50 years. Shifts in histological types and differences in gender distribution have also accompanied the changed incidence of lung malignancies. METHODS: A total of 590 lung cancer patients were interviewed at Kaohsiung Chang-Gung Memorial Hospital, a medical center of Southern Taiwan, in 1997 and 2002. A retrospective investigation confirmed the age-adjusted incident rate in the hospital and demographic variations by different histological types for both genders. The statistical differences were evaluated using the heterogeneity chi-squared test and Cox regression. RESULTS: Results indicated that from 1997 to 2002, the age-adjusted rates of lung cancer decreased by 3.64% at the hospital. The largest percentage of increases in the age-adjusted rate was observed for small cell lung cancer (approximately 8.18%), whereas it decreased by 31.2% for squamous cell carcinoma and increased by 1.62% for adenocarcinoma. Female patients were found to be younger and had longer survival duration. The frequency was the highest for lesions in the upper lobe and patients had more advanced stage in all histological types. The 6-month relative survival rate between the two time-periods did not change appreciably. CONCLUSIONS: The age-adjusted incidence rate of adenocarcinoma at the hospital has increased, as well as small cell lung carcinoma. During the study period, early-staging diagnosis and 6-months survival rate did not change appreciably for the different histological lung cancer patients, suggesting that therapeutic and diagnostic advances, prevention or screening procedures had mild effects in southern Taiwan. Further studies are needed for confirmation of our results.