Faculty Bibliography

OBJECTIVE: Video-assisted lobectomy is an increasingly used technique to treat patients with non-small cell lung cancer but it does not usually afford lung palpation. METHODS: A prospective study was conducted on patients with tumors amenable to video-assisted lobectomy (noncentral lesion and <5 cm) who underwent open lobectomy via thoracotomy. All patients underwent 64-slice helical computed tomographic scan with intravenous contrast at 5-mm intervals and had integrated 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography computed tomography 30 days or less before thoracotomy. Unsuspected malignant pulmonary nodules that were palpated and removed (from a different lobe than the one resected) and that were not imaged preoperatively were defined as cancer that would have been missed by video-assisted lobectomy. RESULTS: From January 2006 to February 2007, 166 patients had non-small cell lesions that were resected via thoracotomy, despite being amenable to video-assisted surgery, by one surgeon. Thirty-seven (22%) patients had pulmonary nodules that probably would have been missed by video-assisted lobectomy; 14 (8.4%) of these nodules were malignant. These were unsuspected M1 pulmonary lesions in 9 patients and unsuspected different types of primary non-small cell lung cancers in 5 patients. All missed lesions were less than 6 mm and in different lobes from the one resected. Nine (64%) of these 14 patients' primary known lesions were pathologic T1 lesions. Nine patients received adjuvant chemotherapy because of these unsuspected M1 nodules. CONCLUSIONS: Open lobectomy that affords palpation of the rest of the lung may discover nonimaged malignant pulmonary nodules in different lobes in 8% to 9% of patients with non-small cell lung cancer despite preoperative fine-cut chest computed tomographic scan with contrast and integrated integrated 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography computed tomographic scanning. The clinical impact of these findings is unknown.

BACKGROUND: Transesophageal EUS-guided FNA (EUS-FNA) is safe, accurate, and cost effective in staging patients with non-small-cell lung cancer (NSCLC). However, the impact of EUS-FNA on patient survival has not been demonstrated. OBJECTIVE: To determine the impact of metastatic disease in mediastinal lymph nodes as determined by EUS staging on treatment choice and survival in patients with NSCLC. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Tertiary university-based referral center. PATIENTS: Patients with biopsy-proven NSCLC who underwent staging EUS-FNA. The relationship between the EUS nodal status and patient survival was evaluated. Cox proportional hazards models were used to determine the significance of EUS nodal status and patient characteristics on patient survival. MAIN OUTCOMES MEASUREMENTS: Impact of EUS-FNA on therapy and survival in patients with NSCLC. RESULTS: Of 125 patients with NSCLC, EUS-FNA confirmed metastatic disease in 46% of the patients. Patients who were node positive were more likely to receive chemotherapy and/or radiation therapy and were less likely to undergo surgery compared with patients who were node negative (P< .0001). Patients with N2 or N3 disease by EUS-FNA had a shorter survival time than patients who were node negative (P= .004). Adjusting for age, race, and sex, EUS-FNA was the most important predictor of survival of patients with NSCLC in this cohort of patients (hazard ratio 2.34, 95% CI 1.31-4.21). LIMITATIONS: Lack of surgical reference standard in all patients and referral to a tertiary center. CONCLUSIONS: Patients with node-positive NSCLC as detected by EUS-FNA have a shorter survival time compared with patients who were node negative. They are more likely to receive neoadjuvant therapy and less likely to receive surgery. Preoperative EUS-FNA is a minimally invasive technique that provides important prognostic information in patients with NSCLC.

Patients with malignant pleural mesothelioma and negative N2 stage lymph nodes may benefit from extrapleural pneumonectomy with adjuvant therapy. The objective of this study is to describe the use of EUS-FNA to determine N2 stage status in patients with mesothelioma and its impact in the management of such patients. Six patients (mean age, 62 yr; median age, 63 yr; range, 52-70 yr; 5 men; 1 woman) underwent EUS-FNA for staging of N2 lymph nodes from July 2000 to July 2006. Follow-up included operative notes, treatment summaries, and surgical pathology. Eight sites were aspirated: four subcarinal lymph nodes, three aorto-pulmonary window lymph nodes, and one paraesophageal mass. Two of 8 (25%) aspirates were positive for metastatic disease in two different patients. Two false negative EUS-FNAs were observed and were attributed to sampling error not diagnostic error. No complications were observed. EUS-FNA is a safe N2 node staging technique in patients with mesothelioma. A positive N2 lymph node by EUS-FNA may be a contraindication to definitive surgery in patients with malignant mesothelioma.

BACKGROUND: The ideal time to repeat a 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan to accurately restage a patient after neoadjuvant chemoradiotherapy for non-small cell lung cancer (NSCLC) is unknown. METHODS: This retrospective cohort study used a prospective database of patients who underwent neoadjuvant chemoradiotherapy, an initial and repeat FDG-PET/CT scan, and pathologic staging. The accuracy of the clinical stage suggested by repeat FDG-PET/CT was compared with the actual pathologic stage. Receiver operating characteristic (ROC) curves were used to determine when it was most accurate to repeat the FDG-PET/CT after the completion of the last dose of chest radiation. RESULTS: The study comprised 109 patients, 93 of whom patients received 60 Gy (or higher) of radiotherapy. The median time to restaging was 24 days (range, 2 to 88 days). ROC analysis showed the optimal time to restage patients was 26 days for overall staging (area under the curve [AUC], 0.88) and 29 days for N2 restaging (AUC, 0.82). The accuracy for overall stage was 3 (38%) of 8 for patients for less than 10 days, 28 (72%) of 39 for patients between 11 and 20 days, 42 (88%) of 49 between 21 and 30 days, and 8 (62%) of 13 for 31 days or more. The accuracy for these time intervals for the restaging of the N2 lymph node was 50% (1/2) 40% (2/5), 88% (7/8), and 100% (3/3), respectively. CONCLUSIONS: The optimal time to perform a repeat FDG-PET/CT scan after the completion of neoadjuvant chemotherapy and high-dose radiotherapy to maximize its accuracy for restaging patients with NSCLC is about 1 month after the last dose of radiation.

BACKGROUND: The purpose of this study was to assess the efficacy of the different techniques of lymph node biopsies in patients with suspected metastatic non-small cell lung cancer (NSCLC) in the subaortic (station #5) and paraaortic (station #6) lymph nodes. METHODS: This was a retrospective cohort study conducted of a prospective database of patients between January 2003 and June 2006 with suspected N2 disease only in the #5 or #6 lymph nodes, or both. All patients had integrated 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography, and nodal biopsy or thoracotomy, or both, with complete thoracic lymphadenectomy. RESULTS: There were 112 patients with clinically suspected N2 disease in lymph node stations #5 or #6, or both. The primary tumor was in the left upper lobe in 98 (88%) and in the left lower lobe in 14 (13%), and 58 had pathologic N2 disease in #5 or #6 lymph node stations only. Mediastinoscopy, used in all patients found, unsuspected N3 disease in 4 patients (3.6%) and N2 (#4L) disease in 12 (11%). Endoscopic ultrasound with fine needle aspiration (EUS-FNA), implemented in 62 patients (56%), correctly identified 41 patients (66%). Left single-incision video-assisted thoracic surgery (VATS) was used in 39 patients and was correct in 100%. Of the 58 patients, 53 (91%) completed neoadjuvant chemoradiotherapy, followed by resection, and their 5-year survival was 64%. CONCLUSIONS: EUS-FNA is less accurate for the #5 and #6 lymph node stations than left VATS. We prefer left VATS over the Chamberlain procedure for patients with suspected nodal metastases isolated only to #5 or #6 stations, and if positive, we prefer neoadjuvant therapy. The advantage of neoadjuvant therapy followed by resection compared with resection followed by adjuvant therapy remains controversial; and hence, the role for biopsy of these nodes is also controversial.

BACKGROUND: Factors that predict poor survival or increased risk of recurrence for patients with N1 disease may be dependent on tumor characteristics. METHODS: This study was a retrospective review of a prospective database of consecutive patients who had clinical or pathologic N1 non-small cell lung cancer (NSCLC) who underwent preoperative 2-[18F] fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) scans and complete resection with thoracic lymphadenectomy. RESULTS: There were 135 patients (88 men). The 5-year disease-free rate was 55%. Kaplan-Meier analysis showed that poor differentiation (p = 0.036), multiple N1 stations (p = 0.010), and the lack of adjuvant chemotherapy (p = 0.039) were all associated with a shorter 5-year disease-free rate. Multivariate disease-free analysis demonstrated that only multiple stations (p = 0.002) were independently associated with recurrence. The overall 5-year survival was 48%. Univariate analysis showed that multiple nodes within one station (p = 0.016), multiple station involvement (p = 0.041), and lack of adjuvant chemotherapy (p = 0.039) and moderate-to-poor tumor differentiation (p = 0.046) were associated with decreased survival. Multivariate analysis found that multiple stations, multiple nodes, and lack of adjuvant chemotherapy were independent predictors of poor survival. Integrated PET-computed tomography (CT) was significantly more sensitive for staging N1 disease than dedicated FDG-PET (p = 0.032). Neoadjuvant chemotherapy given to 48 nonrandomized patients did not seem to impact disease recurrence or overall 5-year survival rates (p = 0.349). CONCLUSIONS: Factors that predict a poor outcome in patients with resected N1 NSCLC are the involvement of multiple N1 stations, multiple N1 nodes, and the lack of adjuvant chemotherapy. Integrated PET-CT is more sensitive for detecting N1 disease then dedicated PET. These data may influence preoperative or postoperative therapy, or both.

BACKGROUND: The impact that smoking cigarettes has on the characteristics and survival of patients with non-small cell lung cancer (NSCLC) is disputed. METHODS: A retrospective cohort study using a prospective database of patients with NSCLC over a 6-year period. Clinical and histologic characteristics and survival rates were compared between smokers and never-smokers. RESULTS: There were 730 patients; 562 patients (77%) were smokers and 168 patients (23%) were never-smokers. The overall 5-year survival rate was greater in never-smokers (64%) compared to smokers (56%; p = 0.031). Never-smokers were more likely to be younger (p = 0.04), female (p = 0.01), symptomatic at the time of presentation (p < 0.001), have poorly differentiated tumors (p = 0.04), and have a higher maximum standardized uptake value (maxSUV) on positron emission tomography (PET) (p = 0.026) than smokers. The stage-specific 5-year survival rate was greater for never-smokers compared to smokers for stage I disease (62% vs 75%, respectively; p = 0.02), stage II disease (46% vs 53%, respectively; p = 0.09), and stage III disease (36% vs 41%, respectively; p = 0.13). The 5-year survival rate was significantly lower in patients who had a smoking history of > 20 pack-years. CONCLUSIONS: Never-smokers in whom NSCLC develops are more likely to be young, female, and have poorly differentiated tumors with higher maxSUV values on PET scans. Never-smokers with early-stage cancer have a significantly better survival rate than smokers. Patients with a smoking history of > or = 20 pack-years have worse survival. Thus, smoking not only causes lung cancer, but once NSCLC is diagnosed, the prognosis becomes worse. A biological, hormonal, and genetic explanation is currently lacking to explain these findings, and these data may help to improve treatment and surveillance.