Faculty Bibliography

OBJECTIVES: The American College of Surgeons Oncology Group trial Z0060 is a prospective multi-institutional trial with a primary objective to evaluate whether positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) detects evidence of metastastic disease that precludes esophagectomy in patients with esophageal cancer who are surgical candidates after routine staging. METHODS: Patients with resectable, biopsy-proven carcinoma were enrolled after computed tomography of chest and abdomen demonstrated no evidence of metastasis. FDG-PET was performed according to specified standards. FDG-PET findings suggesting metastases required confirmation and patients without metastases on PET were expected to proceed to surgery. RESULTS: A total of 262 patients were registered. Of these, 199 were deemed eligible and of these, 189 patients were evaluable. Seventy-three patients were ineligible or unevaluable. Reasons for ineligibility included nonresectable disease by routine staging (39), missing or outdated staging procedures (12), PET technical protocol violations (10), no cancer (4), pre-PET induction therapy (3), claustrophobia (1), and other causes (4). There were 145 (78%) patients who went on to have surgery, 42 (22%) who did not, and 2 patients for whom the surgical status was not determined. The reasons for no resection included the following: M1 disease found by PET and confirmed (9), M1 disease found by PET and not confirmed (2), M1 disease at exploration not found by PET (7), decline or death before surgery (10), patient refusal of surgery (7), unresectable local tumor at exploration (5), and extensive N1 disease precluding operation (2). Eight (4.2%) patients undergoing resection had a recurrence in the first 6 months. CONCLUSIONS: Although 22% of eligible patients did not undergo esophagectomy, FDG-PET after standard clinical staging for esophageal carcinoma identified confirmed M1b disease in at least 4.8% (95% confidence interval: 2.2%-8.9%) of patients before resection. Unconfirmed PET evidence of M1 disease and regional adenopathy (N1 disease) led to definitive nonsurgical or induction therapy in additional patients.

Conventional treatments are not adequate for the majority of lung cancer patients. Conditionally replicating adenoviruses (CRAds) represent a promising new modality for the treatment of neoplastic diseases, including non-small cell lung cancer. Specifically, following cellular infection, the virus replicates selectively in the infected tumor cells and kills the cells by cytolysis. Next, the progeny virions infect a new population of surrounding target cells, replicate again and eradicate the infected tumor cells while leaving normal cells unaffected. However, to date, there have been two main limitations to successful clinical application of these CRAd agents; i.e. poor infectivity and poor tumor specificity. Here we report the construction of a CRAd agent, CRAd-CXCR4.RGD, in which the adenovirus E1 gene is driven by a tumor-specific CXCR4 promoter and the viral infectivity is enhanced by a capsid modification, RGD4C. This agent CRAd-CXCR4.RGD, as expected, improved both of the viral infectivity and tumor specificity as evaluated in an established lung tumor cell line and in primary tumor tissue from multiple patients. As an added benefit, the activity of the CXCR4 promoter was low in human liver as compared to three other promoters regularly used for targeting tumors. In addition, this agent has the potential of targeting multiple other tumor cell types. From these data, the CRAd-CXCR4.RGD appears to be a promising novel CRAd agent for lung cancer targeting with low host toxicity.

Injury from blunt or penetrating trauma to the esophagus is relatively rare. Treatment strategy is contingent on the clinical status of the patient, associated injuries, and the degree of esophageal injury and the time of injury until diagnosis. Although nonoperative intervention may be acceptable in highly selected patients with contained injuries or those who are more than 24 hours removed from the injury and are clinically stable, operative intervention is the most conservative and safest approach. There are many potential surgical approaches but resection or diversion should be discouraged. Operative approaches include either side of the neck or chest, and an abdominal approach for selected injuries. Sometimes combined incisions are needed. The goal of any operation for a traumatic esophageal injury is removal of infected material, debridement of the esophagus, assessment of the distal and proximal extent of the injury, decortication of the lung if the injury soils the pleural space, primary closure of the esophageal defect if possible with buttressing of the closure with autologous pedicles tissue or muscle flaps, and to ensure distal patency without esophageal pathology.

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.

OBJECTIVE: The treatment of non-small cell lung cancer depends on the stage, and this is clinically best determined by using fluorodeoxyglucose-positron emission tomography/computed tomography. We evaluated the effect smoking has on the accuracy of this test. METHODS: We performed a prospective cohort study evaluating the accuracy of clinical stage compared with pathologic stage between cigarette smokers and nonsmokers with non-small cell lung cancer. All patients were assigned a clinical TNM stage after fluorodeoxyglucose-positron emission tomographic/computed tomographic scanning and then underwent meticulously pathologic TNM staging. If N2, N3, or M1 negative, patients underwent thoracotomy with complete thoracic lymphadenectomy. The clinical and pathologic stages were compared. RESULTS: There were 246 patients: 52 never smoked (NS group), 112 quit at least 1 month before fluorodeoxyglucose-positron emission tomography/computed tomography (Q group), and 82 were still smokers (S group). The 3 groups were similar for stage and histology. The overall accuracy was 83%, 80%, and 64% for the NS, Q, and S groups, respectively (P = .03). The accuracy for the T status was 88%, 84%, and 86%; accuracy for the N2 lymph nodes was 96%, 75%, and 72%; and accuracy for the N1 lymph nodes was 92%, 78%, and 80%, respectively, favoring the NS group. The greater the pack-year history, the greater the N2 inaccuracy (P = .04). Multivariate analysis showed that status of smoking (P = .026) and maxSUV value (P = .014) were independent predictors of fluorodeoxyglucose-positron emission tomography/computed tomography accuracy. CONCLUSIONS: Patients with non-small cell lung cancer who continue to smoke at the time of their fluorodeoxyglucose-positron emission tomographic/computed tomographic scan have less accurate clinical staging compared with those who stopped 1 month before or who never smoked. As the pack-years increase, the accuracy for the N2 nodes decrease. Nonsmokers have the most accurate clinical staging.

BACKGROUND: Despite normal mediastinal (N2) lymph nodes shown on positron emission tomography (PET) and CT, some physicians routinely perform mediastinoscopy and/or endoscopic ultrasound fine-needle aspiration (EUS-FNA) in patients with non-small cell lung cancer (NSCLC). METHODS: A prospective trial on patients with NSCLC who were clinically staged N2 negative by both integrated PET/CT and CT scan. All underwent mediastinoscopy and EUS-FNA and if N2 negative underwent thoracotomy with thoracic lymphadenectomy. RESULTS: There were 153 patients (107 men). Of these, 136 patients were clinically staged N0 and 17 patients were clinically staged N1. Of the 136 patients who were staged as N0, 5 patients (3.7%) had positive EUS-FNA results (three in the subcarinal node), and 4 patients (2.9%) had positive mediastinoscopy results (all in the #4R node; one was N3). Six of the remaining 127 patients (4.7%) had N2 disease after resection. Seventeen patients were clinically staged as N1 by integrated PET/CT. Four patients (23.5%) had positive EUS-FNA results (two in the subcarinal node), 3 patients (17.6%) had positive mediastinoscopy results (all in #4R node; two were N2 and one was N3), and none of the remaining 10 patients had N2 disease after resection. Patients with unsuspected N2 disease were twice as likely (relative risk, 2.1; 95% confidence interval, 1.24 to 2.51; p = 0.02) to have a maximum standardized uptake value (maxSUV) > 10 and poorly differentiated cancer (relative risk, 2.1; 95% confidence interval, 1.14 to 2.38; p = 0.03). CONCLUSION: We do not recommend routine mediastinoscopy or EUS-FNA in patients who are clinically staged as N0 after both integrated PET/CT and CT. However, these procedures should both be considered in patients clinically staged as N1 after PET/CT, and/or in those with adenocarcinoma, upper-lobe tumors, or tumors with a maxSUV > or = 10.

OBJECTIVE: Bronchogenic malignancy is the number one cause of cancer deaths in both men and women worldwide. National registry-based studies have shown gender disparity in clinicopathologic characteristics and in survival. This study evaluates the risk factors and trends of lung cancer between genders. METHODS: A prospective cohort of consecutive patients with non-small cell lung cancer (NSCLC) who were carefully clinically (all underwent dedicated positron emission tomography scans) and pathologically staged with stage I, II, or III disease underwent homogenous treatment algorithms and were followed up over a period of 7 years. Primary outcomes were 5-year survival and response to neoadjuvant therapy. RESULTS: There were 1,085 patients (671 men and 414 women). Groups were similar for race, pulmonary function, smoking history, comorbidities, neoadjuvant therapy, histology, and resection rates. Women were younger (p = 0.014), had a higher incidence of adenocarcinoma (p = 0.01), and presented at an earlier pathologic stage (p = 0.01) than men. The overall age-adjusted and stage-adjusted 5-year survival rate favored women (60% vs 50%, respectively; p < 0.001). Women had better stage-specific 5-year survival rates (stage I disease, 69% vs 64%, respectively [p = 0.034]; stage II disease, 60% vs 50%, respectively [p = 0.042]; and stage III disease, 46% vs 37%, respectively [p = 0.024]). Women who received neoadjuvant chemotherapy alone (n = 76) were more likely to be a complete or partial responder than men (n = 142; p = 0.025). CONCLUSIONS: Despite uniform staging and treatment, the 5-year survival rate of women with stage I to III NSCLC was better than men overall and at each stage. Women are more likely to have adenocarcinoma, to present with earlier stage disease, and to be younger. Interestingly, women respond better to neoadjuvant chemotherapy.

BACKGROUND: Treatment of non-small cell lung cancer depends on stage. Patients with T4 lesions represent a heterogeneous group. METHODS: A case-control study of patients with pathologically proven, node-negative T4 lesions (T4 N0 M0) was conducted. Patients with T4 disease were stratified as T4 from a satellite nodule (T4-satellite) or T4 from local invasion (T4-invasion). T4-satellite patients were matched 1:4 for sex and histology with resected control patients with stage IA, IB, and IIA non-small cell lung cancer and matched 1:3 with stage II non-small cell lung cancer. Survival and the maximal standardized uptake value on F-18 fluorodeoxyglucose-positron emission tomography scans were compared. RESULTS: There were 337 patients, 26 patients with T4-satellite lesions, 25 with T4-invasion lesions, and 286 controls (104 patients with T1 N0 M0, 104 with T2 N0 M0, and 78 with T1 N1 M0 or T2 N1 M0 lesions). The two T4 groups were similar for age, race, sex, and neoadjuvant therapy rates. The 5-year survival was 80% for the T1 N0 M0 patients, 68% for T2 N0 M0, 57% for T4-satellite N0 M0, 45% for T1 N1 M0 or T2 N1 M0, and 30% for the T4-invasion N0 M0 patients (p = 0.016). Multivariate analysis showed that only the type of T4 impacted survival (p = 0.011). The median maximal standardized uptake values of the cancers were 4.2 for T1 N0 M0, 4.8 for T4-satellite, 5.4 for T2 N0 M0, 7.8 for T1 N1 M0 or T2 N1 M0, and 8.8 for the T4-invasion patients. CONCLUSIONS: Larger studies are needed; however, patients with T4-satellite non-small cell lung cancer who undergo complete resection have survival and maximal standardized uptake values similar to patients with stage IB and stage IIA lesions. Their survival is significantly better than those with T4-invasion. Patients with T4-satellite N0 M0 lesions should not be classified as stage IIIB and should not be grouped with patients with T4-invasion, and resection should be considered.