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1.  Phase III Trial of Trimodality Therapy With Cisplatin, Fluorouracil, Radiotherapy, and Surgery Compared With Surgery Alone for Esophageal Cancer: CALGB 9781 
Purpose
The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery, although primary radiation therapy with concurrent chemotherapy produces similar results. As both have curative potential, there has been great interest in the use of trimodality therapy. To this end, we compared survival, response, and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer.
Patients and Methods
Four hundred seventy-five eligible patients were planned for enrollment. Patients were randomly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2/d for 4 days on weeks 1 and 5 concurrent with radiation therapy (50.4 Gy total: 1.8 Gy/fraction over 5.6 weeks) followed by esophagectomy with node dissection.
Results
Fifty-six patients were enrolled between October 1997 and March 2000, when the trial was closed due to poor accrual. Thirty patients were randomly assigned to trimodality therapy and 26 were assigned to surgery alone. Patient and tumor characteristics were similar between groups. Treatment was generally well tolerated. Median follow-up was 6 years. An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy (exact stratified log-rank, P = .002). Five-year survival was 39% (95% CI, 21% to 57%) v 16% (95% CI, 5% to 33%) in favor of trimodality therapy.
Conclusion
The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer, and support trimodality therapy as a standard of care for patients with this disease.
doi:10.1200/JCO.2007.12.9593
PMCID: PMC5126644  PMID: 18309943
2.  Differential Matrix Metalloproteinase Levels in Adenocarcinoma and Squamous Cell Carcinoma of the Lung 
Objective
The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes with diverse proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns would differ between NSCLC histologic type.
Methods
NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n=22) or adenocarcinoma (n=19) histology. Absolute concentrations for each of the MMP subclasses; collagenases (MMP-1, 8, -13), gelatinases (MMP-2,-9), lysins (MMP-2, -7) and elastase (MMP-12) were determined by a calibrated and validated multiplex suspension array.
Results
Overall, MMP levels were significantly increased in NSCLC compared to normal. For example, MMP-1 and MMP-7 increased by approximately 10 fold in NSCLC (p<0.05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1,-8,-9 and -12 increased by over 4-fold in squamous cell versus adenocarcinoma (p<0.05). In those patients who recurred within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (p<0.05).
Conclusion
Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets.
doi:10.1016/j.jtcvs.2009.12.016
PMCID: PMC2844342  PMID: 20304142
matrix metalloproteinases; lung cancer; multiplex; recurrence
3.  A Simple Two-Gene Prognostic Model for Adenocarcinoma of the Lung 
Objective
We hypothesized that clinical outcome of resected early stage adenocarcinoma of the lung can be predicted by the expression of a few critically important genes as measured by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) in formalin fixed paraffin-embedded (FFPE) primary tumors.
Methods
Twenty-two prognostic genes for the metastatic phenotype were identified through cDNA microarray analysis of four cancer cell lines and bioinformatics analysis. Expression levels of a subset of these genes (n=13) were measured by real-time RT-PCR in FFPE primary adenocarcinoma from patients who recurred within 2 years (n=9) and who did not recur (n=11). ROC curve analysis was performed to establish prognostic values of single genes. The most informative gene was combined with the remaining genes to determine if there was a particular pair(s) that yielded high diagnostic accuracy. A small validation study was performed.
Results
ROC curve analysis of the single genes revealed that high expression of CK19 was associated with non-recurrence (AUC=0.859, CI=0.651–0.970). The CK19/EpCAM2 gene ratio had the most reproducible prognostic accuracy, followed by the CK19/P-cadherin ratio. A Kaplan Meier survival analysis generated from the CK19/EpCAM2 ratio resulted in highly significant curves as a function of marker positivity (p=0.0007; HR=10.7). Significance declined but was maintained in the validation study.
Conclusions
This preliminary study provides evidence that the CK19/EpCAM2 and/or CK19/P-cadherin ratio(s) may be a simple and accurate prognostic indicator of clinical outcome in early stage adenocarcinoma of the lung. If further validation studies from large patient cohorts confirm the results, adjuvant therapy could be targeted to this high risk group.
doi:10.1016/j.jtcvs.2007.10.058
PMCID: PMC2774741  PMID: 18329483
lung cancer; molecular markers
4.  Underuse of Surgical Resection for Localized, Non–Small Cell Lung Cancer Among Whites and African Americans in South Carolina 
The Annals of thoracic surgery  2008;86(1):220-227.
Background
Early studies using Medicare data reported racial disparities in surgical treatment of localized, non–small cell lung cancer. We analyzed the independent effect of race on use of surgical resection in a recent, population-based sample of patients with localized non–small cell lung cancer, controlling for comorbidity and socioeconomic status.
Methods
All cases of localized non–small cell lung cancer reported to our state Cancer Registry between 1996 and 2002 were identified and linked to the Inpatient/Outpatient Surgery Files and 2000 Census. Comorbidity (Romano-Charlson index) was calculated using administrative data codes. Educational level and income were estimated using census data. Characteristics of white and African American patients were compared using ×2 tests. Odds ratios of resection and 95% confidence intervals were calculated using logistic regression.
Results
We identified 2,506 white and 550 African American patients. African Americans were more likely to be younger, male, not married, less educated, poor, and uninsured or covered by Medicaid (all p < 0.0001), and to reside in rural communities (p = 0.0005). Use of surgical resection across races was lower than previously reported, and African Americans were significantly less likely to undergo surgery compared with whites (44.7% versus 63.4%; p < 0.0001). Even after controlling for sociodemographics, comorbidity, and tumor factors, the adjusted odds ratio for resection for African Americans was 0.43 (95% confidence interval, 0.34 to 0.55).
Conclusions
Underuse of surgical resection for localized, non–small cell lung cancer is a persistent problem, particularly among African Americans. Further studies are urgently needed to identify the patient, physician, and health system–related factors underlying these observations and optimize resection rates for non–small cell lung cancer.
doi:10.1016/j.athoracsur.2008.02.072
PMCID: PMC4161276  PMID: 18573427

Results 1-4 (4)