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The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction ( E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy ( CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib ( G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a ( American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000 mg/m2/day) and cisplatin (20 mg/m2/day) as continuous infusions over days 1-4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250 mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no- G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no- G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [ HR] 0.64, 95% confidence interval [ CI] = 0.45-0.91, P = 0.012), recurrence-free survival ( HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence ( HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer. [ABSTRACT FROM AUTHOR]

SUMMARY Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries ( P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated ( P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated. [ABSTRACT FROM AUTHOR]

Our objectives were to determine the likelihood of true folate deficiency among patients tested for this disorder, to identify whether there were differences between the clinical indications for folate testing in folate-normal and folate-deficient patients and to assess the impact of a diagnosis of folate deficiency on patient management. The results of all blood samples analyzed for serum and erythrocyte folate levels during the year 2001 at the Cleveland Clinic Foundation were retrieved. Folate deficient patients were identified and their medical charts were reviewed to determine the indications, patient characteristics, and impact of this diagnosis on patient management. For comparison, medical chart review was also conducted on a control group composed of an equal number of randomly selected patients with normal serum folate values. A total of 6024 (4689 serum and 1335 erythrocyte) samples from 4985 patients were collected. In the study, 77 (1.6%) of the serum folate levels, from 74 patients, were identified as low. When compared with the control group, patients with low serum folate levels had lower hemoglobin and a greater red cell distribution width. Mean corpuscular volume, however, did not differ between the two groups. No significant differences in the clinical indications for serum folate level determinations could be identified. Only 39 of the 74 patients with low serum folate levels were given folate replacement, representing only 0.9% of the clinically suspected and tested patients. We conclude that determination of serum folate level infrequently led to appropriate folate replacement therapy. Moreover, even when suspected, true folic acid deficiency is rare and clinical indications are not helpful in diagnosis. [ABSTRACT FROM AUTHOR]