Esophageal cancer: current and emerging therapy modalities.

During the last few years, there has been a gradual increase in treatment options for patients with esophageal malignancies. Several clinical studies have been performed, covering not only radiation and chemotherapy, but also the introduction of novel biological agents into the treatment arsenal. Patients with esophageal carcinoma are now offered second-line and sometimes even third-line treatments, and the number of research protocols is increasing. Despite the newly awakened interest in this malignancy, the overall 5-year survival rate has remained at approximately 10% since the 1980s. This review contains a compilation of available studies of esophageal malignancies and discusses current treatment options as well as newly developed therapies targeted at growth factor receptors.

Telomerase activity is not a key determinant of sensitivity to standard cytotoxic drugs in human esophageal carcinoma cell lines.

The aim of the present study was to investigate if basal telomerase activity levels may predict sensitivity to cytotoxic drugs in a panel of human esophageal carcinoma cell lines. The TRAPeze telomerase detection assay was used to investigate telomerase activity in the cell lines. Cytotoxic drug sensitivity for 20 standard cytotoxic agents was assessed using the fluorometric microculture cytotoxicity assay (FMCA). Telomerase activity was detected in all cell lines with a broad range of activity levels. Drug sensitivity also varied considerably between the cell lines. Except for a P value towards a correlation between mitoxantrone and telomerase activity (P=0.054), no statistically significant correlation was found between telomerase activity levels and sensitivity to investigated drugs, including key drugs such as cisplatin (P=0.9), 5-fluorouracil (P=0.8) and doxorubicin (P=0.54). We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines.

High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study.

BACKGROUND: Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. METHODS: We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. RESULTS: HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). CONCLUSION: Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma.

The role of cystatin C and the angiogenic cytokines VEGF and bFGF in patients with esophageal carcinoma.

Angiogenesis is the formation of new blood vessels out of the existing vascular bed. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent circulating angiogenic factors, whereas cystatin C is one of the most important extracellular inhibitors of several cysteine proteinases. Because proteases degrade interstitial connective tissue and basement membranes during tumor growth and metastasis, an association between cystatin C and the angiogenic factors seems plausible. The primary aim of the present study was to investigate if such a correlation exists between these serum markers. The secondary aim was to determine the prognostic value of these circulating cytokines and cystatin C, collected prior to therapy, in patients with esophageal carcinoma.A total of 42 patients with esophageal carcinoma donated serum samples prior to therapy. VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p = 0.04), whereas bFGF was not (p = 0.08). VEGF was significantly correlated with cystatin C (p = 0.027). Survival analysis showed that VEGF regarded as a continuous variable was associated with a significantly poorer survival in the univariate analysis (p = 0.023); however, this was not found for bFGF (p = 0.46). Neither of the angiogenic factors were associated with survival in the multivariate analysis. In the univariate analysis, cystatin c was correlated with survival (p = 0.01), but this was not found in the multivariate analysis (p = 0.28). In conclusion, VEGF was correlated with cystatin C, possible explanations being discussed in the present article. Results of the present study indicate that use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, appears limited.

The presence of anti-p53 antibodies in sera from patients with oesophageal carcinoma: correlation to treatment, tumour volume and survival.

BACKGROUND: A correlation between mutations in the p53 gene and the presence of anti-p53 antibodies in sera has been reported. The aim of the present study was to analyse anti-p53 antibodies in sera from patients with oesophageal carcinoma and their implications for clinical outcome and survival PATIENTS AND METHODS: Between 1996 and 2002, patients treated for oesophageal carcinoma at the Department of Oncology, Uppsala University Hospital, Sweden, were asked to donate serum samples during treatment and follow-up. A total of 42 patients, with serum samples collected prior to therapy, were analysed for expressions of anti-p53 antibodies using a commercially available sandwich ELISA (Dianova, Hamburg, Germany). RESULTS: Anti-p53 antibodies did not correlate with investigated laboratory parameters. No correlation between anti-p53 antibodies and tumour volume was found (n=31; r=0.08;p=0.66). Anti-p53 antibodies as a continuous variable was not associated with survival (p = 0.42). Neither was the presence of anti-p53 antibodies (according to defined cut-off of 1.1, provided by the manufacturer) associated with survival (p = 0.99). CONCLUSION: The presence of anti-p53 antibodies correlated neither to tumour volume nor to clinical parameters.

A retrospective study focusing on clinical predictive factors in 126 patients with oesophageal carcinoma.

In Sweden, approximately 400 patients are diagnosed each year with oesophageal carcinoma. Despite the introduction of different treatment schedules, only modest improvements in survival have been accomplished. To be able to select patients in whom a more favourable outcome of radiation/-chemotherapeutic treatment could be expected, the present study reviewed the charts from 126 consecutive patients with oesophageal carcinoma. All patients were treated at the Department of Oncology, Uppsala University Hospital, Sweden, between 1990 and 2000. The charts were reviewed with focus on known and potential prognostic factors. Performance status, smoking habits, swallowing function, localisation of the tumour, leucocytes and albumin levels at first admittance, and stage of the disease were prognostic factors. However, performance status and stage of the disease only remained as significant independent prognostic factors in the multivariate analysis (both with p-values < 0.001). The results imply that further characterisation of tumour biology in oesophageal carcinoma is needed to find additional predictive factors for survival and future treatment strategies.