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Multimodal therapy is increasingly utilized in the management of esophageal cancer. The optimum dose and fraction is unclear, and this retrospective analysis compared two radiation regimens in multimodality regimens where the chemotherapy arm and the type and magnitude of surgery was constant. Ninety-three consecutive patients with squamous cell carcinoma or adenocarcinoma of the esophagus were reviewed. Forty patients received the conventional unit regimen of 44 Gy in 22 daily fractions (2 Gy/fraction), and 40 patients received an increased dose per fraction (40 Gy in 15 daily fractions [2.67 Gy/fraction]). All patients received two courses of 5-fluorouracil and cisplatin and surgery was carried out within 8 weeks of completing therapy. The median overall survival in the group receiving the increased dose per fraction group was 25 months compared with 17 months in the conventional dose per fraction group (P=0.08). At 1, 3, and 5 years, 66%, 38%, and 38%, of patients in the increased dose per fraction group were alive, compared with 65%, 18%, and 15% in the conventional dose per fraction group (P=0.13), respectively. In the conventional dose per fraction group, two patients developed esophageal fistulae and one patient died postoperatively due to hemorrhage from an aorto-enteric fistula. There were no significant differences observed between treatment groups, but a trend toward improved efficacy appeared with the increased dose per fraction.

Multimodal therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilized in gastroesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. However, up to 70% of patients show an incomplete or no response to the neoadjuvant regimen, and the identification of factors which predict a response would be of considerable clinical benefit. A retrospective analysis of a prospectively updated esophageal cancer database was performed. The predictive values of the following clinicopathological factors were investigated: age, sex, tobacco, alcohol, weight, clinical history, tumor type, site, length, width, morphology and differentiation. Statistical analysis was performed using Chi-square test with Pearson's test or Kruskal-Wallis test. One hundred and seventy-six patients were identified who had undergone neo-adjuvant chemoradiotherapy at St James's Hospital Dublin, between January 1990 and June 2003. A complete pathological response was seen in 40 cases (23%). There was a significant (P < 0.05) relationship between response to chemoradiotherapy and pretreatment tumor length. The median tumor length in the pCR group was 2 cm (1-5 cm) compared with 3 cm (2-7 cm) in non-responders (P < 0.05). Body weight, sex, tobacco or alcohol usage, tumor site, or differentiation were not predictive of response, although a trend (P = 0.08) was observed for squamous cell cancer compared with adenocarcinoma. Smaller tumor length was predictive of a greater response to chemotherapy and radiation therapy. This may reflect different tumor biology, perhaps with acquired resistance to treatment-induced apoptosis in the larger tumors. A simpler explanation is that the existing dose and treatment schedule for combination chemoradiotherapy is suboptimal in patients with larger tumors.

The National Cancer Institute (NCI) in Bethesda, Maryland has developed a broadcast-quality teleconferencing system known as the Telesynergy system to address the need to convey expert information between larger cancer centers and their remote counterparts. This system is available to "Partnerships in Science Program" partners across the U.S. Recently, it has been made available in Ireland under a "Memorandum of Understanding" among the Department of Health and Children of Ireland, the Department of Health and Social Services in Northern Ireland, and the NCI. The Telesynergy system is capable of transmitting not only broadcast-quality teleconferencing among several different sources, but also diagnostic-quality radiology and pathology images. Remote operated microscopes and video cameras allow biopsy specimens to be discussed and manipulated from several different locations. Smear preparations of blood, bone marrow, and other cytological specimens can be examined in detail by a remote operator. The system can also transmit conventional x-ray images and paper documents. The Telesynergy system ensures that each patient, regardless of location, will receive an expert assessment and be given optimal therapy. While the system is currently being developed in Ireland for use in oncology, it is hoped that other specialties can benefit from it in the future.

Ordered cell proliferation relies on a complex interplay between diverse cell types, interstitial stroma and organ vasculature. At a cellular level the response to growth stimuli is dependent on the bidirectional exchange of information between the cell membrane and nucleus. Specific regulatory molecules enable the transfer of growth signals and constitute the signal transduction pathways. In malignant disease deregulation of growth regulatory pathways is believed to contribute to the characteristic features of neoplasia, unrestricted cell proliferation, direct invasion of surrounding tissues and the formation of distant metastases. Many proto-oncogenes and oncogenes encode proteins that are strongly suspected to function in aberrant signal transduction (Table 1).