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Reducing Toxicity of Combined-Modality Treatment for Esophageal Cancer

Reducing Toxicity of Combined-Modality Treatment for Esophageal Cancer

SAN ANTONIO, Texas—Although combined-modality therapy is considered
the standard of care for patients with advanced esophageal cancer, the
anatomical and physiological characteristics of the esophagus pose serious
limitations on dose escalation. Cytoprotective strategies that might allow
clinicians to circumvent these limitations were reviewed by Charles R.
Thomas. Jr., MD.

The mucosal layer of the esophagus is a rapid turnover cell-renewal
system and is dominant in early-responding tissue, Dr. Thomas noted.
"Eventually there is some regeneration with these tissues if the dose
isn’t too high. In mouse studies, large fractions produce vacuolization
and thinning of the keratinized squamous cell layer by day 3, but there are
foci of proliferating basal cells and regeneration of epithelium with
concurrent areas of complete denudation by days 7 to 14, and near complete
regeneration of esophageal layers by day 21," Dr. Thomas explained. He
is associate professor and vice chairman of the Department of Radiation and
adjunct associate professor of medical oncology at the University of Texas
Health Science Center in San Antonio and the San Antonio Cancer Institute.

Acute changes in humans closely parallel the murine model. However, not
all patients with acute esophagitis have direct pathologic correlation.

"Late changes are mostly related to muscle wall problems. The basal
epithelial layer contains the target cells accounting for most acute
radiation effects. Late effects are predominantly due to muscle cell layer
compromise and to infiltration of fibroblasts and inflammatory cells into
the esophageal muscle wall," Dr. Thomas said.

Higher Toxicity

Radiation Therapy Oncology Group study RTOG 85-01 randomized patients
with esophageal cancer to radiation therapy alone vs chemoradiation therapy.
Toxicity in a number of areas was much higher in patients who received the
combined-modality regimen despite a benefit in survival.

"Intergroup protocol 0123 failed to show that dose escalation of
radiation therapy in a multi-institutional setting could be done
safely," Dr. Thomas said.


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