Background: Cancer of the esophagus continues to be a formidable treatment challenge. In the past, patients who were not candidates for surgery were treated with radiotherapy alone. The results were poor, with five-year survival rates of only about 5 percent. These patients were often in poor medical condition with multiple comorbid medical problems who could not tolerate therapy well.

Progress is being made. Large, randomized trials by national cancer groups such as ECOG and RTOG have shown the superiority of combined chemotherapy and radiotherapy over radiotherapy alone with acceptable toxicity.

External beam radiotherapy: To minimize the toxicity of combined therapy, good radiotherapy techniques are essential. Tumor volumes (including the primary tumor and the draining lymph nodes) are defined by information from the endoscopy, CT scan and barium swallow done at the time of simulation to precisely localize the extent of the tumor and the position of the esophagus, especially in relation to the normal lungs, heart and spinal cord. A computer isodose plot is generated, showing the dose to the target volume as well as to the critical normal tissues (Figures 6A to 6D). Multiple-shaped RT fields are used with customized lead blocking to protect the normal tissues. Fields are verified every week. Treatments are given with linear accelerators, and patients are treated daily for approximately six to seven weeks. Patients are monitored closely for side effects including esophagitis, pneumonitis and low blood counts. Acute side effects usually resolve within a few weeks after the completion of therapy.

Figures 6A to 6D -- Treatment planning simulation fields for radiotherapy

Figure 6A

Figure 6B

Figure 6C

Figure 6D

Endoscopic high-dose-rate radio-brachytherapy: The dose to the tumor can be increased with the use of endo-esophageal implants. This involves placing a catheter in the esophagus at the time of endoscopy. The target volume to cover the area of the tumor seen at endoscopy is again verified at the time of simulation. A radioactive source is then placed into the catheter. Previously, this was done with a low-dose-rate Iridium-192 source. These sources would remain in place for approximately 24 to 48 hours, which would require an inpatient stay for that period of time. Recently, the low-dose-rate implants have been replaced by high-dose-rate implants, which can be done as an outpatient. The HDR Iridium-192 source can deliver the same dose in just minutes. The patient is admitted through the Short Procedure Unit and taken to the Esophagoscopy Laboratory for catheter placement. From there, the patient goes to Radiation Therapy, where treatment planning is carried out and the radiation is given. The catheter is removed, and the patient is discharged home. The result is greater patient comfort and convenience. Typically, three to four brachytherapy sessions are done about one week apart.

Intraoperative radio-brachytherapy: Another way to deliver a high dose of irradiation to the tumor is to implant radioactive seeds directly into the region of the tumor. At Allegheny General, we have been placing Iodine-125 vicryl mesh intraoperatively with the thoracic surgeon for esophageal and lung cancers. The Iodine-125 seeds are embedded in suture material like beads on a string. We suture the seeds into an absorbable vicryl mesh to cover the area of the tumor bed. The thoracic surgeon then places the mesh directly into the tumor bed. The Iodine-125 seeds remain in permanently. The iodine seeds have a low activity; however, they deliver a high dose of irradiation locally of about 12,000 cGy. This is much more than can be given with external beam RT, but because the dose falls off very rapidly, minimal dose is delivered to the normal tissues. In addition, there is minimal exposure to hospital personnel or family members, so no special precautions need to be taken while the patient is in the hospital or at home after discharge.

Preoperative radiotherapy: Improved results have also been seen recently with the use of preoperative combined chemotherapy and radiotherapy followed by surgery. A recent randomized study from Ireland, published in the New England Journal of Medicine, showed increased survival with neoadjuvant chemotherapy and radiotherapy plus surgery as compared to surgery alone. At Allegheny General, we are initiating a protocol involving chemotherapy and external beam radiotherapy followed by esophagectomy with intraoperative I-125 vicryl mesh radio-brachytherapy placement.

Palliative radiotherapy: Radiotherapy is also effective for palliation of symptoms such as dysphagia in locally advanced or metastatic esophageal carcinoma. External beam radiation therapy is a noninvasive and relatively rapid way to palliate dysphagia. High-dose-rate endoesophageal radio-brachytherapy can also be used in this setting to provide a quick, high dose of radiation therapy internally to alleviate symptoms. In addition, the radiation can be combined with chemotherapy, photodynamic therapy, Nd:YAG laser and endoesophageal stent placement. We are initiating a clinical protocol for the palliation of dysphagia involving external beam radiation therapy with or without chemotherapy followed by either photodynamic therapy and laser ablation, or esophageal stents and high-dose-rate endo-esophageal radio-brachytherapy.

Summary: Radiation therapy remains an important approach for the treatment of esophageal carcinoma. It can be used alone or, preferably, with other treatment modalities (i.e. chemotherapy and possible surgery) to improve the overall success in the management of esophageal carcinoma. The team of radiation oncologists, medical oncologists and thoracic surgeons at the Allegheny Center for Lung and Thoracic Disease works in an integrated fashion to provide the most important continuum of care for the patient suffering from this disorder.

References

1. Sischy B, et al. Interim report of EST phase III protocol for the evaluation of combined modalities in the treatment of patients with carcinoma of the esophagus. Proceedings of ASCO Vol. 9, 1990;105.

2. Herskovic A, et al. Combined chemotherapy and radiotherapy compared with radiosurgery alone in patients with cancer of the esophagus. New Eng J Med 1992;326:1593-1598.

3. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TPJ. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. New Eng J Med 1996;335:462-467.

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