What is the updated evaluation of the results of radiotherapy or brachytherapy in adenocarcinomas of the esophagogastric junction? How can the tumor response after irradiation be evaluated?
B.G. Taal, B.M.P. Aleman, H. Boot (Amsterdam)
At the time of the diagnosis, the majority of patients with esophageal cancer are in an advanced stage of their disease, when "curative surgery" is no longer a real option and hence prognosis is poor. Palliation of the most invalidating symptom, dysphagia, is the main goal of treatment. Fast relief of dysphagia and subsequently improved quality of life may be achieved by various treatment modalities, such as laser coagulation, stenting or radiotherapy especially brachytherapy. The choice of treatment is based on tumor stage, but patients characteristics (old age, malnutrition and additional pulmonary or cardial diseases) may very well limit the therapeutic possibilities.
When aiming at rapid tumor regression at the cost of minimal side effects, brachytherapy has become a useful treatment modality in recent years, when application techniques changed and remote control techniques using high-dose-rate equipment became available. The apparent advantage of brachytherapy is the delivery of a high radiation dose directly on the tumor and not to the healthy surrounding tissues. The main disadvantage is a rapid decrease of radiation dose beyond 1 cm resulting in a much lower and less effective dose to the outer layers of the tumor process. Anyway, a single application induced improvement of dysphagia in 54% as described in a large series of 197 patients . However, this figure was applicable to patients with a short life expectancy of only 4 months, similar to our experience  and probably comparable with the results of the new generation of self-expandable stents which are easily introduced.
To achieve long-term palliation in inoperable esophageal cancer brachytherapy has been combined with external beam irradiation to reach the deeper layers of the tumor. Most often brachytherapy has been applied as a booster to a small tumor residue as in gynaecological tumors [3-9]. We prefer to start with brachytherapy  to induce fast tumor reduction, to improve dysphagia and prevent further weight loss, resulting in the need of less dilation procedures during the external irradiation. Overall results were encouraging (Table I) with symptomatic improvement in 70% and tumor reduction in 80-90% of patients.
Literature data on side effects are scarce: patient selection as well as the choice of radiation scheme are of importance. Deep ulceration of the tumor is generally considered a contraindication for brachytherapy due to a high risk of fistula formation. Also total dose as reported by Hishikawa , dose per fraction  and the source for brachytherapy (high dose rate, or medium dose rate) are limiting factors. As radiation ulcers usually cause intractable pain or life threatening esophagorespiratory fistula, it is of utmost importance to be aware of the small therapeutic range of the combined use of bachytherapy and external radiotherapy.
How can tumor response be evaluated?
The main subject of palliation is improvement of dysphagia. The evaluation in the various series is far from uniform: variations in the scoring system as well as time points. The scale most often referred to consists of the following sequence: normal food, soft food, mashed food, liquids, nothing at all. Interpretation of response on barium swallow is difficult and even at endoscopy it might be impossible to differentiate tumor residu from radiation ulcer. Despite these limitations, endoscopy is the most reliable method of evaluation at the moment. Whether endoscopic ultrasound (EUS) in tumor assessment will be more helpful is not yet known. Tumor response will be recognized by reduction of thickness and depth of infiltration; on the other hand radiation of normal esophageal tissue may result in thickening of the submucosa, but with intact architecture. Encouraging results have been reported by Tio  in a series of 23 patients treated with medium-dose-rate brachytherapy and external irradiation. More accurate documentation of response, as indicated in clinical trials, will be based on endoscopy combined with EUS in future studies.
1. Brewster AE, Davidson SE, Makin WP, Stout R, Burt PA. Intraluminal brachytherapy using the high dose rate microselectron in the palliation of carcinoma of the oesophagus. Clin Oncol 1995;7:102-105.
4. Hyden EC, Langholz B, Tilden T, Lam K, Luxton G, Astrahan M, Jepson J, Petrovich Z. External beam and intraluminal radiotherapy in the treatment of carcinoma of the esophagus. J Thorac Cardiovasc Surg 1988;96:237-241.
7. Hishikawa Y, Kurisu K, Taniguchi M, Kamikonya N, Miura T. High-dose-rate intraluminal brachytherapy for esophageal cancer: 10 years experience in Hyogo College of Medicine. Radiother Oncol 1991;21:107-114.
8. Sur RK, Singh DP, Sharma SC, Singh MT, Kochar R, Negi PS, Sethi T, Patel F, Ayyagari S, Bhatia SPS, Gupta BD. Radiation therapy of esophageal cancer: role of high dose rate brachytherapy. Int J Rad Oncol Biol Phys 1992;22:1043-1046.
11. Taal BG, Aleman BMP, Koning CCE, Boot H. Modulation of toxicity following external beam irradiation preceded by high dose rate brachytherapy in inoperable oesophageal cancer. Eur J Cancer 1996;in press.
12. Tio LT, Blank LECM, Wijers OB, den Hartog Jager FCA, van Dijk JDP, Tytgat GNJ. Staging and prognosis using endosonography in patients with inoperable esophageal carcinoma treated with combined intraluminal and external irradiation. Gastrointest Endosc 1994;40:304-310.