CLINICAL INVESTIGATION
Outcome of patients receiving photodynamic therapy for early esophageal cancer

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Abstract

Purpose: Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer.

Methods and Materials: Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300–800 mW of power, energy dose of 200–300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months).

Results: The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy.

Conclusion: PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.

Introduction

The incidence of esophageal cancer varies widely with the geographic area, ranging from 5 to 100 new cases per 100,000 population 1, 2. Epidemiologic studies in Italy showed that there were 2233 new cases in 1990 (3). Several dietary factors (e.g., exposure to mycotoxins or silicon fibers) may account for the high incidence of the disease in the eastern world, but alcohol consumption and tobacco use are the main causes of cancer of the esophagus in Western developed countries (4).

Because the clinical outcome in patients with locally advanced esophageal cancer is very poor (5), early detectionwith screening tests, especially in geographic areas where there is high incidence, is considered crucial in reducing the rate of mortality 6, 7. Surgery, with or without post- or preoperative chemoradiotherapy, is considered the standard treatment for early operable disease; the combination of radiotherapy and cytotoxic drugs is the alternative when the tumor is inoperable for medical reasons (5).

Photodynamic therapy (PDT) was recently introduced into the clinical practice of oncology, and has shown remarkable efficacy in eradicating small tumors of the genitourinary tract, lung, or head-neck area 8, 9, 10, 11, 12. The present study examined the role of PDT for early inoperable esophageal cancers.

Section snippets

Materials and methods

Sixty-two patients with esophageal cancer that were medically inoperable (hepatic cirrhosis, cardiovascular disease; 54 patients) or inoperable for personal reasons (8 patients) were prospectively treated in the Department of Radiotherapy, General Hospital of Padua, Italy, with a protocol consisting of PDT alone or followed by radiotherapy.

Patient characteristics are shown in Table 1. The performance status (World Health Organization scale) of our patients ranged from 0 to 2 (median, 1).

Response and survival

Table 2 shows the responses observed after PDT with or without subsequent radiotherapy. PDT alone yielded an overall CR rate of 37% (23/62); the addition of radiotherapy increased the overall CR rate to 82% (51/62). Figure 1 shows an esophageal tumor partially obstructing the lumen before any therapy (Fig 1a). CR was achieved after the second laser application (Fig. 1b). CR rate after PDT alone was statistically higher (p = 0.04) in Tis/T1 lesions (21 of 48; 44%) than in T2-stage tumors (2 of

Discussion

PDT is considered a promising approach for cancers that are accessible directly or endoscopically. PDT for esophageal cancer has been used since the early 1990s. In 1990, Okunaka et al. observed in a study of 20 patients with esophageal cancer, that PDT elicited a high CR rate among those with superficial lesions (15). Imamura et al. (12) reported PR to PDT in patients with superficial gastrointestinal tract cancer using HpD as the photosensitizer. Jin et al. (16) reported on the experience of

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