**6. Esophageal cancer and high-grade Barrett's esophagus**

Similar to lung cancer, the dosing for porfimer sodium is 2 mg/kg [17]. The laser light diffuser utilized however, is different. In esophageal cancer a laser light diffuse of 200 J/cm is utilized, and in Barrett's esophagus, a laser light diffuser of 130 J/ cm is used, see **Figure 2** for current available laser light diffusers [17]. High-grade Barrett esophagus is the final precancerous stage before progressing to esophageal cancer [32]. Typically, high- grade Barrett esophagus is treated by surgical resection [32]. Treatment of high-grade Barrett's esophagus is an approved indication for photodynamic therapy if surgical resection is not an option [17, 33]. Treatment of esophageal cancer is an approved treatment for photodynamic therapy if there is complete obstruction of the esophagus by tumor or a partial obstruction that cannot adequately be treated by laser therapy/debridement [17, 33]. Given that the esophagus travels just posterior to the trachea and mainstem bronchi, the risks of fistula formation are the same and primarily to the trachea, blood vessels, and mediastinum. Specifically, if a tumor has already spread into these structures, there is a higher risk of fistula formation as the malignant cells are destroyed from photodynamic therapy. Esophageal varices are veins within the esophagus that are enlarged. These veins are at high risk for bleeding and rupture at baseline, and photoactivation of the photosensitizer in these veins could lead to significant bleeding [17]. Specifically, if these varices are >1 cm in diameter, the risk is likely too great [17]. Following treatment of Barrett esophagus, there is a risk of esophageal strictures resulting in food dysphagia (inability to swallow) [34]. In research studies these strictures occurred in 38% of subjects within six months of initiating photodynamic therapy. This is typically treated with dilation of the stricture, but it may require other treatments, depending upon the severity [17].

In esophageal cancer the timeline from injection to photoactivation of the photosensitizer is the same as in lung cancer. The time of injection (time zero) to photoactivation (40–50 hours from time zero) to potential second photoactivation (96–120 hours) is the same [17]. However, the duration of the treatment is different, the exposure to light is 12.5 minutes (750 seconds) [17]. A minimum of 30 days between injections of porfimer sodium is recommended with similar distancing between radiation therapy and photodynamic therapy [17]. Additionally, just as in lung cancer, endoscopic re-evaluation between treatments is recommended to ensure no complications have occurred such as fistula formation [17]. Barrett's esophagus has similar injection to photoactivation of the photosensitizer is the same as in lung cancer and esophageal cancer [17]. The time of injection (time zero) to photoactivation (40–50 hours from time zero) is the same [17]. The duration of treatment with light can however vary depending upon the length of the laser light diffuser utilized to deliver therapy with a maximum length of 7 cm treated at any one time [17]. In high-grade Barrett's esophagus, the time interval between injections of porfimer sodium is a minimum of 90 days [17].
