**5. Approach to photodynamic therapy in lung cancer**

Airway lesions must first be identified then confirmed bronchoscopically to ensure the lesions can be reached and light can be applied to the desired areas.

#### *Clinical Usage of Photodynamic Therapy DOI: http://dx.doi.org/10.5772/intechopen.95473*

Additionally, it is important to note the anatomy of the area surrounding the lesions. If the lesion location is adjacent to the large blood vessels surrounding the airway, the risk of massive hemoptysis should be considered prior to administering therapy [29]. This is also true for large central airway tumors that may have large vascular beds [29, 30]. As necrosis occurs, these perforating vessels can potentially lead to significant bleeding. The risk of further airway compromise in an already partially compromised airway (i.e. from the central airway tumor) is already significant in these scenarios. This is a greater consideration when there is malignancy both intrinsic and extrinsic to the airway. Additionally, there is a risk of fistula formation into the surrounding structures of the thorax such as: the esophagus, mediastinum, or blood vessels (pulmonary artery, superior vena cava, innominate vein, etc.) [31]. It should also be noted that mediastinal anatomy, especially airways and blood vessels will shift out of their traditional anatomic locations in the presence of large tumor burden. Being aware of these changes can be vital when reviewing a patient for consideration of photodynamic therapy. Depending upon the shape and course of the lesions, consideration should be given to the anticipated inflammatory effects during photodynamic therapy as the process of controlled and uncontrolled cell death occurs. The areas particularly at risk are the trachea, carina, and main stem bronchi [17, 29]. In these cases, long or circumferential tumors would be at a higher risk of obstructing the airway given the expansion associated with edema that would be anticipated with photodynamic therapy [17]. Additionally, individuals with impaired liver and/or renal function can have delayed clearance of porfimer sodium [17]. This delayed clearance can prolong the period of photosensitivity beyond 90 days when it would typically be ~30 days [5, 12, 28].

Skin/systemic photosensitivity is the most significant and common adverse effect associated with photodynamic therapy [17]. Following the injection of the photosensitizer, it is important to ensure that patients are able to protect their skin until the photosensitizer is fully cleared [17]. This can be as short as two weeks and sometimes as long as three months [5, 6, 12]. Ensuring patients remain indoors for this period to prevent serious collateral skin damage from occurring is vital to safely administering this therapy [17]. Porfimer sodium has not been extensively studied in pregnant and lactating women, but there are animal studies that have demonstrated adverse effects [17]. This has led to porfimer sulfate having an FDA pregnancy category of C, ie animal studies demonstrating adverse fetus effects without any well-controlled human studies, but the benefits may warrant consideration in this population. Similarly, there are no studies on lactation either, so it is not known if porfimer sulfate is secreted in breast milk [17].

Porfimer sodium is injected systemically at a dosage of 2 mg/kg intravenously over 3–5 minutes; this is considered time zero [2, 28]. From this point onwards, the patient will be extremely photosensitive and must wear protective clothing. Additionally, there can be ocular sensitivity, so it is important for patients to wear dark glasses that transmit <4% of white light over the next 30 days [17]. Over the next 2–3 days from time zero, the porfimer sodium will preferentially localize to the desired areas of malignancy over this period of time [5, 6]. Next, the patient will be brought in for a bronchoscopy for the second stage of the treatment [17]. This typically will occur 40–50 hours from time zero [1, 2]. Upon reidentification of the lesions of interest, here a laser light diffuser illuminating at a wavelength of 620 nm with 200 J/cm for the length of the diffuser is utilized, **Figure 2** shows available diffusers [17]. The duration of illumination is eight minutes and twenty seconds (five hundred seconds) [17]. If the tissue of the lesion is soft and allows, the fiber can be positioned interstitially, otherwise the fiber remains within the lumen of the airway for the five hundred seconds of illumination [17]. During this period all

#### **Figure 2.**

*Comercially available laser diffuser fibers for endobronchial use. Photo used with permission from Pinnacle Biologics.*

individuals, including the patient receiving therapy, in the procedure room wear eye protection. Following endoillumination of the desired lesions, it is often advisable to have the patients hospitalized for observation [17]. As the tumor sloughs off, it can often be necessary to debride the necrotic tissue to prevent obstruction of the airway [17]. This is recommended to be done 48–72 hours after the light treatment, or 88–122 hours from time zero [17]. If it is clinically indicated a second light treatment can be performed 96–120 hours from time zero [17]. Given there is an overlap between when tissue debridement is performed and when a second light therapy can be indicated, they are sometimes performed simultaneously. Although the tumor debridement is recommended to be 48–72 hours from light therapy, there can often be a very robust tissue response, and the debridement may need to be done sooner and multiple times before the photodynamic effect is fully realized. Given that airway obstruction can be an emergent and life-threatening condition if not intervened upon quickly, there is a strong reason to keep patients hospitalized for the duration of this therapy.

Following the first injection of Porfimer sodium, subsequent injections and light exposures can be repeated as described above up to three times [17]. However, each treatment must be separated by thirty days. If radiation therapy was performed at any point there should be a period of approximately four weeks from the completion of radiation before photodynamic therapy is attempted [17]. After exposure to porfimer sodium, exposure to sunlight can cause a significant skin reaction, but indoor light can help clear the residual photosensitizer [17]. The duration of the of photosensitivity period can vary from patient to patient, and should be individualized, but a minimum of thirty days should be considered [17]. To determine if there is any residual photosensitivity, patients can be instructed to expose an area of skin to sunlight for approximately ten minutes and then observe for any skin reaction over the subsequent twenty-four hours. As it may be difficult to remember exactly where the exposure was, using a pen or marker to outline the sun-exposed area can help identify this area. Following treatment, chest discomfort secondary to the associated inflammatory effect may require temporary analgesia until the inflammation subsides [17].
