General description of procedure, equipment, technique

Photodynamic Therapy (PDT)

Initially defined in 1995 and subsequently described in European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines, interventional pulmonology is “the art and science of medicine as related to the performance of diagnostic and invasive therapeutic procedures that require additional training and expertise beyond that required in a standard pulmonary medicine training program.” Clinical entities encompassed within the discipline include complex airway management, benign and malignant central airway obstruction, pleural diseases, and pulmonary vascular procedures.

Diagnostic and therapeutic procedures pertaining to these areas include rigid bronchoscopy, transbronchial needle aspiration, autofluorescence bronchoscopy, endobronchial ultrasound, transthoracic needle aspiration and biopsy, laser bronchoscopy, endobronchial electrosurgery, argon-plasma coagulation, cryotherapy, airway stent insertion, balloon bronchoplasty and dilatation techniques, endobronchial radiation (brachytherapy), photodynamic therapy, percutaneous dilatational tracheotomy, transtracheal oxygen catheter insertion, medical thoracoscopy, and image-guided thoracic interventions. This presentation focuses on photodynamic therapy (PDT).

PDT is based on light activation of an intravenously injected photosensitizing agent, which is preferentially taken up by neoplastic cells (although some normal cells also are affected), leading to cytotoxicity. The photosensitizer (PS), once activated by light, loses energy generating singlet oxygen species, hydroxyl radical, superoxide, and direct cytotoxicity leading to rapid vascular ablation and cell necrosis and apoptosis.

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The only available PS agent for clinical use is porfirmer sodium (Photofrin®). A dose of 2 mg/kg is slowly injected intravenously over five to ten minutes. The agent is preferentially retained in tumor cells and vascular endothelium, limiting collateral damage. Forty-eight hours following injection, the tumor is exposed to light energy through a bronchoscope, triggering the cytotoxic reaction in tumor cells.

Indications and patient selection

PDT provides a safe, potentially curative, endobronchial option in treatment of early-stage lung cancer, and palliation of central airway obstruction due to malignancy. Some investigators have examined PDT use for downstaging tumors to improve operability, and in post-operative patients to treat positive surgical margins.



Details of how the procedure is performed

The photosensitizing agent porfimer sodium, (Photofrin®) is injected intravenously forty-eight hours prior to the bronchoscopic procedure.

The most commonly used bronchoscopic design incorporates a cylindrical diffuser that emits light in a 360-degree arc near its tip. Once the tumor is visualized, a light fiber with a known diffuser length is introduced through the working channel of the bronchoscope. The light energy delivered to the tissue is dependent on the length of the diffuser, the power setting of the laser, and the time of exposure. A typical exposure dose is 200 joules/cm of tissue for most airway applications. If the physician is targeting a 1 cm endobronchial lesion and plans a standard dose of 200 joules/cm, then she would calculate the power setting for the laser (400 milliwatts) and the time of exposure (8 minutes 20 seconds)[0.4 Watts times 500 seconds using a 1 cm diffuser = 200 joules/cm]. The tumor is exposed to the light for the specified time to create the cytotoxic reaction. Repeat bronchoscopy is performed in forty-eight hours to debride necrotic tissue. Additional exposures to the light can be performed up to 96 hours post-infusion without the need for repeat porfirmer dosing.

Interpretation of results

Not applicable.

Performance characteristics of the procedure (applies only to diagnostic procedures)

Not applicable.

Outcomes (applies only to therapeutic procedures)

PDT has been shown in multiple publications to have an excellent cure rate in early-stage endobronchial cancer–that is, carcinoma in situ. In a large study of 175 patients who underwent PDT for Stage 0 endobronchial cancer, the five-year disease-related survival rate was 93 percent. Other studies have shown similar results.

PDT used for palliation has demonstrated similar results to those of other endoscopic techniques. In a randomized, controlled trial, PDT was compared to Nd:Yag laser, and relief of symptoms was similar. Survival was significantly longer in the PDT group, although the study was small and not controlled for stage distribution.

Alternative and/or additional procedures to consider

Not applicable.

Complications and their management

The most common adverse event of PDT is skin photosensitivity. Patient instruction on necessary precautions, especially those regarding photosensitivity, is paramount. Patients are at risk for four to six weeks following injection, so light-protective gear must be worn throughout the period.

What’s the evidence?

Allison, R, Moghissi, K, Downie, G, Dixon, K. “Photodynamic therapy (PDT) for lung cancer”. Photodiag Photodyn Thera. vol. 8. 2011. pp. 231-239. (A comprehensive review of PDT for lung cancer.)

Cortese, DA, Edell, ES, Kinsey, JH. “Photodynamic therapy for early stage squamous cell carcinoma of the lung”. Mayo Clin Proc. vol. 72. 1997. pp. 595(Early description of the use of PDT.)

Diaz-Jimenez, Martinez-Ballarin, JE, Llunell, A. “Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction”. Eur Respir J. vol. 14. 1999. pp. 800(A large series reporting on the use of PDT.)

Dougherty, TJ, Marcus, SL. “Photodynamic therapy”. Eur J Cancer. vol. 28A. 1992. pp. 1734(A description of the physics underlying the use of PDT.)

Gomer, CJ, Dougherty, TJ. “Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue”. Cancer Res. vol. 39. 1979. pp. 146(A comprehensive review of the photosensitizing drug used in PDT.)

Kato, H, Okunaka, T, Shimatani, H. “Photodynamic therapy for early stage bronchogenic carcinoma”. J Clin Laser Med Surg. vol. 14. 1996. pp. 235(An excellent paper outlining the success of PDT.)

McCaughan, JS. “Photodynamic therapy of endobronchial and esophageal tumors: an overview”. J Clin Laser Med Surg. vol. 14. 1996. pp. 223(An overview of the use of PDT in treatment of lesions of the esophagus.)

McCaughan, JS, Williams, TE. “Photodynamic therapy for endobronchial malignant disease: A prospective fourteen-year study”. J Thorac Cardiovasc Surg. vol. 114. 1997. pp. 940(A study reporting on the long-term use of PDT and patient follow-up.)

Moghissi, K, Dixon, K, Stringer, M. “The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: Experience of 100 cases”. Eur J Cardiothorac Surg. vol. 15. 1999. pp. 1(An excellent large study on the use of PDT in advanced lung cancer.)
**The original authors for this chapter were Drs. Francis D. Sheski and Praveen N. Mathur. The chapter was revised by Dr. J. Scott Ferguson.