ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Endobronchial photodynamic therapy in the management of airway disease in adults

Endobronchial photodynamic therapy in the management of airway disease in adults
Literature review current through: Jan 2024.
This topic last updated: Mar 02, 2023.

INTRODUCTION — Photodynamic therapy (PDT) is a non-thermal ablative technique. Cells in tissue, which previously received a photosensitizing chemical, die when exposed to a specific light wavelength.

Since the early 1900s, PDT has been used to treat cancers of the esophagus, stomach, bladder, skin, oropharynx, pleura, and biliary tree. The same principles of PDT can be applied using bronchoscopes to treat airway disease, primarily endobronchial non-small cell lung cancer (NSCLC).

The principles and procedure, as well as the indications, contraindications, expected adverse events, and complications of bronchoscopic PDT, are reviewed in this topic. Other bronchoscopic techniques used to manage airway disease and the use of PDT for the treatment of other types of cancers are described separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults" and "Endobronchial electrocautery" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and "Airway stents" and "Flexible bronchoscopy balloon dilation for nonmalignant airway strictures (bronchoplasty)" and "Endobronchial brachytherapy" and "Ampullary carcinoma: Treatment and prognosis", section on 'Minimally invasive nonsurgical therapies' and "Early gastric cancer: Treatment, natural history, and prognosis", section on 'Other endoscopic modalities' and "Bronchoscopic cryotechniques in adults" and "Treatment and prognosis of low-risk cutaneous squamous cell carcinoma (cSCC)", section on 'Photodynamic therapy' and "Treatment of actinic keratosis", section on 'Photodynamic therapy' and "Treatment and prognosis of basal cell carcinoma at low risk of recurrence", section on 'Photodynamic therapy'.)

PRINCIPLES OF PHOTODYNAMIC THERAPY

Phototoxic reaction — The phototoxic reaction depends upon the cellular uptake of a photosensitizing agent, which is usually administered intravenously (see 'Photosensitizing agent administration' below). Photosensitized tissue is subsequently exposed to light (usually 48 hours later) (see 'Bronchoscopic phototherapy' below). The light induces a type II photo-oxidative intracellular reaction, in which molecular oxygen is transformed to singlet reactive oxygen species (ROS) [1,2]. The presence of excessive amounts of intracellular ROS results in cell death and, consequently, tissue necrosis.

Tumor cells and the neovascular endothelium of tumors preferentially retain the photosensitizer such that the cytotoxic reaction is somewhat selective for neoplastic cells [3]. Capillary damage and tumor necrosis begin within hours after illumination; however, the maximal clinical effect of tissue destruction takes a few days to be appreciated. This is key to understanding that PDT is a delayed effect therapy and debridement bronchoscopy needs to be scheduled within a couple of days after illumination/activation.

Light source — A laser light source, typically administered via a flexible bronchoscope, with a specific wavelength (eg, optimal wavelength for photofrin is 630 nm) is required for photodynamic therapy (PDT) to be effective. Tissue is typically destroyed to a depth of approximately 5 to 10 mm [4] (see 'Bronchoscopic phototherapy' below). The most commonly used light source is the diode laser (picture 1). Since these lasers emit non-thermal laser light, the effects of PDT are not immediate; however, the non-thermal property eliminates the risk of airway fire, an adverse effect that may occur with thermal techniques (eg, bronchoscopic laser, electrocautery, or argon plasma coagulation) if the fraction of inspired oxygen (FiO2) is higher than 0.4. (See "Bronchoscopic laser in the management of airway disease in adults" and "Endobronchial electrocautery" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults".)

Dosimetry — Total energy delivered depends upon the timing of illumination after injection of the photosensitizing agent and the energy delivered through the fiber:

Timing – According to the drug package insert, endoscopic introduction of the light source should be scheduled 40 to 50 hours after injection. In practice, most interventionalists generally schedule light application approximately 24 to 72 hours after injection (usually 48 hours). This allows for the sensitizer to concentrate in tumor cells and wash out of normal mucosa, thus minimizing damage to adjacent nonmalignant tissue. Treatment at shorter times will lead to indiscriminate damage because there is equal concentration of photosensitizing agent in tumor and normal tissues. The concentration is sufficient in the tumor for approximately five to seven days, thus making a second light application effective at the clean-up bronchoscopy (three days after first treatment and five days after injection). A second light application is only occasionally needed when there is residual viable endobronchial tumor that significantly narrows the airway lumen.

Energy – It is recommended initially to apply 200 Joules per cm treated (range 50 to 300 Joules). Higher amounts of energy may be administered for larger, bulky, obstructing lesions, while smaller amounts are usually administered for smaller or distal lesions. If a profound response is expected for tracheal and mainstem bronchial lesions, it is sometimes safer to use a lower energy to avoid sloughing of necrotic tissues, which can acutely worsen airway obstruction. Additional energy may be applied during a follow-up bronchoscopy two days later if needed after the clean-up (ie, debridement) bronchoscopy. Additional photosensitizer should not be administered any more than every six weeks to limit toxicity.

Although animal models suggest that t light dosing administered as a lower power delivered over a longer time achieved local tumor control [5], human studies are needed for this "slow and low” approach.

While bronchoscopists sometime customize the laser settings based on the tumor’s location, length, vascular supply, and degree of airway obstruction, light dosimetry is not usually determined based on the thickness of the lesion. Dosimetry is impacted, however, by the length of the lesion, with fibers selected so that the entire length (vertical extent) of the lesion is being illuminated. The settings can be entered manually, but the laser software also automatically calculates the power and time based on the desired energy (Joules) and laser fiber length (cm). One commercial laser is used only for its illumination properties and not for thermal ablation, so it is not used for other purposes such as coagulation or ablation outside of its PDT application.

INDICATIONS AND EFFICACY — Photodynamic therapy (PDT) therapy is typically a palliative or adjunctive therapy used to relieve non-life-threatening symptomatic airway obstruction (eg, dyspnea, cough, hemoptysis) due to malignant or, less commonly, nonmalignant conditions that are not amenable to first-line therapies. It may also be used to treat patients with inoperable radiographic occult lung cancer (ROLC) or patients with stump recurrence following resective surgery. Ideal lesions are intraluminal and short (ie, <1 to 1.5 cm) and with an endoluminal surface that is without significant necrotic debris; extrinsic lesions should not be treated with PDT.

The management of patients with central airway obstruction and the choice of modality used to treat this population, including locally ablative bronchoscopic techniques, are discussed separately (table 1 and table 2). (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

Airway obstruction

Malignant

Tumor or patient characteristics — The most common indication for bronchoscopic PDT is symptomatic obstruction of a central airway due to an intrinsic tumor (table 3). In general, PDT is a palliative therapy used in patients for whom other first-line treatment modalities are not feasible (eg, surgery). Occasionally, it is used adjunctively before salvage chemotherapy, radiation (eg, external beam radiation or brachytherapy), or surgical resection. For optimal effects, lung units distal to the obstruction should be functioning or "recruitable," and repeated therapies are sometimes required.

Selecting patients who have tumors likely to respond to PDT is critical. Similar to patients with lung cancer who present with mediastinal or parenchymal masses, patients with airway malignancy should undergo an identical staging process, during which computed tomography (CT), bronchoscopy, and endobronchial ultrasound (EBUS)-transbronchial needle aspiration are typically performed (table 4). This process is important for several reasons (see "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer" and "Selection of modality for diagnosis and staging of patients with suspected non-small cell lung cancer"):

Assessing tumor extent – For most patients with intraluminal tumor, but in particular those with post-resectional stump recurrence and ROLC (ie, early lung cancer or carcinoma in situ) for which PDT is being considered (often with a curative intent), EBUS evaluation of tumor extent is particularly important. Assessment without EBUS may lead to underestimation of tumor invasion in the airway wall and may reduce the efficacy of PDT [6]. The identification of additional tumors, mediastinal, hilar or interlobar nodal involvement, or tumor beyond the airway wall may result in the avoidance of PDT and prompt alternate therapies (eg, radiotherapy). Commercially available EBUS scopes (outer diameters of 6.7 to 6.9 mm depending on the brand) can be advanced to the lobar bronchi but are usually larger than segmental airways. The balloon-based radial probe, however, can be advanced further but it is not widely commercially available. (See 'Radiographic occult lung cancer' below.).

Assessing tumor characteristics – For all patients with symptomatic airway obstruction from an intraluminal tumor, assessing the macroscopic tumor characteristics are easily performed prior to PDT with bronchoscopy and CT.

When applied for curative intent in patients with early airway lung cancer, the ideal lesions are short, typically <1 to 1.5 cm (ie, no longer than the length of the light diffuser). While there is no specific upper limit of the lesion’s thickness, for curative intent, PDT should be offered for lesions that do not extend beyond the airway cartilage as assessed on imaging [6]. For palliative intent, lesions that are deep or shallow and lesions that are associated with complete or partial obstruction that is non-life-threatening can be treated with PDT. However, necrotic debris and blood interfere with light penetration such that mechanical debridement with a rigid bronchoscope, cryotherapy, or a variety of flexible bronchoscopic techniques prior to PDT is required in such cases. Although most cases of symptomatic airway obstruction are located centrally (ie, trachea and mainstem bronchi), lesions down to the second or third order of bronchi can be successfully treated with PDT, which is an advantage over bronchoscopic laser, where there is increased risk of airway and vessel perforation in lobar and segmental airways.

Long, extensive lesions of the airway (especially if they extend to segmental airways) cannot be effectively treated with PDT. Airway patency beyond the level of obstruction is usually necessary for PDT to be effective. Since PDT requires direct or close contact with the tumor for it to be effective, it cannot be used for lesions that cause external compression (image 1). In addition, PDT should not be used for tumors associated with life-threatening obstruction (ie, critical tracheal or bilateral mainstem bronchial tumors), since its effect is not immediate and tumor sloughing following illumination may transiently worsen the degree of airway obstruction prior to debridement bronchoscopy. These and other contraindications are discussed separately. (See 'Contraindications' below.)

Although laser, electrocautery, and argon plasma coagulation are bronchoscopic ablative therapies that are immediate acting, PDT is longer lasting, may have a survival benefit when compared with neodymium-doped yttrium aluminum garnet (Nd;YAG) laser [7,8], and can be used following ablation to maintain local control of large, bulky tumors. (See "Endobronchial electrocautery" and "Airway stents" and "Flexible bronchoscopy balloon dilation for nonmalignant airway strictures (bronchoplasty)" and "Endobronchial brachytherapy" and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults" and "Bronchoscopic cryotechniques in adults".)

Non-small cell lung cancer (NSCLC), particularly squamous cell carcinoma, is the most common malignancy subjected to bronchoscopic PDT. However, case reports of successful management of other types of malignancy have been described, including small cell lung cancer and endobronchial metastases of nonpulmonary malignancies [9,10]. Histologic type needs to be clarified prior to PDT as certain tumor types have a more profound response, which may result in excessive tumor sloughing (eg, small cell carcinoma).

Efficacy — In most patients (up to 80 percent), PDT can palliate the symptoms associated with central airway obstruction (ie, trachea and mainstem bronchi), as well as those associated with distal endobronchial obstruction (eg, down to the second or third order of bronchi) (figure 1) [9,11-19]. As examples:

In an analysis of patients with stage III and IV NSCLC and central airway obstruction, addition of PDT resulted in a similar mortality to patients treated with radiation and chemotherapy. However, addition of non-PDT ablation showed higher mortality compared with the radiation and chemotherapy group [8].

In a more subsequent analysis, patients treated with PDT, radiation and chemotherapy had a lower mortality than patients treated with radiation alone, (50 and 53 percent lower, respectively) [20].

In an observational study of 175 patients with endobronchial NSCLC, PDT resulted in palliation of symptoms (cough, dyspnea, hemoptysis) in most patients [16].

In another retrospective study of 133 patients with airway obstruction (mostly NSCLC), two-thirds of whom were inoperable, two or more PDT treatments resulted in improved airway patency (81 percent) and dyspnea (74 percent); median survival was 4.4 years [9]. Most cases of airway obstruction were located in the mainstem bronchi (>50 percent); one case was located in the trachea, and the remainder were in the second and third order bronchi (eg, bronchus intermedius, orifice of the right middle or lower lobe).

In a retrospective study of 100 patients with airway obstruction due to advanced inoperable bronchogenic cancer (mostly NSCLC), mean endoluminal obstruction decreased from 86 to 18 percent, and lung function improved as evidenced by an increase in mean forced vital capacity (increased by 430 mL) and forced expiratory volume in one second (increased by 280 mL) [15]. Median survival was five months, and overall two-year survival was 1 percent.

Case reports also describe successful use of PDT as an adjunctive therapy (eg, PDT plus chemotherapy, sleeve lobectomy, bronchoscopic laser, or bronchoscopic brachytherapy) in the treatment of NSCLC [21-26]. Similarly, it has been used successfully for local control in patients with intractable endobronchial disease who have failed other therapies (eg, surgery, chemotherapy, or radiation) [27]. Whether ionizing radiation can activate porfimer sodium (Photofrin) has not been studied. Therefore, it is recommended that two to four weeks be allowed after PDT before starting radiotherapy. Similarly, if PDT is to be given after radiotherapy, the acute inflammatory reaction from radiotherapy usually subsides within four weeks after completing radiotherapy, after which PDT may be given.

Comparison with other ablative procedures — Although there are no high-quality studies comparing the use of PDT with other bronchoscopic ablative therapies, when used appropriately, they all appear to result in similar rates of airway patency and symptom palliation (hemoptysis, dyspnea, cough). As an example, in one randomized trial of 31 patients with inoperable NSCLC that directly compared PDT with bronchoscopic laser, both treatments resulted in similar rates of symptom palliation (>80 percent) [7]. However, the effects of PDT were longer lasting.

According to two analyses from the Surveillance, Epidemiology, and End Results Program database of patients with stage III and IV NSCLC, the addition of PDT to radiation therapy may offer a survival benefit over radiation therapy alone, while addition of non-PDT ablation showed higher mortality compared with patients treated with radiation and chemotherapy [8,20].

Choosing which therapy to use in patients with obstructing airway tumors is dependent upon the tumor and patient characteristics, as well as local expertise and costs, and should therefore be individualized for each patient. In addition, in practice, a combination of local therapies is often used to optimize and maintain patency. Among these modalities, only PDT and brachytherapy are longer lasting than the others. PDT has a shallower depth of penetration when compared with neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, thus, PDT as a non-thermal modality may be used without the increased risk of airway fire or perforation that is of concern with the thermal techniques. The advantages and disadvantages of each bronchoscopic modality and choosing among the therapeutic options (both immediate-acting and maintenance therapies) in patients with airway obstruction are discussed in detail separately (table 1 and table 2). (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Choosing among modalities' and "Endobronchial electrocautery" and "Airway stents" and "Flexible bronchoscopy balloon dilation for nonmalignant airway strictures (bronchoplasty)" and "Endobronchial brachytherapy" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and "Bronchoscopic cryotechniques in adults".)

Nonmalignant — There are fewer data to support PDT for the treatment of inoperable nonmalignant airway obstruction (table 3). Only case reports and case series report successful treatment of symptoms of airway obstruction due to nonmalignant conditions including idiopathic airway stenosis, stenosis from aspergillus and granulation tissue (eg, post-transplant), as well as endobronchial recurrent respiratory papillomatosis (RRP), arteriovenous malformations, and nonmalignant tracheal polyps [9,28,29]. A retrospective case series of eight patients suggests that PDT can be a safe and effective tool when treating tracheobronchial RRP, including those lesions with malignant transformation, but prospective studies will be needed to fully determine its effectiveness.

Hemoptysis — Bronchoscopic PDT has been reported as successfully achieving hemostasis in patients with hemoptysis due to malignant or nonmalignant airway lesions, most often the former [9,28]. As an example, in one case series of 133 patients with mixed etiologies for airway obstruction, hemoptysis resolved with PDT in 114 of the 115 patients presenting with this symptom. PDT may be considered for treating hemoptysis from airway tumors that result in mild or moderate volume hemoptysis and if patients have stable cardiopulmonary status.

Radiographic occult lung cancer — PDT has been used to treat patients with early-stage NSCLC confined to the airway wall (also known as ROLC) that is not amenable to surgery [11,13,14,16,17,30-36]. However, although the intent is curative, large randomized studies have not adequately proven that PDT or other locally ablative therapies can cure ROLC. As examples:

In one review of 15 studies (totaling 626 patients with ROLC), the complete response rate of PDT ranged from 30 to 100 percent with a median five-year survival of 61 percent [34].

In another prospective study of 48 patients with operable ROLC and a tumor length of <1 cm, the complete response rate of PDT was 94 percent [30]. However, 20 percent developed local recurrence, and 13 percent died during follow-up from additional primary lung cancers that were not originally treated by PDT but developed subsequent to therapy.

The response rate for early airway lung cancer depends on the length (vertical extent) of the lesion [36]. In a series of 204 patients, the overall complete response rate was 85 percent; a subgroup analysis revealed a complete response of 95 percent when the lesions were <1 cm in extent, 80 percent for those of 1 to 2 cm, and 44 percent for tumors longer than 2 cm [36]. Predictors of recurrence include not only the length but also segmental involvement and inability to determine the distal margins in the segmental airways.

Stump recurrence and residual disease postresection — The evidence to support the use of PDT in patients who present with symptomatic stump recurrence following resective surgery is derived from case series that included individual cases with stump recurrence, as well as from our personal experience [11,12,18,37]. In addition, recurrence at this location is ideally suited to PDT due to its small size and easy access with minimal risk of airway perforation.

Another related indication is incomplete resection (R1) with mucosal residual disease in patients who are not candidates for surgical reintervention. In a case series of 11 patients with bronchial mucosal R1 resection, PDT was applied along the stump site. The local control rate was 91 percent without complications [38].

Investigational — PDT has been reported as a treatment for the following indications, which should be considered investigational:

Pleural metastases – Rare case reports have described using PDT to treat pleural dissemination from NSCLC, thymoma, and mesothelioma. However, in our opinion, PDT may only be of value in those with oligometastasis (up to four metastases), while patients with extensive pleural disease are likely not good candidates [39-41].

Peripheral lung cancer – Treatment of peripheral lung cancer with PDT has been reported with limited success. This was illustrated by an uncontrolled trial of nine patients who underwent CT-guided PDT for treatment of peripheral lung cancer [42]. Only a partial response was achieved in seven patients. These results suggest that differences in the location of the tumor and/or the technique used to administer PDT may affect the outcome. Bronchoscopic PDT has been reported in several case series of peripheral lung tumors using different dosimetry and photosensitizers and was found to be feasible and safe without pneumothoraces or bleeding [43,44].

Two feasibility United States-based multicenter studies have also been completed for evaluating the safety of bronchoscopic PDT for inoperable, peripheral lung cancer, but their results have not yet been published (NCT02916745, NCT03344861).

CONTRAINDICATIONS

Patients with extrinsic compression — Since a lesion requires direct illumination for photodynamic therapy (PDT) to be effective, airway obstruction solely due to extrinsic compression of the airway is a contraindication to PDT. However, for patients who have lesions with both extrinsic and intrinsic components, the latter may be subjected to PDT, if indicated. (See 'Indications and efficacy' above.)

Patients with life-threatening symptoms — Since the effect of PDT is delayed, it should not be used for patients with life-threatening obstruction or hemoptysis who need immediate relief. Similarly, it cannot be used in patients with significant airway obstruction who are at risk of airway compromise due to airway edema, which is common following the procedure. In such cases, therapies that have an immediate ablative effect should be used (eg, surgical coring, or bronchoscopic laser, electrocautery or argon plasma coagulation). (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Life-threatening central airway obstruction' and "Bronchoscopic laser in the management of airway disease in adults" and "Endobronchial electrocautery" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and 'Photodynamic therapy specific' below.)

Patients with lesions adjacent to or eroding a major blood vessel — PDT is generally avoided in patients with lesions that are adjacent to or invading a major artery since the risk of massive hemoptysis and exsanguination is high. (See "Evaluation and management of life-threatening hemoptysis" and "Etiology of hemoptysis in adults".)

Contraindications to bronchoscopy — Bronchoscopic PDT involves either flexible or rigid bronchoscopy and typically requires moderate or deep sedation or general anesthesia. Thus, patients with contraindications to bronchoscopy, moderate or deep sedation, or anesthesia are not candidates for PDT. (See "Overview of anesthesia", section on 'Types of anesthesia' and "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications", section on 'General considerations and precautions' and "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Contraindications'.)

Other — PDT should be avoided in the following populations:

Patients in whom mucus plugging is likely to worsen respiratory failure – Mucus plugging from tissue sloughing is common in the first few days following bronchoscopic PDT. Thus, it should be avoided when it is assessed by the clinician that mucus plugging cannot be managed adequately such that it may prompt respiratory failure requiring mechanical ventilation (eg, patients with severe underlying cardiopulmonary disease) or induce life-threatening airway obstruction (eg, patients with significant tracheal compromise). In such cases, contact electrocautery, laser, or argon plasma coagulation are alternatives for local symptom management. (See "Bronchoscopic laser in the management of airway disease in adults" and "Endobronchial electrocautery" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults".)

Patients with photosensitivity disorder – PDT should be avoided in those with severe photosensitivity (eg, fair-skinned individuals with significant reactions following previous treatment or patients with photosensitivity disorder [eg, porphyria]) due to the high risk of sunburn. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection" and "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment".)

Patients with long airway lesions or fistulas – Patients with long airway lesions that exceed the length of the longest available airway diffuser (eg, >2.5 cm) are not ideal candidates for PDT as an initial therapy. The commercially available 5 cm diffuser is for esophageal (not airway) lesions. As in long esophageal tumors, successive light applications may be added at the initial treatment (if the distal tumor can be visualized), or further distal treatment may be given at the clean-up bronchoscopy. In patients whose tumors shrink by other means (eg, laser, chemotherapy), then PDT may be applied at a later date for additional local control.

Patients with stents – The presence of an airway stent may be considered a relative contraindication to PDT. PDT can be performed in patients with bare metal stents because the laser light shines directly on the tumor, but covered stents theoretically attenuate the laser light, thus delivering considerably less energy to the tumor, potentially resulting in less than ideal treatments. This is likely mostly for the thick-walled silicone stents, not for the covered or partially covered self-expandable metallic stents.

Although animal studies showed that PDT at different power outputs (150 to 300 MW) can be performed through transparent silicone stents [45], clinical human studies are needed before recommending PDT in patients with indwelling silicone stents.

Tracheo- or bronchopleural fistula – Photodynamic therapy is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula since PDT will exacerbate the fistula and prevent healing.

Patients who will not be compliant with photosensitive precautions – As patients will be photosensitive for up to six weeks, it is recommend they wear wide-brimmed hats, UV protective sun glasses, and long-sleeves in order to prevent phototoxicity. If patients are not compliant, severe phototoxicity can occur.

PROCEDURE — Photodynamic therapy (PDT) should only be performed by operators trained in its use. The team usually includes a bronchoscopist, a nurse, and an anesthesiologist with expertise in airway management. The materials needed include a photosensitizing agent, a bronchoscope (flexible and/or rigid), and a laser light source. (See "Supraglottic devices (including laryngeal mask airways) for airway management for anesthesia in adults" and "Direct laryngoscopy and endotracheal intubation in adults".)

Photosensitizing agent administration — Agents used are generally a mixture of different porphyrin-based oligomers. Among the agents, porfimer sodium (Photofrin) is the most common and the only agent in the United States that is approved for PDT use. A standard dose of 2 mg/kg of total body weight (not predicted body weight) is injected intravenously slowly over 3 to 5 minutes. The drug is cleared from most organs within 72 hours but is retained longer in tumors, skin (up to 30 days), liver, and spleen. Retention in the skin is responsible for prolonged photosensitivity following the procedure, which is the most common adverse effect of PDT. (See 'Photodynamic therapy specific' below.)

New photosensitizers with more specificity for cancerous tissue and, therefore, less associated photosensitivity, as well as photosensitizers with a shorter half-life, are under development and may further improve the safety, efficacy, and efficiency of the procedure.

Anesthesia — Adequate anesthesia is mandatory in order to eliminate coughing and inadvertent repositioning of the light source, which could result in damage to adjacent normal endobronchial mucosa. Bleeding may result in reduced light penetration and could make the procedure less effective. Thus, most patients require deep sedation and/or general anesthesia (eg, propofol and/or remifentanil infusions) together with topical anesthesia (eg, 1 or 2 percent lidocaine) to achieve this goal. (See "Supraglottic devices (including laryngeal mask airways) for airway management for anesthesia in adults" and "Flexible bronchoscopy in adults: Overview" and "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications" and "Direct laryngoscopy and endotracheal intubation in adults" and "Anesthesia for adult bronchoscopy".)

Bronchoscopic phototherapy — Following the administration of a photosensitizing agent (usually 40 to 50 hours) (see 'Photosensitizing agent administration' above), the lesion is exposed to light energy (see 'Light source' above), which triggers the cytotoxic reaction. (See 'Phototoxic reaction' above.)

The light source is introduced via a flexible or rigid bronchoscope, usually the former. However, the use of a rigid bronchoscope may be preferable in patients who are unstable or significantly hypoxemic who may require recanalization prior to light application.

Once the tumor is visualized and ensuring that the surface is clear of surface debris, the light source is delivered through the working channel of a flexible bronchoscope or through the open barrel of a rigid bronchoscope such that it is 2 to 3 cm away from the distal end of the bronchoscope.

The chosen diffuser length depends upon the length of the lesion. Diffusing fibers are mounted at the tip of a one-meter fiberoptic cable, which can be placed in the biopsy channel of most flexible bronchoscopes and is fitted with a connector for easy attachment to the light source. Standard diffusers are 1.07 mm (flexible diffuser) or 1.7 mm (rigid diffuser) in diameter with available lengths of 10, 15, 20, 25, and 50 mm. The 50 mm diffuser is not recommended for airway applications. Ideally, the diffuser length should roughly equal the tumor’s vertical extent. If the lesion is longer than the chosen diffuser, the light fiber is repositioned to the non-treated area, and an additional light application is administered until the entire tumor has been treated (typically estimated visually). Each treatment usually takes approximately eight minutes (to deliver a total of 200 Joules). The most commonly used design is a cylindrical diffuser, which emits light laterally in a 360-degree arc near its tip (picture 2).

For bulky tumors, if possible, the rigid or flexible diffusers should be nearly completely embedded into the lesion since PDT works best by transillumination. This not only protects healthy mucosa from light exposure but also delivers more energy to the tumor itself. Inserting the tip is difficult to perform for lesions smaller than 0.5 cm as well as nonobstructing lesions. In such cases, the fiber should be as close to the lesion as possible to avoid light attenuation through air (ie, adjacent location) In addition, for hypervascular lesions, we prefer that the probe be adjacent to the target tissue rather than embedded in the lesion to avoid bleeding, which could interfere with light penetration into the tumoral tissue.

Once the diffuser is in place, light is applied at a typical initial energy of 200 Joules per cm (range is 50 to 300 Joules). This usually takes six to eight minutes with a diode laser. A lower energy may be used for tracheal and mainstem bronchial lesions in case a profound response is expected. A second light application can be applied after the initial debridement bronchoscopy in case there is residual obstructing untreated tumor. (See 'Dosimetry' above.)

After the light has been applied, the probe is removed, secretions are suctioned, and the bronchoscope is removed.

Tissue remains sensitive to light for up to three to six weeks such that PDT can be repeated without readministering the photosensitizing agent during this period. Some centers perform one PDT session only, while others routinely perform two sessions (eg, one initial session and a second at the time of follow-up bronchoscopy). However, in our experience, the number of sessions varies depending on the tumor size and tumor response. Follow-up bronchoscopy for secretion clearance is most frequently performed within two to four days after each illumination, during which time repeat illumination of the target lesion may be performed if additional response is needed (picture 3A-C). Repeat illumination for more profound effect should be carefully considered as the delayed effect of tissue necrosis of up to 6 mm could potentially damage the airway wall and adjacent vasculature. In our experience, if the airway lumen patency is satisfactorily restored (<50 percent obstruction) after the debridement of the necrotic tissues, then reillumination is not needed. (see 'Follow-up' below)

COMPLICATIONS — Complications of bronchoscopic photodynamic therapy (PDT) can be due to the PDT itself or due to bronchoscopy and/or procedural sedation [9,11-19,46,47]. The rate of reported complications ranges from 5 to 15 percent, with photosensitivity as the most common. As an example, in one retrospective study of 529 operations performed on 133 patients, morbidity occurred in 15 percent (eg, reintubation due to respiratory distress, photosensitivity, myocardial infarction) [9]. The operative mortality was 9 percent, but no deaths were directly related to the procedure itself, and may have been related to suboptimal patient selection.

Photodynamic therapy specific — Several PDT-specific complications have been described:

Photosensitivity – The main adverse effect of PDT is photosensitivity (ie, sunburn) of the skin, which in general occurs in <5 percent of patients, but has been reported in up to 20 percent of treated patients. Patients can remain susceptible to sunlight for up to six weeks following injection. The necessary precautions and the treatment of sunburn are discussed separately. Surgical procedures may be performed at any time during the PDT treatment. In some cases, PDT is scheduled specifically to coincide with operative intervention. No photosensitization has occurred, as long as patients are covered in protective standard surgical draping. Although there are no data on timing of PDT and ionizing radiation therapy, there is a theoretical risk that radiation (a photon source) may activate the drug. However, there are no reports of adverse effects of PDT and radiation therapy. Because of the lack of definitive data, it is probably prudent to plan a two to four week interval between sensitizer injection and the initiation of ionizing radiation. (See 'Photosensitivity precautions' below and "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment" and "Sunburn".)

Airway edema and secretions – Within 24 to 48 hours after treatment, edema and secretions due to tissue sloughing may lead to airway compromise or respiratory insufficiency that sometimes requires intubation and mechanical ventilation (typically <2 percent). This is especially worrisome in patients with life-threatening tracheal lesions or patients treated with higher energy levels, as well as patients with poor cardiopulmonary reserve. Therapeutic bronchoscopy is typically necessary to clean up debris should this complication occur.

Hemoptysis – Cough with some blood-streaked sputum is not uncommon after the procedure. However, massive hemorrhage from the treated tumor or from inadvertent treatment/rupture of an adjacent blood vessel can occur a few days after the procedure (<1 percent). However, careful selection of suitable tumors not adjacent to major blood vessels may reduce the risk of this complication. (See 'Other' above.)

Chest pain – Chest discomfort related to the inflammatory response is occasionally noted by some patients.

Death associated with PDT has been reported but is usually not directly due to the procedure itself, but rather due to the sedation, underlying disease, or recurrent cancer. Procedure–related death is rare but may be due to massive hemoptysis, and critical airway obstruction. These are likely preventable events if the operators avoid treating critical tracheal/carinal obstruction and tumors invading pulmonary vasculature, respectively.

Since the light is non-thermal, unlike some of the thermally ablative bronchoscopic techniques (eg, laser, argon plasma coagulation, electrocautery), immediate complications including airway perforation or airway fire have not been reported. (See "Endobronchial electrocautery", section on 'Complications' and "Bronchoscopic laser in the management of airway disease in adults", section on 'Complications' and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults", section on 'Complications'.)

Because of epithelial damage associated with PDT, scar formation and strictures can occur as a late complication, weeks to months after the procedure, especially when PDT was applied for superficial airway lesions.

Bronchoscopy specific — Many of the complications associated with PDT are related to bronchoscopy, sedation, or anesthesia (eg, myocardial infarction, respiratory arrest). These complications are discussed separately. (See "Rigid bronchoscopy: Intubation techniques", section on 'Complications' and "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications", section on 'Anticipating and mitigating Complications' and "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Complications' and "Overview of anesthesia", section on 'Risk assessment'.)

FOLLOW-UP — Bronchoscopic photodynamic therapy (PDT) does not require any particular immediate follow-up care in the absence of complications, other than that required routinely for bronchoscopy. Patients usually return home the same day when performed as an outpatient procedure. Incentive spirometry is encouraged for secretion clearance. However, repeat bronchoscopy is generally required within two to four days for clearance of endobronchial debris, during which time repeat illumination is sometimes performed, if necessary. Although of unproven value, many experts perform a clinical evaluation at six weeks to assess the symptomatic response, as well as chest radiography, lung function, and six-minute walk testing to assess the radiographic and physiologic response.

Many experts, however, admit patients for observation if PDT was applied for main airway involvement, especially in patients with poor performance status, those at high risk of developing a significant complication, or those who travel from afar who may not be able to access the facility quickly enough in the event of a complication.

The general follow-up of patients who undergo bronchoscopy or treatment for central airway obstruction (eg, follow up computed tomography [CT]) is discussed separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Follow-up' and "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Postprocedure monitoring'.)

Repeat bronchoscopy — A repeat bronchoscopy is performed in 48 to 72 hours following illumination/activation, when the inflammatory response is particularly prominent and the resulting secretions can cause airway compromise. At that time, all debris should be removed with a flexible bronchoscope, which is usually sufficient. Repeat illumination/activation may be performed at that time, particularly if a response is observed and it is assessed by the clinician that the patient may benefit from additional therapy (ie, significant residual airway obstruction postdebridement). (See 'Bronchoscopic phototherapy' above.)

Although not mandatory, many clinicians perform repeat bronchoscopy at six weeks to assess efficacy (eg, degree of airway patency). This is especially relevant these days in the era of immunotherapy as pseudo-progressive or hyper-progressive disease could result in early recurrent airway obstruction. Repeat PDT may be planned for the future, depending upon the observed response. Photosensitizing agent is administered no more than once every six weeks.

For patients with radiographically occult squamous cell carcinoma of the airway (ie, microinvasive carcinoma) who are treated with curative-intent photodynamic therapy, the American College of Chest Physicians (ACCP) recommends surveillance bronchoscopy at one, two, and three months and thereafter at three-month intervals during the first year, then every six months until five years [48].

Photosensitivity precautions — For six weeks following the procedure, patients should use protective clothing and eyewear whenever exposed to sunlight or sunbeds. Sunscreen does not provide effective protection, since it does not filter all visible wavelengths. Shaded light, light from most artificial light sources, and light from television do not generally pose problems. However, if it is predicted that the patient will be in strong artificial light for a prolonged period (eg, operating room or intensive care unit), covering their skin to avoid skin activation is prudent. Eye and dental exams should be avoided during the photosensitivity period. The protection against and treatment of phototoxicity are discussed separately. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection' and "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment", section on 'Treatment'.)

FUTURE DIRECTIONS — Active research looks to expand the usefulness of photodynamic therapy (PDT). In 2012, experts called for an organized approach to the use of PDT among the institution members of the National Comprehensive Cancer Networks (NCCN) including a web-based PDT registry because it would be a critical tool for assembling data and linking institutions [49].

Areas for expansion of PDT being explored include the use of ancillary devices such as navigational bronchoscopy [50] and ultrasound guidance for interstitial treatment [51]. Combination of photosensitizer and chemotherapeutic agents into nanoparticles is another line of investigation [52]. It is being combined with radiation therapy to take advantage of potential enhancement by ionizing radiation [53]. Also, it is being evaluated as neoadjuvant treatment prior to definitive resection [25]. While bronchoscopic PDT for peripheral lesions seems to be feasible and safe based on a few reports, the exact dosimetry and effectiveness of PDT for peripheral lung tumors remains to be determined in future studies.

SUMMARY AND RECOMMENDATIONS

Bronchoscopic photodynamic therapy (PDT) is a non-thermal ablative technique that can be used to treat central airway disease in adults. A photosensitizing agent, which is administered systemically, is preferentially taken up by neoplastic tissue. Approximately 48 hours later, photosensitized tissue is exposed to light of a specific wavelength, which induces a cytotoxic reaction, resulting in cell death and tissue necrosis. (See 'Introduction' above and 'Principles of photodynamic therapy' above.)

Bronchoscopic PDT is typically a palliative or adjunctive therapy used to relieve non-life-threatening symptomatic airway obstruction due to malignancy (usually non-small cell lung cancer [NSCLC]) that is not amenable to first-line therapies. Less commonly, it may be used to treat hemoptysis due to airway lesions, inoperable nonmalignant conditions of the airway (eg, papillomatosis, granulation tissue), inoperable radiographic occult lung cancer (ROLC), and stump recurrence and residual mucosal disease following resective surgery. Ideal lesions for curative intent treatment are intraluminal and short with an endoluminal surface that is without significant necrotic debris. In most patients with obstructing carcinoma (up to 80 percent), PDT can palliate the symptoms associated with airway disease. (See 'Indications and efficacy' above.)

Patients with extrinsic lesions or life-threatening airway symptoms should not be treated with PDT. In addition, PDT should be avoided in those at risk of adverse effects from bronchoscopy, sedation/anesthesia, or worsening respiratory failure from necrotic debris, as well as in those with known photosensitivity or lesions close to invading a major blood vessel. (See 'Contraindications' above.)

PDT should be performed by physicians trained in its use. Adequate anesthesia is mandatory in order to eliminate coughing and inadvertent repositioning of the light source during the procedure. The photosensitizing agent is injected intravenously (eg, porfimer sodium 2 mg/kg of total body weight). Approximately 48 hours later, a light source, typically diode laser, is introduced via a flexible or rigid bronchoscope. The laser diffuser should preferentially be embedded into the lesion or placed as close to it as possible. Light is applied at a typical initial energy of 200 Joules per cm (range is 50 to 300 Joules) with no more than three or four treatments per lesion in one session. The probe is removed, secretions are suctioned, and the bronchoscope is removed. (See 'Procedure' above.)

Complications can be PDT specific or due to bronchoscopy and/or procedural sedation. They occur in 5 to 15 percent of patients, with photosensitivity as the most common reported PDT-specific adverse reaction. Other PDT-related complications include airway edema and secretions that can worsen respiratory failure, as well as hemoptysis and chest pain. (See 'Complications' above.)

Bronchoscopic PDT does not require any particular, immediate follow-up care in the absence of complications, other than that required routinely for bronchoscopy and incentive spirometry for secretion clearance. However, repeat bronchoscopy is generally required within two to three days for clearance of endobronchial debris, during which time repeat illumination is sometimes performed, if necessary. After six weeks, repeat PDT may be planned for the future (eg, six weeks or longer), depending upon the observed response. In the special case of curative-intent PDT for early airway squamous cell carcinoma, scheduled surveillance flexible bronchoscopy is recommended. (See 'Follow-up' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Armin Ernst, MD, FCCP, who contributed to an earlier version of this topic review.

  1. Dougherty TJ. Hematoporphyrin derivative for detection and treatment of cancer. J Surg Oncol 1980; 15:209.
  2. Edell ES, Cortese DA. Photodynamic therapy. Its use in the management of bronchogenic carcinoma. Clin Chest Med 1995; 16:455.
  3. Gomer CJ, Dougherty TJ. Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue. Cancer Res 1979; 39:146.
  4. Dougherty TJ, Marcus SL. Photodynamic therapy. Eur J Cancer 1992; 28A:1734.
  5. Shafirstein G, Bellnier DA, Oakley E, et al. Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer. Br J Cancer 2018; 119:1191.
  6. Miyazu Y, Miyazawa T, Kurimoto N, et al. Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy. Am J Respir Crit Care Med 2002; 165:832.
  7. Diaz-Jiménez JP, Martínez-Ballarín JE, Llunell A, et al. Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Eur Respir J 1999; 14:800.
  8. Jayadevappa R, Chhatre S, Soukiasian HJ, Murgu S. Outcomes of patients with advanced non-small cell lung cancer and airway obstruction treated with photodynamic therapy and non-photodynamic therapy ablation modalities. J Thorac Dis 2019; 11:4389.
  9. Minnich DJ, Bryant AS, Dooley A, Cerfolio RJ. Photodynamic laser therapy for lesions in the airway. Ann Thorac Surg 2010; 89:1744.
  10. McCaughan JS Jr. Survival after photodynamic therapy to non-pulmonary metastatic endobronchial tumors. Lasers Surg Med 1999; 24:194.
  11. Moghissi K. Role of bronchoscopic photodynamic therapy in lung cancer management. Curr Opin Pulm Med 2004; 10:256.
  12. McCaughan JS Jr. Photodynamic therapy of endobronchial and esophageal tumors: an overview. J Clin Laser Med Surg 1996; 14:223.
  13. Kato H, Okunaka T, Shimatani H. Photodynamic therapy for early stage bronchogenic carcinoma. J Clin Laser Med Surg 1996; 14:235.
  14. Cortese DA, Edell ES, Kinsey JH. Photodynamic therapy for early stage squamous cell carcinoma of the lung. Mayo Clin Proc 1997; 72:595.
  15. Moghissi K, Dixon K, Stringer M, et al. The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases. Eur J Cardiothorac Surg 1999; 15:1.
  16. McCaughan JS Jr, Williams TE. Photodynamic therapy for endobronchial malignant disease: a prospective fourteen-year study. J Thorac Cardiovasc Surg 1997; 114:940.
  17. Maziak DE, Markman BR, MacKay JA, et al. Photodynamic therapy in nonsmall cell lung cancer: a systematic review. Ann Thorac Surg 2004; 77:1484.
  18. Hugh-Jones P, Gardner WN. Laser photodynamic therapy for inoperable bronchogenic squamous carcinoma. Q J Med 1987; 64:565.
  19. Simone CB 2nd, Friedberg JS, Glatstein E, et al. Photodynamic therapy for the treatment of non-small cell lung cancer. J Thorac Dis 2012; 4:63.
  20. Chhatre S, Vachani A, Allison RR, Jayadevappa R. Survival Outcomes with Photodynamic Therapy, Chemotherapy and Radiation in Patients with Stage III or Stage IV Non-Small Cell Lung Cancer. Cancers (Basel) 2021; 13.
  21. Freitag L, Ernst A, Thomas M, et al. Sequential photodynamic therapy (PDT) and high dose brachytherapy for endobronchial tumour control in patients with limited bronchogenic carcinoma. Thorax 2004; 59:790.
  22. Santos RS, Raftopoulos Y, Keenan RJ, et al. Bronchoscopic palliation of primary lung cancer: single or multimodality therapy? Surg Endosc 2004; 18:931.
  23. DeArmond DT, Mahtabifard A, Fuller CB, McKenna RJ Jr. Photodynamic therapy followed by thoracoscopic sleeve lobectomy for locally advanced lung cancer. Ann Thorac Surg 2008; 85:e24.
  24. Lee JE, Park HS, Jung SS, et al. A case of small cell lung cancer treated with chemoradiotherapy followed by photodynamic therapy. Thorax 2009; 64:637.
  25. Akopov A, Rusanov A, Gerasin A, et al. Preoperative endobronchial photodynamic therapy improves resectability in initially irresectable (inoperable) locally advanced non small cell lung cancer. Photodiagnosis Photodyn Ther 2014; 11:259.
  26. Jheon S, Kim T, Kim JK. Photodynamic therapy as an adjunct to surgery or other treatments for squamous cell lung cancers. Laser Ther 2011; 20:107.
  27. Cai XJ, Li WM, Zhang LY, et al. Photodynamic therapy for intractable bronchial lung cancer. Photodiagnosis Photodyn Ther 2013; 10:672.
  28. McCaughan JS Jr, Hawley PC, LaRosa JC, et al. Photodynamic therapy to control life-threatening hemorrhage from hereditary hemorrhagic telangiectasia. Lasers Surg Med 1996; 19:492.
  29. Lieder A, Khan MK, Lippert BM. Photodynamic therapy for recurrent respiratory papillomatosis. Cochrane Database Syst Rev 2014; :CD009810.
  30. Endo C, Miyamoto A, Sakurada A, et al. Results of long-term follow-up of photodynamic therapy for roentgenographically occult bronchogenic squamous cell carcinoma. Chest 2009; 136:369.
  31. Usuda J, Ichinose S, Ishizumi T, et al. Management of multiple primary lung cancer in patients with centrally located early cancer lesions. J Thorac Oncol 2010; 5:62.
  32. Vonk-Noordegraaf A, Postmus PE, Sutedja TG. Bronchoscopic treatment of patients with intraluminal microinvasive radiographically occult lung cancer not eligible for surgical resection: a follow-up study. Lung Cancer 2003; 39:49.
  33. Furukawa K, Kato H, Konaka C, et al. Locally recurrent central-type early stage lung cancer < 1.0 cm in diameter after complete remission by photodynamic therapy. Chest 2005; 128:3269.
  34. Moghissi K, Dixon K. Update on the current indications, practice and results of photodynamic therapy (PDT) in early central lung cancer (ECLC). Photodiagnosis Photodyn Ther 2008; 5:10.
  35. Furuse K, Fukuoka M, Kato H, et al. A prospective phase II study on photodynamic therapy with photofrin II for centrally located early-stage lung cancer. The Japan Lung Cancer Photodynamic Therapy Study Group. J Clin Oncol 1993; 11:1852.
  36. Kato H, Usuda J, Okunaka T, et al. Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital. Lasers Surg Med 2006; 38:371.
  37. Allison R, Moghissi K, Downie G, Dixon K. Photodynamic therapy (PDT) for lung cancer. Photodiagnosis Photodyn Ther 2011; 8:231.
  38. Mehta HJ, Biswas A, Fernandez-Bussy S, et al. Photodynamic Therapy for Bronchial Microscopic Residual Disease After Resection in Lung Cancer. J Bronchology Interv Pulmonol 2019; 26:49.
  39. Chen KC, Hsieh YS, Tseng YF, et al. Pleural Photodynamic Therapy and Surgery in Lung Cancer and Thymoma Patients with Pleural Spread. PLoS One 2015; 10:e0133230.
  40. Simone CB 2nd, Cengel KA. Photodynamic therapy for lung cancer and malignant pleural mesothelioma. Semin Oncol 2014; 41:820.
  41. Friedberg JS, Mick R, Stevenson JP, et al. Phase II trial of pleural photodynamic therapy and surgery for patients with non-small-cell lung cancer with pleural spread. J Clin Oncol 2004; 22:2192.
  42. Okunaka T, Kato H, Tsutsui H, et al. Photodynamic therapy for peripheral lung cancer. Lung Cancer 2004; 43:77.
  43. Usuda J, Inoue T, Tsuchida T, et al. Clinical trial of photodynamic therapy for peripheral-type lung cancers using a new laser device in a pilot study. Photodiagnosis Photodyn Ther 2020; 30:101698.
  44. Chen KC, Lee JM. Photodynamic therapeutic ablation for peripheral pulmonary malignancy via electromagnetic navigation bronchoscopy localization in a hybrid operating room (OR): a pioneering study. J Thorac Dis 2018; 10:S725.
  45. Ohtani K, Usuda J, Maehara S, et al. A combination therapy of photodynamic therapy (PDT) and airway stent placement using a transparent silicone stent. Lasers Med Sci 2020; 35:1035.
  46. Vrouenraets MB, Visser GW, Snow GB, van Dongen GA. Basic principles, applications in oncology and improved selectivity of photodynamic therapy. Anticancer Res 2003; 23:505.
  47. Capella MA, Capella LS. A light in multidrug resistance: photodynamic treatment of multidrug-resistant tumors. J Biomed Sci 2003; 10:361.
  48. Colt HG, Murgu SD, Korst RJ, et al. Follow-up and surveillance of the patient with lung cancer after curative-intent therapy: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e437S.
  49. Ross P Jr. Moving photodynamic medicine forward by stimulating collaboration between the laboratory and the clinic. J Natl Compr Canc Netw 2012; 10 Suppl 2:S1.
  50. Musani AI, Veir JK, Huang Z, et al. Photodynamic therapy via navigational bronchoscopy for peripheral lung cancer in dogs. Lasers Surg Med 2018; 50:483.
  51. Harris K, Oakley E, Bellnier D, Shafirstein G. Endobronchial ultrasound-guidance for interstitial photodynamic therapy of locally advanced lung cancer-a new interventional concept. J Thorac Dis 2017; 9:2613.
  52. Thapa P, Li M, Bio M, et al. Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy. J Med Chem 2016; 59:3204.
  53. Wang GD, Nguyen HT, Chen H, et al. X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy. Theranostics 2016; 6:2295.
Topic 4382 Version 30.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟