Photodynamic Therapy

Photodynamic Therapy

Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction

https://www.ncbi.nlm.nih.gov/pubmed/10573224

Landmark Article 

Reference: Diaz-jiménez JP, Martínez-ballarín JE, Llunell A, Farrero E, Rodríguez A, Castro MJ. Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Eur Respir J. 1999;14(4):800-5.

Background: Prospective, randomized controlled trial comparing Nd:YAG laser resection vs. photodynamic therapy (PDT) with dihematoporphyrinether (DHE) in patients with partially or totally obstructing endobronchial NSCLC

PICO:

Populations:

  • 31 patients with inoperable endobronchial NSCLC

Intervention:

  • Randomized to Nd:YAG laser resection (n=17) vs. PDT (n=14) and followed for 24 months

Comparison:

  • Nd:YAG resection vs. PDT for:
  • Time to local recurrence
  • Symptomatic relief at 30 days
  • Safety

Outcome:

  • Median time for relapse was longer in the PDT group (50 vs. 38 days, P=.03).
  • Survival was longer in the PDT group (265 vs. 95 days, P=.007); however, the PDT group had less patients with advanced disease compared with the laser group.
  • Degree of symptomatic relief was similar across groups.
  • Patients in the PDT group had more overall adverse effects (mainly bronchitis and photosensitization)

Take Home: When compared with single-modality Nd:YAG laser resection in patients with endobronchial central airway obstruction (CAO) by NSCLC who are not surgical candidates, PDT with DHE may offer longer time to recurrence and survival and similar symptomatic relief at the cost of more side effects. Caution should be applied as PDT group overall had less advanced disease.


 Preoperative endobronchial photodynamic therapy improves resectability in initially irresectable (inoperable) locally advanced non small cell lung cancer

https://www.ncbi.nlm.nih.gov/pubmed/24704942

Clinical Trial

Reference: Akopov A, Rusanov A, Gerasin A, Kazakov N, Urtenova M, Chistyakov I. Preoperative endobronchial photodynamic therapy improves resectability in initially irresectable (inoperable) locally advanced non small cell lung cancer. Photodiagnosis Photodyn Ther. 2014;11(3):259-64.

Background: Prospective, randomized-controlled trial evaluating the addition of preoperative PDT to neoadjuvant chemotherapy in downgrading of stage 3A and 3B NSCLC.

PICO:

Populations:

  • Stage 3A or 3B endobronchial NSCLC which is either unresectable or resectable in a patient with poor lung function precluding surgery.

Intervention:

  • Preoperative PDT + neoadjuvant paclitaxel/carboplatin chemotherapy (n=21)

Comparison:

  • Preoperative neoadjuvant paclitaxel/carboplatin chemotherapy alone (n=21)

Outcome:

  • Groups compared in terms of a) degree of response: complete response (CR), partial response (PR), or no response (NR) as assessed by imaging; and b) surgical treatment offered to patients with CR or PR
  • No difference between groups in degree of CR or PR.
  • No difference in rate of patients achieving staging downgrade to become resectable; however, more patients in the PDT arm were offered R0 resection as compared with the non-PDT arm (P=.038).
  • Safety: One post-operative death in each group.

Take Home: In patients with stage 3A or 3B endobronchial disease which is either unresectable or resectable but the patient is a poor surgical candidate due to poor lung function, the addition of PDT to neoadjuvant chemotherapy with paclitaxel/carboplatin did not result in higher rates of CR or PR; however, more patients in the PDT arm were offered R0 resection (secondary outcome), as compared with the non-PDT arm.


 Outcomes of patients with advanced non-small cell lung cancer and airway obstruction treated with photodynamic therapy and non-photodynamic therapy ablation modalities

https://www.ncbi.nlm.nih.gov/pubmed/31737325

Clinical Trial 

Reference: 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(10):4389-4399.

Background: Exploratory analysis of the SEER database comparing Medicare patients with stage 3 or 4 NSCLC who received: a) PDT ablation + radiation therapy (RT) ± chemotherapy; b) non-PDT bronchoscopic ablation + RT ± chemotherapy; or c) RT ± chemotherapy.

PICO:

Populations:

  • SEER-Medicare database; Patients 18 years or older with a diagnosis of stage 3 or 4 NSCLC between 2000 and 2011 (n=43,783)

Intervention:

  • Comparison between:
  • PDT ablation + RT ± chemotherapy (n=39) for CAO
  • Non-PDT bronchoscopic ablation + RT ± chemotherapy (n=558) for CAO
  • RT ± chemotherapy (n=43,186) – the authors assume that this group had no CAO requiring intervention

Comparison:

  • PDT and non-PDT ablation groups were compared to RT ± chemotherapy in terms of
  • Mortality (all-cause and cause-specific)
  • Need for subsequent treatments (PDT and non-PDT ablation groups only)

Outcome:

  • All-cause mortality was similar between PDT ablation and RT ± chemotherapy group [hazard ratio (HR)=1.03; 0.73-1.45] and was higher for non-PDT ablation when compared with RT ± chemotherapy group (HR=1.22; 1.13-1.33).
  • Lung cancer-related mortality was similar between PDT ablation and RT ± chemotherapy group (HR=1.04; 0.71-1.51) and was higher for non-PDT ablation compared with RT ± chemotherapy group (HR=1.10; 1.01-1.20).
  • PDT-ablation patients had a non-statistically significant (P=0.44) 29-day increase in the time to repeat intervention when compared with non-PDT ablation patients.

Take Home: In patients with advanced-stage NSCLC and CAO, PDT-ablation combined with RT ± chemotherapy is associated with all-cause and lung cancer-specific mortality rates similar to advanced-stage NSCLC patients without CAO (assuming that receiving RT ± chemotherapy only indeed meant no CAO); whereas in patients with advanced-stage NSCLC and CAO, non-PDT-ablation combined with RT ± chemotherapy is associated with higher all-cause and lung cancer-specific mortality rates when compared with advanced-stage NSCLC patients without CAO.


 Photodynamic laser therapy for lesions in the airway

https://www.ncbi.nlm.nih.gov/pubmed/20494021

Retrospective 

Reference: Minnich DJ, Bryant AS, Dooley A, Cerfolio RJ. Photodynamic laser therapy for lesions in the airway. Ann Thorac Surg. 2010;89(6):1744-8.

Background: Retrospective cohort study of patients who underwent PDT in a single high-volume USA center; this cohort includes a mix of participants, including some with non-NSCLC endobronchial lesions.

PICO:

Populations:

  • Total of 529 procedures in 133 patients with central endobronchial disease; 67% with NSCLC, 23% with thoracic metastatic disease, 5% with benign disease, and 3% with SCLC; 95% of participants presented with dyspnea and 86% presented with hemoptysis

Intervention:

  • Photofrin™ PDT via a rigid bronchoscope

Comparison:

  • None

Outcome:

  • Mean PDT treatments 1.58/participant.
  • Dyspnea improved in 74% and hemoptysis resolved in 99%.
  • Airway patency (not clearly defined) achieved in 81%.
  • 12 deaths, none related to the procedure
  • Complication rate was 20%, most commonly respiratory failure requiring intubation

Take Home: PDT may be considered for patients with central endobronchial disease (variety of etiologies) presenting with dyspnea and/or hemoptysis. This data should be interpreted with caution due to the lack of comparison group, diverse etiologies for CAO, and single-center highly experienced report.


 Results of long-term follow-up of photodynamic therapy for roentgenographically occult bronchogenic squamous cell carcinoma

https://www.ncbi.nlm.nih.gov/pubmed/19318660

Retrospective 

Reference: 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(2):369-375.

Background: Retrospective cohort of PDT with Photofrin™ in patients with early-stage radiographically occult endobronchial squamous cell carcinoma (SqCC) coming from a high-volume, highly-experienced center in Japan.

PICO:

Populations:

  • Medically operable patients with non-metastatic, radiographically-occult endobronchial SqCC, which is completely visible bronchoscopically and ≤10 mm in length (n=48, all male).

Intervention:

  • All participants underwent PDT with Photofrin™ and were followed with imaging, cytology (brush), and/or pathology (biopsy), for a median follow-up period of 63 months.

Comparison:

  • None

Outcome:

  • CR as defined by negative cytology/pathology for at least 4 weeks vs. non-CR. Local recurrence was defined as recurrence at the same location as PDT after CR.
  • CR recorded in 45/48 participants.
  • Local recurrence following CR occurred in 9/45 participants within 3-47 months (mean: 25 months).
  • 10 participants developed metachronous airway lesions. Survival was significantly compromised in those with metachronous cancer.

Take Home: In high-volume, highly experienced PDT centers, PDT with Photofrin™ and close bronchoscopic surveillance can be considered in early-stage operable patients with endobronchial, radiographically-occult SqCC. However, given no comparison group, these results should be interpreted with caution. Safety indices were also not reported.