As a practicing physician, Dr.Osts perspective on the use of
photodynamic therapy (PDT) in the treatment of lung cancer is
informative and helpful, particularly regarding its application in
the multimodality setting. My comments represent the viewpoint of a
scientist involved in the clinical use of PDT in an academic tertiary
Many lung cancer patients with obstructive disease who are referred
to our institution have not responded to or have suffered a
recurrence following radiation therapy and/or chemotherapy.
Therefore, we are rarely in a position to develop a rational
treatment plan that integrates the various modalities for the optimal
benefit to the patient. Despite this, our outcomes are similar to
those reported by others.
Integrating PDT Into the Overall Treatment Plan
This brings up an important point: In general, PDT can be used
effectively even after other treatments. However, given a choice, how
would PDT best be integrated into the overall treatment plan for
nonsurgical patients with nonsmall-cell lung cancer? Would it
be best to first administer radiation therapy or possibly
chemotherapy followed by PDT? Or, would the reverse sequence of
administration be superior?
The clinical trial conducted by Lam et al,[reference 57 in Dr.
Osts article] which compared PDT followed by radiation therapy
to radiation therapy alone, reported that radiation therapy following
PDT produced superior results to radiation alone. However, Lam et al
did not evaluate the reverse sequence of therapies; namely, PDT
followed by radiation. In their study, radiation therapy alone often
opened the airway (as determined by chest x-ray), but residual tumor
was generally found during endoscopy.
From a theoretical standpoint, the use of PDT to debulk the tumor
prior to radiation therapy makes sense. Unlike PDT, radiation or
chemotherapy kills cells exponentially; ie, each dose destroys a
given fraction of the remaining cells. Therefore, the fewer cells
present at the start of radiation therapy or chemotherapy, the
greater the chance for a good outcome.
PDT and the LIFE System for Detecting Early-Stage Lung Cancer
With respect to early-stage lung cancer, Dr. Ost alludes to an
approach that takes advantage of the natural fluorescence (ie,
without the addition of a fluorescing agent) of the normal
endobronchial mucosa vs that of dysplasia or early-stage cancer to
aid in the early detection of lung cancer. We have been evaluating
this approach for about 2 years, selecting patients with a prior
history of lung cancer. This so-called LIFE (light-induced
fluorescence endoscopy) system incorporates white light and
fluorescence bronchoscopy in a single unit. The data presented to the
Food and Drug Administration (FDA) that led to the approval of the
LIFE system indicated its greatly enhanced ability to detect lung
cancer at an early stage when the two methods (white light and
fluorescence bronchoscopy) were used together, compared to the use of
white light bronchoscopy alone.
With about 70 patients evaluated to date, we have detected seven
cases, most of which were not indicated on chest x-ray or white light
bronchoscopy alone. This result appears to confirm, in a preliminary
way, the results of the larger study reported by Lam et al. The LIFE
system, combined with PDT when appropriate, has the potential to have
a major impact on the outcome of patients with lung cancer.
It is important to examine the studies that led to health agency
approvals of PDT in the United States, Germany, France, and elsewhere
for early-stage lung cancer. These studies, unlike most phase III
clinical trials, were open-label, noncomparative investigations
conducted in four institutions using similar, but not identical,
methodologies. The studies were based largely on much earlier work
carried out by Edell and Cortese, Kato et al, and Sutedja et
al.[references 46, 47, and 49 in the Ost paper] The point to be
emphasized is that numerous investigators in various countries using
somewhat different methodologies have arrived at similar results; ie,
that PDT is effective and safe for this group of lung cancer patients.
PDT in Late-Stage Lung Cancer
Much of the early work that examined PDT in advanced lung cancer was
carried out by Balchum et al. Balchum was the first to devise
dosimetry for these patients, to apply an interstitial means of light
delivery, and, very importantly, to emphasize the absolute need to
perform toilet bronchoscopy in all patients within 2 days of PDT.
The necessity for this last measure was brought home to us in the
early 1980s, when a patient treated for an obstructive tumor near the
carina developed a plug of mucosa and tumor debris that
ultimately blocked both mainstem airways, resulting in
asphyxiation. By the time the patient was in distress, the
material had become too hard to be removed with the biopsy forceps.
Since that time, we routinely subject all patientsboth those
with early- and late-stage lung cancersto toilet bronchoscopy 2
days following PDT, or sooner, if indicated. In some cases,
especially in patients with large tumors, multiple
clean-out bronchoscopies over several days are required.
Thus, although PDT is generally safe and easily performed, care must
be taken in the immediate few days following treatment, especially in
this group of debilitated patients.
1. Lam S, Kennedy T, Unger M, et al: Localization of bronchial
intraepithelial neoplastic lesions by fluorescence bronchoscopy.
Chest 113:696-702, 1998.
2. Balchum O, Doiron D: Photoradiation therapy of endobronchial lung
cancer: Large obstructing tumors, nonobstructing tumors, and
early-stage bronchial cancer lesions. Clin Chest Med 6:255-75, 1985.
3. Vincent R, Dougherty T, Rao U, et al: Photoradiation therapy of
advanced carcinomas of the trachea and bronchus. Chest 85:29-33, 1984.