Photodiagnosis and Photodynamic Therapy (2004) 1, 253—262

Photodynamic therapy (PDT) for lung cancer:

the Yorkshire Laser Centre experience
K. Moghissia, Kate Dixona,∗, J.A.C. Thorpea, C. Oxtobya, M.R. Stringerb

a The Yorkshire Laser Centre, Woodland Avenue, Goole, East Yorkshire, DN146RX, UK
b Department of Medical Physics, The University of Leeds, UK
Available online 2 November 2004

KEYWORDS Summary
Lung cancer; Background: The Yorkshire Laser Centre team have been engaged in photodynamic
Bronchoscopic therapy (PDT) since 1990. In this article we review our experience in bronchoscopic
photodynamic therapy PDT for lung cancer and outline our current indications and results.
Methods: 160 patients in 2 groups entered into a prospective study: Group A (N = 144)
were symptomatic with advanced inoperable disease and with presence of >50%
bronchial obstruction. Group E (N = 16) with early stage cancer and presence of
superficial lesion confined to bronchial tree. All patients had standard investiga-
tion and work-up bronchoscopy and biopsy confirmation of cancer by cyto-histology.
PDT method was intravenous administration of 2 mg/kg BW of Photofrin (Porfimer
Sodium) followed by bronchoscopic illumination of 630 nm laser light.
Results: There was no treatment-related mortality. Nine patients (5.6%) presented
with skin photosensitivity reaction and another eight with respiratory complica-
tion. Group A: Symptom relief was achieved in all. This was matched by significant
improvement in bronchial opening (58.1%). Survival was 9.6 months (mean) and 5
months (median), respectively. This was greater in patients with better performance
status and lower stage of disease. Group E: Every patient had a complete response
to treatment, some after two treatments. Survival in this group was 75.4 months
(mean) and 69 months (median).
Conclusions: Bronchoscopic PDT is indicated in both advanced and early stage lung
cancer. In the former it provides symptomatic relief in all and survival benefit in
some; in the latter it achieves long survival and potential cure.
© 2004 Elsevier B.V. All rights reserved.

Introduction

Photodynamic therapy (PDT) is a treatment method

that relies upon the excitation of a chemical pho-
tosensitiser (the drug) by light of an appropriate
* Corresponding author. Tel.: +44 1724 290456;
fax: +44 1724 290456.
wavelength, in order to stimulate the production
E-mail address: kdixon@yorkshirelasercentre.org of highly reactive singlet oxygen species (1 O2 ) via
(K. Dixon). a process of molecular energy transfer. It is a two-

1572-1000/$ — see front matter © 2004 Elsevier B.V. All rights reserved.
doi:10.1016/S1572-1000(04)00047-X
254
phase process, firstly involving the administration
of the photosensitiser to the target tissue, usually
systemically, by drug injection. There is then a la-
tent period allowing for drug distribution and ac-
cumulation in the target tissue. The second phase
involves a controlled light exposure of the sensi-
tised target tissue. Ultimately, the production of
sufficient cytotoxic oxygen species results in tissue
necrosis. The significance of PDT in cancer ther-
apy is that a degree of treatment selectivity allows
tumour destruction with minimal involvement of
healthy tissue. This is achieved by a combination of
the accumulation of a higher concentration of drug
within the target (tumour contrast) and by control
of the light geometry and illumination parameters.
In the early 1970s Dougherty et al. [1,2] showed
that PDT was effective against a variety of experi-
mental and naturally occurring human cancers. By
virtue of its high incidence and low resection rate,
lung cancer became one of the first cancers to be
considered for PDT. This was particularly the case
for the central type of tumours with identifiable en-
dobronchial lesions which could be easily accessed
bronchoscopically for illumination. The first bron-
choscopic PDT was carried out by Hayata et al. [3]
at Tokyo Medical University for a case of early stage
disease in a fit patient who declined surgical resec-
tion. It is reported that the patient survived over 4
years and died from a non-cancer related cause [4].
In the early 1980s other groups undertook bron-
choscopic PDT for early and advanced staged dis-
ease [5—7]. Thus far, in an overall majority of cases,
PDT has been used for central types of lung can-
cer with illumination using bronchoscopic access.
There are, however, a small number of reported
cases of peripheral tumours treated by PDT [8]. Our
group began a trial of bronchoscopic PDT for ad-
vanced central type lung cancer in 1990 [9]. Since
then we have expanded our use of PDT to include
both early and advanced inoperable cancer. We
have also carried out a feasibility study in accessing
peripheral tumours thoracoscopically [10]. In this
article we present our updated experience in PDT
for lung cancer and critically review the appropri-
ate published literature, the aim being to present
current indications and expected results of PDT in
the spectrum of this disease and to sum up the
lessons learnt.
Material and method
During a 13-year period, 166 patients with inoper-
able primary lung cancer were submitted to PDT of
whom 160 patients received bronchoscopic PDT and
K. Moghissi et al.
6 had thoracoscopic and/or intra-operative treat-
ment. The subject of this article are those patients
having bronchoscopic PDT; the other six cases will
be referred to in the discussion. Patients were di-
vided into two groups:
Group A: Those with advanced disease stages III
and IV of TNM classification [11] with an unre-
sectable tumour.
Group E: Those with early disease (intra-epithelial
neoplasia [TIS]) and stage I who were oncologically
operable but ineligible for resectional surgery on
account of inadequacy of their cardio-respiratory
function or their poor general fitness for opera-
tion.
Patients in both groups were entered into an on-
going prospective study. They were referred to us
by specialist physicians/oncologists and had been
fully investigated and diagnosed with lung cancer
by the referral source. A substantial number had
undergone surgery, radiotherapy, chemotherapy or
other treatment, either individually or in combina-
tion, prior to referral for PDT. Some patients in the
series were the subjects of specific studies and pre-
vious publications [12,13]. On admission to our care
every patient had recording of symptoms, clinical
examinations, routine laboratory tests such as full
blood count and biochemical profile in addition to
other specific investigations as warranted. Spirom-
etry and performance status were recorded in all.
For the latter we used the WHO scale (Table 1).
Every patient had a plain chest radiograph (CXR)
and CT of the thorax and abdomen. Other imag-
ing examinations were undertaken as indicated.
Pre-PDT work-up included clinical staging of the
tumour and endoscopy consisting of bronchoscopy
in all and oesophagoscopy and mediastinoscopy in
some. At bronchoscopy topography and extent of
tumour within the bronchial tree were mapped out
and samples taken for cyto/histopathology. For the
past 3 years, since the availability of fluorescence
bronchoscopy in our institution, we have used the
Table 1 WHO scale.
1 Able to carry out all normal activity without
restriction
2 Restricted in strenuous activity but ambulatory
and able to carry out light work
3 Ambulatory and capable of all self-care but
unable to carry out light work; up and about
more than 50% of waking hours
4 Capable of only limited self-care; confined to
bed or chair more than 50% of waking hours
5 Completely disabled; cannot carry out any
self-care
Photodynamic therapy (PDT) for lung cancer: the Yorkshire Laser Centre experience
technique in addition to white light bronchoscopy
both for mapping of tumour extent and for more
accurate cyto/histological sampling.
Patient selection and PDT method
Due to referral pattern many of our patients were
pre-selected and referred to us for bronchoscopic
PDT. However, allocation to the two groups (A and
E) was made according to the stage of the patient’s
cancer and with two provisos: (1) visible evidence
of the tumour at bronchoscopy with confirmation
of it being cancer on microscopic examination, and
(2) unsuitability for surgical resection.
Our PDT protocol consists of:
• Patient information and counselling: After pa-
tient selection and before photosensitisation of
the tumour, patients are given information on
PDT. They are counselled on all possible ad-
verse events, notably skin photosensitivity reac-
tion (skin burn) in response to direct or reflected
sunlight. We stress the problems associated with
photosensitivity repeatedly at all stages of the
procedure and verbally discuss its prevention and
treatment and issue written guidelines in a pa-
tient information sheet.
• Photosensitisation: In our early experience we
used Photofrin II, but more recently, with the
development of Photofrin® (Porfimer Sodium)
we have used this preparation. In all cases the
drug was injected intravenously at 2 mg/kg body
weight. The latent period between drug admin-
istration and light exposure was 24—72 h.
• Light delivery and dosimetry: An activation wave-
length of 630 nm was used. In our early stud-
ies this was provided by a copper vapour dye
laser. More recently, a semiconductor diode laser
has been used. Both devices are capable of de-
livering variable power up to 2 W, although the
diode laser offers significant advantages in terms
of ease-of-use, running costs and stability. Light
is delivered to the patient via a flexible fibre-
optic; these are constructed with a diffusing tip
of 0.5—3 cm designed to emit light of uniform in-
tensity over a cylindrical geometry. Alternatively,
we use a micro-lens fibre to allow superficial illu-
mination over a defined area. The total light dose
depends upon the target volume. For bulky tu-
mours that demand interstitial fibre placement,
light is delivered at 200 J/cm of diffuser length
at a rate of 400 mW/cm for 500 s. Superficial tu-
mours receive 100—150 J/cm2 . In unusual situa-
tions, such as treatment of a bronchial stump for
recurrence, we adopt variable light parameters
to suit individual circumstances.
255
• Instrumentation and illumination: Our routine is
to carry out bronchoscopic PDT under general
anaesthesia (GA) for the majority of patients with
endoluminal obstructive tumours requiring inter-
stitial (intra tumour) treatment and effective fa-
cilities for suction and bronchial cleansing dur-
ing the procedure [9]. Patients with superficial
early cancer are given the choice of either lo-
cal/topical anaesthesia (LA) or GA. Topical anaes-
thetic is also used in patients deemed unsuitable
for/or choose not to have GA. The flexible fibre-
optic instrument alone is used for bronchoscopy
under LA. Both rigid and fibreoptic bronchoscopes
are employed for patients under GA where, in the
first place the rigid instrument is placed in the
trachea for ventilation (using jet ventilation or
an injector). The flexible fibreoptic instrument is
then introduced through the rigid bronchoscope
for localisation of the endobronchial lesion and
for illumination. The latter is preceded by the
introduction of the delivery fibre through the
biopsy channel of the fibreoptic instrument. For
interstitial illumination an appropriate size dif-
fuser is inserted into the tumour mass (Fig. 1).
For superficial tumours the micro-lens or diffuser
tip is placed at a pre-determined distance from
the lesion (Fig. 2).
• Post-illumination clean up procedure (debride-
ment): In patients with bronchial obstructive le-
sions we carry out bronchial cleaning immedi-
ately after completion of illumination and repeat
this 4—5 days later at which time re-illumination
of any residual tumour is undertaken if required.
For debridement we use a rigid instrument with
large biopsy forceps in order to remove necrotic
tissue and particles of tumour mixed with clotted
material. Normal saline (50—100 ml body temper-
ature) is then injected into the bronchial tree for
lavage; this is aspirated, thus removing small par-
ticles of debris. Whilst we are rigorous in debride-
ment for bulky tumours within the main bronchi,
we rely on physiotherapy and patient expectora-
tion in superficial or segmental tumours.
• Assessment of results: Four to six weeks after il-
lumination the immediate results are assessed on
the basis of:
◦ Mortality.
◦ Adverse events (complications).
◦ Patient satisfaction to treatment.
◦ Relief of symptoms.
◦ Spirometry.
◦ Chest radiography and changes in the lung
fields.
◦ Changes in performance status.
• Follow up: Patients are reviewed and broncho-
scoped 4—6 weeks post-PDT and then at 3 and
256 K. Moghissi et al.

Figure 2. (a) Superficial tumour seen at the entrance to

the left upper lobe. (b) Light delivery via the micro-lens
Figure 1. (a) Bulky tumour obstructing the bronchial lu- (forward illumination) for early superficial cancer.
men. (b) Diffusing tip of the fibre in the tumour for in-
terstitial illumination.
of sample proves positive for malignancy. No re-
sponse (NR) is when neither the volume of tumour
6 monthly intervals as required. The follow-up nor the cyto/histology has changed.
continues to the patient’s death. At follow up
bronchoscopy the macroscopic extent of the tu-
Statistics
mour is visually evaluated and biopsy, brush or
lavage samples are collected from treated areas
for histo/cytology. Based on bronchoscopic evi- A comparison of pre- and post-PDT values is per-
dence and microscopic results of the samples, lo- formed using Log Rank. Survival curves are con-
cal response to treatment is defined as complete structed using the Kaplan—Meier method.
response/remission (CR) when neither macro-
scopic visualisation at bronchoscopy, nor micro-
scopic cyto/histology of samples, show evidence Results
of cancer. Partial response/remission (PR) is de-
fined when reduction in tumour volume at post- One hundred and sixty patients received 280 bron-
PDT bronchoscopy is >50% or if the cyto/histology choscopic PDT treatments (mean 1.7 treatments/
Photodynamic therapy (PDT) for lung cancer: the Yorkshire Laser Centre experience 257

Table 2 Characteristics of patients in Group A (advanced stage) and Group E (early stage), respectively.
Parameter All patients Group A Group E
Number of patients 160 144 16
Number of PDT 280 261 19
Male 119 106 13
Female 41 38 3
Age range (mean) 44—88 (65.5) 44—88 (64.6) 53—86 (65.8)
Histology
Squamous cell 109 98 11
Adeno carcinoma 32 29 3
Small cell carcinoma 12 12 0
Other NSCLCa 5 5 0
Carcinoma in situ 2 0 2
a NSCLC: non-small cell lung cancer.

patient). They were divided into two groups. Group Group A

A: 144 patients with advanced staged disease and
Group E: 16 patients with early stage cancer. De-
mography and characteristics of the patients in the
two groups are shown on Table 2.
There was no procedure-related mortality in ei-
ther group. A total of nine cases of photosensitiv-
ity skin reaction (skin burn) occurred in the entire
series, an incidence of 5.6% of patients or 3.2% of
treatments. The skin burn in our cases was classified
as mild and consisted of erythema and oedema of
exposed parts (hands and/or face) in eight patients
with the addition of a few blisters over the dor-
sum of the hands in one case. These subsided within
3—5 days assisted by topically applied steroidal skin
cream.
Post-PDT bronchitis and respiratory system in-
fection occurred in eight patients during our initial
experience. In the last 100 cases we have admin-
istered one dose of an antibiotic (1.5 g Cephurox-
ime) intravenously peri-operatively as a prophylac-
tic measure in patients with bulky endobronchial
lesions or in those who were smokers. This has re-
sulted in elimination of post-PDT pulmonary com-
plications. We have not observed frank haemoptysis
due to PDT.
Every patient in both groups expressed their to-
tal satisfaction with the treatment.
All patients in this group were symptomatic,
85% had previously been treated by radiotherapy,
chemotherapy and/or bronchoscopic NdYAG laser
therapy. All had substantial (≥50%) obstruction en-
doluminally. At 6—8 weeks post-PDT every patient
in this group had symptom relief particularly in re-
lation to dyspnoea. The improvement was matched
with a parallel amelioration of CXR and relief of
obstruction. Table 3 shows the pre-and post-PDT
extent of bronchial obstruction expressed as a per-
centage of total luminal obliteration. The table also
shows spirometry values and performance status
(PS), respectively. The improvement of PS as a re-
sult of PDT was statistically significant (P < 0.005
log rank). However, the improvement in FVC and
FEV1 seen in Table 3 did not reach statistical signif-
icance.
Every patient had local response to treatment.
Response was complete (CR) for a limited period
between 2 and 21 months in 18 patients. In all other
patients, partial response (PR) was recorded; mean
and median survival for patients in this group was
9.6 months (±1.04 months) and 5 months (±0.69
months), respectively. Fig. 3 shows the survival
curve of patients in Group A. Fig. 4 shows the sur-
vival curve of patients with PS ≤ 2 (good PS) and

Table 3 Details of pre- and post-operative spirometry and performance status (PS) in patients with advanced lung
cancer (Group A).
Parameters Pre-PDT (mean + S.D.) Post-PDT (mean + S.D.) Changes
Percent obstruction (percent range) 78.4 ± 27.2 (50—100) 20.3 ± 19.43 (0—90) −58.1
FVC (litres) 1.55 ± 0.76 1.8 + 0.8 +0.25
FEV1 (litres) 1.38 ± 0.32 1.7 + 0.58 +0.32
PS: WHO <2 N = 72 N = 115 +43
PS: WHO >2 N = 58 N = 15 −43
258
Figure 3. Kaplan—Meier survival curve of all Group A pa-
tients.
that of patients with PS > 2 (moderate—poor PS),
respectively.
Of note is that, in 12 patients in this group, the
histology was small cell lung cancer. Eight of these
had previously had chemotherapy; four other pa-
tients had PDT and chemotherapy concurrently.
Group E
All patients in this group had cough and sputum.
Some had blood-stained expectoration. No patient,
at presentation, had significant endoluminal ob-
struction or dyspnoea related to the cancer. Post-
PDT improvement in cough occurred in 10 out of 17
and blood-staining of sputa ceased in all. There was
no amelioration of FVC and FEV1 in group E patients
and performance status did not change significantly
as a result of treatment. Response to treatment was
Figure 4. Kaplan—Meier survival curve of Group A pa-
tients according to WHO performance status.
K. Moghissi et al.
Figure 5. Kaplan—Meier survival curve of Group E pa-
tients.
monitored in every patient except one who died un-
expectedly 1 month after PDT from myocardial in-
farction. In this patient bronchoscopic check was
not carried out. Fifteen other patients had com-
plete response lasting 6—24 months following a sin-
gle treatment. Those with tumour recurrence were
re-treated and again had complete response. Mean
and median survival of patients in this group is 75.4
(S.D. 14.4) months and 69 (S.D. 37.9) months, re-
spectively. Fig. 5 shows the survival curve of pa-
tients in this group.
Discussion
In 1933 Graham and Singer [14] reported the first
successful case of pneumonectomy for lung cancer
and laid down the foundation of surgical resection
which has continued to be the mainstay and stan-
dard method of treatment for this disease. The im-
mediate consequence of the event was such that
in the next 25 years any patient with lung cancer,
whose general condition allowed the operation, was
submitted to thoracotomy. However, this initial en-
thusiasm and the ethos of ‘‘operation for all’’ was
tempered by subsequent experience and the real-
isation that unqualified surgical resectability nei-
ther equates with oncological operability nor influ-
ences survival. In fact, it became clear that the
long-term survival was largely dependent on the
extent of the primary tumour and its metastatic
ramification. The concept of pre-operative work-
up, including tumour staging procedure and selec-
tion of patients for surgical resection as is cur-
rently practiced, resulted from the above experi-
ence assisted by the availability of computed to-
Photodynamic therapy (PDT) for lung cancer: the Yorkshire Laser Centre experience
mography (CT) and development of sophisticated
methods of investigation. However, paradoxically,
one of the consequences of these developments in
the face of late presentations of lung cancer was
that a more rigorous process was applied in select-
ing patients for operation. The result was that only
15—20% of patients could be submitted to or could
benefit from surgical resection; this rate has not al-
tered significantly over the years [15,16]. It follows
that in practical terms some 80% of lung cancer pa-
tients require treatment other than surgical resec-
tion. Over the past 20 years bronchoscopic PDT has
been used effectively for some of this large popu-
lation of patients. There are cases with lung can-
cer whose tumour can be identified and, therefore,
be treated bronchoscopically. From a therapeutic
point of view, this subset comprises of two groups;
advanced (Group A) and early (Group E) stage dis-
ease.
A substantial majority of patients in our series
had advanced inoperable disease. Initially we se-
lected patients with advanced disease for bron-
choscopic PDT on the basis of oncological inoper-
ability, the presence of symptoms and evidence of
an endobronchial exophytic lesion causing a sub-
stantial (>50%) endoluminal obstruction. The ma-
jority of these patients had either failed to respond
to radiotherapy and chemotherapy or had recur-
rence following these treatments. With experience
it became apparent that, notwithstanding symp-
tom relief, the patients with stage IV metastatic
disease had a limited post treatment survival ben-
efit [13]. In effect, although PDT had controlled
the cancer locally in the bronchial tree, patients
were succumbing as a result of general metastatic
disease. We also showed that patients with poor
performance status (>3 WHO scale) had a shorter
survival than those with better performance sta-
tus. In the present updated series we confirm the
latter finding (Fig. 3). Similar observations were
made by McCaughan and Williams [17] in a large
series of patients with advanced disease undergo-
ing bronchoscopic PDT. Therefore, our present pol-
icy is not to select patients for bronchoscopic PDT
from those with advanced disease and extratho-
racic metastases (Stage IV) or those with poor PS.
At our centre such patients would receive broncho-
scopic NdYAG laser treatment aimed at relief of
symptoms.
Some debate has recently been centred on
the merit of offering patients with advanced dis-
ease and endobronchial exophytic tumours bron-
choscopic PDT instead of submitting them to other,
seemingly less complex, endobronchial interven-
tions, notably NdYAG laser. We believe such a de-
bate should be based on the understanding that the
259
mechanism of NdYAG laser relates solely to its ther-
mal effects (evaporation and charring) which is non-
specific and without any distinct oncological effect.
NdYAG laser photoradiation and its destructive ac-
tion per se cannot discriminate between cancer and
non-cancer tissues. In contrast PDT, by virtue of its
specific action, is endowed with the power of dis-
crimination. This is, firstly, because of the selective
concentration of drug in the tumour compared with
that of normal tissue and then due to targeted illu-
mination with the light ‘‘homing in’’ on the pre-
sensitised target. It should also be noted that a
number of studies, notably three randomised trials
comparing bronchoscopic application of YAG laser
with that of PDT [12,18,19] have shown that pa-
tients undergoing PDT require less frequent hospital
attendance for re-treatment than in NdYAG treat-
ment. Furthermore, there is a higher incidence of
major adverse events and serious complications as-
sociated with NdYAG laser therapy than with PDT.
It is, however, important to emphasise that bron-
choscopic PDT is not suitable for patients with a
major malignant tracheo-bronchial obstruction pre-
senting with an emergency clinical situation of dys-
pnoea and stridor. Such patients require immediate
relief of the obstruction which is achieved expedi-
tiously with bronchoscopic NdYAG laser for tumour
evaporation. In these and in some selected cases of
lung cancer we have used NdYAG laser in sequence
with PDT [20]. The combined treatment is particu-
larly useful in exophytic tumours of the main-stem
bronchus extending to the carina or trachea. The
principal is to debulk the tumour by YAG laser and
then 4—6 weeks later to use PDT to more specifi-
cally affect the cancer.
Our current policy on bronchoscopic PDT for ad-
vanced stage lung cancer is that patients are se-
lected on the basis of:
• Existence of substantial endobronchial disease
with existing or impending related symptoms.
• Acceptable performance status (≤3 WHO scale
and preferably ≤2).
• Absence of extra thoracic metastases.
When the tumour is in the main-stem bronchus
near the carina and/or extends to the trachea, we
undertake sequential bronchoscopic NdYAG laser
treatment and PDT separated by an interval of
about 4 weeks.
Our experience in bronchoscopic PDT in early
stage lung cancer is relatively small. This partly
relates to the referral pattern in the UK and our
attitude that surgical operation should be consid-
ered in patients with early stage lung cancer if at
all possible. We, therefore, submit to resection as
many patients as possible, employing such methods
260
as broncho-vascular plastic operations and minimal
access surgery to improve resectability rate. Thus,
far all of our bronchoscopic PDT for early stage lung
cancer cases have been amongst patients who were
considered to be unsuitable for surgical resection.
The unsuitability was either due to pulmonary func-
tional insufficiency or existence of metachronous
endobronchial lesions in patients previously treated
by surgical resection. Nevertheless, both our mod-
est experience and review of over 800 cases from
the literature [20] shows that bronchoscopic PDT
in early stage cancer cases achieves long survival.
We, therefore, suggest that the aim of PDT in such
patients should be curative in intent. Kato and co-
workers [4,8] have repeatedly shown that in many
patients with early intraepithelial cancer there are
multi-focal lesions. This emphasises the importance
of meticulous bronchoscopic evaluation of endo-
bronchial lesions. Fluorescence bronchoscopy can
improve detection rates of these lesions and assist
biopsy of the site most likely to be representative
of the lesion [22]. The notion of multi-focality and
multiplicity of lesions is also relevant in choosing
a treatment option which can effectively deal with
this difficult clinical situation. In practical terms,
surgery as a treatment option is helpful when bron-
choplastic procedures can be undertaken. However,
this option has defined indications which do not
include multi-focal lesions affecting different lo-
bar and segmental bronchi. In our view, PDT is an
ideal mode of treatment for early endobronchial
cancer not amenable to surgical operation, those
with high-risk co-morbidity and patients with poor
predicted post-operative pulmonary function who
could become a respiratory cripple if submitted to
resectional surgery involving parenchymal loss.
Adverse reactions in PDT
Photosensitivity skin reaction
The most frequently observed adverse event of PDT
is photosensitivity skin reaction (sunburn). In this
and our previously reported series the incidence,
with the use of Photofrin, has remained within the
range of 3.5—5% of patients. In a review study of
the literature [21] concerned with 1153 patients the
incidence was between 0 and 40%. The reason for
such an enormous range in the different series is not
totally clear. We believe one of the reasons might be
the variation in meticulousness of the counselling
and information to patients by different teams. For
our part, the issue of photosensitivity needs to be
addressed with the understanding that every pa-
tient undergoing PDT is a potential candidate for
skin burn when the photosensitising drug is admin-
K. Moghissi et al.
istered systemically (intravenously). This being the
case, the counselling of patients and their close rel-
atives should be written into all PDT protocols. To
a large measure both the incidence and severity of
PDT skin burn can be reduced through appropriate
counselling and repeated warning to patients.
Other adverse events:
• Haemorrhage: Blood-stained expectoration is not
an unusual event after 3—4 days following inter-
stitial PDT and does not constitute an adverse
reaction. Neither in this nor in our other pub-
lished series we have experienced serious post-
PDT haemorrhagic events. Literature review of
636 patients with advanced endobronchial dis-
ease undergoing bronchoscopic PDT and reported
in 12 articles [20] shows that overall there were
4 (approximately 0.6%) fatal haemorrhages and
18 (<3%) cases of serious non-fatal haemopty-
sis. In the same review article of 517 patients
with early stage disease undergoing broncho-
scopic PDT no haemorrhagic complication was re-
ported. We believe post-PDT haemorrhagic com-
plications should be viewed in the light of the fact
that any cancer treatment whose mechanism of
action depends on tumour necrosis would poten-
tially be liable to cause haemorrhage if a blood
vessel is contained within the tumour mass be-
ing targeted. In PDT an inadvertent accidental
and/or incidental illumination of a pre-sensitised
mass of cancer tissue in the wall of a major blood
vessel could lead to serious haemorrhage. This
risk should be borne in mind.
PDT in peripheral lung cancer
Compared with bronchoscopic PDT, which targets
central types of lung cancer, only a small number
of patients with peripheral lung cancer have been
treated by PDT. There are a number of reasons for
this paucity of cases; the first and foremost amongst
these is that many peripheral tumours can be sur-
gically treated using standard minimal access and
video-assisted thoracoscopic techniques. Some pa-
tients, however, will not be selected for, or will
decline, the surgical operation. Such cases would
benefit from PDT providing that the tumour can be
accessed for illumination. Technical difficulty of ac-
cess for illumination and monitoring of response to
treatment are two of the most obvious problems of
PDT in peripheral lung cancer. Review of the lit-
erature indicates that two access methods of il-
lumination have been tried. Kato et al. [8] have
adopted a guided percutaneous method of illumi-
nation. Moghissi et al. [10] have used the thora-
coscopic approach. The number of cases is small
Photodynamic therapy (PDT) for lung cancer: the Yorkshire Laser Centre experience
and result assessment so far, by imaging techniques
alone, lack cyto/histological confirmation which is
the gold-standard of response to cancer therapy. It
is obvious that repeated percutaneous biopsy of a
peripheral lung tumour is not a practical proposi-
tion.
Conclusions
What have we learnt?
This experience, added to the published literature,
indicates that bronchoscopic PDT is an effective as
well as a safe method of lung cancer treatment.
It should be regarded as an oncological method of
therapy in central type lung cancer.
• The prerequisite for bronchoscopic PDT is
a visually identifiable tumour confirmed by
histo/cytological diagnosis.
• Two subgroups benefit from bronchoscopic PDT,
each with a different aim:
◦ Those with oncologically advanced and inop-
erable disease. The primary objective for this
subgroup is palliation. Patients with distant
metastatic disease and those with poor perfor-
mance status appear to have no survival ben-
efit and should not be offered PDT. In patients
with disease localised to chest and good perfor-
mance status there appears also to be survival
benefit.
◦ Patients with oncologically early operable dis-
ease who are unsuitable for surgical pulmonary
resection and those who decline surgery. In
these patients PDT is with curative intent.
Amongst this subgroup are patients with mul-
tiple superficial bronchial lesions or cases with
metachronous disease following previous re-
section. These subsets of patients are particu-
lar subjects for PDT.
• The most important adverse event in PDT is
photosensitization skin reaction. This is largely
preventable and avoidable by effective patient
counselling.
◦ As a rule PDT is managed as a day-case pro-
cedure. Patient investigation, work-up and
preparations are undertaken on an out patient
basis.
In our experience, patient information and coun-
selling is an essential component of PDT. Also, ac-
cess of patients to the PDT team in order to answer
queries and/or address concerns should be consid-
ered when constructing the infrastructure of such a
team. This will underpin the patient’s comfort and
261
confidence and will enhance the chances of a good
result and diminish the risk of complication.
Acknowledgment
This work has been supported by the Yorkshire Laser
Centre, East Yorkshire, UK.
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