wowecoin : cryptocurrency cancer treatment :Ngpdt case studies 2014

N e x t G e n e r a t i o n P D T Page 1
Index
Introduction of PDT .........................................................................................................6
A Statement on the Benefits of Photodynamic Therapy...................................................6
Cervical and Gynecological Cancer.................................................................................7
Breast Cancer .................................................................................................................7
Lung Cancer....................................................................................................................7
Prostate Cancer ..............................................................................................................8
Esophagus Cancer..........................................................................................................8
Peritoneal/Sarcoma.........................................................................................................8
Skin Cancer ....................................................................................................................8
Bile Duct Cancer .............................................................................................................8
Stomach Cancer .............................................................................................................8
Brain Cancer ...................................................................................................................9
Cutaneous Lymphoma ....................................................................................................9
Liver Metastases.............................................................................................................9
Malignant Melanoma.......................................................................................................9
Bladder Cancer ...............................................................................................................9
Ovarian Cancer.............................................................................................................10
Pancreas Cancer ..........................................................................................................10
Barrett’s Esophagus (Pre Malignant condition of the esophagus)..................................10
Head and Neck Cancer.................................................................................................10
Rectal Cancer ...............................................................................................................11
General .........................................................................................................................11
Cervical and Gynecological Cancer Journal Articles......................................................11
Breast Cancer Journal Articles ......................................................................................13
Lung Cancer Journal Articles ........................................................................................17
Prostate Cancer Journal Articles ...................................................................................22
Esophageal Cancer Journal Articles..............................................................................23
Intraperitoneal Cancer Journal Articles..........................................................................27
Skin Cancer Journal Articles .........................................................................................30
Bile Duct Cancer Journal Articles ..................................................................................33
Stomach Cancer Journal Articles ..................................................................................36
Brain Cancer Journal Articles ........................................................................................37
Cutaneous Lymphoma Journal Articles .........................................................................38
Liver Cancer Journal Articles.........................................................................................40
Malignant Melanoma Journal Articles............................................................................43
Bladder Cancer Journal Articles ....................................................................................44
Ovarian Cancer Journal Articles....................................................................................47
Pancreatic Cancer Journal Articles................................................................................50
Barrett’s Esophagus Journal Articles.............................................................................51
Head and Neck Cancer Journal Articles........................................................................55
Rectal Carcinoma Journal Articles.................................................................................57
General Journal Articles of Interest ...............................................................................59
Generation of effective antitumor vaccines using photodynamic therapy………………..59
Photodynamic therapy: a clinical reality in the treatment of cancer………………………59

The immunological consequences of photodynamic treatment of cancer, a
literature review.............................................................................................................60
The role of apoptosis in response to photodynamic therapy: What,
where, why and how......................................................................................................60
Photodynamic therapy-mediated immune response against subcutaneous
mouse tumors ...............................................................................................................61
Photodynamic therapy: a new antimicrobial approach to infectious disease?................62
Introduction of Next Generation PDT.............................................................................64
NGPDT Advancements over PDT .................................................................................65
Advanced Photodynamic Medical Techniques ..............................................................66
Superior 4th generation photosensitive agent called "Photosoft" ...................................68
Multi-frequency, deep penetrating laser with wavelengths infra-red and higher.............69
Clinical observation of next-generation photodynamic therapy (NGPDT)
for advanced non-small cell lung cancer........................................................................70
NGPDT Phase I trials....................................................................................................73
NGPDT Interstitial Studies.............................................................................................74
Introduction ...................................................................................................................74
Reason for this Study....................................................................................................74
Protocols.......................................................................................................................74
Case Study ...................................................................................................................74
Case Studies.................................................................................................................75
Patient Case Female 56 years old.................................................................................75
Treatment times and Scans...........................................................................................75
Conclusion ....................................................................................................................76
Patient Case Male 62 years old.....................................................................................76
Treatment times and Scans...........................................................................................76
Conclusion ....................................................................................................................77
NGPDT Interstitial Lymph Node & Nasal Treatment......................................................78
Patient:Ali......................................................................................................................78
NGPDT Laser Fiber and Interstitial Treatment Protocol.................................................79
Patient:Stephen.............................................................................................................83
NGPDT Interstitial Treatment Protocol ..........................................................................85
Image taken prior to NGPDT treatment .........................................................................85
NGPDT Interstitial Treament Protocol ...........................................................................86
Endoscope Image (base of the tongue)after NGPDT ....................................................86
Endoscope Image (base of the tongue)after NGPDT ....................................................87
Summary.......................................................................................................................90
Follow Up......................................................................................................................90
Summary.......................................................................................................................91
Follow Up......................................................................................................................92
NGPDT Interstitial Bone Cancer Treatment...................................................................93
Summary.......................................................................................................................99
NGPDT life expectancy comparison............................................................................100
Introduction ................................................................................................................100
What is Staging? .........................................................................................................100
Cancer Staging ...........................................................................................................100

What is the TNM system? ...........................................................................................101
Tumor Grade...............................................................................................................101
What is tumor grade?..................................................................................................102
How is tumor grade determined?.................................................................................102
How are tumor grades classified? ...............................................................................102
What are some of the cancer type-specific grading systems? .....................................103
How does tumor grade affect patient's treatment options? ..........................................104
How does cancer cause death? ..................................................................................104
Case studies in this document.....................................................................................105
Case Study:Nurul........................................................................................................106
Summary History.........................................................................................................106
Cancer Type: Pancreatic cancer metastasis to the liver ..............................................106
Treatment Summary of NGPDT ..................................................................................106
PET/CT before NGPDT:..............................................................................................107
PET/CT report before NGPDT 30th August 2012 ........................................................107
PET/CT images of the pancreas prior to NGPDT ........................................................108
CT After 3 Courses of NGPDT ....................................................................................109
After NGPDT...............................................................................................................109
Case Study John.........................................................................................................110
Medical Condition........................................................................................................110
Cancer Type: Kidney Renal Cancer metastasis to liver and lungs...............................110
Medical History............................................................................................................110
5 NGPDT Treatments..................................................................................................110
CT Comparisons showing NGPDT treatment response...............................................115
Conclusion ....................................................................................................................27
Case Study Madam Thoo............................................................................................116
Cancer Type:Invasive ductile breast cancer with metastasis right armpit lymph node .116
Madam Thoo with Scott Waters...................................................................................117
First NGPDT Treatment ..............................................................................................118
Summary findings .......................................................................................................118
Second NGPDT Treatment .........................................................................................119
Summary findings .......................................................................................................119
Early PET/CT scan......................................................................................................120
Third NGPDT Treatment .............................................................................................120
Comparative PET/CT scan shown after NGPDT no metabolic activity to the breast
tumor...........................................................................................................................120
Comparative PET/CT scan shown after NGPDT with two metabolic tumors not active
and once new metabolic area of the breast .................................................................122
Treatment in Summary................................................................................................124
Case Study:Anna ........................................................................................................125
Cancer Type:Non Small Cell Lung Cancer metastatic lymph nodes and bone ............125
PET/CT shows response to NGPDT treatment............................................................126
PET/CT January before NGPDT .................................................................................127
PET/CT March after NGPDT.......................................................................................128
Summary from PET/CT...............................................................................................128
Impression before: ......................................................................................................128
Impression after: .........................................................................................................128
NGPDT treatment summary........................................................................................129
Case Study:Beatrix......................................................................................................130
Cancer Type:Breast Cancer........................................................................................130
Mammography before NGPDT....................................................................................131

PET/CT after NGPDT..................................................................................................131
Case Study : Richard ..................................................................................................134
Cancer Type: Naso Pharyngeal Carcinoma and extension to the Lymph node of
the neck ......................................................................................................................134
Treatment in Summary................................................................................................136
Case Study : Joseph ...................................................................................................137
Links to News Articles: ................................................................................................137
Cancer Type: Re Occurrence of Naso Pharyngeal Carcinoma and extension to
the Lymph nodes and Lung.........................................................................................137
NGPDT treatments......................................................................................................138
Histopathology before NGPDT....................................................................................138
Case Study : Irene ......................................................................................................141
Links to Interview: .......................................................................................................141
Cancer Type: Post operation to Lung Cancer, Metastatic disease to Lymph nodes
and bone (sacrum) ......................................................................................................141
PET/CT before NGPDT (3 pages)...............................................................................143
PET/CT after NGPDT (2 pages)..................................................................................144
PET/CT Sacrum Images before NGPDT .....................................................................145
PET/CT sacrum images after NGPDT.........................................................................145
Case Study:Nadine .....................................................................................................148
Links to Interview: .......................................................................................................148
Summary Points of condition prior to NGPDT..............................................................148
Cancer Type: Hodgkins Lymphoma metastasis throughout.........................................148
PET/CT PRIOR TO NGPDT........................................................................................150
NGPDT Treatment ......................................................................................................151
PET/CT scan dated 21/06/2010 ..................................................................................152
CT scan dated 16/09/2011 ..........................................................................................152
Compared PET/CT scan results dated 16/09/2011......................................................154
Conclusions from results of NGPDT............................................................................154
Case Study:Chew .......................................................................................................155
Links to Interview:http://www.youtube.com/watch?......................................................155
Cancer Type – Brain Astrocytoma and metastatic to lungs and nodes ........................155
The PET/CT before NGPDT Impression......................................................................155
The PET/CT after NGPDT Impression.........................................................................155
Treatment Summary....................................................................................................156
PET/CT Report before NGPDT ...................................................................................157
Page 1 PET/CT Report after two courses of NGPDT ..................................................158
Page 2 PET/CT Report after two courses of NGPDT ..................................................159
PET/CT images of the brain before NGPDT................................................................160
PET/CT images of the lungs before NGPDT ...............................................................161
PET/CT images of the neck before NGPDT ................................................................162
PET/CT images of the brain after NGPDT...................................................................163
PET/CT images of the brain after NGPDT...................................................................164
PET/CT Image of lymph nodes after NGPDT ..............................................................164
PET/CT image of the lungs after NGPDT....................................................................167
PET/CT image of the body after NGPDT.....................................................................168
Fai PET/CT scans show response after NGPDT treatments .......................................168
Case Study : Monika ...................................................................................................169
Cancer Type: Invasive ductile breast cancer with extensive bone metastases ............169
PET/CT prior to NGPDT treatments ............................................................................170

TECHNIQUE:............................................................................................................: 170
FINDINGS:..................................................................................................................170
IMPRESSION:.............................................................................................................171
PET/CT after 2 courses of NGPDT treatments............................................................172
Treatment Summary....................................................................................................174
Case Study : Briony.....................................................................................................175
Cancer Type: Cervical cancer and metastasis to lymph nodes....................................175
Link to her Story..........................................................................................................175
PET/CT January after NGPDT ....................................................................................176
Biopsy Report..............................................................................................................177
Conventional Smear....................................................................................................178
Document summary ....................................................................................................180

Introduction of PDT
Photodynamic Therapy is a proven and approved form of cancer therapy. It is minimally invasive
and minimally toxic, hence effective with minimal side effects.
To date, the U.S. food and Drug Administration (FDA) has approved PDT to treat skin and
precancerous lesions in patients with Barrett esophagus cancer using earlier or first generation
PDT’s.
Three key components are involved to treat cancer: a photosensitizer, a light source and tissue
oxygen. The combination of these three components leads to the chemical destruction of any
tissues which have either taken up the photosensitizer and have been locally exposed to light. The
wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce
reactive oxygen species. These relative oxygen species generated through PDT are free radicals
generated through electron abstraction or transfer from a substrate molecule and highly reactive
stage of oxygen known as singlet oxygen.
A Statement on the Benefits of Photodynamic Therapy
A new therapy for Cancer known as Photodynamic Therapy (PDT) is an approved, proven, safe
and effective treatment for many types of cancer and numerous photosensitizer agents are
approved for use in the US, Europe and most countries in the developed world. Clinical studies
undertaken at the world’s most prestigious Medical Institutions increasingly demonstrate the
favourable results of this therapy for a wide variety of cancers. Notably the results are achieved
with few side effects, high patient's satisfaction, increased quality of life with less morbidity and
better functional and cosmetic outcome.
The many positive results using PDT have been achieved with existing approved photosensitizers.
Next Generation Photosensitizer®, a newer more advanced agent, offers many advantages such
as better selectivity, less toxicity, oral administration and rapid elimination with reduced periods of
photosensitisation. Significantly, these advances permit the light therapy to be delivered to large
areas of the body with the use of a patented ‘Light Delivery System’. We have designated this
extension in PDT from a localized treatment to a ‘whole body’ therapy, (Next Generation PDT).
Preliminary clinical data suggest favorable patient responses to a wide variety of cancer indications
even in the presence of wide spread disease. Regulatory approval with appropriate certified
toxicology, pharmacokinetics and clinical studies has begun for this promising advance in cancer
therapy.

A partial list of types of cancers and the corresponding scientific evidence of the efficacy and
effectiveness of the PDT therapy (shown as exhibits) is listed below with a brief summary of the
studies. Many of these medical journal articles are obtained from the New England Journal of
Medicine website www.nejm.org. The New England Journal of Medicine is one of the world most
respected professional medical journals and is widely read by the Medical Professions throughout
the world.
Cervical and Gynaecological Cancer
(See corresponding scientific articles beginning page 11)
Photodynamic therapy is effective not only in treating cervical intraepithelial neoplasia (CIN) but
also for eradicating cervical human papilloma virus (HPV), a causal factor in the formation of
cancer. Many of the common surgical procedures for cervical cancer lead to infertility and
significantly PDT has the potential to preserve fertility while simultaneously successfully treating
the cancer. If patients are not informed of this option in the treatment of their cervical cancer which
can preserve fertility they are significantly disadvantaged.
Breast Cancer
Photodynamic therapy offers a highly successful treatment for recurrent breast cancer on the chest
wall with few side effects, high patient satisfaction, quality of life and possible repetitive application.
PDT using m-THPC (a medicine approved for use in Europe) resulted in complete response (no
evidence of residual tumor) in all patients treated for recurrent breast cancer.
Lung Cancer
Photodynamic therapy (PDT) has now achieved the status of a standard treatment modality for
centrally located, early-stage lung cancer and is introduced on the home page of the US National
Cancer Institute. As an increasing number of patients consider quality of life after therapy, the
indications for PDT are expected to expand. PDT is a promising new technique for curative
treatment of localized, peripheral lung cancer less than 1cm in size in patients who are unfit for
surgery or radiotherapy.

Prostate Cancer
Photodynamic therapy has great potential in the treatment of prostate carcinoma. The principle
side effects of prostate surgery are incontinence, impotence and infections. These can be
potentially avoided with PDT. However, most all patients are not even informed of the option nor
are offered the therapy.
Oesophagus Cancer
(See corresponding scientific articles beginning at the bottom of page 23)
PDT is an effective and safe treatment method in esophageal cancer. In advanced disease it
improves swallowing. In early stage disease it offers long survival and the prospect of cure in some
patients.
Peritoneal/Sarcoma
Debulking surgery with intraperitoneal PDT for sarcomatosis is feasible. Preliminary response data
suggest prolonged relapse-free survival in some patients.
Skin Cancer
(See corresponding scientific articles beginning at the bottom of page 31)
With a single course of verteporfin (an approved medicine) PDT showed treatment benefit for
patients with multiple non-melanoma skin cancers.
Bile Duct Cancer
Photodynamic therapy (PDT) of bile duct cancer have shown astonishingly good results in the
reduction of cholestasis, improvement of quality of life, and even prolongation of the survival time.
In one of the articles the study was terminated prematurely because PDT proved to be so superior
to simple stenting treatment that further randomization was deemed unethical. Yet this therapy is
not even mentioned to most patients with bile duct cancer.
Stomach Cancer
PDT was found to be a safe, feasible treatment that could improve symptoms resulting from
advanced gastric cancer.

Brain Cancer
The selectivity of the process makes PDT appealing in the brain, where conservation of healthy
tissue is vital. Many new photosensitizing compounds and varying methods of light delivery are
being studied. This technology shows promise for the treatment of primary brain malignancies.
Cutaneous Lymphoma
The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This
modality appears to be very effective and can be used successfully for MF treatment.
Liver Metastases
With the use of multiple devices, ablation of liver tumors seems to be possible, and no severe side
effects or toxicities related to the treatment are reported. PDT can become a clinically relevant
adjunct in the locoregional therapy strategies. Another study demonstrates that mTHPC (an
approved medicine in Europe) is retained in an intrahepatic tumor and that mTHPC-PDT is capable
of inducing complete tumor remission of liver tumors.
Malignant Melanoma
PDT with chlorin e(6) for skin metastases from melanoma is effective and well tolerated. Further
clinical investigation of PDT with chlorin e(6) is warranted.
Bladder Cancer
More than half of the patients with TCC refractory to traditional intravesical therapy received benefit
from a single PDT session. Patients who achieve a complete recovery (CR) have less likelihood of
and longer time interval before needing cystectomy for progressive disease than no response (NR)
patients. The PDT protocol is associated with minimal morbidity in these high-risk patients.

Ovarian Cancer
These preliminary results suggest that PDT with an OC125 immunoconjugate may be an effective
therapy for the management of advanced ovarian cancer. Clinical application of this therapy
needs to be further optimised and may require multiple treatments, similar to fractionated radiation
therapy and cyclic chemotherapy, in order to control malignant disease with acceptable toxicity to
normal tissue. Examples of benefits are as follows: Of the 51 patients enrolled and treated with IP
PDT two are alive without evidence of recurrence. Eleven of 45 patients showed no evidence of
recurrence 3 months after treatment. No evidence of recurrence was noted in 7/17 sarcoma
patients, 2 of 13 ovarian cancer patients, and 2 of 15 gastrointestinal cancer patients.
Pancreas Cancer
ICG PDT induces consistent and dramatic pancreatic cancer cell death. Since neither ICG nor
laser alone caused toxicity, combination therapy may offer effective control of tumor growth with
minimal side effects in patients with unresectable primary or metastatic pancreatic cancer.
Barrett’s Oesophagus (Pre Malignant condition of the oesophagus)
PDT increases life expectancy and is cost-effective when compared to endoscopic surveillance
and surgical oesophagectomy.
Head and Neck Cancer
In 25 (86%) of 29 tumors, a complete remission of the primary tumor was obtained. In the 4
recurrences, salvage was achieved by conventional therapy. In none of the patients was any long-
term functional deficit detected. CONCLUSIONS: This study confirms that PDT is a powerful
treatment modality that could be considered as an alternative to surgery or radiotherapy in specific
cases of head and neck cancer. The major advantage of PDT over these conventional therapies is
the reduction in long-term morbidity. Radiotherapy or surgery could be reserved for salvage
therapy in the event of a recurrence or second primary tumors. Often surgery for head and neck
cancer leaves the patient with grotesque cosmetic side effect and severe functional speech
disabilities. Most if not all of these patients have not been informed of this option nor give the
choice of this much less invasive and destructive therapy.

Rectal Cancer
In a group of patients who are at high risk for recurrence irrespective of initial treatment, PDT can
be used as a successful alternative to surgical excision for anal carcinoma in situ. Surgery in this
area can lead to lifelong problems with incontinence.
General
PDT can lead to specific tumor auto vaccination that is neither possible nor observed with
traditional therapies. It is hypothesized that PDT destroys the structure of a tumor, thereby
enabling direct interaction between immune cells and tumor cells resulting in the systemic anti-
tumor immune response.
The scientific evidence for the effectiveness of PDT with specific journal references is shown in the
following exhibits.
Cervical and Gynaecological Cancer Journal Articles
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Abstract from Medline: return to Search Results
Int J Clin Oncol, October 1, 2003; 8(5): 322-5.
Eradication and reinfection of human papillomavirus after photodynamic
therapy for cervical intraepithelial neoplasia.
H Ichimura, S Yamaguchi, A Kojima, T Tanaka, K Niiya, M Takemori, K Hasegawa, and R
Nishimura

Department of Obstetrics and Gynecology, Hyogo Medical Center for Adults, 13-70 Kitaoji-cho,
673-8558, Akashi, Japan.
MEDLINE ABSTRACT
BACKGROUND: Photodynamic therapy (PDT) has been
proven to be a promising therapeutic modality for selected
dysplasias and malignancies in a variety of organs. We assessed
the effectiveness of PDT for treating cervical intraepithelial
neoplasia (CIN) by cytological and histological examinations
and investigated its impact on human papillomavirus (HPV)
infection. METHODS: A series of 31 patients with CIN (2 with
CIN2, 29 with CIN3) were given polyhematoporphyrin
ether/ester (PHE) 2 mg/kg IV. After 60 h their cervices were
exposed to a 630-nm YAG-OPO laser. HPV-DNA extracted
from cervical smears was amplified by the polymerase chain
reaction and typed for HPV using restriction fragment length
polymorphism. RESULTS: At 3 months after PDT, cytology
and directed biopsy of the cervix revealed regression of the
disease in 28 [complete remission (CR) rate 90%] of 31 patients,
and HPV-DNA could be no longer detected in the cervical smears of 22 (76%) of 29 HPV-positive
patients. After 12 months, all 31 patients had achieved a CR on biopsy, although HPV-DNA was
still present in the cervical smears of 6 patients. The types of HPV-DNA detected 12 months after
PDT were different from those seen before PDT in each of the 6 patients, suggesting that they
might be reinfected with other HPV types after PDT. CONCLUSION: PDT is effective not only in
improving the cytological and histological measures when treating CIN but also for eradicating
cervical HPV.
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Articles in Medline by Author:
Ichimura, H
Yamaguchi, S
Kojima, A
Tanaka, T
Niiya, K
Takemori, M
Hasegawa, K
Nishimura, R
Lasers Surg Med, January 1, 2002; 30(4): 273-9.

Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial
neoplasia using topically applied 5-aminolevulinic acid.
MK Fehr, R Hornung, A Degen, VA Schwarz, D Fink, U Haller, and P Wyss
Department of Obstetrics and Gynecology, Division of Gynecology, University Hospital, CH-8091
Zurich, Switzerland. Mathias.Fehr@fhk.usz.ch
MEDLINE ABSTRACT
BACKGROUND AND OBJECTIVES: To determine the
feasibility of photodynamic therapy (PDT) of vulvar and vaginal
condyloma and intraepithelial neoplasia (VIN, VAIN) and to
compare PDT results with conventional treatments. STUDY
DESIGN/MATERIALS AND METHODS: Thirty-eight patients
with vulvar or vaginal intraepithelial neoplasia (VIN) grade
II/III (n = 22) or condyloma (n = 16) had 10% 5-aminolevulinic
acid (ALA)-gel applied topically. After 2-4 hours, 80-125
J/cm(2) laser light at a wavelength of 635 nm was applied. PDT
was compared to conventional treatments for condyloma (CO(2)
laser evaporation) and for VIN III (laser evaporation, surgical
excision). RESULTS: The complete clearance rate for
condyloma treated by PDT was 66% and the rate for IN was
57% (as determined by biopsy). Of the neoplasia patients, none
with hyperkeratotic VIN (n = 4) responded, and only one of four
with increased pigmentation cleared. No scarring occurred, and postoperative discomfort lasted 4.9
+/- 3.4 days. Reduced disease-free survival (DFS) was associated with multifocal VIN (P = 0.02,
OR 2.17, 95% CI 1.15-4.08), but DFS did not vary with treatment mode. CONCLUSIONS:
Although PDT is not equally efficacious for all subgroups, PDT for condyloma and intraepithelial
neoplasia appears to be as effective as conventional treatments, but with shorter healing time and
excellent cosmetic results.
Publisher's Full Text Link
Fehr, MK
Hornung, R
Degen, A
Schwarz, VA
Fink, D
Haller, U
Wyss, P

Breast Cancer Journal Articles
Int J Cancer, September 1, 2001; 93(5): 720-4.
Photodynamic therapy of locoregional breast cancer recurrences using a
chlorin-type photosensitizer.
P Wyss, V Schwarz, D Dobler-Girdziunaite, R Hornung, H Walt, A Degen, and M Fehr
Department of Obstetrics and Gynecology, University Hospital, Zürich, Switzerland.
Pius.Wyss@fhk.usz.ch
MEDLINE ABSTRACT
Chest wall recurrences are a frequent problem in patients treated
by mastectomy for breast cancer. Surgery and ionizing radiation
are established treatment modalities in these cases.
Photodynamic therapy (PDT) provides an alternative treatment
modality using a photosensitizer and laser light to induce
selective tumor necrosis. PDT was performed as compassionate
use in 7 patients aged 57.6 years (+/-12.6 SD). A total of 89
metastatic skin nodes were treated in 11 PDT sessions. As
photosensitizer meta-tetra(hydroxyphenyl)chlorin (m-THPC)
was applied intravenously. Patients (n = 3) photosensitized with
a drug dose of 0.10 mg/kg bodyweight were irradiated 48 hr
after drug application at a lightdose of 5 J/cm(2). Patients (n = 4)
were illuminated by an optical dose of 10 J/cm(2) 96 hr after
photosensitization with 0.15 mg/kg. Laser light at a wavelength
of 652 nm was generated by a diode laser and applied by a front
lens light diffuser using a fluence rate of 20--25 mW/cm(2). PDT using m-THPC resulted in
complete response in all patients. Response to treatment did not differ when using the 2 different
Wyss, P
Schwarz, V
Dobler-Girdziunaite, D
Hornung, R
Walt, H
Degen, A
Fehr, M

drugdose protocols. Healing time depended mainly on the size of the illumination field but not on
the lightdose. Pain score usually raised 1 day after PDT and lasted at higher levels for about 10
days. Healing time usually ranged between 8--10 weeks. Photodynamic technique offers a minimal-
invasive, outpatient treatment modality for recurrent breast cancer on the chest wall with few side
effects, high patient's satisfaction and with possible repetitive application.
Cancer, January 1, 2001; 91(1): 1-8.
Photodynamic therapy for chest wall progression from breast carcinoma
is an underutilized treatment modality.
R Allison, T Mang, G Hewson, W Snider, and D Dougherty
Department of Photodynamic Therapy, Buffalo General Hospital, Buffalo, New York, USA.
MEDLINE ABSTRACT
BACKGROUND: Chest wall progression of breast carcinoma
after failure of salvage surgery, radiation, and chemohormonal
therapy is a quagmire with limited therapeutic options. Because
photodynamic therapy (PDT) offers excellent results in
cutaneous lesions, PDT may play a role in this indication.
However, to the authors' knowledge, published data for this
subgroup of patients using the only commercially available
photosensitizing agent, Photofrin, often show high treatment
morbidity, limiting PDT's usefulness. The authors report the
feasibility of decreasing the photosensitizer drug dose as a
means of exploiting photobleaching kinetics to improve the
therapeutic ratio for these individuals. METHODS: One hundred
Allison, R
Mang, T
Hewson, G
Snider, W
Dougherty, D

two chest wall sites were treated with PDT after failure of multimodality salvage therapy. In these
9 patients, lesion size ranged from 0.57 to 9 cm. Photodynamic therapy consisted of outpatient
intravenous infusion of 0.8 mg/kg of Photofrin, followed 48 hours later by 630 nm light treatment
of 135-170 J/cm2 delivered by a KTP:YAG laser coupled to dye unit. Two patients underwent a
second PDT procedure due to new lesion formation. All patients were observed for a minimum of
6 months, and none was lost to follow-up. RESULTS: Photodynamic therapy was well tolerated
with no photosensitivity reported. Despite all patients having failed surgery, full dose radiation and
multiagent chemohormonal therapy, chest wall lesions healed with no scarring. Only 1 (9 cm)
lesion took longer than 3 months to granulate over. The authors were able to evaluate all treatment
sites, and complete response, defined as total lesion elimination, was noted in 89% of the lesions;
reduction without regrowth occurred in 8% with no response in 3% of the lesions.
CONCLUSIONS: Despite having prior treatment and fragile tissues, low dose Photofrin-induced
PDT offers excellent clinical response with minimal morbidity. These results show that PDT
should play an important role in the management of chest wall failure from breast carcinoma.
Ann. Surg. Oncol., March 1, 2004; 11(3): 322-7.
Breast cancer with chest wall progression: treatment with photodynamic
therapy.
RE Cuenca, RR Allison, C Sibata, and GH Downie
Photodynamic Therapy Program, Leo Jenkins Cancer Center, Department of Surgery, The Brody
School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
cuencar@mail.ecu.edu

MEDLINE ABSTRACT
BACKGROUND: Chest wall progression of breast carcinoma
affects up to 5% of breast cancer patients and is a major source
of their pain. Treatment options are limited or may not be
offered to these patients. Low-dose Photofrin-induced
photodynamic therapy (PDT) offers an excellent clinical
response with minimal morbidity. We report our continued
experience with PDT in this setting. METHODS: Fourteen patients with more than 500 truncal
metastases were treated with PDT. All received off-label Photofrin (.8 mg/kg) i.v. and light
treatment at 630 nm from a diode laser with a microlens at a fluence of 1800 mW and a total light
dose of 150 to 200 J/cm2 at 48 hours. One patient required re-treatment because of extensive
disease. RESULTS: Follow-up was at least 6 months, and several extended to >24 months. All
patients demonstrated tumor necrosis, with 9 of 14 complete responses, including with lesions >2
cm in thickness. Disease progression occurred outside of the treatment field. Several patients had
initial regression of untreated lesions. Wound care, especially with disease in the deep tissues, was
an issue. CONCLUSIONS: Low-dose Photofrin-induced PDT offers patients with chest wall
progression a treatment option with an excellent clinical response. To date, the response is
prolonged and offers good local control. Surgical oncologists have an active role in this treatment
option
Cuenca, RE
Allison, RR
Sibata, C
Downie, GH
Lung Cancer Journal Articles
Nippon Geka Gakkai Zasshi, February 1, 2002; 103(2): 258-62.
[Photodynamic therapy for lung cancer: state of the art and expanded
indications]
T Okunaka and H Kato

Department of Surgery, Tokyo Medical University, Tokyo, Japan.
MEDLINE ABSTRACT
Photodynamic therapy (PDT) has now achieved the status of a
standard treatment modality for centrally located, early-stage
lung cancer and is introduced on the home page of the US
National Cancer Institute. Over the past decade, 145 patients
(191 lesions) with central-type early-stage lung cancers have
been treated with PDT in our hospital. Overall complete
remission was obtained in 86.4% of the total number of lesions.
In patients with advanced stage III disease, however, bronchi
opening was successful in 61 out of 81 lesions (75%) for the PDT group compared with 143 of 177
(81%) in the Nd-YAG laser therapy group. Although quite recent, treatment using PDT has been
introduced for the first time in patients with peripheral lung cancer, who did not previously meet
the criteria for surgery. Eight patients underwent this trial, of which 3 achieved partial remission.
No serious complications except for one case of pneumothorax, were noted. As increasing number
of patients consider quality of life after therapy, the indications for PDT are expected to expand.
The success in clinical trials of PDT for cancer treatment offers encouragement for its future use.
Okunaka, T
Kato, H
Lung Cancer, January 1, 2004; 43(1): 77-82.
Photodynamic therapy for peripheral lung cancer.
T Okunaka, H Kato, H Tsutsui, T Ishizumi, S Ichinose, and Y Kuroiwa
Department of Surgery, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-
0023, Japan. okunaka@topaz.ocn.ne.jp

MEDLINE ABSTRACT
Photodynamic therapy (PDT) has now achieved the status of a
standard treatment modality for centrally located early-stage
lung cancer. In the last decade, CT screening for lung cancer
has attracted much attention for its ability to detect early
peripheral lung cancer. Extremely recently, treatment using
PDT has been introduced for the first time in patients with
peripheral lung cancer, who did not meet the previous criteria
for surgery. The procedure was carried out with local anesthesia
with xylocain infiltrated into the chest wall, 48 h after Photofrin
administration. Needles (19 gauge) containing an internal
catheter were inserted percutaneously under CT guidance. The
needles were then extracted and a diffuser fiber with a 2 cm long
tip for light delivery was positioned in the tumor through the
catheter. Of the nine patients enrolled in this trial, seven achieved partial remission (PR). No
serious complications, except for two cases of pneumothorax, were noted. As an increasing number
of patients consider quality of life after therapy, the indications for PDT are expected to expand.
We conclude that PDT is a promising new technique for curative treatment of localized, peripheral
lung cancer less than 1cm in size in patients who are unfit for surgery or radiotherapy.
Okunaka, T
Kato, H
Tsutsui, H
Ishizumi, T
Ichinose, S
Kuroiwa, Y
Clin Lung Cancer, August 1, 2001; 3(1): 37-41; discussion 42.
Photodynamic therapy for patients with advanced non-small-cell
carcinoma of the lung.
BU Jones, M Helmy, M Brenner, DL Serna, J Williams, JC Chen, and JC Milliken
Division of Cardiothoracic Surgery and Pulmonary/Critical Care Medicine, The University of
California, Irvine Medical Center, Orange 92868, USA.

MEDLINE ABSTRACT
Patients with advanced non-small-cell lung carcinoma (NSCLC)
have poor prognoses and experience negative sequelae of
disease. Patients often suffer from dyspnea and/or hemoptysis,
with overall pulmonary compromise. Patients with advanced,
inoperable disease have limited options for treatment. This study
summarizes our early experience and findings using
photodynamic therapy (PDT) as an effective modality in the
palliation of hemoptysis, dyspnea, and physical airway
obstruction in cases of inoperable lung cancer. A retrospective
review was conducted for the first 10 patients diagnosed with
stage III/IV obstructive NSCLC who underwent PDT at our
institution. Endobronchial lesions were identified by
bronchoscopy. Treatments were initiated 48 hours after
intravenous injection of 2 mg/kg of the photosensitizing agent
porfimer sodium (Photofrin, QLT PhotoTherapeutics,
Vancouver, BC). The porfimer sodium was then activated by illumination with a 630 nm
wavelength light using a Coherent argon ion laser through a flexible bronchoscope. Repeated
bronchoscopies were performed 1-3 days following initial PDT for evaluation and airway
debridement. In 8 cases, a second treatment of PDT was administered within 72 hours of the first
injection. One patient received a third treatment several months later. Three patients also received
endobronchial stents after PDT. Overall, all 10 patients responded to PDT. Physical airway
obstruction was reduced in all patients, with a noted improvement in bronchoscopic luminal
diameter. Acute hemoptysis resolved in all 7 symptomatic patients. Median survival was 5.5
months post-PDT, while median survival postdiagnosis was 10.5 months. Three patients are alive
at the time of this review at 5-21 months following therapy. Patients with unresectable late-stage
NSCLC have few options for treatment. Our early experience with PDT indicates effective relief of
hemoptysis, dyspnea, and airway obstruction and improves their quality of life.
Jones, BU
Helmy, M
Brenner, M
Serna, DL
Williams, J
Chen, JC
Milliken, JC

Lung Cancer, October 1, 2003; 42(1): 103-11.
Phase II clinical study of photodynamic therapy using mono-L-aspartyl
chlorin e6 and diode laser for early superficial squamous cell carcinoma
of the lung.
H Kato, K Furukawa, M Sato, T Okunaka, Y Kusunoki, M Kawahara, M Fukuoka, T Miyazawa, T
Yana, K Matsui, T Shiraishi, and H Horinouchi
Department of Surgery, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-
0023, Japan.
MEDLINE ABSTRACT
Photofrin is the most commonly used photosensitizer for
photodynamic therapy (PDT). The major side effect of
Photofrin is cutaneous photosensitivity. A second generation
photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) has shown
anti-tumor efficacy and rapid clearance from skin. Therefore, we
conducted a phase II clinical study to investigate the anti-tumor
effects and safety of NPe6 in patients with early superficial
squamous cell carcinoma of the lung. Enrollment criteria
consisted of endoscopically evaluated early stage lung cancer
with normal chest X-ray and CT images, no lymph node or
distant metastasis. Tumors were located no more peripherally
than subsegmental bronchi, the peripheral margin had to visible,
and the tumor size had to not more than 2 cm in diameter. The
histologic type of the tumor had to squamous cell carcinoma.
Laser irradiation (100 J/cm2) using a diode laser was performed
at 4 h after administration of NPe6 (40 mg/m2). Among 41
patients with 46 lesions, 40 with 45 lesions were eligible for
safety evaluation, and 35 patients with 39 lesions were judged as
eligible for efficacy evaluation. No serious adverse drug
reactions were observed. Disappearance of skin photosensitivity
was recognized within 2 weeks in 28 of 33 patients (84.8%) and
in all the other seven patients first tested at 15-18 days. Complete response (CR) was seen in 84.6%
of lesions (82.9% of patients). This study demonstrated excellent anti-tumor effects and safety,
especially low skin photosensitivity in patients with early stage lung cancer. PDT using the second
generation photosensitizer NPe6 and a diode laser will likely become a standard modality of PDT
for central type early superficial squamous cell carcinoma of the lung.
Kato, H
Furukawa, K
Sato, M
Okunaka, T
Kusunoki, Y
Kawahara, M
Fukuoka, M
Miyazawa, T
Yana, T
Matsui, K
Shiraishi, T
Horinouchi, H

Prostate Cancer Journal Articles
Curr Urol Rep, June 1, 2003; 4(3): 221-8.
Photodynamic therapy: a new approach to prostate cancer.
R Muschter
Diakoniekrankenhaus Academic Teaching Hospital, Rotenburg, Germany. muschter@diako-
online.de
MEDLINE ABSTRACT
Photodynamic therapy (PDT) is based on the concept that light
irradiation can change an inert substance into an active one. In
urology, hematoporphyrin derivative (HpD) and Photofrin
(Axcan Scandipharm Inc., Birmingham, AL) are used most
commonly as photosensitizing agents predominantly for the
treatment of transitional cell carcinoma of the bladder. To
investigate the basics for PDT of prostate cancer, several
studies were performed on the optical characteristics of prostate tissue and prostate carcinoma
tissue in vitro and in vivo and on the penetration depths of different laser wavelengths. Initial
experimental studies to treat prostate cancer with PDT using HpD were done on Dunning tumors
in rats. Combined with interstitial applicators, photodynamic therapy seems to have a great
potential in the treatment of prostate carcinoma. However, it is an experimental treatment and even
a preliminary evaluation will be possible only after the conclusion of clinical studies.
Muschter, R

Nat Rev Cancer, May 1, 2003; 3(5): 380-7.
Photodynamic therapy for cancer.
DE Dolmans, D Fukumura, and RK Jain
Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts
General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
MEDLINE ABSTRACT
The therapeutic properties of light have been known for
thousands of years, but it was only in the last century that
photodynamic therapy (PDT) was developed. At present, PDT
is being tested in the clinic for use in oncology--to treat cancers
of the head and neck, brain, lung, pancreas, intraperitoneal
cavity, breast, prostate and skin. How does PDT work, and how
can it be used to treat cancer and other diseases?
Dolmans, DE
Fukumura, D
Jain, RK
Oesophageal Cancer Journal Articles
Scientific Links
(PDT) in esophageal cancer: a surgical view of its indications based on 14
years experience.
K Moghissi and K Dixon

Photodynamic therapy Technol Cancer Res Treat, August 1, 2003; 2(4): 319-26.
Commentary: Comparison of PDT results in Group A with results of other palliative treatment
methods, indicates that palliation can be achieved in all intraluminal cancer using PDT which is at least
as good as other treatments. There is, in addition, advantage over other methods in patients with cervical
esophageal cancer and in cases with re-growth of tumor obstructing previously placed stents. In early
cases PDT appears capable of replicating surgical results in selected cases. PDT is an effective and safe
treatment method in esophageal cancer. In advance disease it improves swallowing. In early stage
disease it offers long survival and the prospect of cure in some patients.

Technol Cancer Res Treat, February 1, 2003; 2(1): 65-76.
Photodynamic therapy for esophageal cancer: a useful and realistic
option.
H Barr, C Kendall, and N Stone
Cranfield Postgraduate Medical School, Gloucestershire Royal Hospital, Great Western Road,
Gloucester, GL1 3NN, UK. barr@gloucr-tr.swest.nhs.uk
MEDLINE ABSTRACT
The use of light therapy for tissue destruction is highly attractive
for the endoscopic and minimally invasive therapy of
esophageal cancer. Photodynamic therapy (PDT) offers the
possibility of palliation of advanced obstructing tumors.
However, there are other competing techniques, which can be
used to open the esophageal lumen. It has also proved very
effective in providing prolonged palliation of patients with
advanced irresectable cancer. Completely obstructing tumors,
tortuous and long lesions, and tumors near the upper end of the
esophagus are particularly suitable for photodynamic therapy.
Patients with obstruction to an esophageal prosthesis are also well palliated with PDT. A more
interesting and exciting development is its use for the eradication of early asymptomatic mucosal
disease. Photodynamic therapy is particularly useful for the eradication of field cancerous change in
patients with pre-malignant Barrett's esophagus, or early tumors in patients unfit for radical
therapy.
Barr, H
Kendall, C
Stone, N

Bull Acad Natl Med, January 1, 2000; 184(8): 1731-44; discussion 1744-7.
[Local curative treatment of superficial adenocarcinoma in Barrett's
esophagus. First results of photodynamic therapy with a new
photosensitizer]
J Etienne, N Dorme, G Bourg-Heckly, P Raimbert, and F Fekete
Centre de Thérapie photodynamique pluridisciplinaire, Clinique Les Martinets, 97 avenue Albert
Ier-92500 Rueil-Malmaison.
MEDLINE ABSTRACT
Pre-cancerous lesions and mucosally confined superficial
cancers can benefit from local therapy given with curative intent
due to the absence of near metastatic lymph nodes.
Photodynamic therapy (PDT) which acts by laser irradiation
with an appropriate wave-length after administration of a
photosensitiser retained preferentially by the cancerous tissue
can destroy tumor cells selectively, but its efficiency depends
upon the photosensitiser. The results presented concern 10 sites
on Barrett's mucosa (BO). They consisted of either an
association of intramucosal cancer (IMC) with high-grade
dysplasia (HGD) or of high-grade dysplasia alone. The method
consisted of intravenous injection of Temoporfin 0,15 mg/kg 4
days before irradiation of the lesion with a green laser light emitting 514 nm through a windowed
diffuser. The light fluence was 75 J per cm2 and irradiation 100 mW per cm2. Irradiation time was
12,5 mn. Omeprazole was routinely prescribed after treatment at a dose of 40 mg daily. The follow-
up protocol was 2 years with endoscopic surveillance at 2, 3, 6, 12, 18 and 24 months. Biopsies
obligatory at 2 and 3 months were in fact carried out at all the other delays. Efficacy was judged on
the absence of high-grade dysplasia or intra mucosal carcinoma on biopsies at treated sites.
Undesirable side effects noted have been moderate for the most part. No stenosis appeared.
Treatment has been 100% successful for the 10 lesion after 15 treatments with PDT. The follow up
varies from 6-36 months and was more than 18 months for 6 lesions on 5 patients. Our series has
demonstrated a great heterogeneity in lesions which were sometimes visible and highly localised,
but more often invisible, multi-focal and diagnosable only by biopsy at different levels. In keeping
with the literature and our experience, PDT has several advantages over the other locally curative
therapies, mucosectomy and thermocoagulation. These are the possible treatments without general
anaesthesia, selectively for cancer cells, an action on more extensive areas with eradication of non
visible lesions. Temoporfin has contributed notably to the field of photodynamic therapy compared
to previously used sensitisers. It is a pure, synthetic product which guarantees more reproducible
results. Compared with Photofrin, Temoporfin has many advantages with smaller doses of drugs
and less energy, better selectivity and rapid elimination which reduce the risk period for
photosensitisation. The frequency of important undesirable side effects is diminished. Finally, it
produces a consistent effect on the surface and in depth producing a complete reepithelialisation of
the treated zones. Subject to validation of the method on a greater number of patients, the first
Etienne, J
Dorme, N
Bourg-Heckly, G
Raimbert, P
Fekete, F

results obtained on superficial cancer in Barrett's aesophagus allow us to propose green light
Temoporfin PDT as an alternative first line therapy with curative intent.

Intraperitoneal Cancer Journal Articles
Ann. Surg. Oncol., April 1, 2001; 8(3): 254-9.
Preliminary report of photodynamic therapy for intraperitoneal
sarcomatosis.
TW Bauer, SM Hahn, FR Spitz, A Kachur, E Glatstein, and DL Fraker
Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
MEDLINE ABSTRACT
INTRODUCTION: Sarcomatosis is the disseminated
intraperitoneal spread of sarcoma. It is a condition for which
there is no effective treatment. Photodynamic therapy (PDT) is a
cancer treatment modality that uses a photosensitizing agent and
laser light to kill cells. We report our preliminary Phase II
clinical trial experience using PDT for the treatment of
intraperitoneal sarcomatosis. METHODS: From May 1997 to
December 1998 eleven patients received twelve PDT treatments
for intraperitoneal sarcomatosis. Photofrin (PF) 2.5 mg/kg was
administered intravenously 48 hours before surgical debulking
to a maximum residual tumor size of less than 5 mm. Light
therapy was administered at a fluence of 2.5 J/cm2 of 532 nm
green light to the mesentery and serosa of the small bowel and
colon; 5 J/cm2 of 630 nm red light to the stomach and duodenum; 7.5 J/cm2 of red light to the
surface of the liver, spleen, and diaphragms; and 10 J/cm2 of red light to the retroperitoneal gutters
and pelvis. Light fluence was measured with an on-line light dosimetry system. Response to
treatment was evaluated by abdominal CT scan at 3 and 6 months, diagnostic laparoscopy at 3 to 6
months, and clinical examination every 3 months. RESULTS: Adequate tumor debulking required
Bauer, TW
Hahn, SM
Spitz, FR
Kachur, A
Glatstein, E
Fraker, DL

an omentectomy in eight patients (73%), small bowel resection in seven patients (64%), colon
resection in four patients (36%), splenectomy in one patient (9%), and a left spermatic cord
resection in one patient. Five patients (45%) have no evidence of disease at follow-up (range, 1.7-
17.3 months), including patients at 13.8 and 17.3 months examined by CT. Two patients (18%)
died from disease progression. Four patients (36%) are alive with disease progression. Toxicities
related to PDT included substantial postoperative fluid shifts with volume overload, transient
thrombocytopenia, and elevated liver function tests. One patient suffered a postoperative
pulmonary embolism complicated by adult respiratory distress syndrome (ARDS).
CONCLUSIONS: Debulking surgery with intraperitoneal PDT for sarcomatosis is feasible.
Preliminary response data suggest prolonged relapse-free survival in some patients. Additional
follow-up with more patients will be necessary for full evaluation of the added benefit of PDT and
aggressive surgical debulking in these patients.
Int J Oncol, March 1, 2004; 24(3): 711-7.
Patterns of recurrence in patients treated with photodynamic therapy for
intraperitoneal carcinomatosis and sarcomatosis.
JJ Wilson, H Jones, M Burock, D Smith, DL Fraker, J Metz, E Glatstein, and SM Hahn
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wilson, JJ

MEDLINE ABSTRACT
The purpose of this study was to evaluate the patterns of
recurrence in patients treated with Photofrin-mediated
intraperitoneal photodynamic therapy (IP PDT). Sixty-six
patients with gastrointestinal cancers, ovarian cancers, and
sarcomas have been enrolled to date and 51 patients underwent
IP PDT. Photofrin, 2.5 mg/kg, was administered intravenously
48 h prior to surgical debulking and intraoperative light
treatment. Forty-five, and 49 patients were evaluable for response rates, and patterns of recurrence,
respectively. Response to treatment was evaluated by CT or MRI scans of the abdomen and pelvis
every 3 months. Patterns of recurrence were determined by evaluating the abdomen as a
combination of different treatment regions. Of the 51 patients enrolled and treated with IP PDT two
are alive without evidence of recurrence. Eleven of 45 patients showed no evidence of recurrence 3
months after treatment. No evidence of recurrence was noted in 7/17 sarcoma patients, 2 of 13
ovarian cancer patients, and 2 of 15 gastrointestinal cancer patients. The most common site of
recurrence as determined by radiographs was the pelvis, which was noted in 19 of 49 (39%)
patients. The presence of gross residual disease before light treatment (as determined by the
attending surgeon) did not affect the site of recurrence. When studying those patients who had only
locoregional recurrence, 9 of 33 evaluated radiographically and 10 of 24 evaluated operatively
recurred only in peritoneal areas not previously involved with gross disease. The pelvis was the site
with the highest rate of recurrence after IP PDT. A significant minority of patients recurred only in
sites not previously involved with gross disease. Patients with gross residual disease before light
therapy had similar recurrence rates to those without gross residual disease. Since sites involved
with gross residual tumor often received boost doses of light, this could suggest a dose-response
relationship for IP PDT.
Jones, H
Burock, M
Smith, D
Fraker, DL
Metz, J
Glatstein, E
Hahn, SM
Skin Cancer Journal Articles
Arch Dermatol, January 1, 2004; 140(1): 26-32.

Photodynamic therapy of multiple nonmelanoma skin cancers with
verteporfin and red light-emitting diodes: two-year results evaluating
tumor response and cosmetic outcomes.
H Lui, L Hobbs, WD Tope, PK Lee, C Elmets, N Provost, A Chan, H Neyndorff, XY Su, H Jain, I
Hamzavi, D McLean, and R Bissonnette
Division of Dermatology, University of British Columbia and Vancouver General Hospital,
Vancouver, Canada. hlui@interchange.ubc.ca
MEDLINE ABSTRACT
BACKGROUND: Efficient treatment of patients with multiple
synchronous nonmelanoma skin cancers represents a therapeutic
challenge. OBJECTIVE: To study the safety and efficacy of
photodynamic therapy (PDT) with verteporfin and red light in
the treatment of multiple nonmelanoma skin cancers. DESIGN:
Open-label, randomized, multicenter, dose-ranging phase 2
study conducted at 4 North American university-based
dermatology clinics. PATIENTS: Fifty-four patients with 421
multiple nonmelanoma skin cancers including superficial and
nodular basal cell carcinoma and squamous cell carcinoma in
situ (Bowen disease). METHODS: A single intravenous infusion
of 14 mg/m(2) of verteporfin followed 1 to 3 hours later by
exposure of tumors to 60, 120, or 180 J/cm(2) of red light (688
+/- 10 nm) from a light-emitting diode panel. MAIN
OUTCOME MEASURES: Pathologic response of treated sites
was assessed at 6 months. Clinical and cosmetic responses were
assessed and graded at 6 weeks, 3 months, and 6 months after
verteporfin PDT, with optional follow-up visits at 12, 18, and 24
months. RESULTS: The histopathologic response, defined as
absence of tumor on biopsy specimens 6 months after
verteporfin PDT, ranged from 69% at 60 J/cm(2) to 93% at 180
J/cm(2). At 24 months of follow-up (276 tumors in 31 patients), the clinical complete response rate
ranged from 51% at 60 J/cm(2) to 95% at 180 J/cm(2). No significant systemic adverse events were
observed; most events occurred at the treated tumor sites and included events such as pain. Overall,
65% (95% confidence interval, 58%-71%) of tumors were judged to have good to excellent
cosmesis at 24 months. CONCLUSION: A single course of verteporfin PDT showed treatment
benefit for patients with multiple nonmelanoma skin cancers.
Lui, H
Hobbs, L
Tope, WD
Lee, PK
Elmets, C
Provost, N
Chan, A
Neyndorff, H
Su, XY
Jain, H
Hamzavi, I
McLean, D
Bissonnette, R

J Dermatolog Treat, January 1, 2002; 13 Suppl 1: S25-9.
The emerging role of 5-ALA-PDT in dermatology: is PDT superior to
standard treatments?
CA Morton
Department of Dermatology, Falkirk Royal Infirmary, Falkirk, UK. colin.morton@fvah.scot.nhs.uk
MEDLINE ABSTRACT
Several open studies report the efficacy of topical photodynamic
therapy (PDT) in the treatment of non-melanoma skin cancer
and pre-cursor lesions. For a new therapy to change clinical
practice, comparison studies with standard therapies are
required, assessing efficacy, adverse events and cosmetic
outcome. This review considers the evidence for using topical
PDT over standard therapies in non-melanoma skin cancer.
Limited data indicates topical PDT to be superior to cryotherapy and equivalent to topical 5-
fluorouracil in clearing non-hyperkeratotic actinic keratoses, and to achieve a superior cosmetic
outcome. Topical PDT is superior to topical 5-fluorouracil, and equivalent to cryotherapy, in the
treatment of squamous cell carcinoma in situ (Bowen's disease), again with fewer adverse
reactions. Similarly, PDT is as effective as cryotherapy for basal cell carcinoma, but with superior
healing and cosmesis. PDT may be particularly advantageous for large and/or multiple lesions and
for those in sites where disfigurement or poor healing from conventional therapies is a particular
risk. There remains a lack of comparison data concerning routine surgery, curettage, and
radiotherapy, but topical PDT would appear as effective as, and in certain aspects superior to,
standard therapies in the treatment of non-melanoma skin cancer.
Morton, CA

Bile Duct Cancer Journal Articles
Gastroenterology, November 1, 2003; 125(5): 1355-63.
Successful photodynamic therapy for nonresectable cholangiocarcinoma:
a randomized prospective study.
MEDLINE ABSTRACT
BACKGROUND & AIMS: In nonrandomized trials,
photodynamic therapy (PDT) had a promising effect on
nonresectable cholangiocarcinoma (NCC). This prospective,
open-label, randomized, multicenter study with a group
sequential design compared PDT in addition to stenting (group
A) with stenting alone (group B) in patients with NCC.
METHODS: In patients with histologically confirmed
cholangiocarcinoma, endoscopic or percutaneous double
stenting was performed. Patients fulfilling inclusion criteria
were randomized to group A (stenting and subsequent PDT) and
group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt
was injected intravenously 2 days before intraluminal
photoactivation (wavelength, 630 nm; light dose, 180 J/cm(2)).
Further treatments were performed in cases of residual tumor in
the bile duct. The primary outcome parameter was survival time.
Secondary outcome parameters were cholestasis and quality of
life. RESULTS: PDT resulted in prolongation of survival (group
A: n = 20, median 493 days; group B: n = 19, median 98 days; P
< 0.0001). It also improved biliary drainage and quality of life.
CONCLUSIONS: PDT, given in addition to best supportive care, improves survival in patients
with NCC. The study was terminated prematurely because PDT proved to be so superior to simple
stenting treatment that further randomization was deemed unethical.
Ortner, ME
Caca, K
Berr, F
Liebetruth, J
Mansmann, U
Huster, D
Voderholzer, W
Schachschal, G
Mossner, J
Lochs, H

Am J Gastroenterol, July 1, 2001; 96(7): 2093-7.
Photodynamic therapy for palliation of nonresectable bile duct cancer--
preliminary results with a new diode laser system.
T Zoepf, R Jakobs, JC Arnold, D Apel, A Rosenbaum, and JF Riemann
Department of Gastroenterology, Academic Teaching Hospital, Ludwigshafen, Germany.
MEDLINE ABSTRACT
OBJECTIVES: Preliminary results of photodynamic therapy
(PDT) of bile duct cancer have shown astonishingly good
results in the reduction of cholestasis, improvement of quality of
life, and even prolongation of the survival time. Unfortunately,
the existing dye laser systems are large and costly, and their
maintenance is expensive. Therefore, we investigated the
feasibility of a diode laser system for PDT of nonresectable bile
duct cancer. METHODS: Eight patients with nonresectable bile
duct cancer were treated. Forty-eight hours after i. v. application
of 2 mg/kg body weight of Photosan-3, light activation was
performed by a transpapillary (four patients) or percutaneus
(four patients) access. We used a cylindrical diffusor tip and
illuminated using a wavelength of 633+/-3 nm and a total energy
of 200 J/cm2. All patients were additionally provided with bile
duct endoprostheses after PDT. RESULTS: Four weeks after initial PDT all patients showed a
marked reduction of bile duct stenosis. The median serum bilirubin value declined from 5.8 mg/dl
(2.0-10.1) to 1.0 mg/dl (0.8-4.4). The median survival time at the time of writing is 119 days (52-
Zoepf, T
Jakobs, R
Arnold, JC
Apel, D
Rosenbaum, A
Riemann, JF

443). Five patients are still alive. In four patients we could change from percutaneous to
transpapillary drainage after PDT, two patients showed infectious complications. CONCLUSION:
PDT with the diode laser system seems to be effective in reducing malignant bile duct stenosis.
This treatment is minimally invasive and has a low specific complication rate. Randomized,
controlled studies comparing PDT with the insertion of endoprostheses and long term follow-up of
results are needed to confirm the promising short term results.
Gastroenterology, November 1, 2003; 125(5): 1355-63.
Successful photodynamic therapy for nonresectable cholangiocarcinoma:
a randomized prospective study.
ME Ortner, K Caca, F Berr, J Liebetruth, U Mansmann, D Huster, W Voderholzer, G Schachschal,
J Mossner, and H Lochs
Division de Gastro-entérologie et Hépatologie, BH-10N, Centre Hospitalier Universitaire Vaudois,
CH-1011 CHUV-Lausanne, Switzerland. Maria-Anna.Ortner@hospvd.ch
MEDLINE ABSTRACT
BACKGROUND & AIMS: In nonrandomized trials,
photodynamic therapy (PDT) had a promising effect on
nonresectable cholangiocarcinoma (NCC). This prospective,
open-label, randomized, multicenter study with a group
sequential design compared PDT in addition to stenting (group
A) with stenting alone (group B) in patients with NCC.
METHODS: In patients with histologically confirmed
cholangiocarcinoma, endoscopic or percutaneous double
stenting was performed. Patients fulfilling inclusion criteria
were randomized to group A (stenting and subsequent PDT) and
group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt
was injected intravenously 2 days before intraluminal
photoactivation (wavelength, 630 nm; light dose, 180 J/cm(2)).
Further treatments were performed in cases of residual tumor in
the bile duct. The primary outcome parameter was survival time.
Secondary outcome parameters were cholestasis and quality of
life. RESULTS: PDT resulted in prolongation of survival (group
A: n = 20, median 493 days; group B: n = 19, median 98 days; P
< 0.0001). It also improved biliary drainage and quality of life.
CONCLUSIONS: PDT, given in addition to best supportive care, improves survival in patients
with NCC. The study was terminated prematurely because PDT proved to be so superior to simple
stenting treatment that further randomization was deemed unethical.
Ortner, ME
Caca, K
Berr, F
Liebetruth, J
Mansmann, U
Huster, D
Voderholzer, W
Schachschal, G
Mossner, J
Lochs, H

Stomach Cancer Journal Articles
Int J Gastrointest Cancer, January 1, 2002; 32(2-3): 139-42.
The pilot experience of immunotherapy-combined photodynamic therapy
for advanced gastric cancer in elderly patients.
Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Ube,
Yamaguchi, Japan. h.yanai@yamaguchi-u.ac.jp
MEDLINE ABSTRACT
BACKGROUND: Therapeutic efficacy of endoscopic
photodynamic therapy (PDT) for advanced gastric cancer is
limited. Recent animal studies have clarified the very important
role of host immune cells in PDT. We expected a potential
cooperative effect of PDT and immunotherapy, and developed
immunotherapycombined PDT (I-PDT) for advanced gastric
cancer. METHODS AND MATERIALS: We applied I-PDT for
two elderly patients with complicated advanced gastric cancer
(92- and 89-yr-old males). Tumor bleeding prevented them from
leading an ordinary home life. Initial simple PDT was not
effective. Patients received over 109 activated T-lymphocyte-
predominant autologous immune cells, mainly intravenously, 5x
for one course. PDT was performed endoscopically on the day
of the third infusion. RESULTS: Two or three courses of I-PDT
safely stopped tumor bleeding, and the initial poor prognoses of
a few months of survival seemed to be improved (patient 1, over
32 mo; patient 2, 14 mo). CONCLUSIONS: I-PDT was found to
be a safe, feasible treatment that could improve symptoms
resulting from advanced gastric cancer.
Yanai, H
Kuroiwa, Y
Shimizu, N
Matsubara, Y
Okamoto, T
Hirano, A
Nakamura, Y
Okita, K
Sekine, T

Brain Cancer Journal Articles
J Neurosci Nurs, December 1, 2001; 33(6): 296-300.
Photodynamic therapy: a novel treatment for primary brain malignancy.
TT Goodell and PJ Muller
Oregon Medical Laser Center/Providence St. Vincent Medical Center, 9205 SW Barnes Road,
Portland, OR 97225, USA.
MEDLINE ABSTRACT
Providing therapy that conserves healthy brain tissue while
effectively killing cancerous tissue remains a major challenge in
the treatment of primary malignant brain tumors. The most
common primary brain malignancies tend to recur despite
intensive therapy, and the side effects of radiotherapy and
chemotherapy can have considerable influence on health and
quality of life. Photodynamic therapy (PDT) is a new
technology being investigated to fulfill the need for a targeted
cancer treatment that may reduce tumor recurrence and extend survival with few adverse effects.
An investigational treatment, PDT employs wavelength-specific light in combination with a
photosensitizing agent. The photosensitizing agent accumulates in tumor cells and is activated by
nonthermal light, producing radical oxygen species that locally kill tumor cells. The selectivity of
the process makes PDT appealing in the brain, where conservation of healthy tissue is vital. The
most widely studied photosensitizer causes several weeks of ocular and cutaneous photosensitivity.
Nursing care of the PDT patient includes intracranial pressure monitoring, neurological
assessment, and intensive patient and family education. Many new photosensitizing compounds
and varying methods of light delivery are being studied. This technology shows promise for the
treatment of primary brain malignanc
Goodell, TT
Muller, PJ

Cutaneous Lymphoma Journal Articles
Dermatol Surg, August 1, 2000; 26(8): 765-9; discussion 769-70.
Photodynamic therapy of cutaneous lymphoma using 5-aminolevulinic
acid topical application.
A Orenstein, J Haik, J Tamir, E Winkler, H Trau, Z Malik, and G Kostenich
Center of Advanced Technologies, Plastic Surgery Department, Sheba Medical Center, Tel
Hashomer, Israel.
MEDLINE ABSTRACT
BACKGROUND: Photodynamic therapy (PDT) with topical
application of 5-aminolevulinic acid (ALA) is a new and
effective modality for treatment of superficial basal and
squamous cell carcinomas. OBJECTIVE: We present the
kinetics of ALA-induced protoporphyrin IX (PP) accumulation
and the results of ALA PDT treatment on two patients with
different stages (stage I and stage III) of mycosis fungoides
(MF)-type cutaneous T-cell lymphoma (CTCL). METHODS:
ALA-Decoderm cream was applied to the lesions for 16 hours.
Spectrofluorescence measurements of PP accumulation were
carried out before, during, and 1 hour after photoirradiation
(580-720 nm) using the VersaLight system. RESULTS:
Different patterns of PP fluorescence kinetics were observed in
patients with early and advanced stages of the disease. During
photoirradiation the intensity of fluorescence decreased
depending on the lesion thickness. One hour after the photoirradiation procedure no PP
Orenstein, A
Haik, J
Tamir, J
Winkler, E
Trau, H
Malik, Z
Kostenich, G

fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP
fluorescence reappeared; after an additional 10-15 minutes of irradiation PP fluorescence
disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion
after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response
was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and
24 months, respectively). CONCLUSION: The results showed a high response of both stage I and
stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used
successfully for MF treatment.
Eur J Med Res, November 25, 2002; 7(11): 477-9.
Remission of a cutaneous Mycosis fungoides after topical 5-ALA
sensitisation and photodynamic therapy in a patient with advanced HIV-
infection.
V Paech, T Lorenzen, A Stoehr, K Lange, H Merz, WN Meigel, and A Plettenberg
Ifi-institute for interdisciplinary Infectiology and Immunology GmbH, Hamburg, Germany.
MEDLINE ABSTRACT
BACKGROUND: Treatment of Mycosis fungoides (MF) in
HIV-infected patients is controversially discoursed.
Photodynamic therapy (PDT) after topical sensitization with 5-
aminolevulinic acid (5-ALA) is a new and effective modality for
treatment of skin malignancies. OBJECTIVE: In this report we
describe, what is, to our knowledge, the first case of a patient
with MF through advanced HIV-infection, successfully
experiencing topical 5-ALA sensitization and PDT.
METHODS: 5-ALA ointment was applied to plaques and held
in occlusion for 4 hours. PDT was applied using the PDT 1200
irradiation source (Waldmann Medizintechnik System) with 180
J/cm superset 2. RESULTS: Complete remission of MF was
achieved, after two completed cycles of photodynamic therapy.
CONCLUSION: MF lesions in the presended case showed a
high response to 5-ALA sensitization and PDT. This modality appeared to be very effective in
treatment of MF in a HIV-infected patient and could be a valuable treatment option for cutaneous
T-cell lymphoma in HIV-infected patients.
Paech, V
Lorenzen, T
Stoehr, A
Lange, K
Merz, H
Meigel, WN
Plettenberg, A

Liver Cancer Journal Articles
Effective treatment of liver metastases with photodynamic therapy, using the
second-generation photosensitizer meta-tetra (hydroxyphenyl) chlorin
(mTHPC), in a rat model.
JP Rovers, AE Saarnak, A Molina, JJ Schuitmaker, HJ Sterenborg, and OT Terpstra
Department of Surgery, Leiden University Medical Centre, The Netherlands
Br J Cancer, October 1, 1999; 81(4): 600-8.
The only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable
candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for
palliation. Photodynamic therapy (PDT) could be a selective, minimally invasive treatment for patients with
liver metastases. . Damage to normal liver tissue was mild and transient as serum aspartate
aminotransferase and alanine aminotransferase levels normalized within a week after PDT treatment. Long-
term effects of mTHPC-PDT were studied on day 28 after treatment. Regardless of drug dose and drug-light
interval, PDT with mTHPC resulted in complete tumor remission in 27 out of 31 treated animals (87%), with
only four animals in which tumor regrowth was observed. Non-responding tumors proved to be significantly
larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an
intrahepatic tumor and that mTHPC-PDT is capable of inducing complete tumor remission of liver tumors.
Eur Radiol, March 26, 2004; .
Interstitial photodynamic laser therapy in interventional oncology.
Thomas J. Vogl, Katrin Eichler, Martin G. Mack, Stephan Zangos, Christopher Herzog, Axel

Thalhammer, and Kerstin Engelmann
Department of Diagnostic and Interventional Radiology, University of Frankfurt, Theodor-Stern-
Kai 7, 63590, Frankfurt/Main, Germany.
MEDLINE ABSTRACT
Photodynamic therapy (PDT) is a well-investigated locoregional
cancer treatment in which a systemically administered
photosensitizer is activated locally by illuminating the diseased
tissue with light of a suitable wavelength. PDT offers various
treatment strategies in oncology, especially palliative ones. This
article focuses on the development and evaluation of interstitial
PDT for the treatment of solid tumors, particularly liver tumors.
The PDT is mostly used for superficial and endoluminal lesions
like skin or bladder malignancies and also more frequently
applied for the treatment of lung, esophageal, and head and neck
cancer. With the help of specially designed application systems,
PDT is now becoming a practicable option for solid lesions,
including those in parenchymal organs such as the liver. After
intravenous treatment with the photosensitizer followed by
interstitial light activation, contrast-enhanced computed tomography shows the development of
therapy-induced necrosis around the light-guiding device. With the use of multiple devices,
ablation of liver tumors seems to be possible, and no severe side effects or toxicities related to the
treatment are reported. PDT can become a clinically relevant adjunct in the locoregional therapy
strategies. .
Vogl, TJ
Eichler, K
Mack, MG
Zangos, S
Herzog, C
Thalhammer, A
Engelmann, K
Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr, May 1, 2003; 175(5):
682-7.

[Interstitial photodynamic laser therapy for liver metastases: first results
of a clinical phase I-study]
K Engelmann, MG Mack, K Eichler, R Straub, S Zangos, and TJ Vogl
Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Frankfurt, Johann-
Wolfgang-Goethe-Universität. engelmann@em.uni-frankfurt.de
MEDLINE ABSTRACT
PURPOSE: Development and evaluation of a new
photodynamic treatment technique for the laser therapy of liver
malignancies MATERIAL AND METHODS: The combination
with new catheter systems enables the use of the photodynamic
therapy (PDT) to treat also tumors in parenchymal organs. So
far it is mainly used to treat superficial or endoluminal tumors.
The presented study is part of a multicenter phase I-study. We
treated 5 patients with colorectal liver metastases with the new
photosensitizer SQN 400 and following interstitial
photodynamic laser treatment. Evaluation of tumors were
performed by contrast-enhanced CT scans. RESULTS: In the
contrast enhanced CT scans the development of a complete
necrosis within a radius of 1 cm around every single fibre could
be shown. Additional the ablation of tumors with the combined
use of several fibres is possible. Severe complications or toxicities were not observed.
CONCLUSION: The photodynamic laser therapy of liver malignancies is a minimal invasive
procedure with little side effects which produces sharply defined yet small volumes of necrosis.
Engelmann, K
Mack, MG
Eichler, K
Straub, R
Zangos, S
Vogl, TJ

Malignant Melanoma Journal Articles
Photodermatol Photoimmunol Photomed, February 1, 2004; 20(1): 21-6.
Photodynamic therapy with chlorin e(6) for skin metastases of melanoma.
SV Sheleg, EA Zhavrid, TV Khodina, GA Kochubeev, YP Istomin, VN Chalov, and IN Zhuravkin
Department of Chemotherapy, N.N. Alexandrov Research Institute of Oncology and Medical
Radiology, P.O. Lesnoy-2, Minsk 223052, Republic of Belarus. ssheleg@tut.by
MEDLINE ABSTRACT
BACKGROUND: Photodynamic therapy (PDT) has been
successfully applied in clinical settings to destroy neoplasms,
but the efficacy of such a treatment is dependent on the type of
neoplasm and the photosynthesizer used. Here, we perform a
clinical assessment of PDT for skin metastases of pigmented
melanoma using chlorin e(6). STUDY DESIGN/MATERIALS
AND METHODS: PDT with chlorin e(6) photosensitizer was
administered to 14 patients with skin metastases from melanoma
(10 females, four males, mean age 49.6 years). Chlorin e(6) at a
dose of 5 mg/kg of patient's weight was intravenously injected.
The treatment course consisted of two courses of PDT exposure
1 h after intravenous chlorin e(6) injection and 24 h post-
injection. The light energy density for each skin tumor was 80-
120 J/cm(2) per treatment, with a light power density of 250-300
mW/cm(2). RESULTS: All skin melanoma metastases that received PDT showed complete
regression with no recurrence during the study period. The complete response of all skin
metastases from melanoma occurred in eight cases after one PDT treatment. In the remaining six
Sheleg, SV
Zhavrid, EA
Khodina, TV
Kochubeev, GA
Istomin, YP
Chalov, VN
Zhuravkin, IN

individuals, tumors required multiple PDT courses prior to complete regression. No cases of
photodermatitis were registered. The Karnofsky performance scale score of the patients with skin
metastases from melanoma showed no significant difference before and after PDT. No patients had
significant changes in blood cell counts that would indicate chlorin e(6) systemic toxic effect.
Blood chemistry and urinalysis did not show any evidence of chlorin e(6) renal and hepatic injury.
CONCLUSIONS: PDT with chlorin e(6) for skin metastases from melanoma is effective and well
tolerated. Further clinical investigation of PDT with chlorin e(6) is warranted.

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