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?

Photodynamic therapy for cancer

CA : A Cancer Journal for Clinicians

NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer J Clin 2011;61:250-281. V C

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Photodynamic therapy of cancer: An update†‡

A review of reported tissue optical properties summarizes the wavelength-dependent behavior of scattering and absorption. Formulae are presented for generating the optical properties of a generic tissue with variable amounts of absorbing chromophores (blood, water, melanin, fat, yellow pigments) and a variable balance between small-scale scatterers and large-scale scatterers in the ultrastructures of cells and tissues.

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Optical properties of biological tissues: a review.

We have measured tissue optical properties during a Phase II clinical trial to treat peritoneal carcinomatosis. Physiological properties before and after PDT will be reported.

Rapid in-vivo measurement of optical and physiological properties in human intraperitoneal tissues before and after photodynamic therapy

Photodynamic therapy (PDT) involves interactions between the three main components of light fluence,
photosensitizer concentration, and oxygenation. Currently, singlet oxygen explicit dosimetry (SOED) has focused on
the first two of these components. The macroscopic model to calculate reacted singlet oxygen has previously
involved a fixed initial ground state oxygen concentration. A phosphorescence-based oxygen probe was used to
measure ground state oxygen concentration throughout treatments for mice bearing radioactively induced
fibroscarcoma tumors. Photofrin-, BPD-, and HPPH-mediated PDT was performed on mice. Model-calculated
oxygen and measured oxygen was compared to evaluate the macroscopic model as well as the photochemical
parameters involved. Oxygen measurements at various depths were compared to calculated values. Furthermore, we
explored the use of noninvasive diffuse correlation spectroscopy (DCS) to measure tumor blood flow changes in
response to PDT to improve the model calculation of reacted singlet oxygen. Mice were monitored after treatment to
see the effect of oxygenation on long-term recurrence-free survival as well as the efficacy of using reacted singlet
oxygen as a predictive measure of outcome. Measurement of oxygenation during treatment helps to improve SOED
as well as confirm the photochemical parameters involved in the macroscopic model. Use of DCS in predicting
oxygenation changes was also investigated.

Oxygen measurements to improve singlet oxygen dosimetry

Bengt E. Bjärngard, Ph.D.

We present a novel fiber optic based singlet oxygen luminescence probe coupled to an InGaAs/InP single photon avalanche diode (SPAD) detector. Patterned time gating limited unwanted dark counts and eliminated the strong photosensitizer luminescence background.

A compact fiber optic based singlet oxygen luminescence sensor

Purpose: To determine whether a course of hyperfractionated radiation therapy concomitant with escalated radiosensitizing platinum compounds can be admhustered wltb acceptable morbidity and achieve a high rate of locoregional control for Stage ID and IV head and neck cancer and whether the patients can be tumor free at the primary site after initial therapy and cured by the additional chemoradiation without radical resection of the primary tumor. Methods and Materials: Patients with Stage III/IV head and neck cancer were treated in this multicenter Phase II Study with 1.8 Gy fraction radiotherapy for 2 weeks, with escalation to 1.2 Gy b.i.d. hyperfractionation to 46.8 Gy. Concomitant continuous infusion cisplantinum (CDDP) 20 mg per meter square on day 1 to 4 and 22 to 25 was given. Reassessment by biopsy of primary and nodes was done. Patients with a complete response continued with hyperfractionated radiotherapy to 75.6 Gy with simultaneous carboplatinum (Carbo), 25 mg per meter square b.i.d. for 12 consecutive treatment days. Patients with residual disease at 46.8 Gy required curative surgery. Seventy-four patients were treated at the three institutions; 20 were Stage III and 54 were Stage IV. All patients had daily mouth care, nutritional, and psychosocial support. Results: This regime was well tolerated. Eighty-five percent of toxicities were Grade 1 or 2 and there was only one Grade 4 hematologic toxicity. Late toxicities included xerostomia in 25 patients, dysphasia in 18, and mild speech impediment in 11. Biopsies of primary site were done after the first course of treatment in 59 patients. Neck dissections were performed in 35 patients. Forty-four of 59 (75%) primary sites and 16 of 35 (46%) lymph nodes had pathologically complete response (CR). Of the 74 patients, only 12 required surgical resection of the primary site. Thirty-five of the 50 node positive patients had neck dissections, 16 of these were CRs at surgery. At 4 years (median follow-up of 26 months), disease-specific survival is 63%. The actuarial survival for all patients is 51%. Patients with pathological CR after initial treatment have disease specific survival of 73% at 4 years vs. 48% of patients with partial response (PR) only. Conclusion: This study, developed on the basis of radiobiological and cell kinetic precepts, produced results that compare favorably with other reports of management of patients with advanced head and neck cancer. In comparison with our previous study, these results are comparable, not impressively better. The associated morbidity was somewhat worse. 0 1997 Elsevier Science Inc. Advanced stage bead and neck cancer, Trimodality treatment.

l Clinical Investigation CONCURRENT PLATINUM-BASED CHEMOTHERAPY AND HYPERFRACTIONATED RADIOTHERAPY WITH LATE INTENSIFICATION IN ADVANCED HEAD AND NECK CANCER

Timothy C. Zhu

Papers

Rapid in-vivo measurement of optical and physiological properties in human intraperitoneal tissues before and after photodynamic therapy

Oxygen measurements to improve singlet oxygen dosimetry

Bengt E. Bjärngard, Ph.D.

A compact fiber optic based singlet oxygen luminescence sensor

l Clinical Investigation CONCURRENT PLATINUM-BASED CHEMOTHERAPY AND HYPERFRACTIONATED RADIOTHERAPY WITH LATE INTENSIFICATION IN ADVANCED HEAD AND NECK CANCER