Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.

Photodynamic Therapy

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

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Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

A Consensus Conference sponsored by the Archstone Foundation of Long Beach, California, was held February 17–18, 2009, in Pasadena, California. The Conference was based on the belief that spiritual care is a fundamental component of quality palliative care. This document and the conference recommendations it includes builds upon prior literature, the National Consensus Project Guidelines, and the National Quality Forum Preferred Practices and Conference proceedings.

https://growthhouse.org/spirit/files/spiritual_care_consensus_report.pdf

Improving the Quality of Spiritual Care as a Dimension of Palliative Care: The Report of the Consensus Conference

An increasingly recognized resistance mechanism to androgen receptor (AR)-directed therapy in prostate cancer involves epithelial plasticity, in which tumor cells demonstrate low to absent AR expression and often have neuroendocrine features. The etiology and molecular basis for this 'alternative' treatment-resistant cell state remain incompletely understood. Here, by analyzing whole-exome sequencing data of metastatic biopsies from patients, we observed substantial genomic overlap between castration-resistant tumors that were histologically characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same individuals over time points to a model most consistent with divergent clonal evolution. Genome-wide DNA methylation analysis revealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a role in the induction and/or maintenance of this treatment-resistant state. This study supports the emergence of an alternative, 'AR-indifferent' cell state through divergent clonal evolution as a mechanism of treatment resistance in advanced prostate cancer.

/pdf/divergent-clonal-evolution-of-castration-resistant-15o38ilal4.pdf

Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer

Background. In the last decades, thyroid cancer incidence has continuously and sharply increased all over the world. This review analyzes the possible reasons of this increase. Summary. Many experts believe that the increased incidence of thyroid cancer is apparent, because of the increased detection of small cancers in the preclinical stage. However, a true increase is also possible, as suggested by the observation that large tumors have also increased and gender differences and birth cohort effects are present. Moreover, thyroid cancer mortality, in spite of earlier diagnosis and better treatment, has not decreased but is rather increasing. Therefore, some environmental carcinogens in the industrialized lifestyle may have specifically affected the thyroid. Among potential carcinogens, the increased exposure to medical radiations is the most likely risk factor. Other factors specific for the thyroid like increased iodine intake and increased prevalence of chronic autoimmune thyroiditis cannot be excluded, while other factors like the increasing prevalence of obesity are not specific for the thyroid. Conclusions. The increased incidence of thyroid cancer is most likely due to a combination of an apparent increase due to more sensitive diagnostic procedures and of a true increase, a possible consequence of increased population exposure to radiation and to other still unrecognized carcinogens.

/pdf/worldwide-increasing-incidence-of-thyroid-cancer-update-on-1wx00tyl3z.pdf

Worldwide increasing incidence of thyroid cancer: Update on epidemiology and risk factors

CA : A Cancer Journal for Clinicians

All photosensitizers applied in experimental- and clinical-photochemotherapy (PCT) have broad absorption spectra stretching from the ultraviolet up to 6 - 700 nm. Light of wavelengths in the red part of the spectrum is chosen for PCT even though the extinction coefficients of the sensitizers are usually smaller in this wavelength region than at shorter wavelengths. Thus, if one wants to treat superficial tumors or skin disorders, this may be a wrong choice. Two pieces of information are needed in order to make a proper choice of wavelength to treat a lesion of a given depth: the wavelength dependence of the optical penetration depth into tissue, and the action spectrum for tumor destruction. Additionally, the skin photosensitivity induced by the drug should be considered. We have non-invasively measured the optical penetration spectra of human tissues in vivo and the fluorescence excitation spectra for several sensitizers, including protoporphyrin (PpIX), in cells. Assuming that the action spectrum for cell inactivation can be approximated by the fluorescence excitation spectrum of the sensitizer -- which is indeed the case for a number of sensitizers in cells in vitro -- we have considered the situation for 5-aminolevulinic acid-induced PpIX in human tissue. All the way down to about 2 mm below the surface light in the Soret band (-410 nm) would give the largest cell inactivation, while at depth exceeding 2 mm, the conventional 635 nm light would be optimal. Light at the argon laser wavelength 514.5 nm is more efficient than light at 635 nm down to 1 mm. From the surface and down to 6 mm, the 635 nm peak of the excitation spectrum of PpIX, as evaluated per photon incident on the skin surface, is redshifted by less than 2 nm. In some cases photosensitizing photoproducts are formed during PCT, such as photoprotoporphyrin during PCT with PpIX. In such cases it may be advantageous to apply a broad-band light source with a spectrum that covers also part of the action spectrum of this photoproduct.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Choice of the proper wavelength for photochemotherapy

The objectives of this work were: (1) To determine whether repeated exposures to small doses from a commercial sun bed (Wolff Solarium Super Plus 100 W) over 5 weeks gave less vitamin D than repeated exposures to twice as large, but still nonerythemogenic, doses. (2) To investigate whether the contribution to the vitamin D status from such sessions of exposures was dependent on the baseline status before the start of the sessions. (3) To determine the decay rate of the induced increment of vitamin D. The sun bed sessions raised the 25-hydroxyvitamin D levels from typical winter values to typical summer values. The mean value after exposure being 80 nm (+/-14) and the increase being 15 nm on average. Persons with the lowest initial levels got the largest increase. The level in this group was back to the pre-exposure level after 2-4 weeks. To maintain a summer level through the winter, when no vitamin D is produced by the sun in northern countries, one should consider increasing the recommended intake of vitamin D intake significantly, or encouraging the population to get moderate, nonerythemal sun bed exposures.

Sunbeds as vitamin D sources.

Solar radiation is of fundamental importance for human development and health: On the one hand, too much of it can lead to skin ageing and skin cancer, whilst on the other, too little of it can result in vitamin D deficiency, and, thereby lead to high incidence and poor prognosis of internal cancer as well as a number of other diseases. The following data, mostly from Norway, will be reviewed: Variation of ambient solar ultraviolet radiation (UV) and vitamin D status with season and latitude, variation of incidence rates and prognosis of skin cancer and variation of prognosis of internal cancer with latitude and season. In short, the following issues are discussed: 1) Vitamin D level varies with season, but probably not with latitude in Norway, because of an increased intake of vitamin D in the north; 2) Skin cancer incidence rates increase from north to south, as do annual fluence rates of UV radiation, while there seems to be a slight improvement in prognosis from north to south; 3) Prognosis of internal cancer is best for cases diagnosed in the seasons with the best vitamin D status, i.e. in summer and autumn; 4) Incidence rates of cutaneous melanomas have increased from 1960 to 1990, but have decreased slightly thereafter for young people; 5) Changes in sun exposure habits have taken place; 6) An increase in body mass index (BMI) of the population has occurred, which may have led to a worsening of the vitamin D status.

Solar radiation, vitamin D and cancer incidence and mortality in Norway.

Hexyl Aminolaevulinate Is a More Effective Topical Photosensitiser Precursor than Methyl Aminolaevulinate and 5-Aminolaevulinic Acids When Applied in Equimolar Doses

Johan Moan

Papers

CA : A Cancer Journal for Clinicians

Choice of the proper wavelength for photochemotherapy

Sunbeds as vitamin D sources.

Solar radiation, vitamin D and cancer incidence and mortality in Norway.

Hexyl Aminolaevulinate Is a More Effective Topical Photosensitiser Precursor than Methyl Aminolaevulinate and 5-Aminolaevulinic Acids When Applied in Equimolar Doses