Rosa E. Cuenca

Photosensitizers in clinical PDT

Photosensitizers in photodynamic therapy allow for the transfer and translation of light energy into a type II chemical reaction. In clinical practice, photosensitizers arise from three families-porphyrins, chlorophylls, and dyes. All clinically successful photosensitizers have the ability to a greater or lesser degree, to target specific tissues or their vasculature to achieve ablation. Each photosensitizer needs to reliably activate at a high enough light wavelength useful for therapy. Their ability to fluoresce and visualize the lesion is a bonus. Photosensitizers developed from each family have unique properties that have so far been minimally clinically exploited. This review looks at the potential benefits and consequences of each major photosensitizer that has been tried in a clinical setting.

Sentinel lymph node biopsy during pregnancy: initial clinical experience.

The diagnosis of breast cancer or melanoma in a pregnant patient presents some unique and difficult challenges for both patients and providers. Lymphatic mapping and sentinel lymph node (SLN) biopsy has become an attractive alternative to elective lymphadenectomy procedures for patients with breast cancer and melanoma. However, there is no data on the safety or utility of sentinel node mapping in pregnant patients. Therefore, we reviewed our experience with mapping in gravid patients. Academic institutions throughout North Carolina were asked to contribute cases of mapping performed during pregnancy. A total of nine women underwent sentinel node mapping during pregnancy. All nine were Caucasian with an average age of 32. SLN were found in all cases and mapping procedures were for breast cancer (three), and melanoma (six). There were no adverse reactions to the SLN procedures and one patient developed a seroma at a biopsy site. All went on to have term deliveries without known adverse effects.This limited experience shows that SLN mapping procedures are feasible in pregnant patients. However, this is not a general endorsement of such procedures in pregnant patients. We suggest that potential risks of vital dye or radioactive tracers be clearly explained to the parents when the mother is a candidate for a mapping procedure, and be balanced against the risk of delaying therapy or omitting nodal staging.

Breast Cancer With Chest Wall Progression: Treatment With Photodynamic Therapy

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) IV 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.

The future of photodynamic therapy in oncology.

The medicinal properties of light-based therapies have been appreciated for millennia. Yet, only in this century have we witnessed the birth of photodynamic therapy (PDT), which over the last few decades has emerged to prominence based on its promising results and clinical simplicity. The fundamental and distinguishing characteristics of PDT are based on the interaction of a photosensitizing agent, which, when activated by light, transfers its energy into an oxygen-dependent reaction. Clinically, this photodynamic reaction is cytotoxic and vasculotoxic. While the current age of PDT is based on oncological therapy, the future of PDT will probably show a significant expansion to non-oncological indications. This harks back to much of the original work from a century ago. Therefore, this paper will attempt to predict the future of PDT, based in part on a review of its origin.

Clinical photodynamic therapy of head and neck cancers—A review of applications and outcomes

As local control is tantamount to cure in head and neck cancer, an aggressive regimen of surgery and radiation remains the standard of care for most patients. Despite significant technical advances, these treatments are highly morbid. Further, patients who fail treatment have limited salvage options. Photodynamic therapy (PDT) and photodiagnosis (PD) of head and neck cancer offer significant potential for improved outcomes in a myriad of clinical indications ranging from in situ to recurrent disease. However, despite promising results, these modalities remain at the fringe of head and neck treatment options. Photofrin(®), Photosan and Foscan(®) are photosensitizers used clinically in head and neck PD/PDT. In addition, aminolevulinic acid (ALA), which gives origin to Protoporphyrin IX, an endogeneous photosensitizer, is also used for PD/PDT. We review the clinical literature on these photosensitizers to assist in the integration of these important modalities into the mainstream of head and neck oncological therapy.

PD/PDT for gynecological disease: A clinical review

The evolution of diagnostic and interventional procedures for gynecologic disease has led to organ, sexual and reproductive sparing treatments. Photodiagnosis (PD) and photodynamic therapy (PDT) may play a great role for gynecological patients as both offer the potential to achieve these goals. PD/PDT for a wide variety of diagnostic and therapeutic interventions have shown potential for excellent clinical outcomes. However, significant limitations remains, both clinically and dosimetrically, that prevent consistent results. When those limitations are resolved PD/PDT could move to the forefront of gynecological therapy. This clinical review highlights the outcomes and shortcomings of PD/PDT through the peer reviewed literature for gynecological sites.

Modeling of a Type II Photofrin‐mediated Photodynamic Therapy Process in a Heterogeneous Tissue Phantom

Abstract We present a quantitative framework to model a Type II photodynamic therapy (PDT) process in the time domain in which a set of rate equations are solved to describe molecular reactions. Calculation of steady-state light distributions using a Monte Carlo method in a heterogeneous tissue phantom model demonstrates that the photon density differs significantly in a superficial tumor of only 3 mm thickness. The time dependences of the photosensitizer, oxygen and intracellular unoxidized receptor concentrations were obtained and monotonic decreases in the concentrations of the ground-state photosensitizer and receptor were observed. By defining respective decay times, we quantitatively studied the effects of photon density, drug dose and oxygen concentration on photobleaching and cytotoxicity of a photofrin-mediated PDT process. Comparison of the dependences of the receptor decay time on photon density and drug dose at different concentrations of oxygen clearly shows an oxygen threshold under which the receptor concentration remains constant or PDT exhibits no cytotoxicity. Furthermore, the dependence of the photosensitizer and receptor decay times on the drug dose and photon density suggests the possibility of PDT improvement by maximizing cytotoxicity in a tumor with optimized light and drug doses. We also discuss the utility of this model toward the understanding of clinical PDT treatment of chest wall recurrence of breast carcinoma.

A clinical review of PDT for cutaneous malignancies

More critical than for most other anatomy, intervention to cutaneous malignancy must not only be therapeutically successful but also achieve excellent cosmetic and functional outcome. As it can achieve those ends, PDT has moved to the forefront in the management of skin cancer. A number of well designed clinical trials and large patient series have reported outstanding outcomes for many histologies. This paper will review the rationale and outcomes of cutaneous PDT to malignancy using both topical and systemic photosensitizers. The benefits and drawbacks of cutaneous PDT are also examined.

Photodynamic therapy for chest wall recurrence from breast cancer

Breast cancer is common with over 230,000 new cases diagnosed each year in North America alone. While great strides have been made to achieve excellent cancer control and survival, a significant minority of patients fail locally. While initial salvage to regain disease control is of the utmost importance, it is not universally successful. This leads to a therapeutic quagmire. Additional surgery, radiation and chemo-hormonal therapy are possible, but they are usually highly morbid with low success rates. Photodynamic therapy appears to be an underutilized salvage modality for this unfortunate patient population. This report analyzes and reviews the role of photodynamic therapy for patients with chest wall re-recurrence from breast cancer.

Photodynamic therapy for anal cancer.

Invasive anal cancers are generally successfully treated by combined chemotherapy with radiation therapy (XRT). For those patients who locally fail this intervention many are salvaged by surgery which generally results in permanent colostomy. We examined the treatment and outcome of Photofrin based photodynamic therapy (PDT) in a cohort of patients with anal cancer who failed locally despite chemo-radiation (N=6) and two patients with positive margins of resection after excision of small T(1) squamous cell anal cancers who refused further surgery or chemo-radiation. PDT consisted of outpatient infusion of Photofrin at 1.2mg/kg followed 48 h later by outpatient illumination. Red light (630 nm) illumination was delivered by a 5 cm diffusing fiber, treating transphincterally at 300 J/cm followed by microlens illumination at 200 J/cm(2) to the perianal tumor bed with 2 cm margin. All patients completed PDT without incident and all have maintained local control of disease in the anal region for the length of follow up (18-48 months). PDT may serve as a new means to salvage local failures and perhaps could be employed as a primary treatment modality in select patients with early stage of disease.