REVIEWPhotodynamic therapy for chest wall recurrence from breast cancer
Introduction
Dramatic advances have occurred in the early detection and treatment of breast cancer. However, even with 90% or higher local control rates reported at 5-year follow up, a considerable number of women still suffer local regional failure [1]. Potentially, in North America alone, this translates to nearly 20,000 of the 230,000 new breast cancer cases diagnosed each year requiring salvage therapy for local-regional failure. Further, it is well documented that local failure increases with longer follow-up. Eventually more than 15% of these patients will require local salvage by 15 years post-treatment despite “curative” therapy [2].
Generally initial salvage for patients who fail breast-conserving therapy of lumpectomy and radiation is modified radical mastectomy [3]. For patients who fail mastectomy full course radiation therapy is employed to the chest wall and regional lymphatics. Fortunately in both situations salvage therapy is generally successful with minimal acute morbidity for most patients. Salvage in these situations usually incurs risk of arm edema as the most common chronic side effect. Overall, several large series show that nearly 90% of patients undergoing salvage will regain local control [2], [4], [5], [6]. For lumpectomy and radiation patients with isolated recurrence at the initial tumor site survival is nearly equivalent to similar patients who did not recur. Most patients who experience recurrence will undergo additional chemotherapy though no randomized series exist to examine this important question and the benefit of this treatment.
Given the large number of patients diagnosed with breast cancer, the real risk of local failure, and the fact that local control from salvage does not approach 100%, a significant minority of breast cancer patients will re-recur loco-regionally. These individuals will most likely have already undergone one or more major surgical procedures for local control, full dose radiation and multi-agent chemo-hormonal therapy. Clearly, additional salvage options with these modalities are limited. Photodynamic therapy (PDT) [7], [8] has had considerable success in the treatment of cutaneous primary and metastatic malignant lesions and should be considered for these unfortunate individuals. PDT has the additional benefit of being a potentially painless outpatient procedure that is repeatable. PDT can work in combination with other salvage regimens or as a stand-alone therapy. In a simplistic overview, PDT has three main components: first a sensitizing agent, which preferentially accumulates in malignant/pre-malignant tissues and/or clears faster from surrounding normal tissue; second, a source of intense illumination, which at the appropriate wavelength will activate the sensitizer. This leads to the third component of PDT, oxygen, which in the course of the photodynamic reaction is transformed into singlet oxygen. The generation of singlet oxygen allows for the rapid cytotoxic/vasculotoxic activity associated with PDT. We will analyze and review the PDT literature, based on published peer reviewed papers, concerning this important patient population.
Section snippets
Natural history of chest wall lesions
Once tumor cells have invaded dermal lymphatics, they appear free to travel extensively in this cutaneous system [9]. As these lymphatics are without direction, due to lack of valves, metastasis originating from the chest wall can spread to the contra-lateral chest, abdomen and even the back. This extensive spread explains the virtual complete failure of nidusectomy, attempted at what appears to be a solitary metastasis. As these lesions grow, they often cause intensive signs and symptoms.
Photosensitizers
Photosensitizers are substances that transfer and translate light energy into a type II photodynamic reaction [28]. The oxygen-based reaction creates toxic singlet oxygen species for tumor ablation. Photosensitizers may be natural or synthetic. In general the three main families for photosensitization are porphyrin based, chlorophyll based or dye based [29], [30], [31], [32], [33]. The porphyrins are ring structures. Those tried in breast cancer treatment included hematoporphrin derivatives
Photofrin®
Photofrin®, a hematoporphyrin derivative, is a member of the porphyrin family which has been employed in a number of trials [34], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65]. In addition to highly variable drug dose, light dose and drug to light interval time, dissimilar patient populations also appear to exist. Complicating matters even more, the reporting of response varies from series to series, sometimes including lesions response rates, patient response, and volume response
Patient positioning
Unlike many patients who undergo PDT, patients with chest wall disease pose certain unique considerations. First and foremost patients generally have numerous lesions requiring therapy. Since ideally each lesion should be treated appropriately, a system of identifying the lesion and ensuring it is illuminated is essential. As some individuals will have 50 treatment fields, memory will not suffice. We recommend an anatomical drawing to be used in conjunction with patient coordinates and
Photosensitivity
All sensitizers will offer sunlight photosensitivity [28]. For Photofrin® at 2 mg/kg, 4–8 weeks of precautions are needed. At 0.8 mg/kg we have found sunlight photosensitivity rare after 4 weeks. Purlytin patients were sensitive for 2 weeks [73] and Foscan® [72] patients to 10 days. In general, sunlight precautions apply only to sunlight or similar intense light. Patients’ skin must be covered and wrap around sunglasses as well as a wide brim hat is recommended. Reflected light, for example from
Conclusion
PDT can reliably salvage individuals with chest wall recurrence despite fragile tissues from surgical, radiation and chemotherapeutic intervention. PDT can not only control chest wall recurrence, but offer the potential for superior cosmetic results. This is particularly noteworthy as these patients are all too often denied any additional salvage, and are left with daily growing reminders of their mortality.
Local treatment may have an impact on survival, particularly if infected open tumor
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