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Photodynamic Therapy Using Topical Methyl Aminolevulinate vs Surgeryfor Nodular Basal Cell Carcinoma
Abstract
Photodynamic therapy (PDT) is increasingly used as a noninvasive treatment for nodular basal cell carcinoma (BCC), without a sound evidence base.
To compare topical PDT, with the use of the sensitizer methyl aminolevulinate, and standard excision surgery in nodular BCC.
Prospective, randomized study.
University dermatology departments.
A total of 101 adults with previously untreated nodular BCC.
Patients received methyl aminolevulinate PDT (n = 52) or surgery (n = 49). The PDT was given twice, 7 days apart, with methyl aminolevulinate cream (160 mg/g) and 75 J/cm(2) red light (570-670 nm). Thirteen patients with a noncomplete response to PDT at 3 months (24% lesions) were retreated.
Primary end point was clinically assessed lesion clearance at 3 months after treatment. Secondary end points were sustained response rate at 12 months and cosmetic outcome at 3 and 12 months. Cosmesis and lesion recurrence were further assessed at 24 months.
Data from 97 patients (105 lesions) were included in the 3-month per-protocol analysis. Complete response rates did not differ significantly between groups (51/52 [98%] lesions with surgery vs 48/53 [91%] lesions with methyl aminolevulinate PDT; difference [95% confidence interval], 4.8% (-3.4% to 13.0%]; P =.25). At 12 months, tumor-free rates were 50 (96%) of 52 lesions with surgery vs 44 (83%) of 53 with methyl aminolevulinate PDT (P =.15). More patients treated with methyl aminolevulinate PDT than surgery had an excellent or good cosmetic outcome at all time points (significant at 12 and 24 months on patient assessment, P<.05, and at 3, 12, and 24 months on investigator evaluation, P<.001). At 24 months, 5 lesions that had initially cleared with methyl aminolevulinate PDT had recurred, compared with 1 after surgery.
Methyl aminolevulinate PDT is an effective treatment for nodular BCC, and while there is a trend for higher recurrence with this modality, it conveys the advantage over surgery of better cosmesis.
... The serious AEs reported were considered not to be related to either treatment modality [55]. 3 trials randomized patients to receive either PDT or SE [51][52][53][54]56]. In two of them, ALA cream was utilized, and the results exhibited higher recurrence rates in comparison with SE, especially at 5 years after treatment [51,52,56]. ...
... A novel low-irradiance ambulatory PDT with two of those studies which included both nBCC and sBCC already discussed above and presented at Tables 1 and 2 [45,46]. Similar to sBCC trials, for inclusion histological confirmation was required [50][51][52][53][54][55][56][57][58]. For the assessment of response to treatment (Table 3), clinical evaluation, with histological confirmation to be utilized only in cases of residual or recurrent lesions, was the preferred method [50-54,57]. ...
... The AFXL pre-treatment did not influence pain sensation during illumination[57].According to the data reviewed, both ALA-PDT and MAL-PDT can be termed as generally effective and welltolerated treatment modalities for the treatment of thin and small sBCC and nBCC. In terms of efficacy, similar CR were observed between PDT and most of the other interventions, except for SE and imiquimod which demonstrated better results[36][37][38][39][40][41][51][52][53][54]56]. The main weakness of surgery, especially when compared to PDT, was the cosmetic outcome, with PDT being superior and exhibiting more often good or excellent aesthetic results. ...
Introduction:
Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities are approved for the treatment of BCC, making it difficult for physicians to choose the most suitable option for every patient. Photodynamic therapy (PDT) using either 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) as photosensitizing agents is an established treatment option for low-risk BCC.
Objectives:
This review aims to summarize the available evidence from randomized clinical trials (RCTs) that utilize either ALA or MAL PDT and compare it with other treatment modalities. The main outcomes related to the effectiveness, adverse events, cosmetic outcomes and pain sensation, along with data from long-term follow-ups will be presented and discussed.
Methods:
Thorough literature searches were conducted through the electronic databases ClinicalTrials. gov and Pubmed/MEDLINE from inception up to 28 March 2023. Only studies in English were included. All relevant data were extracted accordingly from the eligible studies.
Results:
Eight RCTs included superficial BCC (sBCC) alone, 7 included nodular BCC (nBCC), 2 included both sBCC and nBCC and 1 included BCC of unspecified subtype. Follow-up duration ranged from 3 months to 5 years. Both ALA-PDT and MAL-PDT demonstrated acceptable efficacy, adverse events, cosmetic outcomes and pain sensation while no major differences were observed between them. PDT was less effective than surgery but with better reported cosmetic outcomes.
Conclusions:
PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC.
... Primary nodular Bcc can also respond to MAL-PDT with a clinical clearance of 91% at 3 months and a sus-tained lesion clearance response rate of 76% after 5 years of follow-up [57,58]. Poorer histological response rates with MAL-PDT for nodular Bcc of 73% was reported in one study and 33% in another [59,60]. ...
... MAL-PDT is equivalent to surgery for superficial Bcc but inferior to excision for nodular Bcc in pivotal studies each with 5 year follow-up, but cosmetic outcome is superior following PDT compared with surgery [57,58]. MAL-PDT is equivalent in efficacy to cryotherapy with overall clearance after 5 years identical at 76% but with superior cosmesis following PDT [55]. ...
Topical photodynamic therapy has become an established therapy option for superficial non-melanoma skin cancers with a substantial evidence base. In this update the increased choice in photosensitizers and light sources are reviewed as well as novel protocols to move beyond lesional treatment and address field therapy. Daylight PDT is emerging as an alternative to conventional office/hospital-based PDT that offers the advantage of much reduced pain. Although most studies have assessed efficacy of PDT in immune-competent patients, there is accumulating evidence for topical PDT being considered an option to assist in reducing the skin cancer burden in organ transplant recipients. The fluorescence associated with photosensitizer application can help delineate lesions prior to full treatment illumination and offers a useful adjunct to treatment in patients where diagnostic uncertainty or poor lesion outline complicates clinical care. PDT may also offer significant benefit in delaying/preventing new cancer development and combined with its recognized photo-rejuvenating effects, is emerging as an effective therapy capable of clearing certain superficial skin cancers, potentially preventing new lesions as well as facilitating photo-rejuvenating effects in treated areas.
... Mit primärem Debulking wurden beim nBCC initiale Abheilungsraten (3 Monate nach MAL-PDT) von 91 % erzielt. Beim Follow-up nach 5 Jahren betrug die Abheilungsrate nach PDT immer noch 76 % [61,62]. ...
Zusammenfassung
Die photodynamische Therapie (PDT) ist eine minimal-invasive Behandlungsoption, welche auf der dynamischen Wechselwirkung von drei Komponenten basiert, einem Photosensibilisator, Lichtenergie und molekularem Sauerstoff. Das Zusammenspiel dieser Komponenten führt einerseits zur Schädigung bzw. Zerstörung des Zielgewebes, andererseits auch zur Aktivierung von immunmodulierenden Prozessen. Die topische PDT wird sowohl als läsionsgerichtete als auch als feldgerichtete Therapie eingesetzt. In der Dermatologie kommt die topische PDT in der Behandlung aktinischer Keratosen, dem Morbus Bowen und dem Basalzellkarzinom, aber auch off-label bei einer Reihe weiterer Indikationen wie Viruswarzen, Lichtalterung, Akne und Leishmaniose zum Einsatz. Als topische Photosensibilisatoren werden Vorläufer des Häm-Biosynthesewegs, insbesondere 5‑Aminolävulinsäure (5-ALA) oder deren Ester, Methylaminolevulinat (MAL), verwendet. Studien der letzten Jahre deuten darauf hin, dass in der Behandlung oberflächlicher nichtmelanozytärer Hauttumoren der Einsatz von Tageslicht als Lichtquelle (Daylight-PDT) zu vergleichbaren Ergebnissen führt wie die konventionelle PDT unter Anwendung künstlicher Lichtquellen. Im Allgemeinen wird die PDT sehr gut vertragen, die meisten Nebenwirkungen sind vorübergehender Natur und geringfügig, wobei Schmerz während der Behandlung am häufigsten auftritt. Die seit Einführung der topischen PDT anfangs der 1990er Jahre kontinuierlich zunehmende Zahl präklinischer und klinischer Studien haben die PDT mittlerweile als festen Bestanteil der therapeutischen Möglichkeiten in der Dermatologie verankert.
... Thermotherapy comprises two categories, that is, hyperthermia and thermal ablation, depending on the range of temperatures in the treatments. Hyperthermia encompasses a temperature range between 41 and 45°C, while thermal ablation encompasses temperatures above 46°C [37][38][39]. Thermotherapy supplies heat through different energy sources, for example, radio frequency, microwaves, high-intensity ultrasound, light (visible, near-infrared [NIR], and ultraviolet [UV]), and magnetic fields [40], and its name depends on the energy source. ...
The problem of bacterial resistance is based on the abuse of antibiotics such as trimethoprim, fluoroquinolones, chloramphenicol, and some carbapenems. For this reason, conventional treatments to treat diseases caused by bacteria have become ineffective. Therefore, developing new therapies with multifunctional materials to combat bacteria is mandatory. In this context, photodynamic treatment (PDT) and photothermal treatment (PTT) have been proposed to combat bacteria. These light-stimulated treatments are minimally invasive and have a low incidence of side effects. In addition, they are simple, fast, and profitable. The antibacterial effect of PDT, PTT, or synchronic PDT/PTT arises from the generation of reactive oxygen species (ROS) and heat caused by a photoactivated specific photosensitizer (PS) and photothermal agents (PTAs), respectively. The effectiveness of photoinduced treatment depends, among other parameters, on the nature and concentration of the PS/PTAs, light dose, and irradiation wavelength. PS/PTAs based on carbon-based materials (CBMs), such as graphene oxide, reduced graphene oxide, carbon dots, and carbon nanotubes as antibacterial agents, will be discussed in this chapter. These CBMs have emerged as excellent antibacterial alternatives due to their excellent physicochemical properties, biocompatibility, low toxicity in the dark, specificity, and excellent response to light. Moreover, several composites and hybrids employing polymers, metal oxides, and metals have been tested to enhance the antibacterial activity of the CBMs.
... Non-surgical therapy has certainly its indication in superficial and small BCC lesions, in which the course of the therapy can be well assessed by inspection. Various therapeutic forms, including topical chemotherapy [22], cryotherapy [11,22,23], photodynamic therapy [24] and even radiotherapy [12,[25][26][27][28] showed recurrence rates of approximately 10%, which are significantly higher than the presented SST excision results and hence associated with high costs resulting from repeated treatment and follow-up outpatient appointments, with subsequent reduction of patient comfort. The frequently evoked cosmetic superiority of results in non-surgical therapy should be set against much larger and more stigmatising surgical procedures if lesions recur. ...
... There are reports of pediatric Gorlin patients who benefited from PDT for the treatment of radiotherapy-induced BCCs (Walter et al., 1997;Oseroff et al., 2005). In adult patients, MAL-PDT or nanoemulsion ALA-PDT are considered for non-aggressive, lowrisk BCC, that is, small superficial and nodular types not exceeding 2 mm tumor thickness, where surgery is impractical or contraindicated, or avoidance of scarring is a priority (Rhodes et al., 2004;Peris et al., 2019). Ultrasound may be useful to assess BCC thickness prior to treatment and assign Gorlin patients to a PDT treatment, as demonstrated by Loncaster et al. (2009). ...
Photodynamic therapy (PDT) is a photochemotherapy based on local application of a photosensitive compound and subsequent exposure to a light source of adequate wavelength. It is a non-invasive therapeutic procedure widely used in oncodermatology for treatment of numerous skin cancers, but in the last years its use has been gradually extended to an increasing list of skin diseases of both infectious and inflammatory nature. Although PDT is proven as a safe and effective therapeutic option in adults, its use is not well standardized in the pediatric population. In this review, we will focus on clinical applications, mechanisms of action, protocols, and adverse events in children and adolescents. Most of pediatric experiences concerned treatment of skin cancers in Gorlin syndrome and xeroderma pigmentosum, acne vulgaris, and viral warts, but other applications emerged, such as cutaneous lymphoma and pseudo-lymphomas, necrobiosis lipoidica, hidradenitis suppurativa, dissecting cellulitis, leishmaniasis, angiofibromas, verrucous epidermal nevus, and linear porokeratosis. In these pediatric diseases, PDT appeared as an effective therapeutic alternative. The results on vitiligo were limited and not fully encouraging. Although highly versatile, PDT is not a therapy for all skin diseases, and a deeper knowledge of its mechanisms of action is required to better define its spectrum of action and safety in pediatric patients.
... Clinical trials (68) demonstrated the efficacy of MAL PDT (red light is preferred as the excitation light) in the treatment of severe acne, nonhyperkeratotic AK on the face and scalp, Bowen's disease, and NMSCs such as BCC that are not suitable for conventional surgery. Rhodes et al. (69) confirmed that MAL PDT is not inferior to surgery for nBCC after 3 and 24 months of follow-up. Szeimies et al. (70) reached the same conclusion after 3 months of follow-up, but the recurrence rate was significantly higher in the MAL PDT group than in the surgery group at 12 months. ...
Comprehensive cancer treatments have been widely studied. Traditional treatment methods (e.g., radiotherapy, chemotherapy), despite ablating tumors, inevitably damage normal cells and cause serious complications. Photodynamic therapy (PDT), with its low rate of trauma, accurate targeting, synergism, repeatability, has displayed great advantages in the treatment of tumors. In recent years, nanotech-based PDT has provided a new modality for cancer treatment. Direct modification of PSs by nanotechnology or the delivery of PSs by nanocarriers can improve their targeting, specificity, and PDT efficacy for tumors. In this review, we strive to provide the reader with a comprehensive overview, on various aspects of the types, characteristics, and research progress of photosensitizers and nanomaterials used in PDT. And the application progress and relative limitations of nanotech-PDT in non-melanoma skin cancer and melanoma are also summarized.
... Отмечалось большое преимущество фотодинамической терапии в оценке эстетических последствий проведенного лечения, наличия потенциальных осложнений лечения и выраженности побочных эффектов. В 87% случаев эстетический результат фотодинамической терапии оценивался как хороший и отличный против 54% после хирургического иссечения [69]. ...
The article presents the results of the studies on the effectiveness of treatment basal cell carcinoma of the skin with photodynamic therapy with 5-aminolevulinic acid and methyl aminolevulinate. The results of the comparing trials between photodynamic therapy with methyl aminolevulinate and different other treatment modalities are presented.
... Its incidence is on the rise. 1 Its morbidity is attributable to local tissue invasion and destruction. 2 Ultraviolet radiation (UVR) and genetic predisposition are considered as most important cause. BCC are most common in fifth and sixth decades of life. ...
Objective: To assess patient and observer reported scar quality after Basal cell carcinoma surgery of face using the Patient and Observer Scar Assessment Scale (POSAS).
Study Design: Quasi experimental study.
Place and Duration of Study: Dermatology Department, Tertiary Care Hospitals at Multan and Karachi and Plastic Surgery Department, Tertiary Care Hospital Multan, from Apr to Sep 2020.
Methodology: Patients with basal cell carcinoma that full filled inclusion and exclusion criteria were enrolled by consecutive sampling technique at Dermatology and Plastic Surgery Department after informed consent. Surgical excision was followed by reconstruction of defect either by direct closure or by rotation or advancement flap. Surgical scar was assessed independently at 8 weeks by POSAS. Data was analyzed with SPSS-23.
Results: A total of 27 patients were enrolled in study. There were 11 (37.9%) males and 16 (59.25%) females between ages of 45-70 years. Basal cell carcinoma was located on cheek in 15 (55.5%), nose in 9 (33.3%), temple 2 (7.4%) and forehead 1 (3.7%) cases. Direct closure was performed in 6 (22.2%), rotation flaps in 10 (40.7%), and advancement flaps in 11 (40.7%) cases. Mean score of observer opinion about surgical scar between different surgical techniques was not statistically significant (p=0.191). How-ever, mean score of patient opinion of scar between different surgical techniques was statistically significant (p=0.032).
Conclusion: POSAS is a valid tool for scar evaluation by patient and observer-reported scar qualities after Basal cell carcinoma surgery.
... In a 12-month follow-up study was found to have a higher rate (9%) than surgical treatment, which had no recurrence [15]. In a 5-year follow-up study this recurrence increased by 14% with PDT and by 4% for surgery [16]. ...
Background
Photodynamic therapy (PDT) has been reported as an excellent option for the treatment of small nodular basal cell carcinomas(nBCC). The standard protocol consists of two sessions, one week apart. Sometimes, returning to the hospital after one week can be impractical for elderly patients, due to comorbidities and mobility issues. Therefore, a new technique performed in one day could be affordable for those patients.
Objective
Evaluate the effectiveness of a PDT Single-visit protocol comparing to the standard protocol, as well as the pain and the long-term recurrence-free follow-up for nBCC.
Methods
A total of 120 nBCC were treated through a Standard PDT protocol(two sessions, one week apart), and 120 nBCC were treated through a Single-visit PDT(two sessions in one day). A 30-day-after biopsy was performed in order to evaluate the results after the treatment. The lesions that had successful treatment were clinically and dermoscopically evaluated every 6 months up to 60 months. The pain score was compared between the groups(assessed every 3 minutes during PDT)
Results
A complete response at 30-days-after biopsy was observed in 85% of Standard PDT and in 93.3% of Single-visit PDT. Regarding the pain during the illumination, less pain was observed during the second session of the Single-visit PDT. The recurrence-free follow up showed, after 60 months, an 69.0% cumulative probability of recurrence-free for Standard PDT and 80.6% for Single-visit PDT.
Conclusions
The suggested Single-visit PDT protocol resulted in better outcomes at 30-day-after biopsy and in lower recurrence rates than the Standard PDT protocol. A more comfortable and more efficient treatment was offered for the patients, with lower pain.
... urticaria in the treated area, hyper-and hypopigmentation, and rarely, scarring and contact sensitization). 88 Some studies indicate a possible role for PDT in treating nodular BCC, although 5-year follow-up studies indicate efficacy rates of no more than 76% at best: 89 2-year cure rate of 94% for standard surgical excision and 74% for PDT; 90 5-year cure rates of 96% and 76%, respectively; 89 12-month cure rates of 79% and 62%, respectively; 68 3-year cure rates of 97 7% and 69 7%, respectively; 91 and 5-year cure rates of 98% and 72% for PDT, respectively. 92 Guidelines regarding use of PDT in BCC can be found in the BAD and British Photodermatology Group updated guidelines for topical PDT. ...
The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of basal cell carcinoma (BCC). The document aims to:
• offer an appraisal of all relevant literature up to 24th January 2020 focusing on any key developments
• address important, practical clinical questions relating to the primary guideline objective
• provide guideline recommendations and if appropriate research recommendations.
... Die Effektivität von MAL-PDT bei Niedrig-Risiko-BZK wurde in einer Vielzahl von Studien untersucht, mit Abheilungsraten von 82 %-97 % für das superfizielle und 33 %-91 % für das noduläre BZK [71][72][73][74][75][76]. Langzeitstudien berichten nach fünf Jahren eine Rezidivrate von 22 % für das superfizielle BZK und eine geschätzte fortbestehende Abheilungsrate von 76 % für das noduläre BZK [75,76]. ...
Zusammenfassung
Das Basalzellkarzinom (BZK) ist der häufigste maligne Tumor bei hellhäutigen Menschen und macht circa 75 % aller Hautkrebsfälle aus. Seit Jahrzehnten werden weltweit steigende Inzidenzraten berichtet. Hauptrisikofaktoren sind UV-Strahlung, männliches Geschlecht, heller Hauttyp, fortgeschrittenes Alter, langandauernde Immunsuppression, eine positive Familien-/Eigenanamnese sowie bestimmte Genodermatosen. Das BZK metastasiert selten und die Mortalität ist gering, allerdings kann es zu einer erheblichen Morbidität führen. In der Pathogenese sind genetische Mutationen, welche insbesondere den Hedgehog-Signalweg betreffen, bedeutsam. In der Diagnostik werden neben der Inspektion mit dem freien Auge und der Dermatoskopie zunehmend auch nichtinvasive Verfahren (optische Kohärenztomographie, konfokale Laserscanmikroskopie) eingesetzt, wobei auf die histologische Diagnosesicherung nur in Ausnahmefällen verzichtet werden kann. Klinisch und histologisch werden zahlreiche Unterformen unterschieden. Die Unterscheidung zwischen BZK mit hohem und niedrigem Rezidivrisiko beeinflusst die Therapieplanung maßgeblich. Die allermeisten BZK können effektiv und sicher mit chirurgischen Standardverfahren beziehungsweise in ausgewählten Fällen mit topischen Therapien behandelt werden. Lokal fortgeschrittene und metastasierte BZK werden einer Radiatio oder Systemtherapie zugeführt. Die Strahlentherapie ist zudem eine Option für ältere Patienten, wenn Kontraindikationen gegen eine Operation bestehen. In der Systemtherapie sind in Europa aktuell die Hedgehog-Inhibitoren Vismodegib und Sonidegib zugelassen. Eine Zulassung für den PD1-Inhibitor Cemiplimab in der Zweitlinientherapie ist zu erwarten.
... The efficacy of MAL-PDT in low-risk BCC has been evaluated in a large number of studies, with healing rates of 82-97 % for superficial BCC and 33-91 % for nodular BCC [71][72][73][74][75][76]. Long-term studies found a recurrence rate of 22 % after five years for superficial BCC and an estimated continued response of 76 % for nodular BCC [75,76]. ...
Basal cell carcinoma (BCC) is the most common malignant tumor in light‐skinned people and amounts to about 75 % of all cases of skin cancer. Increasing incidence rates have been reported for decades all over the world. The main risk factors include UV radiation, male sex, light skin type, advanced age, long‐term immunosuppression, a positive individual or family history, and certain genodermatoses. BCC metastasizes only rarely, and its mortality is low, but it is associated with significant morbidity. Genetic mutations especially in the hedgehog pathway play an important role in BCC pathogenesis. Non‐invasive procedures such as optical coherence tomography or confocal laser scan microscopy are increasingly utilized for diagnostics in addition to visual inspection and dermatoscopy, but only in exceptional cases can histological confirmation of the diagnosis be dispensed with. Various clinical and histological subtypes have been defined. Differentiating between BCC with high and low risk of recurrence has a significant influence on the choice of treatment. Most BCC can be treated effectively and safely with standard surgery, or in selected cases with topical treatment. Locally advanced and metastasized BCC must be treated with radiation or systemic therapy. Radiation is also an option for older patients with contraindications for surgery. The hedgehog inhibitors vismodegib and sonidegib are currently approved for systemic therapy of BCC in Europe. Approval for the PD1 inhibitor cemiplimab as second‐line therapy is expected in the near future.
... PDT with MAL is a cosmetically attractive alternative to conventional destructive treatments, including cryotherapy or surgical removal of skin cancers, such as precancerous actinic keratoses [4]. However, clinical use of PDT with MAL has been limited due to adverse side effects, the frequent recurrence of thick skin lesions, and a relapse rate of between 14 and 33% [5][6][7][8][9][10][11]. The treatment time is crucial in the clinic, and MAL needs to be converted to protoporphyrin IX (PpIX) in the cell before it is active. ...
The high incidence of sunlight-induced human skin cancers reveals a need for more effective photosensitizing agents. In this study, we compared the efficacy of prophylactic photodynamic therapy (PDT) when methylene blue (MB), riboflavin (RF), or methyl aminolevulinate (MAL) were used as photosensitizers. All mice in four groups of female C3.Cg/TifBomTac hairless immunocompetent mice (N = 100) were irradiated with three standard erythema doses of solar-simulated ultraviolet radiation (UVR) thrice weekly. Three groups received 2 × 2 prophylactic PDT treatments (days 45 + 52 and 90 + 97). The PDT treatments consisted of topical administration of 16% MAL, 20% MB, or 20% RF, and subsequent illumination that matched the photosensitizers’ absorption spectra. Control mice received no PDT. We recorded when the first, second, and third skin tumors developed. The pattern of tumor development after MB-PDT or RF-PDT was similar to that observed in irradiated control mice (p > 0.05). However, the median times until the first, second, and third skin tumors developed in mice given MAL-PDT were significantly delayed, compared with control mice (256, 265, and 272 vs. 215, 222, and 230 days, respectively; p < 0.001). Only MAL-PDT was an effective prophylactic treatment against UVR-induced skin tumors in hairless mice.
... Randomized trials and meta-analyses have established the efficacy of surgery compared to non-surgical treatment modalities for NMSCs. [1][2][3][4][5] Electrodesiccation and curettage (ED&C) is a cost-effective first-line treatment for selected small, nonaggressive NMSCs. [6][7][8] While few trials report post-ED&C recurrence rates, one prospective study documented 5-year recurrence rates of approximately 5%, compared to 3.5% after excision, and 2.1% after MMS. 9 A major drawback includes lack of histologic margin confirmation. ...
Cutaneous surgery has become critical to comprehensive dermatologic care, and dermatologists must therefore be equipped to manage the risks associated with surgical procedures. As complications may occur at any point along the continuum of care, assessing, managing and preventing risk from beginning to end becomes essential. This review focuses on preventing surgical complications pre- and post-operatively as well as during the surgical procedure.
Photodynamic therapy (PDT) is a promising treatment that uses light to excite photosensitizers in target tissue, producing reactive oxygen species for localized cell death. It is recognized as a minimally invasive, clinically approved cancer therapy with additional preclinical applications in arthritis, atherosclerosis, and infection control. A hallmark of ideal PDT is delivering disease‐specific cytotoxicity while sparing healthy tissue. However, conventional photosensitizers often suffer from non‐specific photoactivation, causing off‐target toxicity. Activatable photosensitizers have emerged as more precise alternatives, offering controlled activation. Unlike traditional photosensitizers, they remain inert and photoinactive during circulation and off‐target accumulation, minimizing collateral damage. These photosensitizers are designed to “turn on” in response to disease‐specific biostimuli, enhancing therapeutic selectivity and reducing off‐target effects. This review explores the principles of activatable photosensitizers, including quenching mechanisms stemming from activatable fluorescent probe and applied to activatable photosensitizers (RET, PeT, ICT, ACQ, AIE), as well as pathological biostimuli (pH, enzymes, redox conditions, cellular internalization), and bioresponsive constructs enabling quenching and activation. We also provide a critical assessment of unresolved challenges in aPS development, including limitations in targeting precision, selectivity under real‐world conditions, and persistent issues and potential solutions (dual‐lock, targeting moieties, biorthogonal chemistry and artificial receptors).
Photodynamic therapy (PDT) is a promising treatment that uses light to excite photosensitizers in target tissue, producing reactive oxygen species and localized cell death. It is recognized as a minimally invasive, clinically approved cancer therapy with additional preclinical applications in arthritis, atherosclerosis, and infection control. A hallmark of ideal PDT is delivering disease‐specific cytotoxicity while sparing healthy tissue. However, conventional photosensitizers often suffer from non‐specific photoactivation, causing off‐target toxicity. Activatable photosensitizers (aPS) have emerged as more precise alternatives, offering controlled activation. Unlike traditional photosensitizers, they remain inert and photoinactive during circulation and off‐target accumulation, minimizing collateral damage. These photosensitizers are designed to “turn on” in response to disease‐specific biostimuli, enhancing therapeutic selectivity and reducing off‐target effects. This review explores the principles of aPS, including quenching mechanisms stemming from activatable fluorescent probes and applied to activatable photosensitizers (RET, PeT, ICT, ACQ, AIE), as well as pathological biostimuli (pH, enzymes, redox conditions, cellular internalization), and bioresponsive constructs enabling quenching and activation. We also provide a critical assessment of unresolved challenges in aPS development, including limitations in targeting precision, selectivity under real‐world conditions, and potential solutions to persistent issues (dual‐lock, targeting moieties, biorthogonal chemistry and artificial receptors). Additionally, it provides an in‐depth discussion of essential research design considerations needed to develop translationally relevant aPS with improved therapeutic outcomes and specificity.
Basal cell carcinoma (BCC) is the most common cutaneous malignancy in the periocular area. While the mortality from BCC is low, it is capable of extensive tissue destruction and the morbidity may be considerable. The main risk factor is ultraviolet irradiation. The most important diagnostic evaluation is histopathologic examination of the excised tissue. The main treatment modality for BCC is surgical excision of the lesion with microscopic monitoring of its margins or Mohs’ microsurgery. Long-term clinical follow-up after treatment is necessary.
Skin cancer is a prevalent and sometimes lethal cancer that affects a wide range of people. UV radiation exposure is the main cause of skin cancer. Immunosuppression, environmental factors, and genetic predisposition are other contributing variables. Fair-skinned people and those with a history of sunburns or severe sun exposure are more likely to experience this condition. Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are the three main forms. Melanoma poses a bigger hazard because of its tendency for metastasis, while SCC and BCC have limited metastatic potential. Genetic mutations and changes to signalling pathways such as p53 and MAPK are involved in pathogenesis. Early diagnosis is essential, and molecular testing, biopsy, dermoscopy, and visual inspection can all help. In addition to natural medicines like curcumin and green tea polyphenols, treatment options include immunotherapy, targeted therapy, radiation, surgery, and chemotherapy. Reducing the incidence of skin cancer requires preventive actions, including sun protection and early detection programs. An overview of skin cancers, including their forms, pathophysiology, diagnosis, and treatment, highlighting herbal therapy, is given in this review.
Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell apoptosis. Although photosensitizers have shown efficacy in clinical practice, they are associated with certain disadvantages, such as a certain degree of toxicity and limited availability. Recent studies have shown that natural product photosensitizers offer promising options due to their low toxicity and potential therapeutic effects. In this review, we provide a summary and evaluation of the current clinical photosensitizers that are commonly used and delve into the anticancer potential of natural product photosensitizers like psoralens, quinonoids, chlorophyll derivatives, curcumin, chrysophanol, doxorubicin, tetracyclines, Leguminosae extracts, and Lonicera japonica extract. The emphasis is on their phototoxicity, pharmacological benefits, and effectiveness against different types of diseases. Novel and more effective natural product photosensitizers for future clinical application are yet to be explored in further research. In conclusion, natural product photosensitizers have potential in photodynamic therapy and represent a promising area of research for cancer treatment.
Topical photodynamic therapy (PDT) is widely used as an effective and well‐tolerated treatment for field change actinic keratosis, Bowen disease and superficial basal cell carcinoma. There is a strong evidence base to support its use and guidelines, which summarise the evidence and clinical utility of this therapy. There are also standards available for guidance with respect to establishing PDT services in dermatology and emphasis is placed on the availability of PDT for practitioners affiliated with a skin cancer multi‐disciplinary team. Developments in photosensitisers and light delivery, such as through the increasing application of daylight PDT, have greatly improved the tolerance, acceptability and uptake of PDT, such that this should be widely available through dermatology services. Further refinements in photosensitiser and light delivery will be expected to continue to improve PDT outcomes and the uptake of this invaluable therapeutic approach.
Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen’s disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients.
Basal cell carcinoma (BCC) is the most common skin cancer, for which there are multiple treatment options, including the gold standard Mohs micrographic surgery (MMS), surgical excision, electrodesiccation and curettage, radiation therapy, cryosurgery, and photodynamic therapy (PDT). While PDT is currently approved for treating actinic keratosis, it has been used off-label to treat BCC patients who may not tolerate surgery or other treatment modalities. We present a review of the efficacy of these modalities and describe important considerations that affect the usage of PDT and MMS. ALA-PDT and MAL-PDT are both efficacious treatment options for lower-risk BCC that can serve as non-invasive alternatives to surgical excision with favorable cosmetic outcomes in patients unsuitable to undergo surgery. In particular, PDT may be considered an adjuvant for the prevention and treatment of BCC lesions in patients with some genetic syndromes such as Gorlin syndrome, and in combination with surgical excision in lesions presenting in certain locations. Limitations to PDT include lack of margin control to prevent recurrence, pain, and cost of certain photosensitizers. Future studies should investigate the role of PDT as adjunctive therapy, standardization of protocols, and causes and ways to address recurrence following PDT treatment.
Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.
Graphical Abstract
Photodynamic therapy (PDT) is a form of phototherapy involving a photosensitizer, a light source, and tissue oxygen. Aminolevulinic acid (ALA) and its ester derivative methyl aminolevulinate (MAL) are commonly used photosensitizers acting as prodrugs for protoporphyrin IX (PpIX). PpIX accumulates in abnormal epidermis and upon subsequent exposure to and activation by the appropriate light source generates reactive oxygen species that selectively destroy diseased lesions. PDT has been established to be a safe and effective treatment for superficial skin cancers and premalignant skin lesions. Pain is the most severe adverse effect but can be effectively managed. Porphyria is an important contraindication. Common approved PDT protocols include Levulan 20% solution ALA-PDT activated with blue light and BF200-Ameluz 10% nanoemulsion ALA-PDT activated with red light for treatment of AK in the United States and superficial basal cell carcinoma and low-risk nodular basal cell carcinoma in Europe, and Metvix/Metvixia MAL-PDT for treatment of AK, Bowen’s disease, and basal cell carcinoma in Europe. Off-label, ALA-/MAL-PDT have been reported to treat invasive squamous cell carcinoma, cutaneous T-cell lymphoma, Kaposi’s sarcoma, Paget’s disease, and various benign inflammatory disorders and to prevent recurrence of squamous cell carcinoma in organ transplant recipients. Combination therapy of PDT with other treatment modalities such as cryotherapy, surgery, and field therapies is being explored with preliminary data suggesting improved efficacy, tolerability, and long-term results. In addition, PDT offers enhanced cosmetic outcome compared to cryotherapy or surgery. PDT can also be used for skin photorejuvenation.
Targeted superficial radiation therapy (SRT) may be used on most skin cancers and certain benign conditions such as keloids. Key to treatment effectiveness is image guidance with ultrasound for depth. SRT is useful in therapy of difficult surgical sites such as the pretibial region, ear, and nose. This chapter is organized with background information on non-melanoma skin cancer (NMSC) and keloids. Followed by a discussion of the various modalities used in the nonsurgical (and surgical) management of NMSC and keloids with an expanded section on the use of image-guided superficial radiotherapy (IGSRT).
Topical photodynamic therapy is widely used for the treatment of superficial non‐melanoma skin cancer and dysplasia and has been shown to be at least as effective as non‐surgical standard comparators such as topical fluorouracil and cryotherapy. British and European guidelines are available for its use, and treatment is undertaken on an out‐patient basis and is generally well tolerated, with the exception of pain during irradiation in a significant proportion of patients. Optimization of treatment regimens to improve efficacy and reduce side effects have included refinements in pro‐drug development and delivery and in the methods of light delivery, in particular using reduced irradiance regimens. The use of topical photodynamic therapy (PDT) has also been applied to a wide range of other diverse skin diseases including acne vulgaris and recalcitrant viral warts and it may have a role in some of these conditions, although further studies are required. It is important that topical PDT services are widely available in dermatology, particularly to those involved in skin cancer management, through the multidisciplinary team, and that standards and clinical governance for PDT are established.
Photodynamic therapy (PDT) is an attractive, non-invasive therapeutic procedure successfully used in oncodermatology for the treatment of numerous skin cancers. Photosensitizers commonly used in PDT by dermatologists are the prodrug 5-aminolaevulinic acid (ALA) or its methylated ester (MAL), which are converted to protoporphyrin IX (PpIX) inside the target cells. The activation of photosensitizer by an artificial light source (conventional PDT) or by sunlight (daylight PDT) leads to the production of reactive oxygen species (ROS), with destruction of target cells and induction of immune modulating response. In oncodermatology, PDT has well-established indications, such as actinic keratosis, Bowen’s disease (SCC in situ), and superficial and thin nodular basal cell carcinomas. Recently, treatment of cancerization field and cutaneous T-cell lymphoma with PDT has shown encouraging results. In this chapter, we will provide an overview of the mechanisms of action of PDT and its anti-cancer properties. Then we will analyze both approved and emerging indications of PDT in oncodermatology, with a look on differences between conventional PDT and daylight PDT and the advantages of combination therapies.Keywords5-aminolaevulinic acid (ALA)Actinic keratosisBasal cell carcinomaBowen’s diseaseMethylaminolevulinate (MAL)Photodynamic therapy (PDT)Reactive oxygen species (ROS)Squamous cell carcinoma
Basal cell carcinoma (BCC) is the most common cutaneous malignancy in the periocular area. While the mortality from BCC is low, it is capable of extensive tissue destruction, and the morbidity may be considerable. The main risk factor is ultraviolet irradiation. The most important diagnostic evaluation is histopathologic examination of the excised tissue. The main treatment modality for BCC is surgical excision of the lesion with microscopic monitoring of its margins or Mohs’ microsurgery. Long-term clinical follow-up after treatment is necessary.
Background
Photodynamic therapy (PDT) is increasingly used for the treatment of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, it is unknown whether photodynamic therapy is more effective than other commonly used treatment modalities for these cancers.
Purpose
The aim of this study was to determine the relative efficacy and safety of PDT compared with placebo or other interventions for the treatment of skin carcinomas.
Methods
Searches were performed in PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials comparing the PDT with other interventions in adults skin BCC or SCC that reported on lesion response, recurrence, cosmetic appearance, or safety outcomes.
Results
Seventeen unique randomized controlled trials, representing 22 study arms from 21 publications were included. The included trials included 2,166 participants, comparing methyl aminolevulinic (MAL) PDT (six studies) or aminolevulinic acid (ALA) PDT (two studies). Comparators included placebo, surgery, hexaminolevulinic (HAL) PDT, erbium: yttrium-aluminum-garnet ablative factional laser (YAG-AFL) PDT, fluorouracil, and imiquimod. There were few studies available for each comparison. Mantel-Haenszel fixed effects risk ratios were calculated for response, recurrence, cosmetic outcomes, and adverse events. MAL-PDT had similar response rates to surgery, ALA-PDT, fluorouracil and imiquimod at 3- and 12 months post-intervention. The rate of recurrence was similar, showing few differences at 12 months, but at later time points (24–60 months), fewer lesions recurred with surgery and imiquimod than with PDT. PDT also caused more adverse events and pain than other interventions. However, PDT treatment was more likely to receive a “good” or “excellent” rating for cosmetic appearance than surgery or cryotherapy.
Conclusion
This systematic review and meta-analysis demonstrates that the choice of treatment modality for BCC or SCC is best chosen in the context of the location and size of the lesion, the socioeconomic circumstances of the patient, as well as the patient’s preferences. We call for more high quality studies to be done, in order to enable more reliable interpretations of the data.
Systematic review registration
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=368626 , identifier CRD42022368626.
Numerous surgical and nonsurgical modalities are available to treat basal cell carcinoma (BCC), but their true effectiveness and safety is unknown. This article summarizes the evidence presented in a recent Cochrane review and aims to facilitate the interpretation of the review's findings for the Spanish and Latin American scientific communities. Much of the evidence the reviewers found came from single studies, preventing meta-analysis. Conventional surgical excision continues to be the most effective treatment for low-risk BCC. Most studies had small sample sizes, and some had problems with blinding, limitations which will have affected the assessment of subjective outcomes, such as pain and cosmetic results. The authors identified a lack of standardization in relation to recurrences and cosmetic outcomes that threatens not only the internal validity of the studies but also their external validity and reproducibility.
Objective
Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves vocal wound healing and reduces scar formation in both prophylactic and remodeling procedures performed in vivo.
Study Design
In vivo.
Methods
Vocal fold stripping was performed in Sprague–Dawley rats. PDT was performed with intraperitoneal injection of 100 mg/kg 5‐Aminolevulinic Acid (5‐ALA) and 635 nm laser irradiation of 20, 40, and 60 J/cm². PDT was performed immediately after surgery to study the prophylactic effect and 4 weeks after surgery to study the remodeling effect. Gene expression was evaluated with real‐time PCR at 1 week after PDT. Histologic evaluations were performed 12 weeks after PDT, including hematoxylin–eosin, Masson, Alcian blue staining, and immunohistochemical staining of collagen I and III.
Results
PDT induced similar effects on the vocal fold wound healing outcomes in both prophylactic and remodeling procedures. Expression of MMP8, MMP13, HAS2, and TGFβ1 was significantly elevated. Histologic evaluation revealed significantly increased thickness, decreased density of collagen, and increased deposition of hyaluronic acid in the lamina propria. Immunohistochemistry also revealed better distribution and reduced density of collagen I and III. The most obvious changes were seen in the 60 J/cm² PDT group.
Conclusion
PDT could significantly improve vocal wound healing by providing both prophylactic effects and remodeling effects. It may be a minimally invasive treatment for vocal fold lesions with slight vocal scarring, and may be used to treat acute or chronic vocal injury to reduce vocal scarring.
Level of Evidence
N/A Laryngoscope, 133:1943–1951, 2023
Riassunto
Pur trattandosi di un trattato di chirurgia, va ricordato che il trattamento di alcuni tumori cutanei del volto non è solo chirurgico e che la scelta terapeutica va fatta in collaborazione con un dermatologo, un chirurgo e un radioterapista e che va anche presa in considerazione la richiesta del paziente. Il trattamento dipende anche dalle possibilità terapeutiche locali. Il ricorso a una riunione di consultazione pluridisciplinare (RCP) non è sistematico ma è riservato alle forme ad alto rischio di recidiva o di estensione regionale o generale. I tumori eventualmente trattati chirurgicamente sono i tumori benigni, più frequenti, alcuni stati precancerosi e i tumori di cui esistono sei varietà principali: carcinoma basocellulare (CBC), carcinoma epidermoide, melanoma, tumore di Merkel, dermatofibrosarcoma di Darrier e Ferrand e carcinomi annessiali. L’anestesia locale è preferita per i tumori di piccole o medie dimensioni. La resezione chirurgica deve rispettare delle regole perfettamente definite per il tipo istopatologico di ciascun tumore al fine di avere dei margini sani e di limitare così il rischio di recidiva. La collaborazione dell’anatomopatologo è quindi fondamentale per studiare questi margini o in maniera estemporanea e possibilmente secondo il metodo micrografico di Mohs o in maniera differita, eseguendo un intervento chirurgico in due fasi. Le tecniche di riparazione sono numerose; esse devono tenere conto dell’età del paziente, delle dimensioni della resezione cutanea e di molti fattori, come le linee di Langer o di Kreise, l’elasticità della pelle e così via. I principi fondamentali della riparazione con degli esempi sono richiamati alla fine di questo articolo.
Photodynamic therapy (PDT), as the name suggests is a light-based, non-invasive therapeutic treatment method that has garnered immense interest in the recent past for its efficacy in treating several pathological conditions. PDT has prominent use in the treatment of several dermatological conditions, which consequently have cosmetic benefits associated with it as PDT improves the overall appearance of the affected area. PDT is commonly used for repairing sun-damaged skin, providing skin rejuvenation, curbing pre-cancerous cells, treating conditions like acne, keratosis, skin-microbial infections, and cutaneous warts, etc. PDT mediates its action by generating oxygen species that are involved in bringing about immunomodulation, suppression of microbial load, wound-healing, lightening of scarring, etc. Although there are several challenges associated with PDT, the prominent ones being pain, erythema, insufficient delivery of the photosensitizing agent, and poor clinical outcomes, still PDT stands to be a promising approach with continuous efforts towards maximizing clinical efficacy while being cautious of the side effects and working towards lessening them. This article discusses the major skin-related conditions which can be treated or managed by employing PDT as a better or comparable alternative to conventional treatment approaches such that it also brings about aesthetic improvements thereof.
Resumen
Existen numerosas modalidades de tratamiento para el manejo de los carcinomas basocelulares (CBC), pero se desconoce la real eficacia y seguridad entre las alternativas quirúrgicas y no quirúrgicas disponibles. Este artículo resume la evidencia encontrada en la reciente revisión Cochrane de Thomson et al. y facilita la interpretación de sus resultados entre la comunidad científica iberolatinoamericana. La gran mayoría de la evidencia evaluada proviene de estudios individuales que impidieron la realización de una revisión sistemática cuantitativa. La escisión quirúrgica convencional continúa siendo la terapia más eficaz para el tratamiento de los CBC de bajo riesgo. La mayoría de estudios incluyeron tamaños de muestra pequeños y algunos tuvieron problemas con el cegamiento, lo que influiría en resultados subjetivos tales como el dolor o la cosmesis. Existe una falta de estandarización en relación con los desenlaces de recurrencia y de resultados cosméticos, lo que en conjunto afecta no solo la validez interna sino también la validez externa y la reproducibilidad de los estudios.
For years, photodynamic therapy (PDT) has been an established procedure in dermatological practice, which is increasingly used due to the constantly increasing number of epithelial skin tumors and their precursors (actinic keratoses). The treatment of actinic keratoses (AK) remains a major indication for PDT. In addition, however, other skin tumors such as Bowen’s disease or superficial or nodular basal cell carcinomas are increasingly being treated with PDT. PDT is occasionally used for the treatment of inflammatory dermatoses and has long since made its way into esthetic dermatology. Here, it is primarily used for skin rejuvenation processes. As a rule, the classic PDT with red light is used, whereby newer variants, such as daylight or artificial daylight PDT, also deliver promising results. All these aspects are examined in more detail in this chapter.
The review highlights the current understanding of the epidemiology, etiology, pathogenesis, existing classifications of mycosis fungoides. Methods for diagnosis and treatment of the pathology are described, among which photodynamic therapy (PDT) plays an important role. The main advantages of PDT for mycosis fungoides include the absence of systemic toxicity, non-invasiveness, selectivity, absence of carcinogenic potential, the possibility of repeated courses of treatment, and good cosmetic results. This review collects and analyzes the results of clinical trials of PDT in patients with mycosis fungoides. The analysis showed high efficiency of PDT in patients with mycosis fungoides with isolated or limited spots and plaques. PDT can be considered as the therapy of choice in patients with facial lesions when a good cosmetic result is one of the main requirements, and radiation therapy, nitrogen mustard or carmustine can leave permanent and visible scars. Plaques located in the axillary or inguinal skin folds that are inaccessible to phototherapy can also be treated with PDT.
Resumen
Aunque éste es un tratado de cirugía, se debe recordar que el tratamiento de determinados tumores cutáneos de la cara no es únicamente quirúrgico, y la elección terapéutica se debe tomar en conjunto con un dermatólogo, un cirujano y un radioterapeuta, y, además, debe tener en cuenta las preferencias del paciente. También depende de las posibilidades terapéuticas locales. El recurso a un comité multidisciplinar (CM) no es sistemático, sino que se reserva para las formas con alto riesgo de recidiva o de extensión regional o general. Los tumores que pueden tratarse mediante cirugía son los tumores benignos, que son los más frecuentes, algunos estados preneoplásicos y los cánceres, de los que existen seis variedades principales: carcinoma basocelular (CBC), carcinoma epidermoide, melanoma, tumor de Merkel, dermatofibrosarcoma de Darier y Ferrand, y carcinoma anexial. La anestesia local es preferible para los tumores pequeños o medianos. La resección quirúrgica debe respetar reglas perfectamente definidas para el tipo histopatológico de cada tumor con el fin de disponer de márgenes sanos y limitar así el riesgo de recidiva. Por lo tanto, la colaboración del anatomopatólogo es indispensable para estudiar estos márgenes, ya sea de forma extemporánea y, si es posible, según el método micrográfico de Mohs, o de forma diferida, mediante una cirugía en dos tiempos. Las técnicas de reparación son numerosas y deben tenerse en cuenta la edad del paciente, el tamaño de la resección cutánea y muchos factores, como las líneas de Langer o de Kreise, la elasticidad de la piel, etc. Los principios fundamentales de la reparación, con ejemplos, figuran al final de este artículo.
The review highlights the current understanding of the epidemiology, etiology, pathogenesis, existing classifications of mycosis fungoides. Methods for diagnosis and treatment of the pathology are described, among which photodynamic therapy (PDT) plays an important role. The main advantages of PDT for mycosis fungoides include the absence of systemic toxicity, non-invasiveness, selectivity, absence of carcinogenic potential, the possibility of repeated courses of treatment, and good cosmetic results. This review collects and analyzes the results of clinical trials of PDT in patients with mycosis fungoides. The analysis showed high efficiency of PDT in patients with mycosis fungoides with isolated or limited spots and plaques. PDT can be considered as the therapy of choice in patients with facial lesions when a good cosmetic result is one of the main requirements, and radiation therapy, nitrogen mustard or carmustine can leave permanent and visible scars. Plaques located in the axillary or inguinal skin folds that are inaccessible to phototherapy can also be treated with PDT.
Multidisciplinary work is necessary for the development and improvement of techniques for the diagnosis and treatment of diseases, with physics playing a prominent role. For example, in-depth knowledge of the interaction of electromagnetic (ionizing and non-ionizing) and mechanical (sound and ultrasound) waves with biological tissues is important for the development of protocols for the management of skin cancer. In this paper, we review the developments carried out at the São Carlos Institute of Physics that resulted in new technologies and protocols for the diagnosis and treatment of non-melanoma skin lesions. Photodynamic therapy (PDT), a technique that combines light and a photosensitive molecule, was improved, and more than 2000 patients were directly treated in our clinical trials. Our research group pioneered the technique in Brazil, and we developed several fundamental studies involving cell culture and animal studies that demonstrated the effectiveness of this technique in treating cancer. Based on these results, multicenter clinical studies in Brazil have been implemented for the treatment of non-melanoma skin cancer. These studies generated commercial prodrugs and irradiation devices that are currently being considered for incorporation into the Brazilian public health system. In addition, nine countries in Latin America have implemented our technique. In this paper, we also show the physical fundamentals of PDT, the new developments that will allow us to overcome current challenges such as the use of ultrasound to treat cancer. Developments in the diagnosis of cancer will also be discussed.
Introduction
The treatment of tumors is one of the most difficult problems in the medical field at present. Patients often use a comprehensive therapy that combines surgery, radiotherapy and chemotherapy. Photodynamic therapy (PDT) has prominent potential for eradicating various cancers. Chlorin-based photosensitizers (PSs), as one of the most utilized photosensitizers, have many advantages over conventional photosensitizers, however, a successful chlorin-based PDT needs multi-functional nano-carriers for selective photosensitizer delivery. The number of researches about nanoparticles designed for improved chlorin-based PSs is increasing in the current era. In this article, we give a brief review focused on the recent research progress in design of chlorin-based nanoparticles for the treatment of malignant tumors with photodynamic therapy.
Areas covered
This review focuses on the current nanoparticle platforms for PDT, and describes different strategies to achieve controllable PDT by chlorin-nano-delivery systems. The challenges and prospects of PDT in clinical applications are also discussed.
Expert opinions
The requirement for PDT to eradicate cancers has increased exponentially in recent years. The major clinically used photosensitizers are hydrophobic. The main obstacles in effective delivery of PSs are associated with this intrinsic nature. The design of nano-delivery systems to load PSs is pivotal for PSs’ widespread use.
Background
Basal cell carcinoma (BCC) is the commonest cancer affecting white‐skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs.
Objectives
To assess the effects of interventions for primary BCC in immunocompetent adults.
Methods
We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We used standard methodological procedures expected by Cochrane.
Results
We included 52 RCTs with 6990 participants (median age 65 years, range 20‐95). Mean study duration was 13 months (range 6 weeks to 10 years). Ninety‐two percent (48/52) of studies exclusively included histologically low‐risk BCC (nodular and superficial subtypes). The certainty of evidence was predominantly low or moderate for the outcomes of interest. Overall, surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for primary, facial BCC (high‐risk histological subtype or located in the 'H‐zone' or both) (low‐certainty evidence). Non‐surgical treatments, when used for low‐risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior.
Conclusions
Surgical interventions have lower recurrence rates and remain the gold‐standard for high‐risk BCC. Of the non‐surgical treatments, topical imiquimod has the best evidence to support its efficacy for low‐risk BCC. Priorities for future research include agreement on core outcome measures and studies with longer follow‐up.
Depletion of the ozone layer has been observed on a global scale, and is probably related to halocarbon emissions. Ozone depletion increases the biologically harmful solar ultraviolet radiation reaching the surface of the Earth, which leads to a variety of adverse effects, including an increase in the incidence of skin cancer. The 1985 Vienna Convention provided the framework for international restrictions on the production of ozone-depleting substances. The consequences of such restrictions have not yet been assessed in terms of effects avoided. Here we present a new method of estimating future excess skin cancer risks which is used to compare effects of a 'no restrictions' scenario with two restrictive scenarios specified under the Vienna Convention: the Montreal Protocol, and the much stricter Copenhagen Amendments. The no-restrictions and Montreal Protocol scenarios produce a runaway increase in skin cancer incidence, up to a quadrupling and doubling, respectively, by the year 2100. The Copenhagen Amendments scenario leads to an ozone minimum around the year 2000, and a peak relative increase in incidence of skin cancer of almost 10% occurring 60 years later. These results demonstrate the importance of the international measures agreed upon under the Vienna Convention.
5-Aminolaevulinic acid (ALA) is a precursor of protoporphyrin IX (Pp IX) in the biosynthetic pathway for haem. Certain types of cells have a large capacity to synthesize Pp IX when exposed to an adequate concentration of exogenous ALA. Since the conversion of Pp IX into haem is relatively slow, such cells tend to accumulate photosensitizing concentrations of Pp IX. Pp IX photosensitization can be induced in cells of the epidermis and its appendages, but not in the dermis. Moreover, since ALA in aqueous solution passes readily through abnormal keratin, but not through normal keratin, the topical application of ALA in aqueous solution to actinic keratoses or superficial basal cell or squamous cell carcinomas induces Pp IX photosensitization that is restricted primarily to the abnormal epithelium. Subsequent exposure to photoactivating light selectively destroys such lesions. In our ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated. The cosmetic results have been excellent, and patient acceptance has been very good.
These guidelines on the management of basal cell carcinoma have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
Fifty-eight patients with 119 nodular (2 mm or more in thickness) basal cell carcinomas successfully treated with photodynamic therapy were included in this 1-year follow-up study. The initial cure rate at 3 ^6 months was 92% after photodynamic therapy, which included an initial debulking procedure and topical application of dimethylsulphoxide in order to enhance penetration of 5-aminolevulinic acid (20% in cream) to which the lesions were exposed for 3 h prior to exposure to light. At examination 12 ^26 months (mean 17 months) after treatment 113 lesions (95%) were still in complete response. Six lesions (5%) had recurred, located on the face, scalp and ear. The cosmetic outcome was evaluated as excellent to good in 91%. Microscopic examination of biopsies taken from healed areas in 7 patients did not reveal any sign of damage in 5 and only minor alterations in 2.Key words: photodynamic therapy; nodular basal cell carcinoma; 5-aminolevulinic acid; curettage; dimethylsulphoxide.
Because it is not possible to monitor skin cancer accurately using routine methods, special surveys have been undertaken in Nambour, a typical subtropical community in Queensland, Australia. Estimates of inci- dence reported here are based on skin cancers medically treated between 1985 and 1992 and new cases diagnosed by dermatologist s in two examination clinics in 1986 and 1992. Among men and women aged 18-69 years in 1986, age-adjusted incidence rates of basal cell carcinoma were 2,074 and 1,579 per 100,000 per year, respectively—the highest incidence rates of a specific cancer ever reported. Squamous cell carcinoma occurred at half the rate of basal cell carcinoma among men and at about one third the rate among women. Although as expected, fair skin, a history of repeated sunburns, and nonmalignant solar skin damage diagnosed by dermatologist s were strongly associated with both types of skin cancer, outdoor occupation was not. Significant self-selection was observed among outdoor workers, whereby people with fair or medium complexions and a tendency to sunburn were systematically underrepresented among those in long-term outdoor occupations although they accounted for more than 80 percent of the community study sample. The mitigating effect of this selection bias may partly explain the paradox of the lack of quantitative evidence of a causal link between sun exposure and skin cancer in humans. Am J Epidemiol 1996;144:1034-40. bias (epidemiology); cohort studies; incidence; risk factors; skin neoplasms
Multicentre randomized controlled studies now demonstrate high efficacy of top- ical photodynamic therapy (PDT) for actinic keratoses, Bowen's disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. Long- term follow-up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evi- dence does not support the use of topical PDT for squamous cell carcinoma. PDT can reduce the number of new lesions developing in patients at high risk of skin cancer and may have a role as a preventive therapy. Case reports and small series attest to the potential of PDT in a wide range of inflammatory ⁄infective dermato- ses, although recent studies indicate insufficient evidence to support its use in psoriasis. There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required. In addition to high-quality treatment site cosmesis, several studies observe improvements in aspects of photoageing. Management of treatment-related pain ⁄discomfort is a challenge in a minority of patients, and the modality is otherwise well tolerated. Long-term studies provide reassurance over the safety of repeated use of PDT.
These guidelines on the management of basal cell carcinoma have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
Background Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA.Objectives To assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment.Methods Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2–4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g−1 was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm−2. Fibrosis was assessed histologically in 23 biopsies.Results The overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies.Conclusions We conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.
Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is based on photosensitization by endogenous synthesis of protoporphyrin IX and its transient accumulation especially in malignant epithelially derived tissues. Recent studies have indicated that ALA-PDT is effective for the treatment of solar keratoses (SK), but there has been a lack of long-term clinical follow-up. The goal of the present study was to investigate the immediate and long-term effect of ALA-PDT on SK. Twenty-eight patients with a total of 251 SK were enrolled in the study. Standard treatment involved the topical application of 20% ALA, under occlusive and light-shielding dressing for 4 hours before exposure to UVA and/or different wave bands or wave band combinations of polychromatic visible light (full-spectrum visible light, and/or different wave bands of filtered visible light >515, >530, >570, or >610 nm) in one or two treatment sessions. The primary complete response rate of SK to ALA-PDT was 64% after one treatment, but 85% when the responses to a second treatment were included. Taken all treatments together, the complete response rate for lesions on face, scalp and neck was 93% for full-spectrum visible light, 96% for the combination of full-spectrum visible light and filtered light, 91% for different wave bands of filtered visible light, and 100% for the combination of long wave UVA and full-spectrum visible light, respectively. The complete response rate for lesions on forearms and hands was 51% for full-spectrum visible light and 33% for the combination of full-spectrum visible light and filtered light. The greater response rate for SK on the face, scalp, and neck was associated with a higher surface fluorescence and immediate response rate after ALA photosensitization at these sites (X2: p = 0.0001). However, due to the treatment protocol the mean light dose applied to lesions on the face, scalp and neck (50 J cm−2) was substantially higher than that for lesions on forearms and hands (35 J cm−2). In the long term follow-up of SK on face scalp and neck, the projected disease-free rate at 36 months after therapy was 71% for lesions treated with full-spectrum visible light versus 23% for lesions treated with different wave bands of filtered light (Log rank - Mantel Cox; p = 0.0001). These results indicate that treatment with full-spectrum visible light at higher light doses may be the most effective and promising form of light exposure in ALA-PDT of SK.
This is the third report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 588 previously untreated (primary) BCCs removed by surgical excision. The cumulative 5-year recurrence rate was 4.8%. This is a statistically significant lower recurrence rate (P = .034) than 135 previously treated BCCs that had a re-recurrence rate of 11.6%. For the primary BCCs, multivariate analysis showed that location on the head (P = .010) and being male (P = .004) were independent risk factors for recurrence. The patient's age, the duration of the BCC, its maximum diameter, or the time span (1955-1963, 1964-1972, 1973-1982) in which it was treated did not significantly affect the recurrence rate. The 5-year recurrence rate for BCCs excised from various anatomic sites were as follows: 1) neck, trunk, and extremities = 0.7%; 2) head--less than 6 mm in diameter = 3.2%; 3) head--6 to 9 mm in diameter = 8.0% (treated since 1964 = 5.2%); and 4) head--10 mm or more in diameter = 9.0%. Surgical excision is a highly effective method for removal of BCCs, and achieved a good to excellent cosmetic outcome in about 85% of the recurrence-free treatment sites.
5-Aminolaevulinic acid (ALA) is a precursor of protoporphyrin IX (Pp IX) in the biosynthetic pathway for haem. Certain types of cells have a large capacity to synthesize Pp IX when exposed to an adequate concentration of exogenous ALA. Since the conversion of Pp IX into haem is relatively slow, such cells tend to accumulate photosensitizing concentrations of Pp IX. Pp IX photosensitization can be induced in cells of the epidermis and its appendages, but not in the dermis. Moreover, since ALA in aqueous solution passes readily through abnormal keratin, but not through normal keratin, the topical application of ALA in aqueous solution to actinic keratoses or superficial basal cell or squamous cell carcinomas induces Pp IX photosensitization that is restricted primarily to the abnormal epithelium. Subsequent exposure to photoactivating light selectively destroys such lesions. In our ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated. The cosmetic results have been excellent, and patient acceptance has been very good.
We reviewed all studies (since 1947) reporting recurrence rates for treatment of primary (previously untreated) basal cell carcinomas using surgical excision, radiotherapy, cryotherapy, curettage and electrodesiccation, and Mohs micrographic surgery. Our findings indicate that recurrences following treatment of primary basal cell carcinoma appear later than is generally acknowledged in the literature. We found that less than one-third of all recurrences appear in the first year following treatment; only 50% appear within the first 2 years following treatment; and only 66%, or nearly two-thirds, appear within the first 3 years following treatment. A good rule of thumb is that the 10-year recurrence rate is double, or 2 times, that of the 2-year recurrence rate. Furthermore, 18% of recurrences appear between the fifth and tenth year following treatment. These results held true, irrespective of treatment modality examined. Seventy-two studies reporting short-term recurrence rates (follow-up less than 5 years) had a weighted average recurrence rate of 4.2%, whereas 34 long-term studies (follow-up of 5 years) had a weighted average recurrence rate of 8.7%, or more than 2 times the short-term rate. Five-year recurrence rates by treatment modality are as follows: Mohs micrographic surgery 1.0%, surgical excision 10.1%, curettage and electrodesiccation 7.7%, radiation therapy 8.7%, and cryosurgery 7.5%. We conclude that the reporting of recurrence rate data for basal cell carcinoma should be standardized using 5-year life table analysis, and even more important is our conclusion that lifetime follow-up is necessary after treatment of primary basal cell carcinoma in order both recurrences and new primaries.
Non‐melanoma skin cancer (NMSC) comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in humans in many countries. Sunlight plays a major part in the development of these tumours which appear predominantly on areas of the most frequently exposed skin.
The site distribution for BCC and SCC is not the same, with SCC being most common on the sites of very heavy exposure and BCC becoming more common on areas of only moderate exposure, e.g. upper trunk in men and women and lower leg in women.
Incidence rates of NMSC, where they are being recorded, show rises over time. Mortality rates, on the other hand, have been dropping most of this century until they have been levelling out recently. The case fatality rate due to SCC appears to be between 1–2%. The malignant transformation rate of actinic keratoses to SCC appears to be very low.
Studies on similar populations at different latitudes allow estimates to be made of increases which might occur with increasing exposure to ultraviolet radiation (UVR) over a life time. These have been used to estimate the possible increases in NMSC due to stratospheric ozone depletion.
Finally, recent studies on the reduction of existing actinic keratoses and prevention of new ones with regular use of sunscreen augurs well for prevention of NMSC in the future.
The incidence of actinic keratoses (AK) is rising and there is still a need for therapeutic alternatives.
To demonstrate the efficacy and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) in the treatment of AK.
Ten patients with 36 lesions (19 at hands and arms, 17 on the head) received ALA-PDT once (occlusive application of a 10% ALA emulsion for 6 h, irradiation with red light, 580-740 nm, 150 J/cm2) and were then monitored for 3 months. Therapeutic efficacy was judged using a score evaluating infiltration and keratosis of AK.
After 28 days, significantly lower score sums were observed (head: mean = 15%; hand: mean = 67%) compared to the initial score (100%). Complete remission was achieved in 71% of AK localized on the head. No notable side effects were observed.
This study demonstrated the potential of good efficacy and tolerability in the treatment of AK using topical ALA-PDT. How efficacy for lesions on the hand can be improved and whether PDT is able to concur with established treatment modalities remains to be shown in further studies.
Because it is not possible to monitor skin cancer accurately using routine methods, special surveys have been undertaken in Nambour, a typical subtropical community in Queensland, Australia. Estimates of incidence reported here are based on skin cancers medically treated between 1985 and 1992 and new cases diagnosed by dermatologists in two examination clinics in 1986 and 1992. Among men and women aged 18-69 years in 1986, age-adjusted incidence rates of basal cell carcinoma were 2,074 and 1,579 per 100,000 per year, respectively-the highest incidence rates of a specific cancer ever reported. Squamous cell carcinoma occurred at half the rate of basal cell carcinoma among men and at about one third the rate among women. Although as expected, fair skin, a history of repeated sunburns, and nonmalignant solar skin damage diagnosed by dermatologists were strongly associated with both types of skin cancer, outdoor occupation was not. Significant self-selection was observed among outdoor workers, whereby people with fair or medium complexions and a tendency to sunburn were systematically underrepresented among those in long-term outdoor occupations although they accounted for more than 80 percent of the community study sample. The mitigating effect of this selection bias may partly explain the paradox of the lack of quantitative evidence of a causal link between sun exposure and skin cancer in humans.
The use of 5-aminolevulinic acid (ALA) as a protoporphyrin IX (PpIX) precursor for photodynamic therapy (PDT) became very popular in a short time. However, despite its advantages, ALA also has a drawback; it shows a poor ability to diffuse through biological membranes because of its low lipophilicity. As a consequence, a high dose of ALA must be administered in order to increase PpIX in the afflicted tissue at a level sufficient for PDT. A possible solution to this problem is the use of derivatives of ALA. ALA prodrugs are expected to have better diffusing properties as a result of their enhanced lipophilicity and are converted into the parent ALA after enzymatic hydrolysis. In this report, results are presented of the synthesis of a number of ALA derivatives. The ALA prodrugs were investigated regarding the optimum conditions for cell penetration and PpIX formation in an in vitro cellular test system. It is shown that several prodrugs do indeed enhance the amount of accumulated PpIX considerably as compared to ALA. Finally, the most promising prodrugs were tested in an animal model and showed increased PpIX formation under these conditions as well.
Topically applied delta-aminolevulinic acid is used efficiently for the treatment of solar keratoses by photodynamic therapy. Recent animal studies suggest that porphyrin sensitization of epithelial tissue is improved by using esters rather than free delta-aminolevulinic acid. The present study examines porphyrin metabolite formation after topical application of delta-aminolevulinic acid or delta-amino-levulinic acid methylester in human solar keratoses versus adjacent normal skin. Level of total porphyrins, porphyrin metabolites and protein were measured in skin samples excised after 1 and 6 h. Higher levels of porphyrins were observed in solar keratoses than in normal skin with both substances. Maximum porphyrin levels were present in solar keratoses treated with delta-aminolevulinic acid for 6 h. However, the ratio of porphyrins in solar keratoses versus adjacent normal skin was higher with delta-aminolevulinic acid methylester. The pattern of porphyrins showed no significant difference between normal and afflicted skin, protoporphyrin being predominant. The results suggest that application of free delta-aminolevulinic acid may be more effective in sensitizing solar keratoses. However, treatment with delta-aminolevulinic acid methylester leads to a preferential enrichment of porphyrins within lesional skin.
Photodynamic therapy (PDT) is a treatment modality using a photosensitising drug and light to kill cells. The clinical use of PDT requires the presence of a photosensitising agent, oxygen and light of a specific wavelength which matches the absorption characteristics of the photosensitiser. When the photosensitiser is activated by the appropriate wavelength of light, it interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. The appeal of PDT in oncology is that the photosensitiser tends to be retained in tumour tissues for a longer period of time as compared with normal tissues resulting in a large therapeutic index. This potential for minimal normal tissue toxicity has prompted an interest in studying PDT as a cancer treatment. Furthermore, the use of PDT is not precluded by prior radiotherapy, chemotherapy or surgery. The development of PDT has been hampered by the limitations of the older photosensitisers, namely limited depth of tissue penetration, and extended skin phototoxicity which limits the number of applications during a course of treatment. However, newer photosensitisers are being developed which allow greater depth of tissue penetration and have minimal skin phototoxicity allowing for multiple fractionated treatments. With such advancements, PDT has great potential to become an integral part of cancer treatment in the future.
Fifty-eight patients with 119 nodular (2 mm or more in thickness) basal cell carcinomas successfully treated with photodynamic therapy were included in this 1-year follow-up study. The initial cure rate at 3-6 months was 92% after photodynamic therapy, which included an initial debulking procedure and topical application of dimethylsulphoxide in order to enhance penetration of 5-aminolevulinic acid (20% in cream) to which the lesions were exposed for 3 h prior to exposure to light. At examination 12-26 months (mean 17 months) after treatment 113 lesions (95%) were still in complete response. Six lesions (5%) had recurred, located on the face, scalp and ear. The cosmetic outcome was evaluated as excellent to good in 91%. Microscopic examination of biopsies taken from healed areas in 7 patients did not reveal any sign of damage in 5 and only minor alterations in 2.
To systematically review the literature for studies reporting on recurrence rates of basal cell carcinomas (BCCs) after different therapies.
We reviewed all studies published in English, French, German, Dutch, Spanish, or Italian between 1970 and 1997 that prospectively examined recurrence rates for at least 50 patients with primary BCCs observed for at least 5 years after treatment with Mohs micrographic surgery, surgical excision, curettage and electrodesiccation, cryosurgery, radiotherapy, immunotherapy with interferon or fluorouracil, or photodynamic therapy.
Department of Dermatology, University Hospital Maastricht, Maastricht, the reference center for dermatologic oncology and Mohs micrographic surgery in the Netherlands.
The recurrence rates after different therapies for BCCs, resulting in the development of guidelines for the treatment of these disorders.
Of 298 studies found in several electronic databases, only 18 met the requirements and could be used for analysis. Tumors treated with Mohs micrographic surgery show the lowest recurrence rates after 5 years, followed in order by those treated with surgical excision, cryosurgery, and curettage and electrodesiccation.
Recurrence rates for different therapies could not be compared because of a lack of uniformity in the method of reporting, so evidence-based guidelines could not be developed. We surmise that Mohs micrographic surgery should be used mainly for larger, morphea-type BCCs located in danger zones. For smaller BCCs of the nodular and superficial types, surgical excision remains the first treatment of choice. Other treatment modalities can be used in patients in whom surgery is contraindicated. Immunotherapy and photodynamic therapy are still investigative.
Superficial basal cell carcinomas of the skin (sBCC) often respond poorly to single-treatment aminolaevulinic acid-based photodynamic therapy (ALA-PDT), with a number of reports indicating a relapse rate of 50% or more.
To determine whether a second treatment at seven days can improve the response.
Twenty-six lesions were treated twice with ALA-PDT, with an interval of 7 days between the two treatment sessions.
We observed a complete response rate of 100% 1 month after treatment. Only one lesion relapsed (16 months post-PDT), a relapse rate of 4% (median follow up 27 months; range 15-45 months). Cosmetic results were excellent.
We consider routine double treatments with ALA-PDT to be an effective approach to the management of sBCC, particularly those located in anatomically difficult, or cosmetically sensitive, sites.
A previously reported randomized clinical trial showed treatment of Bowen's disease using photodynamic therapy (PDT) with topically applied delta-aminolaevulinic acid (ALA) to be at least as effective as cryosurgery and to be associated with fewer adverse effects.
To compare ALA-PDT and cryotherapy in the treatment of histopathologically verified basal cell carcinomas (BCCs) in a non-blinded, prospective phase III clinical trial.
One lesion from each of 88 patients was included. The BCCs were divided into superficial and nodular lesions. The follow-up period was restricted to 1 year with close follow-up for the first 3 months. Efficacy was assessed as the recurrence rate 12 months after the first treatment session, verified by histopathology. Tolerability was evaluated as the time of healing, pain and discomfort during and after the treatment, and final cosmetic outcome.
Histopathologically verified recurrence rates in the two groups were statistically comparable and were 25% (11 of 44) for ALA-PDT and 15% (six of 39) for cryosurgery. However, clinical recurrence rates were only 5% (two of 44) for PDT and 13% (five of 39) for cryosurgery. Additional treatments, usually one, had to be performed in 30% of the lesions in the PDT group. The healing time was considerably shorter and the cosmetic outcome significantly better with PDT. Pain and discomfort during the treatment session and in the following week were low, and were equivalent with the two treatment modalities.
In terms of efficacy, ALA-PDT is comparable with cryosurgery as a treatment modality for BCCs. Retreatments are more often required with PDT than with cryosurgery. This can easily be performed due to the shorter healing time, less scarring and better cosmetic outcome that follows ALA-PDT.
Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA.
To assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment.
Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2-4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g(-1) was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm(-2). Fibrosis was assessed histologically in 23 biopsies.
The overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies.
We conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.
Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Several non-coherent and coherent light sources are effective in PDT. Optimal disease-specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA-PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.
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