Complete remission of nodular basal cell carcinoma after combined treatment with photodynamic therapy and imiquimod 5% cream
Published Web Locationhttps://doi.org/10.5070/D309g8q3w0
Complete remission of nodular basal cell carcinoma after combined treatment with photodynamic therapy and imiquimod 5% creamDepartment of Dermatology, "La Sapienza" University, Rome, Italy
Valeria Devirgiliis, Vincenzo Panasiti, Michela Curzio, Silvia Gobbi, Mariarita Rossi, Vincenzo Roberti, Stefano Calvieri
Dermatology Online Journal 14 (2): 25
Basal cell carcinoma is the most common human cancer. We present a case of nodular basal cell carcinoma treated with a combination of photodynamic therapy and topical imiquimod. Clinical clearing was obtained and there has been no sign of recurrence over 15 months.
Basal cell carcinoma (BCC) is the most common malignancy worldwide  and its incidence has increased worldwide over the last three decades . Several therapies have been proposed for the treatment of this neoplasia, such as surgery, electrodesiccation, curettage, cryosurgery, radiation therapy, laser therapy and pharmacological therapies (topical 5-fluorouracil) . In the past few years, two different non-invasive techniques, namely photodynamic therapy (PDT) and topical application of imiquimod (IQ), have been developed for the treatment of BCC.
In June 2006 a 92-year-old man was referred to our department for a nodule of 0.4 mm thickness, ulcerated, on the left side of the nose (Fig. 1A).
The lesion was diagnosed by cytopathological examination as nodular basal cell carcinoma. The patient had suffered of hypertensive heart failure and had developed an acute ischemic stroke for which he started anticoagulant therapy. Therefore, we preferred to treat the lesion with a non-invasive technique before surgery.
We started treatment with a combination therapy with methyl aminolevulinate-PDT (MAL-PDT) and IQ 5-percent cream (Aldara®, Meda Pharma). After informed consent, the patient underwent a course of MAL-PDT every 2 weeks for a total of two courses; then, after 10 days, he started topical application of IQ 5-percent cream, five times a week for 3 weeks.
Before application of 160 mg/g MAL cream (Metvix®, Galderma, France) the lesion was scraped in order to amplify penetration of the active agent; then the cream was applied, approximately 1 mm thick, on the lesion and 5-10 mm of surrounding skin.
The lesion was then covered by an adhesive, occlusive dressing for 3 hours after which time the cream was removed by rinsing with saline solution. The lesion was immediately illuminated with an LED light source (Aktilite® CL16 & CL128 lamps, PhotoCure ASA, Norway) which emits red light at an average wavelength of approximately 630 nm at the dosage of 37 J/cm².
Imiquimod 5 percent cream was applied on the lesion and removed by rinsing off with water after about 8 hours. The patient after two courses of MAL-PDT obtained a partial response with a reduction of more than 50 percent of the lesion; then, after topical application of IQ 5 percent cream, obtained a complete response. (Figure 1B) Clinical follow up at 15 months did not show any relapse of the disease.
Surgery is the gold standard in the treatment of nodular BCC but unfortunately, it is not always practicable. In our case, old age, concomitant diseases, and anticoagulant therapy induced us to prefer a non-invasive therapy.
PDT is a therapeutic modality usually employed in the treatment of superficial BCC, with a complete response rate variable from 79 percent to 87 percent,  whereas, alone, is effective only in the 52.2 percent of cases of nodular basal cell carcinoma . Therefore, we decided to treat the lesion with a combined therapy based on MAL-PDT and IQ 5-percent cream.
Photodynamic therapy is based on a combination of light and photosensitizing drugs to damage the tumor tissue; reactive oxygen species (ROS), in particular singlet oxygen, generated after the activation of the photosensitizer with the appropriate light, modify either cellular functions or induce cell death by necrosis or apoptosis. Moreover, PDT induces inflammation and enhances anti-tumor immunity .
The antigen presenting cells (APCs), crucial for anti-tumor immunity,  are activated in response to tissue damage and cell death induced by PDT  and, through the production of IL-12, are critical for the formation of interferon-γ (IFN-γ) secreting effector T cells .
Also IQ, a member of a group of agents called immune-response modifiers, acts amplifying the anti-tumor immune-response; in fact through the Toll-like receptors 7 and 8 and activation of the transcription factor NF-kB, promotes the release of Th1 cytokines, including interleukin (IL)-12 . In fact, the histological examination of the inflammatory cell infiltrate of different superficial malignant tumors during the treatment with IQ 5-percent cream revealed the prevalence of T-helper lymphocytes with a significant population of CD8+ cytotoxic cells .
These findings support the hypothesis that antitumor activity of IQ 5-percent cream should result from both a cytotoxic T-cell mediated immune response and the enrollment of dendritic cells to the skin . In our case, we speculate that MAL-PDT, used before IQ cream, established a favorable micro-environment enhancing the activity of IQ on the immune response. This synergic effect is confirmed by the shorter duration (3 weeks instead of 6, as usually requested) of the treatment required to obtain a complete remission.
Further studies are necessary to confirm our result; however, in our case, MAL-PDT associated to the application of IQ 5-percent cream, has demonstrated to be effective and well-tolerated and it is currently established that this treatment provides very good cosmetic outcome and high patient satisfaction.
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