Therapy For Basal Cell Carcinoma Research Articles

41913 Treatment Effect of Intense Photodynamic Therapy in Basal Cell Carcinoma

41913 Treatment Effect of Intense Photodynamic Therapy in Basal Cell Carcinoma

D‐OCT‐assisted and histology‐controlled evaluation of 1064 nm Nd:YAG laser therapy of basal cell carcinomas

AbstractBackgroundBasal cell carcinomas (BCC) have classically been surgically removed. Alternative treatments for superficial BCC include local immunotherapy, topical chemotherapy and photodynamic therapy. Recent data suggest 1064 nm Nd:YAG laser as a new treatment for those lesions.Dynamic optical coherence tomography (D‐OCT) is an established imaging procedure analysing BCC margins and its vascular plexus.ObjectivesOur goal is to further evaluate 1064 nm Nd:YAG laser therapy of BCC as a potential alternative treatment, employing D‐OCT and histopathology to standardise effective treatment protocols.MethodsIn this retrospective cohort study, 50 histologically confirmed superficial and nodular BCC with tumour thickness ≤1 mm were treated with 1064 nm Nd:YAG laser. Initial D‐OCT scans were performed and repeated for 3 months posttreatment. Tumoral clearance was histologically confirmed and local adverse effects, patient tolerability and satisfaction were recorded. Clinical remission was evaluated after 1 year.ResultsComplete clearance was achieved in 78% of BCC (39/50) at a 3‐month follow‐up. Treatment failures were slightly more likely to correspond to superficial BCC (91%, 10/11) of thickness ≤0.5 mm (73%, 8/11), located on the trunk (64%, 7/11). No treated lesions presented scarring. Patient satisfaction and tolerability displayed excellent results. Remission at 1 year occurred in 100% of initially cleared BCC (35/35, four patients were lost to follow‐up due to nonmedical reasons).ConclusionsOCT‐assisted 1064 nm Nd:YAG laser treatment of superficial BCC is a safe and effective method with excellent patient satisfaction, tolerability, practicability and cosmetic end result.

271 The invasive niche confers resistance to therapy in basal cell carcinoma

271 The invasive niche confers resistance to therapy in basal cell carcinoma

Dermoscopic Structures Predictive of Response to Photodynamic Therapy in Basal Cell Carcinoma.

Abstract is missing (Short communication)

283 Photodynamic therapy for basal cell carcinoma enhanced by pretreatment with oral vitamin D: interim results of a prospective clinical trial

Photodynamic therapy (PDT) is used in Europe to treat basal cell carcinoma (BCC), but it is not approved in the USA due to uncertainties about efficacy. Vitamin D3 (VD3; cholecalciferol) treatment prior to PDT improves BCC responses in mice. A prospective, double-blind, crossover clinical trial [NCT03467789] was designed to test whether oral VD3 pretreatment enhances BCC response to blue light PDT. Participants received 3 PDT treatments (20% ALA, 4 h; 417 nm, 30 min) 2 months apart. High-dose VD3 or placebo was administered prior to each of the first two PDT sessions.

Update on Hedgehog Pathway Inhibitor Therapy for Patients with Basal Cell Naevus Syndrome or High-frequency Basal Cell Carcinoma.

Some patients with basal cell carcinoma develop a large number of basal cell carcinomas during their lives. The most common underlying genetic disease that causes multiple basal cell carcinomas is basal cell naevus syndrome. Basal cell naevus syndrome is caused by a germline mutation in patched-1 (PTCH1), a tumour suppressor gene of the hedgehog signalling pathway. However, in a significant portion of patients with multiple basal cell carcinomas, no underlying genetic cause is found. Nevertheless, these patients can experience a treatment burden comparable to that of patients with basal cell naevus syndrome. They are referred to as high-frequency basal cell carcinoma patients. Hedgehog pathway inhibitors were the first group of targeted therapy for basal cell carcinomas. This study reviews the literature on hedgehog pathway inhibitor therapy for patients with basal cell naevus syndrome and high-frequency basal cell carcinoma, to provide an overview on efficacy, safety, dosing regimens, tumour resistance and reoccurrence, and health-related quality of life.

Sonidegib potentiates the cancer cells’ sensitivity to cytostatic agents by functional inhibition of ABCB1 and ABCG2 in vitro and ex vivo

Sonidegib (LDE-225) is a Hedgehog pathway inhibitor used for the therapy of basal cell carcinoma. In addition, the drug is a subject of clinical trials for the treatment of other solid tumors including non-small cell lung cancer (NSCLC). In this study, we explored the potential of sonidegib to act as a perpetrator of drug-drug interactions (DDIs) and modulator of transporter- and enzyme-mediated multidrug resistance (MDR). First, we found that transport functions of ABCB1 and ABCG2 were effectively inhibited by sonidegib in accumulation studies. In contrast, the drug did not cause fluctuations in mRNA levels of tested efflux transporters. In drug combination assays, sonidegib synergistically enhanced the cytotoxicity of daunorubicin and mitoxantrone in ABCB1- and ABCG2-overexpressing cells, respectively. Notably, similar phenomena were also observed in explant tumor cultures derived from NSCLC-suffering patients. In addition, the anticancer effects of sonidegib were not hampered by the expression of the ABC transporters associated with MDR. Last, sonidegib had no significant influence on the activity of CYP3A4 isoform in vitro. In summary, our work suggests that sonidegib can be considered a potential perpetrator of clinical DDIs on ABCB1 and ABCG2. After in vivo evaluation, its chemosensitizing properties might be projected into efficient and safe treatment regimen for the clinical management of NSCLC patients with high ABCB1/ABCG2 expression.

Photodynamic Therapy for Basal Cell Carcinoma: The Clinical Context for Future Research Priorities.

Photodynamic therapy (PDT) is an established treatment option for low-risk basal cell carcinoma (BCC). BCC is the most common human cancer and also a convenient cancer in which to study PDT treatment. This review clarifies challenges to researchers evident from the clinical use of PDT in BCC treatment. It outlines the context of PDT and how PDT treatments for BCC have been developed hitherto. The sections examine the development of systemic and subsequently topical photosensitizers, light delivery regimens, and the use of PDT in different patient populations and subtypes of BCC. The outcomes of topical PDT are discussed in comparison with alternative treatments, and topical PDT applications in combination and adjuvant therapy are considered. The intention is to summarize the clinical relevance and expose areas of research need in the BCC context, ultimately to facilitate improvements in PDT treatment.

Photodynamic diagnosis and photodynamic therapy in basal cell carcinoma using a novel laser light source.

The aim of the present study was evaluating the effects and safety of new laser light source in PDD and PDT of basal cell carcinoma, BCC. The patients presented challenging localizations of the tumor or tumor combined with Gorlin syndrome. The PDD and PDT was performed in 50 patients with 54 histologically confirmed BCCs. The photosensitizer precursor, 5-ALA in cream, was used and the tumors were then illuminated, for PDD at 405 nm, and for PDT at 638 nm by means of newly designed laser. The novel feature of the laser was the combination of violet and red light in a single fiber output which enabled us to perform PDD and PDT alternatingly. The patients received one or more PDT sessions and they were observed during the next 36 months. The complete responses (CR, remissions) of the lesions were considered as no visible tumor after that time period. CR were observed in 87 % of the lesions in the entire group of patients. The results of present study show that the new laser allowing for both PDD and PDT was effective in producing satisfactory responses in the treatment of basal cell carcinoma.

[Diagnosis and treatment of basal cell carcinoma : A question of the risk of recurrence].

Basal cell carcinoma is the most common type of cancer in Central Europe and has ahigh medical relevance. Due to its high tendency of recurrence, an important parameter in the planning of therapy is the risk of recurrence. After clinical and histological diagnosis, the majority of tumors are treated surgically, although radiation and topical procedures are also possible therapeutic alternatives in certain constellations. Hedgehog inhibitors, acompletely new class of substances, have recently been approved for rare metastatic and locally advanced diseases, thus significantly expanding the range of treatments. This article provides an overview of the current guideline-based diagnosis and therapy of basal cell carcinomas in Germany.

Vismodegib Treatment in Patients with Advanced Basal Cell Carcinoma: LongTerm Efficacy and Safety Data with Focus on Secondary Resistance and Underlying Resistance Mechanism

Background: The smoothened inhibitor vismodegib is an effective targeted therapy for basal cell carcinoma (BCC) with a manageable and consistent safety profile. The occurrence of secondary resistance during treatment is a major problem and is associated with hedgehog pathway reactivation, predominantly through Smoothened (SMO) gene mutations. Objectives: To analyse efficacy and safety data after long-term follow-up of patients treated with vismodegib for advanced BCC in the University Hospital of Leuven, focusing on underlying genetic mechanisms of primary and secondary resistance to vismodegib. Methods: Twenty seven patients were retrospectively included in the study. We performed targeted sequencing of hedgehog pathway genes in 7 tumor samples from 4 patients with primary or secondary resistance to vismodegib. Results: Mean duration of follow-up was 29.9 months (1-77.7 months). Mean treatment duration was 13.3 months (1-64.5 months). The response rate to vismodegib was 93% (25/27 patients), with a partial response in 18/27 patients and a complete response in 7/27 patients. One patient maintained a complete response up to >3 years after vismodegib discontinuation. Six out of 27 patients (24%) developed secondary resistance during treatment, in three of them we detected acquired pathogenic SMO mutations in resistant tumor tissue. One patient with Bazex–Dupré–Christol syndrome showed primary resistance to vismodegib. No unexpected safety signals were detected in our analysis, however progression of Multiple Sclerosis (MS) was observed in one patient. Conclusions: We deliver new data about the response duration after vismodegib discontinuation and describe MS progression as a possible new adverse event to vismodegib. We describe for the first time vismodegib treatment and primary resistance to vismodegib in a patient with Bazex–Dupré–Christol syndrome. We highlight the problem of occurrence of secondary resistance in >20% of responders and confirm the previously reported resistance mechanism through acquired SMO mutations.

Treatment of keratinocyte carcinoma in elderly patients - a review of the current literature.

A large percentage of the patients with keratinocyte carcinoma (KC, formerly known as non‐melanoma skin cancer) is of advanced age and often too frail for standard therapies. However, no specific treatment recommendations are given for this population. This review aimed to give an overview of the current literature on the best practice for the treatment of elderly patients with KC. A literature search was performed in MEDLINE, using ‘keratinocyte carcinoma’, ‘elderly’, ‘treatment’ and various synonyms. Case reports, reviews, comments, non‐English literature and studies with a sample size <15 were excluded. After selection, a total of 47 studies were reviewed. Two types of studies were identified, focusing on (I) the effect of age on treatment outcomes and (II) alternative treatment schedules for elderly patients. Studies on surgery, the gold standard, describe larger lesions and defect size in the elderly population. Recurrence rate, complication rate and disease‐specific survival were not affected by age. Depending on the expected morbidity of a suggested (re‐)excision and patient preferences, a conservative watchful waiting policy can be agreed upon as a shared decision. Other common treatment modalities, such as adjuvant radiotherapy, photodynamic therapy and systemic therapy for basal cell carcinoma (BCC), show comparable results in the elderly and younger population. Alternative treatment schedules for elderly patients include primary hypofractionated radiotherapy, which seems effective and well‐tolerated, although research is limited to case series. Additionally, localized and topical treatments seem safe and effective especially for low‐risk tumours. Data are lacking on the efficacy of systemic therapies of metastatic KC in elderly patients. Efficacy of most treatments (with the exception of photodynamic therapy) is not dependent on age. There is need for more research on the efficacy of adjusted treatment modalities, such as hypofractionated radiotherapy and palliative or curative systemic treatment.

Topical 5-aminolevulinic acid-mediated photodynamic therapy for basal cell carcinoma.

Topical 5-aminolevulinic acid-mediated photodynamic therapy is an established approach for the treatment of basal cell carcinoma. This study with 5- aminolevulinic acid drug Levulon was conducted in patients with superficial skin basal cell carcinoma. The study included 82 patients with overall number of tumor foci of 119. Tumor sites were as follows: head and neck, trunk, extremities.A total of two photodynamic therapy sessions, four weeks apart were performed using a laser with a wavelength of 630 nm and energy density of 350 J/cm2. A complete response was recorded in 77 patients (114 foci) with an excellent cosmetic result. According to the analysis of survival in the group of patients with a complete response, the overall RFS was as follows: 1-year rate - 92.1 %, 3-year - 88.3 %. Photodynamic therapy with topical Levulon in patients with superficial BCC of the skin was effective and safe.

The potential utility of integrated reflectance confocal microscopy-optical coherence tomography for guiding triage and therapy of basal cell carcinomas.

The increasing rate of incidence and prevalence of basal cell carcinomas (BCCs) worldwide, combined with the morbidity associated with conventional surgical treatment has led to the development and use of alternative minimally invasive non-surgical treatments. Biopsy and pathology are used to guide BCC diagnosis and assess margins and subtypes, which then guide the decision and choice of surgical or non-surgical treatment. However, alternatively, a noninvasive optical approach based on combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) imaging may be used. Optical imaging may be used to guide diagnosis and margin assessment at the bedside, and potentially facilitate non-surgical management, along with long-term monitoring of treatment response. Noninvasive imaging may also complement minimally invasive treatments and help further reduce morbidity. In this paper, we highlight the current state of an integrated RCM/OCT imaging approach for diagnosis and triage of BCCs, as well as for assessing margins, which therefore may be ultimately used for guiding therapy.

ORAL LESIONS OF THROMBOCYTOPENIC PURPLE: CASE REPORT

A male patient, 72 years of age and white, complained of bubbles in the mouth for 10 days. Past medical history: Received renal transplant (2001), diabetes mellitus, coronary artery bypass graft, and radiation therapy for basal cell carcinoma in the head region (2014). Extraoral examination showed basal cell carcinomas in the right and left ears and blood lesions in the arms. At intraoral examination, we observed hemorrhagic blister and ulcerated lesion with superficial shallow edges, preceded by blister both in the lower lip mucosa, blood injury, slightly high edges, blackish coloration, and located in the mucosa of the cheek. Differential diagnosis: Angina bullosa × thrombotic thrombocytopenic purpura. Management: Cytologic examination of oral mucous membrane lesions, diagnosed with acute inflammatory process with presence of squamous cells of regenerative aspect. Complete blood count with platelet count of 66,000/mm3 was requested. Therapy: Mouthwash with chlorhexidine and hematologist evaluation.

A Sampling of Highlights from the Literature

New clonotypes recruited (by Staff Sergeant K. Brasier via U.S. Air Force)To identify which tumor-specific T cells are active after anti–PD-1 therapy of basal cell carcinomas, single cells from biopsies before and after treatment were analyzed for gene expression and TCR usage. T cells already exhausted before anti–PD-1 therapy were not reactivated. Instead, novel clonotypes (only a small fraction of which had previously expressed TCF7) replaced those, transiting from memory to activated states. This was also true of squamous cell carcinoma, suggesting that checkpoint blockade prompts a new wave of immunoevolution and that the tumor's ability to constantly attract new T cells may be key to successful responses.Yost KE, …, Chang HY. Nat Med 2019 Aug 1;25:1251–9.CD163+ TAMs infiltrating melanomas (from Fig. 1C Etzerodt et al. J Exp Med 2019)Tumor-associated macrophages (TAMs) can contribute to tumor cell immune evasion, which is dependent on their phenotype and the tumor microenvironment (TME). Barkal et al. show that ovarian and breast cancers overexpress CD24, which relays “don't eat me” signals to TAMs via interaction with Siglec-10. Etzerodt et al. demonstrate that in melanomas refractory to anti–PD-1, CD163+ TAMs are elevated. Immunotherapies that target either surface molecules (such as CD24) or cell types (such as CD163+ TAMs) that promote immune evasion can alter the TME, resulting in enhanced antitumor immunity.Barkal AA, …, Weissman IL. Nature 2019 Aug 15;572:392–6.Etzerodt A, …, Lawrence T. J Exp Med 2019 Aug 2. DOI: 10.1084/jem.20182124.Optimizing the anti–PD1 schedule (by Best Picko via Flickr)Optimizing the efficacy of combination therapies involves determining their ideal schedule. In anti–PD-1–resistant murine tumor models, peptide vaccination plus anti–PD-1 slows tumor growth, whereas exposure to anti–PD-1 before combination treatment abrogates effectiveness. Anti–PD-1 causes suboptimal antigen priming of intratumoral CD8+ T cells, leading to increased dysfunction, higher PD-1+ CD38hi frequency, and more death. Anti–PD-1 responder patients have fewer intratumoral PD-1+ CD38+ CD8+ T cells compared to nonresponders, suggesting a predictive biomarker for anti–PD-1. Thus, T-cell priming prior to anti–PD-1 therapy is crucial for its efficacy.Verma V, …, Khleif SN. Nat Immunol 2019 Sep 1;20:1231–43.IFN opposing itself (via Max Pixel)Resistance to immune checkpoint blockade (ICB) is complex. Tumor-produced IFNγ sets up feedback loops that promote intrinsic tumor resistance and inhibit innate and adaptive immunity. Blocking IFN-stimulated gene expression from MHC class Ilow tumors can restore ICB responsiveness, stimulating tumor killing via TRAIL by NK and type 1 innate lymphoid cells (ILC1s). ICB treatment enhances IFNγ produced by CD8+ exhausted T (TEX) cells (that had been inactivated through PD-1 engagement), which supports NK/ILC1 cell maturation; TEX cells can also kill those tumor cells with adequate MHC class I, via the granzyme B/perforin pathway.Benci JL, …, Minn AJ. Cell 2019 Aug 8;178:933–48.e14.Engineering increased functionality (by N. Pawar via MotorsGarage)The affinity of a TCR for its target can affect antileukemia responses in patients with acute myeloid leukemia (AML) treated by hematopoietic cell transplantation (HCT). Engineered T cells bearing a high-affinity TCR targeting antigen WT1 (called TCRC4) can kill AML cells, are polyfunctional, and have increased persistence in vivo. When infused into patients after HCT, TCRC4 T cells reduced AML relapse. Thus, these engineered T cells could extend antileukemia T-cell persistence and reduce relapse in high-risk AML patients after HCT or other standards of care.Chapuis AG, …, Greenberg PD. Nat Med 2019 Jul 3;25:1064–72.Conditioning of hosts (by didkog via Pixabay)The efficacy of adoptive cell therapy (ACT) for cancer depends on prior lymphodepletion of recipients: IL-1β increases after this “conditioning.” Adding IL-1β to ACT therapy greatly improves therapeutic responses by increasing the number of effector CD8+ T cells in tumors and tumor-draining lymph nodes compared to ACT alone, in an IL-2/IL-15–mediated manner. IL-1β improves the trafficking of CD8+ T cells into peripheral organs and primes the host to better support effector CD8+ T-cell survival in these organs. Thus, treating patients with IL-1β may improve ACT efficacy.Lee P-H, …, Restifo NP. J Exp Med 2019 Aug 12. DOI: 10.1084/jem.20181218.

115 Hexylaminolevulinate and Aminolevulinic acid Nanoemulsion have Similar Tolerability, Initial Efficacy and Cosmetic Outcome as Methylaminolevulinate in Photodynamic Therapy of Basal Cell Carcinoma in a Prospective Randomized Double-blinded Trial

115 Hexylaminolevulinate and Aminolevulinic acid Nanoemulsion have Similar Tolerability, Initial Efficacy and Cosmetic Outcome as Methylaminolevulinate in Photodynamic Therapy of Basal Cell Carcinoma in a Prospective Randomized Double-blinded Trial

Histologic subtype of treatment failures after noninvasive therapy for superficial basal cell carcinoma: An observational study

There have been concerns that recurrences after noninvasive therapy for basal cell carcinoma (BCC) transform into a "more aggressive" histologic subtype. We sought to evaluate the proportion of patients with a nonsuperficial treatment failure after noninvasive therapy for superficial BCC. An observational study was performed using data from a single blind, noninferiority, randomized controlled trial (March 2008-August 2010) with 5-year follow-up in patients with primary superficial BCC treated with methylaminolevulinate-photodynamic therapy, 5-fluorouracil, or imiquimod. Data were used from 166 adults with a histologically confirmed treatment failure. A nonsuperficial subtype was found in 64 of 166 treatment failures (38.6%). Proportions with a more aggressive subtype than the primary tumor were 51.3% (38/74) for early and 28.3% (26/92) for later treatment failures (P=.003). The proportion of more aggressive early failures was significantly lower after imiquimod (26.3%) compared with methylaminolevulinate-photodynamic therapy (54.8%, P=.086) and 5-fluorouracil (66.7%, P=.011). There was limited information on the exact time of occurrence of treatment failures. More aggressive treatment failure recurrences after noninvasive therapy for superficial BCC occur most often within the first 3months posttreatment, probably indicating underdiagnosis of more aggressive components in the primary tumor rather than transformation.

Shedding light on photodynamic therapy for basal cell carcinoma

Linked Article:Collier et al. Br J Dermatol 2018; 179:1277–1296.

Photodynamic therapy for basal cell carcinoma

Photodynamic therapy for basal cell carcinoma