Basal Cell Cancer Research Articles

Mohs Micrographic Surgery for Treatment of Non-melanoma Skin Cancer

The aims of this report are to review literature supporting the use of Mohs micrographic surgery for treatment of non-melanoma skin cancer and to address indications and potential limitations of this form of therapy for non-melanoma skin cancer. The first randomized controlled trial comparing standard excision to Mohs micrographic surgery for treatment of facial basal cell carcinoma has recently been published, demonstrating a lower recurrence rate after Mohs surgery compared to standard excision after a 5-year and 10-year follow-up period, supporting its use in the treatment of high-risk basal cell skin cancer. Mohs micrographic surgery is indicated for treatment of basal cell carcinomas and cutaneous squamous cell carcinomas at high risk of recurrence and for tumors located in areas where tissue conservation and/or functional preservation is desired.

FLUORESCENT DIAGNOSTICS OF MALIGNANT SKIN TUMORS WITH CHLORIN SERIES PHOTOSENSITIZERS

The article shows possibilities in fluorescence imaging of malignant skin tumors with chlorin series photosensitizers (PS) photolon and fotoditazin. The regularities of photosensitizer accumulation from the data of local fluorescence spectroscopy depending on the PS and its dose, the clinical picture and the histological form of the malignant skin neoplasm is investigated. It is shown that the level and selectivity of PS accumulation in the tumor focus depends on the PS dose. In studies on 10 patients with basal cell skin cancer after the introduction of fotoditazin at a dose less than 1 mg/kg, fluorescent contrast between tumor and healthy tissue varied between 1.3 and 9.5, the average was 2.8±0.3; for patients who had the administered fotoditazin dose of 1 mg/kg, fluorescent contrast was 2.9±0.4, varying from 1.4 to 5. In a study with 127 patients after the introduction of photolon in the dose of 0.7-1 mg/kg, the average value of the fluorescence intensity in relative units in the intact skin was 6.9±0.3 (min 4.6, max 12.2), at a dose of 1.1 to 1.4 mg/kg – 8.0±0.3 (min 4.6, max 12.5), at a dose of 1.5-2 mg/kg – 9.9±0.7 (min 5.7, max 20.3). It is also shown that fluorescence intensity of malignant neoplasm of the skin with the same dose of the photosensitizer depends on the neoplasm’s clinical and histological forms. So, 3 hours after the introduction of photolon at a dose of 1.3 mg/kg the average fluorescent contrast in the surface type of skin cancer was 2.7±0.5, in the nodal form – 2.3±0.2, in erosive-ulcerative form – 3.6±0.3. In patients with nodular form of squamous skin cancer after the introduction of photolon at a dose of 1.3 mg/kg fluorescent contrast was significantly higher (p<0.05) (average of 2.8±0.2) than in the nodular form of basal cell carcinoma after the introduction of photolon at the same dose (average of 2.1±0.2).

242 Risk of nonmelanoma skin cancer after exposure to statin drugs: A report from the RADAR (Research on Adverse Drug events and Reports) project

Statin exposure and nonmelanoma skin cancer (NMSC) association is unclear. The aim of this study is to determine if there is an association between statin exposure and NMSC [basal cell cancer (BCC) and squamous cell cancer (SCC)], in a large patient population. The Northwestern Medicine Enterprise Data Warehouse medical record data repository (> 5 million patients) was searched for patients aged 18-89 years with at least 5 years of in-clinic follow-up. The statin-exposed population consisted of all patients taking a chronic statin medication (atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) for at least 12 months, while the control population consisted of non-statin-exposed patients. Data on age, gender, race, and NMSC diagnosis were collected. Adjusted odds ratios (aORs) were determined by multivariate logistic regression. Of 440,289 patients meeting inclusion criteria, 56,117 had statin exposure, of whom 3,590 (6.4%) were diagnosed with NMSC, yielding a significant association between NMSC and statin exposure (aOR: 2.39; 95%CI 2.30-2.49; p < 0.0001). Data for the 40 to 75-year-old group chosen to follow recent statin recommendations from US Preventative Services Task Force also showed a significant association between statin exposure and subsequent NMSC diagnosis (aOR: 1.63; 95%CI 1.56-1.70; p < 0.0001). In addition, statin exposure and subsequent diagnoses of BCC or SCC were examined in separate populations. This yielded further significant associations between statin exposure and subsequent BCC diagnosis (aOR: 1.46; 95%CI 1.38-1.53; p < 0.0001), as well as subsequent SCC diagnosis (aOR: 2.12; 95%CI 1.97-2.29; p < 0.0001). These findings highlight an association between chronic statin exposure and subsequent incident NMSC in the study population.

164 Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility

164 Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility

205 ARP-T1 is a protein associated with a novel ciliopathy in inherited basal cell cancer of Bazex-Dupré-Christol Syndrome

205 ARP-T1 is a protein associated with a novel ciliopathy in inherited basal cell cancer of Bazex-Dupré-Christol Syndrome

Systematic Review and Meta-Analysis of the Accuracy of Confocal Microscopy in the Diagnosis of Skin Cancer

Background: Nonmelanoma skin cancer (Basal Cell Cancer (BCC) and Squamous Cell Cancer (SCC)) are the most prevalent cancer in the light-skinned population. The incidence of melanoma has been increasing steadily throughout the world. Early recognition of skin cancer without doing biopsy remains challenging. The development of noninvasive diagnostic technologies is highly relevant and desired. Confocal Laser Scanning Microscopy (CLSM) enables in vivo and ex vivo imaging of human skin at a quasi-histologic resolution. Methods and Materials: Several databases like Medline, Embase, all EBM reviews (ACP Journal Club, Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects) and Journals@Ovid were used to perform a literature search on CLSM in the diagnosis of melanoma and non melanoma skin cancers. Standards for Reporting of Diagnosis Accuracy (STARD) initiative checklist and National Institute for Health and Clinical Excellence (NICE) guidelines on methodology were used to assess the quality of the studies found. Eight studies fulfilling relevant criteria inclusive of assessment of diagnostic accuracy of CSLM and histopathology were selected. Heterogeneity among the studies was assessed and the data was pooled for meta- analysis. Results: The eight included studies did not have considerable heterogeneity between them. The pooled sensitivity for melanoma diagnosis was 91.4% and for BCC diagnosis was 90.1%. Pooled specificities were 79.9% and 92.6% for malignant melanoma and BCC respectively. Diagnostic odds ratios for melanoma and BCC were 80.1 and 358.1 respectively. Conclusions: From the limited good quality available literature we found that CLSM has the potential to be an additional noninvasive diagnostic test to dermoscopy for the diagnosis of BCC and melanoma.

Hedgehog Inhibitors are Effective Treatment for Basal Cell Cancer Recurrence

Hedgehog Inhibitors are Effective Treatment for Basal Cell Cancer Recurrence

PHOTODYNAMIC THERAPY FOR HEAD AND NECK BASAL CELL SKIN CANCER WITH ADDITIONAL INTERSTITIAL LASER IRRADIATION

The article is devoted to the development and evaluation of the effi ciency of photodynamic therapy (PDT) with photosensitizer photolon with additional interstitial laser irradiation in patients with head and neck basal cell skin cancer (BCSC). Treatment was performed in 55 patients. On the fi rst stage, all patients underwent photodynamic therapy with interstitial irradiation using fl exible optical fi bers with cylindrical diffuser, on the second stage PDT with distant delivery of laser at a dose of 50-300 J/cm2 was carried out. During the follow- up period of 6 months to 4 years in 13 (23.6%) of the 55 patients a recurrence of the disease was diagnosed. A higher rate of recurrence was in the group of patients who underwent PDT for recurrent neoplasms compared with patients with primary disease (37.5% and 4.3%, respectively), in patients with endophytic growth of the tumor compared to patients with exophytic component (30.0% and 16.0%, respectively) and in patients with large tumors (up to 2.0 cm – 14.3%, from 2.0 to 5.0 cm – 16.7% and more than 5.0 cm – 54.4%).

028 Increased Risk of Incident Cancer in men with Peyronie's Disease: Analysis of United States Claims Data

Peyronie′s disease (PD) is inherited in autosomal dominant fashion in a subset of men. Recent work examining genetic risk factors identified genes involved in human carcinogenesis. Here, we examine the risk of cancer among a large sample of men with PD. We analyzed subjects contained within the Truven Health MarketScan claims database from 2007-2014. This U.S. database provides information of insurance claims filed for the care of privately-insured individuals with employment-based insurance. Men with PD or erectile dysfunction (ED) were identified through diagnosis (ICD-9) codes. An age and follow-up time matched control cohort of men was also created. men with any claim with a diagnosis code for cancer before the index date or within 1 year after the index date were excluded (ICD9 140–209, excluding skin squamous cell, basal cell, and non-invasive cancers). The incidence of cancer was compared among each group utilizing a Cox regression model.

Auricular Acupuncture and Skin-Cancer Detection: An Opportunity.

Background: Auricular acupuncture is effective for many patients with pain. Many skin malignancies and precancerous lesions are found on the head and neck. Practitioners of acupuncture are in a unique situation to detect cutaneous malignancy at an early state. Case: An 83-year-old man referred for Battlefield Acupuncture was found to have a scalp lesion suspicious for malignancy as well as several precancerous lesions. Results: Referral to a dermatologist led to excision of a basal-cell cancer and treatment of actinic keratoses. Conclusions: Practitioners of auricular acupuncture should be familiar with common skin cancers and precancerous lesions; these practitioners are in a unique situation to detect these common skin lesions.

PUVA - Induced Skin Cancer in Dark - Skin Patient : A Case Report

Non-melanoma skin cancer is reported to be a cancer with highest prevalence in the world. Different risk factors have been identified, e.g., Genetic factors, skin-type, ethnicity, and iatrogenic. The main iatrogenic factors are radiation and drugs, mainly immunosuppressive medications, and oral psoralen and ultraviolet-A (PUVA). It is known in the literature that exposure to more than 250 sessions of PUVA could be a risk for developing skin cancer. However, it was reported in fair skin patients. Herein, we report for the first time, a PUVA-induced basal cell cancer in a type-4 skin patient after receiving 400 sessions.

Systematic Analysis of Transcriptomic Profile of Renal Cell Carcinoma under Long-Term Hypoxia Using Next-Generation Sequencing and Bioinformatics.

Patients with clear cell renal cell carcinoma (ccRCC) are often diagnosed with both von Hippel-Lindau (VHL) mutations and the constitutive activation of hypoxia-inducible factor-dependent signaling. In this study, we investigated the effects of long-term hypoxia in 786-O, a VHL-defective renal cell carcinoma cell line, to identify potential genes and microRNAs associated with tumor malignancy. The transcriptomic profiles of 786-O under normoxia, short-term hypoxia and long-term hypoxia were analyzed using next-generation sequencing. The results showed that long-term hypoxia promoted the ability of colony formation and transwell migration compared to normoxia. In addition, the differentially expressed genes induced by long-term hypoxia were involved in various biological processes including cell proliferation, the tumor necrosis factor signaling pathway, basal cell carcinoma and cancer pathways. The upregulated (L1CAM and FBN1) and downregulated (AUTS2, MAPT, AGT and USH1C) genes in 786-O under long-term hypoxia were also observed in clinical ccRCC samples along with malignant grade. The expressions of these genes were significantly correlated with survival outcomes in patients with renal cancer. We also found that long-term hypoxia in 786-O resulted in decreased expressions of hsa-mir-100 and hsa-mir-378 and this effect was also observed in samples of metastatic ccRCC compared to samples of non-metastatic ccRCC. These findings may provide a new direction for the study of potential molecular mechanisms associated with the progression of ccRCC.

Videodermoscopy and Curettage: The Value of Simple Procedures During Mohs Surgery.

Mohs surgery (MS) is regarded as one of the most efficient surgical procedures for the treatment of skin tumors. Delineating tumor margins accurately is important in limiting broad excisions during conventional surgery and in reducing the number of stages during Mohs procedure. This study aimed to evaluate the role of 2 simple procedures, curettage and videodermoscopy (VDS), in determining margins during MS for the treatment of basal cell carcinoma (BCC) of the head and neck. The use of both procedures offered a good intraoperative margin definition and consequently small surgical defects in 197 patients affected by BCC. Recurrences in basal cell cancers, which included both primary and recurrent lesions, occurred less frequently than in the institution's previous experience, appearing in only 8 of 197 cases (approx. 4%). In the authors' experience, both VDS and curettage were found advantageous in delineating tumor margins while treating BCC with MS.

Genomic Stability in Syndromic Basal Cell Carcinoma

Basal cell cancers (BCCs) are characterized by upregulation of Hedgehog pathway through loss of PTCH1 or activation of SMO, and SMO inhibitors, such as vismodegib, are effective therapies for advanced BCCs. Although most BCCs are sporadic, rare individuals with basal cell nevus syndrome (BCNS) harbor germline defects in PTCH1 and develop up to hundreds of tumors that are histopathologically indistinguishable from sporadic BCCs. Interestingly, BCNS-BCCs are more responsive to SMO inhibitors than sporadic BCCs, with minimal development of resistance. Given differences in clinical course and therapy response, we sought to characterize BCCs in the setting of BCNS. We found that BCNS individuals with low tumor burden demonstrated significantly fewer UV signature somatic mutations and lower overall somatic mutational load compared to BCNS individuals with high burden, supporting a role of UV exposure in driving BCC development in BCNS individuals. However, compared with sporadic BCCs, BCNS-BCCs have a significantly lower mutational load, lower proportion of UV mutagenesis, increased genomic stability, and harbor fewer functionally resistant SMO mutations at baseline, explaining why BCNS-BCCs lack intrinsic resistance to SMO inhibitors. BCNS-BCCs appear to have reduced mutator phenotype compared with sporadic BCCs, which may contribute to their relatively more indolent clinical course and responsiveness to therapy.

Individualized surface brachytherapy for the treatment of synchronous/metachronous multifocal basal cell cancer of the face

Individualized surface brachytherapy for the treatment of synchronous/metachronous multifocal basal cell cancer of the face

D EMOGRAPHIC CHARACTERISTICS OF BASAL CEL L CARCINOMA: A RETROSPECTIVE STUDY OF 1884 LESIONS

Basal cell carcinoma represents one of the most frequent skin cancers, accounting for around 75% of all skin cancers. Numerous etiological factors contribute to its development (from the genetics to sun exposure). To present the demographic characteristics and distribution of basal cell carcinoma and to evaluate the topography of lesions and their correlations with gender, age, location, size and recurrence rate. This retrospective study included 1734 patients with 1884 lesions, treated at the Clinic of Plastic and Reconstructive Surgery at the Clinical Center Nis, from January 2012 to December 2016. The following parameters were evaluated: age, gender, location, size, histologic type, margin of excision and recurrence rate. Out of the total of 1884 tumors, there were 1621 primary and 263 recurrent cases. High risk localizations included 82.8% of primary and 68.4% of recurrent tumors. With respect to gender, primary tumors were present in 56% of men and 44% of women, while recurrent tumors were present in 41.8% of men and 58.2% of women. Concerning the tumor size, 85.3% of primary and 72.6% of recurrent tumors had a maximum of 2 cm in diameter, whereas 14.7% of primary and 27.4% of recurrent tumors had a diameter of over 2 cm. Complete excision represents a key surgical treatment of basal cell skin cancer. The obtained algorithm can be a useful guide for the monitoring and surgical treatment of basal cell skin cancer.

Mutations in ACTRT1 and its enhancer RNA elements lead to aberrant activation of Hedgehog signaling in inherited and sporadic basal cell carcinomas.

Basal cell carcinoma (BCC), the most common human cancer, results from aberrant activation of the Hedgehog signaling pathway. Although most cases of BCC are sporadic, some forms are inherited, such as Bazex-Dupré-Christol syndrome (BDCS)-a cancer-prone genodermatosis with an X-linked, dominant inheritance pattern. We have identified mutations in the ACTRT1 gene, which encodes actin-related protein T1 (ARP-T1), in two of the six families with BDCS that were examined in this study. High-throughput sequencing in the four remaining families identified germline mutations in noncoding sequences surrounding ACTRT1. These mutations were located in transcribed sequences encoding enhancer RNAs (eRNAs) and were shown to impair enhancer activity and ACTRT1 expression. ARP-T1 was found to directly bind to the GLI1 promoter, thus inhibiting GLI1 expression, and loss of ARP-T1 led to activation of the Hedgehog pathway in individuals with BDCS. Moreover, exogenous expression of ACTRT1 reduced the in vitro and in vivo proliferation rates of cell lines with aberrant activation of the Hedgehog signaling pathway. In summary, our study identifies a disease mechanism in BCC involving mutations in regulatory noncoding elements and uncovers the tumor-suppressor properties of ACTRT1.

Hypofractionated radiation therapy for basal and squamous cell skin cancer: A meta-analysis

PurposeTo characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell cancers (BCCs/SCCs). MethodsA PICOS/PRISMA/MOOSE selection protocol was performed to identify 344 articles published between 1985–2016 evaluating patients with T1–2 N0 SCCs/BCCs treated with definitive RT. Biologically equivalent doses with α/β=3 (BED3s) were calculated. The primary endpoint was post-treatment cosmesis. Mixed effects regression models were used to estimate weighted linear relationships between BED3 and cosmetic outcomes. ResultsA total of 21 studies were identified detailing the treatment of 9729 skin BCC/SCC patients, across seven countries, with external beam RT (n=9255) or brachytherapy (n=474). Median follow-up was 36months (range: 12–77). Median dose was 45Gy/11 fractions (interquartile range: 37.5Gy/6–55Gy/18) at 4Gy/fraction (interquartile range: 2.5–6Gy); most hypofractionated 18.75Gy/1. There was a trend to decreased “good” cosmesis with higher total dose: −3.4% “good” cosmesis/10Gy BED3, p=0.01. Similarly, there was a trend to increased “fair” cosmesis with higher dose: +3.8% “fair” cosmesis/10Gy BED3,p=0.006. At a BED3 of 100Gy, the expected rate of “good” cosmesis is 79% (95% confidence interval: 70%, 88%). Hypofractionated schedules produced similar cosmesis to conventionally fractionated schedules, at the same BED3. Fewer than 8% of patients experienced “poor” cosmesis, independent of dose or fractionation regimen. ConclusionHypofractionated RT has favorable cosmesis for patients with skin BCCs/SCCs. We recommend clinicians consider these commonly-used regimens, which all have BED3 of ∼100Gy: 50Gy/15 fractions, 36.75Gy/7 fractions, or 35Gy/5 fractions, as they result in “good” cosmesis in 80% of patients.

Extended Follow-up of Patients Treated With Bendamustine for Lymphoid Malignancies.

Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR]). Patients who did not achieve a CR or PR did not respond well to subsequent treatments. Malignancies following bendamustine were diagnosed in 11% (21) of patients (first line [7] and salvage [14]), including squamous (8) or basal cell (4) skin cancers; prostate cancer (3), renal cancer (3), bladder cancer (2), melanoma (2), lung cancer (1), and histiocytic sarcoma (1). There were no occurrences of therapy-related myelodysplastic syndrome or acute myelogenous leukemia reported. Infections occurred in 63% of patients; however, no deaths were attributable to bendamustine. Bendamustine is an effective therapy with limited long-term sequelae in patients with lymphoid malignancies.

Response of germline and somatic smoothened (SMO) mutations in non-small cell lung cancer (NSCLC) to hedgehog inhibitor vismodegib.

9062 Background: Smoothened (SMO) gene somatic mutations activate hedgehog signaling in basal cell cancers (BCC) and medulloblastomas but have not been reported in NSCLC. We detected somatic and germline SMOmutations in NSCLC patients (A-C) and sought to characterize the mutations further. Methods: We performed tumor/blood germline sequencing of SMO mutations, familial germline mutation testing (saliva specimens), somatic mutation analysis of TCGA lung carcinoma datasets, and germline mutation analysis of the TCGA and 3 additional large cohorts (n = 1933). To evaluate the functional significance of SMOP641A, HCC4011 lung cancer cells were transfected with a wild-type SMO or SMOP641A expression vector and a predictive model was created. Results: NSCLC SMOP641A in vitro activated the hedgehog pathway, and vismodegib/cyclopamine inhibited tumor cell growth. Structural modeling suggests that SMO P641A induces conformational changes and disrupts PTCH-SMO interaction leading to constitutive activation. In the NSCLC TCGA databases, somatic SMO mutations occur 1.7%. In the overall TCGA database, germline SMO P641A occurred in 0.11% of cancer patients (multiple cancers) compared with 0% in cancer-free individuals. Patient A (never-smoking SCC) had a 46% RECIST reduction within 6 weeks for 6 months on vismodegib. His 3-generation family pedigree identified germline SMOP641A in one daughter (who developed BCC early). Two additional NSCLC patients (B – germline P641A and C –M525L received vismodegib; B initially stabilized but stopped vismodegib after 14 weeks for toxicity while patient C had no response. Conclusions: SMO mutations are targetable, potentially heritable, oncogenic drivers in NSCLC and other cancers. Tumor genetic profiling should consider including SMO gene, especially in never-smoking lung SCC patients. Additional studies are needed to define the role of germline/somatic SMO alterations in promoting carcinogenesis, interactions with P53 alterations, and the responsiveness of different SMO mutations to hedgehog inhibitors. Currently, the ongoing ECOG-ACRIN MATCH study (NCT02465060) treats SMO/PTCH mutated patients with vismodegib.