Non-melanoma skin cancer

Madan, Vishal; Lear, John T.; Szeimies, Rolf‐Markus

doi:10.1016/s0140-6736(09)61196-x

Cited by 748 publications

(801 citation statements)

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“…[1][2][3] Cytokines released by the inflammatory cells may promote SCC invasion and progression by stimulating the production of invasion-associated proteinases by tumor cells. Moreover, production of certain cytokines by tumor cells has been shown to regulate the local immune response against tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…At present, no specific molecular markers are available for assessing the progression of premalignant actinic keratoses to invasive cutaneous squamous cell carcinoma (SCC) The incidence of melanoma and nonmelanoma skin cancer is increasing globally. [1][2][3] Nonmelanoma skin cancers, including basal cell carcinoma (approximately 80%) and squamous cell carcinoma (SCC) (approximately 20%), are among the most common cancers worldwide, and SCC has been reported as the second most common cutaneous malignancy in the white population. [1][2][3] Although early excision of cutaneous SCC is associated with a favorable outcome, for patients with metastatic disease (6%), the long-term prognosis is poor.…”

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confidence: 99%

“…[1][2][3] Nonmelanoma skin cancers, including basal cell carcinoma (approximately 80%) and squamous cell carcinoma (SCC) (approximately 20%), are among the most common cancers worldwide, and SCC has been reported as the second most common cutaneous malignancy in the white population. [1][2][3] Although early excision of cutaneous SCC is associated with a favorable outcome, for patients with metastatic disease (6%), the long-term prognosis is poor. 4 Important risk factors for cutaneous SCC include exposure to UV radiation, immunosuppression, and chronic skin ulceration.…”

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confidence: 99%

“…4 Important risk factors for cutaneous SCC include exposure to UV radiation, immunosuppression, and chronic skin ulceration. [1][2][3] An example of the latter is individuals with recessive dystrophic epidermolysis bullosa (RDEB), who often develop rapidly progressing cutaneous SCCs at sites of chronic ulceration and scarring. 5,6 At present, no specific molecular markers for progression of cutaneous SCC are available.…”

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confidence: 99%

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Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Farshchian

Kivisaari

Ala-aho

et al. 2011

The American Journal of Pathology

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The incidence of keratinocyte-derived nonmelanoma skin cancers is increasing worldwide because of cumulative recreational exposure to sunlight. At present, no specific molecular markers are available for assessing the progression of premalignant actinic keratoses to invasive cutaneous squamous cell carcinoma (SCC). We examined the role of the Serpin family in skin SCCs. Expression profiling of cutaneous SCC cell lines (n ‫؍‬ 8) revealed up-regulation of SerpinA1 compared with normal epidermal keratinocytes (n ‫؍‬ 5). Analysis with quantitative RT-PCR showed that the mean level of SerpinA1 mRNA was markedly up-regulated in cutaneous SCC cell lines (n ‫؍‬ 8) compared with in normal keratinocytes. SerpinA1 production by SCC cells was dependent on p38 mitogen-activated protein kinase activity and was upregulated by epidermal growth factor, tumor necrosis factor-␣, interferon-␥, and IL-1␤. Immunostaining of tissue arrays with 148 human tissue samples revealed tumor cell-associated expression of SerpinA1 in 19 of 36 actinic keratoses, 22 of 29 Bowen's disease samples, 67 of 71 sporadic SCCs, and all 12 recessive dystrophic epidermolysis bullosa-associated SCCs examined. Moreover, tumor cell-associated SerpinA1 staining was detected in all chemically induced mouse skin SCCs studied (n ‫؍‬ 17). Overexpression of SerpinA1 mRNA was also detected by quantitative RT-PCR in chemically induced mouse skin SCCs (n ‫؍‬ 14) compared with control tissues (n ‫؍‬ 14). These data identify SerpinA1 as a novel tumor cell-associated biomarker for progression of cutaneous SCCs.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Farshchian

Kivisaari

Ala-aho

et al. 2011

The American Journal of Pathology

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“…Surgery, the primary course of treatment for most BCCs, and radiotherapy are often not viable options in advanced BCC 1, 2, 3. In recent years, hedgehog (Hh) pathway inhibitors (HPIs) were developed to block aberrant Hh signalling that is found in most sporadic BCCs; HPIs have demonstrated efficacy in patients with laBCC and those with mBCC 4, 5, 6, 7, 8, 9, 10, 11, 12, 13…”

Section: Introductionmentioning

confidence: 99%

Long‐term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30‐month analysis of the randomized phase 2 BOLT study

Lear

Migden

Lewis

et al. 2017

Acad Dermatol Venereol

155

183

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BackgroundPatients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difficult‐to‐treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in laBCC based on results from the BOLT trial.ObjectiveTo evaluate long‐term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18‐ and 30‐month analyses.MethodsBOLT (NCT01327053, ClinicalTrials.gov), a double‐blind phase 2 study, enrolled patients from July 2011 until January 2013. Eligible HPI‐treatment–naïve patients with laBCC not amenable to curative surgery/radiotherapy or mBCC were randomized 1 : 2 to sonidegib 200 mg (laBCC, n = 66; mBCC, n = 13) or 800 mg (laBCC, n = 128; mBCC, n = 23). Tumour response was assessed per central and investigator review.ResultsWith 30 months of follow‐up, among patients treated with sonidegib 200 mg (approved dose), objective response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in mBCC. Tumour responses were durable as follows: median duration of response was 26.1 months (central) and 15.7 months (investigator) in laBCC and 24.0 months (central) and 18.1 months (investigator) in mBCC. Five patients with laBCC and three with mBCC in the 200‐mg arm died. Median overall survival was not reached in either population; 2‐year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efficacy was similar regardless of aggressive or non‐aggressive histology. Sonidegib 200 mg continued to have a better safety profile than 800 mg, with lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs. 40.0%).ConclusionSonidegib continued to demonstrate long‐term efficacy and safety in these populations. These data support the use of sonidegib 200 mg per local treatment guidelines.

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Recurrence After Treatment of Nonmelanoma Skin Cancer

Chren

Torres²,

Stuart³

et al. 2011

Arch Dermatol

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To determine long-term tumor recurrence rates after treatment of primary nonmelanoma skin cancer (NMSC). Data are currently insufficient to permit evidence-based choices among treatments for NMSC.Design: Prospective study of an inception cohort observed for a median of 6.6 years after treatment.Setting: Dermatology clinic at a Veterans Affairs hospital. Care was provided by dermatology resident or attending physicians.Patients: Consecutive sample of all 495 patients with 616 primary NMSCs diagnosed in 1999 and 2000 and treated with electrodessication and curettage (ED&C), excision, or Mohs surgery. Follow-up was available for 608 tumors (99%).Main Outcome Measure: Tumor recurrence, deter-mined by medical record review, with validation by clinical examination. Results:The mean age at diagnosis was 71 years; 97% were men. Overall, 127 tumors were treated with ED&C (20.9%); 309 with excision (50.8%); and 172 with Mohs surgery (28.3%). Over the course of the study, 21 tumors recurred (3.5% [95% confidence interval (CI), 2.2%-5.2%]): 2 after ED&C (1.6% [95% CI, 0.2%-5.6%]), 13 after excision (4.2% [95% CI, 2.2%-7.1%]), and 6 after Mohs surgery (3.5% [95% CI, 1.3%-7.4%]).Conclusions: Recurrence of primary NMSC after treatment occurred in less than 5% of tumors. The recurrence rate after ED&C was lower than expected, and the recurrence rate after Mohs surgery was higher than expected. These findings may be related to the risk for recurrence in the treatment groups.

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Non-melanoma skin cancer

Cited by 748 publications

References 140 publications

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Long‐term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30‐month analysis of the randomized phase 2 BOLT study

Recurrence After Treatment of Nonmelanoma Skin Cancer

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