Surgery and Adjuvant Radiotherapy in Patients with Cutaneous Head and Neck Squamous Cell Carcinoma Metastatic to Lymph Nodes: Combined Treatment Should be Considered Best Practice

Veness, Michael J.; Morgan, Gary J.; Palme, Carsten E.; Gebski, Val

doi:10.1097/01.mlg.0000158349.64337.ed

Cited by 269 publications

(257 citation statements)

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“…83% of immunosuppressed patients in the SCC group had poor outcomes. In reported series of SCC patients, the incidences of metastatic disease do not exceed 16% [4] and the reported incidence of recurrent disease is 28% [8]. In our study, immunosuppressed SCC patients had a higher incidence of poor outcomes (83%) than non-immunosuppressed patients (67%), but the difference did not reach statistical significance.…”

Section: Discussioncontrasting

confidence: 69%

Poor Outcomes in Head and Neck Non-Melanoma Cutaneous Carcinomas

Huoh¹,

Wang

2011

TOOTORJ

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Abstract:Objectives: Head and neck nonmelanoma cutaneous carcinomas (NMCC) may have poor outcomes, such as metastasis and recurrence. It remains unclear which patients are at increased risk for poor outcomes. We characterize a population of NMCC seen in a head and neck surgical practice. We sought to identify predictors of poor outcome in head and neck NMCC.Study Design: A retrospective cohort study of 161 patients with head and neck NMCC who presented to a university based otolaryngology-head and neck surgery practice over a 13 year period was performed. The study group included 127 men and 34 women, age range: 33 -92 years. Subjects and Methods:Tumor characteristics of the study population were recorded, and statistical analysis and KaplanMeier survival calculations were performed to determine predictors of poor outcomes.Results: 113 squamous cell carcinomas (SCC) and 48 basal cell carcinomas (BCC) were identified. Among SCC patients, there was a 44% incidence of metastasis and a 47% incidence of recurrence. Among BCC patients, there was a 10% incidence of metastasis and a 50% incidence of recurrence. Twenty percent of SCC patients had a history of immunosuppression. Among SCC patients with immunosuppression, 83% had metastasis or recurrence. Survival for SCC patients with metastatic disease was significantly worse than patients without metastases. The presence of parotid metastases in SCC conferred a survival advantage when compared to other sites of metastases. Conclusion:The incidence of poor outcomes in NMCC was higher in our series than reported in the literature. Survival patterns of our study parallel those of similar studies in the literature.

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Section: Discussioncontrasting

confidence: 69%

Poor Outcomes in Head and Neck Non-Melanoma Cutaneous Carcinomas

Huoh¹,

Wang

2011

TOOTORJ

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“…3 one metastasis contained an additional silent mutation which is unlikely to affect the protein, and one metastasis contained an additional splice site mutation. 4 one metastasis also contained a mutation in intron 1A which is unlikely to affect the protein. 5 one metastasis contained an additional silent mutation (case with positive p14 immunostaining).…”

Section: P16mentioning

confidence: 99%

“…1,2 The outcome of these patients once metastasized is poor, with a 5-year survival rate between 25 and 50%. 3,4 Genetic alterations in CSCCs which might serve as prognostic biomarkers are not well investigated.TP53 mutations are the most frequent genetic alterations in CSCC with incidences of up to 50%. 5,6 TP53 mutations are early events in skin carcinogenesis, with a similar mutation frequency of 50% in actinic keratosis, a precancerous skin lesion that potentially can progress to CSCC.…”

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confidence: 99%

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CDKN2A but not TP53 mutations nor HPV presence predict poor outcome in metastatic squamous cell carcinoma of the skin

Küsters‐Vandevelde

Leeuwen

Verdijk

et al. 2009

Intl Journal of Cancer

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Genetic alterations in metastatic cutaneous squamous cell carcinoma (CSCC) which might serve as prognostic biomarkers are not well investigated. We investigated the mutation status and protein expression of the CDKN2A (INK4a-ARF) and TP53 genes in metastatic CSCCs and correlated this with clinicopathological variables, HPV presence, and survival data. Sequence analysis was performed on formalin-fixed and paraffin-embedded tissue of 35 metastases and their primary tumors, and was correlated with immunohistochemical stainings for p53, p16 and p14. Beta-PV and alpha-PV DNA was detected using PCRbased assays. Kaplan-Meier and Cox regression methods were used for survival assessment. CDKN2A was mutated in 31% of the metastases and their primary tumors, while the TP53 gene was mutated in 51% of the metastases. P53 protein expression was significantly associated with missense type of mutations (p 5 0.002). No persistent HPV types were detected. CDKN2A mutations were significantly associated with disease-specific death (p 5 0.001). A significant difference was observed in disease-specific survival between patients with or without a CDKN2A mutation (p 5 0.010), while this was not the case for TP53. At univariate Cox's regression analysis tumor size (p 5 0.010), invasion depth (p 5 0.030) and CDKN2A mutations (p 5 0.040) were significantly related to shorter disease-specific survival. At multivariate Cox's regression only tumor size had an adverse effect on survival (p 5 0.002). In conclusion, our study indicates that the CDKN2A mutation status might be of prognostic value in metastatic CSCCs. In most cases, CDKN2A and TP53 mutations are early genetic events in CSCC tumorigenesis. The possible role of HPV in metastatic CSCC needs further exploration.Cutaneous squamous cell carcinoma (CSCC) is the second most common malignancy in Caucasians, after basal cell carcinoma, and its incidence is still rising. 1 Generally the risk of metastasis is reported up to 5%, while immunocompromised patients have a larger tendency to metastasize (5-10%). 1,2 The outcome of these patients once metastasized is poor, with a 5-year survival rate between 25 and 50%. 3,4 Genetic alterations in CSCCs which might serve as prognostic biomarkers are not well investigated.TP53 mutations are the most frequent genetic alterations in CSCC with incidences of up to 50%. 5,6 TP53 mutations are early events in skin carcinogenesis, with a similar mutation frequency of 50% in actinic keratosis, a precancerous skin lesion that potentially can progress to CSCC. 7 Mutations in the CDKN2A (INK4a-ARF) locus are reported in CSCC with frequencies ranging up to 24% in sporadic CSCC. [8][9][10] This gene maps to chromosome 9p21, which by alternative transcripts encodes for 2 cell cycle regulatory proteins, p16 INK4a (Exons 1a, 2 and 3) and p14 ARF (Exons 1b, 2 and 3). 10,11 The exact role of the CDKN2A gene in skin carcinogenesis is not well understood. Especially in metastatic CSCCs alterations in the CDKN2A gene have not been investigated. In a small previous stud...

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“…12 Patients who receive that combined treatment achieve a better outcome (increased survival) compared with patients who receive either surgery alone or radiotherapy alone. 13 Currently, there is no model with which to prognosticate the outcome of patients who develop metastatic HN cSCC. By using a large database of patients who were treated with curative intent, we developed a simple model using competing risks analysis that allows clinicians to assign a 3-tiered risk score.…”

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confidence: 99%

Metastatic cutaneous squamous cell carcinoma of the head and neck

Oddone

Morgan

Palme

et al. 2009

Cancer

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118

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BACKGROUND:The authors propose a prognostic score model using a prospective study of patients with regional metastatic cutaneous squamous cell carcinoma of the head and neck.METHODS:Two‐hundred fifty patients were analyzed using a competing risks model to identify risk factors for survival. A risk score was obtained using the significant coefficients from the regression model, and cutoff points were determined that separated the score into 3 risk groups (low risk, moderate risk, and high risk).RESULTS:At a median follow‐up of 54 months (range, 1.3‐212 months) 70 of 250 patients (28%) developed recurrent disease: Most were regional recurrences (51 of 70 patients; 73%) in the treated lymph node basin. After regional recurrence, a majority (73%) died of disease. The following 4 variables were associated significantly with survival: immunosuppression (hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.39‐7.05), treatment (HR, 0.32; 95% CI, 0.16‐0.66), extranodal spread (HR, 9.92; 95% CI, 1.28‐77.09), and margin status (HR, 1.85; 95% CI, 1.85‐3.369); and those 4 variables (immuosuppression, treatment, extranodal spread, and margin status) were used to calculate the ITEM score. The 5‐year risk of dying from disease for patients with high‐risk (>3.0), moderate‐risk (>2.6‐3.0), and low‐risk (≤2.6) ITEM scores were 56%, 24%, and 6%, respectively. Fifty‐six of 250 patients (22%) died from another cause.CONCLUSIONS:Patients who underwent surgery and received adjuvant radiotherapy had a better outcome compared with patients who underwent surgery alone. Patients who had moderate‐ or high‐risk ITEM scores, usually because of extranodal spread and involved excision margins, had a poor outcome. The authors recommend considering these patients for inclusion in adjuvant chemoradiotherapy trials. Cancer 2009. © 2009 American Cancer Society.

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Surgery and Adjuvant Radiotherapy in Patients with Cutaneous Head and Neck Squamous Cell Carcinoma Metastatic to Lymph Nodes: Combined Treatment Should be Considered Best Practice

Abstract: In patients with metastatic cutaneous head and neck SCC, surgery and adjuvant radiotherapy provide the best chance of achieving locoregional control and should be considered best practice.

Cited by 269 publications

References 20 publications

Poor Outcomes in Head and Neck Non-Melanoma Cutaneous Carcinomas

Poor Outcomes in Head and Neck Non-Melanoma Cutaneous Carcinomas

CDKN2A but not TP53 mutations nor HPV presence predict poor outcome in metastatic squamous cell carcinoma of the skin

Metastatic cutaneous squamous cell carcinoma of the head and neck

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