Time to Treatment and Disease-free Survival of Patients With High-risk Head-neck Cutaneous Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to investigate the association between time to treatment (defined as date of pathological diagnosis to date of start treatment) and disease free survival in patients with high risk cutaneous squamous cell carcinoma in the head-neck region.

Detailed Description
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Skin cancer is the most common type of cancer in the Netherlands. Cutaneous squamous cell carcinoma (cSCC) accounts for 20% of all cutaneous malignancies. The incidence of cSCC has been rising over the years in the Netherlands, from 8,966 new cSCCs cases registered in 2012 to 14,873 cases in 2022. cSCCs mostly involve patients aged 75 years and older. Since exposure to UV radiation is the main risk factor for the development, cSCCs particularly occur on sun exposed areas of the skin such as in the head-neck region and the extremities. Other risk factors include a Fitzpatrick skin type I or II, use of immunosuppression, exposure to arsenic, and infection with human papilloma virus. Risk of metastasis and recurrence in general cSCCs are 2.6-5% and 1.9-3.7%, respectively. However, these risk ratios may increase to 37% in high-risk cSCCs. High risk cSCCs are defined as cSCCs with risk factors for development of metastatic disease or recurrence, e.g. poor histological differentiation, perineural/lymphovascular infiltration, diameter ≥20 mm. Due to the increasing incidence, advanced age, risk of metastasis and recurrence, and the high risk-location in the head-neck region related to functional and cosmetic importance, high-risk cSCCs in the head-neck region (high-risk HNcSCCs) require complex and multidisciplinary care. Therefore, care pathways have been developed. An important part of these care pathways are waiting times and, in particular, the time to treatment. For example, in mucosal head-neck tumors, prolonged waiting times have been described to be associated with reduced survival rates. This led to the hypothesis that prolonged waiting times result result in lower survival rates for patients with high-risk HNcSCCs. This study aimed to investigate the association between time to treatment defined as date of pathological diagnosis to date of start treatment) and disease free survival in patients with high risk HNcSCCs.

Official Title
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Association Between Time to Treatment and Disease-free Survival of Patients With High-risk Cutaneous Squamous Cell Carcinoma in the Head and Neck Region.

Conditions
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Carcinoma, Squamous Cell, Skin Cancer, Carcinoma, Squamous Cell, Skin, Carcinoma, Squamous Cell of Head and Neck, Recurrence, Metastasis

Intervention / Treatment
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* Other: Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient diagnosed with high-risk HNcSCCs, defined as T2 to T4 HNcSCC Treated in the Maastricht University Medical Center+ (MUMC+) or Radboud University Medical Center (RadboudUMC) Treated between 2010 to 2018 Exclusion Criteria: Patients aged younger than 18 years Patients with a T1 HNcSCC Patients with recurrence or metastatic disease of a previously treated HNcSCC

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Short time to treatment (<30 days)<br>Patients with high-risk HNcSCC with a time to treatment (date of pathological diagnosis to date of start treatment) of less than 30 days. | Other: Treatment<br>* Patients were treated with surgery, radiotherapy or surgery with postoperative radiotherapy.<br>|
| Long time to treatment (30 days or more)<br>Patients with high-risk HNcSCC with a time to treatment (date of pathological diagnosis to date of start treatment) of 30 days or more. | Other: Treatment<br>* Patients were treated with surgery, radiotherapy or surgery with postoperative radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association time to treatment and survival | The association between time to treatment (in days) and disease-free survival (e.g. no recurrence or metastasis occurred), expressed as adjusted hazard ratio with 95% confidence intervals and p values, from multivariate Cox regression analysis. | 5 years after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5 year disease free survival between short and long time to treatment | 5 year cumulative probability of disease free survival in patients with a short (<30 days) versus long (30 days or more) time to treatment, presented as percentages with 95% confidence intervals and p-values using Kaplan Meier survival curves and the log-rank test. | 5 years after treatment | 
| 5 year disease specific survival between short and long time to treatment | 5 year cumulative probability of disease specific survival in patients with a short (<30 days) versus long (30 days or more) time to treatment, presented as percentages with 95% confidence intervals and p-values using Kaplan Meier survival curves and the log-rank test. | 5 years after treatment | 
| 5 year overall survival between short and long time to treatment | 5 year cumulative probability of overall survival in patients with a short (<30 days) versus long (30 days or more) time to treatment, presented as percentages with 95% confidence intervals and p-values using Kaplan Meier survival curves and the log-rank test. | 5 years after treatment | 
| 5 year disease free survival between participating centers | 5 year cumulative probability of disease free survival in patients treated at the Maastricht University Medical Center+ versus Radboud University Medical Center, presented as percentages with 95% confidence intervals and p-values using Kaplan Meier survival curves and the log-rank test. | 5 years after treatment | 
| 5 year disease specific survival between participating centers | 5 year cumulative probability of disease specific survival in patients treated at the Maastricht University Medical Center+ versus Radboud University Medical Center, presented as percentages with 95% confidence intervals and p-values using Kaplan Meier survival curves and the log-rank test. | 5 years after treatment | 
| 5 year overall survival between participating centers | 5 year cumulative probability of overall survival in patients treated at the Maastricht University Medical Center+ versus Radboud University Medical Center, presented as percentages with 95% confidence intervals and p-values using Kaplan Meier survival curves and the log-rank test. | 5 years after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Disease free survival, Survival, Multicenter, Time to treatment, Waiting times