Immune System Modulation and Outcome in High-risk cSCC Treated With Surgery and Radiotherapy

Study Overview
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Brief Summary
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Treatment with adjuvant radiotherapy modulates immune system in many diseases as witnessed by dynamic changes of humoral and cellular immunity. Moreover, the persistent lymphopenia after radiation therapy is a negative prognostic factor. This study is aimed to explore the changes in immune-cell populations during radiotherapy given as adjuvant treatment for high-risk cutaneous squamous cell carcinomas and to correlate them with patient's outcome.

Official Title
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Immune System Modulation and Outcome in High-risk Cutaneous Squamous Cell Carcinoma Treated With Surgery and Radiotherapy: a Prospective Study

Conditions
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Squamous Cell Carcinoma of the Skin

Intervention / Treatment
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* Other: Peripheral blood sampling in order to evaluate changes in the circulating immune population


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Signed written informed consent. Histologically confirmed diagnosis of cSCC. cSCC categorized as high risk according to ASTRO Guidelines: close or positive margins that cannot be corrected with further surgery (secondary to morbidity or adverse cosmetic outcome). gross perineural spread, as identified by radiological or pathological assessment. disease recurrence after a prior margin-negative resection. pathological stage T3 and T4. desmoplastic or infiltrative tumors in the setting of chronic immunosuppression at pathological exam, cSCC involving regional lymphnodes, with the exception of a single, small (<3 cm) cervical lymph node harboring carcinoma, without extracapsular extension. cSCC addressed to adjuvant radiotherapy as per clinical practice (a complete post-operative treatment should be administered with 50-54 or 60-66 Gy depending on the margin status). Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. Exclusion Criteria: cSCC not eligible for surgery. cSCC not eligible for adjuvant radiotherapy for any condition depending on disease characteristics or patient characteristics, co-morbidities or refusal. Any concurrent investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent treatment with chemotherapy for the purpose of cSCC cure. History or current evidence of any condition that, in the opinion of the treating investigator, might interfere with the subject's participation for the full duration of the trial. Any major surgery, different from that planned for the protocol, in the 15 days before the protocol starting. Any radiotherapy treatment in the 28 days before the protocol starting Pregnant or breastfeeding.

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 |
| --- | --- |
| Patient with cSCC addressed to adjuvant radiotherapy as per clinical practice<br>The aim of the study is to evaluate patient's outcome according to the post-radiation lymphocytes count and to the changes induced in the immune cell population by a loco-regional treatment as radiotherapy. The way to objectivate these results is to collect some blood samples and analyze them. | Other: Peripheral blood sampling in order to evaluate changes in the circulating immune population<br>* Eveluation: circulating T cells CD3+CD8+ and CD3+CD4+, absolute lymphocyte count (ALC) and neutrophil counts (ANC) and neutrophil/lymphocyte ratio (NLR), Treg lymphocytes, Naïve/Memory T lymphocytes CD4+ and CD8+,myeloid-derived suppressor cells, Plasmacytoid Dendritic Cells NK cells dimension and bright, NKT cells, Myeloid Dendritic cells, Monocytes subsets, B lymphocytes ,Analysis of plasma cytokines (TNFalpha, TGFbeta, IL-6, IL-10) by ELISA,FN signature: real-time PCR on mRNA from peripheral blood mononuclear cells (PBMCs)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) of patients with ALC < 500 cells/mL 28 days after the end of radiotherapy treatment | Disease-free survival (DFS) of patients with ALC < 500 cells/mL 28 days after the end of radiotherapy treatment | 28 days after the end of radiotherapy treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of changes (Δ) in the circulating immune-cells population before the start of radiotherapy and 28 days after the end of radiotherapy | Evaluation of changes (Δ) in the circulating immune-cells population before the start of radiotherapy and 28 days after the end of radiotherapy. Correlation between DFS and circulating immune cell population | Before and 28 days after the end of radiotherapy treatment |