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

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

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.

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.