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

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.

Sex

All

Minimum age

18 Years

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.

• BACKGROUNDLin AJ, Gang M, Rao YJ, Campian J, Daly M, Gay H, Oppelt P, Jackson RS, Rich J, Paniello R, Zevallos J, Hallahan D, Adkins D, Thorstad W. Association of Posttreatment Lymphopenia and Elevated Neutrophil-to-Lymphocyte Ratio With Poor Clinical Outcomes in Patients With Human Papillomavirus-Negative Oropharyngeal Cancers. JAMA Otolaryngol Head Neck Surg. 2019 May 1;145(5):413-421. doi: 10.1001/jamaoto.2019.0034. PMID 30920592
• RESULTQue SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018 Feb;78(2):237-247. doi: 10.1016/j.jaad.2017.08.059. PMID 29332704
• RESULTStratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, Dreno B, Fargnoli MC, Forsea AM, Frenard C, Harwood CAlpha, Hauschild A, Hoeller C, Kandolf-Sekulovic L, Kaufmann R, Kelleners-Smeets NW, Malvehy J, Del Marmol V, Middleton MR, Moreno-Ramirez D, Pellecani G, Peris K, Saiag P, van den Beuken-van Everdingen MHJ, Vieira R, Zalaudek I, Eggermont AMM, Grob JJ; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC). European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer. 2020 Mar;128:60-82. doi: 10.1016/j.ejca.2020.01.007. Epub 2020 Feb 26. PMID 32113941
• RESULTStratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, Dreno B, Concetta Fargnoli M, Forsea AM, Frenard C, Harwood CA, Hauschild A, Hoeller C, Kandolf-Sekulovic L, Kaufmann R, Kelleners-Smeets NWJ, Malvehy J, Del Marmol V, Middleton MR, Moreno-Ramirez D, Pellecani G, Peris K, Saiag P, van den Beuken-van Everdingen MHJ, Vieira R, Zalaudek I, Eggermont AMM, Grob JJ; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC). European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment. Eur J Cancer. 2020 Mar;128:83-102. doi: 10.1016/j.ejca.2020.01.008. Epub 2020 Feb 26. PMID 32113942