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

Squamous Cell Carcinoma of the Skin Clinical Trial

— HR-cSCC  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05246228
• Other study ID #: ASST Spedali Civili di Brescia
• Status: Not yet recruiting
• Start date: March 1, 2022
• Est. completion date: December 30, 2025

Study information

• Verified date: February 2022
• Source: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Contact: Aldo Roccaro, MD
• Phone: +39 0303996851
• Email: coordinamento.ricerca[@]asst-spedalicivili.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 42
• Est. completion date: December 30, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of the Skin

Intervention

Other:
• Peripheral blood sampling in order to evaluate changes in the circulating immune population
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)

Locations

Country	Name	City	State
n/a

Sponsors (8)

Lead Sponsor	Collaborator
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	ASST Bergamo Ovest, ASST Valcamonica, Azienda Ospedaliera di Padova, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, IRCCS Sacro Cuore Don Calabria di Negrar, Istituti Ospitalieri di Cremona, San Gerardo Hospital

References & Publications (17)

Bottomley MJ, Thomson J, Harwood C, Leigh I. The Role of the Immune System in Cutaneous Squamous Cell Carcinoma. Int J Mol Sci. 2019 Apr 24;20(8). pii: E2009. doi: 10.3390/ijms20082009. Review. — View Citation

Carvalho HA, Villar RC. Radiotherapy and immune response: the systemic effects of a local treatment. Clinics (Sao Paulo). 2018 Dec 10;73(suppl 1):e557s. doi: 10.6061/clinics/2018/e557s. Review. — View Citation

Farberg AS, Hall MA, Douglas L, Covington KR, Kurley SJ, Cook RW, Dinehart SM. Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management. Curr Med Res Opin. 2020 Au — View Citation

Harris BN, Pipkorn P, Nguyen KNB, Jackson RS, Rao S, Moore MG, Farwell DG, Bewley AF. Association of Adjuvant Radiation Therapy With Survival in Patients With Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck. JAMA Otolaryngol Head Neck Surg — View Citation

Jarosz-Biej M, Smolarczyk R, Cichon T, Kulach N. Tumor Microenvironment as A "Game Changer" in Cancer Radiotherapy. Int J Mol Sci. 2019 Jun 29;20(13). pii: E3212. doi: 10.3390/ijms20133212. Review. — View Citation

Kuo P, Bratman SV, Shultz DB, von Eyben R, Chan C, Wang Z, Say C, Gupta A, Loo BW Jr, Giaccia AJ, Koong AC, Diehn M, Le QT. Galectin-1 mediates radiation-related lymphopenia and attenuates NSCLC radiation response. Clin Cancer Res. 2014 Nov 1;20(21):5558- — View Citation

Lin 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. — View Citation

Litchman GH, Fitzgerald AL, Kurley SJ, Cook RW, Rigel DS. Impact of a prognostic 40-gene expression profiling test on clinical management decisions for high-risk cutaneous squamous cell carcinoma. Curr Med Res Opin. 2020 Aug;36(8):1295-1300. doi: 10.1080/ — View Citation

Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K — View Citation

Pike LRG, Bang A, Mahal BA, Taylor A, Krishnan M, Spektor A, Cagney DN, Aizer AA, Alexander BM, Rahma O, Balboni T, Ott PA, Hodi FS, Schoenfeld JD. The Impact of Radiation Therapy on Lymphocyte Count and Survival in Metastatic Cancer Patients Receiving PD — View Citation

Porceddu SV, Bressel M, Poulsen MG, Stoneley A, Veness MJ, Kenny LM, Wratten C, Corry J, Cooper S, Fogarty GB, Collins M, Collins MK, Macann AMJ, Milross CG, Penniment MG, Liu HY, King MT, Panizza BJ, Rischin D. Postoperative Concurrent Chemoradiotherapy — View Citation

Porceddu SV, Daniels C, Yom SS, Liu H, Waldron J, Gregoire V, Moore A, Veness M, Yao M, Johansen J, Mehanna H, Rischin D, Le QT. Head and Neck Cancer International Group (HNCIG) Consensus Guidelines for the Delivery of Postoperative Radiation Therapy in C — View Citation

Que 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. Review. — View Citation

Stratigos 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, Mor — View Citation

Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, Dreno B, Fargnoli MC, Forsea AM, Frenard C, Harwood C?, Hauschild A, Hoeller C, Kandolf-Sekulovic L, Kaufmann R, Kelleners-Smeets NW, Malvehy J, Del Marmol V, Middleton MR, Moreno-Ramir — View Citation

Wild AT, Ye X, Ellsworth SG, Smith JA, Narang AK, Garg T, Campian J, Laheru DA, Zheng L, Wolfgang CL, Tran PT, Grossman SA, Herman JM. The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancr — View Citation

Wysong A, Newman JG, Covington KR, Kurley SJ, Ibrahim SF, Farberg AS, Bar A, Cleaver NJ, Somani AK, Panther D, Brodland DG, Zitelli J, Toyohara J, Maher IA, Xia Y, Bibee K, Griego R, Rigel DS, Meldi Plasseraud K, Estrada S, Sholl LM, Johnson C, Cook RW, S — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluation of changes (?) in the circulating immune-cells population before the start of radiotherapy and 28 days after the end of radiotherapy	Evaluation of changes (?) 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