A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma

Abstract Background Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort. Methods Patients with unresectable locally and or regionally advanced pathologically confirmed cSCC (stage III-IVa) deemed fit for CRIO by consensus of the Multidisciplinary meeting will be eligible. In the first stage of a two-stage minimax design, we aim to recruit a total of 15 patients. If fewer than 7 patients achieved a complete response in the first stage, we will conclude the treatment is not more effective than standard treatment. The co-primary endpoints of CRIO are the safety of treatment (acute and late toxicities) and the rate of complete response. Secondary endpoints would include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers (CD73, CD39, PD-1, PD-L1) will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET/CT scan will be explored. Discussion CRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent and adjuvant durvalumab for patients with unresectable stage III-IVa cSCC. Trial registration: Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246)

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A Prospective Study Investigating the Efficacy and Toxicity of Definitive ChemoRadadiation and ImmunOtherapy (CRIO) in Locally and/or Regionally Advanced Cutaneous Squamous Cell Carcinoma.

10.21203/rs.3.rs-88311/v1 ◽

2020 ◽

Author(s):

Charles Lin ◽

Trishna Ballah ◽

Michelle Nottage ◽

Karen Hay ◽

Benjamin Chua ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prospective Study ◽

Cell Carcinoma ◽

Squamous Cell ◽

Locally Advanced ◽

Cutaneous Squamous Cell Carcinoma ◽

Significant Activity ◽

Clinical Trial Registry ◽

Curative Intent ◽

Regional Metastases

Abstract Background: Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort. Our hypothesis is that >70% of patients with locally-advanced primary disease or regional metastases can be safely treated for cure using ChemoRadiation and ImmunOtherapy (CRIO) compared to the null hypothesis of ≤50%. Methods: Patients with unresectable locally and or regionally advanced pathologically confirmed cSCC deemed suitable for CRIO by consensus of the Head and Neck Multidisciplinary meeting will be eligible. We aim to accrue a total of 15 patients. The co-primary endpoints of CRIO will be the safety of treatment and the complete response rate. Secondary endpoints will include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET scan will be explored.Discussion: CRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent durvalumab for patients with inoperable locally advanced cSCC.Trial registration Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246)

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Faculty Opinions recommendation of Prospective study of sentinel node biopsy for high-risk cutaneous squamous cell carcinoma of the head and neck.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725486356.793508151 ◽

2015 ◽

Author(s):

Ian Maher ◽

Stephanie R Jackson Cullison

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Prospective Study ◽

Sentinel Node ◽

Cell Carcinoma ◽

Head And Neck ◽

Sentinel Node Biopsy ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Node Biopsy

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Prognostic Impact of Perineural Invasion in Cutaneous Squamous Cell Carcinoma: Results of a Prospective Study of 1,399 Tumors

Journal of Investigative Dermatology ◽

10.1016/j.jid.2020.01.035 ◽

2020 ◽

Vol 140 (10) ◽

pp. 1968-1975 ◽

Cited By ~ 3

Author(s):

Konrad Haug ◽

Helmut Breuninger ◽

Gisela Metzler ◽

Thomas Eigentler ◽

Martin Eichner ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prospective Study ◽

Cell Carcinoma ◽

Squamous Cell ◽

Perineural Invasion ◽

Cutaneous Squamous Cell Carcinoma ◽

Prognostic Impact ◽

A Prospective Study

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Concurrent radiation therapy with programmed cell death protein 1 inhibition leads to a complete response in advanced cutaneous squamous cell carcinoma

JAAD Case Reports ◽

10.1016/j.jdcr.2019.06.026 ◽

2019 ◽

Vol 5 (9) ◽

pp. 763-766 ◽

Cited By ~ 4

Author(s):

Poorva Vaidya ◽

Arjun Mehta ◽

Omar Ragab ◽

Sonia Lin ◽

Gino K. In

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Death ◽

Radiation Therapy ◽

Programmed Cell Death ◽

Cell Carcinoma ◽

Squamous Cell ◽

Complete Response ◽

Cutaneous Squamous Cell Carcinoma ◽

Cell Death Protein

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Prospective study of sentinel node biopsy for high-risk cutaneous squamous cell carcinoma of the head and neck

Head & Neck ◽

10.1002/hed.24120 ◽

2015 ◽

Vol 38 (S1) ◽

pp. E884-E889 ◽

Cited By ~ 36

Author(s):

Sinclair M. Gore ◽

Douglas Shaw ◽

Richard C. W. Martin ◽

Wendy Kelder ◽

Kathryn Roth ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Prospective Study ◽

Sentinel Node ◽

Cell Carcinoma ◽

Head And Neck ◽

Sentinel Node Biopsy ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Node Biopsy

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Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8

10.32388/yvpz7a ◽

2020 ◽

Author(s):

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Stage Iii

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Dramatic radiotherapy response of a giant T4 cutaneous squamous cell carcinoma of the scalp with extensive bone destruction: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-03213-6 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Isabella Gruber ◽

Oliver Koelbl

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Antibody Therapy ◽

Bone Destruction ◽

Complete Response ◽

Cutaneous Squamous Cell Carcinoma ◽

Secondary Intention ◽

Sagittal Sinus ◽

Good Cosmetic

Abstract Background Patients with large cutaneous squamous cell carcinoma of the scalp are a treatment challenge. We report a case of dramatic radiotherapy response of a patient with a giant cutaneous squamous cell carcinoma of the scalp with extensive skull destruction and suspected infiltration of the dura mater and superior sagittal sinus. This case is the first report of this kind in the literature that shows that large bone defects can heal with the resolution of tumor and inflammation by secondary intention without surgical reconstruction. We want to put an end to concerns about radiocurability of tumors with extensive bone involvement, and show sustained complete response after definitive radiotherapy and programmed cell death protein-1 inhibiting antibody therapy. Case presentation A 74-year-old White man presented with a 7.2 × 6.8 × 5.5 cm painless tumor on the right parietal region of the scalp. Medical imaging revealed widespread destruction of the skull and suspected infiltration of the dura mater and superior sagittal sinus. Biopsies showed cutaneous squamous cell carcinoma (cT4a cN0 cM0, stage IVA). The patient was treated with a total dose of 60 Gy, at 2 Gy per daily fraction with volumetric modulated arc therapy using 6 megavoltage photons. The biologically effective dose (alpha/beta 10 Gy) was 72 Gy. The tumor response correlated with dose received. The patient had a massive tumor necrosis secondary to tumor shrinkage after 18 fractions (36 Gy, biologically effective dose 43.2 Gy). Leakage of cerebrospinal fluid did not occur. Radiotherapy did not hamper the patient’s quality of life. The patient had a clear regression of the initial tumor on the final day of radiotherapy. The bone defect healed by secondary intention without surgical interventions. The patient achieved a complete response with a good cosmetic result after 82 days follow-up. He started a programmed cell death protein-1 inhibiting antibody therapy with cemiplimab 2 months after radiotherapy, and is now at 10 months follow-up without evidence of recurrence. Conclusion Definitive radiotherapy is a safe and highly effective therapy for giant tumors of the scalp with extensive bone destruction. We report a sustained complete response with a good cosmetic result after secondary wound healing.

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