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CASE REPORT
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Recurrent squamous cell carcinoma of the skin treated with immunotherapy


1 Department of Medical Oncology, HCG-SC, Bengaluru, Karnataka, India
2 Department of Radiation Oncology, HCG-SC, Bengaluru, Karnataka, India
3 Department of Clinical Oncology, Harare Oncology Centre, Harare, Zimbabwe
4 Department of Histopathology, HCG-SC, Bengaluru, Karnataka, India

Date of Submission22-Jul-2020
Date of Decision09-Sep-2020
Date of Acceptance05-Jan-2021
Date of Web Publication22-Jun-2022

Correspondence Address:
BJ Srinivasa,
Department of Medical Oncology, HCG-SC, Bengaluru - 560 027, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1018_20

 > Abstract 


Squamous cell carcinoma (SCC) has a good prognosis, while metastatic tumors have aggressive behavior. Immunotherapy has become a standard line of treatment in metastatic cancers; pembrolizumab has shown promising results and improved quality of life in recurrent and metastatic cancers. We report a case of recurrent SCC of the skin with extensive disease and a known case of human immunodeficiency virus. He completed standard lines of treatment and currently on immunotherapy. After 3 cycles of immunotherapy plus chemotherapy, he got a complete metabolic response. Our experience showed palliative benefits and increased quality of life.

Keywords: Immunosuppression, immunotherapy, pembrolizumab, squamous cell carcinoma



How to cite this URL:
Srinivasa B J, Sridhar P S, Lalkota BP, Tsikai N, Niyati P S, Shah M, Anuradha S, Roopesh R, Ramaswamy V, Naik R, Ajaikumar B S. Recurrent squamous cell carcinoma of the skin treated with immunotherapy. J Can Res Ther [Epub ahead of print] [cited 2022 Jul 2]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=347785




 > Introduction Top


Squamous cell carcinoma (SCC) evolves from keratinocytes, and it is the second most common cancer after basal cell carcinoma.[1] Most of the cutaneous SCC cases have a good prognosis, while cases with lymph node involvement, recurrence, and metastatic tumors have aggressive tumors.[2] Immunosuppression is a modestly elevated high risk for developing SCC.[3] We report a case of a recurrent cutaneous SCC patient, who underwent surgery followed by radiotherapy and failed on multiple lines of chemotherapy. He was treated with chemotherapy with the addition of immunotherapy and achieved a complete metabolic response.


 > Case Report Top


A 46-year-old male patient was diagnosed in 2015 as SCC of a mass around 2 cm, which is originating from the angle of the eye or lower eyelid. The patient was a known case of human immunodeficiency virus (HIV) and antiviral treatment. A biopsy was taken from the mass and reported as SCC [Figure 1]. As per the standard line of treatment, he underwent surgery, followed by radiotherapy. After 3 years of disease-free survival, the patient presented with an ulcer on the left side of his eye. He underwent enucleation of the left eye and consequently treated with 6 cycles of chemotherapy; he had 6 months of progression-free survival. The disease was recurred in January 2019 and treated with 6 cycles of chemotherapy. In March 2020, he got a progressive disease of the ulcer on the left side of his face with a bigger lesion of around 12 cm × 12 cm × 8 cm nodularity with pus discharge [Figure 2]. Fluorodeoxyglucose positron emission tomography–computed tomography (FDG PET-CT) scan shows 11.9 cm × 6.5 cm × 9.1 cm metabolically active heterogeneously enhancing mass involving the left orbital cavity with to nasal cavity and ethmoid sinus extension. Multiple bilateral submental, jugular, and left posterior cervical lymph nodes were noted. The patient biopsy was tested for immunotherapy markers; programmed death-ligand 1 (PD-L1) [Figure 3] shows no expression and microsatellite instability-low (MSI-L). The patient was started with Nab-paclitaxel and carboplatin with pembrolizumab. The patient completed 3 cycles of treatment until May 2020. He tolerated the treatment well and clinically tumor regression observed [Figure 4]. Tumor assessment with fluorodeoxyglucose FDG PET-CT scan showed partial response (PR) with interval regression of ulcerative thickening involving the left orbital, cheek, preauricular region, buccal mucosa with mild residual soft thickening, and regression of multiple bilateral cervical lymph nodes [Figure 5]. The patient was planned to continue the same treatment for 3 more cycles.
Figure 1: Immunohistochemistry shows poorly differentiated squamous cell carcinoma (×20)

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Figure 2: Extensive recurrent disease before starting pembrolizumab plus chemotherapy treatment

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Figure 3: Tumor cells are negative for PD-L1 expression (×40)

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Figure 4: Tumor shrinkage after 3 cycles of pembrolizumab plus chemotherapy treatment

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Figure 5: Positron emission tomography–computed tomography scan shows extensive disease before starting pembrolizumab plus chemotherapy (left); the scan shows good response after pembrolizumab plus chemotherapy (right)

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 > Discussion Top


The immune system recognizes foreign antigens and destroys them, along with protecting damaged tissue. Immune checkpoint inhibitors increase the immune system to identify and destroy cancer cells.[4] Immunotherapy has become a standard treatment for several cancers, providing a long-lasting and reliable response for advanced cancer patients.[5] These checkpoint inhibitors using antibodies block immune inhibitory pathways such as programmed cell death protein 1 (PD-1)/PD-ligand 1 (PD-L1). Pembrolizumab is a monoclonal antibody that binds to the programmed cell death 1 (PD-1) receptor to block interaction with its ligand (PD-L1 and PD-L2).[6],[7] Recently, FDA approved pembrolizumab for patients with recurrent or metastatic cutaneous SCC based on the keynote-629 trial[8] and other immune checkpoint inhibitor cemiplimab specifically for advanced SCC. SCC has a high tumor mutational burden,[9] and this may be the reason for good responses with immunotherapy. Plenty of studies show that PD-L1 or PD-1 expression, deficient mismatch repair (dMMR) and MSI as a predictive biomarker for clinical response of immune checkpoint inhibitors.[10]

The patient has treated with standard treatment protocols such as surgery followed by radiotherapy and multiple lines of chemotherapy. The patient got recurrence with extensive disease and negative for PD-L1 and MMR, immunocompromised by antiviral treatment. He received chemotherapy plus pembrolizumab as a palliative treatment without any toxicity and increased quality of life. Our patient clinical outcome is consistent with reported case reports and achieves PRs to anti-PD1 therapy.[11] Tio et al. demonstrated that cancer patients on antiviral treatment simultaneously treated with immunotherapy have shown 33% complete or PRs.[12] A retrospective analysis of advanced cancer patients including HIV treated with immunotherapy has achieved 28% of overall response rate.[13] Heppt et al. analyzed a series of HIV patients who received immunotherapy for metastatic cancers and observed 30% of overall response.[14]


 > Conclusion Top


We report a case of recurrent extensive disease of cutaneous SCC with negative biomarkers for immunotherapy and showing good tumor shrinkage. Our experience showed palliative benefits in addition to a reduction in symptoms and improved quality of life.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. The patient has given consent for his images and clinical information to be reported in the journal. The patient understands that his names and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Allen T, Khoni SN, Court NB. Immunotherapy and squamous cell carcinoma. Cancer Rep Rev 2017;1:1-3.  Back to cited text no. 1
    
2.
Cheng J, Yan S. Prognostic variables in high-risk cutaneous squamous cell carcinoma: A review. J Cutan Pathol 2016;43:994-1004.  Back to cited text no. 2
    
3.
Wilkins K, Turner R, Dolev JC, LeBoit PE, Berger TG, Maurer TA. Cutaneous malignancy and human immunodeficiency virus disease. J Am Acad Dermatol 2006;54:189-206.  Back to cited text no. 3
    
4.
Brahmer JR, Pardoll DM. Immune checkpoint inhibitors: Making immunotherapy a reality for the treatment of lung cancer. Cancer Immunol Res 2013;1:85-91.  Back to cited text no. 4
    
5.
Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018-28.  Back to cited text no. 5
    
6.
Raedler LA. Keytruda (pembrolizumab): First PD-1 inhibitor approved for previously treated unresectable or metastatic melanoma. Am Health Drug Benefits 2015;8:96.  Back to cited text no. 6
    
7.
Chang AL, Kim J, Luciano R, Chang SL, Colevas AD. A case report of unresectable cutaneous squamous cell carcinoma responsive to pembrolizumab, a programmed cell death protein 1 inhibitor. JAMA Dermatol 2016;152:106-8.  Back to cited text no. 7
    
8.
Grob JJ, Gonzalez R, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, et al. Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: A single-arm phase II trial (KEYNOTE-629). J Clin Oncol 2020;38:2916-25.  Back to cited text no. 8
    
9.
Migden MR, Khushalani NI, Chang AL, Rischin D, Schmults CD, Hernandez-Aya L, et al. Primary analysis of phase 2 results of cemiplimab, a human monoclonal Anti–PD-1, in patients with locally advanced cutaneous squamous cell carcinoma. Head Neck 2019;62:79-5.  Back to cited text no. 9
    
10.
Yi M, Jiao D, Xu H, Liu Q, Zhao W, Han X, et al. Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors. Mol Cancer 2018;17:1-14.  Back to cited text no. 10
    
11.
Varra V, Ross RB, Gastman B, Diaz-Montero CM, Geiger J, Koyfman SA. Complete response after treatment with pembrolizumab in a patient with metastatic cutaneous squamous cell carcinoma involving. Appl Radiat Oncol 2019;8:42-4.  Back to cited text no. 11
    
12.
Tio M, Rai R, Ezeoke OM, McQuade JL, Zimmer L, Khoo C, et al. Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection. Eur J Cancer 2018;104:137-44.  Back to cited text no. 12
    
13.
Shah NJ, Al-Shbool G, Blackburn M, Cook M, Belouali A, Liu SV, et al. Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection. J Immunother Cancer 2019;7:1-8.  Back to cited text no. 13
    
14.
Heppt MV, Schlaak M, Eigentler TK, Kähler KC, Kiecker F, Loquai C, et al. Checkpoint blockade for metastatic melanoma and Merkel cell carcinoma in HIV-positive patients. Ann Oncol 2017;28:3104-6.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

 
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    -  Srinivasa B J
    -  Sridhar P S
    -  Lalkota BP
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    -  Anuradha S
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