scholarly journals Complete Response to Nivolumab in Recurrent/Metastatic HPV-Positive Head and Neck Squamous Cell Carcinoma Patient After Progressive Multifocal Leukoencephalopathy: A Case Report

2022 ◽  
Vol 11 ◽  
Author(s):  
Laura Deborah Locati ◽  
Mara Serena Serafini ◽  
Andrea Carenzo ◽  
Silvana Canevari ◽  
Federica Perrone ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Normal Values ◽  
Neck Squamous Cell Carcinoma ◽  
Human Polyomavirus ◽  
Durable Response ◽  
Immune Profile

In an immune-competent context nivolumab showed long-term benefit in overall survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC); however, in special cancer population such as these patients with immunodeficiency and viral infections, data on checkpoint inhibitors (ICI) activity are scant. Herein, we report a patient with a Human papilloma virus (HPV)-related oropharyngeal cancer (OPC) and CD4 lymphocytopenia. After a first-line treatment complete remission, the patient experienced Human Polyomavirus (JCV) infection in the brain. Consequently, to the recovery from progressive multifocal leukoencephalopathy (PML) the patient metastasized and was enrolled in a single-arm trial with nivolumab (EudraCT number: 2017-000562-30). A complete and durable response (more 3 years) was observed after 10 nivolumab injections Q2wks, interrupted for persistent drug related G2 diarrhea and a syndrome of inappropriate antidiuretic hormone secretion. We describe the circulating immune profile (before-, during-, and after nivolumab), consistent with the clinical history. Moreover, during nivolumab treatment, brain MRI evidenced the presence of small punctuate areas of contrast enhancement, reflecting a mild immune response in perivascular spaces. By cytofluorimetry, we observed that during JCV infection the CD4/CD8 ratio of the patient was under the normal values. After JCV infection recovery and before nivolumab treatment, CD4/CD8 ratio reached the normality threshold, even if the CD4+ T cell count remained largely under the normal values. During ICI, gene expression xCell analyses of circulating immune cells of the patient, showed a progressive normalization of the total immune profile, with significant boost in CD4+ and CD8+ T cells and a reduction in NK T, comparable to the circulating immune profile of reference tumor-free HNSCC patients. The present case supports the activity of ICI in a population of special cancer patients; whether JCV and HPV infections (alone or together) might have a possible role as immune booster(s), require further investigations.

A combined genomic and immune profile in patients with head and neck squamous cell carcinoma treated with immunotherapy: A pilot study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18506-e18506
Author(s):  
Andrea Botticelli ◽  
Silvia Mezi ◽  
Giulia Pomati ◽  
Ilaria Zizzari ◽  
Bruna Cerbelli ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Pilot Study ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Genetic Alterations ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Profile ◽  
Immune Profile ◽  
Early Progression

e18506 Background: In head and neck squamous cell carcinoma (HNSCC) only a small subset of patients (pts) really benefits from immunotherapy, suggesting the need of validated molecular and immunological predictive biomarkers. The aim of the study was to evaluate both the genomic and immune profile of HNSCC correlating it to early progression to immunotherapy. Methods: This is a pilot study evaluating immune and molecular profile in platinum-refractory HNSCC pts treated with Nivolumab. Blood samples were collected at baseline (T0) and at second cycle of therapy (T1). The immune profile was studied by multiplex assay, evaluating circulating: CD137, CTLA4, PD1, PDL1, PDL2, CD27, TIM3, LAG3, GITR, HVEM, BTLA, CD80, CD28 and IDO. The comprehensive genomic profile was evaluated at baseline on formalin-fixed paraffin-embedded samples of the tumor through Foundation One Cdx test. The results obtained were correlated with early progression (within 3 months from the start of therapy). Results: Ten pts were enrolled in the study. Early progression occurred in 6 pts (60%). Median progression free survival and overall survival were 3 months (1-11) and 6.5 months (1-12), respectively. In all patients ≥ 5 genetic mutations were detected; median number of mutation was 6 (5-14); 8/10 pts had a tumor mutational burden less than 10 Muts/mb. The more frequent genetic alterations involved the cycline-dependent-kynase pathway (9/10), the transcription factor associated gene TP53 (8/10) and the PI3K-Akt-PTEN signaling pathways (5/10). Less frequent alterations involved FGFR family (4/10), NOTCH signaling pathway (3/10) and TERT (4/10). Early progression was slightly associated with the number of mutations detected (p = 0.06). The rising or falling trend of circulating levels of biomarkers were detected in 9/10 pts and included modification in IDO (1/10), LAG3 (3/10), GITR (3/10), BTLA (3/10), CD137 (4/10), CTLA4 (4/10), PD1 (2/10), Tim3 (3/10), CD28 (3/10), HVEM (3/10), CD80 (2/10). No modifications were recorded in PDL1, PDL2 and CD27. Conclusions: Our results, although in a small cohort, highlighted the complexity and heterogeneity of landscape in HNSCC pts. A novel evaluation that combines molecular and immune profile is needed. In the context of a poor prognosis disease the combination of personalized molecular and immune approaches could represent a promising strategy to improve survival.

Hubungan ekspresi p53, Bcl-2, c-Myc dan MMP-9 dengan gambaran klinikopatologi karsinoma sel skuamosa kepala-leher

2016 ◽  
Vol 46 (1) ◽  
pp. 53
Author(s):  
Azwar Azwar ◽  
Sofia Mubarika ◽  
Agus Surono
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tumor Location ◽  
Neck Squamous Cell Carcinoma ◽  
Second Primary ◽  
Cross Sectional ◽  
P53 Expression ◽  
Local Metastasis

Latar belakang: Karsinoma sel skuamosa kepala dan leher merupakan salah satu kanker terseringdi seluruh dunia. Pendekatan pengobatan agresif dan multidisiplin telah dilakukan, namun belum adapeningkatan yang signifikan dalam kelangsungan hidup 5 tahun, selama 20 tahun terakhir. Kegagalanpengobatan terjadi dalam bentuk kekambuhan lokoregional, metastasis jauh, dan/atau tumor primer kedua.Berbagai penanda molekular tumor telah diteliti untuk mengetahui potensinya dalam memprediksi hasilpenyakit atau respon terhadap terapi.Tujuan: Mengetahui hubungan ekspresi protein p53, Bcl-2, c-Myc,dan MMP-9 berdasarkan gambaran klinikopatologis karsinoma sel skuamosa kepala dan leher di RumahSakit dr. Zainoel Abidin.Metode: Studi menggunakan desain cross sectional. Sampel terdiri dari 60blok parafin karsinoma sel skuamosa kepala dan leher. Prosedur pewarnaan imunohistokimia dilakukandengan menggunakan antibodi monoklonal terhadap p53, Bcl-2, c-Myc, dan MMP-9. Ekspresi proteinp53, Bcl-2, c-Myc, dan MMP-9 dianalisis secara imunohistokimia pada karsinoma sel skuamosa kepaladan leher kemudian hasilnya dihubungkan dengan parameter klinikopatologis seperti usia, jenis kelamin,lokasi tumor, diferensiasi tumor, metastasis kelenjar getah bening dan stadium tumor, kemudian dianalisisstatistik dengan Chi square.Hasil: Hasil penelitian menunjukkan terdapat hubungan bermakna tingkatekspresi p53 dengan metastasis lokal (p=0,021) dan ada hubungan bermakna tingkat ekspresi MMP-9dengan lokasi tumor (p=0,026). Tidak terdapat hubungan ekspresi p53, Bcl-2, cMyc, dan MMP-9 terhadapusia, jenis kelamin, stadium tumor, diferensiasi histologi, tingkat T, N, dan metastasis jauh.Kesimpulan:Ada hubungan ekpresi p53 dengan metastasis kelenjar limfe regional dan ekspresi MMP-9 dengan lokasitumor pada karsinoma sel skuamosa kepala dan leher. Kata kunci: Karsinoma sel skuamosa kepala dan leher, p53, Bcl-2, c-Myc, MMP-9 ABSTRACTBackground: Head and neck squamous cell carcinoma (HNSCC) is one of the most commoncancers world wide. Although aggressive and multidisciplinary approach to the treatment has been done,there is no significant improvement in 5-year survival in the last 20 years. Treatment failure occurredin the form of locoregional recurrence, distant metastasis, and/or a second primary tumor. A variety oftumor molecular markers have been studied to determine their potential in predicting disease outcome orresponse to the therapy. Purpose: To investigate correlation p53, Bcl-2, c-Myc, and MMP-9 expressionto clinicopathologic parameter in head and neck squamous cell carcinoma patient in dr. Zainoel Abidinhospital. Methods: Cross sectional design study. The sample was consisted of 60 paraffin blocks ofhead and neck squamous cell carcinoma. Procedure of immunohistochemical staining used monoclonalantibodies against p53, Bcl-2, c-Myc, and MMP-9. Expression of p53 protein, Bcl-2, c-Myc, and MMP-9were analyzed by immunohistochemistry in head and neck squamous cell carcinoma. Then, the results were linked to clinicopathologic parameters such as age, sex, tumor location, tumor differentiation,lymph node metastasis and tumor stage, and statistically analyzed with Chi square. Results: The resultsshowed there were significant correlation between p53 expression level with local metastasis (p=0,021)and significant correlation of MMP-9 expression levels with tumor location (p=0,026). There were norelationship of p53, Bcl-2, cMyc and MMP-9 expressions based on age, sex, stage tumor, histologicdifferentiation, level of T, N, and distant metastases. Conclusion: There were relationships between p53expression with local metastasis and MMP-9 expression with tumor location in head and neck squamouscell carcinoma. Keywords: Head and neck squamous cell carcinoma, p53, Bcl-2, c-Myc, MMP-9

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