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1.
J Dent Res ; : 220345241271992, 2024 Oct 06.
Article in English | MEDLINE | ID: mdl-39370694

ABSTRACT

The introduction of immune checkpoint inhibitors (ICIs) to oncological care has transformed the management of various malignancies, including head and neck squamous cell carcinoma (HNSCC), offering improved outcomes. The first-line treatment of recurrent and malignant HNSCC for many years was combined platinum, 5-fluorouracil, and cetuximab. Recently, the ICI pembrolizumab was approved as a first-line treatment, with or without chemotherapy, based on tumor and immune cell percentage of programmed-death ligand 1 (PD-L1). Multiple head and neck (HN) cancer trials have subsequently explored immunotherapies in combination with surgery, chemotherapy, and/or radiation. Immunotherapy regimens may be personalized by tumor biomarker, including PD-L1 content, tumor mutational burden, and microsatellite instability. However, further clinical trials are needed to refine biomarker-driven protocols and standardize pathological methods to guide combined regimen timing, sequencing, and deescalation. Gaps remain for protocols using immunotherapy to reverse oral premalignant lesions, particularly high-risk leukoplakias. A phase II nonrandomized controlled trial, using the ICI nivolumab, showed a 2-y cancer-free survival of 73%, although larger trials are needed. Guidelines are also needed to standardize the role of dental evaluation and care before, during, and after immunotherapy, specifically in regard to oral immune-related adverse events and their impact on cancer recurrence. Standardized diagnostic and oral care coordination strategies to close these gaps are needed to ensure continued success of HN cancer immunotherapy.

2.
Ann Oncol ; 30(3): 471-477, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30596812

ABSTRACT

BACKGROUND: The survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab-PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab-C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control. PATIENTS AND METHODS: Eligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0-4N2b-2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0-3 or HPV-negative and T0-2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3-4. Patient reported outcomes were carried out. RESULTS: A total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups. CONCLUSION: The observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.


Subject(s)
Neoplasm Recurrence, Local/drug therapy , Papillomaviridae/pathogenicity , Papillomavirus Infections/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Cetuximab/administration & dosage , Cisplatin/administration & dosage , Docetaxel/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Induction Chemotherapy/adverse effects , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/virology , Neoplasm Staging , Paclitaxel/administration & dosage , Papillomaviridae/drug effects , Papillomaviridae/genetics , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Progression-Free Survival , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/virology
3.
Br J Dermatol ; 174(1): 169-71, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26252413

ABSTRACT

A 55-year-old woman with GATA2 deficiency and neurofibromatosis 1 was diagnosed with Merkel cell carcinoma (MCC). This polyomavirus-associated cutaneous malignancy has previously been associated with immunosuppression and acquired immunodeficiencies such as HIV/AIDS. However, MCC has not been previously reported in the setting of underlying primary or inherited immunodeficiency.


Subject(s)
Carcinoma, Merkel Cell/immunology , GATA2 Transcription Factor/deficiency , Immunologic Deficiency Syndromes/immunology , Skin Neoplasms/immunology , Carcinoma, Merkel Cell/pathology , Female , Humans , Immunologic Deficiency Syndromes/pathology , Middle Aged , Skin Neoplasms/pathology
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