Publications by authors named "Glenn J Hanna"

Immune-checkpoint inhibitors (ICIs) are being tested as neoadjuvant therapies in various solid tumours, including in patients with head and neck squamous cell carcinoma (HNSCC), with promising results. Key findings thus far include that this approach is well-tolerated with favourable clinical outcomes including promising pathological response rates in initial studies. Pathological responses are likely to be increased by combining other agents with anti-PD-(L)1 antibodies.

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  • The study focused on brain metastasis (BM) in patients with head and neck squamous cell carcinoma (HNSCC), analyzing 61 cases from various institutions to understand their molecular characteristics and immune responses.
  • Key findings included that most patients were around 59 years old, with a significant number being HPV-positive and showing frequent genetic alterations like ATM, KMT2A, and TP53, which are potential therapeutic targets.
  • The research revealed low densities of immune cells in BM samples and a median survival of 9 months post-diagnosis, suggesting areas for future research in immunotherapy and better treatment strategies.
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Background: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Testing for plasma tumor tissue modified viral (TTMV)-HPV DNA has emerged as a biomarker strategy for post-treatment surveillance to identify recurrent disease. We aimed to understand the prognostic and predictive potential of TTMV-HPV DNA when monitoring patients who had developed recurrent or metastatic (R/M) HPV+OPSCC.

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Importance: Immune checkpoint inhibition (ICI) is a frontline treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but questions remain surrounding optimal duration of therapy, benefits and risks of ICI rechallenge, and efficacy in first vs subsequent lines of therapy.

Objectives: To estimate survival in US patients receiving ICI-based treatment for R/M HNSCC, compare outcomes associated with treatment discontinuation vs continuation at 1 or 2 years, and assess outcomes after immunotherapy rechallenge.

Design, Setting, And Participants: This retrospective, population-based cohort study included adult patients in the Flatiron Health nationwide oncology database treated with immunotherapy for R/M HNSCC from 2015 to 2023.

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Objectives: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer.

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Purpose: Many patients with locoregionally advanced human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) relapse. ctDNA has the potential to identify minimal residual disease, but its clinical utility for virus-negative HNSCC is not well understood.

Experimental Design: We retrospectively evaluated a personalized, commercial ctDNA assay (Signatera, Natera) during clinical care of patients treated for predominantly newly diagnosed human papillomavirus-negative HNSCC.

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  • The article examines various oral cancer precursor syndromes, particularly focusing on hereditary disorders like dyskeratosis congenita and Fanconi anemia that elevate cancer risk.
  • It highlights oral potentially malignant disorders, especially leukoplakia, emphasizing the roles of genetics and immune factors in their development.
  • Lastly, the discussion includes management strategies for leukoplakia, such as surgery and immune therapies, while addressing the difficulties in creating effective preventive methods.
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Importance: In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities.

Objective: To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population.

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Purpose: Adenoid cystic carcinoma (ACC) is an uncommon salivary gland cancer with no approved therapies available to treat advanced, incurable disease. Recent molecular profiling efforts have identified two important subtypes: the more aggressive ACC-I is characterized by Notch pathway alterations and MYC amplification whereas ACC-II demonstrates a more indolent phenotype and TP63 overexpression.

Experimental Design: This retrospective observational cohort study involved de-identified samples from 438 patients with ACC with tumor samples sent for commercially-available molecular profiling (Caris Life Sciences).

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Introduction: The programmed death-1 (PD-1) immune checkpoint inhibitor pembrolizumab is currently approved in the US for the first-line (1L) treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), either alone or in combination with platinum and 5-fluorouracil (5-FU). However, the toxicity of 5-FU has motivated the study of alternate combinations that replace 5-FU with a taxane. The objective of the current study was to describe the baseline characteristics, treatment patterns and sequences, and real-world outcomes of individuals receiving pembrolizumab + platinum + taxane as 1L treatment for R/M HNSCC in the US.

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Article Synopsis
  • - Recent trials indicate that PD-1-directed immunotherapy, specifically pembrolizumab, may help some patients with anal squamous cell carcinoma, but there is a need for reliable biomarkers to predict who will respond to the treatment.
  • - In a phase II clinical trial involving 32 patients, the objective response rate (ORR) to pembrolizumab was low at 9.4%, with a median progression-free survival of only 2.2 months, and most patients showed low levels of beneficial immune cells.
  • - Some patients had long-term responses to pembrolizumab, with one patient lasting over 5 years, particularly those with HPV-positive tumors and no liver metastases, but challenges remain due to ongoing HPV infection
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Purpose: Cemiplimab is approved for treating locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). Solid organ transplant recipients have been excluded from immunotherapy trials, given concern for allograft rejection despite their increased risk of skin cancers. Chronic immunosuppression is necessary to prevent organ rejection but may attenuate antitumor response with PD-1 inhibitors.

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Surveillance for survivors of head and neck cancer (HNC) is focused on early detection of recurrent or second primary malignancies. After initial restaging confirms disease-free status, the use of surveillance imaging for asymptomatic patients with HNC is controversial. Our objective was to comprehensively review literature pertaining to imaging and biomarker surveillance of asymptomatic patients treated for head and neck squamous cell carcinoma and to convene a multidisciplinary expert panel to provide appropriate use criteria for surveillance in representative clinical scenarios.

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Introduction: NUT carcinoma (NC) is an underdiagnosed and aggressive poorly differentiated or squamous cell cancer. A subset of NC is sensitive to chemotherapy, but the optimal regimen is unknown. Experts have recommended platinum- and ifosfamide-based therapy based on case reports.

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Objectives: Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.

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Tweetable abstract Immunotherapy for head and neck cancer shows promising new directions - and challenges ahead. What can we learn from recent trials to improve patient selection and optimize combination therapy?

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  • - Proliferative verrucous leukoplakia (PVL) is a serious oral condition with a high chance of becoming invasive cancer, and there's currently no effective treatment. Recent findings point to a strong immune presence in PVL, leading researchers to explore immune checkpoint therapy as a potential treatment option.
  • - This study aimed to assess the safety and effectiveness of anti-PD-1 therapy (nivolumab) for treating high-risk PVL in a phase 2 clinical trial with 33 participants, monitored over about 21 months.
  • - Results showed that 36% of patients experienced a significant reduction in their condition, while some faced worsening disease; researchers also looked at immune responses and genetic factors as part of the treatment
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About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking.

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Purpose: This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC).

Patients And Methods: Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily.

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Purpose: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance.

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  • * Surgical removal is the primary treatment method, supplemented by radiation and systemic therapies as needed.
  • * Effective management typically requires a team of specialists, and the review discusses both current treatment standards and promising new research aimed at improving patient outcomes.
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We review chimeric antigen receptor (CAR) T-cell therapy for solid tumors. We discuss patient selection factors and aspects of clinical management. We describe challenges including physical and molecular barriers to trafficking CAR-Ts, an immunosuppressive tumor microenvironment, and difficulty finding cell surface target antigens.

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