Oral oncology最新文献

Background: Locally advanced papillary thyroid carcinoma (PTC) with RET fusion-positive poses significant challenges for surgical resection due to tumor invasion into critical structures. Neoadjuvant targeted therapies are a promising approach to reduce the tumor burden and improve the resectability. Selperctinib, a RET kinase inhibitor, has been approved for the treatment of advanced or metastatic RET-altered thyroid cancer. However, the efficacy of selperctinib as a neoadjuvant treatment for locally advanced RET-altered thyroid cancer is unclear.

Case presentation: We report two cases of RET fusion-positive PTC that received neoadjuvant treatment with selperctinib (160 mg twice daily) to reduce the tumor size and enable for radical resection. Tumor sizes were reduced after neoadjuvant treatment with selperctinib. Patients successfully underwent R0 resection with no major surgical complications.

Conclusion: Selperctinib isa potential neoadjuvant treatment for PTC with RET fusion-positive.

Head and neck squamous cell carcinoma (HNSCC) poses a considerable challenge due to its high incidence and mortality rates. Immunotherapy targeting PD-(L)1 emerges as a promising approach for HNSCC, as it has the potential to trigger a broad and long-lasting anti-tumor response. Nevertheless, the effectiveness of immunotherapy encounters hurdles, and only a small proportion of patients benefit, with many eventually experiencing relapse. Consequently, there is a pursuit of strategies to enhance overall treatment outcomes. Understanding the mechanisms driving resistance to PD-(L)1 inhibition and devising strategies to overcome these challenges are vital for advancing more effective treatments. Furthermore, gaining insights into the mechanisms of action and safety profiles of novel combination therapies is critical for their successful adoption in clinical practice. As a result, current research is dedicated to investigating various immunotherapeutic agents beyond the PD-1/PD-L1 axis. This review offers a comprehensive overview of the existing immunotherapy strategies in HNSCC with a focus on TIM-3, TIGIT, LAG-3, and VISTA. The aim is to lay a strong foundation for the continual advancement of therapies for HNSCC.

Objective: Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT).

Methods: HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC).

Results: The populations of CD4⁺ T cells, CD8⁺ T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.05. Almost all markers showed a lower expression in the PR patients after treatment, resulting lower post/pre-treatment ratios of positive cell densities in the PR patients relative to the NPR patients. Following treatment, TIM3⁺ T cells and LAG3⁺ T cells exhibited significantly diminished levels in the PR cohort relative to the NPR cohort, with post/pre-treatment expression ratios showing significant differences (P < 0.05). Tumor infiltration lymphocyte analysis revealed that the PR group exhibited a considerably higher average density of CD8⁺ T cells infiltrating in the tumor marginal zone.

Conclusion: The presence of T cells demonstrated significant predictive capability for responses to neoadjuvant immunotherapy in HNSCC patients. Furthermore, TIM3⁺ T cells and LAG3⁺ T cells were found to be remarkably lower in the partial response (PR) cohort than in the non-partial response (NPR) cohort post-treatment. This research contributes critical understanding of the physiological changes occurring in immune cell responses.

Introduction: Studies reported inferior outcomes when radiotherapy starts >6-8 weeks post-surgery for head and neck squamous cell carcinoma (HNSCC) but are limited due to time variable dichotomization. We assessed the relationship between survival and the time between surgery and radiotherapy as a continuous variable, hypothesising there would be no change in patients' survival at 6-8 weeks post-surgery.

Methods/materials: Inclusion criteria: patients with HNSCC who underwent surgery and adjuvant (chemo)radiotherapy, Jan 2014-Dec 2020. A sub-cohort included patients with oral cavity squamous cell carcinoma (OCSCC) treated at the same institution, Jan 2016-Dec 2020. The primary endpoint was overall survival (OS); a multivariable Cox model was fitted. For the OCSCC sub-cohort, the endpoint of interest was progression-free survival (PFS); a multivariable competing risk regression model was fitted.

Results: 386 patients with HNSCC were included (main cohort). The median time between surgery and radiotherapy was 44 days (IQR: 14 days). Plotting time intervals vs log(hazard) did not demonstrate a threshold time where risk of death increases. The time interval between surgery and radiotherapy was not associated with OS (HR 1.00; 95 % CI 0.99-1.02; p = 0.4). In the sub-cohort of 208 patients with OCSCC, the time interval between surgery and radiotherapy was not associated with increased risk of cancer vs competing events (HR 1.01; 95 % CI 0.99-1.03; p = 0.5).

Conclusion: Increasing time interval between surgery and radiotherapy was not associated with inferior survival outcomes. We suggest patients are considered for radiotherapy >6-8 weeks post-surgery and that no threshold is considered for patient selection.

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of malignancies with multifactorial aetiologies. High-risk human papillomavirus (hrHPV) infections, particularly HPV16, and the dysregulation of telomerase activity, specifically through its catalytic subunit, telomerase reverse transcriptase (TERT) are among the key contributors to HNSCC development and progression. HPV promotes oncogenesis via the E6 and E7 oncoproteins, which inactivate tumour suppressors TP53 and RB1, leading to unchecked cellular proliferation. Concurrently, telomerase activation plays a critical role in HNSCC by maintaining telomere length, thus enabling cellular immortality, and facilitating tumour development and progression. The interplay between HPV and telomerase is significant; HPV oncoprotein E6 enhances telomerase activity through multiple regulatory mechanisms, including upregulating TERT expression. Beyond telomere maintenance, TERT influences signalling pathways, cellular metabolism, and the tumour microenvironment, contributing to aggressive tumour behaviour and poor prognosis. This review integrates the roles of HPV and telomerase in HNSCC, focusing on their molecular mechanisms and interactions that drive carcinogenesis and influence disease progression. Understanding the synergistic effects of HPV and TERT in HNSCC may be crucial for risk stratification, prognostic assessment, and the development of novel therapeutic strategies targeting these specific molecular pathways.

Background: Pembrolizumab with/without platinum + 5-FU is approved for the first-line (1L) treatment of R/M HNSCC, and its monotherapy use requires PD-L1 Combined Positive Score (CPS) ≥ 1. We aimed to understand PD-L1 testing patterns and associations with patient characteristics and treatment choice in R/M HNSCC.

Methods: Adults with R/M HNSCC initiating 1L systemic therapy were included from a U.S. nationwide database primarily compromised of community practices (07/01/2019-12/31/2023). PD-L1 testing patterns, treatment sequence, and time gaps related to testing and treatment initiation were summarized. Logistic regression was used to test associations between patient characteristics and PD-L1 testing patterns, and between CPS scores and 1L pembrolizumab monotherapy use.

Results: Of 2,207 patients, 32.7 % received PD-L1 testing before 1L therapy initiation, 17.4 % after 1L therapy initiation, and 50.0 % were never tested. Most patients (55.9 %) who tested positive before 1L therapy received pembrolizumab monotherapy while those who tested negative received pembrolizumab + platinum + 5-FU most commonly (31.6 %). Among patients untested before 1L therapy, the most common 1L treatment was pembrolizumab monotherapy (24.3 %). Patients with an ECOG ≥ 2 had higher odds of being tested before 1L therapy (OR: 1.42, p < 0.01). CPS scores were associated with higher odds of receiving 1L pembrolizumab monotherapy (OR: 4.11 and 4.96 for CPS 1-19 and ≥ 20, respectively; both p < 0.0001).

Conclusions: This study revealed low utilization of PD-L1 testing to guide treatment choice and impactful gaps between specimen collection, the receipt of results, and 1L therapy initiation. There is a need to improve clinician awareness of the importance of PD-L1 testing and an opportunity for updated guidelines on testing.