Publications by authors named "Brett G M Hughes"

Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54).

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The Royal Brisbane and Women's Hospital (RBWH) Swallowing and Nutrition Management Guidelines for Patients with Head and Neck Cancer were developed to enable evidence-based decision-making by the Head and Neck Multidisciplinary Team (H&N MDT) regarding enteral nutrition support options. The purpose of this study was to revalidate these guidelines in a cohort of patients receiving helical intensity-modulated radiotherapy (H-IMRT) compared to a historical cohort who received primarily 3D-conformal radiotherapy. Eligible patients attending the RBWH H&N MDT between 2013 and 2014 (n = 315) were assessed by the guidelines, with high-risk patients being recommended proactive gastrostomy tube placement.

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Background: Head and neck squamous cell carcinoma (HNSCC) is linked to human papillomavirus (HPV) infection. HPV-positive and HPV-negative HNSCC exhibit distinct molecular and clinical characteristics. Although checkpoint inhibitors have shown efficiency in recurrent/metastatic HNSCC, response variability persists regardless of HPV status.

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Article Synopsis
  • - The phase 2 EMPOWER-CSCC-1 study showed that cemiplimab is effective against advanced cutaneous squamous cell carcinoma (CSCC), specifically in metastatic and locally advanced cases.
  • - The study involved different treatment groups receiving either weight-based or fixed-dose cemiplimab, with a significant overall response rate (ORR) of 47.2% after 42.5 months and noted long-duration responses.
  • - While the findings are promising, the study's limitations include its nonrandomized design and the fact that the primary endpoint was not based on survival rates.
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  • Advanced head and neck squamous cell carcinoma (HNSCC) is challenging to treat, prompting research into combining immunotherapies like epacadostat (IDO inhibitor) with pembrolizumab (PD-1 inhibitor) for potential better outcomes compared to single treatments.
  • The KEYNOTE-669/ECHO-304 clinical trial examined the effectiveness and safety of this combination versus pembrolizumab alone and the standard EXTREME regimen in patients with recurrent/metastatic HNSCC, with results cut off in January 2019 after early study enrollment cessation.
  • Results showed varying objective response rates: 31% for the combination therapy, 21% for pembrolizumab alone, and 34% for EXTREME,
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Background: Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response.

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  • The JAVELIN Lung 101 trial tested avelumab, an immune checkpoint inhibitor, alongside lorlatinib or crizotinib (tyrosine kinase inhibitors) in advanced non-small cell lung cancer (NSCLC).
  • The study aimed to determine the maximum tolerated dose (MTD) and evaluate the treatment's effectiveness based on patient response rates, focusing on dose-limiting toxicities (DLTs).
  • Results showed that avelumab with lorlatinib was manageable with a response rate of 52%, while avelumab with crizotinib was less feasible, with a lower response rate of 25% and high DLT incidence.
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Patients with head and neck squamous cell carcinoma (HNSCC) are at a high risk of developing recurrence and secondary cancers. This study evaluates the prognostic and surveillance utilities of circulating tumour cells (CTCs) in HNSCC. A total of 154 HNSCC patients were recruited and followed up for 4.

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Introduction: Dysregulated MET is an established oncogenic driver in non-small cell lung cancer (NSCLC). MET signaling may also suppress anticancer immune responses. Concomitant MET inhibition with capmatinib (a MET inhibitor) synergistically enhanced the efficacy of immunotherapies in murine cancer models, regardless of tumor dependency to MET signaling.

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Background: Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC.

Methods: In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy.

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  • Cemiplimab (Libtayo) is an approved antibody used to treat advanced skin cancer (CSCC) in patients who can't undergo surgery or radiation, and it's typically given every three weeks.
  • A study tested giving a higher dose (600 mg) every four weeks instead, involving 63 patients who were monitored for tumor response over 48 weeks.
  • Results showed a 62% objective response rate with significant antitumor activity and manageable side effects like diarrhea and fatigue, suggesting this new dosing schedule could be effective but needs further data for comparison with the standard treatment.
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  • Lurbinectedin is a new treatment option for small cell lung cancer (SCLC) after patients have not responded to platinum-based therapies, showing promise in real-world settings in Australia.
  • A study involved 46 individuals who received lurbinectedin, revealing a 33% response rate and 50% disease control rate, with various levels of side effects experienced during treatment.
  • The median progression-free survival was 2.5 months and overall survival was 4.5 months, indicating results comparable to previous clinical trials.
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Introduction: At first interim analysis of KEYNOTE-629, health-related quality of life (HRQoL) with pembrolizumab was stable or improved over 48 weeks in recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). HRQoL results from the second interim analysis in R/M or locally advanced (LA) cSCC are presented.

Methods: Patients received pembrolizumab 200 mg every 3 weeks for ≤ 2 years.

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Background: We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival.

Methods: This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1.

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Background: Helical intensity-modulated radiotherapy (H-IMRT) provides excellent limitation of dose to tissues not requiring treatment, although acute toxicity still occurs. The present study aimed to determine how treatment-related acute toxicities affect nutrition outcomes in patients with head and neck cancer.

Methods: A prospective observational study was conducted in 194 patients undergoing curative intent H-IMRT with or without other treatment modalities.

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Background And Objective: Since 2016, new therapies have transformed the standard of care for lung cancer, creating a need for up-to-date evidence for health economic modelling. We developed a discrete event simulation of advanced lung cancer treatment to provide estimates of survival outcomes and healthcare costs in the Australian setting that can be updated as new therapies are introduced.

Methods: Treatment for advanced lung cancer was modelled under a clinician-specified treatment algorithm for Australia in 2022.

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Mucosal head and neck squamous cell carcinoma (HNSCC) are the seventh most common cancer, with approximately 50% of patients living beyond 5 years. Immune checkpoint inhibitors (ICIs) have shown promising results in patients with recurrent or metastatic (R/M) disease, however, only a subset of patients benefit from immunotherapy. Studies have implicated the tumor microenvironment (TME) of HNSCC as a major factor in therapy response, highlighting the need to better understand the TME, particularly by spatially resolved means to determine cellular and molecular components.

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Introduction: Over the past decade, ALK tyrosine kinase inhibitors have delivered unprecedented survival for individuals with -positive () lung cancers. Real-world data enhance the understanding of optimal drug sequencing and expectations for survival.

Methods: Multicenter real-world study of individuals with pretreated advanced lung cancers managed on a lorlatinib access program between 2016 and 2020.

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Background: Alectinib is a second generation of -tyrosine kinase inhibitors (-TKIs), which has attracted much attention in the treatment of -positive non-small cell lung cancer (NSCLC). At present, there are few reports on the efficacy and safety of alectinib in Chinese population. Moreover, biomarkers reflecting prognosis and efficacy are exceedingly needed.

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Background: CD73 is widely expressed on immune cells playing a critical role in immunomodulatory functions including cell adhesion and migration, as a costimulatory molecule for T cells and in production of adenosine. The function of CD73 expressed on B cells has not been fully characterized. Mupadolimab is an anti-human CD73 antibody that activates B cells.

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Background: In the phase 2 double-blind Study 211, a starting dose of lenvatinib 18 mg/day was compared with the approved starting dose of 24 mg/day in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Predefined criteria for noninferiority for efficacy in the 18 mg arm were not met; safety was similar in both arms. Impact of lenvatinib treatment on health-related quality-of-life (HRQoL) was a secondary endpoint of Study 211.

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Background: Enteral nutrition (EN) is often required in patients with head and neck cancer (HNSCC); however, initiation criteria is limited or inconsistent. This study aimed to describe the relationship of treatment toxicities and requirement for EN and investigate toxicity and baseline characteristics association with EN duration.

Methods: Acute toxicities and baseline characteristics were collected from patients with HNSCC (n = 110) undergoing H-IMRT.

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Purpose: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented.

Methods: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy.

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Article Synopsis
  • - The study explored the effectiveness of cemiplimab as a neoadjuvant therapy for patients with resectable cutaneous squamous-cell carcinoma, aiming to determine its impact on achieving a pathological complete response before surgery.
  • - Out of 79 participants, 51% achieved a pathological complete response, while 68% showed a positive response on imaging; these outcomes suggest cemiplimab is effective for this patient group.
  • - However, 87% of patients experienced adverse events, highlighting the need for careful monitoring and further research to balance treatment benefits with potential side effects.
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Sarcopenia is a known independent prognostic factor for decreased survival in patients with head and neck cancer; yet, its importance for the growing number of younger patients diagnosed with human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC+) has not been established. This systematic literature review aimed to determine the prevalence and impact of computed tomography (CT)-defined sarcopenia on survival outcomes for adult OPC+ patients (>18 y) undergoing any treatment modality. Prospective studies were searched using PubMed, Embase, CENTRAL, CINAHL, and Web of Science up until and including February 2022.

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