Human papillomavirus associated oropharyngeal cancer now the most common mucosal head and neck cancer in Queensland.

INTRODUCTION: The profile and outcomes of head and neck cancer throughout Australia has changed over the past decade. The aim of this study was to perform a population-based analysis of incidence, demographics, stage, treatments and outcomes of patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC), with a particular focus on HPV-associated disease. METHODS: This was a retrospective analysis of prospectively collected data within the Queensland Oncology Repository (QOR) and analysed by the Queensland Cancer Control Analysis Team. The cohort included patients diagnosed in Queensland between 1 January 2015 and 31 December 2019. Outcome measures included incidence of new OPSCC cases, age-standardised rates (ASR) (3-year average), demographics, p16 status, stage (8th Edition American Joint Commission on Cancer), treatments, and 2- and 5-year overall survival. RESULTS: There were 1527 newly diagnosed OPSCC, representing 96% (1527/1584) of all oropharyngeal cancers. It was the most common head and neck cancer diagnosed, with oral cavity cancer being the second most common (n = 1171). Seventy-seven percent were p16 positive (1170/1527), of which 87% (1019/1170) were male. The median age was 61 years and 49% (568/1170) presented with Stage I disease. The ASR was 6.3/100,000, representing a 144% incidence increase since 1982 (2.6/100,000). Radiotherapy was utilised in 91% of p16+ cases with 2- and 5- year overall survival of 89% and 79%, respectively. CONCLUSION: OPSCC is now the most common mucosal head and neck cancer diagnosed in Queensland, having surpassed oral cavity cancer. The majority are HPV-associated (p16+), presenting with early-stage disease with a favourable prognosis.

Understanding the tumor microenvironment in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of tumors. While significant progress has been made using multimodal treatment, the 5-year survival remains at 50%. Developing effective therapies, such as immunotherapy, will likely lead to better treatment of primary and metastatic disease. However, not all HNSCC tumors respond to immune checkpoint blockade therapy. Understanding the complex cellular composition and interactions of the tumor microenvironment is likely to lead to new knowledge for effective therapies and treatment resistance. In this review, we discuss HNSCC characteristics, predictive biomarkers, factors influencing immunotherapy response, with a focus on the tumor microenvironment.

Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in.

BACKGROUND: There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma. METHODS: DREAM was a multicentre, single-arm, open-label, phase 2 trial done in nine hospitals in Australia. Eligible patients were aged 18 years or older and had histologically confirmed malignant pleural mesothelioma considered unsuitable for cancer-directed surgery, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease as per the modified Response Evaluation Criteria in Solid Tumors version 1.0 (mRECIST) for mesothelioma that was previously untreated with systemic therapy. All histological subtypes were eligible. The first six participants were treated for two cycles in a safety run-in. All participants received cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and durvalumab 1125 mg intravenously on day 1 of a 3-weekly schedule for a maximum of six cycles. Change from cisplatin to carboplatin with an area under the curve of 5 was permitted. Durvalumab was continued for a maximum of 12 months. The primary endpoint was progression-free survival at 6 months, measured according to mRECIST for malignant pleural mesothelioma and analysed in the intention-to-treat population. Safety analyses included all participants who receive at least one dose of any study drug. This study is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12616001170415. FINDINGS: Between Dec 28, 2016, and Sept 27, 2017, 55 participants were enrolled. 54 patients were eligible and were followed up for a median of 28·2 months (IQR 26·5-30·2). 31 (57%; 95% CI 44-70) of 54 patients were alive and progression-free at 6 months. The most common grade 3-4 adverse events were neutropenia (seven [13%] patients), nausea (six [11%]), and anaemia (four [7%]). A total of 60 serious adverse events occurred in 29 participants, five of which were considered possibly related to durvalumab. Five patients died during the study treatment; none of these five deaths were attributed to study treatment. INTERPRETATION: The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomised phase 3 trial. FUNDING: AstraZeneca.

Immune checkpoint inhibitors: Navigating a new paradigm of treatment toxicities.

Immune checkpoint inhibitors have recently emerged as an exciting new treatment paradigm across a broad spectrum of malignancies. This new class of agents also challenges oncologists with a unique set of immune-based toxicities. Early recognition and precise management of these toxicities can result in better outcomes, with minimization of toxicity and harm to the patient. This article provides a comprehensive review of immune-based toxicities caused by immune checkpoint inhibitors, including recommendations for their investigation and guidelines for specific management.

Concurrent chemoradiation with cisplatin and vinorelbine followed by consolidation with oral vinorelbine in locally advanced non-small cell lung cancer (NSCLC): the phase II CONCAVE study.

AIM: Despite recent advances, outcomes for patients with stage III non-small cell lung cancer (NSCLC) with concurrent chemoradiotherapy (CRT) remain poor. We evaluated the combination of ciplatin/vinorelbine and concurrent thoracic radiotherapy followed by consolidation oral vinorelbine in this phase II study. METHODS: Eligible patients with unresectable stage III NSCLC received cisplatin intravenous (IV) 40 mg/m2 and vinorelbine IV 20 mg/m2 on days 1, 8, 22 and 29 concurrent with thoracic radiotherapy of 60 Gy in 30 fractions. Four to eight weeks later, oral vinorelbine 60 mg/m2 day 1 and 8 every 3 weeks was given for 3 cycles. The primary end point was overall response rate (ORR). Secondary end points were safety, quality of life, progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-seven eligible patients were enrolled from December 2007 to June 2010 before the trial was prematurely closed due to toxicity concerns. The median age was 63 years (range, 42-71), 56% were male, 52% ECOG 0 and 52% stage IIIa. The ORR was 81% (including 37% complete response rate) and disease control rate of 93%. The median PFS was 11 months and median OS was 26 months. Consolidation vinorelbine was associated with significant grade 3/4 toxicity (68%) including grade 3-5 febrile neutropenia (27%) and respiratory infections (36%) including two deaths in the consolidation phase (9%). CONCLUSIONS: Consolidation oral vinorelbine after CRT was associated with significant toxicity. Overall, this regimen achieved a high ORR and survival results comparable to other CRT protocols but the significant toxicity precludes further evaluation of this approach.

Single institution retrospective review of perioperative chemotherapy in adult and adolescent patients with operable osteosarcoma.

AIMS: Perioperative chemotherapy has improved the prognosis for patients with operable osteosarcoma. The literature is conflicting about which regimen is optimal. The aim of this study was to evaluate the survival outcomes of two cohorts of patients with operable osteosarcoma treated with different perioperative chemotherapy regimens. METHODS: This was a retrospective review of patients diagnosed with operable osteosarcoma treated at the Princess Alexandra Hospital from 1986 to 2009. The standard perioperative chemotherapy regimen changed from the modified T10 Rosen protocol to cisplatin/doxorubicin in 1997. Using the Kaplan-Meier method, overall survival (OS) and disease-free survival (DFS) curves were generated for the cisplatin/doxorubicin and the modified T10 Rosen cohorts. RESULTS: Seventy-one patients were identified of whom 63 had potentially curable disease. Of these, 24 received the modified T10 Rosen regimen and 39 received cisplatin/doxorubicin. There was a non-significant trend toward better OS and DFS in the patients who received the modified T10 Rosen protocol. CONCLUSION: The trend toward poorer survival in the cisplatin/doxorubicin cohort, in combination with current evidence, has prompted our institution to change its practice.