Disease trajectories, place and mode of death in people with head and neck cancer: findings from the ‘Head and Neck 5000’ population-based prospective clinical cohort study

Background: Few large studies describe initial disease trajectories and subsequent mortality in people with head and neck cancer. This is a necessary first step to identify the need for palliative care and associated services. Aim: To analyse data from the Head and Neck 5000 study to present mortality, place and mode of death within 12 months of diagnosis. Design: Prospective cohort study. Participants: In total, 5402 people with a new diagnosis of head and neck cancer were recruited from 76 cancer centres in the United Kingdom between April 2011 and December 2014. Results: Initially, 161/5402 (3%) and 5241/5402 (97%) of participants were treated with ‘non-curative’ and ‘curative’ intent respectively. Within 12 months, 109/161 (68%) in the ‘non-curative’ group died compared with 482/5241 (9%) in the ‘curative’ group. Catastrophic bleed was the terminal event for 10.4% and 9.8% of people in ‘non-curative’ and ‘curative’ groups respectively; terminal airway obstruction was recorded for 7.5% and 6.3% of people in the same corresponding groups. Similar proportions of people in both groups died in a hospice (22.9% ‘non-curative’; 23.5% ‘curative’) and 45.7% of the ‘curative’ group died in hospital. Conclusions: In addition to those with incurable head and neck cancer, there is a small but significant ‘curative’ subgroup of people who may have palliative needs shortly following diagnosis. Given the high mortality, risk of acute catastrophic event and frequent hospital death, clarifying the level and timing of palliative care services engagement would help provide assurance as to whether palliative care needs are being met

Presenting symptoms and long‐term survival in head and neck cancer

Objectives To assess how type and number of symptoms are related to survival in patients with head and neck cancer. Design Patients were followed up for over 10 years from the Scottish Audit of Head and Neck Cancer (national cohort of head and neck cancer patients in Scotland 1999‐2001). September 2013, cohort was linked to national mortality data. First, second and third presenting symptoms were recorded at diagnosis. Setting National prospective audit—Scotland. Participants A subset of 1589 patients, from the original cohort of 1895, who had cancer arising from one of the four main subsites; larynx, oropharynx, oral cavity and hypopharynx. Main outcome measures Median survival in relation to patients’ presenting symptoms. Results A total of 1146 (72%) males and 443 (28%) females, mean age at diagnosis 64 years (13‐95). There was a significant difference in survival in relation to the number of the patient's presenting symptoms; one symptom had a median survival of 5.3 years compared with 1.1 years for three symptoms. Patients who presented with weight loss had a median survival of 0.8 years, compared to 4.2 years if they did not (P < .001). Patients who presented with hoarseness had a median survival of 5.9 years compared to 2.6 years without (P < .001). There was no significant difference in long‐term survival for patients who presented with an ulcer, compared to those that did not (P = .105). Conclusions This study highlights the importance of patients’ presenting symptoms, giving valuable information in highlighting appropriate “red flag” symptoms and subsequent treatment planning and prognosis

Squamous cell carcinoma of the nasal cavity:A descriptive analysis of cases from the Head and Neck 5000 study

OBJECTIVES: This paper aims to provide contemporary epidemiological data on squamous cell carcinoma (SCC) of the nasal cavity, which represents a rare type of head and neck cancer.DESIGN, SETTING &amp; PARTICIPANTS: A descriptive analysis of people with nasal cavity SCC treated with curative intent from the Head and Neck 5000 study; a multicentre clinical cohort study of people from the UK with head and neck cancer. People with tumours of the nasopharynx, paranasal sinuses and other sub-sites of the head and neck were excluded.MAIN OUTCOME MEASURES: Demographic data and treatment details are presented for all participants. The main outcomes were overall survival and survival according to categories of characteristics (e.g. smoker vs non-smoker); these were explored using Kaplan-Meier plots.RESULTS: Thirty people with nasal cavity SCC were included in the study, of which most were male (67%) and current or ex-smokers (70%). The majority (70%) presented with early stage (T1/2, N0) tumours. Cervical lymph node metastases at presentation were rare, occurring in only one person. Nine people died during the follow up period (30%). Worse survival outcomes were seen in people with moderate or severe co-morbidities.CONCLUSIONS: This paper provides epidemiological data on nasal cavity SCC in the UK. Patterns of disease and survival outcomes are described, identifying high-risk groups. Further studies should explore whether primary treatment modality alters survival. This article is protected by copyright. All rights reserved.</p

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial

Background Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit appeared to be independent of the phosphoinositide 3-kinase (PI3K)/AKT/phosphatase and tensin homologue (PTEN) pathway alteration status of tumours, as ascertained using assays available at the time. Here, we report updated progression-free survival and overall survival results, and a prespecified examination of the effect of PI3K/AKT/PTEN pathway alterations identified by an expanded genetic testing panel on treatment outcomes. Methods This randomised, multicentre, double-blind, placebo-controlled, phase 2 trial recruited postmenopausal adult women aged at least 18 years with ER-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer and an Eastern Cooperative Oncology Group performance status of 0–2, who had relapsed or progressed on an aromatase inhibitor, from across 19 hospitals in the UK. Participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a 500 mg loading dose on day 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off, starting on cycle 1 day 15. Treatment continued until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment was allocated by an interactive web-response system using a minimisation method (with a 20% random element) and the following minimisation factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival in the intention-to-treat population. Secondary endpoints shown in this Article were overall survival and safety in the intention-to-treat population, and the effect of tumour PI3K/AKT/PTEN pathway status identified by an expanded testing panel that included next-generation sequencing assays. Recruitment is complete. The trial is registered with ClinicalTrials.gov, number NCT01992952. Findings Between March 16, 2015, and March 6, 2018, 183 participants were screened for eligibility and 140 (77%) were randomly assigned to receive fulvestrant plus capivasertib (n=69) or fulvestrant plus placebo (n=71). Median follow-up at the data cut-off of Nov 25, 2021, was 58·5 months (IQR 45·9–64·1) for participants treated with fulvestrant plus capivasertib and 62·3 months (IQR 62·1–70·3) for fulvestrant plus placebo. Updated median progression-free survival was 10·3 months (95% CI 5·0–13·4) in the group receiving fulvestrant plus capivasertib compared with 4·8 months (3·1–7·9) for fulvestrant plus placebo (adjusted hazard ratio [HR] 0·56 [95% CI 0·38–0·81]; two-sided p=0·0023). Median overall survival in the capivasertib versus placebo groups was 29·3 months (95% CI 23·7–39·0) versus 23·4 months (18·7–32·7; adjusted HR 0·66 [95% CI 0·45–0·97]; two-sided p=0·035). The expanded biomarker panel identified an expanded pathway-altered subgroup that contained 76 participants (54% of the intention-to-treat population). Median progression-free survival in the expanded pathway-altered subgroup for participants receiving capivasertib (n=39) was 12·8 months (95% CI 6·6–18·8) compared with 4·6 months (2·8–7·9) in the placebo group (n=37; adjusted HR 0·44 [95% CI 0·26–0·72]; two-sided p=0·0014). Median overall survival for the expanded pathway-altered subgroup receiving capivasertib was 38·9 months (95% CI 23·3–50·7) compared with 20·0 months (14·8–31·4) for those receiving placebo (adjusted HR 0·46 [95% CI 0·27–0·79]; two-sided p=0·0047). By contrast, there were no statistically significant differences in progression-free or overall survival in the expanded pathway non-altered subgroup treated with capivasertib (n=30) versus placebo (n=34). One additional serious adverse event (pneumonia) in the capivasertib group had occurred subsequent to the primary analysis. One death, due to atypical pulmonary infection, was assessed as possibly related to capivasertib treatment. Interpretation Updated FAKTION data showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer. The expanded biomarker testing suggested that capivasertib predominantly benefits patients with PI3K/AKT/PTEN pathway-altered tumours. Phase 3 data are needed to substantiate the results, including in patients with previous CDK4/6 inhibitor exposure who were not included in the FAKTION trial. Funding AstraZeneca and Cancer Research UK

Can linked emergency department data help assess the out-of-hospital burden of acute lower respiratory infections? A population-based cohort study

<p>Abstract</p> <p>Background</p> <p>There is a lack of data on the out-of-hospital burden of acute lower respiratory infections (ALRI) in developed countries. Administrative datasets from emergency departments (ED) may assist in addressing this.</p> <p>Methods</p> <p>We undertook a retrospective population-based study of ED presentations for respiratory-related reasons linked to birth data from 245,249 singleton live births in Western Australia. ED presentation rates <9 years of age were calculated for different diagnoses and predictors of ED presentation <5 years were assessed by multiple logistic regression.</p> <p>Results</p> <p>ED data from metropolitan WA, representing 178,810 births were available for analysis. From 35,136 presentations, 18,582 (52.9%) had an International Classification of Diseases (ICD) code for ALRI and 434 had a symptom code directly relating to an ALRI ICD code. A further 9600 presentations had a non-specific diagnosis. From the combined 19,016 ALRI presentations, the highest rates were in non-Aboriginal children aged 6–11 months (81.1/1000 child-years) and Aboriginal children aged 1–5 months (314.8/1000). Croup and bronchiolitis accounted for the majority of ALRI ED presentations. Of Aboriginal births, 14.2% presented at least once to ED before age 5 years compared to 6.5% of non-Aboriginal births. Male sex and maternal age <20 years for Aboriginal children and 20–29 years for non-Aboriginal children were the strongest predictors of presentation to ED with ALRI.</p> <p>Conclusions</p> <p>ED data can give an insight into the out-of-hospital burden of ALRI. Presentation rates to ED for ALRI were high, but are minimum estimates due to current limitations of the ED datasets. Recommendations for improvement of these data are provided. Despite these limitations, ALRI, in particular bronchiolitis and croup are important causes of presentation to paediatric EDs.</p