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Purpose The main aim of this paper is to present baseline demographic and clinical characteristics and HRQOL in the two groups of the Patient Concerns Inventory (PCI) trial. The baseline PCI data will also be described. Methods This is a pragmatic cluster preference randomised control trial with 15 consultant clusters from two sites either ‘using' (n = 8) or ‘not using’ (n = 7) the PCI at a clinic for all of their trial patients. The PCI is a 56-item prompt list that helps patients raise concerns that otherwise might be missed. Eligibility was head and neck cancer patients treated with curative intent (all sites, stage of disease, treatments). Results From 511 patients first identified as eligible when screening for the multi-disciplinary tumour board meetings, 288 attended a first routine outpatient baseline study clinic after completion of their treatment, median (IQR) of 103 (71–162) days. At baseline, the two trial groups were similar in demographic and clinical characteristics as well as in HRQOL measures apart from differences in tumour location, tumour staging and mode of treatment. These exceptions were cluster (consultant) related to Maxillofacial and ENT consultants seeing different types of cases. Consultation times were similar, with PCI group times taking about 1 min longer on average (95% CL for the difference between means was from − 0.7 to + 2.2 min). Conclusion Using the PCI in routine post-treatment head and neck cancer clinics do not elongate consultations. Recruitment has finished but 12-month follow-up is still ongoing.

Purpose The patient concerns inventory (PCI) is a prompt list allowing head and neck cancer (HNC) patients to discuss issues that otherwise might be overlooked. This trial evaluated the effectiveness of using the PCI at routine outpatient clinics for one year after treatment on health-related QOL (HRQOL). Methods A pragmatic cluster preference randomised control trial with 15 consultants, 8 ‘using’ and 7 ‘not using’ the PCI intervention. Patients treated with curative intent (all sites, disease stages, treatments) were eligible. Results Consultants saw a median (inter-quartile range) 16 (13–26) patients, with 140 PCI and 148 control patients. Of the pre-specified outcomes, the 12-month results for the mean University of Washington Quality of Life (UW-QOLv4) social-emotional subscale score suggested a small clinical effect of intervention of 4.6 units (95% CI 0.2, 9.0), p = 0.04 after full adjustment for pre-stated case-mix. Results for UW-QOLv4 overall quality of life being less than good at 12 months (primary outcome) also favoured the PCI with a risk ratio of 0.83 (95% CI 0.66, 1.06) and absolute risk 4.8% (− 2.9%, 12.9%) but without achieving statistical significance. Other non-a-priori analyses, including all 12 UWQOL domains and at consultant level also suggested better HRQOL with PCI. Consultation times were unaffected and the number of items selected decreased over time. Conclusion This novel trial supports the integration of the PCI approach into routine consultations as a simple low-cost means of benefiting HNC patients. It adds to a growing body of evidence supporting the use of patient prompt lists more generally.

We studied the progression from dysplasia to invasive carcinoma and subsequent second primaries or locoregional recurrences in 11 patients with recurrent squamous cell carcinoma (SCC). Between one and six samples were sequenced/patient. DNA samples were prepared, and libraries multiplexed to between 40 and 80 samples/lane of an Illumina HiSeq 3000 and sequenced with 2 × 100 bp paired end sequencing. Copy number data were generated by CNAnorm (Bioconductor package). Samples of recurrent SCC showed unique patterns of descent when compared with earlier samples from the primary tumour, and three main patterns emerged. In four patients there was convincing evidence that the later lesion was descended directly from cells from the first, and in a further four there were no detectable genomic events between the two lesions. Three patients had some shared events between the early and later lesions, but although there were enough differences to deduce that the two lesions had a shared ancestor, they were not directly descended from each other. We present the patients’ characteristics in detail, including the overall survival in each group. There was a distinct genomic pattern after a second episode of SCC in all the groups. A larger study that uses similar methods and a longer duration could provide reliable conclusions with respect to survival. With the use of new techniques, genomic data can be available to clinical teams during the planning of treatment.

The study of the relationships between pre-cancer and cancer and identification of early driver mutations is becoming increasingly important as the value of molecular markers of early disease and personalised drug targets is recognized, especially now the extent of clonal heterogeneity in fully invasive disease is being realized. It has been assumed that pre-cancerous lesions exhibit a fairly passive progression to invasive disease; the degree to which they, too, are heterogeneous is unknown. We performed ultra-deep sequencing of thousands of selected mutations, together with copy number analysis, from multiple, matched pre-invasive lesions, primary tumours and metastases from five patients with oral cancer, some with multiple primary tumours presenting either synchronously or metachronously, totalling 75 samples. This allowed the clonal relationships between the samples to be observed for each patient. We expose for the first time the unexpected variety and complexity of the relationships between this group of oral dysplasias and their associated carcinomas and, ultimately, the diversity of processes by which tumours are initiated, spread and metastasize. Instead of a series of genomic precursors of their adjacent invasive disease, we have shown dysplasia to be a distinct dynamic entity, refuting the belief that pre-cancer and invasive tumours with a close spatial relationship always have linearly related genomes. We show that oral pre-cancer exhibits considerable subclonal heterogeneity in its own right, that mutational changes in pre-cancer do not predict the onset of invasion, and that the genomic pathway to invasion is neither unified nor predictable. Sequence data from this study have been deposited in the European Nucleotide Archive, Accession No. PRJEB6588.

Verrucous carcinoma of the oral cavity (OVC) is considered a subtype of classical oral squamous cell carcinoma (OSCC). Diagnosis is problematic, and additional biomarkers are needed to better stratify patients. To investigate their molecular signature, we performed low-coverage copy number (CN) sequencing on 57 OVC and exome and RNA sequencing on a subset of these and compared the data to the same OSCC parameters. CN results showed that OVC lacked any of the classical OSCC patterns such as gain of 3q and loss of 3p and demonstrated considerably fewer genomic rearrangements compared to the OSCC cohort. OVC and OSCC samples could be clearly differentiated. Exome sequencing showed that OVC samples lacked mutations in genes commonly associated with OSCC (TP53, NOTCH1, NOTCH2, CDKN2A and FAT1). RNA sequencing identified genes that were differentially expressed between the groups. In silico functional analysis showed that the mutated and differentially expressed genes in OVC samples were involved in cell adhesion and keratinocyte proliferation, while those in the OSCC cohort were enriched for cell death and apoptosis pathways. This is the largest and most detailed genomic and transcriptomic analysis yet performed on this tumour type, which, as an example of non-metastatic cancer, may shed light on the nature of metastases. These three independent investigations consistently show substantial differences between the cohorts. Taken together, they lead to the conclusion that OVC is not a subtype of OSCC, but should be classified as a distinct entity.

A busy head and neck or oral and maxillofacial (OMFS) National Health Service (NHS) clinic treats patients with many different conditions. A large proportion will have cancer of the head and neck, and they will be at different stages of their treatment. Their clinical needs may be different from a larger group of patients who have been referred through the “two-week wait” referral pathway, and who are present in the same clinic for their biopsy results. We present our early experience of “fast-track” referrals and their potential effect on the overall volume of work. They are only a small number of the patients who are typically seen in a nurse-led clinic.

Background It is frequently assumed that pre-invasive lesions are simpler precursors of cancer and will contain a limited subset of the genomic changes seen in their associated invasive disease. Driver mutations are thought to occur early, but it is not known how many of these are present in pre-invasive lesions. These assumptions need to be tested with the increasing focus on both personalised cancer treatments and early detection methodologies. Methods We examined genomic copy number changes in 256 pre-invasive and invasive samples from 69 oral cancer patients. Forty-eight samples from 16 patients were further examined using exome sequencing. Results Evidence of a shared ancestor of both dysplasia and carcinoma was seen in all but one patient. One-third of dysplasias showed independent copy number events. The remainder had a copy number pattern that was similar to or simpler than that of the carcinoma. All dysplasias examined contained somatic mutations absent in the related carcinoma. Previously observed copy number changes and TP53 mutations were very frequently observed, and almost always shared between dysplasia and carcinoma. Other gene changes were more sporadic. Pathway analysis confirmed that each patient’s disease developed in a different way. Examining the numbers of shared mutations and the rate of accumulation of mutations showed evidence that all samples contain a population of sub-clones, with little evidence of selective advantage of a subset of these. Conclusions These findings suggest that most of the genomic changes driving oral cancer occur in the pre-cancerous state by way of gradual random accumulation rather than a dramatic single event. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0442-0) contains supplementary material, which is available to authorized users.

Reliable assessment of the perfusion of free tissue transfers has always been a challenge for reconstructive microsurgeons. The complexities of flap microcirculation are often difficult to assess despite all the subjective and objective examination techniques available today, particularly when the free tissue transfer is buried, and not visible for monitoring. We investigated the post-operative management of free tissue transfers to the head and neck in the United Kingdom. Selected results from our survey show that the majority of units performed between two and five free tissue transfers to the head and neck region per month ( n = 60, mean = 4.13, range 1–12). Clinical tests were used to monitor the flaps post-operatively in all units questioned. Hand held doppler was the most commonly used adjunctive technique, being routinely used for post-operative monitoring by twenty six units, and available for use in eighteen other units with the most common indications for use were, slow capillary refill and pale colour. Frequency and location of monitoring post-operatively was highly variable. Nurses were responsible for the routine monitoring of flaps in almost every unit. Thirty four units (57%) had a written protocol in place governing the monitoring of free tissue transfers post-operatively. We note the wide variation in practice on a national level, and make certain recommendations.

A circadian rhythm in CO2 production was observed in three cultivars of Anthurium andraeanum Andre ('Jaya', 'Fla-range', 'Leonette') flowers. The rhythmicity was not affected by light, darkness, and detachment. However, the amplitude was dampened in darkness and after detachment. Spadix respiration accounted for 90% of the total flower respiration. Rhythmicity in CO 2 production continued after spathe removal. Less pronounced rhythmicity was observed following spadix removal. sured with an infrared CO 2 analyzer (Analyti- cal Development Co., Herts, U.K.). The respi- ration chamber was made of plexiglass with a removable top to allow the introduction of the flower, and a small groove was cut in one of the side walls to hold the peduncle. The air temperature around the flower was controlled by continuous circulation of water into a water

The use of next-generation sequencing technologies to produce genomic copy number data has recently been described. Most approaches, however, reply on optimal starting DNA, and are therefore unsuitable for the analysis of formalin-fixed paraffin-embedded (FFPE) samples, which largely precludes the analysis of many tumour series. We have sought to challenge the limits of this technique with regards to quality and quantity of starting material and the depth of sequencing required. We confirm that the technique can be used to interrogate DNA from cell lines, fresh frozen material and FFPE samples to assess copy number variation. We show that as little as 5 ng of DNA is needed to generate a copy number karyogram, and follow this up with data from a series of FFPE biopsies and surgical samples. We have used various levels of sample multiplexing to demonstrate the adjustable resolution of the methodology, depending on the number of samples and available resources. We also demonstrate reproducibility by use of replicate samples and comparison with microarray-based comparative genomic hybridization (aCGH) and digital PCR. This technique can be valuable in both the analysis of routine diagnostic samples and in examining large repositories of fixed archival material.