Correlation of the treatment sensitivity of patient-derived organoids with treatment outcomes in patients with head and neck cancer (SOTO): protocol for a prospective observational study.

INTRODUCTION: Organoids have been successfully used in several areas of cancer research and large living biobanks of patient-derived organoids (PDOs) have been developed from various malignancies. The characteristics of the original tumour tissue such as mutation signatures, phenotype and genetic diversity are well preserved in organoids, thus showing promising results for the use of this model in translational research. In this study, we aim to assess whether we can generate PDOs from head and neck squamous cell carcinoma (HNSCC) samples and whether PDOs can be used to predict treatment sensitivity in HNSCC patients as well as to explore potential biomarkers. METHODS AND ANALYSIS: This is a prospective observational study at a single centre (Guy's and St Thomas' NHS Foundation Trust) to generate PDOs from patients' samples to assess treatment response and to correlate with patients' treatment outcomes. Patients will be included if they are diagnosed with HNSCC undergoing curative treatment (primary surgery or radiotherapy) or presenting with recurrent or metastatic cancers and they will be categorised into three groups (cohort 1: primary surgery, cohort 2: primary radiotherapy and cohort 3: recurrent/metastatic disease). Research tumour samples will be collected and processed into PDOs and chemosensitivity/radiosensitivity will be assessed using established methods. Moreover, blood and other biological samples (eg, saliva) will be collected at different time intervals during treatment and will be processed in the laboratory for plasma and peripheral blood mononuclear cell (PBMC) isolation. Plasma and saliva will be used for circulating tumour DNA analysis and PBMC will be stored for assessment of the peripheral immune characteristics of the patients as well as to perform co-culture experiments with PDOs. SOTO study (correlation of the treatment Sensitivity of patient-derived Organoids with Treatment Outcomes in patients with head and neck cancer) uses the collaboration of several specialties in head and neck cancer and has the potential to explore multiple areas of research with the aim of offering a valid and effective approach to personalised medicine for cancer patients. ETHICS AND DISSEMINATION: This study was approved by North West-Greater Manchester South Research Ethics Committee (REC Ref: 22/NW/0023) on 21 March 2022. An informed consent will be obtained from all participants prior to inclusion in the study. Results will be disseminated via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT05400239.

Setting up a nurse-led 2-week-wait head and neck cancer diagnostic service.

The number of urgent '2-week-wait' referrals to hospital for people with suspected head and neck cancer being sent by primary care is constantly growing and it is becoming increasingly difficult for head and neck cancer services to meet this demand. In order for trusts to meet their Faster Diagnosis Standards, there needs to be an effective and efficient way to ensure there is capacity for patients to receive the appropriate assessments and diagnostic investigations without compromising the quality of care delivered. This article presents the proposal of introducing a nurse-led 2-week-wait clinic to meet the ever-growing demands on the service. There is discussion of the consultant-led training programme used to upskill an advanced nurse practitioner in a single-centre study, as well as explanation of the processes followed to maintain patient safety throughout the pilot project. There will also be consideration of clinical governance and discussion of how patient satisfaction with the novel service will be measured.

New robotic platform for transoral robotic surgery: an IDEAL stage 0 study.

Objectives: This study aims to assess the feasibility to perform transoral robotic surgery (TORS) with a new robotic platform, the Versius Surgical System (CMR Surgical, UK) in a preclinical cadaveric setting in accordance to stage 0 of the IDEAL-D framework. Design: IDEAL stage 0 preclinical assessment of the Versius Robotic System in TORS in human cadavers. Setting: All procedures were performed in a simulated operating theatre environment at a UK surgical training centre. Participants: 11 consultant head and neck surgeons from the UK, mainland Europe and the USA took part in TORS procedures on six human cadavers. Interventions: 3 key index procedures were assessed that represent the core surgical workload of TORS: lateral oropharyngectomy, tongue base resection and partial supraglottic laryngectomy. Main outcome measures: The primary outcome was the successful completion of each surgical procedure. Secondary outcomes included the optimisation of system setup, instrumentation and surgeon-reported outcomes for feasibility of each component procedural step. Results: 33 cadaveric procedures were performed and 32 were successfully completed. One supraglottic laryngectomy was not fully completed due to issues dividing the epiglottic cartilage with available instrumentation. Surgeon-reported outcomes met the minimal level of feasibility in all procedures and a consensus that it is feasible to perform TORS with Versius was reached. Available instrumentation was not representative of other robotic platforms used in TORS and further instrument optimisation is recommended before wider dissemination. Conclusions: It is feasible to perform TORS with the Versius Surgical System (CMR Surgical) within a pre-clinical cadaveric setting. Clinical evaluation is needed and appropriate with the system. Further instrument development and optimisation is desirable.

Prospective development study of the Versius Surgical System for use in transoral robotic surgery: an IDEAL stage 1/2a first in human and initial case series experience.

PURPOSE: Transoral robotic surgery is well established in the treatment paradigm of oropharyngeal pathology. The Versius Surgical System (CMR Surgical) is a robotic platform in clinical use in multiple specialities but is currently untested in the head and neck. This study utilises the IDEAL framework of surgical innovation to prospectively evaluate and report a first in human clinical experience and single centre case series of transoral robotic surgery (TORS) with Versius. METHODS: Following IDEAL framework stages 1 and 2a, the study evaluated Versius to perform first in human TORS before transitioning from benign to malignant cases. Iterative adjustments were made to system setup, instrumentation, and technique, recorded in accordance with IDEAL recommendations. Evaluation criteria included successful procedure completion, setup time, operative time, complications, and subjective impressions. Further evaluation of the system to perform four-arm surgery was conducted. RESULTS: 30 TORS procedures were successfully completed (15 benign, 15 malignant) without intraoperative complication or conversion to open surgery. Setup time significantly decreased over the study period. Instrumentation challenges were identified, urging the need for TORS-specific instruments. The study introduced four-arm surgery, showcasing Versius' unique capabilities, although limitations in distal access were observed. CONCLUSIONS: TORS is feasible with the Versius Surgical System. The development of TORS-specific instruments would benefit performance and wider adoption of the system. 4-arm surgery is possible however further evaluation is required. Multicentre evaluation (IDEAL stage 2b) is recommended.

Robotic assisted orbital surgery for resection of advanced periocular tumours - a case series report on the feasibility, safety and outcome.

PURPOSE: Orbital surgery benefits from well-designed instrumentation that offers gentle tissue manipulation, high manoeuvrability and control. Nevertheless, in confined spaces, tissue manipulation must be accomplished with exceptionally high accuracy and precision. This is where robotic surgery offers an advantage. We aimed to evaluate a robotic-assisted surgical system's feasibility, safety and outcome in assisting tumour clearance. PATIENTS AND METHODS: A case series of patients with advanced periocular tumours undergoing robotic-assisted globe-sparing resection was performed using the DaVinci XI system (Intuitive Surgical, Inc). Institutional ethics and multidisciplinary approval were sought in all cases. RESULTS: Four patients with advanced periocular tumours underwent robotic-assisted orbital surgery at a mean age of 63 years (range 42-86). Two patients were diagnosed with squamous cell carcinoma, and two had basal cell carcinoma. One patient was found to have positive lymph nodes at the time of surgery and underwent simultaneous parotidectomy and lymph node clearance. Clear resection of the primary tumour was achieved in all patients; three patients underwent further resection due to narrow margins prior to reconstruction. Patients were follow-up for at least one year, and three remained disease-free. One patient with pre-existing extra-orbital disease developed metastatic disease four months post-op. All patients preserved vision peri-operatively, with no complaints of diplopia. Moderate ocular surface disease was noted in two patients. CONCLUSION: Our series highlights the potential advantage of three-dimensional optics, multi-directional instrumentation and motion scaling technology to achieve globe-sparing tumour resection in advanced periocular tumours. However, further robotic instrumentation development is required for orbital surgery.

Soft Tissue Robotic Assisted Orbital Surgery Using da Vinci SP: A Cadaveric Experience.

PURPOSE: Robotic surgical techniques have transformed many surgical specialties however robotic techniques and applications have been much more limited in ophthalmology. This study aims to evaluate the feasibility of robotic assisted orbital surgery using a single-port novel robotic platform, the da Vinci SP. METHODS: A series of orbital procedures were performed in cadaveric specimens utilizing the da Vinci SP robotic system. The procedures performed included lacrimal gland dissection and biopsy, medial and lateral orbital wall dissections, enucleation, and lid-sparing orbital exenteration. Successful completion of each procedure was defined by the operating surgeon and was considered the primary outcome and marker of feasibility. RESULTS: Seven cadaveric procedures were performed in 3 cadaveric specimens. All 7 procedures were completed successfully without complication. Setup optimization occurred throughout the study and setup and operative times were acceptable. Three instrument arms and 1 endoscope were utilized throughout the study allowing 3 arm operating and dynamic retraction. Instrument size was found to limit surgical access and precision particular at the orbital apex. CONCLUSIONS: This preclinical study demonstrates that the da Vinci SP can be utilized within the orbit and is feasible for several applications. Robotic surgical systems offer significant advantages over conventional techniques and should be embraced. However, current commercially available robotic platforms are not optimized for the orbit and have their limitations although they may be suitable for some clinical applications.

Thyroglossal duct cyst carcinoma case series-Management strategy and outcomes.

OBJECTIVE: To review the clinical presentation, diagnosis, pathology and management strategies in a modern cohort of patients with thyroglossal duct cyst carcinoma. STUDY DESIGN: Retrospective case series following PROCESS Guidelines. SETTING: Comprehensive cancer centre. METHODS: Data recorded included: gender, age at diagnosis, clinical presentation, thyroid function, diagnostic investigations, cytological results, final histology, staging and follow up status. The risk of malignancy in cytological analysis was stratified according to the Royal College of Pathologists classification in United Kingdom. RESULTS: Twelve patients were included. The majority of patients (66.7%) presented with an isolated thyroglossal duct cyst. Only 4 patients had preoperative cytological suspicion of carcinoma (sensitivity: 33.3%). At the time of presentation all patients were euthyroid. Following diagnosis of malignancy, a total thyroidectomy was performed in all patients, with the exception of 2, who had a thyroglossal duct cyst carcinoma of less than 10mm. Among the 10 patients who underwent total thyroidectomy, 7 (70%) patients had proven carcinoma in the thyroid gland, 3 with deposits of less than 10mm. The average size of the thyroid cancer deposits was 7.2mm (1-20mm). With a mean follow-up of is 44 months (5-120), all patients were alive and free of recurrence at the end of the study period. CONCLUSION: Thyroglossal duct cyst carcinoma is a rare condition and its management should be discussed in a multidisciplinary meeting. As with differentiated thyroid cancer originating in the thyroid gland, it bears extraordinary survival rates. Accordingly, the management of these cancers has shifted towards a more conservative approach although its peculiarities must be taken into account: ease of extracystic invasion and possible different lymph node invasion.

Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study.

BACKGROUND: Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αß, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues. METHODS: We undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1-4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×107-1×109 T4+ T-cells, administered without prior lymphodepletion. RESULTS: Despite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4+ T-cells into the circulation following intratumoral delivery, and injection of radiolabeled cells demonstrated intratumoral persistence. Despite rapid progression at trial entry, stabilization of disease (Response Evaluation Criteria in Solid Tumors V.1.1) was observed in 9 of 15 subjects (60%) at 6 weeks post-CAR T-cell administration. Subsequent treatment with pembrolizumab and T-VEC oncolytic virus achieved a rapid complete clinical response in one subject, which was durable for over 3 years. Median overall survival was greater than for historical controls. Disease stabilization was associated with the administration of an immunophenotypically fitter, less exhausted, T4 CAR T-cell product. CONCLUSIONS: These data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC.

Mechanistic insights into the interactions between cancer drivers and the tumour immune microenvironment.

BACKGROUND: The crosstalk between cancer and the tumour immune microenvironment (TIME) has attracted significant interest in the latest years because of its impact on cancer evolution and response to treatment. Despite this, cancer-specific tumour-TIME interactions and their mechanistic insights are still poorly understood. METHODS: Here, we compute the significant interactions occurring between cancer-specific genetic drivers and five anti- and pro-tumour TIME features in 32 cancer types using Lasso regularised ordinal regression. Focusing on head and neck squamous cancer (HNSC), we rebuild the functional networks linking specific TIME driver alterations to the TIME state they associate with. RESULTS: The 477 TIME drivers that we identify are multifunctional genes whose alterations are selected early in cancer evolution and recur across and within cancer types. Tumour suppressors and oncogenes have an opposite effect on the TIME and the overall anti-tumour TIME driver burden is predictive of response to immunotherapy. TIME driver alterations predict the immune profiles of HNSC molecular subtypes, and perturbations in keratinization, apoptosis and interferon signalling underpin specific driver-TIME interactions. CONCLUSIONS: Overall, our study delivers a comprehensive resource of TIME drivers, gives mechanistic insights into their immune-regulatory role, and provides an additional framework for patient prioritisation to immunotherapy. The full list of TIME drivers and associated properties are available at http://www.network-cancer-genes.org .

Water soluble swallow for leak detection after total laryngectomy post radiotherapy.

AIM: Pharyngeal leak (PL) and pharyngocutaneous fistula (PCF) are serious complications following total laryngectomy and their incidence is higher in the salvage setting. The aim of this study is to describe the accuracy of water soluble swallow (WSS) to rule out salivary postoperative leak after salvage total laryngectomy (STL) to expedite start of oral intake. MATERIAL AND METHODS: Retrospective study including patients undergoing STL between 2008 and 2021 at Guy's Hospital. WSS was routinely performed within 15 days post operation. RESULTS: Sixty-six patients underwent STL. Nine developed clinically diagnosed PCF; one died before having WSS. Fifty-six patients underwent WSS post STL. WSS was performed within 15 days after STL when no postoperative complications occurred (76.8%). Among patients undergoing WSS with no clinical suspicion for fistula (56), PL was identified in 15 cases (26.8%). They were managed conservatively; PCF was avoided in 7(46.7%) cases. Three patients (7.3%) developed PCF after having started oral intake with a negative WSS. These three cases were further analysed, 2 cases where recorded at the beginning of the studied period when less experience was available possibly leading to incorrect results. Sensitivity and negative predictive value (NPV) for fistula prediction were 72.7% and 92.7%, respectively. CONCLUSION: Taking into account the high NPV of WSS, it is safe to start oral intake after negative WSS. Further studies to evaluate its accuracy earlier on after SLT are justified taking into account the results and the impact that delayed feeding has on patient's quality of life.

Clinical outcomes in relapsed oropharyngeal cancer after definitive (chemo) radiotherapy.

OBJECTIVES: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT]. MATERIALS AND METHODS: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS). RESULTS: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). CONCLUSION: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS.

Neck Dissection Timing in Transoral Robotic or Laser Microsurgery in Oropharyngeal Cancer: A Systematic Review.

Objective: This review assesses the effect on intra- and postoperative patient outcomes of the timing of neck dissection in relation to transoral surgery. Outcome measures include postoperative bleeding, intra- and postoperative fistula formation, and disease-specific and overall survival. Data Sources: A search was conducted across the MEDLINE, Embase, US National Library of Medicine, and Cochrane databases with search terms in July 2021. Review Methods: Articles that conformed with specified inclusion criteria were included. Included articles were scanned for bias with the ROBINS-I tool. Results: Nineteen articles were selected for qualitative analysis, including 546 patients who had neck dissection in conjunction with transoral robotic surgery/transoral laser microsurgery (TORS/TLM). Seventy-one (18%) patients had neck dissection prior to TORS/TLM, 39 (10%) had neck dissection performed after TORS/TLM, and 281 (72%) had concurrent procedures. In patients with neck dissection before TORS/TLM, 3% experienced major postoperative bleeding, and fistula rates were 0%. In the cohort with neck dissection after TORS/TLM, 3% experienced minor postoperative hemorrhage, and 8% had intraoperative fistulae. In the concurrent cohort of patients, 1% had major postoperative bleeds and 0.3% had minor bleeds, while 4% developed intraoperative fistulas and 0.3% developed postoperative fistulas. Conclusion: Current evidence indicated that there appears to be no correlation between timing of neck dissection and complications. This systematic review found insufficient data to comment on whether the timing of neck dissection in relation to TORS/TLM affects the outcomes of patients.

Reducing the unknowns: A systematic review & meta-analysis of the effectiveness of trans-oral surgical techniques in identifying head and neck primary cancer in carcinoma unknown primary.

OBJECTIVES: The use of transoral robotic surgery (TORS), transoral laser microsurgery (TLM) and more recently reported transoral endoscopic electrocautery (TOEC) in identifying the primary cancer in head and neck Carcinoma Unknown Primary (CUP) patients have gained popularity. This review aims to assess the effectiveness of TORS, TLM and TOEC. MATERIALS & METHODS: A systematic review and meta-analysis was carried out. EMBASE, MEDLINE and CINAHL databases were searched from inception to September 2020. All primary studies were considered for inclusion. Primary outcome measure was detection rates of primary cancer of the different techniques. Secondary outcome measures were complications and length of hospital stay. RESULTS: 289 studies were identified of which 30 met the inclusion criteria. The primary cancer was identified in 567 /777 patients (pooled results was 64% (95% CI 54-73). The primary identification rates were 45% and 32% in lingual (n = 273) and palatine tonsillectomy (n = 118) respectively. The primary cancer identification rates by surgical techniques are: TORS was 60% (95% CI 49-70), TLM was 80% (95% CI 0.58, 1.01), TOEC was 41% (95% CI 0.05, 0.76). 529/777 (68%) tumours were Human Papilloma Virus (HPV) related. The pooled data of studies that reported on detection rates relating to HPV status were 178/216 (82%) for HPV +ve and 7/59 (12%) for HPV -ve tumours. Coefficient of variation results suggest heterogenous data for TORS and TLM. The commonest complication was haemorrhage (5.3%). The length of reported hospital stay ranged from 1.4 to 7 days. CONCLUSIONS: This is the largest systematic review in the subject. The quality of studies and heterogeneity of data limit conclusive findings. Lingual tonsillectomy is an effective procedure in CUP work up. Further larger, multicentre, prospective studies of PET CT negative CUP patients is needed to draw conclusive results.

Outcomes of head and neck cancer management from two cancer centres in Southern and Northern Europe during the first wave of COVID-19.

OBJECTIVE: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC). METHODS: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London). RESULTS: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [p = 0.058] and 40% vs 8% [p = 0.025]). Multivariate logistic regression analyses confirmed our data (p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different (p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%). CONCLUSIONS: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Role of Thyroidectomy in Recurrent Laryngeal Carcinoma.

OBJECTIVE: Management of recurrent laryngeal cancer presents a major challenge, and salvage laryngectomy is complicated by previous oncologic treatments. Thyroidectomy as part of salvage laryngectomy adds a nonnegligible degree of morbidity. The purpose of this study is to assess the rate of thyroid gland invasion in patients undergoing salvage laryngectomy to determine relevant predictive factors. STUDY DESIGN: Case series with chart review. SETTING: Department of Otorhinolaryngology, Head and Neck Surgery, Guy's Hospital, London, United Kingdom. METHODS: A retrospective review of patients undergoing salvage laryngectomy between 2009 and 2019 was undertaken. Preoperative cross-sectional imaging and histopathological analysis were performed to define evidence and predictors of thyroid gland invasion (TGI). RESULTS: Fifty-one patients had salvage laryngectomy. Histological evidence of TGI was found in 4 patients (7.8%). No significant relationship was found between histological TGI and subsite of primary carcinoma, degree of differentiation, T staging, or radiological TGI. Preoperative computed tomography had a high negative predictive value for TGI. CONCLUSION: Thyroidectomy should be carefully considered in patients undergoing salvage laryngectomy, and its extent should be defined on an individual basis. Total thyroidectomy should not routinely be performed in salvage laryngectomy or pharyngolaryngectomy in patients with no preoperative radiological evidence of TGI on cross-sectional imaging, unless there is intraoperative evidence of TGI.

Treating the N0 neck in early stage oral cancer: a pause for re-assessment?

The incidence of metastases following neck dissection in the apparent lymph node negative neck in oral cancer is between 7% and 33%; early resection of cervical metastases may well increase survival. Modern imaging techniques can reduce the yield of previously undiagnosed metastatic nodes in elective neck dissection (END). An audit of 112 consecutive cases was conducted to determine the proportion of undiagnosed nodal metastases, after END. There were neck metastases in 10 cases (9%), which were mainly (but not all) micrometastic. The 20% likelihood of nodal metastases was only apparent in primary tumours greater than 6 mm thick. The length of inpatient stay was increased from 3.7 to 16.5 days with free vascularised transfer. There were complications including cranial nerve damage. There were two peri-operative deaths. No ipsilateral neck failures occurred, median follow up was 937 days. To reduce unnecessary END, resection can be undertaken as a prior procedure, subsequently only carrying out END on tumours greater than 6 mm, or with unfavourable tumour characteristics.

Locally Advanced Scalp Tumors: Clinical and Survival Outcomes of a Tertiary Unit.

INTRODUCTION: Locally advanced nonmelanoma skin cancers of the head and neck are well described in the current literature. However, data about clinical and survival outcomes are lacking. We present survival data from a tertiary head and neck cancer unit in London. METHODS: A retrospective analysis of data collected from a single institution was conducted. All patients with locally advanced cutaneous scalp carcinomas invading the skull between 2011 and 2019 were included. Data included patient demographics, tumor, comorbidities, interventions, flap survival, and metal work exposure. Survival outcomes were examined using Kaplan-Meier analysis. RESULTS: Twenty-three patients were identified. The mean age was 72 years. Eighteen patients were male, and 5 were female. Five patients were immunosuppressed. Nineteen patients underwent outer cortex drill-down/full-thickness calvarial resection, followed by reconstruction with free tissue transfer. Six patients had titanium mesh reconstruction after segmental skull resections. Three patients underwent further surgery because of exposed metalwork. Disease-free survival at 3 years after surgery was 60%. CONCLUSIONS: Locally advanced nonmelanoma skin cancers invading the bone are sporadic. There are little published data on clinical and survival outcomes in this group. Despite the nature of these skin lesions, a high degree of local control can be obtained by extensive surgical resection, outer table drill-down, and calvarial resection. We conclude that aggressive management of the bony invasion improves disease-free survival and improves local control.

Risk stratified follow up for head and neck cancer patients - An evidence based proposal.

Head and neck squamous cell carcinoma (HNSCC) has a significant impact on patients' quality of life and treatment can be associated with severe morbidity. Following completion of treatment, patients are followed up in order to detect potentially salvageable recurrences and to manage long-term toxicities. In recent years, a growing interest has been given to risk stratified follow-up interventions to prevent and detect recurrences and manage treatment toxicities in other tumour sites as well as to transfer some of that care to community services. We review the literature for HNSCC and propose a risk stratified follow up protocol to address these issues and assist clinicians in decision making. A shift in patterns of care is suggested in order to provide a basis to improve care for HNSCC patients after complete response to primary treatment.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

PURPOSE: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. MATERIAL AND METHODS: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. RESULTS: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. CONCLUSION: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.