Improved survival prediction for oropharyngeal cancer beyond TNMv8.

PURPOSE: For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction. MATERIAL AND METHODS: All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model. RESULTS: Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE] ±â€¯SE = 0.72 ±â€¯0.02 vs 0.53 ±â€¯0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPE = 0.79 vs 0.79, p = 0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76 ±â€¯0.02). CONCLUSIONS: TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease.

Transoral laser microsurgery versus radiotherapy for T2 glottic squamous cell carcinoma: a systematic review of local control outcomes.

BACKGROUND: Systematic reviews comparing treatment of early glottic cancer with transoral surgery or radiotherapy demonstrate similar oncological outcomes. Most studies of 'early-stage' laryngeal cancer include Tis, T1a, T1b and T2 cases. The data are dominated by patients with T1 and Tis tumours, although extrapolating these results and applying them for T2 cases may be inappropriate. No previous systematic reviews have focused on T2 cancers as a separate group. OBJECTIVE OF REVIEW: This review compares local control outcomes for T2 glottic squamous cell carcinoma, treated with transoral microsurgery or external beam radiotherapy. TYPE OF REVIEW: This is a systematic review of case series and comparison studies, focusing on oncological outcomes. SEARCH STRATEGY: Independent searches of MEDLINE, EMBASE and the Cochrane Database were conducted by two authors, using the search terms: laryngeal/glottic/vocal cord combined with carcinoma/cancer/tumour and laser/microsurgery or radiotherapy. Studies of adult patients treated for primary T2N0 glottic squamous cell carcinoma (SCC) with laser surgery or curative radiotherapy were included. EVALUATION METHOD: Full text of studies satisfying the inclusion criteria were reviewed with extraction of local control and survival data and laryngeal preservation rates. The primary endpoint is local control at 5 years. RESULTS: Initial searches identified 3252 studies. Following full-text review of 183 papers, 59 studies met the inclusion criteria, all level IV evidence. A total of 48 studies specified 5-year local control for 1156 patients treated with transoral laser surgery and 3191 patients treated with radiotherapy. Weighted averages of local control at 5 years demonstrated similar results: 75.81% for radiotherapy versus 77.26% for transoral laser surgery. CONCLUSIONS: The results of this review indicate no difference in 5-year local control between radiotherapy and transoral surgery for T2 glottic SCC. The data demonstrated higher rates of local failure for T2b compared with T2a cases, although outcomes were similar between laser excision and radiotherapy for each substage. Further research focusing upon functional outcomes for T2 glottic tumours is imperative to guide decision-making, ideally with subgroup analysis of T2a and T2b cases.

Surgery in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Surgery is one of the key modalities used in head and neck cancer treatment. Recent advances and a greater awareness of the short- and long-term toxicities associated with non-surgical modalities and newer technologies that permit minimal access resections have led to a resurgence in surgery. This paper provides an overview of the role of surgery in head and neck cancer practice.

Management of lateral skull base cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition. Recommendations • All patients with more than one of: chronic otalgia, bloody otorrhoea, bleeding, mass, facial swelling or palsy should be biopsied. (R) • Magnetic resonance and computed tomography imaging should be performed. (R) • Patients should undergo audiological assessment. (R) • Carotid angiography is recommended in select patients. (G) • The modified Pittsburg T-staging system is recommended. (G) • The minimum operation for cancer involving the temporal bone is a lateral temporal bone resection. (R) • Facial nerve rehabilitation should be initiated at primary surgery. (G) • Anterolateral thigh free flap is the workhorse flap for lateral skull base defect reconstruction. (G) • For patients undergoing surgery for squamous cell carcinoma, at least a superficial parotidectomy and selective neck dissection should be carried out. (R).

Subcranial craniofacial resection for advanced sinonasal malignant tumours involving the anterior skull base.

BACKGROUND: The subcranial approach is a modification of traditional craniofacial resection. It provides similar broad access to the anterior skull base, but with lower mortality and morbidity. It has been the surgical technique of choice at our institution since 2006 for treating advanced stage sinonasal tumours (American Joint Committee on Cancer stage III or above). This paper reports our experience and outcomes. METHOD AND RESULTS: Eighteen patients underwent subcranial craniofacial resection over a seven-year period, this being combined with a second adjunctive procedure in 89 per cent of cases. Forty per cent of patients required reconstruction of the primary defect. No peri-operative deaths occurred. One patient had a transient cerebrospinal fluid leak. The major complication rate was 33 per cent, of which 67 per cent were directly related to soft tissue reconstruction. Tumour recurrence rate was 17 per cent and the five-year disease-free survival estimate was 40 per cent. CONCLUSION: The subcranial approach is a safe and effective technique that may be used to successfully treat advanced sinonasal malignancies with anterior skull base extension.

Transoral laser surgery versus radiotherapy for tumour stage 1a or 1b glottic squamous cell carcinoma: systematic review of local control outcomes.

BACKGROUND: Previous literature reviews comparing transoral laser surgery versus radiotherapy for glottic carcinoma treatment have analysed 'early stage' disease as one group. The current review aimed to assess local control outcomes, comparing these two treatment modalities, specifically for either tumour stage 1a or stage 1b lesions. METHODS: The three authors conducted independent, structured literature searches. Simple weighted means were calculated. RESULTS: Thirty-six publications were analysed. Three-year local control rates for tumour stage 1a tumours were 88.9 per cent for transoral laser surgery (n = 1308) and 89.3 per cent for radiotherapy (n = 2405). For tumour stage 1b tumours, the local control rates were 76.8 per cent for transoral laser surgery (n = 194) and 86.2 per cent for radiotherapy (n = 492). CONCLUSION: From this analysis of level four evidence, there was no demonstrable difference in local control rates for tumour stage 1a glottic squamous cell carcinoma treated by transoral laser surgery or radiotherapy. There was a trend towards improved local control of tumour stage 1b tumours treated with radiotherapy, but this finding was based on a limited number of published outcomes (n = 194).

Nasopharyngeal carcinoma: a retrospective review of demographics, treatment and patient outcome in a single centre.

AIMS: Nasopharyngeal cancer (NPC) is relatively uncommon, especially in the Western world. We report our single institution experience of 20 years of data in 128 patients with NPC, including responses to different treatment modalities and outcomes by histological subtype. MATERIALS AND METHODS: NPC patients presenting from 1992 to 2005 were located on the cancer registry database. Demographic data included age, gender, length of presenting symptoms and stage. World Health Organization classification (2005) was used for histological subtyping. The date of recurrence and survival outcomes were analysed using Kaplan-Meier curves. RESULTS: Presentation data were analysed from 128 patients; the survival analysis included 123 patients. The median age at presentation was 57.7 years. Stage III and IV presentation rates were 34 and 38%, respectively. The most common presenting symptom was a palpable neck lump (55%) and the median duration of symptoms was 16 weeks. Forty-eight patients received radiotherapy alone and 75 received chemoradiotherapy. The median overall survival in chemoradiotherapy patients was 80.3 months versus 28.5 months with radiotherapy alone (P = 0.003). A significant difference was also seen with recurrence-free survival (RFS) (P = 0.017). Type 1 keratinising carcinoma had a significantly worse overall survival (P = 0.04) and a similar but non-statistically significant trend was seen for RFS (P = 0.051). The multivariate analysis for overall survival showed that histological subtype (hazard ratio 2.7, 95% confidence interval 1.3-5.5, P = 0.034), age (hazard ratio 2.3, 95% confidence interval 1.1-4.9, P = 0.018) and N stage (hazard ratio 3.7, 95% confidence interval 1.4-9.4, P = 0.024) were prognostic factors. CONCLUSIONS: We present the first large-scale, single-centre retrospective review of NPC in a UK-based population. Demographic data were similar to that in other Western populations, with a significantly worse survival outcome in the keratinising group. Further prospective study of outcome in Western populations accounting for newer radiotherapy techniques such as intensity-modulated radiotherapy and dose escalation, particularly in the keratinising population who were more likely to present with an isolated local recurrence, is recommended.

Lack of prognostic effect of carbonic anhydrase-9, hypoxia inducible factor-1α and bcl-2 in 286 patients with early squamous cell carcinoma of the glottic larynx treated with radiotherapy.

AIMS: To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy. MATERIALS AND METHODS: In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50-55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2. RESULTS: At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance. CONCLUSIONS: High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker.

Outcomes following pharyngolaryngectomy reconstruction with the anterolateral thigh (ALT) free flap.

We retrospectively reviewed 15 cases of pharyngolaryngectomy for advanced laryngeal carcinoma reconstructed with the anterolateral thigh (ALT) free flap. Thirteen patients had primary surgery and adjuvant treatment (radiotherapy or chemoradiotherapy), and two had salvage surgery. Thirteen had stage III or IV disease, and eight had cervical nodal extracapsular spread. In this series all the flaps survived, and at median follow-up of 14.5 months (range 3.7-31.2), 12 of the 15 patients were alive. One patient developed a chronic pharyngocutaneous fistula, and five required repeat balloon dilatations for late pharyngeal strictures. Six patients enjoyed restoration of full oral intake, seven were able to take a soft diet, and two were dependent on feeding by percutaneous endoscopic gastrostomy. Four patients developed adequate tracheo-oesophageal speech, and one successfully developed oesophageal speech. In this series many of the surgical problems associated with pharyngolaryngectomy reconstruction were addressed successfully by the ALT, but late dysphagia remained troublesome in an appreciable minority. While adjuvant radiotherapy could have contributed to this, future innovations will focus on the reduction of late strictures.

Functional results of pharyngo-laryngectomy and total laryngectomy: a comparison.

OBJECTIVE: To compare the key functional results (regarding swallowing and voice rehabilitation) in patients treated by pharyngo-laryngectomy with flap reconstruction, versus standard, wide-field, total laryngectomy. METHOD: We studied 97 patients who had undergone total laryngectomy and pharyngo-laryngectomy with flap reconstruction. The main outcome measures were swallowing (i.e. solid food, soft diet, fluid or enteral feeding) and fluent voice development. RESULTS: There were 79 men and 18 women, with follow up of one to 19 years. Voice (p = 0.037) and swallowing (p = 0.041) results were significantly worse after circumferential pharyngo-laryngectomy than after non-circumferential pharyngo-laryngectomy. There was no significant difference in voice (p = 0.23) or swallowing (p = 0.655) results, comparing total laryngectomy and non-circumferential pharyngo-laryngectomy. The presence of a post-operative fistula significantly influenced voice (p = 0.001) and swallowing (p = 0.009) outcomes. CONCLUSION: The additional measures involved in pharyngo-laryngectomy do not confer any functional disadvantage, compared with total laryngectomy, but only if the procedure is non-circumferential. Functional results of circumferential pharyngo-laryngectomy are worse than those of both non-circumferential pharyngo-laryngectomy and total laryngectomy. If oncologically possible and safe, it is better to keep a pharyngo-laryngectomy non-circumferential.

Thyroid lymphoma: acute presentation and long-term outcome.

BACKGROUND: Thyroid lymphomas are relatively uncommon. This study aimed to analyse our experience of thyroid lymphoma management and outcome. MATERIALS AND METHODS: A retrospective case note analysis of 63 patients treated in the previous 13 years was conducted. RESULTS: The five-year survival rate was 68 per cent, with most patients dying of their lymphoma. This is at odds with the British Thyroid Association statement that the prognosis of this condition is 'generally excellent'. The only presenting symptom found to be significantly associated with prognosis was dysphagia (p = 0.001). Dual modality treatment provided a significantly better outcome than single modality treatment (p = 0.014). Thyroid lymphoma can present to the head and neck surgeon 'in extremis'; however, it can respond rapidly to appropriate treatment. CONCLUSION: The outcome of thyroid lymphoma seems unrelated to the acuteness of its presentation. Thyroid surgery has no role other than for diagnosis. However, 51 per cent of the study patients underwent some form of thyroidectomy, indicating the need to implement better diagnostic pathways.

Effect of central compartment neck dissection on hypocalcaemia incidence after total thyroidectomy for carcinoma.

INTRODUCTION: Central compartment neck dissection is increasingly performed as part of surgical management of differentiated thyroid carcinoma. However, elective central neck dissection remains controversial due to complications and lack of evidence of survival benefit. OBJECTIVE: To investigate and compare rates of transient and permanent hypocalcaemia following total thyroidectomy alone, compared with total thyroidectomy with central neck dissection, for differentiated thyroid carcinoma. METHODS: Retrospective study of 127 consecutive patients referred with differentiated thyroid carcinoma, 2004-2006; 78 patients had undergone total thyroidectomy (group one) and 49 total thyroidectomy with central compartment node dissection (group two). Surgery was performed in various hospitals by both otolaryngologists and endocrine surgeons. RESULTS: In groups one and two, the incidence of transient hypocalcaemia was 18 per cent (14/78) and 51 per cent (25/49) (p < 0.001), and the incidence of permanent hypocalcaemia 1 per cent (one of 77) and 12 per cent (six of 49) (p < 0.01), respectively. Most patients undergoing central neck dissection had evidence of pathological level six lymphadenopathy (29/49). CONCLUSION: Total thyroidectomy combined with central neck dissection for the treatment of differentiated thyroid carcinoma is more likely to result in transient (51 per cent) and permanent (12 per cent) hypocalcaemia. Elective neck dissection should be performed selectively, with a high expectation of post-operative hypocalcaemia.

The role of nervus intermedius in side specific nasal responses.

BACKGROUND: Nervus intermedius (NI) dysfunction is common in patients who have had vestibular schwannoma (VS) surgery. Such patients have a unilateral parasympathetic-denervated nasal cavity. A number of side-specific nasal reflexes have been demonstrated in normal individuals, including hand cold-water immersion. It is not understood whether these reflexes have parasympathetic or sympathic efferent pathways. We aimed to evaluate the side specific nasal reflex to cold-water immersion in post-operative VS patients with NI dysfunction, in order to determine the nature of the efferent pathway of these reflexes. METHOD: Side specific responses to cold-water immersion were tested by acoustic rhinometry in 10 normal individuals and 18 patients with NI dysfunction (proven by Schirmer s test) after VS surgery. RESULTS: A consistent pattern of ipsilateral congestion and contralateral decongestion after the cold-water immersion was seen in normal individuals (p smaller than 0.001). We found no consistent response in VS patients both ipsilateral and contralateral to the side of NI dysfunction. CONCLUSIONS: We confirm the consistent side-specific nasal reflexes to cold-water hand immersion in normal individuals. This is disturbed in patients with NI dysfunction. We have also shown unexpectantly that the contralateral side-specific reflex is disturbed in these patients. These data suggest that the reflex is parasympathetic and crosses the midline.

Use of multiple biological markers in radiotherapy-treated head and neck cancer.

OBJECTIVE: Management of patients with head and neck squamous cell carcinoma is often based on clinical parameters, with little appreciation of the underlying tumour biology. Single biological marker studies fail to acknowledge the complexity of these tumours. Our aim was to define a profile of biological markers associated with outcome. DESIGN: This retrospective study involved consecutive patients with oropharyngeal squamous cell carcinoma treated with primary radiotherapy between 1996 and 2001. Pre-treatment biopsies were used to study the immunohistochemical expression of nine biological markers. Markers were chosen to reflect biologically relevant pathways. RESULTS: Following analysis of nine markers, a profile of two markers was derived (carbonic anhydrase 9 and major vault protein), the co-expression of which conferred a significantly poor probability of locoregional control. The prognostic effect of these biomarkers in combination was greater than their effect individually. CONCLUSION: Biomarker profiles can be established which highlight large differences in locoregional control. Identifying tumours that express both carbonic anhydrase 9 and major vault protein may facilitate patient selection for more aggressive treatment.

Electroglottogram approximate entropy: a novel single parameter for objective voice assessment.

BACKGROUND: The electroglottogram approximate entropy value is a numerical variable which gives an overall measure of voice quality. It is derived by analysing the complexity of the electroglottogram waveform using regulatory statistics. AIMS: (1) To use electroglottogram approximate entropy to measure voice quality in patients with glottic pathology and in normal subjects, to ascertain whether this parameter can distinguish between pathological and normal voices. (2) To ascertain whether electroglottogram approximate entropy can measure voice change over time within individual subjects. (3) To determine any correlation between electroglottogram approximate entropy and the grade-roughness-breathiness-asthenia-strain scale. METHODS: One hundred and forty-one normal volunteers were recruited to characterise electroglottogram approximate entropy in the normal voice. One hundred and eighty-six patients with glottic squamous cell carcinoma underwent electroglottogram approximate entropy measurement prior to radiotherapy and then three to six months and one year after treatment. Subjects' voices were categorised by a speech therapist using the grade-roughness-breathiness-asthenia-strain scale. RESULTS: The mean electroglottogram approximate entropy of the normal volunteers was 0.302 (range 0.05-0.42). The mean electroglottogram approximate entropy of the glottic squamous cell carcinoma patients was significantly lower prior to treatment, at 0.227 (range 0.001-0.397; p < 0.0005), but improved after radiotherapy to 0.277 at three to six months and 0.282 at one year. Electroglottogram approximate entropy results correlated significantly with grade-roughness-breathiness-asthenia-strain scale results. CONCLUSION: Electroglottogram approximate entropy can be used to assess change in voice quality resulting from glottic morphological abnormality. Electroglottogram approximate entropy values improve as voice quality improves after treatment. Electroglottogram approximate entropy values correlate significantly with grade-roughness-breathiness-asthenia-strain scale results.

The role of HPV type in Recurrent Respiratory Papillomatosis.

OBJECTIVE: Human Papillomavirus (HPV) 6 and 11 are the aetiological agents responsible for Recurrent Respiratory Papillomatosis (RRP). There is general consensus that HPV11 results in more aggressive disease compared to HPV6. METHOD: Pubmed was searched using the terms respiratory papillomatosis, HPV 6 and HPV11. Comparisons were made in the outcomes of HPV6 versus HPV11 positive RRP disease. RESULTS: There are numerous sub-types or variants of both HPV6 and HPV11. These sub-types have different activities at least in-vitro. The numbers of different HPV types within RRP tissue may be more extensive than initially appeared. This depends specifically upon the HPV types tested for. CONCLUSION: The clinical differences between HPV6 and HPV11 disease may not be accurately predictable as these viruses exist in numerous sub-types. Also, RRP tissue may contain more than one subtype or even be co-infected with other viruses that may influence outcome. In-vitro studies upon cell lines are a reasonable starting point for evaluation of these differences.

Radiological balloon dilatation of post-treatment benign pharyngeal strictures.

AIMS: To assess the technical success, clinical outcomes and complications of radiologically guided balloon dilatation of benign strictures developing after treatment for head and neck cancer. MATERIALS AND METHODS: Forty-six balloon dilatations were performed in 20 patients. All dilatations were performed over a guidewire. RESULTS: Technical success was 100 per cent. Fifteen of the 20 patients demonstrated clinical improvement in dysphagia scores. Improvement in dysphagia was temporary in all patients (median 102 days), with multiple dilatations usually required (total dilatations ranged from one to seven). Immediate complications were encountered in six of the 46 (13 per cent) dilatations and were all minor. Late complications occurred after two procedures (4 per cent): localised perforation (later complicated by secondary infection) and recurrence of a previous, small, pharyngo-cutaneous fistula. CONCLUSION: Radiologically guided balloon dilatation is straightforward to perform and is well tolerated, but there is a small risk of perforation. Relief of symptoms is likely to be temporary, requiring multiple subsequent dilatations. A minority of patients will obtain no symptomatic relief.