Isabel Sassoon

Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer

PURPOSE Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma. METHODS An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up. RESULTS An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%. CONCLUSION These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma.

Use of pentoxifylline and tocopherol in the management of osteoradionecrosis

Osteoradionecrosis (ORN) is a complication of radiotherapy, and is difficult to manage once established. However, its pathogenesis has been reinvestigated, and it is now thought to be potentially amenable to treatment with pentoxifylline and tocopherol (vitamin E). We made a retrospective analysis of 62 patients with established ORN who were treated in this way. When only pentoxifylline and vitamin E was used ORN resolved in 14/25 (56%) but paradoxically, when it was combined with antibiotics, only 6/22 resolved (27%). The next stage would ideally be to incorporate the treatment in a randomised clinical trial against both standard antibiotic treatment and hyperbaric oxygen.

Prophylactic use of pentoxifylline and tocopherol in patients who require dental extractions after radiotherapy for cancer of the head and neck

Osteoradionecrosis (ORN) is a complication seen intermittently in patients who have had radiotherapy to the head and neck, and results of treatment with pentoxifylline and tocopherol (PVe) have been encouraging. As a consequence, some argue that this should be used prophylactically to lower the risk of ORN after dental extractions in this group. We retrospectively analysed data on 390 dental extractions in 82 patients who had had radiotherapy for cancer of the head and neck. Each had been given PVe prophylactically. Only one patient (1.2%) developed ORN (rate/tooth 0.26%). Patients had taken PVe for a mean (SD) of 11 (23) weeks preoperatively and 13.6 (18) weeks postoperatively. The incidence we found was lower than that normally associated with dental extractions in irradiated patients (7%).

Sentinel node in oral cancer: the nuclear medicine aspects. A survey from the sentinel european node trial

Purpose Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed. Methods Three to 24 hours before surgery, all patients received a dose of 99mTc-nanocolloid (10–175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT. Results Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1–10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients. Conclusions Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.

Is benchmarking possible in audit of early outcomes after operations for head and neck cancer

There is a need for a validated means of adjusting for case mix in morbidity audits of patients with cancer of the head and neck. To address this, we did a multicentre audit of 3 U.K. NHS cancer networks that treat patients with head and neck cancer, to compare the incidence of early adverse postoperative outcomes and to develop a means of adjusting for case mix. We did a retrospective and prospective audit of the case notes of 901 consecutive patients who had 1034 operations for squamous cell carcinoma (SCC) of the head and neck under general anaesthesia at 3 NHS hospitals. Analysis of raw data showed postoperative 30-day mortality (n=17) to be consistent between sites (1.7%-1.9%) but 30-day complication rates varied more (34%-49%). Logistic regression models predicting morbidity discriminated well (area under the curve 0.74-0.76). Adjusted morbidity rates for the 3 units were compared on a funnel plot with 95% and 99% confidence intervals to account for random variation. It is possible to benchmark surgical performance by focusing on early postoperative outcomes in head and neck surgery. Morbidity is common and usually has a considerable impact on recovery, bed occupancy, cost, and the patients perception of the quality of care.

Biopsy of the sentinel lymph node in oral squamous cell carcinoma: analysis of error in 100 consecutive cases

UK national guidelines in 2016 recommended that sentinel lymph node biopsy should be offered to patients with early oral cancer (T1-T2 N0) in which the primary site can be reconstructed directly. This study describes the pitfalls that can be avoided in the technique of biopsy to improve outcomes. We retrospectively analysed the data from 100 consecutive patients and recorded any adverse events. Lymphatic drainage of tracer failed in two patients as a result of procedural errors. Two patients with invaded nodes developed recurrence after total neck dissection, one after micrometastases had been diagnosed, and the other as a result of extranodal spread that had led to understaging and therefore undertreatment. Two results would not have been mistakenly classified as clear if all the harvested nodes had been analysed histologically according to the protocol. The disease-specific (96%) and disease-free (92%) survival were better than expected for a group of whom a third had stage 3 disease. If all harvested nodes had been analysed by the correct protocol then two of the three nodes wrongly designated clear would have been detected, two deaths potentially avoided, and the false-negative rate would have fallen from 8.3% to 2.7%. We conclude that minor deviations from protocol can result in a detrimental outcome for the patient.

An Investigation of Argumentation Framework Characteristics

We investigate the relationship between the structural properties of argumentation frameworks and their argument-based characteristics, examining the characteristics of structures of Dung-style frameworks and two generalisations: extended argumentation frameworks and collective-attack frameworks. Our results show that the structural properties of frameworks have an impact on the size of extensions produced, on the proportion of subsets of arguments that determine some topic argument to be acceptable, and on the likelihood that the addition of some new argument will affect the acceptability of an existing argument, all characteristics that are known to affect the performance of argumentation-based technologies. We demonstrate the applicability of our results with two case studies.

Developing a risk stratification tool for audit of outcome after surgery for head and neck squamous cell carcinoma

Patients treated surgically for head and neck squamous cell carcinoma (HNSCC) represent a heterogeneous group. Adjusting for patient case mix and complexity of surgery is essential if reporting outcomes represent surgical performance and quality of care.

Validating a benchmarking tool for audit of early outcomes after operations for head and neck cancer

INTRODUCTION In 2013 all UK surgical specialties, with the exception of head and neck surgery, published outcome data adjusted for case mix for indicator operations. This paper reports a pilot study to validate a previously published risk adjustment score on patients from separate UK cancer centres. METHODS A case note audit was performed of 1,075 patients undergoing 1,218 operations for head and neck squamous cell carcinoma under general anaesthesia in 4 surgical centres. A logistic regression equation predicting for all complications, previously validated internally at sites A‐C, was tested on a fourth external validation sample (site D, 172 operations) using receiver operating characteristic curves, Hosmer‐Lemeshow goodness of fit analysis and Brier scores. RESULTS Thirty‐day complication rates varied widely (34‐51%) between the centres. The predictive score allowed imperfect risk adjustment (area under the curve: 0.70), with Hosmer‐Lemeshow analysis suggesting good calibration. The Brier score changed from 0.19 for sites A‐C to 0.23 when site D was also included, suggesting poor accuracy overall. CONCLUSIONS Marked differences in operative risk and patient case mix captured by the risk adjustment score do not explain all the differences in observed outcomes. Further investigation with different methods is recommended to improve modelling of risk. Morbidity is common, and usually has a major impact on patient recovery, ward occupancy, hospital finances and patient perception of quality of care. We hope comparative audit will highlight good performance and challenge underperformance where it exists.

Towards Argumentation for Statistical Model Selection

The increase in routine clinical data collection coupled with an expectation to exploit this in support of evidence based decision making creates the requirement for a system to support clinicians in this analysis. This paper looks at applying argumentation to this problem, by collating all the relevant statistical approaches and their assumptions into a statistical knowledge base and then representing the model selection process through argumentation. This will form the foundation for the development of a prototype that will enable clinicians to answer their research questions with no statistics, informatics or administrative support.