Steve Connor

Recommendations for imaging tumor response in neurofibromatosis clinical trials

Objective: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Methods: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. Results: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. Conclusions: The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors.

Role of thyroidectomy in advanced laryngeal and pharyngolaryngeal carcinoma

Objective: Total thyroidectomy (TThy) or hemithyroidectomy (HThy) in conjunction with a total laryngectomy (TL) or pharyngolaryngectomy (PL) for laryngeal carcinoma often results in hypothyroidism requiring life-long thyroid hormone replacement. The aims were to determine the incidence of thyroid gland (TG) invasion in patients undergoing TL or TPL with TThy or HThy for laryngeal or hypopharyngeal carcinoma and to assess predicative factors. Study Design: Case series with chart review. Setting: Guys Hospital, London, UK. Subjects and Methods: Thirty-five patients from 2004 to 2008 were reviewed. Specimens were examined to determine the incidence of TG invasion and predicative factors. Preoperative imaging was reviewed to assess the radiological evidence of TG invasion. Results: TL and TThy were performed in 19 patients, TL and HThy in three patients, and PL and TThy in 13 patients. Surgery was performed for primary and recurrent carcinoma in 28 and eight patients, respectively. Histological evidence of invasion of the TG was found in three patients (8.5%). No significant relationship was found between TG invasion and patients sex, subsite of primary carcinoma, stage of primary disease at surgery, degree of differentiation, or the presence of subglottic extension. In addition, no significant relationship was found between the presence of TG invasion and recurrent disease. Definite evidence of radiological invasion of the TG was seen in only one patient. Conclusions: Invasion of the TG in patients undergoing TL or TPL is a rare event and limits the need for TThy in most cases.

The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors

Background Neurofibromatosis 1 (NF1) leads to the development of benign and malignant peripheral nerve sheath tumors (MPNST). MPNST have been described to develop in preexisting benign plexiform neurofibromas (PN) and have a poor prognosis. Atypical neurofibromas (ANF) were recently described as precursor lesions for MPNST, making early detection and management of ANF a possible strategy to prevent MPNST. We aimed to clinically characterize ANF and identify management approaches. Methods We analyzed clinical, imaging, and pathology findings of all patients with NF1 and ANF at 3 institutions. Results Sixty-three patients had 76 ANF (32M/31F; median age 27.1 y). On MRI, most ANF appeared as distinct nodular lesions and were 18F-fluorodeoxyglucose (FDG) avid. Forty-six ANF were associated with pain, 19 with motor weakness, 45 were palpable or visible, and 13 had no clinical signs. Completely resected ANF (N = 57) have not recurred (median follow-up, 4.1 y; range, 0-14 y). Four ANF transformed into MPNST and 17 patients had a history of MPNST in a different location than was their ANF. Conclusions Growth of distinct nodular lesions, pain, and FDG-PET avidity should raise concern for ANF in NF1. Patients with ANF are at greater risk for development of MPNST. Complete resection of ANF may prevent development of MPNST.

Modern Radiology in the Management of Head and Neck Cancer

The accurate staging of head and neck cancer is vital to direct appropriate management strategies and to deliver the best radiation therapy and surgery. Initial challenges in head and neck cancer imaging include determination of T- and N-stage, stage migration with detection of metastatic disease and identification of primary disease in the patient presenting with nodal metastases. In follow-up, imaging has an important role in assessing patients who may require salvage surgery after radiotherapy and assessing clinical change that may represent either residual/recurrent disease or radiation effects. This overview gathers recent evidence on the optimal use of currently readily available imaging modalities (ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography-computed tomography) in the context of head and neck squamous cell cancers.

Management and outcomes of cochlear implantation in patients with congenital cytomegalovirus (cCMV)-related deafness

Objective: Congenital Cytomegalovirus (cCMV) is a well-defined cause for neonatal mortality and morbidity, particularly sensorineural hearing loss and other neurodevelopmental disruption. We present a retrospective study which provides an overview of the assessment and preoperative work-up for patients diagnosed with cCMV and their cochlear implant (CI) outcomes. Method: This was a retrospective case series study of all children with a confirmed diagnosis of cCMV who underwent cochlear implantation at St Thomas’ Hospital from 2003 to 2015. Data were collected on the preoperative audiology, imaging findings, and neurological assessment. CI outcomes were measured using the Speech Intelligibility Rating (SIR), Category of Auditory Performance (CAP), and Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS). Results: Eleven patients underwent cochlear implantation, 45% had severe-to-profound hearing loss, and 55% had bilateral profound hearing loss. The mean age at initial assessment was 2.1 years (median 1.7, range 0.6–7.5) and the mean age of implantation was 4.0 years (median 2.5, range 0.9–11.8). The mean length of follow-up was 4.8 years (median 2.3, range 1.5–14). Six patients had bilateral simultaneous implantation (55%), four bilateral sequential (36%), and one unilateral (9%). Nine patients had white matter changes on magnetic resonance imaging, largely in the periventricular and cortical regions. Of the 11 patients, 4 (36%) had associated neurological comorbidities and 3 (27%) had additional neurocognitive developmental delay of varying severity. The majority of patients showed improvement in auditory outcomes. No statistically significant correlation was found between age of implantation, neurocognitive, and neurological comorbidities or length of follow-up and hearing outcomes. Conclusion: While the overall outcomes were mixed, most children in our cohort were found to benefit from cochlear implantation. Our data also highlight the significant neurodevelopmental comorbidities associated with cCMV and their negative impact on CI outcomes. With the recent advances in medical treatment, this underlines the importance of multidisciplinary management of these patients.

Venous haemangioma of the mandibular division of the trigeminal nerve

OBJECTIVES To present a rare cause of facial pain, and the differential diagnosis of a lesion of the mandibular division of the trigeminal nerve. CASE REPORT A 19-year-old woman presented to a tertiary referral skull base centre with right periorbital pain and a progressive, right-sided deficit of the mandibular division of the trigeminal nerve. Clinical examination revealed right-sided hypoaesthesia in the mandibular division of the trigeminal nerve dermatome, mild trismus and some wasting of the right masseter muscle. Computed tomography and magnetic resonance imaging scans revealed a small area of mildly enhancing soft tissue centred within the foramen ovale, with concentric enlargement. Surgery was undertaken via an infratemporal fossa (Fisch) type D approach. A vascular lesion was found filling the foramen ovale, with no obvious nerve separate from the lesion. The lesion was removed en bloc. Histopathological analysis demonstrated a venous haemangioma within the nerve. CONCLUSION Facial pain is common, and may be wrongly attributed to trigeminal neuralgia. A thorough clinical examination must be performed to identify subtle neurological abnormalities, and appropriate imaging undertaken to exclude rare causes, such as this venous haemangioma of the mandibular division of the trigeminal nerve.

Dosimetric Analysis of the Brachial Plexus using Monte Carlo-based Intensity-modulated Radiotherapy for Head and Neck Cancer

Sir d Oncology patients presenting with febrile neutropenia are a heterogeneous group with varying risks of serious complications. Appropriate use of the Multinational Association of Supportive Care of Cancer (MASCC) risk index score facilitates the safe outpatient management of low-risk patients and this is reflected in local protocols and national guidance [1,2]. Despite its clinical and cost-effectiveness, protocol-driven clinical decision-making can be viewed with suspicion, as it can seem to ignore the clinical acumen of the reviewing clinician [3e5].We sought to assessmissed early discharge opportunities at Addenbrooke’s Hospital, a large tertiary oncology centre in the east of England, and evaluate the barriers to protocol-driven discharge. Our analysis of all suspected febrile neutropenia cases admitted over a 1 year period (n 1⁄4 215) found that 74% of patients eligible for early discharge remained inpatients at 48 h. Forty-six excess inpatient days were accrued as a consequence of missed discharge opportunities in the first 72 h of admission. This analysis and a departmental survey (n 1⁄4 28) highlighted a number of barriers at the organisational, clinical and patient level. Unsurprisingly, patient comorbidities were identified as one of the strongest deterrents to discharge. However, many patients in the study were documented as being ‘well’ at review. Social factors, such care arrangements, were also highlighted, as was clinical acumen. Despite this, most doctors stated that they believed that the MASCC score affected management and had confidence in protocol-driven discharge. Several prevalent misunderstandings with regards to febrile neutropenia management were also identified. For example, doctors agreed that waiting for blood investigations prevented discharge when national and local guidelines state that this is unnecessary. This was also apparent from the retrospective analysis of clinical reviews and highlights a propensity to look for reassurance from laboratory results. Febrile neutropenia has social and financial implications on patients and their families. Not only this, an increased length of stay exposes patients to complications associated with inpatient care. Our results suggest that increasing knowledge of guidelines and encouraging direct reference local protocols may increase the uptake of early discharge opportunities.