Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.
Abstract Background Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival. Methods CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1–T4, N1–N3 or T3–4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1–T4, N2b–N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2—induction chemotherapy followed by arm 1; arm 3—dose-escalated radiotherapy plus concomitant cisplatin; and arm 4—resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5—induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m 2 or weekly 40 mg/m 2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed. Discussion CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients. Trial registration ISRCTN ISRCTN41478539 . Registered on 29 April 2015
#### Summary points
Head and neck cancers include cancers of the upper aerodigestive tract (including the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx), the paranasal sinuses, and the salivary glands. Cancers at different sites have different courses and variable histopathological types, although squamous cell carcinoma is by far the most common. The anatomical sites affected are important for functions such as speech, swallowing, taste, and smell, so the cancers and their treatments may have considerable functional sequelae with subsequent impairment of quality of life. Decisions about treatment are usually complex, and they must balance efficacy of treatment and likelihood of survival, with potential functional and quality of life outcomes. Patients and their carers need considerable support during and after treatment.
#### Sources and selection criteria
We used the terms “head and neck”, “larynx”, “oral”, and “oropharynx”—with each limited by “cancer”, “diagnosis”, and “treatment” separately—to search the Medline, Embase, PubMed, Cochrane, CINAHL, and AMED databases. We also used them to cross check national guidelines, reference lists, textbooks, and personal reference lists. We assessed over 1000 identified abstracts for relevance.
In this first part of a two article series, we review the common presentations of head and neck cancer. We also discuss common investigations and new …
Purpose of review Polymorphous low-grade adenocarcinoma is an entity described in 1984. An increasing number of reports in the pathology literature since then have identified this as the second or the third most common minor salivary gland malignancy. The natural history of polymorphous low-grade adenocarcinoma is distinct from other malignant salivary tumours. The present review will identify the diagnostic difficulties, the treatment options and the treatment outcome of this tumour. Recent findings Polymorphous low-grade adenocarcinoma is a slow-growing tumour that is locally invasive. The most common presentation is that of a lump in the oral cavity, usually on the palate. Diagnosis is established after a biopsy because cytological studies are not helpful. The morphological features can resemble pleomorphic adenoma and adenoid cystic carcinoma. Therapy is primarily wide surgical resection. The role of radiation therapy is not clear in the management of polymorphous low-grade adenocarcinoma. Metastases are rare and recurrences tend to occur more than 5 years after treatment, underlining the need for long-term follow-up. Recurrences can be successfully salvaged in more than 50% of the cases. Summary Polymorphous low-grade adenocarcinoma is primarily a pathologic diagnosis. Surgical resection is the mainstay of treatment. Long-term follow-up of 10 years or more is essential to ensure local control.
Abstract Background Fluorescence-guided precision cancer surgery may improve survival and minimize patient morbidity. Efficient development of promising interventions is however hindered by a lack of common methodology. This methodology review aimed to synthesize descriptions of technique, governance processes, surgical learning and outcome reporting in studies of fluorescence-guided cancer surgery to provide guidance for the harmonized design of future studies. Methods A systematic search of MEDLINE, EMBASE and CENTRAL databases from 2016–2020 identified studies of all designs describing the use of fluorescence in cancer surgery. Dual screening and data extraction was conducted by two independent teams. Results Of 13,108 screened articles, 426 full text articles were included. The number of publications per year increased from 66 in 2016 to 115 in 2020. Indocyanine green was the most commonly used fluorescence agent (391, 91.8%). The most common reported purpose of fluorescence guided surgery was for lymph node mapping (195, 5%) and non-specific tumour visualization (94, 2%). Reporting about surgical learning and governance processes incomplete. A total of 2,577 verbatim outcomes were identified, with the commonly reported outcome lymph node detection (796, 30%). Measures of recurrence (32, 1.2%), change in operative plan (23, 0.9%), health economics (2, 0.1%), learning curve (2, 0.1%) and quality of life (2, 0.1%) were rarely reported. Conclusion There was evidence of methodological heterogeneity that may hinder efficient evaluation of fluorescence surgery. Harmonization of the design of future studies may streamline innovation.
Philippe Gorphe1Bruno Grandbastien2Andreas Dietz3Umamaheswar Duvvuri4Robert L. Ferris5Wojciech Golusinski6Floyd Christopher Holsinger7Sefik Hosal8George Lawson9Hisham Mehanna10Vinidh Paleri11Richard Shaw12,13Giovanni Succo14,15C. René Leemans16†Christian Simon17*†
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)