BackgroundGuidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours.MethodsWe conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials.ResultsTwo hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001).ConclusionSEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours.Clinical Trial RegistrationNIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. A rational plan to manage the neck is necessary for all head and neck primaries. With the emergence of new level 1 evidence across several domains of neck metastases, this guideline will identify the evidence-based recommendations for management.Recommendations• Computed tomographic or magnetic resonance imaging is mandatory for staging neck disease, with choice of modality dependant on imaging modality used for the primary site, local availability and expertise. (R)• Patients with a clinically N0 neck, with more than 15–20 per cent risk of occult nodal metastases, should be offered prophylactic treatment of the neck. (R)• The treatment choice of for the N0 and N+ neck should be guided by the treatment to the primary site. (G)• If observation is planned for the N0 neck, this should be supplemented by regular ultrasonograms to ensure early detection. (R)• All patients with T1 and T2 oral cavity cancer and N0 neck should receive prophylactic neck treatment. (R)• Selective neck dissection (SND) is as effective as modified radical neck dissection for controlling regional disease in N0 necks for all primary sites. (R)• SND alone is adequate treatment for pN1 neck disease without adverse histological features. (R)• Post-operative radiation for adverse histologic features following SND confers control rates comparable with more extensive procedures. (R)• Adjuvant radiation following surgery for patients with adverse histological features improves regional control rates. (R)• Post-operative chemoradiation improves regional control in patients with extracapsular spread and/or microscopically involved surgical margins. (R)• Following chemoradiation therapy, complete responders who do not show evidence of active disease on co-registered positron emission tomography–computed tomography (PET–CT) scans performed at 10–12 weeks, do not need salvage neck dissection. (R)• Salvage surgery should be considered for those with incomplete or equivocal response of nodal disease on PET–CT. (R)
PURPOSE Guidelines advocate molecular profiling in the evaluation of advanced non–small-cell lung cancer (NSCLC) and support the use of plasma circulating tumor DNA (ctDNA)-based profiling for patients with insufficient tissue. Thorough prospective clinical validation studies of next-generation sequencing (NGS)-based ctDNA assays are lacking. We report the multicentered prospective clinical validation of the InVision ctDNA assay in patients with advanced untreated NSCLC. METHODS A total of 264 patients with untreated advanced NSCLC were prospectively recruited, and their plasma was analyzed using a ctDNA NGS assay for detection of genomic alterations in 36 commonly mutated genes. Tumor tissue was available in 178 patients for molecular profiling for comparison with plasma profiling. The remaining 86 patients were included to compare ctDNA profiles in patients with and without tissue for profiling. RESULTS Concordance of InVisionFirst with matched tissue profiling was 97.8%, with 82.9% positive predictive value, 98.5% negative predictive value, 70.6% sensitivity, and 99.2% specificity. Considering specific alterations in eight genes that most influence patient management, the positive predictive value was 97.8%, with 97.1% negative predictive value, 73.9% sensitivity, and 99.8% specificity. Across the entire study, 48 patients with actionable alterations were identified by ctDNA testing compared with only 38 by tissue testing. ctDNA NGS reported either an actionable alteration or an alteration generally considered mutually exclusive for such actionable changes in 53% of patients. CONCLUSION The liquid biopsy NGS assay demonstrated excellent concordance with tissue profiling in this multicenter, prospective, clinical validation study, with sensitivity and specificity equivalent to Food and Drug Administration–approved single-gene ctDNA assays. The use of plasma-based molecular profiling using NGS led to the detection of 26% more actionable alterations compared with standard-of-care tissue testing in this study.
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