Background
The Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) were developed to improve risk stratification of indeterminate nodules. Our aim was to assess the clinical ...utility in a European population with restrictive diagnostic workup.
Methods
Clinical utility of the GEC was assessed in a prospective multicenter cohort of 68 indeterminate nodules. Diagnostic surgical rates for Bethesda III and IV nodules were compared to a historical cohort of 171 indeterminate nodules. Samples were post hoc tested with the GSC.
Results
The GEC classified 26% as benign. Surgical rates between the prospective and historical cohort did not differ (72.1% vs. 76.6%). The GSC classified 59% as benign, but misclassified six malignant lesions as benign.
Conclusion
Implementation of GEC in management of indeterminate nodules in a European country with restrictive diagnostic workup is currently not supported, especially in oncocytic nodules. Prospective studies with the GSC in European countries are needed to determine the clinical utility.
Background
Timely and efficient diagnostic workup of patients with head and neck cancer (HNC) is challenging. This observational study describes the implementation of an optimized multidisciplinary ...oncological diagnostic workup for patients with HNC and its impact on diagnostic and treatment intervals, survival, costs, and patient satisfaction.
Methods
All patients with newly diagnosed HNC who underwent staging and treatment at the Radboud University Medical Center were included. Conventional workup (CW) in 2009 was compared with the fast‐track, multidisciplinary, integrated care program, that is, optimized workup (OW), as implemented in 2014.
Results
The study included 486 patients with HNC (218 with CW and 268 with OW). The time‐to‐treatment interval was significantly lower in the OW cohort than the CW cohort (21 vs 34 days; P < .0001). The 3‐year overall survival rate was 12% higher after OW (72% in the CW cohort vs 84% in the OW cohort; P = .002). After correction for confounders, the 3‐year risk of death remained significantly lower in the OW cohort (hazard ratio, 1.73; 95% confidence interval, 1.14‐2.63; P = .010). Total diagnostic costs were comparable in the 2 cohorts. The general satisfaction score, as measured with the Consumer Quality Index for Oncological Care, was significantly better in a matched OW group than the CW group (9.1 vs 8.5; P = .007).
Conclusions
After the implementation of a fast‐track, multidisciplinary, integrated care program, the time‐to‐treatment interval was significantly reduced. Overall survival and patient satisfaction increased significantly, whereas costs did not change. This demonstrates the impact and improved quality of care achieved by efficiently organizing the diagnostic phase of HNC management.
After the implementation of a fast‐track, multidisciplinary, integrated care program for patients with head and neck cancer, this study shows a significant reduction in the time‐to‐diagnosis and time‐to‐treatment intervals, a significant increase in 3‐year overall survival, and an increase in patient satisfaction without increased diagnostic costs. This demonstrates the impact and improved quality of care achieved by efficiently organizing the diagnostic phase of head and neck cancer management.
Background
Current intraoperative methods of visual inspection and tissue palpation by the surgeon, and frozen section analysis cannot reliably prevent inadequate surgical margins in patients treated ...for oral squamous‐cell carcinoma (OSCC). This study assessed feasibility of MRI for the assessment of surgical resection margins in fresh OSCC specimens.
Methods
Ten consecutive tongue specimens containing OSCC were scanned using 3 T clinical whole‐body MRI. Two radiologists independently annotated OSCC location and minimal tumor‐free margins. Whole‐mount histology was the reference standard.
Results
The positive predictive values (PPV) and negative predictive values (NPV) for OSCC localization were 96% and 75%, and 87% and 79% for reader 1 and 2, respectively. The PPV and NPV for identification of margins <5 mm were 38% and 91%, and 5% and 87% for reader 1 and 2, respectively.
Conclusions
MRI accurately localized OSCC with high inter‐reader agreement in fresh OSCC specimens, but it seemed not yet feasible to accurately assess the surgical margin status.
Primary melanocytic tumors of the central nervous system (CNS) represent a spectrum of rare tumors. They can be benign or malignant and occur in adults as well as in children, the latter often in the ...context of neurocutaneous melanosis. Until recently, the genetic alterations in these tumors were largely unknown. This is in contrast with cutaneous and uveal melanomas, which are known to harbor distinct oncogenic mutations that can be used as targets for treatment with small‐molecule inhibitors in the advanced setting. Recently, novel insights in the molecular alterations underlying primary melanocytic tumors of the CNS were obtained, including different oncogenic mutations in tumors in adult patients (especially GNAQ, GNA11) vs. children (especially NRAS). In this review, the focus is on molecular characteristics of primary melanocytic tumors of the CNS. We summarize what is known about their genetic alterations and discuss implications for pathogenesis and differential diagnosis with other pigmented tumors in or around the CNS. Finally, new therapeutic options with targeted therapy are discussed.
Introduction: Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable ...aberrations, such as NTRK gene fusions. This research aimed to identify these actionable aberrations by combining NGS-based analysis of RNA (gene fusions) and DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients. Methods: RNA and DNA were extracted from archival tissue of 121 patients with various SGC subtypes. Gene fusion analysis was performed using a customized RNA-based targeted NGS panel. DNA was sequenced using a targeted NGS panel encompassing 523 cancer-related genes. Cross-validation of NGS-based NTRK fusion detection and pan-TRK immunohistochemistry (IHC) was performed. Results: Fusion transcripts were detected in 50% of the cases and included both known (MYB-NFIB, MYBL1-NFIB, CRTC1-MAML2) and previously unknown fusions (including transcripts involving RET, BRAF or RAD51B). Only one NTRK fusion transcript was detected, in a secretory carcinoma case. Pan-TRK IHC (clone EPR17341) was false positive in 74% of cases. The proportion of patients with targets for genetically matched therapies differed among subtypes (salivary duct carcinoma: 82%, adenoid cystic carcinoma 28%, mucoepidermoid carcinoma 50%, acinic cell carcinoma 33%). Actionable aberrations were most often located in PIK3CA (n = 18, 15%), ERBB2 (n = 15, 12%), HRAS and NOTCH1 (both n = 9, 7%). Conclusions: Actionable genetic aberrations were seen in 53.7% of all SGC cases on the RNA and DNA level, with varying percentages between subtypes.
Purpose
To assess the impact of an
18
FFDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with ...indeterminate cytology.
Methods
In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent
18
FFDG-PET/CT and were randomised to an
18
FFDG-PET/CT-driven or diagnostic surgery group. In the
18
FFDG-PET/CT-driven group, management was based on the
18
FFDG-PET/CT result: when the index nodule was visually
18
FFDG-positive, diagnostic surgery was advised; when
18
FFDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules.
Results
Patient management was unbeneficial in 42% (38/91 95% confidence interval CI, 32–53%) of patients in the
18
FFDG-PET/CT-driven group, as compared to 83% (34/41 95% CI, 68–93%) in the diagnostic surgery group (
p
< 0.001).
18
FFDG-PET/CT-driven management avoided 40% (25/63 95% CI, 28–53%) diagnostic surgeries for benign nodules: 48% (23/48 95% CI, 33–63%) in non-Hürthle cell and 13% (2/15 95% CI, 2–40%) in Hürthle cell nodules (
p
= 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of
18
FFDG-PET/CT were 94.1% (80.3–99.3%), 39.8% (30.0–50.2%), 95.1% (83.5–99.4%), 35.2% (25.4–45.9%), and 31.1% (23.3–39.7%), respectively.
Conclusion
An
18
FFDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules.
Trial registration number
This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014),
https://clinicaltrials.gov/ct2/show/NCT02208544
.
Background
Differentiating between malignant and benign salivary gland tumors with fine‐needle aspiration cytology (FNAC) can be challenging. This study was aimed at testing the validity of the Milan ...System for Reporting Salivary Gland Cytopathology (MSRSGC) and at assessing possible differences in the sensitivity and specificity of parotid gland FNAC between dedicated head and neck (H&N) centers, subdivided into head and neck oncology centers (HNOCs) and head and neck oncology affiliated centers (HNOACs), and general hospitals (GHs).
Methods
The Dutch Pathology Registry (PALGA) database was searched for patients who had undergone a salivary gland resection between January 1, 2006, and January 1, 2017, and had a preoperative FNAC result. The FNAC reports were retrospectively assigned to MSRSGC categories. The risk of malignancy (ROM) was calculated for each category. The sensitivity and specificity for diagnosing malignancy were calculated and compared among HNOCs, HNOACs, and GHs.
Results
In all, 12,898 FNAC aspirates were evaluated. The ROMs for each category were as follows: 12.5% in MSRSGC I, 10.3% in MSRSGC II, 29% in MSRSGC III, 2.3% in MSRSGC IVa, 28.6% in MSRSGC IVb, 83% in MSRSGC V, and 99.3% in MSRSGC VI. The sensitivity of FNAC was highest in HNOCs (88.1%), HNOACs scored lower (79.7%), and GHs had a sensitivity of 75.0%.
Conclusions
The MSRSGC is a valid tool for reporting parotid gland FNAC; therefore, these results strongly advocate its use. On the basis of the higher sensitivity of FNAC in dedicated H&N centers, the authors recommend that GHs use the presented management strategies to help to minimize the chances of a preoperative misdiagnosis.
The Milan System for Reporting Salivary Gland Cytopathology is a valid tool for reporting parotid gland fine‐needle aspiration cytology. The sensitivity of fine‐needle aspiration cytology is higher at dedicated head and neck centers.
Background
The Milan System for Salivary Gland Cytopathology (MSRSGC) is a categorical system for salivary gland fine‐needle aspiration cytopathology (FNAC) developed to aid clinicians in the ...management of salivary gland lesions. This classification is widely studied and validated, especially in cohorts that consist of mostly parotid gland lesions. However, only sparse literature describes the use of this classification for submandibular gland lesions in particular.
Methods
All patients in the Netherlands that underwent a submandibular gland resection between January 1, 2006, and January 1, 2017, with a FNAC before resection were identified with the use of the Dutch Pathology Registry database (PALGA). All FNAC results were retrospectively classified according to the MSRSGC. The risk of malignancy was calculated for all the MSRSGC categories. The sensitivity and specificity of the MSRSGC classification were calculated for submandibular gland FNAC.
Results
A total of 837 patients who underwent 975 FNAC aspirates from the submandibular glands were included in the analysis. Risks of malignancy for each of the MSRSGC categories were 14.4% in nondiagnostic, 4.4% in nonneoplastic, 37.0% in atypia of unknown significance, 3.9% in benign neoplasms, 40.7% in salivary gland neoplasms of unknown malignant potential, 76.2% in suspected malignant, and 91.3% in malignant cytology results. The sensitivity for diagnosing malignant submandibular gland tumors was 71.6% and specificity was 98.4%.
Conclusions
The results of the present study validate the use of this classification for submandibular gland lesions. Risks of malignancy vary according to the anatomical subsites of the salivary gland lesions.
Lay Summary
The risks of malignancy of the various Milan System for Salivary Gland Cytopathology (MSRSGC) categories vary according to the anatomical subsite of the salivary gland lesion.
The proposed management techniques of the MSRSGC are valid for use with submandibular gland lesions.
The risks of malignancy of the Milan Classification for Salivary Gland Cytopathology (MSRSGC) categories vary according to the anatomical subsite of the salivary gland lesion. The proposed management techniques of the MSRSGC classification are valid for use with submandibular gland lesions, however, because of the high risk of malignancy in the atypia of unknown significance (AUS) category, clinicians may favor surgery in case of a submandibular gland lesions with an AUS result rather than repeating the fine‐needle aspiration cytology.
Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse ...prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, MAPK, TGFβ, estrogen receptor (ER), Hedgehog (HH), and PI3K signaling pathway activity scores (PAS) were determined based on the expression levels of target genes. Additionally, 5-alpha reductase type 1 (SRD5A1) expression was determined. These markers were related to clinical benefit (complete/partial response or stable disease ≥6 months) and progression-free and overall survival (PFS/OS). SRD5A1 expression had the highest general predictive value for clinical benefit and positive predictive value (PPV: 85.7%). AR PAS had the highest negative predictive value (NPV: 93.3%). The fitting of a multivariable model led to the identification of SRD5A1, TGFβ, and Notch PAS as the most predictive combination. High AR, high Notch, high ER, low HH PAS, and high SRD5A1 expression were also of prognostic importance regarding PFS and SRD5A1 expression levels for OS. AR, Notch PAS, and SRD5A1 expression have the potential to predict the clinical benefit of CAB treatment in SDC patients. SRD5A1 expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of SRD5A1 expression forms a rational basis for including SRD5A1-inhibitors in SDC patients’ treatment.
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