Smallridge, Robert C.

Background: Appropriate management of well-differentiated thyroid cancer requires treating clinicians to have access to critical elements of the patient's presentation, surgical management, postoperative course, and pathologic assessment. Electronic health records (EHRs) provide an effective method for the storage and transmission of patient information, although most commercially available EHRs are not intended to be disease-specific. In addition, there are significant challenges for the sharing of relevant clinical information when providers involved in the care of a patient with thyroid cancer are not connected by a common EHR. In 2012, the American Thyroid Association (ATA) defined the critical elements for optimal interclinician communication in a position paper entitled, “The Essential Elements of Interdisciplinary Communication of Perioperative Information for Patients Undergoing Thyroid Cancer Surgery.” Summary: We present a field-by-field comparison of the ATA's essential elements as applied to three contemporary electronic reporting systems: the Thyroid Surgery e-Form from Memorial Sloan-Kettering Cancer Center (MSKCC), the Alberta WebSMR from the University of Calgary, and the Thyroid Cancer Care Collaborative (TCCC). The MSKCC e-form fulfills 21 of 32 intraoperative fields and includes an additional 14 fields not specifically mentioned in the ATA's report. The Alberta WebSMR fulfills 45 of 82 preoperative and intraoperative fields outlined by the ATA and includes 13 additional fields. The TCCC fulfills 117 of 120 fields outlined by the ATA and includes 23 additional fields. Conclusions: Effective management of thyroid cancer is a highly collaborative, multidisciplinary effort. The patient information that factors into clinical decisions about thyroid cancer is complex. For these reasons, EHRs are particularly favorable for the management of patients with thyroid cancer. The MSKCC Thyroid Surgery e-Form, the Alberta WebSMR, and the TCCC each meet all of the general recommendations for effective reporting of the specific domains that they cover in the management of thyroid cancer, as recommended by the ATA. However, the TCCC format is the most comprehensive. The TCCC is a new Web-based disease-specific database to enhance communication of patient information between clinicians in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. We believe the easy-to-use TCCC format will enhance clinician communication while providing portability of thyroid cancer information for patients.

Context: Molecular markers hold the promise of improved diagnostic yield in thyroid fine-needle biopsy. The Afirma gene expression classifier (GEC), available commercially, reports a negative predictive value of 94% in the diagnosis of benign nodules after indeterminate cytology. However, there are currently no independent studies of the performance of this assay. Objective: The aim was to assess the performance of the Afirma GEC in an academic medical center. Design: Samples for the GEC were collected according to the manufacturer's recommended protocol from patients undergoing thyroid fine-needle aspiration. We requested GEC analysis on nodules reported cytologically as follicular neoplasm or atypia or follicular lesion of undetermined significance from patients willing to defer surgery. Patients: All patients undergoing thyroid fine-needle aspiration during the study period, whose cytology was reported as follicular neoplasm or atypia of undetermined significance/follicular lesion of undetermined significance, were offered access to the test and recruited to this study. Intervention: Patients whose GEC was “benign” were offered ultrasound follow-up in lieu of surgery. Those with a “suspicious” GEC were advised to undergo diagnostic lobectomy. Setting: The study was conducted at a large academic medical center. Main Outcome Measure: We measured the rate of benign and suspicious calls from the Afirma GEC and histological diagnosis after surgery. Results: A total of 72 nucleic acid samples were sent for GEC analysis. In 12 (17%) of these samples, there was insufficient mRNA, leaving 60 Afirma results for analysis. Of these, 16 (27%) were benign, whereas 44 (73%) were suspicious. The rate of confirmed malignancy in GEC-suspicious nodules was only 17%. Conclusion: The Afirma GEC demonstrates a lower than expected rate of benign reports in follicular or Hürthle cell neoplasm and a lower than anticipated malignancy rate within GEC-suspicious nodules. These data suggest that the positive predictive value of the GEC is lower than previously reported and call into question the performance of the test when applied in the context of specialized academic cytopathology.

Background: The current systems of healthcare delivery in the United States suffer from problems that often leave patients with inadequate quality of care. In their report entitled “Crossing the Quality Chasm,” the Institute of Medicine (IOM) identified reasons for poor and/or inconsistent quality of healthcare delivery and provided recommendations to improve it. The purpose of this review is to describe features of an innovative web-based program called the Thyroid Cancer Care Collaborative (TCCC) and see how it addresses IOM recommendations to improve the quality of healthcare delivery. Summary: The TCCC addresses the three actionable IOM recommendations directed at healthcare organizations and clinicians to redesign the care process. It does so by exploiting information technology (IT) in ways suggested by the IOM, and it fits within a set of 10 rules provided by the IOM. Some features of the TCCC include: (i) automated disease staging based on three validated scoring systems; (ii) highly illustrated educational videos on all aspects of thyroid cancer care; (iii) personalized clinical decision-making modules for clinicians and physicians; (iv) portability of data to share among treating physicians; (v) virtual tumor boards, “ask the expert,” and frequently asked questions modules; (vi) physician workflow integration; and (vii) data for comprehensive analysis to answer difficult questions in thyroid cancer management. Conclusion: The TCCC has the potential to improve thyroid cancer care delivery and offers several benefits to patients, clinicians, and researchers. The TCCC is a valuable example of how IOM initiatives can improve the healthcare system.

AbstractBackgroundWell‐differentiated thyroid cancer (WDTC) recurs in up to 30% of patients. Guidelines from the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) provide valuable parameters for the management of recurrent disease, but fail to guide the clinician as to the multitude of factors that should be taken into account. The Thyroid Cancer Care Collaborative (TCCC) is a web‐based repository of a patient's clinical information. Ten clinical decision‐making modules (CDMMs) process this information and display individualized treatment recommendations.MethodsWe conducted a review of the literature and analysis of the management of patients with recurrent/persistent WDTC.ResultsSurgery remains the most common treatment in recurrent/persistent WDTC and can be performed with limited morbidity in experienced hands. However, careful observation may be the recommended course in select patients. Reoperation yields biochemical remission rates between 21% and 66%. There is a reported 1.2% incidence of permanent unexpected nerve paralysis and a 3.5% incidence of permanent hypoparathyroidism. External beam radiotherapy and percutaneous ethanol ablation have been reported as therapeutic alternatives. Radioactive iodine as a primary therapy has been reported previously for metastatic lymph nodes, but is currently advocated by the ATA as an adjuvant to surgery.ConclusionThe management of recurrent lymph nodes is a multifactorial decision and is best determined by a multidisciplinary team. The CDMMs allow for easy adoption of contemporary knowledge, making this information accessible to both patient and clinician. © 2014 Wiley Periodicals, Inc. Head Neck 37: 605–614, 2015

Context: The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression. Objective: RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status. Design: BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2–3N1 tumors evaluated in a referral medical center. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes. Patients: BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes. Results: RNA-Seq identified 560 of 13 085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR. Conclusion: BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent of tumors had between one and three fusion transcripts. Functional studies will be required to determine the potential role of these newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-MUT and BRAF-WT tumors.

Pazopanib and paclitaxel produce cytotoxic synergy in thyroid cancer models through inhibition of aurora kinase A.