Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial

Background: Despite endocrine therapy being the mainstay of treatment for hormone receptor positive (HR+)/HER2 12 metastatic breast cancer, patients at risk of visceral crisis or doubt for endocrine sensitivity are still offered first-line chemotherapy. Maintenance hormonal therapy is generally offered at the discontinuation of chemotherapy. The MAINtenance Afinitor study is a randomised, phase III trial comparing maintenance everolimus combined with aromatase inhibitors (AIs) versus AI monotherapy in patients with disease control after first-line chemotherapy. Methods: Patients with stable disease, partial response or complete response after first-line chemotherapy were randomised to everolimus plus AIs (exemestane or letrozole or anastrozole) or to AIs alone. Primary aim was progression-free survival (PFS). Secondary aims included response rate, safety and overall survival (OS). Results: In total, 110 patients were randomised to everolimus + AIs (n = 52) or to AIs (n = 58). Median PFS was 11.0 months (95% confidence interval [CI] 8.1\u201313.8) in the everolimus + AI arm and 7.2 months (95% CI 4.7\u201310.9) in the AI monotherapy arm (hazard ratio [HR] 0.71, 95% CI 0.47\u20131.06). Objective response rate was 22.4% in everolimus + AI arm and 19.2% in AI monotherapy arm. A higher proportion of disease progression as best response was reported in the AI monotherapy arm (28.8% versus 14.3%). Median OS was 35.7 months (95% CI 26.0\u201347.8) in the combination arm versus 33.5 (95% CI 26.4\u201342.7) in the AI alone arm (HR 1.0, 95% CI 0.61\u20131.62). Conclusions: EVE + AIs did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first-line chemotherapy. Also taking into account treatment tolerability, maintenance endocrine therapy remains the standard. Trial registration: EudraCT: 2013-004153-24

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

A concept for a magnetic field detector underpinned by the nonlinear dynamics of coupled multiferroic devices

Multiferroic (MF) composites, in which magnetic and ferroelectric orders coexist, represent a very attractive class of materials with promising applications in areas, such as spintronics, memories, and sensors. One of the most important multiferroics is the perovskite phase of bismuth ferrite, which exhibits weak magnetoelectric properties at room temperature; its properties can be enhanced by doping with other elements such as dysprosium. A recent paper has demonstrated that a thin film of Bi0.7Dy0.3FeO3 shows good magnetoelectric coupling. In separate work it has been shown that a carefully crafted ring connection of N (N odd and N >= 3) ferroelectric capacitors yields, past a critical point, nonlinear oscillations that can be exploited for electric (E) field sensing. These two results represent the starting point of our work. In this paper the (electrical) hysteresis, experimentally measured in the MF material Bi0.7Dy0.3FeO3, is characterized with the applied magnetic field (B) taken as a control parameter. This yields a "blueprint" for a magnetic (B) field sensor: a ring-oscillator coupling of N = 3 Sawyer-Tower circuits each underpinned by a mutliferroic element. In this configuration, the changes induced in the ferroelectric behavior by the external or "target" B-field are quantified, thus providing a pathway for very low power and high sensitivity B-field sensing. (C) 2013 AIP Publishing LLC

Application of the new American Thyroid Association guidelines leads to a substantial rate of completion total thyroidectomy to enable adjuvant radioactive iodine.

BackgroundThe recently published 2015 American Thyroid Association guidelines recognize lobectomy as a viable alternative for low-risk cancers and advise more conservative use of radioactive iodine. Some factors indicating adjuvant treatment with radioactive iodine (and therefore completion total thyroidectomy), however, only can be found upon pathologic investigation.MethodsWe performed a retrospective analysis including patients with American Thyroid Association low- and low-to-intermediate risk well-differentiated thyroid cancer 1-4 cm. We evaluated how often radioactive iodine would be indicated and compared this with our historic rate. A subanalysis was performed to determine the rate of completion total thyroidectomy necessary, based on the indications for adjuvant radioactive iodine therapy.ResultsA total of 394/1,000 (39.4%) patients were included for final analysis. Adjuvant radioactive iodine would have been favored in 101/394 (25.6%) of patients, which is 2.5 times less than was given in our historic cohort. Completion total thyroidectomy to enable adjuvant radioactive iodine would have been recommended in 29/149 (19.5%) patients preoperatively eligible for lobectomy.ConclusionDespite the tightened regulations for radioactive iodine, about 20% of patients with apparently "low-risk" well-differentiated thyroid cancer who are eligible for lobectomy may need completion total thyroidectomy because of pathologic findings for which radioactive iodine use is listed as considered or favored by the current guidelines

Squamous differentiation in papillary thyroid carcinoma: a rare feature of aggressive disease.

BACKGROUND:Papillary thyroid carcinoma with squamous differentiation (PTC-SD) is a poorly understood pathologic finding of unknown clinical significance. Selected case reports have suggested that PTC-SD is an aggressive tumor with a poor prognosis. Here we present the largest case series of PTC-SD reported in the United States. MATERIALS AND METHODS:The cancer registry at our tertiary care referral center was reviewed to identify all patients from 1995-2015 who had been diagnosed with PTC-SD on initial total thyroidectomy or lymph node dissection for recurrent disease. All cases were reviewed by an endocrine pathologist to confirm the diagnosis. Patient demographic, pathology, and outcomes data were collected and reviewed. RESULTS:During the study period, ten patients were diagnosed with PTC-SD, six in the primary tumor at the time of initial surgery, and four in lymph node metastases during surgery for recurrent disease. The median age at diagnosis was 56 y and half of the patients were male. Aggressive features such as multifocality (67%), extrathyroidal extension (67%), positive margin (89%), lymph node metastases (80%), and extranodal extension (60%) were far more prominent than is typically seen in classic PTC. Long-term follow-up (median 56.5 mo) demonstrated high rates of locoregional recurrence (60%), pulmonary metastases (30%), and mortality (10%). CONCLUSIONS:Squamous differentiation is a rare finding in PTC that is associated with aggressive pathologic features and poor long-term outcomes. This phenomenon may represent a step in progression toward dedifferentiation; thus, patients with PTC-SD should have close, life-long surveillance and should be treated according to evidence-based guidelines for high-risk thyroid cancers

Squamous differentiation in papillary thyroid carcinoma: a rare feature of aggressive disease.

BACKGROUND:Papillary thyroid carcinoma with squamous differentiation (PTC-SD) is a poorly understood pathologic finding of unknown clinical significance. Selected case reports have suggested that PTC-SD is an aggressive tumor with a poor prognosis. Here we present the largest case series of PTC-SD reported in the United States. MATERIALS AND METHODS:The cancer registry at our tertiary care referral center was reviewed to identify all patients from 1995-2015 who had been diagnosed with PTC-SD on initial total thyroidectomy or lymph node dissection for recurrent disease. All cases were reviewed by an endocrine pathologist to confirm the diagnosis. Patient demographic, pathology, and outcomes data were collected and reviewed. RESULTS:During the study period, ten patients were diagnosed with PTC-SD, six in the primary tumor at the time of initial surgery, and four in lymph node metastases during surgery for recurrent disease. The median age at diagnosis was 56 y and half of the patients were male. Aggressive features such as multifocality (67%), extrathyroidal extension (67%), positive margin (89%), lymph node metastases (80%), and extranodal extension (60%) were far more prominent than is typically seen in classic PTC. Long-term follow-up (median 56.5 mo) demonstrated high rates of locoregional recurrence (60%), pulmonary metastases (30%), and mortality (10%). CONCLUSIONS:Squamous differentiation is a rare finding in PTC that is associated with aggressive pathologic features and poor long-term outcomes. This phenomenon may represent a step in progression toward dedifferentiation; thus, patients with PTC-SD should have close, life-long surveillance and should be treated according to evidence-based guidelines for high-risk thyroid cancers

Trends of genetic screening in patients with pheochromocytoma and paraganglioma: 15-year experience in a high-volume tertiary referral center.

Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50).Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P < 0.001). A total of 67% followed up on the referral. The prevalence of genetic mutation was 50% (21/42 tested). The percentage with a genetic syndrome was 23%, 28%, and 22% respectively for groups 1, 2, and 3.Referral for genetic counseling significantly increased in the past 15 years. However, only two-thirds of patients followed up with genetic counselors and, therefore, clinicians can do more to improve the adherence rate for genetic counseling