Development of a Magnetoresistive-Based Wearable Eye-Tracking System for Oculomotor Assessment in Neurological and Otoneurological Research—Preliminary In Vivo Tests

Over the past 20 years, several eye-tracking technologies have been developed. This article aims to present a new type of eye tracker capable of producing detailed information on eye and head movements using an array of magnetoresistive detectors fixed on the patient’s head and a small magnet inserted into a contact lens, adapted to the curvature of the cornea of the subject. The software used for data analysis can combine or compare eye and head movements and can represent them as 2D or 3D images. Preliminary data involve an initial patient who was asked to perform several tasks to establish the accuracy, reliability, and tolerance of the magnetic eye tracker and software. The tasks included assessment of saccadic eye movements and pursuit, “drawing” alphabetic shapes or letters, and reading. Finally, a Head Impulse Test (HIT) was performed to estimate the VOR gain, comparing the standard deviation established via vHIT with that established via this magnetic eye tracker (mHIT). This prototypical device is minimally invasive, lightweight, relatively cheap, and tolerable, with a high degree of reliability and precision. All these characteristics could lead to the future use of the magnetic eye tracker in neurological and otoneurological fields

Integrated Akt/PKB Signaling in Immunomodulation and Its Potential Role in Cancer Immunotherapy

T cell development and maturation involve a variety of defined and coordinated developmental stages under the control of a variety of signaling networks. They function as the major mediator in cell-based immunity that defends against pathogen infections and executes immune surveillance against tumor cells. Protein kinase B (PKB, also called Akt) is central to multiple signaling pathways and transduces extracellular signals to dictate cellular responses towards proliferation, migration, anti-apoptosis, and maintenance of metabolic homeostasis. Although the prosurvival function of PKB was thought to be responsible for most of the functions regulated by PKB, emerging evidence has started to dissect its role in immunomodulation. More importantly, hyperactivation of PKB in cancer stroma frequently occurs in patients treated clinically with targeted cancer therapies, where it acts as a key mediator involved in the trapping of host immune cells in the vicinity of tumors, which supports cancer cell invasion and the escape of cancer cells from host immune surveillance. Encouragingly, recent studies have shown that inhibition of PKB improves the recognition of cancer cells by the host immune system, indicating a potential clinical strategy to rekindle the suppressed host immune response through the specific targeting of PKB. In this review, we explore how PKB signaling contributes to T cell development and cellular immune responses and discuss the mechanistic roles that PKB plays in the creation of immunosuppressive conditions and the escaping of immune recognition in the microenvironment of cance

Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study

<p>Abstract</p> <p>Background</p> <p>Cancer patients receiving chemotherapy are at increased risk of thrombosis. Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events (TEs) by about 50% in cancer outpatients receiving chemotherapy. The aims of this retrospective analysis were to evaluate the thromboembolic risk and the benefit of thromboprophylaxis according to type of chemotherapy.</p> <p>Methods</p> <p>Cancer outpatients were randomly assigned to receive subcutaneous injections of nadroparin or placebo. The incidence of symptomatic TEs was assessed according to the type of chemotherapy. Results were reported as risk ratios with associated 95% CI and two-tailed probability values.</p> <p>Results</p> <p>769 and 381 patients have been evaluated in the nadroparin and placebo group, respectively. In the absence of thromboprophylaxis, the highest rate of TEs was found in patients receiving gemcitabine- (8.1%) or cisplatin-based chemotherapy (7.0%). The combination of gemcitabine and cisplatin or carboplatin increased the risk to 10.2%. Thromboprophylaxis reduced TE risk by 68% in patients receiving gemcitabine; with a further decrease to 78% in those receiving a combination of gemcitabine and platinum.</p> <p>Conclusions</p> <p>This retrospective analysis confirms that patients undergoing chemotherapy including gemcitabine, platinum analogues or their combination are at higher risk of TEs. Our results also suggest that outpatients receiving chemotherapy regimens including these agents might achieve an increased benefit from thromboprophylaxis with nadroparin. Clinical Trial registration number: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00951574">NCT 00951574</a></p

HER2/neu expression and hormonal therapy in early breast cancer: can muddy waters become clear?

We have read with great interest the paper by Love et al [1] about the relationship between HER2/neu expression and response to adjuvant endocrine therapy in premenopausal women with breast cancer. Whereas HER2/neu and estrogen receptor (ER) are believed to be important cell survival and cell death factors in human breast cancer, if and how they interact to confer resistance to hormone therapy is still in debate. Several observations are consistent with a major role for c-erbB2 in the development of endocrine resistance, considering also the HER2/neu acquired expression durin

Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases

Purpose: Phase II trials have shown encouraging activity with ipilimumab plus fotemustine and ipilimumab plus nivolumab in melanoma brain metastases. We report the primary analysis and 4-year follow-up of the NIBIT-M2 study, the first phase III trial comparing these regimens with fotemustine in patients with melanoma with brain metastases. Patients and methods: This phase III study recruited patients 18 years of age and older with BRAF wild-type or mutant melanoma, and active, untreated, asymptomatic brain metastases from nine centers, randomized (1:1:1) to fotemustine, ipilimumab plus fotemustine, or ipilimumab plus nivolumab. The primary endpoint was overall survival (OS). Results: From January, 2013 to September, 2018, 27, 26, and 27 patients received fotemustine, ipilimumab plus fotemustine, and ipilimumab plus nivolumab. Median OS was 8.5 months [95% confidence interval (CI), 4.8-12.2] in the fotemustine arm, 8.2 months (95% CI, 2.2-14.3) in the ipilimumab plus fotemustine arm (HR vs. fotemustine, 1.09; 95% CI, 0.59-1.99; P = 0.78), and 29.2 months (95% CI, 0-65.1) in the ipilimumab plus nivolumab arm (HR vs. fotemustine, 0.44; 95% CI, 0.22-0.87; P = 0.017). Four-year survival rate was significantly higher for ipilimumab plus nivolumab than fotemustine [(41.0%; 95% CI, 20.6-61.4) vs. 10.9% (95% CI, 0-24.4; P = 0.015)], and was 10.3% (95% CI, 0-22.6) for ipilimumab plus fotemustine. In the fotemustine, ipilimumab plus fotemustine, and ipilimumab plus nivolumab arms, respectively, 11 (48%), 18 (69%), and eight (30%) patients had treatment-related grade 3 or 4 adverse events, without treatment-related deaths. Conclusions: Compared with fotemustine, ipilimumab plus nivolumab significantly improved overall and long-term survival of patients with melanoma with asymptomatic brain metastases

KEYNOTE-061: Phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer.

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Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: A multivariate analysis of 214 cases

Abstract Background Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence. Methods All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005–2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence. Results Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01–2 mm (OR 7.22; 95% CI 2.73–19.05), BT 2.01–4 mm (OR 7.04; 95% CI 2.54–19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65–474.86) (p  5 mitoses/mm2 (OR 4.87; 95% CI 1.77–13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01–2.00 mm (HR 1.55; 95% CI 0.51–4.71), BT 2.01–4.00 mm (HR 2.42; 95% CI 0.89–6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95–10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm2 (HR 2.34; 95% CI, 1.11–4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19–5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis. Conclusions We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence

Clinical, histopathological and molecular features of dedifferentiated melanomas:An EORTC Melanoma Group Retrospective Analysis

PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.</p

Restricted Mean Survival Time and Cure-Rate Modeling in Estimating Relapse-Free Survival Benefit With Adjuvant Dabrafenib + Trametinib Treatment in Melanoma

Abstract not available