Search

Background. Student departure from university without completing a qualification is a major concern in higher education. Higher Education South Africa reported that in undergraduate studies, 35% of students depart after the first year and only 15% of students who enrol complete their degree within the minimum permissible time. At postgraduate level, the departure from Masters programmes in South Africa (SA) ranged from 30% to 67% in 2010. Early departure refers to students who leave an academic programme within the first semester of commencing their studies. At one SA university, there were a total of 109 first-time Master of Public Health (MPH) student registrations in 2013 and 2014. By the end of the first semester in the respective years, a total of 27 students actively deregistered from the programme and 11 students did not sit the first-semester examinations, representing an aggregate 35% rate of early departure. The factors associated with early departure at the University of KwaZulu-Natal are not well understood.Objective. To understand factors associated with early departure in the MPH programme at the University of KwaZulu-Natal.Method. A mixed-methods design was implemented. Students who departed within the first semester of commencing the MPH programme in 2013/2014 were followed up. Data were collected using self-administered questionnaires and in-depth interviews.Results. Failure to balance work and academic obligations with poor time management, stress and academic demands related to the programme, and insufficient academic progress were found to be associated with student early departure from the MPH programme.Conclusion. Student early departure from the MPH programme was influenced by multifaceted factors. Senior students can mentor new students as early as possible in their programme. The orientation block should include development activities such as time management, stress management and effective study skills to assist mature students to cope with the demands of part-time postgraduate studies.

HIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1) HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2) phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models.We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM) with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2). After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM.SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

Background: Fatigue, cognitive impairment, anxiety, depression, and sleep disturbance are cancer-related behavioral symptoms (CRBS) that may persist years after early-stage breast cancer (BC), affecting quality of life. We aimed at generating a predictive model of long-term CRBS clusters among BC survivors four years post-diagnosis., Methods: Patients with early-stage BC were included from the CANcer TOxicity (NCT01993498). Our outcome was the proportion of patients reporting CRBS clusters four years post-diagnosis (≥3 severe CRBS). Predictors, including clinical, behavioral, and treatment-related characteristics, Behavioral Symptoms Score (BSS; 1 point per severe CRBS at diagnosis) and a pro-inflammatory cytokine (IL-1b, IL-6, TNFα)-genetic risk score, were tested using multivariable logistic regression, implementing bootstrapped Augmented Backwards Elimination. A two-sided p-value < 0.05 defined statistical significance., Results: In the development cohort (N = 3555), 642 patients (19.0%) reported a cluster of CRBS at diagnosis and 755 (21.2%) did so four years post-diagnosis. Younger age (adjusted Odds Ratio [aOR] for 1-year decrement: 1.012; 95% Confidence Interval [CI] 1.003-1.020); previous psychiatric disorders (aOR vs no: 1.27; 95% CI 1.01-1.60); and BSS (aOR ranged from 2.17 [1.66-2.85] for BSS = 1 vs 0 to 12.3 [7.33-20.87] for BSS = 5 vs 0) were predictors of reporting a cluster of CRBS (AUC 0.73 [95%CI 0.71-0.75]). Genetic risk score was not predictive of CRBS. Results were confirmed in the validation cohort (N = 1533)., Conclusion: Younger patients with previous psychiatric disorders and higher baseline symptom burden have greater risk of long-term clusters of CRBS. Our model might be implemented in clinical pathways to improve management and test the effectiveness of risk mitigation interventions among breast cancer survivors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Endocrine therapy plays a crucial role in the treatment of women with hormone receptor-positive breast cancer. However, non-adherence remains a frequent issue known to negatively impact survival. Based on a comprehensive literature review, this article explores the terminologies employed to describe adherence and methods used for its assessment, the adherence data reported with adjuvant endocrine therapy with targeted therapies, the determinants of adherence or non-adherence, and finally, tested solutions to address it. The results show that a better understanding of the causes of non-adherence would help to better identify patients at risk, and to develop personalized intervention programs capable of improving adherence to adjuvant endocrine therapy. In light of the literature, interventions are likely to require a multimodal approach and integration into our future healthcare pathways., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score., Methods: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden's statistic., Results: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95., Conclusion: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies., (© 2024. The Author(s).)

In communication technologies such as digital watermarking, wireless sensor networks (WSNs), and visual light communication (VLC), error-correcting codes are crucial. The Enhanced Hadamard Error-Correcting Code (EHC), which is based on 2D Hadamard Basis Images, is a novel error correction technique that is presented in this study. This technique is used to evaluate the effectiveness of the video watermarking scheme. Even with highly sophisticated embedding techniques, watermarks usually fail to resist such comprehensive attacks because of the extraordinarily high compression rate of approximately 1:200 that is frequently employed in video dissemination. It can only be used in conjunction with a sufficient error-correcting coding method. This study compares the efficacy of the well-known Reed-Solomon Code with this novel technique, the Enhanced Hadamard Error-Correcting Code (EHC), in maintaining watermarks in embedded videos. The main idea behind this newly created multidimensional Enhanced Hadamard Error-Correcting Code is to use a 1D Hadamard decoding approach on the 2D base pictures after they have been transformed into a collection of one-dimensional rows. Following that, the image is rebuilt, allowing for a more effective 2D decoding procedure. Using this technique, it is possible to exceed the theoretical error-correcting capacity threshold of ⌊dmin-12⌋ bits, where dmin is the Hamming distance. It may be possible to achieve better results by converting the 2D EHC into a 3D format. The new Enhanced Hadamard Code is used in a video watermarking coding scheme to show its viability and efficacy. The original video is broken down using a multi-level interframe wavelet transform during the video watermarking embedding process. Low-pass filtering is applied to the video stream in order to extract a certain frequency range. The watermark is subsequently incorporated using this filtered section. Either the Reed-Solomon Correcting Code or the Enhanced Hadamard Code is used to protect the watermarks. The experimental results show that EHC far outperforms the RS Code and is very resilient against severe MPEG compression.

Objectives: Tumor molecular genotyping plays a key role in improving the management of advanced thyroid cancers. Molecular tests are classically performed on Formalin-Fixed Paraffin-Embedded (FFPE) carcinoma tissue. However alternative molecular testing strategies are needed when FFPE tumoral tissue is unavailable. The objective of our study was to retrospectively assess the performance of targeted DNA and RNA-based Next Generation Sequencing (NGS) on the fine needle aspirate from thyroid cancer cervical recurrences to determine if this strategy is efficient in clinical practice., Design/methods: A retrospective study of 33 patients who had had DNA and/or RNA-based NGS on ultrasound (US)-guided fine needle aspirates of cervical thyroid cancer recurrences in our Department from July 2019 to September 2022., Results: In total, 34 DNA and 32 RNA-based NGS analyses were performed. Out of the 34 DNA-based NGS performed, 27 (79%) were conclusive allowing the identification of an oncogenic driver for 18 patients (53%). The most common mutation (n = 13) was BRAF c.1799T>A. Out of the 32 RNA-based NGS performed, 26 were interpretable (81%) and no gene fusion was found. The identification of a BRAFV600E mutation was decisive for one patient in our series, who was prescribed dabrafenib and trametinib., Conclusions: NGS performed on fine needle aspirates of neck lymph node metastases enabled the identification of an oncogenic driver alteration in 53% of the cases in our series of advanced thyroid cancer patients and could significantly alter patient management.

Background: The SARS CoV-2 pandemic disrupted healthcare systems. We compared the cancer stage for new breast cancers (BCs) before and during the pandemic., Methods: We performed a retrospective multicenter cohort study on the data warehouse of Greater Paris University Hospitals (AP-HP). We identified all female patients newly referred with a BC in 2019 and 2020. We assessed the timeline of their care trajectories, initial tumor stage, and treatment received: BC resection, exclusive systemic therapy, exclusive radiation therapy, or exclusive best supportive care (BSC). We calculated patients' 1-year overall survival (OS) and compared indicators in 2019 and 2020., Results: In 2019 and 2020, 2055 and 1988, new BC patients underwent cancer treatment, and during the two lockdowns, the BC diagnoses varied by -18% and by +23% compared to 2019. De novo metastatic tumors (15% and 15%, p = 0.95), pTNM and ypTNM distributions of 1332 cases with upfront resection and of 296 cases with neoadjuvant therapy did not differ (p = 0.37, p = 0.3). The median times from first multidisciplinary meeting and from diagnosis to treatment of 19 days (interquartile 11-39 days) and 35 days (interquartile 22-65 days) did not differ. Access to plastic surgery (15% and 17%, p = 0.08) and to treatment categories did not vary: tumor resection (73% and 72%), exclusive systemic therapy (13% and 14%), exclusive radiation therapy (9% and 9%), exclusive BSC (5% and 5%) (p = 0.8). Among resected patients, the neoadjuvant therapy rate was lower in 2019 (16%) versus 2020 (20%) (p = 0.02). One-year OS rates were 99.3% versus 98.9% (HR = 0.96; 95% CI, 0.77-1.2), 72.6% versus 76.6% (HR = 1.28; 95% CI, 0.95-1.72), 96.6% versus 97.8% (HR = 1.09; 95% CI, 0.61-1.94), and 15.5% versus 15.1% (HR = 0.99; 95% CI, 0.72-1.37), in the treatment groups., Conclusions: Despite a decrease in the number of new BCs, there was no tumor stage shift, and OS did not vary., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Anaplastic thyroid carcinoma (ATC) is a rare and frequently fatal type of thyroid cancer. The degree of heterogeneity in survival rates for ATC is incompletely studied. This study evaluated the factors associated with overall survival (OS) of patients with ATC using multicenter real-world data from a national tertiary care center network in France. Methods: In this multicenter, retrospective cohort study, all patients with ATC diagnosed between 2010 and 2020 were identified from the national database of the French ENDOCAN-TUTHYREF network. Factors associated with OS were examined in multivariable analyses using Cox proportional hazards models. Results: The study included 360 patients. Of these, 220 (61%) were female and the median age was 72 years (interquartile range: 62-80). The percentages of patients with pure and mixed (synchronously-transformed) ATC (p-ATC and st-ATC) were 62.5% and 26.7%, respectively. The median OS was 6.8 months [confidence interval, CI: 5.5-8.1]: not reached for stage IVa, 11.4 months [8.2-17.8] for IVb, and 4.6 months [3.5-5.7] for IVc. Surgery, radiation therapy to the neck, chemotherapy, and best supportive care were administered to 69 (19.2%), 214 (59.4%), 254 (70.6%), and 66 (18.3%) patients, respectively. In a multivariable analysis, including stage IVb-IVc patients, significantly higher OS was observed in patients with Eastern Cooperative Oncology Group performance-status of 0-1 (hazard ratio [HR], 0.6; [CI, 0.4-0.9], p  < 0.02), stage IVb [HR, 0.5; CI, 0.4-0.8, p  < 0.001], and multimodal treatment (surgery and chemoradiotherapy) [HR, 0.07; CI, 0.04-0.1, p  < 0.001]. Variables associated with significantly worse OS included: p-ATC (vs. st-ATC) [HR, 1.83; CI, 1.33-2.51, p  = 0.001] and a neutrophil-to-lymphocyte ratio (NLR) >5.05 [HR, 2.05, CI, 1.39-3.05, p  < 0.001]. Conclusions: Factors independently associated with improved OS in ATC included: European Cooperative Oncology Group performance status, disease stage, multimodality treatment, synchronously transformed ATC, and lower NLR. Long-term OS was observed in selected patients with ATC who underwent multimodal treatment.

Background: Small-cell lung cancer (SCLC) accounts for approximately 15% of lung cancer and is associated with poor prognosis. In platinum-refractory or -resistant SCLC patients, few treatment options are available. Topotecan is one of the standards of care for these patients, however, due to its high toxicity, several different approaches are employed. FOLFIRI (folinate, 5-fluorouracil and irinotecan) is a chemotherapy regimen used in digestive neuroendocrine carcinoma, which shares pathological similarities with SCLC. In this retrospective study, we evaluated the efficacy and safety of FOLFIRI in patients with platinum-resistant/refractory SCLC., Methods: Medical records from all consecutive SCLC patients treated with FOLFIRI in a French University Hospital from 2013 to 2021 were analyzed retrospectively. The primary endpoint was the objective response rate according to RECIST v1.1 or EORTC criteria (ORR); secondary endpoints included duration of response, disease control rate, progression-free survival (PFS), overall survival (OS) and safety profile., Results: Thirty-four patients with metastatic platinum-resistant ( n  = 14) or -refractory ( n  = 20) SCLC were included. Twenty-eight were evaluable for response, with a partial response observed in 5 patients for an overall ORR in the evaluable population of 17.9% (5/28) and 14.7% (5/34) in the overall population. The disease control rate was 50% (14/28) in the evaluable population. The median PFS and OS were 2.8 months (95%CI, 2.0-5.2 months) and 5.3 months (95%CI, 3.5-8.9 months), respectively. All patients were included in the safety analysis. Grade 3 or 4 adverse events occurred in 13 (38.2%) patients. The most common grade 3 or 4 adverse events were asthenia, neutropenia, thrombopenia and diarrhea. There was no adverse event leading to discontinuation or death., Conclusion: FOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response and had an acceptable safety profile. However, caution is needed in interpreting this result. FOLFIRI could represent a potential new treatment for platinum-resistant/refractory SCLC patients. Further prospective studies are needed to assess the benefits of this chemotherapy regimen.HIGHLIGHTSFOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response.FOLFIRI was well-tolerated in platinum resistant/refractory SLCL patients.FOLFIRI could represent a potential new treatment for SCLC, prospective studies are needed.

Purpose: Characterizing oral adjuvant endocrine therapy (ET) non-initiation and non-persistence in young women with breast cancer can inform strategies to improve overall adherence in this population., Methods: We identified 693 women with hormone receptor-positive, stage I-III breast cancer enrolled in a cohort of women diagnosed with breast cancer at age ≤ 40 years. Women were classified as non-initiators if they did not report taking ET in the 18 months after diagnosis. Women who initiated but did not report taking ET subsequently (through 5-year post-diagnosis) were categorized as non-persistent. We assessed ET decision-making and used logistic regression to identify factors associated with non-initiation/non-persistence and to evaluate the association between non-persistence and recurrence., Results: By 18 months, 9% had not initiated ET. Black women had higher odds and women with a college degree had lower odds of non-initiation. Among 607 women who initiated, 20% were non-persistent. Younger age, being married/partnered, and reporting more weight problems were associated with higher odds of non-persistence; receipt of chemotherapy and greater hot flash and vaginal symptom burden were associated with lower odds of non-persistence. Adjusting for age and clinical characteristics, non-persistence was associated with lower odds of recurrence. Women who initiated were more likely to report shared decision-making than non-initiators (57% vs. 38%, p = 0.049), while women who were non-persistent were less likely to indicate high confidence with the decision than women who were persistent (40% vs. 63%, p < 0.001)., Conclusion: Interventions to improve ET decision-making may facilitate initiation and address barriers to adherence in young breast cancer survivors., Trial Registration: www., Clinicaltrials: gov , NCT01468246., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies., Methods: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L., Results: 563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed., Conclusions: These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective., Gov Registration Number: NCT02400476., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arlene Chan: no competing interests to declare. Manuel Ruiz-Borrego: no competing interests to declare. Gavin Marx: no competing interests to declare. A. Jo Chien: Contracted research (personal) from Puma Biotechnology Inc. Hope S. Rugo: Research support for clinical trials through the University of California: Pfizer, Merck, Novartis, Lilly, Roche, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Astellas, and Gilead. Honoraria from: Puma, Samsung, Chugai, Blueprint, and NAPO. Travel: GE Healthcare. Adam Brufsky: Consulting fees (personal) from Puma Biotechnology Inc. Michael Thirlwell: no competing interests to declare. Maureen Trudeau: no competing interests to declare. Ron Bose: Research grant from Puma Biotechnology, and consulting from Genentech. José A. García-Sáenz: consultative and advisory services for Seagen, Gilead, and Sanofi; consultancy/speaker fees from Novartis, Celgene, Eli Lilly, EISAI, AstraZeneca, Daiichi Sankyo, MSD, and Pierre Fabre; institution research funding from AstraZeneca; travel support from Novartis, Roche, and Pfizer. Daniel Egle: advisory services for AstraZeneca, Daiichi Sankyo, MSD, Seagen, Gilead, Novartis, Roche, Pfizer, and Lilly; consultancy/speaker fees from Roche, Pfizer, Novartis, Lilly, AstraZeneca, Daiichi Sankyo, MSD, Seagen, and Gilead; travel support from AstraZeneca and Pfizer. Barbara Pistilli: Consulting fees (personal) from Puma Biotechnology Inc., Pierre Fabre. Contracted research (personal) for Puma Biotechnology Inc. Johanna Wassermann: no competing interests to declare. Kerry A. Cheong: no competing interests to declare. Benjamin Schnappauf: no competing interests to declare. Dieter Semsek: no competing interests to declare. Christian F. Singer: no competing interests to declare. Navid Foruzan: Full-time employment Puma Biotechnology Inc. Ownership interest (stock, stock options) Puma Biotechnology Inc. Daniel DiPrimeo: Full-time employment Puma Biotechnology Inc. Ownership interest (stock, stock options) Puma Biotechnology Inc. Leanne McCulloch: Full-time employment Puma Biotechnology Inc. Ownership interest (stock, stock options) Puma Biotechnology Inc. Sara A. Hurvitz: Contracted research paid to institution: Ambrx, Amgen, Arvinas, AstraZeneca, Bayer, Cytomx, Daiichi Sankyo, Dantari, Dignitana, Genentech/Roche, G1-Therapeutics, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, OBI Pharma, Orinove, Pfizer, Phoenix Molecular Designs, Ltd., Pieris, PUMA, Radius, Samumed, Sanofi, Seattle Genetics/Seagen, Zymeworks; Travel expenses paid to SAH: Lilly (2019); speaking: Daiichi Sankyo (2021). Carlos H. Barcenas: no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Multi-receptor tyrosine kinase inhibitors with anti-angiogenic activity, particularly lenvatinib, have become the standard treatment for radioiodine-refractory metastatic differentiated thyroid cancer but are associated with a high incidence of toxicity. Although patients treated with lenvatinib have been shown to have a significant improvement in progression-free survival, lenvatinib-associated toxicity may result in dose reductions, dose interruptions or even complete lenvatinib withdrawal, compromising anti-tumor efficacy., Areas Covered: The article covers the main cardiological and renal toxicities of lenvatinib, including hypertension, prolonged QT interval, heart failure, arterial and venous thromboembolic events, proteinuria and renal failure, and proposes appropriate management of these events during lenvatinib therapy. We performed a literature review of cardiovascular and renal toxicities of Lenvatinib in radioiodine-refractory differentiated thyroid cancer. We discussed prophylactic and therapeutic management for each toxicity based on literature and clinical expertise., Expert Opinion: Specific pre-therapeutic evaluation and close monitoring of patients treated with lenvatinib is necessary to prevent and detect cardiovascular and/or renal toxicities early, and to propose appropriate management. Oncologists who treat patients with lenvatinib should know how to monitor and treat these adverse events, and when to ask for the advice of a specialist (cardiologist or nephrologist).

Background: Nuclear protein in testis (NUT) carcinomas (NC) are a rare, highly aggressive, subset of squamous cell carcinomas, characterized by a translocation involving the NUTM1 gene. Thyroid location of NUT carcinomas has rarely been described. Methods: We report here two cases of thyroid NC with NSD3::NUTM1 translocation. Results: The first case presented as a very aggressive undifferentiated thyroid carcinoma in a 38-year-old man who died 21 months after the diagnosis. The second case was diagnosed after multiple lymphadenopathy recurrences mainly in the neck in a 37-year-old woman 7 years after total thyroidectomy for papillary thyroid carcinoma with a classic and a solid/trabecular component. Conclusions: Our case reports highlight the challenges in diagnosing these exceptional carcinomas. The therapeutic impact of the administration of pharmacological compounds with epigenetic action, in line with the physiopathology of these carcinomas, is also discussed.

Refractory thyroid cancers include radio-iodine-refractory cancers, metastatic or locally advanced unresectable medullary and anaplastic thyroid cancers. Their management has been based for several years on the use of multi-target kinase inhibitors, with anti-angiogenic action, with the exception of anaplastic cancers usually treated with chemo- and radiotherapy. The situation has recently evolved due to the availability of molecular genotyping techniques allowing the discovery of rare but targetable molecular abnormalities. New treatment options have become available, more effective and less toxic than the previously available multi-target kinase inhibitors. The management of refractory thyroid cancers is therefore becoming more complex both at a diagnosis level with the need to know when, how and why to look for these molecular abnormalities but also at a therapeutic level, innovative treatments being hardly accessible. The cost of molecular analyzes and the access to treatments need also to be homogenized because disparities could lead to inequality of care at a national or international level. Finally, the strategy of identifying molecular alterations and treating these rare tumors reinforces the importance of a discussion in a multidisciplinary consultation meeting., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Multikinase inhibitor (MKI) treatments have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC), but most patients experienced substantial adverse effects. This randomised multicentric study investigated intermittent versus continuous pazopanib administration., Patients and Methods: The PAZOTHYR study included RAIR-TC patients with progressive disease in the last 12 months, who may have received one prior MKI. RAIR-TC patients received pazopanib for 6 months, and patients with stable disease or tumour response were randomly assigned (1:1) to receive continuous (CP) or intermittent (IP) pazopanib until progression. The primary end-point was time to treatment failure (TTF) defined as the time from randomisation to permanent discontinuation of pazopanib, due to any cause. One hundred randomised patients were needed to demonstrate an increase from 50% (CP) to 70% (IP) (hazard ratio (HR) 0.515, 80% power) in the rate of patients still under treatment 6 months (6m-SuT) post-randomisation. Secondary end-points included the overall response rate (ORR), progression-free survival (PFS) under pazopanib and safety., Results: RAIR-TC patients (168) enrolled from June 18, 2013 to January 16, 2018, received 6-month pazopanib treatment and showed 35.6% (95% CI 28.2-43.6) best response rate and 89.4% (83.5-93.7) disease control rate. One hundred patients were randomised (IP:50; CP:50). With a median follow-up of 31.3 months, median TTF was not statistically different between arms (IP:14.7, 95% confidence interval (CI) 9.3-17.4; CP:11.9, 95% CI 7.5-15.6) months (HR 0.79, 0.49-1.27). 6m-SuT rates were similar (IP:80% 66.0-88.7%; CP:78% 63.8-87.2%). Median PFS under pazopanib were not statistically different (IP:5.7 4.8-7.8; CP: 9.2 7.3-11.1) months (HR 1.36, 0.88-2.12). Pazopanib-related adverse events grade 3-4 occurred in 36 (IP: 19, 38%; CP: 17, 34%) randomised patients. Seven pazopanib-related deaths occurred., Conclusions: Intermittent administration of pazopanib did not demonstrate significant superiority in efficacy or tolerance compared with continuous treatment. An intermittent administration scheme cannot be recommended outside clinical trials. This study was registered with ClinicalTrial.gov, number NCT01813136., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In seismology, an increased effort to observe all 12 degrees of freedom of seismic ground motion by complementing translational ground motion observations with measurements of strain and rotational motions could be witnessed in recent decades, aiming at an enhanced probing and understanding of Earth and other planetary bodies. The evolution of optical instrumentation, in particular large-scale ring laser installations, such as G-ring and ROMY (ROtational Motion in seismologY), and their geoscientific application have contributed significantly to the emergence of this scientific field. The currently most advanced, large-scale ring laser array is ROMY, which is unprecedented in scale and design. As a heterolithic structure, ROMY's ring laser components are subject to optical frequency drifts. Such Sagnac interferometers require new considerations and approaches concerning data acquisition, processing and quality assessment, compared to conventional, mechanical instrumentation. We present an automated approach to assess the data quality and the performance of a ring laser, based on characteristics of the interferometric Sagnac signal. The developed scheme is applied to ROMY data to detect compromised operation states and assign quality flags. When ROMY's database becomes publicly accessible, this assessment will be employed to provide a quality control feature for data requests.