Gender influence on work satisfaction and leadership for medical oncologists: a survey of the Spanish Society of Medical Oncology (SEOM)

Gènere; Enquesta; OncologiaGénero; Encuesta; OncologíaGender; Survey; OncologyBackground Women represent an increasing proportion of the oncology workforce; however, globally this does not translate into leadership roles, reflecting disparities in career opportunities between men and women. The Spanish Society of Medical Oncology (SEOM) undertook a survey to investigate gender disparity in the Spanish oncology context. Design An online survey was made available to SEOM medical oncologists between February and May 2019. It included demographics, professional context and achievements, parenthood and family conciliation issues, workplace gender bias, and approaches to address disparities. Results Of the 316 eligible respondents, 71.5% were women, 59.5% were aged 45 or younger, and 66.1% had children. Among women, 12.4% were division or unit heads, compared with 45.5% of men, with most women (74.3%) being attending medical oncologists, compared with 45.5% of men. More males were professors (34.4% versus 14.2% of females), had a PhD (46.7% versus 28.8%), and/or had led clinical research groups (41.1% versus 9.7%). Spending time overseas after completing a residency was also more common for men than women (34.4% versus 20.4%). Professional satisfaction was similar between genders, driven primarily by patient care and intellectual stimulation. More women (40.7%) considered parenthood to have a strong negative impact on their career, compared with men (9.0%). Main perceived barriers to gender equality included a lack of work–life balance (72.6% women, 44.4% men), bias of peers and superiors (50.0% women, 18.9% men), and different career goals (41.2% women, 24.4% men). Preferred solutions included educational programs and scholarships (52.9%), communication and leadership training (35.8%), childcare at conferences (33.2%), and postmaternity return-to-work incentives (32.0%). Conclusion There is a clear paucity of equal opportunities for female oncologists in Spain. This can be addressed by encouraging professional development and merit recognition particularly for younger female oncologists, and empowering women to be involved in management and leadership of institutions and professional societies.This study was funded by the Spanish Society of Medical Oncology (SEOM) (no grant number)

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Determinants of enhanced vulnerability to COVID-19 in UK cancer patients: a European Study

Background: Despite high contagiousness and rapid spread, SARS-CoV-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100.000 as of January 2021. We aimed to compare the national impact of COVID-19 on the risk of death in UK cancer patients versus those in continental Europe (EU). / Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with COVID-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, including oncological and COVID-19 specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk adverse outcome in multivariable Cox regression models. / Findings: Compared to EU (n=924), UK patients (n=468) were characterised by higher case fatality rates (40.38% versus 26.5%, p<0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%, p<0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p<0.01). Receipt of anticancer therapy was lower in UK versus EU patients (p<0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-COVID-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p<0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient’s age, gender, tumour stage and status, number of co-morbidities, COVID-19 severity, receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy post COVID-19 were similar in UK versus EU. / Interpretation: UK cancer patients have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted

Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection. Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974. Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113–148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1·80 [95% CI 1·18–2·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 [95% CI 1·45–8·59]), but dose or regimen adjustments were not (0·84 [0·35–2·02]). Interpretation: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients. Funding: National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust

Quantification of carbon and phosphorus co-limitation in bacterioplankton: new insights on an old topic

Because the nature of the main resource that limits bacterioplankton (e.g. organic carbon [C] or phosphorus [P]) has biogeochemical implications concerning organic C accumulation in freshwater ecosystems, empirical knowledge is needed concerning how bacteria respond to these two resources, available alone or together. We performed field experiments of resource manipulation (2×2 factorial design, with the addition of C, P, or both combined) in two Mediterranean freshwater ecosystems with contrasting trophic states (oligotrophy vs. eutrophy) and trophic natures (autotrophy vs. heterotrophy, measured as gross primary production:respiration ratio). Overall, the two resources synergistically co-limited bacterioplankton, i.e. the magnitude of the response of bacterial production and abundance to the two resources combined was higher than the additive response in both ecosystems. However, bacteria also responded positively to single P and C additions in the eutrophic ecosystem, but not to single C in the oligotrophic one, consistent with the value of the ratio between bacterial C demand and algal C supply. Accordingly, the trophic nature rather than the trophic state of the ecosystems proves to be a key feature determining the expected types of resource co-limitation of bacteria, as summarized in a proposed theoretical framework. The actual types of co-limitation shifted over time and partially deviated (a lesser degree of synergism) from the theoretical expectations, particularly in the eutrophic ecosystem. These deviations may be explained by extrinsic ecological forces to physiological limitations of bacteria, such as predation, whose role in our experiments is supported by the relationship between the dynamics of bacteria and bacterivores tested by SEMs (structural equation models). Our study, in line with the increasingly recognized role of freshwater ecosystems in the global C cycle, suggests that further attention should be focussed on the biotic interactions that modulate resource co-limitation of bacteria.This research was supported by Junta de Andalucía (Excelencia P09-RNM-5376 to JMMS) and the Spanish Ministry Ciencia e Innovación (CGL2011-23681 to PC)

Specialist palliative and end-of-life care for patients with cancer and SARS-CoV-2 infection: a European perspective

Background: Specialist palliative care team (SPCT) involvement has been shown to improve symptom control and end-of-life care for patients with cancer, but little is known as to how these have been impacted by the COVID-19 pandemic. Here, we report SPCT involvement during the first wave of the pandemic and compare outcomes for patients with cancer who received and did not receive SPCT input from multiple European cancer centres. Methods: From the OnCovid repository (N = 1318), we analysed cancer patients aged ⩾18 diagnosed with COVID-19 between 26 February and 22 June 2020 who had complete specialist palliative care team data (SPCT+ referred; SPCT− not referred). Results: Of 555 eligible patients, 317 were male (57.1%), with a median age of 70 years (IQR 20). At COVID-19 diagnosis, 44.7% were on anti-cancer therapy and 53.3% had ⩾1 co-morbidity. Two hundred and six patients received SPCT input for symptom control (80.1%), psychological support (54.4%) and/or advance care planning (51%). SPCT+ patients had more ‘Do not attempt cardio-pulmonary resuscitation’ orders completed prior to (12.6% versus 3.7%) and during admission (50% versus 22.1%, p < 0.001), with more SPCT+ patients deemed suitable for treatment escalation (50% versus 22.1%, p < 0.001). SPCT involvement was associated with higher discharge rates from hospital for end-of-life care (9.7% versus 0%, p < 0.001). End-of-life anticipatory prescribing was higher in SPCT+ patients, with opioids (96.3% versus 47.1%) and benzodiazepines (82.9% versus 41.2%) being used frequently for symptom control. Conclusion: SPCT referral facilitated symptom control, emergency care and discharge planning, as well as high rates of referral for psychological support than previously reported. Our study highlighted the critical need of SPCTs for patients with cancer during the pandemic and should inform service planning for this population

Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: the OnCovid Inflammatory Score

Background: Cancer patients are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and Covid-19. We investigated systemic inflammation as a driver of severity and mortality from Covid-19, evaluating the prognostic role of commonly utilized inflammatory indices in SARS-CoV-2-infected cancer patients accrued to the OnCovid study. Methods: In a multi-center cohort of SARS-CoV-2-infected cancer patients in Europe, we evaluated dynamic changes in neutrophil-lymphocyte ratio (NLR); platelet-lymphocyte ratio (PLR); prognostic nutritional index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow prognostic score (mGPS); and prognostic index (PI) in relationship to oncological and Covid-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results: We evaluated 1,071 eligible patients: 625 (58.3%) males, 420 with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) ≥1 Covid-19 complication. NLR, OIS, and mGPS worsened at Covid-19 diagnosis compared to pre-Covid-19 measurement (P<0.01), recovering in survivors to pre-Covid-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (P<0.001) and shorter median overall survival in the training and validation sets (P<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 – 4.20, P=0.001; adjusted C-index 0.611). Conclusions: Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected cancer patients and can be utilized as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe Covid-19, supporting their use for risk stratification. Reversal of the Covid-19-induced pro-inflammatory state is a putative therapeutic strategy in patients with cancer

Estudio de incidencia y seguimiento del hematoma de glotis en pacientes tratados con acenocumarol Study of incidence and follow-up of glottic haematoma in patients under acenocoumaro/ therapy

Con el objeto de valorar la incidencia y repercusión clínica de complicaciones hemorrágicas que la terapia anticoagulante con acenocumarol genera en la laringe de los pacientes, se desarrolló un estudio prospectivo longitudinal observacional sobre una población así tratada, a la que al menos en una ocasión se le practic6 una exploraci6n endoscópica de laringc, independientemente de que presentaran o no sintomatologfa laríngea. En dos años fueron incluidos un total de 775 pacientes. alcanzando un seguimiento absoluto de 1.238.54 pacientes- año. Fueron detectados 176 desórdenes hemorrágicos en 132 pacientes -el 17,0% del total-, con una incidencia de 14,2/100 pacientes-año. Las manifestaciones hemorrágicas mas frecuentes fueron las epistaxis y las de los tractos genito-urinario y digestivo, quedando en sexto lugar por orden de frecuencia los hematomas laríngeos, con 14 casos -el 7,9% de todas las hemorragias-, con una incidencia de I, 13/100 pacientes-afio. Este tipo de complicación por acenocumarol afectó tfpicamente a pacientes con defectuoso grado de cumplimentaci6n del tratamiento (66.4%), historial previo de otras complicaciones hemorragicas ( 100%), mas alla del primer afio de tratamicnto (78,6%) y con un grado intermedio de desencadenante traumatico (58,2%). La exploraci6n laríngea reveló que el 35,7% de los hematomas de glotis no presentaban sintomatologfa alguna, y cuando lo hadan siempre empezaban con disnea. El 85,7% de los casos evidenció un INR excesivamente prolongado, y hasta el 71.4% de los pacientes mostraba hallaLgos objetivos de laringitis cró- nica. En todos los casos se modific6 la dosis de acenocumarol, llegando a suspcnderse en nueve, y en cinco se procedió al ingreso hospitalario para tratamiento con hemoderivados. Existió un caso en que el hematoma ocluyó por completo la glotis y evolucionó a un desenlace fatal pese a practicar una traqueotomía urgente. El hematoma de glotis no es una complicación inusual del empleo de dicumarfnicos. El mismo debe sospecharse en pacientes con malos controles de su terapeutica anticoagulante, con habito fumador, y descartarse cuando el paciente consulta por disfonía o disnea

Análisis de métodos de fabricación de modelos sintéticos de hombro con componentes protésicos de la artroplastia total aptos para estudios de cargas y ensayos fotoelásticos

En el presente trabajo se desarrollan y comparan dos métodos de fabricación de modelos con dos tipos de prótesis invertidas: Delta (Depuy Sinthes) y SMR (Lima). Los modelos obtenidos a partir de técnicas de reproducción de huesos conservando los elementos anatómicos y accidentes óseos [3], son aptos para estudios con Fotoelasticidad 3D, técnica que permite evaluar la implantación y el problema de contacto de las prótesis con las estructuras óseas