External Validation of a Prognostic Score for Patients with Brain Metastases: Extended Diagnosis-Specific Graded Prognostic Assessment

This is the accepted manuscript version of an article published by Karger Publishers in [Oncology Research and Treatment/2020/43/5/221–226 DOI: 10.1159/000506954 and available on https://www.karger.com/Article/FullText/506954Purpose: The aim of our study was the external validation of an extended variant of the four-tiered diagnosis-specific graded prognostic assessment (DS-GPA) that includes more information about extracranial disease burden and blood test results, and predicts survival of patients with brain metastases. The extracranial DS-GPA (EC-GPA) includes serum albumin, lactate dehydrogenase, and number of extracranial organs involved. Originally, the score was developed in Germany. Patients and Methods: A retrospective analysis of 236 patients with brain metastases treated with primary whole-brain radiotherapy in North-Norway was performed (independent external validation cohort). Results: The fourtiered EC-GPA score showed good discrimination between all prognostic groups (log-rank test p < 0.05 for all pairwise comparisons). One-year survival was 0, 11, 30, and 100%, respectively. Median survival was 0.7 months (95% CI, 0.5–0.9) in the worst prognostic group, with a hazard ratio for death of 44.31 (95% CI, 5.78–339.50) compared to the best group. In the German database, the corresponding HR was 31.64 (median survival 0.4 months). The remaining hazard ratios in this validation study were 7.13 and 12.10, compared with 4.84 and 9.26 in the score development study. Conclusions: This study provides an independent validation of the ECGPA, which was the best prognostic model for defining patients who did not benefit from radiation therapy of brain metastases in terms of overall survival in the original German study. The proposed modification of the established DS-GPA should undergo further validation in multi-institutional databases

Percepções sobre os Porcos: Povos de Faxinais e Lutas Territoriais: Perceptions about Pigs: People of Faxinais and Territorial Struggles

Based on the ethnographic study of the traditional community of Faxinal Meleiro in the southern metropolitan region of Curitiba, the article aims to explore the different conceptions and notions in Faxinal about pig farming in the context of communal land use, which involves exchange and transmission of traditional knowledge, forms of local sociability and rules for land use and management. Therefore, the aim is to understand the importance of pigs in the construction and activation of the Faxinal identity and how the animal emerges as a symbol of the political struggle, associated with the organizational strategies carried out by the social movement of the people living in such areas.A partir del estudio etnográfico de la comunidad tradicional de Faxinal Meleiro, en la región metropolitana sur de Curitiba, el artículo tiene como objetivo explorar las diversas concepciones y nociones faxinalenses sobre la cría de cerdos en el contexto del uso comunal de tierras, lo que implica el intercambio y la transmisión de conocimientos tradicionales, formas de sociabilidad local y reglas de uso y gestión territorial. Por lo tanto, se busca comprender la importancia de los cerdos en la construcción y activación de la identidad faxinalense, y cómo el animal emerge como símbolo de la lucha política, asociado a las estrategias organizativas llevadas a cabo por el movimiento social de los pueblos de faxinales.A partir do estudo etnográfico da comunidade tradicional de Faxinal Meleiro, na região metropolitana sul de Curitiba, o artigo tem como objetivo explorar as diversas concepções e noções faxinalenses acerca da criação de porcos no contexto do uso comunal de terras, o que envolve o intercâmbio e a transmissão de conhecimentos tradicionais, formas de sociabilidade local e regras de uso e gestão territorial. Busca-se, portanto, entender a importância dos porcos na construção e acionamento da identidade faxinalense, e como o animal emerge como símbolo da luta política, associado às estratégias organizativas levadas a cabo pelo movimento social dos povos de faxinais

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases

Background: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO)stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. Methods: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. Results: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n= 213 pts.; 300 lesions) and breast cancer (n= 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control

Na,K-ATPase on a waveguide sensor : supramolecular assembly and side directed binding studies by surface-confined fluorescence

Grell E, Pawlak M, Anselmetti D, Schick E, Lewitzki E, Ehrat M. Na,K-ATPase on a waveguide sensor : supramolecular assembly and side directed binding studies by surface-confined fluorescence. In: Taniguchi K, Kaya S, eds. Na/K-ATPase and related ATPases: proceedings of the 9th International Conference on the Na/K-ATPase and Related ATPases. Excerpta Medica international congress series. Vol 1207. Amsterdam: Elsevier; 2000: 437-440.The functional assembly of FITC-Na,K-ATPase membrane fragments on a surface-modified Ta2O5 waveguide allows to investigate the directed binding of ligands by surface-confined fluorescence studies. The results allow to draw conclusions about the sidedness of interactions. The fluorescence intensity decrease observed upon the selective binding of K+ is attributed to its coordination to a site accessible from the former intracellular membrane side

Povos e Comunidades Tradicionais impactados mas não atendidos: hidrelétricas na geração de pobreza energética

In the context of the climate emergency and the transition of energy matrices, it is necessary to question the overcoming of environmental racism, energy injustice, and coloniality in the Brazilian context. The article aims to address the intersection of these concepts related to indigenous peoples, traditional peoples, and communities in Brazil, in order to examine how energy production, especially through hydroelectric plants, negatively impacts their territories and rights, perpetuating and deepening a scenario of energy poverty - understood as the lack of access to energy, but also as the loss of sociobiodiversity caused by energy projects that impact but do not serve these populations. The methodology includes data collection, as well as a literature review and qualitative data on rights violations and lack of access to energy by these groups, making visible the claims of traditional peoples and communities. The results indicate that energy expansion, in addition to not guaranteeing access to energy for these populations, devastates them with territorial and cultural impoverishment due to this expansion without respect for their self- determination. It is concluded that the expansion of energy projects in Brazil reproduces coloniality and environmental racism by neglecting these populations, resulting in socio-environmental injustices that exacerbate energy poverty and violate fundamental rights, which cannot be accepted in the pursuit of energy transition. The final considerations highlight the urgent need for policies that guarantee prior, free, and informed consultation and consent of these peoples, aiming for a just and inclusive energy transition.No contexto de emergência climática e transição de matrizes energéticas, insta o questionamento sobre superação do racismo ambiental, injustiça energética e colonialidade no contexto brasileiro. O artigo possui como objetivo abordar a interseção desses conceitos relacionados a povos indígenas, povos e comunidades tradicionais no Brasil, a fim de examinar como a produção de energia, especialmente por meio de hidrelétricas, impactam negativamente os seus territórios e seus direitos, perpetuando e aprofundando um cenário de pobreza energética - compreendida como falta de acesso à energia, mas também como perda de sociobiodiversidade causada por empreendimentos de energia que impactam, mas não atendem a essas populações. A metodologia inclui levantamento de dados, além de revisão bibliográfica e dados qualitativos sobre violações de direitos e falta de acesso à energia por esses grupos, visibilizando reivindicações dos povos indígenas, povos e comunidades tradicionais. Os resultados indicam que a expansão energética, além de não garantir acesso à energia a essas populações, as assola com empobrecimento territorial e cultural dessa expansão sem respeito a sua livre determinação. Conclui-se que o avanço de empreendimentos energéticos no Brasil reproduz a colonialidade e o racismo ambiental ao negligenciar essas populações, resultando em injustiças socioambientais que exacerbam a pobreza energética e violam direitos fundamentais, o que não pode ser admitido na busca pela transição energética. As considerações finais destacam a necessidade urgente de políticas que garantam a consulta e consentimento prévio, livre e informado desses povos, visando uma transição energética justa e inclusiva.No contexto de emergência climática e transição de matrizes energéticas, insta o questionamento sobre superação do racismo ambiental, injustiça energética e colonialidade no contexto brasileiro. O artigo possui como objetivo abordar a interseção desses conceitos relacionados a povos indígenas, povos e comunidades tradicionais no Brasil, a fim de examinar como a produção de energia, especialmente por meio de hidrelétricas, impacta negativamente os seus territórios e seus direitos, perpetuando e aprofundando um cenário de pobreza energética - compreendida como falta de acesso à energia, mas também como perda de sociobiodiversidade causada por empreendimentos de energia que impactam, mas não atendem a essas populações. A metodologia inclui levantamento de dados, além de revisão bibliográfica e dados qualitativos sobre violações de direitos e falta de acesso à energia por esses grupos, visibilizando&nbsp; reivindicações dos povos indígenas, povos e comunidades tradicionais. Os resultados indicam que a expansão energética, além de não garantir acesso à energia a essas populações, as assola com empobrecimento territorial e cultural dessa expansão sem respeito a sua livre determinação. Conclui-se que o avanço de empreendimentos energéticos no Brasil reproduz a colonialidade e o racismo ambiental ao negligenciar essas populações, resultando em injustiças socioambientais que exacerbam a pobreza energética e violam direitos fundamentais, o que não pode ser admitido na busca pela transição energética. As considerações finais destacam a necessidade urgente de políticas que garantam a consulta e consentimento prévio, livre e informado desses povos, visando uma transição energética justa e inclusiva

A fotografia como meio de percepção de crianças sobre o bem estar de aves em um zoológico

Anais do III Encontro de Iniciação Científica da Unila - Sessão de Antropologia - 07/11/14 – 08h30 às 11h00 - Unila-PTI - Bloco 09 – Espaço 01 – Sala 03O objetivo do estudo foi identificar as percepções de crianças sobre o bem estar de aves em um zoológico. Participaram deste estudo grupos familiares durante visitação turística no Parque das Aves, localizado em Foz do Iguaçu, Brasil. O uso metodológico de ferramentas quantitativas e qualitativas, destacam o papel de mediação da fotografia nas relações entre crianças e aves. Em análise preliminar dos dados observa- se que as crianças percebem comportamentos e sentimentos nas aves. Sendo significativo a representação destas de forma isolada às inteirações socioecológicas com outros animais, ambientes e pessoas.Bolsista Pibic UNILA - Universidade Federal da Integração Latino-Americana (UNILA

Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma-: the study protocol of the Adrisk trial

Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery will be eligible. Two hun-dred forty patients will be randomly assigned (1:1) to either standard aRCT with cisplatin (standard arm) or aRCT with cisplatin + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months) (interventional arm). Endpoints are event-free and overall survival. Recruitment started in August 2018 and is ongoing

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

PURPOSE: The number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients. METHODS: The XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine-Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs). RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009). CONCLUSIONS: Single-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

IMPORTANCE The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. OBJECTIVE To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. DESIGN, SETTING, AND PARTICIPANTS The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. INTERVENTIONS All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. MAIN OUTCOMES AND MEASURES The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. RESULTS Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). CONCLUSIONS AND RELEVANCE In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone

Predicting cisplatin tolerability in older adults with head and neck cancer - Insights for improved chemoradiation outcomes

PURPOSE Cumulative cisplatin doses of ≥ 200 mg/m$^{2}$ improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing chemoradiation, but many older adults with HNSCC cannot receive this prognostically relevant dose due to toxicities. This study aims to develop predictive models to assess the likelihood of older adults with HNSCC receiving ≥ 200 mg/m$^{2}$ cisplatin during chemoradiation. METHODS 366 patients from the SENIOR database, an international cohort of adults ≥ 65 years with HNSCC, received definitive chemoradiation with single-agent cisplatin and were analyzed. A Generalized Linear Model (GLM), Support Vector Machine (SVM), and Random Forest Model (RFM) were trained and compared for their performance in predicting a cumulative cisplatin dose of ≥ 200 mg/m$^{2}$. RESULTS 195 (53 %) patients achieved a cumulative cisplatin dose of ≥ 200 mg/m$^{2}$. In the GLM, laryngeal carcinoma (β = 1.37, p = 0.01), tumoral p16 positivity (β = 0.69, p = 0.04), higher hemoglobin levels (β = 0.26, p = 0.002), elevated C-reactive protein (CRP) concentration (β = 0.02, p = 0.003), and increased estimated glomerular filtration rate (eGFR) (β = 0.02, p = 0.008) were associated with a higher probability of reaching ≥ 200 mg/m$^{2}$ cisplatin. Hemoglobin, CRP, eGFR, and p16 status constituted the most important features in the SVM and RFM. AUC values for the GLM, SVM, and RFM were 0.70 (95 % CI, 0.67-0.73), 0.71 (95 % CI, 0.68-0.73), and 0.73 (95 % CI, 0.71-0.75), respectively. CONCLUSIONS We developed predictive models to support clinicians in identifying older adults with HNSCC capable of tolerating ≥ 200 mg/m$^{2}$ cumulative cisplatin during chemoradiation. Once validated, these models could improve personalized treatments and enhance shared decision-making in older adults with HNSCC