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1.
Cancers (Basel) ; 13(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638430

RESUMO

For almost 30 years, the term "holobiont" has referred to an ecological unit where a host (e.g., human) and all species living in or around it are considered together. The concept highlights the complex interactions between the host and the other species, which, if disturbed may lead to disease and premature aging. Specifically, the impact of microbiome alterations on the etiology of acute lymphoblastic leukemia (ALL) in children is not fully understood, but has been the focus of much research in recent years. In ALL patients, significant reductions in microbiome diversity are already observable at disease onset. It remains unclear whether such alterations at diagnosis are etiologically linked with leukemogenesis or simply due to immunological alteration preceding ALL onset. Regardless, all chemotherapeutic treatment regimens severely affect the microbiome, accompanied by severe side effects, including mucositis, systemic inflammation, and infection. In particular, dominance of Enterococcaceae is predictive of infections during chemotherapy. Long-term dysbiosis, like depletion of Faecalibacterium, has been observed in ALL survivors. Modulation of the microbiome (e.g., by fecal microbiota transplant, probiotics, or prebiotics) is currently being researched for potential protective effects. Herein, we review the latest microbiome studies in pediatric ALL patients.

2.
Z Rheumatol ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196794

RESUMO

OBJECTIVE: To analyze the composition of the oral microbiome in children and adolescents with chronic nonbacterial osteomyelitis (CNO) with respect to age distribution, gender differences, effects of medication, disease activity and the influence of body site. METHODS: The oral microbiome of 20 patients (12 male and 8 female; median age 10.3 years) and 36 controls were examined. Two different sites of the oral cavity were swabbed at two time points. Current medication and disease activity were evaluated and registered at these time points. Samples were subjected to amplicon sequencing of the V4 region of the 16S rRNA gene and Qiime2 was used to calculate alpha and beta diversity for multiple alternative metrics. RESULTS: On the basis of relative abundances of 975 different suboperational taxonomic units in high throughput next generation sequencing, a significant shift in the composition of the oral microbiome (p < 0.02) was observed among patients being treated with different medications. There was a significant difference in bacterial communities between the group aged 3-8 years old and the group aged 9-14 years old. Significant differences were also seen in bacterial colonization on different sites in the oral cavity, but not with respect to gender or disease activity. CONCLUSION: We present first data of a pilot study of the oral microbiome in children and adolescents with CNO, a rare autoinflammatory bone disease. Differences of the oral microbiome of diseased children to normal adult controls revealed a possible role of the oral microbiome as modulatory target or biomarker in CNO.

3.
PLoS One ; 16(5): e0250695, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939741

RESUMO

Atopic dermatitis is one of the most common skin diseases in dogs. Pathogenesis is complex and incompletely understood. Skin colonizing bacteria likely play an important role in the severity of this disease. Studying the canine skin microbiota using traditional microbiological methods has many limitations which can be overcome by molecular procedures. The aim of this study was to describe the bacterial microbiota of the skin and ear canals of healthy non-allergic and allergic German shepherd dogs (GSDs) without acute flare or concurrent skin infection and to compare both. Bacterial 16S rRNA gene amplicon sequence data revealed no differences of bacterial community patterns between the different body sites (axilla, front dorsal interdigital skin, groin, and ear canals) in non-allergic dogs. The microbiota at the different body sites of non-allergic GSDs showed no significant differences. Only for the samples obtained from the axilla the bacterial microbiota of allergic dogs was characterized by a lower species richness compared to that of non-allergic dogs and the bacterial community composition of the skin and ear canals of allergic dogs showed body site specific differences compared to non-allergic dogs. Actinobacteria was the most abundant phylum identified from the non-allergic dogs and Proteobacteria from allergic dogs. Macrococcus spp. were more abundant on non-allergic skin while Sphingomonas spp. were more abundant on the allergic skin. Forward step redundancy analysis of metadata indicated that the household the dogs came from had the strongest impact on the composition of the skin microbiome followed by sex, host health status and body site.


Assuntos
Meato Acústico Externo/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Hipersensibilidade/microbiologia , Microbiota/genética , Pele/microbiologia , Animais , Cães , Feminino , Masculino
4.
mSystems ; 6(2)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727399

RESUMO

Standard workflows for analyzing microbiomes often include the creation and curation of phylogenetic trees. Here we present EMPress, an interactive web tool for visualizing trees in the context of microbiome, metabolome, and other community data scalable to trees with well over 500,000 nodes. EMPress provides novel functionality-including ordination integration and animations-alongside many standard tree visualization features and thus simplifies exploratory analyses of many forms of 'omic data.IMPORTANCE Phylogenetic trees are integral data structures for the analysis of microbial communities. Recent work has also shown the utility of trees constructed from certain metabolomic data sets, further highlighting their importance in microbiome research. The ever-growing scale of modern microbiome surveys has led to numerous challenges in visualizing these data. In this paper we used five diverse data sets to showcase the versatility and scalability of EMPress, an interactive web visualization tool. EMPress addresses the growing need for exploratory analysis tools that can accommodate large, complex multi-omic data sets.

5.
Biotechnol Biofuels ; 14(1): 74, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743779

RESUMO

BACKGROUND: The transition to a biobased economy involving the depolymerization and fermentation of renewable agro-industrial sources is a challenge that can only be met by achieving the efficient hydrolysis of biomass to monosaccharides. In nature, lignocellulosic biomass is mainly decomposed by fungi. We recently identified six efficient cellulose degraders by screening fungi from Vietnam. RESULTS: We characterized a high-performance cellulase-producing strain, with an activity of 0.06 U/mg, which was identified as a member of the Fusarium solani species complex linkage 6 (Fusarium metavorans), isolated from mangrove wood (FW16.1, deposited as DSM105788). The genome, representing nine potential chromosomes, was sequenced using PacBio and Illumina technology. In-depth secretome analysis using six different synthetic and artificial cellulose substrates and two agro-industrial waste products identified 500 proteins, including 135 enzymes assigned to five different carbohydrate-active enzyme (CAZyme) classes. The F. metavorans enzyme cocktail was tested for saccharification activity on pre-treated sugarcane bagasse, as well as untreated sugarcane bagasse and maize leaves, where it was complemented with the commercial enzyme mixture Accellerase 1500. In the untreated sugarcane bagasse and maize leaves, initial cell wall degradation was observed in the presence of at least 196 µg/mL of the in-house cocktail. Increasing the dose to 336 µg/mL facilitated the saccharification of untreated sugarcane biomass, but had no further effect on the pre-treated biomass. CONCLUSION: Our results show that F. metavorans DSM105788 is a promising alternative pre-treatment for the degradation of agro-industrial lignocellulosic materials. The enzyme cocktail promotes the debranching of biopolymers surrounding the cellulose fibers and releases reduced sugars without process disadvantages or loss of carbohydrates.

6.
Anticancer Res ; 41(2): 877-884, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517293

RESUMO

BACKGROUND/AIM: Prognosis of patients with unresectable squamous cell carcinomas of the head and neck requires improvement. This retrospective study compared accelerated radiotherapy plus chemotherapy to conventional radiochemotherapy. PATIENTS AND METHODS: Patients received definitive treatment with accelerated radiotherapy plus chemotherapy (group A, n=10) or conventional cisplatin-based radiochemotherapy (group B, n=85). Groups were matched for several patient and tumor characteristics and compared for locoregional control (LRC), overall survival (OS) and toxicities. Additionally, accelerated radiotherapy plus chemotherapy and chemotherapy regimens in group B were compared for LRC and OS. RESULTS: Treatment type had no significant impact on LRC (p=0.98) and OS (p=0.57). In group A, toxicities occurred more often, including grade ≥3 mucositis (p=0.041), grade ≥2 lymphedema (p=0.007) and grade ≥3 leucopenia (p=0.007). Best 2-year LRC (p=0.39) and OS (p=0.015) was achieved with 20 mg/m2 cisplatin days 1-5 every 4 weeks; accelerated radiochemotherapy resulted in second-worst outcomes. CONCLUSION: Given the limitations of this study, accelerated radiotherapy plus chemotherapy provided no significant benefit but increased toxicity compared to conventional radiochemotherapy.


Assuntos
Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/efeitos adversos , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Radioterapia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
7.
Anticancer Res ; 41(1): 477-484, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419846

RESUMO

BACKGROUND/AIM: Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments. PATIENTS AND METHODS: Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities. RESULTS: LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients. CONCLUSION: AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.


Assuntos
Quimiorradioterapia , Fracionamento da Dose de Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Resultado do Tratamento
8.
Nat Commun ; 11(1): 5997, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33244003

RESUMO

The vitamin D receptor is highly expressed in the gastrointestinal tract where it transacts gene expression. With current limited understanding of the interactions between the gut microbiome and vitamin D, we conduct a cross-sectional analysis of 567 older men quantifying serum vitamin D metabolites using LC-MSMS and defining stool sub-Operational Taxonomic Units from16S ribosomal RNA gene sequencing data. Faith's Phylogenetic Diversity and non-redundant covariate analyses reveal that the serum 1,25(OH)2D level explains 5% of variance in α-diversity. In ß-diversity analyses using unweighted UniFrac, 1,25(OH)2D is the strongest factor assessed, explaining 2% of variance. Random forest analyses identify 12 taxa, 11 in the phylum Firmicutes, eight of which are positively associated with either 1,25(OH)2D and/or the hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio." Men with higher levels of 1,25(OH)2D and higher activation ratios, but not 25(OH)D itself, are more likely to possess butyrate producing bacteria that are associated with better gut microbial health.


Assuntos
Calcifediol/análise , Calcitriol/análise , Microbioma Gastrointestinal/fisiologia , Idoso , Idoso de 80 Anos ou mais , Butiratos/metabolismo , Calcifediol/metabolismo , Calcitriol/metabolismo , Estudos Transversais , DNA Bacteriano/isolamento & purificação , Fezes/química , Fezes/microbiologia , Humanos , Vida Independente , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Filogenia , RNA Ribossômico 16S/genética
9.
Blood ; 136(18): 2003-2017, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-32911536

RESUMO

The majority of childhood leukemias are precursor B-cell acute lymphoblastic leukemias (pB-ALLs) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1% to 5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. Although infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, by using murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice, even in the absence of infectious stimuli and independent of T cells. By using V4 and full-length 16S ribosomal RNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3983 amplicon sequence variants as proxies for bacterial species. Transplantation of either wild-type (WT) or Pax5+/- hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor genotype-specific manner. Gas chromatography-mass spectrometry (GC-MS) analyses of sera from WT and Pax5+/- mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.


Assuntos
Suscetibilidade a Doenças , Disbiose/complicações , Fezes/microbiologia , Microbioma Gastrointestinal , Leucemia Experimental/prevenção & controle , Fator de Transcrição PAX5/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/prevenção & controle , Animais , Feminino , Leucemia Experimental/genética , Leucemia Experimental/microbiologia , Leucemia Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
10.
Transl Lung Cancer Res ; 9(4): 1067-1073, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953485

RESUMO

Background: The remaining lifespan of patients with metastatic lung cancer should be considered when designing a personalized treatment program. To facilitate the estimation survival in lung cancer patients with bone metastases, a specific scoring system was created. Methods: One-hundred-and-fifty-three patients receiving fractionated radiotherapy for bone metastases without spinal cord compression from lung cancer were included in this retrospective study. Age, gender, Eastern Cooperative Oncology Group (ECOG) performance score, histology, interval from lung cancer diagnosis until irradiation of bone metastases, visceral metastases, additional bone metastases, type and number of irradiated sites, pathological fracture, upfront surgery and previous systemic treatment were evaluated for potential associations with survival. Those factors that were significant (P<0.05) or showed a trend (P≤0.10) on multivariate analysis were used to create the scoring system. Results: On multivariate analysis, ECOG performance score was significant (risk ratio: 2.77, P<0.001), and age showed a trend (risk ratio: 1.34, P=0.10). The following scoring points were assigned: age ≤65 years =1 point, age ≥66 years =0 points, ECOG performance score of 0-1 =1 point, and ECOG performance score of ≥2 =0 points. Three prognostic groups were obtained: 0 points (n=38), 1 point (n=71) and 2 points (n=44). Six-month survival rates were 21%, 41% and 75%, 12-month survival rates 7%, 27% and 56% (P<0.001). Conclusions: This scoring system can help estimate the remaining lifespan of lung cancer patients to be irradiated for bone metastases and will contribute to the personalization of their treatment.

11.
Transl Lung Cancer Res ; 9(4): 1433-1440, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953515

RESUMO

Background: Prognostic tools estimating survival of elderly patients with cerebral metastases from small-cell lung cancer (SCLC) improve treatment personalization. A specific tool for these patients was developed and compared to existing instruments. Methods: One-hundred-and-forty elderly patients (≥65 years) receiving whole-brain irradiation (WBI) for cerebral metastases from SCLC were retrospectively evaluated. WBI-program, age, gender, Karnofsky performance score, number of cerebral lesions, extracerebral metastases, and interval between SCLC-diagnosis and WBI were investigated. Characteristics significantly associated with survival in the multivariate analysis were used for the tool. Scoring points were calculated by dividing 6-month survival rates (%) by 10 and added for patient scores. The tool was compared to existing diagnosis-specific instruments including updated diagnosis-specific graded prognostic assessment (DS-GPA), Rades-SCLC and WBRT-30-SCLC. Results: In the multivariate analysis, KPS (P<0.001), number of cerebral lesions (P=0.013) and extracerebral metastases (P=0.049) were significantly associated with survival. Patient scores of 2 (n=37), 5 (n=69), 8 (n=20) and 11 (n=14) points were obtained; 6-month survival rates were 0%, 9%, 50% and 79% (P<0.001). The positive predictive value (PPV) of the worst group (2 points) to identify patients dying ≤6 months was 100%; PPVs of updated DS-GPA, Rades-SCLC and WBRT-30-SCLC were 94%, 100% and 94%. PPV of the best group (11 points) to identify patients surviving ≥6 months was 79%; PPVs of updated DS-GPA, Rades-SCLC and WBRT-30-SCLC were 86%, 79% and 100%. Conclusions: The most precise instruments were the new tool and Rades-SCLC for identification of patients dying ≤6 months, and the WBRT-30-SCLC to identify patients surviving ≥6 months.

12.
Anticancer Res ; 40(10): 5787-5792, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988906

RESUMO

BACKGROUND/AIM: Hypothalamic-pituitary (HT-P) dysfunction is one of the most common endocrine late effects following cranial radiotherapy. However, there are currently no specific data describing this complication in adult-onset cancer patients after whole brain radiotherapy (WBRT). The present cohort study aims to establish the prevalence of HT-P axis dysfunction in this group of patients. PATIENTS AND METHODS: Twenty-six cancer patients previously treated with WBRT (median follow-up=20.5 months) received standardized endocrine check-up focusing on HT-P function. RESULTS: In 50% of the patients, impaired hypothalamic-pituitary function was detected during follow-up. While functional loss of a single hormonal axis was evident in 34.6% of patients, 7.7% showed an impairment of multiple endocrine axes, and one patient developed adrenocorticotropic hormone deficiency. Hypothalamic-pituitary dysfunction did not directly correlate with the applied WBRT total doses. CONCLUSION: In our cohort, hypothalamic-pituitary dysfunction appeared to be common after WBRT and was diagnosed as early as 6 months following radiation. This finding highlights the need for routine endocrine follow-up even in patients with limited life expectancy.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Sistema Hipotálamo-Hipofisário/efeitos da radiação , Hipófise/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotálamo/fisiopatologia , Hipotálamo/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Hipófise/fisiopatologia , Lesões por Radiação/fisiopatologia
13.
Strahlenther Onkol ; 196(11): 1006-1017, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32399639

RESUMO

PURPOSE: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT). PATIENTS AND METHODS: Thirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2. RESULTS: The median follow-up duration was 39.5 months (18-60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2-3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07-3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12-12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07-154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2-3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9-19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3-17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9-8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1-41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8-13.47) of needing ADT at the last follow-up visit. CONCLUSION: If patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.


Assuntos
Adenocarcinoma/secundário , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Biomarcadores Tumorais/análise , Glutamato Carboxipeptidase II/análise , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/cirurgia , Radioterapia Guiada por Imagem/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Progressão da Doença , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Irradiação Linfática , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Neoplasias da Próstata/química , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Radioterapia Guiada por Imagem/efeitos adversos
14.
Anticancer Res ; 40(5): 2847-2851, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366433

RESUMO

BACKGROUND/AIM: Survival scores are important for treatment personalisation. A score for older patients with cerebral metastasis from non-small cell lung cancer (NSCLC) was generated. PATIENTS AND METHODS: Dose-fractionation of whole-brain irradiation, age, gender, general condition, histology, count of cerebral lesions, extra-cerebral metastatic spread and time between NSCLC-diagnosis and whole-brain irradiation were analysed for survival in 285 patients. Independent prognostic characteristics were utilised for the score, which was compared against five others. RESULTS: Based on general condition (p<0.001) and extra-cerebral spread (p=0.003), three groups were generated according to the score, 2 (n=49), 4-6 (n=206) and 7 (n=30) points. Positive predictive values (PPVs) to predict death ≤6 months and survival for ≥6 months were 100% and 52%, respectively. PPVs of other scores were 88-98% and 60-63%. CONCLUSION: The accuracy of the new score to predict death within ≤6 months was optimal, whereas its accuracy to predict survival for ≥6 months was lower when compared to the other low PPVs of existing scores.


Assuntos
Neoplasias Encefálicas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Idoso , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida
15.
Transl Lung Cancer Res ; 9(2): 232-238, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32420062

RESUMO

Background: The prognosis of patients with recurrent small cell lung cancer (SCLC) remains poor and treatment options are limited. We performed a multi-institution retrospective cohort study to evaluate the outcome of thoracic reirradiation, identify prognostic factors and assess treatment-related toxicity. Methods: Data of 33 patients re-irradiated for recurrent SCLC at 4 international university hospitals, were analysed. Overall survival (OS) acute and late toxicities were evaluated and prognostic factors for reirradiation were identified. Results: Reirradiation (Re-RT) was performed at a median interval time of 24 months after the first thoracic radiotherapy series. Median survival after reirradiation was 7 months (range, 1-54 months). The Re-RT dose in EQD2 ranged from 20 to 87.50 Gy with a median of 32.50 Gy. The 1- and 2-year OS were 33% and 17%, respectively. Patients with a good performance status (KPS >70%), absence of extrathoracic disease, reirradiation dose (EQD2) of >40 Gy and a cumulative dose of first plus second series of radiotherapy (EQD2) >90 Gy were associated with improved OS. Acute pulmonary Grade 1-2 toxicity from re-irradiation was recorded in 11 patients (33%) and grade 3 acute toxicity was encountered 1 patient (3%). Conclusions: Reirradiation for locoregionally recurrent SCLC is safe and shows promising outcomes. Patients reirradiated with doses >40 Gy experienced more favourable survival rates. In contrast, patients with a poor performance status or extrathoracic disease have a poor prognosis and Re-RT should be considered only for symptom control in this group.

16.
In Vivo ; 34(3): 1361-1364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32354931

RESUMO

BACKGROUND/AIM: Secondary brain lesions occur commonly in patients with advanced melanoma. Despite increasing use of local therapies, many elderly patients qualify for whole-brain radiotherapy (WBRT). For these patients, a survival score was created. PATIENTS AND METHODS: Seven characteristics were retrospectively investigated in 35 elderly (≥65 years) patients with melanoma, namely WBRT regimen, age, gender, Karnofsky performance score (KPS), number of brain lesions, non-cerebral metastases and interval from melanoma diagnosis to WBRT. RESULTS: Age ≤71 years (p=0.044) and KPS ≥80% (p=0.005) were significantly associated with more favorable survival. Based on these characteristics, patients received 0 (n=13), 1 (n=12) or 2 points (n=10). Two prognostic groups were designed, 0 or 1 point vs. 2 points, with actuarial 6-month survival rates of 12% and 48%, respectively (p=0.002). CONCLUSION: This simple implement allows quick estimation of the survival of elderly patients receiving WBRT for cerebral metastases from melanoma.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana , Melanoma/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Irradiação Craniana/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Dosagem Radioterapêutica , Resultado do Tratamento
17.
Trials ; 21(1): 424, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32450921

RESUMO

BACKGROUND: Radiotherapy of head-and-neck cancer can be associated with significant toxicities including dermatitis and oral mucositis. Severe toxicities may require interruptions of the radiation treatment associated with impairment of the patients' prognoses. This study will investigate whether the addition of a reminder app to standard care can reduce dermatitis and oral mucositis rates during radiotherapy in these patients. METHODS: This randomized trial compares standard care supported by a reminder app (Arm A) to standard care alone (Arm B) with respect to grade ≥ 2 radiation dermatitis and oral mucositis at 60 Gy of radiotherapy, the minimum planned dose for patients receiving definitive or adjuvant radiotherapy for locally advanced head- and-neck cancer. Moreover, radiation-induced dermatitis and oral mucositis grade ≥ 3 at 60 Gy and both grade ≥ 2 and grade ≥ 3 at the end of radiation treatment (EOT) will be evaluated, as well as quality of life and pain. According to sample size calculations, 80 patients are required per arm within the full analysis set. Taking into account that 5% of patients will not qualify for full analysis set, 168 patients should be randomized. The impact of the reminder app will be considered clinically relevant, if the rates of grade ≥ 2 radiation dermatitis (primary endpoint) and oral mucositis (secondary endpoint) can be reduced by 20%. DISCUSSION: If the addition of a reminder app to standard care will lead to a significant reduction of radiation dermatitis and oral mucositis, it could become a helpful tool for patients with head-and-neck cancer during radiotherapy. TRIAL REGISTRATION: clinicaltrials.gov (NCT04110977). Registered on September 27, 2019. First patient is planned to be included in December 2019.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Aplicativos Móveis , Radiodermatite/prevenção & controle , Higiene da Pele/métodos , Estomatite/prevenção & controle , Humanos , Qualidade de Vida , Radiodermatite/etiologia , Radioterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estomatite/etiologia
18.
Anticancer Res ; 40(4): 2257-2260, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234922

RESUMO

BACKGROUND/AIM: For treatment personalization in elderly cancer patients, survival prognoses should be considered. We developed an instrument to estimate survival of elderly patients with brain metastasis from gynecological cancer. PATIENTS AND METHODS: In 15 patients, whole-brain radiotherapy regimen, tumor site, age, Karnofsky performance score (KPS), number of brain metastases, extra-cerebral metastases and interval from diagnosis of gynecological cancer until radiotherapy were retrospectively evaluated for survival. Characteristics found significant on multivariate analysis were used for the instrument. RESULTS: In the multivariate analysis, KPS ≥70% (hazard ratio=3.71, p=0.0499) and an interval ≥28 months (hazard ratio=3.71, p=0.030) were significantly associated with better survival. Based on these characteristics, patients received 0 (n=6), 1 (n=3) or 2 points (n=6). Six-month survival rates of the groups 0-1 and 2 points were 0% and 50%, respectively (p=0.007). CONCLUSION: This instrument helps estimating survival in elderly patients with brain metastases from gynecological cancer and contributes to personalization of their treatment.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Taxa de Sobrevida
19.
Anticancer Res ; 40(4): 2261-2264, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234923

RESUMO

BACKGROUND/AIM: Personalized therapies may improve outcomes in elderly patients with brain metastases from cancer of unknown primary (CUP). To contribute to this strategy, an instrument for judging their survival time was designed. PATIENTS AND METHODS: This retrospective study included 53 patients, aged ≥65 years and treated with whole-brain irradiation (WBI) for brain metastases from CUP. The WBI-program, age, gender, Karnofsky performance score (KPS), number of brain metastases and non-cerebral metastases were analyzed. RESULTS: KPS≤60 (p<0.001) and presence of non-cerebral metastases (p=0.003) were significantly associated with unfavorable survival. These factors formed the basis for the prognostic implement; patient-scores of zero (n=23), one (n=21) or two points (n=9) were obtained. Corresponding survival rates at 6-months were 0%, 19% and 56% (p<0.001). CONCLUSION: With this instrument, it is easier to judge the remaining survival time of elderly patients with brain metastases from CUP. This information should be used when selecting individual treatment- and WBI-programs.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Longevidade , Neoplasias Primárias Desconhecidas/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Anticancer Res ; 40(4): 2271-2274, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234925

RESUMO

BACKGROUND/AIM: Outcomes of older persons with secondary brain lesions from carcinoma of the breast may be improved by individualized therapy. This process will likely be easier with survival scores. PATIENTS AND METHODS: A retrospective study was performed in 111 older patients with carcinoma of the breast irradiated for secondary brain lesions. Dose-fractionation, age, general condition, number of brain lesions, other visceral metastases and time period from breast cancer detection until radiation therapy were investigated. RESULTS: Post-radiation survival was significantly related to general condition (p<0.0001) and other visceral metastases (p=0.041). When using these characteristics, sum-scores of 0 (n=46), 1 (n=50) or 2 (n=15) points were gained. Six- and 12-month survival was 7% and 3% for 0 points, 43% and 19% for 1 point, and 73% and 52% for 2 points (p<0.0001). CONCLUSION: This survival score contributes to treatment individualisation of older patients with secondary brain lesions from carcinoma of the breast.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Medicina de Precisão/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos
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