Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 396
Filtrar
1.
Radiother Oncol ; 168: 69-74, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35101471

RESUMO

BACKGROUND/PURPOSE: To evaluate the usage of RT in trial protocols for anti-cancer drugs approved by the US Food and Drug Administration (FDA). METHODS: Drugs which had been granted an FDA approval between 2010 and 2017 for the treatment of solid tumors in adults were identified. Use of RT in relation to each drug's approval date was reviewed on ClinicalTrials.gov. RESULTS: Out of 42 drugs, none was initially approved for an indication which mandates RT. One drug (2.4%) has a post-approval label extension for sequential usage after RT. 5846 records were screened, exclusion of non-cancer trials and duplicates resulted in 4254 protocols out of which 2919 were industry-sponsored (68.6%). RT was tested in 350 (8.2%) studies. Out of 75 drug/RT trials which were initiated prior to approval, fourteen had not yet started recruitment, 45 were recruiting, one was completed, one prematurely terminated and fourteen fully-recruited but ongoing at approval time. Out of the fully-recruited or completed studies, results from four studies on three drugs were already published. In 52.4% of drugs, no patient had been treated with a drug/RT combination at the approval date. Drug/RT studies were less likely industry-sponsored (p < 0.001) and more likely initiated post-approval (p < 0.001) compared to drug-only trials. Despite this imbalance, pre-approval drug/RT trials were still mostly industry-sponsored (65.3%). CONCLUSION: No drug/RT data were publicly available in over 90% of newly approved anti-cancer drugs. These results indicate that clinicians must rely on postmarketing surveillance to identify drug/RT interactions as data from trials are unavailable at approval.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Estudos Transversais , Aprovação de Drogas/métodos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Preparações Farmacêuticas , Estados Unidos
2.
Radiat Oncol ; 17(1): 15, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35073955

RESUMO

BACKGROUND: Although glioblastoma (GB) is associated with a devastating prognosis, a small proportion of patients achieve long-term survival rates. We herein present a matched-pair analysis of molecular factors found in long- and short-term survivors (LTS, STS). METHODS: We performed a cross-institutional analysis of 262 patient records and matched a group of 91 LTS (≥ 3 years) with two groups of STS (STS-1, n = 91; STS-2, n = 80). Matching was performed according to age, Karnofsky Performance Status, initial therapy and adjuvant therapy. Molecular factors were compared between LTS (total of 91 patients) v. STS-1, and LTS (subgroup of 80 patients) v. STS-2. We included glial fibrillary acidic protein (GFAP), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase 1 (IDH-1); furthermore, the proliferation index was analyzed (Ki-67/MIB-1). RESULTS: IDH-1 and decreased Ki-67 were numerically associated with LTS but the difference was only significant compared to STS-1 (n.s. v. STS-2). LTS was associated with MGMT promoter hypermethylation (p = 0.013 and p = 0.022) and GFAP expression (p < 0.001 and p = 0.001). Positivity for both factors combined compared to negativity for one factor occurred more often in the LTS group (p = 0.002 and p = 0.006); negativity for both factors combined did not occur in the LTS group. CONCLUSION: In this retrospective analysis, GFAP expression and MGMT promoter methylation were associated with LTS. Given the hypothesis-generating nature of our study, these observations should be confirmed in prospective clinical trials.


Assuntos
Glioblastoma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer , Criança , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Proteína Glial Fibrilar Ácida/genética , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Proteínas Supressoras de Tumor/genética , Adulto Jovem
3.
Front Oncol ; 12: 850351, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371998

RESUMO

Purpose: The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort. Materials/Methods: Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors. Results: A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12-180) months, and age was 58 (27-86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6-20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age <50 remained to be a significant prognostic factor for local recurrence (HR 0.19, 95% CI 0.08-0.47; p < 0.05). The 10-year estimated OS was 81.2%. Conclusion: Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings.

4.
Radiat Oncol ; 16(1): 145, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348765

RESUMO

BACKGROUND: Hypofractionation is increasingly being applied in radiotherapy for prostate cancer, requiring higher accuracy of daily treatment deliveries than in conventional image-guided radiotherapy (IGRT). Different adaptive radiotherapy (ART) strategies were evaluated with regard to dosimetric benefits. METHODS: Treatments plans for 32 patients were retrospectively generated and analyzed according to the PACE-C trial treatment scheme (40 Gy in 5 fractions). Using a previously trained cycle-generative adversarial network algorithm, synthetic CT (sCT) were generated out of five daily cone-beam CT. Dose calculation on sCT was performed for four different adaptation approaches: IGRT without adaptation, adaptation via segment aperture morphing (SAM) and segment weight optimization (ART1) or additional shape optimization (ART2) as well as a full re-optimization (ART3). Dose distributions were evaluated regarding dose-volume parameters and a penalty score. RESULTS: Compared to the IGRT approach, the ART1, ART2 and ART3 approaches substantially reduced the V37Gy(bladder) and V36Gy(rectum) from a mean of 7.4cm3 and 2.0cm3 to (5.9cm3, 6.1cm3, 5.2cm3) as well as to (1.4cm3, 1.4cm3, 1.0cm3), respectively. Plan adaptation required on average 2.6 min for the ART1 approach and yielded doses to the rectum being insignificantly different from the ART2 approach. Based on an accumulation over the total patient collective, a penalty score revealed dosimetric violations reduced by 79.2%, 75.7% and 93.2% through adaptation. CONCLUSION: Treatment plan adaptation was demonstrated to adequately restore relevant dose criteria on a daily basis. While for SAM adaptation approaches dosimetric benefits were realized through ensuring sufficient target coverage, a full re-optimization mainly improved OAR sparing which helps to guide the decision of when to apply which adaptation strategy.


Assuntos
Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Cirurgia Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
6.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202550

RESUMO

In this study, we determined the potential of polyethylene glycol-encapsulated iron oxide nanoparticles (IONPCO) for the intracellular delivery of the chemotherapeutic doxorubicin (IONPDOX) to enhance the cytotoxic effects of ionizing radiation. The biological effects of IONP and X-ray irradiation (50 kV and 6 MV) were determined in HeLa cells using the colony formation assay (CFA) and detection of γH2AX foci. Data are presented as mean ± SEM. IONP were efficiently internalized by HeLa cells. IONPCO radiomodulating effect was dependent on nanoparticle concentration and photon energy. IONPCO did not radiosensitize HeLa cells with 6 MV X-rays, yet moderately enhanced cellular radiosensitivity to 50 kV X-rays (DMFSF0.1 = 1.13 ± 0.05 (p = 0.01)). IONPDOX did enhance the cytotoxicity of 6 MV X-rays (DMFSF0.1 = 1.3 ± 0.1; p = 0.0005). IONP treatment significantly increased γH2AX foci induction without irradiation. Treatment of HeLa cells with IONPCO resulted in a radiosensitizing effect for low-energy X-rays, while exposure to IONPDOX induced radiosensitization compared to IONPCO in cells irradiated with 6 MV X-rays. The effect did not correlate with the induction of γH2AX foci. Given these results, IONP are promising candidates for the controlled delivery of DOX to enhance the cytotoxic effects of ionizing radiation.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Compostos Férricos , Nanopartículas Metálicas , Tolerância a Radiação/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Portadores de Fármacos/química , Compostos Férricos/química , Células HeLa/efeitos dos fármacos , Células HeLa/patologia , Células HeLa/efeitos da radiação , Células HeLa/ultraestrutura , Humanos , Nanopartículas Metálicas/química , Radiação Ionizante
7.
Dtsch Med Wochenschr ; 146(16): e58-e64, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34243217

RESUMO

BACKGROUND: Since December 27, 2020, employees of the health system in Germany have been vaccinated against the SARS coronavirus-2 with the vaccine BNT162B2. Initial observations show that especially among younger vaccinated people side effects are common. In this study, using the example of clinic employees, the self-perceived well-being after the first and second dose of the vaccine was examined. METHODS: Anonymized online questionnaire to be filled out once by all employees after the second dose of BNT162B2 was offered. The severity of side effects was queried using an ordinal numerical rating scale with values between 0 and 10. Other key data points were age, gender, and occupational group. The ability to work in the days following the injections was recorded by self-reporting. RESULTS: Data from 555 respondents were evaluated. The mean age was 40.25 years (standard deviation 12.35). 56 % of the respondents were female, 44.3 % belonged to the medical service, 42.9 % to the nursing service and 12.8 % were assigned to other professional groups with COVID-19 patient contact. Around 2 % of all employees did not experience any side effects at all. The most common side effect was pain at the injection site. Fatigue, headaches and myalgia followed with decreasing frequency. After the first dose, ¾ of the respondents said they had tolerated the vaccination well overall, after the second dose it was only half. After the first dose, over 90 % of the respondents felt that they were able to work again on the following day, after the second dose one third stated that they were only able to work again on the second day. 2.2 % of all employees had to report that they were unable to work for at least one day after the first dose and 19.5 % after the second dose. CONCLUSIONS: Vaccination with BNT162B2 frequently leads to side effects, especially after the second dose. Perception of side effects resulted in 19 % of those questioned being sick after the second dose. Nevertheless, 95 % of all respondents would choose a coronavirus vaccination again.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Recursos Humanos em Hospital , Vacinas Sintéticas/efeitos adversos , Adulto , Fatores Etários , Vacinas contra COVID-19/administração & dosagem , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Recursos Humanos em Hospital/psicologia , Autoimagem , Fatores Sexuais , Inquéritos e Questionários , Vacinas Sintéticas/administração & dosagem
8.
Br J Cancer ; 125(3): 380-389, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34035435

RESUMO

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Mastectomia Segmentar/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Terapia Combinada , Feminino , Humanos , Cuidados Intraoperatórios , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral , Irradiação Corporal Total
9.
Front Cell Dev Biol ; 9: 539893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681189

RESUMO

PURPOSE: Fibroblasts are considered to play a major role in the development of fibrotic reaction after radiotherapy and premature radiation-induced differentiation has been proposed as a cellular basis. The purpose was to relate gene expression profiles to radiation-induced phenotypic changes of human skin fibroblasts relevant for radiogenic fibrosis. MATERIALS AND METHODS: Exponentially growing or confluent human skin fibroblast strains were irradiated in vitro with 1-3 fractions of 4 Gy X-rays. The differentiated phenotype was detected by cytomorphological scoring and immunofluorescence microscopy. Microarray analysis was performed on Human Genome U133 plus2.0 microarrays (Affymetrix) with JMP Genomics software, and pathway analysis with Reactome R-package. The expression levels and kinetics of selected genes were validated with quantitative real-time PCR (qPCR) and Western blotting. RESULTS: Irradiation of exponentially growing fibroblast with 1 × 4 Gy resulted in phenotypic differentiation over a 5-day period. This was accompanied by downregulation of cell cycle-related genes and upregulation of collagen and other extracellular matrix (ECM)-related genes. Pathway analysis confirmed inactivation of proliferation and upregulation of ECM- and glycosaminoglycan (GAG)-related pathways. Furthermore, pathways related to inflammatory reactions were upregulated, and potential induction and signaling mechanisms were identified. Fractionated irradiation (3 × 4 Gy) of confluent cultures according to a previously published protocol for predicting the risk of fibrosis after radiotherapy showed similar downregulation but differences in upregulated genes and pathways. CONCLUSION: Gene expression profiles after irradiation of exponentially growing cells were related to radiation-induced differentiation and inflammatory reactions, and potential signaling mechanisms. Upregulated pathways by different irradiation protocols may reflect different aspects of the fibrogenic process thus providing a model system for further hypothesis-based studies of radiation-induced fibrogenesis.

13.
Adv Radiat Oncol ; 6(1): 100593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33490728

RESUMO

PURPOSE: This study aimed to investigate, in the setting of neoadjuvant gastric irradiation with integrated boost, whether cone beam computed tomography (CBCT)-based adaptive radiation therapy compared with a defined-filling protocol would be beneficial in terms of feasibility and achieving daily reproducible dose volume indexes of the planning target volume (PTV) and organs at risk (OARs) and workflow. METHODS AND MATERIALS: Planning computed tomography (PCT) and 25 CBCT scans of a previously treated patient were used, and neoadjuvant therapy of gastric carcinoma was simulated offline. PTVs and OARs were defined per the TOPGEAR protocol (PTV: 45 Gy/1.8 Gy), and an integrated boost (gross tumor volume [GTV]: 50.4 Gy/2.016 Gy) was added. The patient followed a filling regimen consisting of 12-hour fasting followed by 200 mL of water intake (2 glasses of water) immediately before irradiation. OARs and PTVs were newly contoured on each CBCT. Nonrigid registration of PCT and CBCT scans was performed. Nonadapted plans were recalculated on each CBCT (R-CBCT). Furthermore, an adapted plan was created for the new anatomy (A-CBCT). Dose parameters and comparison of R-CBCT and A-CBCT for the kidneys, liver, and heart were analyzed using a paired t test. RESULTS: A total of 200 plans for R-CBCT and A-CBCT were obtained. Mean gastric volumes were 277.32 cm3 (±54.40 cm3) in CBCT scans and 519.2 cm3 in PCT. Mean doses to the PTV did not differ meaningfully within the CBCT scans, with an average of 1.54%. The D95 improved in GTV coverage by 5.26% compared with the R-CBCT plan. Mean heart, liver, and right kidney doses were reduced with the A-CBCT plan by 35.74%, 10.71% and 29.47%, respectively. The R- and A-CBCT comparison for GTV and OARs was significantly different in all cases (P < .0001). CONCLUSIONS: Adaptive radiation therapy through deformable registration represents an important tool in neoadjuvant gastric irradiation, encompassing daily variability and organ motion, compared with the defined-filling protocol while improving OAR sparing.

14.
Strahlenther Onkol ; 197(1): 39-47, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32813034

RESUMO

PURPOSE: To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x­rays for early breast cancer. METHODS: We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x­rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated. RESULTS: There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N­terminal fragment of B­type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279). CONCLUSION: Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.


Assuntos
Neoplasias da Mama/radioterapia , Cardiomiopatias/etiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Radioterapia Adjuvante/efeitos adversos , Troponina I/sangue , Idoso , Biomarcadores , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Cardiomiopatias/sangue , Cardiotoxicidade/sangue , Cardiotoxicidade/etiologia , Feminino , Humanos , Cuidados Intraoperatórios , Mastectomia Segmentar , Pessoa de Meia-Idade , Estudos Prospectivos
15.
Int J Cancer ; 148(7): 1676-1684, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045097

RESUMO

The aim of the study was to report on the association of trial sponsors with intervention type, treatment intent, recruitment success and reasons to terminate cancer trials. The ClinicalTrials database was searched for interventional Phase 3 cancer trials (01/2006-05/2017). Noncancer studies and ongoing studies were excluded, permanently suspended studies were counted as terminated. Trials were stratified according to sponsors (industry/nonindustry), intervention type, setting (curative/palliative) and intent of intervention (curative/symptom-control/life-extending). We identified 345 terminated trials and 1137 completed studies as a control group. The frequency of premature termination did not differ significantly between sponsors. Time to termination was shorter but recruitment per month prior to termination was higher in industry-sponsored studies (7.0 vs 2.2 patients/month; P < .001). Drug interventions were more common in industry-sponsored, all other interventions in nonindustry-sponsored settings (P < .001). Life-extending palliative interventions occurred more frequently, symptom-control interventions in a curative setting less frequently in industry-sponsored trials (both P < .001). Intervention, setting and intent were not associated with termination in industry-sponsored trials. In nonindustry-sponsored trials, the frequency of drug interventions and life-extending (noncurative) interventions were increased in terminated trials (both P < .05); symptom-control interventions in curative settings occurred more frequently in completed studies. Industry-sponsored trials were more often terminated due to toxicity/inefficacy while lack of accrual occurred more frequently in nonindustry-sponsored trials (P < .01). Interventions, treatment setting/intent and reasons for termination differed between sponsor types. In nonindustry-sponsored trials, drug interventions and life-extending (noncurative) interventions were associated with premature termination and symptom-control interventions (curative setting) were associated with trial completion.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Neoplasias , Projetos de Pesquisa/estatística & dados numéricos , Bases de Dados Factuais , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/terapia
16.
Med Phys ; 48(1): 94-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33119944

RESUMO

PURPOSE: To characterize treatment plan (TP) quality, a quantitative quality control (QC) tool is proposed. The tool is validated using volumetric modulated arc therapy (VMAT) plans for treatment of prostate cancer by estimating the achievable organ at risk (OAR) sparing, based on the knowledge learned from prior plans. METHODS: Prostate TP quality was investigated by evaluating the achieved OAR sparing in the rectum and bladder, based on their proximity to target surface. The knowledge base used in this work comprises 450 plans, consisting of 181 homogenous prostate plans and 269 simultaneous integrated boost (SIB) prostate plans. A knowledge-based algorithm was used to relate the absorbed doses of the OARs (rectum and bladder) and their proximity to the planning target volume (PTV). A metric (Mq,r value) was calculated to characterize the OAR sparing based on the weighted differences of the mean doses at binned distances to the PTV surface. The 90% probability ellipse of the normally distributed OARs Mq,r values was considered to define a threshold above which the treatment plan was re-optimized. RESULTS: Following re-optimization, 8/11 of the homogenous plans and 6/13 of the SIB plans outside the 90% probability ellipse could be re-optimized to gain better OAR sparing while achieving the same or better target coverage. However, 3/4 of the homogenous TPs and 1/9 of the SIB TPs between 80% and 90% were improved. Mq,r values of bladder and rectum after re-optimizing the plans in both groups of homogenous and SIB showed lower values compared to the corresponding values before re-optimization, which implies that better OARs sparing was achieved. CONCLUSIONS: This work demonstrates an effective anatomy-specific QC tool for identifying suboptimal plans and determining the achievable OAR sparing for each individual patient anatomy.


Assuntos
Próstata , Neoplasias da Próstata , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Bases de Conhecimento , Masculino , Órgãos em Risco , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica
17.
Infect Control Hosp Epidemiol ; 42(6): 653-658, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32928337

RESUMO

BACKGROUND: The pressures exerted by the coronavirus disease 2019 (COVID-19) pandemic pose an unprecedented demand on healthcare services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. OBJECTIVE: We describe methods used by a university hospital to forecast case loads and time to peak incidence. METHODS: We developed a set of models to forecast incidence among the hospital catchment population and to describe the COVID-19 patient hospital-care pathway. The first forecast utilized data from antecedent allopatric epidemics and parameterized the care-pathway model according to expert opinion (ie, the static model). Once sufficient local data were available, trends for the time-dependent effective reproduction number were fitted, and the care pathway was reparameterized using hazards for real patient admission, referrals, and discharge (ie, the dynamic model). RESULTS: The static model, deployed before the epidemic, exaggerated the bed occupancy for general wards (116 forecasted vs 66 observed), ICUs (47 forecasted vs 34 observed), and predicted the peak too late: general ward forecast April 9 and observed April 8 and ICU forecast April 19 and observed April 8. After April 5, the dynamic model could be run daily, and its precision improved with increasing availability of empirical local data. CONCLUSIONS: The models provided data-based guidance for the preparation and allocation of critical resources of a university hospital well in advance of the epidemic surge, despite overestimating the service demand. Overestimates should resolve when the population contact pattern before and during restrictions can be taken into account, but for now they may provide an acceptable safety margin for preparing during times of uncertainty.


Assuntos
COVID-19/epidemiologia , Número de Leitos em Hospital , Hospitais Universitários/organização & administração , COVID-19/prevenção & controle , Infecção Hospitalar/prevenção & controle , Previsões , Alemanha/epidemiologia , Hospitais Universitários/estatística & dados numéricos , Humanos , Incidência , Modelos Estatísticos , Segurança do Paciente
18.
Invest New Drugs ; 39(3): 670-685, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33313992

RESUMO

Background Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Methods The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Results Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. Conclusions In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Idoso , Antraciclinas/farmacologia , Antraciclinas/uso terapêutico , Antineoplásicos/farmacologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Reposicionamento de Medicamentos , Genótipo , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Transcriptoma
19.
J Contemp Brachytherapy ; 12(5): 480-486, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33299437

RESUMO

PURPOSE: Radiotherapy is the mainstay in the treatment of locally inoperable tumors. Interstitial electronic needle-based kilovoltage brachytherapy (EBT) could be an economic alternative to high-dose-rate (HDR) brachytherapy or permanent seed implantation (PSI). In this work, we evaluated if locally inoperable tumors treated with PSI at our institution may be suitable for EBT. MATERIAL AND METHODS: A total of 10 post-interventional computed tomography (CT) scans of patients, who received PSI and simulated stepping-source EBT applied with Intrabeam system and needle applicator were used. EBT treatment planning software with 3-dimensional image and projection of applicator were applied for designing trajectories and establishing dwell positions. Dwell position doses were summarized, and doses covering 90% of the target volume (D90) achieved with stepping-source EBT were compared to those of PSI. Additionally, conformality of dose distributions and total irradiation time were assessed using conformation number (CN) or conformal index (COIN). RESULTS: In all patients, D90 of EBT exceeded the prescribed dose or D90 of PSI on average by 4.7% or 21.3% relative to the prescribed dose, respectively. Mean number of trajectories was 5.0 for EBT and 6.9 for PSI. Average CN/COIN for EBT was 0.69, with a mean irradiation time of 27.8 minutes for standardized dose of 13 Gy. CONCLUSIONS: Stepping-source EBT allowed for a conformal treatment of inoperable interstitial tumors with similar D90. Fewer trajectories were required for EBT in majority of cases.

20.
Molecules ; 25(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333753

RESUMO

A polyolefin with certified biocompatibility according to USP class VI was used by our group as feedstock for filament-based 3D printing to meet the highest medical standards in order to print personal protective equipment for our university hospital during the ongoing pandemic. Besides the chemical resistance and durability, as well as the ability to withstand steam sterilization, this polypropylene (PP) copolymer is characterized by its high purity, as achieved by highly efficient and selective catalytic polymerization. As the PP copolymer is suited to be printed with all common printers in fused filament fabrication (FFF), it offers an eco-friendly cost-benefit ratio, even for large-scale production. In addition, a digital workflow was established focusing on common desktop FFF printers in the medical sector. It comprises the simulation-based optimization of personalized print objects, considering the inherent material properties such as warping tendency, through to validation of the process chain by 3D scanning, sterilization, and biocompatibility analysis of the printed part. This combination of digital data processing and 3D printing with a sustainable and medically certified material showed great promise in establishing decentralized additive manufacturing in everyday hospital life to meet peaks in demand, supply bottlenecks, and enhanced personalized patient treatment.


Assuntos
Polienos/química , Polímeros/química , Humanos , Equipamento de Proteção Individual , Polipropilenos/química , Impressão Tridimensional
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...