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1.
Radiother Oncol ; 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35077710

RESUMO

BACKGROUND AND PURPOSE: Genome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension. MATERIALS AND METHODS: Prostate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N=256) and REQUITE (N=1,437). Patients were assessed pre-radiotherapy and followed prospectively for development of toxicity for up to four years. The cumulative probability of hematuria was estimated by the Kaplan-Meier method. Multivariable grouped relative risk models assessed the effect of ACEi on time to hematuria adjusting for clinical factors and stratified by enrollment site. A polygenic risk score (PRS) for blood pressure was tested for association with hematuria in REQUITE and our Radiogenomics Consortium GWAS. RESULTS: Patients taking ACEi during radiotherapy had a reduced risk of hematuria (HR 0.51, 95%CI 0.28 to 0.94, p=0.030) after adjusting for prior transurethral prostate and/or bladder resection, heart disease, pelvic node radiotherapy, and bladder volume receiving 70 Gy, which are associated with hematuria. A blood pressure PRS was associated with hypertension (odds ratio per standard deviation 1.38, 95%CI 1.31 to 1.46, n=5,288, p<0.001) but not hematuria (HR per standard deviation 0.96, 95%CI 0.87 to 1.06, n=5,126, p=0.41). CONCLUSIONS: Our study is the first to show a radioprotective effect of ACEi on bladder in an international, multi-site study of patients receiving pelvic radiotherapy. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects the bladder.

3.
Strahlenther Onkol ; 197(12): 1043-1048, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34515820

RESUMO

PURPOSE: Scientific and clinical achievements in radiation, medical, and surgical oncology are changing the landscape of interdisciplinary oncology. The German Society for Radiation Oncology (DEGRO) working group of young clinicians and scientists (yDEGRO) and the DEGRO representation of associate and full professors (AKRO) are aware of the essential role of radiation oncology in multidisciplinary treatment approaches. Together, yDEGRO and AKRO endorsed developing a German radiotherapy & radiation oncology vision 2030 to address future challenges in patient care, research, and education. The vision 2030 aims to identify priorities and goals for the next decade in the field of radiation oncology. METHODS: The vision development comprised three phases. During the first phase, areas of interest, objectives, and the process of vision development were defined jointly by the yDEGRO, AKRO, and the DEGRO board. In the second phase, a one-day strategy retreat was held to develop AKRO and yDEGRO representatives' final vision from medicine, biology, and physics. The third phase was dedicated to vision interpretation and program development by yDEGRO representatives. RESULTS: The strategy retreat's development process resulted in conception of the final vision "Innovative radiation oncology Together - Precise, Personalized, Human." The first term "Innovative radiation oncology" comprises the promotion of preclinical research and clinical trials and highlights the development of a national committee for strategic development in radiation oncology research. The term "together" underpins collaborations within radiation oncology departments as well as with other partners in the clinical and scientific setting. "Precise" mainly covers technological precision in radiotherapy as well as targeted oncologic therapeutics. "Personalized" emphasizes biology-directed individualization of radiation treatment. Finally, "Human" underlines the patient-centered approach and points towards the need for individual longer-term career curricula for clinicians and researchers in the field. CONCLUSION: The vision 2030 balances the ambition of physical, technological, and biological innovation as well as a comprehensive, patient-centered, and collaborative approach towards radiotherapy & radiation oncology in Germany.

5.
Comput Biol Med ; 135: 104624, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34247131

RESUMO

The prediction by classification of side effects incidence in a given medical treatment is a common challenge in medical research. Machine Learning (ML) methods are widely used in the areas of risk prediction and classification. The primary objective of such algorithms is to use several features to predict dichotomous responses (e.g., disease positive/negative). Similar to statistical inference modelling, ML modelling is subject to the class imbalance problem and is affected by the majority class, increasing the false-negative rate. In this study, seventy-nine ML models were built and evaluated to classify approximately 2000 participants from 26 hospitals in eight different countries into two groups of radiotherapy (RT) side effects incidence based on recorded observations from the international study of RT related toxicity "REQUITE". We also examined the effect of sampling techniques and cost-sensitive learning methods on the models when dealing with class imbalance. The combinations of such techniques used had a significant impact on the classification. They resulted in an improvement in incidence status prediction by shifting classifiers' attention to the minority group. The best classification model for RT acute toxicity prediction was identified based on domain experts' success criteria. The Area Under Receiver Operator Characteristic curve of the models tested with an isolated dataset ranged from 0.50 to 0.77. The scale of improved results is promising and will guide further development of models to predict RT acute toxicities. One model was optimised and found to be beneficial to identify patients who are at risk of developing acute RT early-stage toxicities as a result of undergoing breast RT ensuring relevant treatment interventions can be appropriately targeted. The design of the approach presented in this paper resulted in producing a preclinical-valid prediction model. The study was developed by a multi-disciplinary collaboration of data scientists, medical physicists, oncologists and surgeons in the UK Radiotherapy Machine Learning Network.


Assuntos
Ciência de Dados , Aprendizado de Máquina , Algoritmos , Humanos , Modelos Estatísticos
6.
Cancers (Basel) ; 13(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070078

RESUMO

Radiotherapy, a common component in cancer treatment, can induce adverse effects including fibrosis in co-irradiated tissues. We previously showed that differential DNA methylation at an enhancer of diacylglycerol kinase alpha (DGKA) in normal dermal fibroblasts is associated with radiation-induced fibrosis. After irradiation, the transcription factor EGR1 is induced and binds to the hypomethylated enhancer, leading to increased DGKA and pro-fibrotic marker expression. We now modulated this DGKA induction by targeted epigenomic and genomic editing of the DGKA enhancer and administering epigenetic drugs. Targeted DNA demethylation of the DGKA enhancer in HEK293T cells resulted in enrichment of enhancer-related histone activation marks and radiation-induced DGKA expression. Mutations of the EGR1-binding motifs decreased radiation-induced DGKA expression in BJ fibroblasts and caused dysregulation of multiple fibrosis-related pathways. EZH2 inhibitors (GSK126, EPZ6438) did not change radiation-induced DGKA increase. Bromodomain inhibitors (CBP30, JQ1) suppressed radiation-induced DGKA and pro-fibrotic marker expression. Similar drug effects were observed in donor-derived fibroblasts with low DNA methylation. Overall, epigenomic manipulation of DGKA expression may offer novel options for a personalized treatment to prevent or attenuate radiotherapy-induced fibrosis.

7.
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).

8.
Cancers (Basel) ; 13(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946741

RESUMO

Intraoperative radiotherapy (IORT) displays an increasingly used treatment option for early breast cancer. It exhibits non-inferiority concerning the risk of recurrence compared to conventional external irradiation (EBRT) in suitable patients with early breast cancer. Since most relapses occur in direct proximity of the former tumor site, the reduction of the risk of local recurrence effected by radiotherapy might partially be due to an alteration of the irradiated tumor bed's micromilieu. Our aim was to investigate if IORT affects the local micromilieu, especially immune cells with concomitant cytokine profile, and if it has an impact on growth conditions for breast cancer cells as well as mammary mesenchymal stromal cells (MSC), the latter considered as a model of the tumor bed stroma.42 breast cancer patients with breast-conserving surgery were included, of whom 21 received IORT (IORT group) and 21 underwent surgery without IORT (control group). Drainage wound fluid (WF) was collected from both groups 24 h after surgery for flow cytometric analysis of immune cell subset counts and potential apoptosis and for multiplex cytokine analyses (cytokine array and ELISA). It served further as a supplement in cultures of MDA-MB 231 breast cancer cells and mammary MSC for functional analyses, including proliferation, wound healing and migration. Furthermore, the cytokine profile within conditioned media from WF-treated MSC cultures was assessed. Flow cytometric analysis showed no group-related changes of cell count, activation state and apoptosis rates of myeloid, lymphoid leucocytes and regulatory T cells in the WF. Multiplex cytokine analysis of the WF revealed group-related differences in the expression levels of several cytokines, e.g., oncostatin-M, leptin and IL-1ß. The application of WF in MDA-MB 231 cultures did not show a group-related difference in proliferation, wound healing and chemotactic migration. However, WF from IORT-treated patients significantly inhibited mammary MSC proliferation, wound healing and migration compared to WF from the control group. The conditioned media collected from WF-treated MSC-cultures also exhibited altered concentrations of VEGF, RANTES and GROα. IORT causes significant changes in the cytokine profile and MSC growth behavior. These changes in the tumor bed could potentially contribute to the beneficial oncological outcome entailed by this technique. The consideration whether this alteration also affects MSC interaction with other stroma components presents a promising gateway for future investigations.

9.
Radiother Oncol ; 159: 241-248, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33838170

RESUMO

AIM: To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi). MATERIALS AND METHODS: Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 literature-identified SNPs, the 30% most strongly associated with each toxicity were tested. SNP-SNP combinations (named SNP-allele sets) seen in ≥10% of the cohort were condensed into risk (RS) and protection (PS) scores, respectively indicating increased or decreased toxicity risk. Performance of RS and PS was evaluated by logistic regression. RS and PS were then combined into a single PRSi evaluated by area under the receiver operating characteristic curve (AUC). RESULTS: Among 1,387 analysed patients, toxicity rates were 11.7% (rectal bleeding), 4.0% (urinary frequency), 5.5% (haematuria), 7.8% (nocturia) and 17.1% (decreased urinary stream). RS and PS combined 8 to 15 different SNP-allele sets, depending on the toxicity endpoint. Distributions of PRSi differed significantly in patients with/without toxicity with AUCs ranging from 0.61 to 0.78. PRSi was better than the classical summed PRS, particularly for the urinary frequency, haematuria and decreased urinary stream endpoints. CONCLUSIONS: Our method incorporates SNP-SNP interactions when calculating PRS for radiotherapy toxicity. Our approach is better than classical summation in discriminating patients with toxicity and should enable incorporating genetic information to improve normal tissue complication probability models.


Assuntos
Neoplasias da Próstata , Lesões por Radiação , Área Sob a Curva , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Lesões por Radiação/genética , Fatores de Risco
12.
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
13.
Front Oncol ; 10: 541281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178576

RESUMO

Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors. Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity. Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint. Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning.

14.
Front Oncol ; 10: 575909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216838

RESUMO

Background: Acute skin toxicity is a common and usually transient side-effect of breast radiotherapy although, if sufficiently severe, it can affect breast cosmesis, aftercare costs and the patient's quality-of-life. The aim of this study was to develop predictive models for acute skin toxicity using published risk factors and externally validate the models in patients recruited into the prospective multi-center REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve QUalITy of lifE in cancer survivors) study. Methods: Patient and treatment-related risk factors significantly associated with acute breast radiation toxicity on multivariate analysis were identified in the literature. These predictors were used to develop risk models for acute erythema and acute desquamation (skin loss) in three Radiogenomics Consortium cohorts of patients treated by breast-conserving surgery and whole breast external beam radiotherapy (n = 2,031). The models were externally validated in the REQUITE breast cancer cohort (n = 2,057). Results: The final risk model for acute erythema included BMI, breast size, hypo-fractionation, boost, tamoxifen use and smoking status. This model was validated in REQUITE with moderate discrimination (AUC 0.65), calibration and agreement between predicted and observed toxicity (Brier score 0.17). The risk model for acute desquamation, excluding the predictor tamoxifen use, failed to validate in the REQUITE cohort. Conclusions: While most published prediction research in the field has focused on model development, this study reports successful external validation of a predictive model using clinical risk factors for acute erythema following radiotherapy after breast-conserving surgery. This model retained discriminatory power but will benefit from further re-calibration. A similar model to predict acute desquamation failed to validate in the REQUITE cohort. Future improvements and more accurate predictions are expected through the addition of genetic markers and application of other modeling and machine learning techniques.

15.
BMJ ; 370: m2836, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32816842

RESUMO

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. DESIGN: Prospective, open label, randomised controlled clinical trial. SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005). CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned. TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Idoso , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Terapia Combinada , Feminino , Humanos , Cuidados Intraoperatórios , Mastectomia Segmentar , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida
16.
Brachytherapy ; 19(5): 635-641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32651094

RESUMO

PURPOSE: The purpose of the study was to report the outcomes of a single-center adjuvant electronic brachytherapy (e-BT) experience for patients with endometrial carcinoma. METHODS AND MATERIALS: Patients were retrospectively assessed. Intracavitary e-BT was applied through a cylindrical applicator (diameters 2.5-3.5 cm). e-BT single doses ranged between 4 and 7 Gy (EQD2 ∼ 6-12, α/ß of 10 Gy and an relative biological effectiveness of 1.3) at 5-mm depth. Adverse events are reported at first week, 1-3 months, 3-12 months, 12-24 months, and >24 months. The overall survival, disease-free survival, distant disease control rate, and local control rate were estimated using the Kaplan-Meier method. RESULTS: Twenty-nine patients were assessed. The median age was 68 [48-86] years. External beam radiotherapy was added in n = 8 (27.6%) patients. Staging was 13.8% for T1a, 51.7% for T1b, 24.1% for T2, 6.9% for T3a, and 3.4% for T3b. Grading was G3 in 51.7% (n = 15), G2 in 20.7% (n = 6), and G1 in 27.6% (n = 8). Median followup was 47 months [5-88]. Overall Grade 1, 2, and 3 toxicity was 89.7% (n = 26), 17.2% (n = 5), and 6.9% (n = 2), respectively. No Grade 3 cystitis or proctitis or any Grade 4 or 5 toxicity occurred during followup. No local recurrences were detected. Estimated distant disease control rate was 92.1% (n = 2, distant metastasis at 7 and 11 months). Estimated 4-year overall survival was 84.8% (n = 4 events, two unrelated to disease) and disease-free survival was 84.6%. CONCLUSIONS: Our data suggest that e-BT resembles a very-low-toxicity profile and a high local control rate in the adjuvant scenario for patients with endometrial carcinoma.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias do Endométrio/radioterapia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Cistite/epidemiologia , Intervalo Livre de Doença , Eletrônica , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Dor Pélvica/epidemiologia , Proctite/epidemiologia , Lesões por Radiação/epidemiologia , Radioterapia , Estudos Retrospectivos , Taxa de Sobrevida , Doenças Vaginais/epidemiologia
17.
Anticancer Res ; 40(7): 4137-4145, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620663

RESUMO

BACKGROUND/AIM: Lung diseases are common in patients with abdominal aortic aneurysms (AAA). This study evaluates the prevalence of lung cancer (LC) in high-risk patients screened for AAA. PATIENTS AND METHODS: Six hundred and one male patients (≥65 years of age, cardiovascular high-risk profile) were enrolled and followed prospectively over a median of 16.5 months. RESULTS: In 29 patients (4.8%) LC and in another 50 patients (8.3%) AAA were found. The prevalence of LC among patients with AAA was even higher (9 of 50, 18.0%). Twenty-one patients had an initial diagnosis of LC, with an incidence of 12.0% (6 of 50) in patients with AAA. During follow-up, 14 of 70 patients with AAA and/ or LC (20.0%) deceased. The highest mortality was found in patients with LC only (8 of 20, 40.0%), followed by patients with both AAA and LC (3 of 9, 33.3%), while patients with AAA only had the lowest mortality rate (3 of 41, 7.3%). CONCLUSION: In patients with a high cardiovascular risk profile, a high prevalence of both AAA and LC were found, whereby the prognosis is largely determined by the LC. Therefore, LC is of particular importance in the setting of screening and surveillance of AAA.


Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Neoplasias Pulmonares/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Diabetes Mellitus/epidemiologia , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Incidência , Masculino , Programas de Rastreamento , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Fumar/epidemiologia
18.
Radiother Oncol ; 149: 150-157, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32413529

RESUMO

The aim of this review is to provide a comprehensive overview of the role of intraoperative radiation therapy with electrons (IOERT) in breast conserving therapy (BCT), both as partial breast irradiation (PBI) as well as anticipated boost ("IOERT-Boost"). For both applications, the criteria for patient selection, technical details/requirements, physical aspects and outcome data are presented. IOERT AS PBI: The largest evidence comes from Italian studies, especially the ELIOT randomized trial. Investigators showed that the rate of in-breast relapses (IBR) in the IOERT group was significantly greater than with whole breast irradiation (WBI), even when within the pre-specified equivalence margin. Tumour sizes >2 cm, involved axillary nodes, Grade 3 and triple negative molecular subtypes emerged as statistically significant predictors of IBR. For patients at low risk for in-breast recurrence (ASTRO/ESTRO recommendations), full dose IOERT was isoeffective with standard WBI. Hence, several national guidelines now include this treatment strategy as one of the standard techniques for PBI in carefully selected patients. IOERT BOOST: The largest evidence for boost IOERT preceding WBI comes from pooled analyses performed by the European Group of the International Society of Intraoperative Radiation Therapy (ISIORT Europe), where single boost doses (mostly around 10 Gy) preceded whole-breast irradiation (WBI) with 50 Gy (conventional fractionation). At median follow-up periods up to ten years, local recurrence rates around 1% were observed for low risk tumours. Higher local relapse rates were described for grade 3 tumours, triple negative breast cancer as well as for patients treated after primary systemic therapy for locally advanced tumours. Even in this settings, long-term (>5y) local tumour control rates beyond 95% were achieved. These encouraging results are interpreted as being attributable to utmost precision in dose delivery (by avoiding a "geographic and/or temporal miss"), and the possible radiobiological superiority of a single high dose fraction, compared to the conventionally fractionated boost. IOERT also showed favourable results in terms of cosmetic outcome, assumedly thanks to the small treated volumes combined with complete skin sparing.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Terapia Combinada , Elétrons , Europa (Continente) , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia , Radioterapia Adjuvante
19.
Radiat Oncol ; 15(1): 110, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410696

RESUMO

BACKGROUND: Soft tissue sarcomas (STS) treatment remains a therapeutic challenge. Intraoperative radiotherapy (IORT) resembles a safe and efficient for STS treatment. The first data on electronic-IORT (eIORT) using low-energy photons is herein presented. METHODS: Thirty-one patients with newly and recurrent STS were retrospectively assessed. EIORT was applied with low-energy photons during surgery. The dose was either prescribed to the applicator surface (spherical applicators) or 5 mm depth (flat applicators). Overall progression-free survival (O-PFS), local progression-free survival (L-PFS), overall survival (OS) and adverse events were evaluated. RESULTS: Median follow-up was 4.88 (1.0-8.95) years. Twenty-five patients (80.6%) had recurrent STS with prior treatment. The resection status was R1 in 25.8% and R2 in 6.5%. The distribution was 51.7% for extremities, 35.5% for abdomen and pelvis, 9.7% for thorax and 3.2% for head and neck tumors. The median O-PFS was 11.0 months, with 42.6% 5-year estimated O-PFS. The only local recurrence in the primary setting occurred after 22 months. Median L-PFS in recurrent STS was 12.5 months, with 65.5% 5-year estimated L-PFS. The 5-year OS estimated rate was 94.7% (3 events after 7 years). No G3 toxicity related to eIORT was observed. Two patients exhibited G2 acute neuropathic pain. Late neuropathic pain was seen in 6 patients being 3 graded as G1 and 3 as G2. No wound-related toxicity was found. CONCLUSION: Electronic IORT with low-energy photons is a safe treatment option for STS, yielding similar outcomes as historical series reporting IORT with electrons or HDR brachytherapy.


Assuntos
Recidiva Local de Neoplasia/radioterapia , Fótons/uso terapêutico , Radiocirurgia/métodos , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
JAMA Oncol ; 6(7): e200249, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239210

RESUMO

Importance: Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective: To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants: In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions: The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures: A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results: Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80). Conclusions and Relevance: These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration: ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Recidiva Local de Neoplasia , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/cirurgia , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Análise de Sobrevida
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