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1.
Breast Cancer Res Treat ; 184(3): 985-998, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32920743

RESUMO

PURPOSE: We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinicopathological features. METHODS: Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS). RESULTS: We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55; p = 0.0172) and BCSS (HR = 2.10; p < 0.001). CONCLUSIONS: Clinicopathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer-related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.

2.
Sci Rep ; 10(1): 9688, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546843

RESUMO

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.

3.
Eur J Cancer ; 121: 130-143, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31574418

RESUMO

PURPOSE: Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer. MATERIALS AND METHODS: Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up). RESULTS: After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p < 0.001) and male gender (p = 0.045). Although significant differences were not observed, subset analyses for LRF (dose range: 50.4-59 Gy) seemed to favour lower doses (p = 0.412), and when comparing a 2-week gap versus 3 (dose: 59.4 Gy), results suggested 3 weeks might be detrimental (p = 0.245). For a 2-week gap versus none (dose range: 55-59.4 Gy), no difference was observed (p = 0.89). Five-year PFS was 65.7% (95% CI: 62.8-68.5%). Higher PFS rates were observed in women (p < 0.001), smaller tumour sizes (p < 0.001) and shorter OTT (p = 0.025). Five-year overall survival [76.7% (95% CI: 73.9%-79.3%)] correlated positively with female gender (p < 0.001), small tumour size (p = 0.027) and short OTT (p = 0.026). Descriptive toxicity data are presented. CONCLUSION: For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome. Further trials involving modern techniques may better define optimal OTT and total dose.


Assuntos
Neoplasias do Ânus/terapia , Quimiorradioterapia/métodos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Fluoruracila/administração & dosagem , Mitomicina/administração & dosagem , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Quimiorradioterapia/efeitos adversos , Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/métodos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Terapia Combinada , Fluoruracila/efeitos adversos , Humanos , Mitomicina/efeitos adversos , Recidiva Local de Neoplasia/etnologia , Recidiva Local de Neoplasia/terapia , Dosagem Radioterapêutica , Resultado do Tratamento
4.
Strahlenther Onkol ; 195(4): 310-317, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30603857

RESUMO

PURPOSE: Adding a tumour bed boost to whole-breast irradiation in breast-conserving therapy reduces local recurrence rates. The purpose of the present study was to investigate whether the boost technique influences the magnitude of the effect. METHODS: Patients treated with breast-conserving therapy for invasive breast cancer between 2000 and 2007 were included in the analysis. Three groups were considered according to the applied boost technique: electrons, brachytherapy or photons. The endpoints were local recurrence and any recurrence. Cox regression models were used and correction for the confounders in the association between boost technique and outcome was performed using multivariable models. RESULTS: 1879 tumours were included in the analysis. 1448 tumours (77.1%) were treated with an electron boost, 334 (17.8%) with a brachytherapy boost and 97 (5.2%) with a photon boost. Median follow-up was 13.1 years. The 10-year local recurrence rate was 2.2%. In multivariable analysis with correction for age, pathological Tumour or Node stage (pT, pN), chemotherapy and hormonal therapy, there was no significant difference between the three groups for the local recurrence risk (p = 0.89). 10-year any recurrence rate was 10.8%. In multivariable analysis with correction for age, pT, pN, resection margins, radiotherapy, year of diagnosis, chemotherapy and hormonal therapy, there was no significant difference between the brachytherapy group and the electron group or the photon group (p = 0.11 and p = 0.28, respectively). The photon group had more recurrences compared to the electron group (Hazard Ratio 1.81, 95% Confidence Interval 1.12; 2.92, p = 0.02). CONCLUSIONS: The local recurrence risk reduction of the tumour bed boost in breast-conserving therapy is not influenced by the applied boost technique.


Assuntos
Braquiterapia , Neoplasias da Mama/radioterapia , Mastectomia Segmentar , Recidiva Local de Neoplasia/etiologia , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Elétrons/uso terapêutico , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática/patologia , Análise Multivariada , Estadiamento de Neoplasias , Fótons/uso terapêutico
5.
Radiother Oncol ; 128(2): 192-197, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29729847

RESUMO

OBJECTIVE: To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy. METHODS AND MATERIALS: During four consensus meetings (Cambridge, Essen, Liverpool, and Marseille), conventional field-based TV has been translated into image-guided high-precision craniospinal TV by a group of expert paediatric radiation oncologists and enhanced by MRI images of liquor distribution. RESULTS: The CTVcranial should include the whole brain, cribriform plate, most inferior part of the temporal lobes, and the pituitary fossa. If the full length of both optic nerves is not included, the dose received by different volumes of optic nerve should be recorded to correlate with future patterns of relapse (no consensus). The CTVcranial should be modified to include the dural cuffs of cranial nerves as they pass through the skull base foramina. Attempts to spare the cochlea by excluding CSF within the internal auditory canal should be avoided. The CTVspinal should include the entire subarachnoid space, including nerve roots laterally. The lower limit of the spinal CTV is at the lower limit of the thecal sac, best visible on MRI scan. There is no need to include sacral root canals in the spinal CTV. CONCLUSION: This consensus guideline has the potential to improve consistency of craniospinal TV delineation in an era of high-precision radiotherapy. This proposal will be incorporated in the RTQA guidelines of future SIOPE-BTG trials using CSI.


Assuntos
Neoplasias Encefálicas/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Consenso , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Adulto Jovem
6.
Radiother Oncol ; 123(3): 424-430, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28478912

RESUMO

BACKGROUND AND PURPOSE: The phase III EORTC 1219-DAHANCA 29 intergroup trial evaluates the influence of nimorazole in patients with locally advanced head and neck cancer when treated with accelerated radiotherapy (RT) in combination with chemotherapy. This article describes the results of the RT Benchmark Case (BC) performed before patient inclusion. MATERIALS AND METHODS: The participating centers were asked to perform a 2-step BC, consisting of (1) a delineation and (2) a planning exercise according to the protocol guidelines. Submissions were prospectively centrally reviewed and feedback was given to the submitting centers. Sørensen-Dice similarity index (DSI) and the 95th percentile Hausdorff distance (HD) were retrospectively used to evaluate the agreement between the centers and the expert contours. RESULTS: Fifty-four submissions (34 delineation and 20 planning exercises) from 19 centers were reviewed. Nine (47%) centers needed to perform the delineation step twice and three (16%) centers 3 times before receiving an approval. An increase in DSI-value and a decrease in HD, in particular for the prophylactic Clinical Target Volume (pCTV), could be found for the resubmitted cases. No unacceptable variations could be found for the planning exercise. CONCLUSIONS: These BC-results highlight the need for effective and prospective RTQA in clinical trials. Even with clearly defined protocol guidelines, delineation and not planning remain the main reason for unacceptable protocol variations. The introduction of more objective quantitative analysis methods, such as the HD and DSI, in future trials might strengthen the evaluation by experts.


Assuntos
Benchmarking , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Garantia da Qualidade dos Cuidados de Saúde , Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Nimorazol/uso terapêutico , Órgãos em Risco , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
7.
Radiat Oncol ; 11(1): 160, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27978843

RESUMO

Beam Output Auditing (BOA) is one key process of the EORTC radiation therapy quality assurance program. Here the results obtained between 2005 and 2014 are presented and compared to previous results.For all BOA reports the following parameters were scored: centre, country, date of audit, beam energies and treatment machines audited, auditing organisation, percentage of agreement between stated and measured dose.Four-hundred and sixty-one BOA reports were analyzed containing the results of 1790 photon and 1366 electron beams, delivered by 755 different treatment machines. The majority of beams (91.1%) were within the optimal limit of ≤ 3%. Only 13 beams (0.4%; n = 9 electrons; n = 4 photons), were out of the range of acceptance of ≤ 5%. Previous reviews reported a much higher percentage of 2.5% or more of the BOAs with >5% deviation.The majority of EORTC centres present beam output variations within the 3% tolerance cutoff value and only 0.4% of audited beams presented with variations of more than 5%. This is an important improvement compared to previous BOA results.


Assuntos
Garantia da Qualidade dos Cuidados de Saúde , Radioterapia (Especialidade)/normas , Humanos
8.
Acta Oncol ; 52(7): 1405-10, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23957564

RESUMO

BACKGROUND: Radiation-induced lung damage (RILD) is an important problem. Although physical parameters such as the mean lung dose are used in clinical practice, they are not suited for individualised radiotherapy. Objective, quantitative measurements of RILD on a continuous instead of on an ordinal, semi-quantitative, semi-subjective scale, are needed. METHODS: Hounsfield unit (HU) changes before versus three months post-radiotherapy were correlated per voxel with the radiotherapy dose in 95 lung cancer patients. Deformable registration was used to register pre- and post-CT scans and the density increase was quantified for various dose bins. The dose-response curve for increased HU was quantified using the slope of a linear regression (HU/Gy). The end-point for the toxicity analysis was dyspnoea ≥ grade 2. RESULTS: Radiation dose was linearly correlated with the change in HU (mean R(2) = 0.74 ± 0.28). No differences in HU/Gy between groups treated with stereotactic radiotherapy, conventional radiotherapy alone, sequential or concurrent chemo- radiotherapy were observed. In the whole patient group, 33/95 (34.7%) had dyspnoea ≥ G2. Of the 48 patients with a HU/Gy below the median, 16 (33.3%) developed dyspnoea ≥ G2, while in the 47 patients with a HU/Gy above the median, 17 (36.1%) had dyspnoea ≥ G2 (not significant). Individual patients showed a nearly 21-fold difference in radiosensitivity, with HU/Gy ranging from 0 to 10 HU/Gy. CONCLUSIONS: HU changes identify objectively the whole range of individual radiosensitivity on a continuous, quantitative scale. CT density changes may allow more robust and accurate radiogenomics studies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Dispneia/diagnóstico por imagem , Genômica , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/diagnóstico por imagem , Radioterapia/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Dispneia/etiologia , Dispneia/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/patologia , Radiografia Torácica , Dosagem Radioterapêutica , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Tomografia Computadorizada por Raios X
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