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1.
Cancers (Basel) ; 13(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578746

RESUMO

Glioblastoma (GBM) is the most malignant primary brain tumor for which no curative treatment options exist. Non-invasive qualitative (Visually Accessible Rembrandt Images (VASARI)) and quantitative (radiomics) imaging features to predict prognosis and clinically relevant markers for GBM patients are needed to guide clinicians. A retrospective analysis of GBM patients in two neuro-oncology centers was conducted. The multimodal Cox-regression model to predict overall survival (OS) was developed using clinical features with VASARI and radiomics features in isocitrate dehydrogenase (IDH)-wild type GBM. Predictive models for IDH-mutation, 06-methylguanine-DNA-methyltransferase (MGMT)-methylation and epidermal growth factor receptor (EGFR) amplification using imaging features were developed using machine learning. The performance of the prognostic model improved upon addition of clinical, VASARI and radiomics features, for which the combined model performed best. This could be reproduced after external validation (C-index 0.711 95% CI 0.64-0.78) and used to stratify Kaplan-Meijer curves in two survival groups (p-value < 0.001). The predictive models performed significantly in the external validation for EGFR amplification (area-under-the-curve (AUC) 0.707, 95% CI 0.582-8.25) and MGMT-methylation (AUC 0.667, 95% CI 0.522-0.82) but not for IDH-mutation (AUC 0.695, 95% CI 0.436-0.927). The integrated clinical and imaging prognostic model was shown to be robust and of potential clinical relevance. The prediction of molecular markers showed promising results in the training set but could not be validated after external validation in a clinically relevant manner. Overall, these results show the potential of combining clinical features with imaging features for prognostic and predictive models in GBM, but further optimization and larger prospective studies are warranted.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33385265

RESUMO

PURPOSE: To spare DCIS patients from overtreatment, treatment de-escalated over the years. This study evaluates the influence of these developments on the patterns of care in the treatment of DCIS with particular interest in the use of breast conserving surgery (BCS), radiotherapy following BCS and the use and type of axillary staging. METHODS: In this large population-based cohort study all women, aged 50-74 years diagnosed with DCIS from January 1989 until January 2019, were analyzed per two-year cohort. RESULTS: A total of 30,417 women were diagnosed with DCIS. The proportion of patients undergoing BCS increased from 47.7% in 1995-1996 to 72.7% in 2017-2018 (p < 0.001). Adjuvant radiotherapy following BCS increased from 28.9% (1995-1996) to 89.6% (2011-2012) and subsequently decreased to 74.9% (2017-2018; p < 0.001). Since its introduction, the use of sentinel lymph node biopsy (SLNB) increased to 63.1% in 2013-2014 and subsequently decreased to 52.8% in 2017-2018 (p < 0.001). Axillary surgery is already omitted in 55.8% of the patients undergoing BCS nowadays. The five-year invasive relapse-free survival (iRFS) for BCS with adjuvant radiotherapy in the period 1989-2010, was 98.7% [CI 98.4% - 99.0%], compared to 95.0% [CI 94.1% -95.8%] for BCS only (p < 0.001). In 2011-2018, this was 99.3% [CI 99.1% - 99.5%] and 98.8% [CI 98.2% - 99.4%] respectively (p = 0.01). CONCLUSIONS: This study shows a shift toward less extensive treatment. DCIS is increasingly treated with BCS and less often followed by additional radiotherapy. The absence of radiotherapy still results in excellent iRFS. Axillary surgery is increasingly omitted in DCIS patients.

3.
Int J Cancer ; 148(1): 48-56, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32621785

RESUMO

Our study was performed to determine the frequency of recall for bilateral breast lesions at screening mammography and compare its outcome with respect to unilateral recall. We included 329 132 screening mammograms (34 889 initial screens and 294 243 subsequent screens) from a Dutch screening mammography program between January 2013 and January 2018. During a 2-year follow-up, we collected radiological data, pathology reports and surgical reports of all recalled women. At bilateral recall, the lesion with the highest Breast Imaging Reporting and Data System score was used as the index lesion when comparing screening mammography characteristics at bilateral vs unilateral recall. A total of 9806 women were recalled at screening (recall rate, 3.0%). Bilateral recall comprised 2.8% (271/9806) of all recalls. Biopsy was more frequently performed after bilateral recall than unilateral recall (54.6% [148/271] vs 44.1% [4201/9535], P < .001), yielding a lower positive predictive value (PPV) of biopsy after bilateral recall (42.6% vs 51.7%, P = .029). The PPV of recall was comparable for both groups (23.2% [63/271] vs 22.8% [2173/9535], P = .85). Invasive cancers after bilateral recall were larger than those diagnosed after unilateral recall (P = .02), but histological subtype, histologic grading, receptor status and proportions of lymph node positive cancers were comparable. Bilateral recall infrequently occurs at screening mammography. Biopsy is more frequently performed following bilateral recall, but the PPV of recall is similar for unilateral and bilateral recall. Invasive cancers of both groups show comparable pathological features except of a larger tumor size after bilateral recall.

4.
Nature ; 587(7832): 126-132, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32879494

RESUMO

Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes1,2. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution1,3,4. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Parallel evolutionary events, which cause disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within separate subclones, were present in 37% of tumours. Most recurrent losses probably occurred before whole-genome doubling, that was found as a clonal event in 49% of tumours. However, loss of heterozygosity at the human leukocyte antigen (HLA) locus and loss of chromosome 8p to a single haploid copy recurred at substantial subclonal frequencies, even in tumours with whole-genome doubling, indicating ongoing karyotype remodelling. Focal amplifications that affected chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (CCNE1) and 8q24.1 (MYC) were frequently subclonal yet appeared to be clonal within single samples. Analysis of an independent series of 1,024 metastatic samples revealed that 13 focal SCNAs were enriched in metastatic samples, including gains in chromosome 8q24.1 (encompassing MYC) in clear cell renal cell carcinoma and chromosome 11q13.3 (encompassing CCND1) in HER2+ breast cancer. Chromosomal instability may enable the continuous selection of SCNAs, which are established as ordered events that often occur in parallel, throughout tumour evolution.

5.
J Community Genet ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32880035

RESUMO

Individuals having a genetic predisposition to cancer and their partners face challenging decisions regarding their wish to have children. This study aimed to determine the effects of an online decision aid to support couples in making an informed decision regarding their reproductive options. A nationwide pretest-posttest study was conducted in the Netherlands among 131 participants between November 2016 and May 2018. Couples were eligible for participation if one partner had a pathogenic variant predisposing for an autosomal dominant hereditary cancer syndrome. Participants completed a questionnaire before use (T0), and at 3 months (T3) after use of the decision aid to assess the primary outcome measure informed decision-making, and the secondary outcome measures decisional conflict, knowledge, realistic expectations, level of deliberation, and decision self-efficacy. T0-T3 comparisons show an overall positive effect for all outcome measures (all ps < 0.05; knowledge (ES = - 1.05), decisional conflict (ES = 0.99), participants' decision self-efficacy (ES = -0.55), level of deliberation (ES = - 0.50), and realistic expectations (ES = - 0.44). Informed decision-making increased over time and 58.0% of the participants made an informed reproductive decision at T3. The online decision aid seems to be an appropriate tool to complement standard reproductive counseling to support our target group in making an informed reproductive decision. Use of the decision aid may lessen the negative psychological impact of decision-making on couples' daily life and wellbeing.

6.
Qual Life Res ; 29(12): 3363-3374, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32816222

RESUMO

PURPOSE: We aimed to evaluate quality of life (QoL) using the European Quality of Life Five-Dimensions questionnaire (EQ-5D-3L) in a real-world cohort of Dutch advanced breast cancer (ABC) patients. Secondary, we reported differences in QoL between subgroups of patients based on age, comorbidity, tumor-, and treatment characteristics, and assessed the association of duration of metastatic disease and time to death with QoL. METHODS: ABC patients who attended the outpatient clinic between October 2010 and May 2011 were asked to fill out the EQ-5D-3L questionnaire. Patient-, disease-, and treatment characteristics were obtained from the medical files. Health-utility scores were calculated. Subgroups were described and compared for utility scores by parametric and non-parametric methods. RESULTS: A total of 92 patients were included with a median utility score of 0.691 (Interquartile range [IQR] 0.244). Patients ≥ 65 years had significantly worse median utility scores than younger patients; 0.638 versus 0.743, respectively (p = 0.017). Moreover, scores were significantly worse for patients with versus those without comorbidity (medians 0.620 versus 0.725, p = 0.005). Utility scores did not significantly differ between subgroups of tumor type, type of systemic treatment, number of previous palliative treatment(s), or number or location of metastatic site(s). The remaining survival was correlated with utility scores (correlation coefficient (r) = 0.260, p = 0.0252), especially in the subgroup < 65 years (r = 0.340, p = 0.0169), whereas there was no significant correlation with time since metastatic diagnosis (r = - 0.106, p = 0.3136). CONCLUSION: Within this real-world cross-sectional study, QoL was significantly associated with age, comorbidity, and remaining survival duration. The observation of a lower QoL in ABC patients, possibly indicating the last period of life, may assist clinical decision-making on timing of cessation of systemic antitumor therapy.

7.
Crit Rev Oncol Hematol ; 153: 102988, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32599374

RESUMO

This review aims to evaluate the role of chemotherapy-containing regimens in the treatment of advanced breast cancer (ABC), with the purpose to optimize selection, sequencing and duration of treatment with the currently available agents for clinical practice. Data from observational as well as randomized phase II and III studies were included. Chemotherapy yielded a median overall survival (OS) of 2 years in registration studies, with comparable efficacy of different agents. Combining chemotherapy agents did not yield OS improvement and caused greater toxicity compared with single-agent chemotherapy. Continuing chemotherapy till progression or unacceptable toxicity generated greater efficacy without detrimental impact on quality of life compared with a limited amount of cycles. In real-world studies, benefits after third-line chemotherapy were modest compared with first- and second-line. Furthermore, effects of previous chemotherapy predicted effects of next-line therapy in real-world. Physicians increasingly prescribed capecitabine or taxanes as first- or second-line chemotherapy over time.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Humanos , Qualidade de Vida , Taxoides/uso terapêutico
8.
Acta Oncol ; 59(9): 1123-1130, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32544366

RESUMO

Background: In 2013, eribulin was reimbursed under a coverage with evidence development (CED) as third or later chemotherapy line for advanced breast cancer (ABC) patients in the Netherlands because of uncertain cost effectiveness. In 2016, the final decision of reimbursing eribulin was taken without considering the evidence collected during CED research. We analysed the cost effectiveness of eribulin versus non-eribulin chemotherapy, using real-world data.Methods: A three health states (progression-free, progressed disease, dead) partitioned survival model was developed. The SOuth East Netherlands Advanced BREast Cancer (SONABRE) registry informed the effectiveness and costs inputs. Health state utility values were obtained from the literature. Incremental cost-effectiveness ratio (ICER) between the eribulin and matched non-eribulin chemotherapy was estimated. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed. The financial risk (i.e., the expected value of perfect information (EVPI) plus the expected monetary loss (eML) associated with reimbursing eribulin) and budget impact associated with reimbursing eribulin were calculated.Results: Eribulin led to higher health benefits (0.07 quality-adjusted life year (QALY)) and costs (€15,321) compared with non-eribulin chemotherapy. This resulted in an ICER of €220,608. At a €80,000 per QALY threshold, the risk of reimbursing eribulin was €9,791 per patient (EVPI €13, eML €9,778). Scaled up to the Dutch population, the estimated annual budget impact was €1.9 million and the annual risk of reimbursing eribulin was €2.7 million.Conclusion: From a Dutch societal perspective, eribulin is not cost effective when considering its list price as third and later chemotherapy line for ABC patients.

9.
Br J Cancer ; 123(2): 325-332, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32390006

RESUMO

BACKGROUND: Delay in detection of breast cancer may worsen tumour characteristics, with progression of tumour size and a higher risk of metastatic lymph nodes. The purpose of this study was to investigate delayed breast cancer diagnosis after repeated recall for the same mammographic abnormality at screening. METHODS: This was a retrospective study performed in two cohorts of women enrolled in a mammography screening programme in the Netherlands. All women aged 50-75 who underwent biennial screening mammography either between January 1, 1997 and December 31, 2006 (cohort 1) or between January 1, 2007 and December 31, 2016 (cohort 2) were included. RESULTS: The cohorts showed no difference in proportions of women with delayed breast cancer diagnosis of at least 2 years (2.2% versus 2.8%, P = 0.29). Most delays were caused by incorrect BI-RADS classifications after recall (74.2%). An increase in mean tumour size was seen when comparing sizes at initial false-negative recall and at diagnosis of breast cancer (P < 0.001). CONCLUSIONS: The proportion of women with a long delay in breast cancer confirmation following repeated recall at screening mammography has not decreased during 20 years of screening. These delays lead to larger tumour size at detection and may negatively influence prognosis.

10.
Acta Oncol ; 59(8): 895-903, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32319845

RESUMO

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens.Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model.Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9-77.2 months). Median OS (21.9 months; 95% CI: 16.9-27.0 months) was comparable between treatment groups (logrank p = .88), confirmed in the fully adjusted and PS weighted model (p > .05). Grades 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31-10.87; p = .01). The occurrence of grades 3-5 late toxicities was not different between treatment groups.Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC.

11.
Breast Cancer Res Treat ; 181(1): 77-86, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32236826

RESUMO

PURPOSE: We assessed the uptake of fertility preservation (FP), recovery of ovarian function (OFR) after chemotherapy, live birth after breast cancer, and breast cancer outcomes in women with early-stage breast cancer. METHODS: Women aged below 41 years and referred to our center for FP counseling between 2008 and 2015 were included. Data on patient and tumor characteristics, ovarian function, cryopreservation (embryo/oocyte) and transfer, live birth, and disease-free survival were collected. Kaplan-Meier analyses were performed for time-to-event analyses including competing risk analyses, and patients with versus without FP were compared using the logrank test. RESULTS: Of 118 counseled women with a median age of 31 years (range 19-40), 34 (29%) chose FP. Women who chose FP had less often children, more often a male partner and more often favorable tumor characteristics. The 5-year OFR rate was 92% for the total group of counseled patients. In total, 26 women gave birth. The 5-year live birth rate was 27% for the total group of counseled patients. Only three women applied for transfer of their cryopreserved embryo(s), in two combined with preimplantation genetic diagnosis (PGD) because of BRCA1-mutation carrier ship. The 5-year disease-free survival rate was 91% versus 88%, for patients with versus without FP (P = 0.42). CONCLUSIONS: Remarkably, most women achieved OFR, probably related to the young age at diagnosis. Most pregnancies occurred spontaneously, two of three women applied for embryo transfer because of the opportunity to apply for PGD.

12.
PLoS One ; 15(4): e0230909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271794

RESUMO

OBJECTIVE: In breast cancer patients, treatment at the end of life accounts for a major share of medical spending. However, little is known about the variability of cost trajectories between patients. This study aims to identify underlying latent groups of advanced breast cancer patients with similar cost trajectories over the last year before death. METHODS: Data from deceased advanced breast cancer patients, diagnosed between 2010 and 2017, were retrieved from the Southeast Netherlands Advanced Breast Cancer (SONABRE) Registry. Costs of hospital care over the last twelve months before death were analyzed, and the variability of longitudinal patterns between patients were explored using group-based trajectory modeling. Descriptive statistics and multinomial logistic regression were applied to investigate differences between the identified latent groups. RESULTS: We included 558 patients. Over the last twelve months before death, mean hospital costs were €2,255 (SD = €492) per month. Costs increased over the last five months and reached a maximum of €3,614 in the last month of life, driven by hospital admissions, while spending for medication declined over the last three months of life. Based on patients' individual cost trajectories, we identified six latent groups with distinct longitudinal patterns, of which only two showed a marked increase in costs over the last twelve months before death. Latent groups were constituted of heterogeneous patients, and clinical characteristics explained membership only to a limited extent. CONCLUSIONS: The average costs of advanced breast cancer patients increased towards the end of life. However, we uncovered several latent groups of patients with divergent cost trajectories, which did not reflect the overall increasing trend. The mechanisms underlying the variability in cost trajectories warrants further research.


Assuntos
Neoplasias da Mama/economia , Assistência Terminal/economia , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Feminino , Custos Hospitalares , Hospitalização/economia , Humanos , Modelos Lineares , Modelos Logísticos , Pessoa de Meia-Idade , Países Baixos , Cuidados Paliativos/economia , Taxa de Sobrevida
13.
Breast Cancer Res Treat ; 180(3): 675-685, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124136

RESUMO

PURPOSE: The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. METHODS: We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. RESULTS: Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS. CONCLUSION: No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.

14.
Acta Oncol ; 59(6): 713-722, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32141389

RESUMO

Background: Previously, we showed that reintroduction of the same (first-line) chemotherapy at progression could only partially make up for the loss in efficacy as compared to continuously delivered first-line chemotherapy. Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule.Methods: First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous).Results: Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Median PFS was 3.7 versus 5.0 months (HR 1.07; 95% CI: 0.82-1.38) and median OS 10.9 versus 12.4 months (HR 1.27; 95% CI: 0.98-1.66) for intermittent versus continuous second-line chemotherapy. Second-line PFS was positively influenced by prior hormonal therapy for metastatic disease and longer first-line PFS duration, while triple-negative tumor status had a negative influence. Patients with a shorter time to progression (TTP) in first-line (≤10 months) had a higher probability of starting second-line treatment if they received intermittent compared to continuous chemotherapy (OR 1.97; 95% CI: 1.02-3.80).Conclusion: We recommend continuous scheduling of both the first- and second-line chemotherapy for advanced breast cancer.

15.
Radiology ; 294(3): 528-537, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31990268

RESUMO

Background Trends in the detection of suspicious microcalcifications at mammography screening and the yield of these lesions after recall are unknown. Purpose To determine trends in recall and outcome of screen-detected microcalcifications during 20 years of mammography screening. Materials and Methods The authors performed a retrospective analysis of a consecutive series of 817 656 screening examinations (January 1997 to January 2017) in a national breast screening program. In 2009-2010 (transition period), screen-film mammography (SFM) was gradually replaced by full-field digital mammography (FFDM). The recalls of suspicious microcalcifications from all radiology reports and pathologic outcome of recalled women with 2-year follow-up were analyzed. Screening outcome in the era of SFM (1997-2008), the transition period (2009-2010), and the era of FFDM (2011-2016) were compared. Trends over time and variations between the SFM and FFDM periods were expressed by using proportions with 95% confidence intervals (CIs). In cases where the analysis based on the CI confirmed clear periods (eg, before and after introduction of FFDM), pre- and postchange outcomes were compared by using χ2 tests. Results A total of 18 592 women (median age, 59 years; interquartile range, 14 years) were recalled at mammography screening, 3556 of whom had suspicious microcalcifications. The recall rate for microcalcifications increased from 0.1% in 1997-1998 to 0.5% in 2015-2016 (P < .001). This was temporally associated with the change from SFM to FFDM. The recalls yielding ductal carcinoma in situ (DCIS) increased from 0.3 per 1000 screening examinations with SFM to 1.1 per 1000 screening examinations with FFDM (P < .001), resulting in a decrease in the positive predictive value for recall for suspicious microcalcifications from 51% to 33% (P < .001). More than half of all DCIS lesions were high grade (52.6%; 393 of 747). The distribution of DCIS grades was stable during the 20-year screening period (P = .36). Conclusion The recall rate for suspicious microcalcifications at mammographic screening increased during the past 2 decades, whereas the ductal carcinoma in situ detection rate increased less rapidly, resulting in a lower positive predictive value for recall. © RSNA, 2020.


Assuntos
Neoplasias da Mama , Mama , Calcinose , Mamografia , Idoso , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Calcinose/patologia , Carcinoma Intraductal não Infiltrante , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia/métodos , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Países Baixos , Valor Preditivo dos Testes , Estudos Retrospectivos
16.
JAMA Oncol ; 6(4): 528-534, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999296

RESUMO

Importance: Trials of adjuvant high-dose chemotherapy (HDCT) have failed to show a survival benefit in unselected patients with breast cancer, but long-term follow-up is lacking. Objective: To determine 20-year efficacy and safety outcomes of a large trial of adjuvant HDCT vs conventional-dose chemotherapy (CDCT) for patients with stage III breast cancer. Design, Setting, and Participants: This secondary analysis used data from a randomized phase 3 multicenter clinical trial of 885 women younger than 56 years with breast cancer and 4 or more involved axillary lymph nodes conducted from August 1, 1993, to July 31, 1999. Additional follow-up data were collected between June 1, 2016, and December 31, 2017, from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from February 1, 2018, to October 14, 2019. Interventions: Participants were randomized 1:1 to receive 5 cycles of CDCT consisting of fluorouracil, 500 mg/m2, epirubicin, 90 mg/m2, and cyclophosphamide, 500 mg/m2, or HDCT in which the first 4 cycles were identical to CDCT and the fifth cycle was replaced by cyclophosphamide, 6000 mg/m2, thiotepa, 480 mg/m2, and carboplatin, 1600 mg/m2, followed by hematopoietic stem cell transplant. Main Outcomes and Measures: Main end points were overall survival and safety and cumulative incidence risk of a second malignant neoplasm or cardiovascular events. Results: Of the 885 women in the study (mean [SD] age, 44.5 [6.6] years), 442 were randomized to receive HDCT, and 443 were randomized to receive CDCT. With 20.4 years median follow-up (interquartile range, 19.2-22.0 years), the 20-year overall survival was 45.3% with HDCT and 41.5% with CDCT (hazard ratio, 0.89; 95% CI, 0.75-1.06). The absolute improvement in 20-year overall survival was 14.6% (hazard ratio, 0.72; 95% CI, 0.54-0.95) for patients with 10 or more invoved axillary lymph nodes and 15.4% (hazard ratio, 0.67; 95% CI, 0.42-1.05) for patients with triple-negative breast cancer. The cumulative incidence risk of a second malignant neoplasm at 20 years or major cardiovascular events was similar in both treatment groups (20-year cumulative incidence risk for second malignant neoplasm was 12.1% in the HDCT group vs 16.2% in the CDCT group, P = .10), although patients in the HDCT group more often had hypertension (21.7% vs 14.3%, P = .02), hypercholesterolemia (15.7% vs 10.6%, P = .04), and dysrhythmias (8.6% vs 4.6%, P = .005). Conclusions and Relevance: High-dose chemotherapy provided no long-term survival benefit in unselected patients with stage III breast cancer but did provide improved overall survival in very high-risk patients (ie, with ≥10 involved axillary lymph nodes). High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT03087409.

17.
Radiology ; 294(3): 509-517, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31909697

RESUMO

Background Screening technologists may function as readers in breast cancer screening programs. In the Netherlands, they attend quality assurance sessions. The frequency and characteristics of additional breast cancers detected through these sessions have not been reported. Purpose To determine the frequency and characteristics of cancers detected through quality assurance sessions. Materials and Methods This secondary analysis of a prospective cohort included 466 647 screening mammograms obtained between January 1, 2009, and January 1, 2017. Mammograms were single read by certified screening technologists before being double read by two certified screening radiologists who were not blinded to the technologists' reading. The technologists and a coordinating screening radiologist regularly discussed mammograms that the technologists considered suspicious but that did not prompt recall at radiologist double reading. The coordinating radiologist decided whether secondary recall was indicated. During a 2-year follow-up, radiologic and pathologic outcome data for all recalled women were obtained. Characteristics of cancers detected at radiologist double reading and those detected through quality assurance sessions were compared by using χ2 and Fisher exact tests. Results A total of 14 142 women (mean age, 59 years ± 7.8 [standard deviation]; range, 49-75 years) were recalled (recall rate, 3.0% [14 142 of 466 647]): 14 057 after radiologist double reading and 85 by the coordinating radiologists after quality assurance sessions. This resulted in 3156 screening-detected cancers (6.8 cancers detected per 1000 screenings), of which 26 (0.8% of screening-detected cancers [26 of 3156]) were detected after secondary recall through quality assurance sessions. The latter comprised eight ductal carcinomas in situ (88% intermediate or high grade [seven of eight]) and 18 invasive cancers (14 T1a-c and four T2+ cancers, 89% Nottingham grade I or II [16 of 18]). No significant differences in tumor characteristics were found (P values ranging from .22 to .95). Sensitivity of quality assurance sessions for additional cancer detection was 52% (26 of 50; 95% confidence interval: 38%, 66%). Conclusion The role of quality assurance sessions in additional cancer detection is limited. Tumor characteristics did not differ significantly from those of cancers detected at radiologist double reading. © RSNA, 2020.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Mamografia , Idoso , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Feminino , Pessoal de Saúde , Humanos , Mamografia/métodos , Mamografia/normas , Pessoa de Meia-Idade , Países Baixos , Garantia da Qualidade dos Cuidados de Saúde , Radiologistas , Estudos Retrospectivos
18.
Breast Cancer Res Treat ; 179(3): 677-685, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31782032

RESUMO

BACKGROUND: The Stop&Go study randomized patients with advanced breast cancer to intermittent (two times four) or continuous (eight subsequent cycles) first- and second-line chemotherapy. METHODS: QoL was measured with RAND-36 questionnaires every 12 weeks. The primary objective was to estimate differences in changes from baseline between intermittent and continuous treatment. An effect size of 0.5 SD (5 points) was considered clinically meaningful. RESULTS: A total of 398 patients were included with a median follow-up of 11.4 months (IQR 5.6-22.2). Mean physical QoL baseline scores were 38.0 resp. 38.2, and mental scores 45.0 resp. 42.4 for intermittent and continuous treatment. Physical QoL declined linearly in the intermittent arm causing a clinically meaningful difference of 5.40 points at 24 months (p < 0.001), while scores in the continuous arm stabilized after a small decline of ± 3.4 points at 12 months. Conversely, mental QoL was fairly stable and even improved with 1.58 (p = 0.005) and 2.48 points (p < 0.001) at 12 months for intermittent and continuous treatment, respectively. When comparing arms for both components in changes from baseline, the maximum differences were 2.46 (p = 0.101) and 1.95 points (p = 0.182) for physical and mental scores, both measured at 30 months and in favor of continuous treatment. CONCLUSION: Intermittent first- and second-line chemotherapy in patients with HER2-negative advanced breast cancer showed a trend for worse impact on QoL compared to continuous chemotherapy, with neither significant nor meaningful differences in course. We recommend prescribing chemotherapy continuously until progressive disease or unacceptable toxicity. Trial registration EudraCT 2010-021519-18; BOOG 2010-02.


Assuntos
Neoplasias da Mama/epidemiologia , Qualidade de Vida , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Retratamento , Resultado do Tratamento
19.
Nature ; 575(7781): 210-216, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31645765

RESUMO

Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants. The characteristic mutations of metastatic lesions varied widely, with mutations that reflect those of the primary tumour types, and with high rates of whole-genome duplication events (56%). Individual metastatic lesions were relatively homogeneous, with the vast majority (96%) of driver mutations being clonal and up to 80% of tumour-suppressor genes being inactivated bi-allelically by different mutational mechanisms. Although metastatic tumour genomes showed similar mutational landscape and driver genes to primary tumours, we find characteristics that could contribute to responsiveness to therapy or resistance in individual patients. We implement an approach for the review of clinically relevant associations and their potential for actionability. For 62% of patients, we identify genetic variants that may be used to stratify patients towards therapies that either have been approved or are in clinical trials. This demonstrates the importance of comprehensive genomic tumour profiling for precision medicine in cancer.


Assuntos
Mutação , Metástase Neoplásica/genética , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão , Sequenciamento Completo do Genoma , Células Clonais/metabolismo , Células Clonais/patologia , Variações do Número de Cópias de DNA , Feminino , Humanos , Mutação INDEL , Disseminação de Informação , Masculino
20.
Nat Genet ; 51(10): 1450-1458, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31570896

RESUMO

The whole-genome sequencing of prospectively collected tissue biopsies from 442 patients with metastatic breast cancer reveals that, compared to primary breast cancer, tumor mutational burden doubles, the relative contributions of mutational signatures shift and the mutation frequency of six known driver genes increases in metastatic breast cancer. Significant associations with pretreatment are also observed. The contribution of mutational signature 17 is significantly enriched in patients pretreated with fluorouracil, taxanes, platinum and/or eribulin, whereas the de novo mutational signature I identified in this study is significantly associated with pretreatment containing platinum-based chemotherapy. Clinically relevant subgroups of tumors are identified, exhibiting either homologous recombination deficiency (13%), high tumor mutational burden (11%) or specific alterations (24%) linked to sensitivity to FDA-approved drugs. This study provides insights into the biology of metastatic breast cancer and identifies clinically useful genomic features for the future improvement of patient management.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias da Mama/genética , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Mutação , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Genômica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Prognóstico
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