V2 李苹果 声望 26 2020-07-15 20:06:31 上传
MRI and intraoperative pathology to predict nipple–areola complex (NAC) involvement in patients undergoing NAC-sparing mastectomy
Abstract Background Nipple–areola sparing mastectomy (NSM) with immediate implant reconstruction is an option for patients with non-locally advanced breast cancer. The prediction of occult tumour involvement of the nipple–areola complex (NAC) may help select candidates to NSM. Patients and methods We prospectively recorded clinical and pathological data, magnetic resonance imaging (MRI) results and intraoperative pathological assessments of the subareolar (SD) and proximal nipple ducts (ND) of 112 consecutive breast cancer patients scheduled for NSM. All parameters were correlated with final pathological NAC assessment by univariate and multivariate analysis. Results Thirty-one patients (27.7%) had tumour involvement of the NAC. At univariate analysis, age (p = 0.001), post-menopausal status (0.003), tumour central location (p = 0.03), tumour–NAC distance measured by MRI (p = 0.000) and intraoperative pathologic assessment (SD + ND) (p = 0.000) were significantly correlated with NAC involvement. At multivariate analysis, only MRI tumour–NAC distance (p = 0.008) and menopausal status (p = 0.039) among all preoperative variables retained statistical significance. The sensitivity and specificity of MRI tumour–NAC distance were 32.2% and 88.6% and those of intraoperative pathologic assessment were 46.7% and 100%, respectively. Sensitivity, specificity and accuracy of the double assessment (MRI plus intraoperative pathology) were 50.0%, 96.2% and 84.1%, respectively. Conclusion Intraoperative pathologic assessment and tumour–NAC distance measured by MRI are the most important predictors of occult NAC involvement in breast cancer patients. A negative pathological assessment and a tumour–NAC distance ⩾ 5 mm allow optimal discrimination between NAC positive and NAC negative cases and may serve as a guide for the optimal planning of oncological and reconstructive surgery.
V1 Alexandrea 声望 1 生物信息学与生物统计学 2020-07-15 19:48:55 上传
Risk of oesophageal adenocarcinoma in individuals with Barrett's oesophagus
Abstract Introduction Recent studies have indicated a lower incidence rate of oesophageal adenocarcinoma (OAC) in individuals with Barrett's oesophagus (BO) than most earlier studies. Our objective was to assess the risk of OAC in a Swedish unselected cohort of individuals with BO. Methods This population-based cohort study included all Swedish residents diagnosed with BO in 2006–2013, identified through the Swedish Patient Registry. The cohort members were followed from the date of first BO diagnosis until the first occurrence of OAC, high-grade dysplasia (HGD), death, emigration or end of study period. The main outcome was incidence rates with 95% confidence intervals (CIs) of OAC. Results Among 7932 participants with BO and 18,415 person-years of follow-up, the overall incidence of OAC was 1.47 (95% CI 0.91–2.02) per 1000 person-years. When stratified into follow-up periods after BO diagnosis, the incidence rate of OAC was 15.53 (4.77–26.29) from 7 to 30 d, 4.10 (0.82–7.38) from 31 to 100 d, 1.87 (0.00–3.99) from 101 d to 6 months, 1.44 (0.18–2.70) from >6 months to 1 year, 0.94 (0.36–1.53) from >1 year to 3 years and 2.17 (1.14–3.21) from >3 years to the end of follow-up. The median follow-up time was 2.13 person-years. Conclusion This population-based study indicates that OAC is primarily diagnosed during the first months following an initial diagnosis of BO. This could justify a changed surveillance strategy of BO with a repeated thorough endoscopy shortly after initial BO diagnosis to identify prevalent early OAC or HGD.
V1 道讯 声望 1 生物科学 2020-07-15 19:48:55 上传
Patient-reported outcomes in head and neck and thyroid cancer randomised controlled trials: A systematic review of completeness of reporting and impact on interpretation
Abstract Aim To determine the completeness of reporting of patient-reported outcomes (PROs) of head and neck cancer (HNC) and thyroid cancer randomised-controlled trials (RCTs) and identify PRO measures used. Methods A systematic literature search was conducted for HNC and thyroid cancer RCTs with PRO end-points (January 2004–June 2015). Two investigators independently extracted data, assessed adherence to the International Society for Quality of Life Research (ISOQOL) PRO reporting standards and concordance between hypotheses and PRO measures used. Data were entered into the Patient-Reported Outcomes Measurements Over Time in Oncology (PROMOTION) Registry. Results Sixty-six RCTs were included, 56 (85%) HNC and 10 (15%) thyroid cancer. Twenty-two (33%) included a primary and 44 (67%) included a secondary PRO end-point. A total of 40 unique PRO measures were used. Adherence to the ISOQOL PRO reporting standards was higher for RCTs with primary PRO end-points than for secondary PRO end-points: (mean adherence of 43% and 29% respectively). Completeness of PRO reporting did not improve with time: r = .13, p = .31. ISOQOL checklist items poorly reported included: PRO hypothesis (reported for eight RCTs, 12%), justification chosen of PRO measures (n = 16, 24%), rates of missing PRO data (n = 19, 29%), and generalisability of results (n = 12, 18%). Encouragingly, PROs were identified in 55 RCT abstracts (83%) and PRO results interpreted for 30 RCTs (45%). Conclusions Reporting of PRO end-points was more comprehensive in RCTs with primary rather than secondary PRO end-points. Improvement is needed in the transparent reporting of PRO studies, particularly regarding data collection, analyses and generalisability of PRO results.
V2 User224134 声望 20 2020-07-15 19:41:16 上传
Role of neoadjuvant treatment in clinical T2N0M0 oesophageal cancer: results from a retrospective multi-center European study
Abstract Aims The aims of this study were to compare short- and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy. Methods Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short- and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics. Results No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short- or long-term outcomes. Conclusion The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
V2 姚超 声望 10 生物化学系 2020-07-15 19:34:15 上传
Influence of censoring on conclusions of trials for women with metastatic breast cancer
Abstract Progression-free survival and time-to-progression (PFS/TTP) are used commonly as primary end-points in trials evaluating treatments for metastatic breast cancer (MBC). We reviewed the impact of censoring on interpretation of these end-points. A systematic review identified phase 3 trials in MBC published between 2001 and 2012 that reported hazard ratios (HRs) for PFS/TTP and Kaplan–Meier curves indicating numbers at risk. We calculated HRs for time-to-treatment-failure (TTF) where discontinuation of treatment for any reason is considered an event. Mean HRs for PFS/TTP, TTF, and overall survival (OS) were 0.79, 0.89 and 0.91, respectively. Unbalanced censoring of patients prior to progression was prevalent, usually with more patients censored in the experimental arms. There was moderate-to-poor correlation of HRs of PFS/TTP and TTF with HRs for OS. We suggest that TTF should be reported as supportive analysis in registration trials and extent of missing data due to censoring be considered in decisions made by regulatory agencies.
V1 云想衣裳 声望 2 2020-07-15 19:09:06 上传
Elective unilateral nodal irradiation in head and neck squamous cell carcinoma: A paradigm shift
Abstract There is a long-standing convention to irradiate the great majority of head and neck squamous cell carcinoma (HNSCC) electively to both sides of the neck, to reduce the theoretically increased risk of contralateral regional failure (cRF). With the currently available diagnostic imaging techniques this treatment paradigm means, in our opinion, an overtreatment in considerable proportion of these patients. From all the published studies (n = 11, with 1116 patients treated in total), the incidence of cRF in patients with oropharyngeal cancer treated to one side of the neck is 2.4%. The incidence was higher in patients with tumours involving the midline (12.1%). The low incidence of cRF was also seen in patients with HNSCC treated by local excision combined with unilateral neck dissection or sentinel node procedure. It seems clear from the aggregated data of these studies that a less conservative approach with regard to the selection of patients for unilateral elective nodal irradiation is justified. The fear of leaving the contralateral neck untreated in well-selected groups of patients with HNSCC needs nowadays to be mitigated since the incidence of cRF in lateralised tumours extending to but not crossing the midline is low. Furthermore, the obviously improved diagnostic imaging nowadays could help us to guide the selection of considerable proportion of patients with lateralised HNSCC for unilateral elective nodal irradiation with significant reduction of radiation-related toxicity and improved quality of life.
V1 白鹿之子 声望 2 生物科学与生物技术 2020-07-15 18:14:43 上传
A randomised phase II trial of docetaxel versus docetaxel plus carboplatin in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial
Abstract Background Docetaxel is standard first-line chemotherapy for patients with metastatic castration–resistant prostate carcinoma (mCRPC). Docetaxel re-challenge has never been tested in a prospective randomised controlled study. As some studies support the addition of carboplatin to docetaxel, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel re-treatment in docetaxel pre-treated mCRPC patients. Methods Patients with mCRPC with a progression-free interval of ≥3 months after initial docetaxel treatment were randomised between docetaxel 75 mg/m2 or docetaxel 60 mg/m2 plus carboplatin AUC4. The primary end-point was progression-free survival (PFS; PSA/RECIST). Results Owing to insufficient recruitment, the study was discontinued early after inclusion of 75 patients (targeted 150) PFS and overall survival (OS) were comparable between both groups (median PFS 12.7 months (95% CI 9.9–17.5 months) with docetaxel monotherapy and 11.7 months (95% CI 8.5–21.0 months) with combination therapy (p = 0.98); OS 18.5 months (95% CI 11.8–24.5 months) versus 18.9 months (95% CI 16.0–23.7 months) (p = 0.79). An interim analysis (SEQTEST) showed that the null hypothesis could already be excepted, and no significant difference between both study arms was expected if inclusion would be completed. The incidence of grade 3–4 infections and gastrointestinal side-effects was numerical higher in the carboplatin arm (p = 0.056). Conclusion This early terminated study suggests no benefit from the addition of carboplatin to docetaxel re-treatment in patients with mCRPC, whereas the combination resulted in more toxicity. Re-treatment with docetaxel monotherapy appears to be feasible, save and effective for patients with mCRPC and an initial good response to docetaxel. Trial registration NTR3070.
V2 信仰 声望 18 2020-07-15 18:11:42 上传
Combining high dose external beam radiotherapy with a simultaneous integrated boost to the dominant intraprostatic lesion: Analysis of genito-urinary and rectal toxicity
Abstract Background and purpose Local recurrences after radiotherapy are dose-dependent and occur in the dominant intraprostatic lesion (DIL). The purpose of this study was to evaluate the impact of a simultaneous integrated boost (SIB) to the magnetic resonance imaging (MRI)-defined DIL on toxicity. Materials and methods Four-hundred and ten patients were treated with intensity-modulated radiotherapy. A median dose of 78 Gy was prescribed to the prostate. A SIB of 82 Gy to the DIL was performed in 225 patients (SIB+). Genitourinary and rectal toxicity on fixed time points up to 8 years were compared between SIB− (185 patients) and SIB+ patients. Chi-square, Fisher’s exact and Kaplan–Meier statistics were applied. With a median follow up of 72 months, the six-year actuarial risk of genitourinary and rectal toxicity grade ⩾ 2 was 31% and 12% respectively. The actuarial risk of developing toxicity and incidence of symptoms at fixed time points were not increased with a SIB. Conclusion Performing a SIB did not increase genitourinary or rectal toxicity up to 8 years’ follow-up.
V2 王福幸 声望 1 生物化学与分子生物学 2020-07-15 18:02:14 上传
Blinded double reading yields a higher programme sensitivity than non-blinded double reading at digital screening mammography: A prospected population based study in the south of The Netherlands
Abstract Purpose To prospectively determine the screening mammography outcome at blinded and non-blinded double reading in a biennial population based screening programme in the south of the Netherlands. Methods We included a consecutive series of 87,487 digital screening mammograms, obtained between July 2009 and July 2011. Screening mammograms were double read in either a blinded (2nd reader was not informed about the 1st reader’s decision) or non-blinded fashion (2nd reader was informed about the 1st reader’s decision). This reading strategy was alternated on a monthly basis. Women with discrepant readings between the two radiologists were always referred for further analysis. During 2 years follow-up, we collected the radiology reports, surgical correspondence and pathology reports of all referred women and interval breast cancers. Results Respectively 44,491 and 42,996 screens had been read either in a blinded or non-blinded fashion. Referral rate (3.3% versus 2.8%, p < 0.001) and false positive rate (2.6% versus 2.2%, p = 0.002) were significantly higher at blinded double reading whereas the cancer detection rate per 1000 screens (7.4 versus 6.5, p = 0.14) and positive predictive value of referral (22% versus 23%, p = 0.51) were comparable. Blinded double reading resulted in a significantly higher programme sensitivity (83% versus 76%, p = 0.01). Per 1000 screened women, blinded double reading would yield 0.9 more screen detected cancers and 0.6 less interval cancers than non-blinded double reading, at the expense of 4.4 more recalls. Conclusion We advocate the use of blinded double reading in order to achieve a better programme sensitivity, at the expense of an increased referral rate and false positive referral rate.
V1 申晓强 声望 2 生物工程 2020-07-15 18:01:10 上传
The impact of bevacizumab on health-related quality of life in patients treated for recurrent glioblastoma: Results of the randomised controlled phase 2 BELOB trial
Abstract Background The BELOB study, a randomised controlled phase 2 trial comparing lomustine, bevacizumab and combined lomustine and bevacizumab in patients with recurrent glioblastoma, showed that the 9-month overall survival rate was most promising in the combination arm. Here we report the health-related quality of life (HRQoL) results, a secondary trial end-point. Methods HRQoL was measured at baseline and every 6 weeks until progression using the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and brain module (QLQ-BN20). HRQoL was assessed over time for five preselected scales (global health (GH), physical (PF) and social functioning (SF), motor dysfunction (MD) and communication deficit (CD)). Moreover, mean changes in HRQoL from baseline until progression were determined. Results 138/148 patients with at least a baseline HRQoL assessment were analysed. Over time, HRQoL remained relatively stable in all treatment arms for all five scales, at least during the first three treatment cycles. More than half (54–61%) of the patients showed stable (<10 point change) or improved (⩾10 point change) HRQoL during their progression-free time, except for SF (43%), irrespective of treatment arm. Deterioration of mean HRQoL was most profound at disease progression for all scales except SF, which deteriorated earlier in disease course. Compared to baseline, 40% of patients had clinically relevant (⩾10 points) worse GH, PF and SF, while 44% and 31% had increased MD and CD at disease progression, irrespective of treatment arm. Conclusions Bevacizumab, whether or not in combination with lomustine, did not negatively affect HRQoL in patients treated for recurrent glioblastoma in this randomised study.