V1 iamsujie 声望 1 微生物学与微生物工程系 2024-04-15 11:20:08 上传
The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies
Abstract Background Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). Methods HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables. Results In baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78–0.84]) and 21% in PREVAIL (HR 0.79 [0.76–0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84–0.93]) and 10% (HR 0.90 [0.86–0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies. Conclusion Several baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival.
V1 孟睿 声望 1 植物生物技术 2024-04-15 11:10:52 上传
Recurrent antibiotic exposure may promote cancer formation – Another step in understanding the role of the human microbiota?
Abstract Background Bacterial dysbiosis was previously described in human malignancies. In a recent animal model, tumour susceptibility was transmitted using faecal transplantation. Our aim was to evaluate possible association between antibiotic exposure and cancer risk. Methods We conducted nested case–control studies for 15 common malignancies using a large population-based electronic medical record database. Cases were defined as those with any medical code for the specific malignancy. Individuals with familial cancer syndromes were excluded. For every case, four eligible controls matched on age, sex, practice site and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Adjusted odds-ratios (AORs) and 95% confidence intervals (CIs) were estimated for each antibiotic type using conditional logistic regression. Results 125,441 cases and 490,510 matched controls were analysed. For gastro-intestinal malignancies, the use of penicillin was associated with an elevated risk of oesophageal, gastric and pancreatic cancers. The association increased with the number of antibiotic courses and reached 1.4 for gastric cancers associated with >5 courses of penicillin (95% CI 1.2–1.8). Lung cancer risk increased with the use of penicillin, cephalosporins, or macrolides (AOR for >5 courses of penicillin: 1.4 95% CI 1.3–1.6). The risk of prostate cancer increased modestly with the use of penicillin, quinolones, sulphonamides and tetracyclines. The risk of breast cancer was modestly associated with exposure to sulphonamides. There was no association between the use of anti-virals and anti-fungals and cancer risk. Conclusion Recurrent exposure to certain antibiotics may be associated with cancer risk in specific organ sites.
V2 水漾七七 声望 10 动物生物技术 2024-04-15 11:09:37 上传
The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy
Abstract Background and purpose The derived neutrophil–lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. Materials and methods 258 patients were randomised to receive dCRT ± cetuximab. Kaplan–Meier’s curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). Results An elevated pre-treatment dNLR ≥ 2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29–2.35], p < 0.001) and multivariable analyses (HR 1.64 [1.17–2.29], p = 0.004). Median OS was 36 months (95% CI 27.8–42.4) if dNLR < 2 and 18.4 months (95% CI 14.1–24.9) if dNLR ≥ 2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. Conclusions An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].
V2 目目 声望 6 生物科学与生物技术 2024-04-15 11:08:32 上传
Comparison of three moderate fractionated schedules employed in high-dose-rate brachytherapy monotherapy for clinically localized prostate cancer
Abstract Background Herein, we report the outcomes of 3 schedules of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy for localized prostate cancer. Patients and methods A total of 347 patients were treated with 45.5 Gy/7 fractions (n = 86; 45.5 Gy arm, median follow-up time 131 months), 49 Gy/7 fractions (n = 149; 49 Gy arm, 75.9 months), and 54 Gy/9 fractions (n = 112; 54 Gy arm, 68 months). Results The actuarial 5-year biochemical failure-free survival rates were 86.8%, 94.1%, and 88.5% (p = 0.2023) for the 45.5 Gy, 49 Gy, and 54 Gy arms in the high-risk group; 90.4%, 100%, and 97.4% (p = 0.0818) in the intermediate-risk group; and not available, 100%, and 100% in the low-risk group, respectively. The 5-year distant metastasis-free (and overall) survival rates were 94.4%, 98.2%, and 96.3% (100%, 92.8%, and 99.1%) for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5454 and p = 0.0028), respectively. At 5 years, accumulated incidence of grade ≥2 gastrointestinal toxicity was 1.2%, 2.7%, and 3.4% for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5605), respectively. For genitourinary toxicity, the 49 Gy arm showed a higher grade ≥2 toxicity of 20.5% than those observed in the 45.5 Gy (2.4%) and 54 Gy arms (10.1%). No grade 4 or 5 of either type of toxicity was detected. Conclusions The 3 schedules showed equivocal outcomes in each risk group, with different toxicity profiles. HDR-BT monotherapy with these schedules is an acceptable treatment option for localized prostate cancer.
V2 鹿小妮 声望 10 生物安全 2024-04-15 10:32:35 上传
Determinants for local tumour control probability after radiotherapy of anal cancer
Abstract Background and purpose Anal squamous cell carcinoma is primarily treated with radiotherapy (RT), but the optimal RT dose for anal tumours of different sizes is not known. The purpose of this study was to identify determinants for local tumour control probability (LTCP). Material and methods From a large Nordic database 901 patients who received RT for anal cancer between 2000 and 2007 were selected. LTCP was analysed in a series of uni- and multivariable regression analyses. Results Higher RT dose, female gender and addition of chemotherapy were associated with higher LTCP whereas increasing tumour size, tumour invasiveness (stage T4) and lymph node metastases (N+) were associated with lower LTCP. Male patients needed approximately 10 Gy higher RT dose than female patients for similar LTCP. The addition of chemotherapy corresponded to 5–10 Gy RT dose. Conclusions Our results basically support current guidelines recommending: (1) lower RT dose in small tumours (<4 cm), (2) higher RT dose larger tumours and in stages T4 and /or N+, (3) Chemo should be used in combination with RT. These results will hopefully constitute the basis for future trials, aiming at individualized RT dosing in patients with anal cancer.
V1 贾敏 声望 1 生物工程 2024-04-15 10:28:49 上传
Influence of inhomogeneous radiosensitivity distributions and intrafractional organ movement on the tumour control probability of focused IMRT in prostate cancer
Abstract Purpose To evaluate the influence of radioresistance and intrafractional movement on the tumour control probability (TCP) in IMRT prostate treatments using simultaneous integrated boosts to PSMA-PET/CT-delineated GTVs. Materials and methods 13 patients had PSMA-PET/CT prior to prostatectomy and histopathological examination. Two GTVs were available: GTV-PET and GTV-histo, which is the true cancer volume. Focused IMRT plans delivering 77 Gy in 35 fractions to the prostate and 95 Gy to PTV-PET were produced. For random portions of the true cancer volume, α and α/β were uniformly changed to represent different radiosensitivity reductions. TCP was calculated (linear quadratic model) for the true cancer volume with and without simulated intrafractional movement. Results Intrafractional movement increased the TCP by up to 10.2% in individual cases and 1.2% averaged over all cases for medium radiosensitivity levels. At lower levels of radiosensitivity, movement decreased the TCP. Radiosensitivity reductions of 10–20% led to TCP reductions of 1–24% and 10–68% for 1% and 5% affected cancer volume, respectively. There is no linear correlation but a sudden breakdown of TCPs within a small range of radiosensitivity levels. Conclusion TCP drops significantly within a narrow range of radiosensitivity levels. Intrafractional movement can increase TCP when the boost volume is surrounded by a sufficiently high dose plateau.
V4 萌小兔 声望 23 食品科学与工程 2024-04-15 10:20:03 上传
Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis
Abstract Background There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT. Methods Using our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge. Thus, we could determine the earliest opportunity for reliable meta-analysis and take account of unavailable trials in interpreting results. We searched multiple sources for trials comparing AAP plus ADT versus ADT in men with mHSPC. We obtained results for the primary outcome of overall survival (OS), secondary outcomes of clinical/radiological progression-free survival (PFS) and grade III–IV and grade V toxicity direct from trial teams. Hazard ratios (HRs) for the effects of AAP plus ADT on OS and PFS, Peto Odds Ratios (Peto ORs) for the effects on acute toxicity and interaction HRs for the effects on OS by patient subgroups were combined across trials using fixed-effect meta-analysis. Findings We identified three eligible trials, one of which was still recruiting (PEACE-1 (NCT01957436)). Results from the two remaining trials (LATITUDE (NCT01715285) and STAMPEDE (NCT00268476)), representing 82% of all men randomised to AAP plus ADT versus ADT (without docetaxel in either arm), showed a highly significant 38% reduction in the risk of death with AAP plus ADT (HR = 0.62, 95% confidence interval [CI] = 0.53–0.71, p = 0.55 × 10−10), that translates into a 14% absolute improvement in 3-year OS. Despite differences in PFS definitions across trials, we also observed a consistent and highly significant 55% reduction in the risk of clinical/radiological PFS (HR = 0.45, 95% CI = 0.40–0.51, p = 0.66 × 10−36) with the addition of AAP, that translates to a 28% absolute improvement at 3 years. There was no evidence of a difference in the OS benefit by Gleason sum score, performance status or nodal status, but the size of the benefit may vary by age. There were more grade III–IV acute cardiac, vascular and hepatic toxicities with AAP plus ADT but no excess of other toxicities or death. Interpretation Adding AAP to ADT is a clinically effective treatment option for men with mHSPC, offering an alternative to docetaxel for men who are starting treatment for the first time. Future research will need to address which of these two agents or whether their combination is most effective, and for whom.
V1 卫好唯 声望 1 动物资源科学 2024-04-15 09:57:39 上传
The addition of whole-body magnetic resonance imaging to body computerised tomography alters treatment decisions in patients with metastatic breast cancer
Abstract Aim Accurate evaluation of distribution of disease and response to systemic anti-cancer therapy (SACT) is important in the optimal management of metastatic breast cancer. Whole-body magnetic resonance imaging (WB-MRI) has increased accuracy over computerised tomography of the chest, abdomen and pelvis (CT-CAP) for detecting liver and bone disease, but its effect on patient management is largely unexplored. This study investigates the effects of using WB-MRI alongside CT-CAP on SACT decisions in standard clinical practice for patients with metastatic breast cancer. Methods Metastatic breast cancer patients who had undergone WB-MRI within 14 d of CT-CAP were studied. Data on distribution and extent of disease and SACT response assessment from original WB-MRI and CT-CAP reports were compared. Contemporaneous medical records provided data on therapy decisions at each time point. Results Analyses were performed on 210 pairs of WB-MRI and CT-CAP in 101 patients. In 53.3% of episodes, WB-MRI reported additional sites of disease not reported on CT-CAP. Differences in SACT assessment were found in 28.0% of episodes, most commonly due to progressive disease (PD) on WB-MRI being reported as stable disease on CT-CAP (18.9%). Discordant SACT assessments were less common in first-line SACT than in subsequent lines of SACT (15.0% versus 41.6%; p = 0.0102). In 34.7% of episodes when SACT was changed, PD had been reported on WB-MRI only. Conclusions SACT decisions in routine practice were altered by the use of WB-MRI. Further research is required to investigate whether earlier identification of PD by WB-MRI leads to improved patient outcomes.
V1 shell苏寒 声望 1 生物科学与生物技术 2024-04-15 09:54:26 上传
CT-based radiomic analysis of stereotactic body radiation therapy patients with lung cancer
Abstract Background Radiomics uses a large number of quantitative imaging features that describe the tumor phenotype to develop imaging biomarkers for clinical outcomes. Radiomic analysis of pre-treatment computed-tomography (CT) scans was investigated to identify imaging predictors of clinical outcomes in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). Materials and methods CT images of 113 stage I-II NSCLC patients treated with SBRT were analyzed. Twelve radiomic features were selected based on stability and variance. The association of features with clinical outcomes and their prognostic value (using the concordance index (CI)) was evaluated. Radiomic features were compared with conventional imaging metrics (tumor volume and diameter) and clinical parameters. Results Overall survival was associated with two conventional features (volume and diameter) and two radiomic features (LoG 3D run low gray level short run emphasis and stats median). One radiomic feature (Wavelet LLH stats range) was significantly prognostic for distant metastasis (CI = 0.67, q-value < 0.1), while none of the conventional and clinical parameters were. Three conventional and four radiomic features were prognostic for overall survival. Conclusion This exploratory analysis demonstrates that radiomic features have potential to be prognostic for some outcomes that conventional imaging metrics cannot predict in SBRT patients.
V1 杨驰 声望 0 2024-04-15 09:25:17 上传
Sporadic extra abdominal wall desmoid-type fibromatosis: Surgical resection can be safely limited to a minority of patients
Abstract Background To analyse the natural history of extra-abdominal wall desmoid-type fibromatosis (DF) and compare outcome in patients who underwent initial surgery with those who did not. Patients and methods All consecutive patients affected by primary sporadic extra-abdominal wall DF observed between January 1992 and December 2012 were included. Patients were divided into surgical (SG) or non-surgical groups (NSG) according to initial treatment. Relapse free survival was calculated for SG, and crude cumulative incidence (CCI) of switching to surgery or other treatments for NSG. Results 216 patients were identified, 94 in SG (43%), 122 in NSG (57%). A shift towards a more systematic use of a conservative approach (78% of all comers) was observed in the latter years (2006–2012), although a small proportion of patients (28%) had been offered the conservative strategy even in the early period (1992–2005). Median follow-up (FU) was 49 mo. (interquartile (IQ), 20–89 mo.), 76 months for SG and 39 months for NSG. 5-year relapse-free survival (RFS) for SG was 80% (95% confidence interval (CI), 72–89%). For the NSG, 5-year CCI of switching to surgery was 5% (95% CI: 1.7%, 14%), and 51% to other treatments (95% CI: 41%, 65%). 27 (20%) NSG patients underwent spontaneous regression. Conclusion A non-surgical approach to extra-abdominal wall DF allowed surgery to be avoided in the majority of patients. This approach can be safely proposed and surgery offered as an option in selected cases.