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1.

Background

Overexpression of periostin (POSTN) is associated with prostate cancer (PCa) aggressiveness. We investigated the prognostic significance of POSTN expression in tumor biopsy samples of patients with PCa.

Methods

We scored POSTN expression by immunohistochemistry analysis on 215 PCa biopsy samples using an anti–POSTN-specific antibody. A total immunoreactive score (T-IRS) was calculated by adding the POSTN staining scores of stromal and epithelial tumor cells. Prostate-specific antigen (PSA) progression/recurrence-free survival (PFS), radiographic progression/recurrence-free survival (rPFS), and overall survival (OS) were the study end points.

Results

A total of 143 patients received therapy with radical attempt, whereas 72 had locally advanced or metastatic disease and received hormone therapy alone. Median T-IRS was 9 and 12 (range, 0-20), respectively (P = .001). Overall, we found a weak positive correlation of T-IRS with prebiopsy PSA levels (r = 0.166, P = .016) and Gleason score (r = 0.266, P < .000). T-IRS ≥ 8 independently predicted for shorter PSA-PFS and OS (hazard ratio [HR] [95% confidence interval (CI)] ≥ 8 versus < 8: 1.50 [1.06-2.14], P = .024 and 1.92 [1.20-3.07], P = .007, respectively). In the subgroup analysis, the association between T-IRS and patient outcome was retained in patients who received therapy with radical attempt (HR [95% CI] ≥ 8 vs. < 8: rPFS: 2.06 [1.18-3.58], P = .01; OS: 2.36 [1.24-4.50], P = .009) and in those with low to intermediate Gleason scores (HR [95% CI] ≥ 8 vs. < 8: PSA-PFS: 1.65 [1.06-2.59], P = .028; rPFS: 2.09 [1.14-3.87], P = .018; OS: 2.57 [1.31-5.04], P = .006).

Conclusion

POSTN T-IRS on PCa biopsy samples independently predicted the risk of recurrence, progression, and death in patients with localized disease and in those with low to intermediate Gleason scores.  相似文献   

2.

Background

To investigate the clinical outcomes in patients with high-risk prostate cancer (PCa) treated with neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP).

Patients and Methods

Our NCHT protocol involved complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) plus estramustine phosphate (560 mg). NCHT was provided to 60 patients with PCa before RP, and we compared the clinical and pathologic outcomes with those of 349 patients with high-risk PCa who underwent RP alone using propensity score matching. The data for those who underwent RP alone were obtained from the Michinoku Japan Urological Cancer Study Group database.

Results

In the NCHT group, 10.0% experienced pathologic complete response, 3.3% had positive surgical margins, and 13.3% developed severe complications (Clavien-Dindo grade III or higher) after RP. The median follow-up duration was 42.5 months, and the 5-year biochemical recurrence (BCR)-free survival was 60.1%. In multivariate analysis, pN+ was an independent prognostic factor for BCR (hazard ratio = 5.251, 95%CI 1.300-21.201; P = .020). In propensity score matching, the BCR rate in the NCHT group was significantly lower than that in the RP alone group (P = .021). In subgroup analyses, the BCR rate in patients with a single high-risk factor was significantly lower in the NCHT group than in the RP-alone group (P = .027).

Conclusion

NCHT before RP can reduce the risk of BCR in patients with high-risk PCa, particularly if a single high-risk factor is present. However, the potential for perioperative complications should be considered.  相似文献   

3.

Background

We retrospectively assessed the clinical significance of the Prostate Imaging Reporting and Data System (PI-RADS), version 2, criteria based on biparametric magnetic resonance imaging (bp-MRI), together with the International Society of Urological Pathology (ISUP) grade, for predicting biochemical recurrence (BCR) after radical prostatectomy.

Materials and Methods

The data from 126 patients who had undergone radical prostatectomy were retrospectively analyzed. The prognostic significance of the PI-RADS v2 score based on bp-MRI was assessed with other clinical factors, including the ISUP grade. We defined a positive PI-RADS and ISUP score as ≥ 4 and ≥ 3, respectively. Statistical analysis was performed using Cox proportional hazard models, logistic regression analysis, and the Kaplan-Meier method.

Results

The median age and median prostate-specific antigen level were 66 years and 7.96 ng/mL, respectively. The number of positive PI-RADS scores was 106 (84.1%) and the number of positive ISUP grade scores was 71 (56.3%). PI-RADS ≥ 4 (P = .0031) and ISUP ≥ 3 (P = .070) were the 2 independent prognostic factors predictive of BCR. A positive PI-RADS score was related to tumor volume (P = .014), and a positive ISUP score was related to prostate-specific antigen level (P = .043), extraprostatic extension (P = .029), and Gleason upgrading (P < .0001). After stratifying patients into risk groups according to PI-RADS and ISUP positivity, the poor-risk group (PI-RADS and ISUP grade positive) showed significantly worse BCR-free survival compared with that of the favorable- and intermediate-risk groups (P < .0001), with a median survival difference of 21 months.

Conclusion

Biparametric PI-RADS v2 and ISUP grade criteria predicted for BCR after radical prostatectomy. PI-RADS v2 combined with the ISUP grade might be helpful in choosing the treatment modality of patients with localized prostate cancer.  相似文献   

4.

Objectives

To describe mortality, cause of death, and temporal trends in clinicopathological parameters with up to 20 years of follow-up in a nationwide cohort of prostate cancer (PCa) patients who underwent radical prostatectomy (RP).

Materials and methods

A total of 6857 patients with PCa treated with RP at six different hospitals in Denmark between 1995 and 2011. Data were extracted from the nationwide DaPCa database. Histopathology reports from the RP specimens were manually reviewed. Date and cause of death were obtained from national registries and cross-checked in patient files.The cumulative incidence of PCa specific mortality (PCSM) was analysed with the Aalen-Johansen method for competing risks with non-PCa death as a competing event. Risk of PCSM was analysed in a multivariate Cox regression model using age, preoperative PSA level, surgical margin status, RP Gleason score (GS), pathological T-category, and N-category as explanatory variables.

Results

The median follow-up was 6.4 years. Significant temporal changes in clinicopathological parameters were observed. During the study period, median age at surgery increased from 61.4 to 64.8 years and median preoperative PSA declined from 12.0 to 8.0 ng/ml. The proportion of men with pT2 PCa increased from 65% to 75% whereas the proportion of pT3 cancers decreased from 28% to 25%. The percentage of men with positive surgical margins decreased from 37% to 20%. During follow-up, 644 patients died, whereof 189 (29.3%) died from PCa. The cumulative incidence of PCSM and other-cause mortality after 15 years was 10.3% (95% CI 8.0–12.7) and 18.2% (95% CI 15.4–20.9), respectively. In a multivariate analysis, RP GS (P ≤ 0.001) and pT-category (P ≤ 0.001) were significantly associated with the risk of PCSM. Compared with GS ≤6, both GS +4 (HR 1.47), GS 4 + 3 (HR 2.32), GS 8 (HR 4.8) and GS 9 or 10 (HR 5.26) significantly increased the risk of PCa death. T3a PCa and T3b/T4 was also a significant predictor of PCSM with an increased risk of PCa death compared with pT2 of 2.24 and 4.5, respectively.

Conclusions

In a complete national cohort of men treated with RP during a 17-year period, we described the incidence of mortality after RP and predictors of PCSM. We demonstrated that RP GS and pT-category are the most significant predictors of PCa mortality. We found that an increasing proportion of men undergo RP for low-risk PCa suggesting that early detection of PCa is indeed undergoing in Denmark despite national recommendations. The Danish national results seem to concur with findings from international single- and multi-institutional reports.  相似文献   

5.

Introduction

Patients with ultracentral lung tumors, whose planning target volume directly contacts or overlaps the proximal bronchial tree, trachea, esophagus, pulmonary vein, or pulmonary artery, may be at higher risk of toxicity when treated with stereotactic body radiotherapy (SBRT). We reviewed the outcomes and toxicities of ultracentral lung tumors and compared the results with central lung tumors.

Patients and Methods

A review of our institutional prospective database of patients treated with lung SBRT from January 2006 to December 2015 was conducted. Patients with central tumors (RTOG 0813 definition) and ultracentral tumors were included.

Results

In total, 180 central and 26 ultracentral tumors were analyzed. The majority of patients received 60 Gy in 8 fractions (53.9%) or 48 Gy in 4 fractions (29.1%). The rates of any grade 2 or higher toxicity were 8.4% (n = 16) in the central group and 7.9% (n = 2) in the ultracentral group (P = .88). There were no observed grade 4 or 5 toxicities. In the nonmetastatic primary lung cancer cohort (n = 182), the median overall survival was 39.4 months versus 23.8 months (P = .40) and cause-specific survival was 55.5 months versus 28.2 months (P = .34) for central and ultracentral tumors, respectively. The 2-year cumulative local, regional, and distant failure rates were 3.3% versus 0 (P = .36), 9.1% versus 5.0% (P = .5), and 17.7% versus 18.7% (P = .63) in the central and ultracentral groups, respectively.

Conclusion

In our experience, with strict adherence to planning parameters, SBRT to ultracentral tumors resulted in effective local control and no excessive risk of toxicity compared to central tumors.  相似文献   

6.

Background

African-American (AA) men have the greatest incidence of and disease-specific mortality from prostate cancer of any racial group. Although encouraging oncologic and functional outcomes have been reported with prostate cancer cryotherapy, little is known about how ethnicity can potentially affect the oncologic outcomes of primary cryotherapy. We report the oncologic outcomes of primary cryotherapy in AA patients through a matched-pair analysis.

Patients and Methods

A 1:2 (AA to non-AA) cohort of patients was designed using the Cryo-On-Line Data Registry. The 2 arms were matched for patient age, prostate-specific antigen level, Gleason score, and prostate volume. The oncologic outcome was defined in terms of the biochemical recurrence (BCR) rates after primary cryoablation using Phoenix criteria. The results of “for-cause” post-treatment biopsies and the BCR-free survival rates were also analyzed between the 2 groups.

Results

The 1:2 cohort of AA and non-AA men in the present study included 109 and 218 men, respectively. Their median age (69 vs. 71 years; P = .71), median prostate-specific antigen level (6.5 vs. 6.8 ng/mL; P = .95), median prostate volume (32 vs. 30 cm3; P = .31), Gleason score distribution (P = .97), and prostate cancer risk group (P = .12) were similar statistically. The median postoperative follow-up period was also comparable between the 2 groups (AA, 32 months vs. non-AA, 27 months; P = .52). The BCR rates were similar between the AA and non-AA men (14% vs. 17%; P = .52). Likewise, the rate of positive “for-cause” prostate biopsy findings was similar between the 2 groups (AA vs. non-AA, 25% vs. 36%; P = .44). Furthermore, the 5-year biochemical relapse-free survival rates were comparable for the AA and non-AA patients (74% vs. 71%; P = .37).

Conclusion

When matched for tumor characteristics, cryotherapy as a treatment modality for primary, clinically localized prostate cancer offers men of African-American descent similar oncologic outcomes to those of non-AA men.  相似文献   

7.

Background

To compare oncologic outcomes of different definitive treatment (DT) modalities in a cohort of patients with prostate cancer (PCa) after active surveillance (AS).

Methods

We identified 237 patients with National Comprehensive Cancer Network (NCCN) low- and intermediate-risk prostate cancer diagnosed from 1990 to 2012 who did not undergo immediate DT within 12 months of diagnosis (ie, AS patients as well as watchful waiting and those refusing DT). Charts were examined for clinical/pathologic data and type of DT: surgery (RP), radiation including brachytherapy (XRT), cryotherapy, and androgen deprivation therapy monotherapy (ADT). The impact of DT on oncologic outcomes of biochemical recurrence (BCR), metastasis, disease-specific (DSS), and overall survival (OS) was examined with the Cox proportional hazards model, along with the Kaplan-Meier method and log-rank test.

Results

After median time on AS of 63.4 months, 40% of patients underwent DT: 47% XRT, 28% RP, 14% ADT, and 11% cryotherapy. On multivariable analysis, the use of XRT predicted higher BCR (hazard ratio [HR] 6.1, P = .001) and worse overall mortality (HR 2.1, P = .03) compared with other treatments, controlling for age, Charlson Comorbidity Index (CCI), stage, Gleason score, and NCCN risk category. Median follow-up was 71.7 months. On Kaplan-Meier analysis, 10-year OS was superior for RP versus XRT among patients with prostatic specific antigen (PSA) velocity >2.0 ng/mL/y.

Conclusions

Low- and intermediate-risk patients with PCa who progress to DT after AS may be inadequately treated with radiation therapy compared with other DT modalities, especially when pretreatment PSA velocity is > 2 ng/mL/y.  相似文献   

8.

Background

Smoking increases the risk of developing renal cell carcinoma (RCC) but the effect of tobacco consumption on survival outcome of patients with metastatic RCC (mRCC) treated with targeted therapies has not been well characterized.

Patients and Methods

The primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). Patients with mRCC were categorized as current, former, and nonsmokers at the time of starting targeted therapy. Smoking data from 1980 patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium (IMDC) from 12 international cancer centers.

Results

Although former and nonsmokers had comparable OS times (23.8 vs. 23.4 months; P = .898), current smokers had significantly shorter OS (16.1 months; P < .001) than nonsmokers. Current but not former smoking status was an independent poor prognosis factor (hazard ratio [HR], 1.3; P = .002) when adjusted for the IMDC risk criteria. Each pack-year increased the risk of death by 1% (HR, 1.01; P = .036). The duration of first-line therapy response was not different and was 7.7 months versus 7.5 months versus 6.4 months in never, former (P = .609), and current smokers (P = .839), respectively.

Conclusion

Active smoking is associated with diminished OS in mRCC patients treated with targeted therapy agents. However, patients who quit smoking returned to a similar risk of death from RCC compared with patients who never smoked. Smoking cessation should be a counseling priority among mRCC patients receiving targeted agents and smoking should be considered as a confounding factor in major clinical trials.  相似文献   

9.

Purpose

Although the administration of trastuzumab has improved the survival of human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, resistance remains a major clinical obstacle. We retrospectively evaluated the association of HER2 polymorphisms, tobacco use and alcohol consumption with disease-free survival (DFS) in HER2-positive breast cancer patients.

Patients and Methods

Clinicopathologic and survival data (median follow-up, 7.4 years) were collected from medical records for 236 nonmetastatic trastuzumab-treated HER2-positive breast cancer patients. Tobacco and alcohol consumption were assessed using validated questionnaires, and HER2 polymorphisms (Ile655Val and Ala1170Pro) were determined by TaqMan assay. Multivariate Cox proportional hazard models were used to analyze DFS.

Results

Compared to nonsmokers, patients who smoked before breast cancer diagnosis showed a worse DFS (hazard ratio [HR], 2.63, P = .001), and this association was stronger among patients who smoked > 20 cigarettes per day or who spent more than 2 decades smoking before their diagnosis (HR, 3.65, P = .01, and HR, 3.19, P = .002, respectively). Smoking during trastuzumab treatment was associated with DFS, but only among patients with estrogen receptor–negative tumors (HR, 4.49, P = .02). Compared to nondrinkers, patients who consumed alcohol before breast cancer diagnosis had a significantly better DFS (HR, 0.56, P = .03). No association was observed between alcohol consumption during trastuzumab treatment and DFS. Concerning HER2 polymorphisms, patients with Ile/Val or Val/Val genotype had a significantly worse DFS than those with the Ile/Ile genotype (HR, 4.96, P = .01).

Conclusion

Tobacco and alcohol consumption as well as HER2 Ile655Val polymorphism could influence trastuzumab response. These results need to be confirmed in a larger cohort study.  相似文献   

10.

Background

The optimal number of high-dose cytarabine (HDAC) consolidation cycles before allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia is not fully standardized.

Patients and Methods

This study evaluated the impact of HDAC consolidation cycles before allogeneic HCT in 194 patients with acute myeloid leukemia in first complete remission between 1998 and 2014. The patients were reclassified into 3 groups—no consolidation (C0, n = 20), 1 consolidation (C1, n = 115), and ≥ 2 consolidations (C2, n = 59)—by pre-HCT consolidation cycle.

Results

The 3-year relapse-free survival rates was 45.9%, 66.9%, and 73.3% for the C0, C1, and C2 groups, respectively (P = .064), while the 3-year overall survival rates were 35.0%, 55.2%, and 67.5%, respectively (P = .106). The cumulative incidence of acute graft-versus-host disease (GVHD) was higher in the C2 group (38.7%) than in the C0 (22.2%) or C1 (17.7%) group (P = .018). However, the incidence of chronic GVHD showed no difference between the groups. Multivariate analysis for overall survival revealed the following independent factors: adverse cytogenetic risk (hazard ratio [HR] = 1.84, P = .046), C2 versus C0 (HR = 0.41, P = .037), pre-HCT status beyond CR1 versus CR1 (HR = 5.78, P < .001), and presence of chronic GVHD (HR = 0.45, P = .004).

Conclusion

One or two cycles of HDAC consolidation therapy led to better subsequent HCT outcomes compared to the no–consolidation therapy group.  相似文献   

11.

Background

Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer.

Patients and Methods

We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype.

Results

Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P < .001), high tumor grade (P = .012), and HER2 positivity (P < .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P < .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P < .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P < .001), and lung metastasis (P < .001).

Conclusion

Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome.  相似文献   

12.

Background

The prognostic impact of perineural invasion (PNI) in patients with esophageal cancer who receive neoadjuvant chemoradiotherapy (nCRT) remains unclear.

Methods

A thorough pathological review of PNI was performed on post-nCRT esophagectomy specimens obtained from non-ypT0 patients with esophageal squamous cell carcinoma (ESCC). When PNI was identified, it was classified according to the presence or absence of penetration through the nerve sheath (i.e., PNI surrounding the nerve sheath [PNI-SS] versus PNI penetrating through the nerve sheath [PNI-TS]). The impact of PNI on overall survival (OS) was assessed in combination with clinical and pathological risk factors.

Results

A total of 177 eligible patients were identified between 1998 and 2008. PNI was identified in 43.5% (77/177) of participants. Of them, 33 and 44 had PNI-SS and PNI-TS, respectively. The 5-year OS rate of patients with PNI-TS was significantly lower (6.7%) than that observed in those without PNI (30.6%, P < 0.001). However, the 5-year OS observed in the latter group did not differ significantly from that of patients with PNI-SS (26%, P = 0.68). Multivariate analysis identified PNI-TS (hazard ratio [HR] = 1.965, P = 0.02), LVI (HR = 1.514, P = 0.048), and ypN2 stage (HR = 2.39, P = 0.007) as independent adverse prognostic factors for OS.

Conclusions

The presence of PNI-TS after nCRT is associated with poor survival. A thorough assessment of distinct PNI patterns (i.e., PNI-TS versus PNI-SS) should be part of the routine post-nCRT histopathological work-up of ESCC patients.  相似文献   

13.

Background

We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic.

Materials and Methods

We performed a retrospective cohort study by reviewing the data from 2527 women (4.5% BRCA mutation carriers, 72.2% high risk, and 23.3% intermediate risk using the Modena criteria and the Tyrer-Cuzick model).

Results

We did not find any specific feature of breast cancer (infiltration, hormone receptor and HER2 status, onset before age 35 years, multiple diagnoses) in the CHC users (P > .05). Only 2.0% of women used a preparation with ≥ 50 μg of ethinylestradiol (EE). The use of CHCs was not associated with an increased risk of breast cancer (cumulative hazard: never used, 0.17; CHC users, 0.20; P = .998), regardless of the duration of use (cumulative hazard: never used, 0.17, used < 5 years, 0.20; used 5-10 years, 0.14; used > 10 years, 0.25; P = .414). This was confirmed for the different risk groups when interacted in a Cox proportional hazard regression model. The EE dose did not influence the risk of BC (cumulative hazard, 2.37; 95% confidence interval, 0.53-10.1; never used, 0.18; EE < 20 μg used, 0.04; EE ≥ 20 μg used, 0.16; P = .259). The types of progestins used might influence the risk, with some, such as gestodene (P = .028) and cyproterone acetate (P = .031), associated with an even greater reduced risk.

Conclusions

CHC use does not increase the risk of BC in a population of women with a family history, encouraging CHC use in this group of women.  相似文献   

14.

Background

The neutrophil-to-lymphocyte ratio (NLR), which reflects the cancer-induced systemic inflammation response, has been proposed as a risk factor for poor long-term prognosis in cancer. We investigated the prognostic role of the NLR and the relationship between the NLR and TNM stage in pancreatic ductal adenocarcinoma (PDAC) patients following curative resection.

Methods

One-hundred thirty-eight consecutive patients with resected PDAC were enrolled between 2004 and 2014. Univariate and multivariate analyses identified variables associated with overall survival (OS) and recurrence-free survival (RFS). Patients were stratified according to the NLR, with an NLR cut-off value of 2.2 being estimated by receiver operating characteristic curve.

Results

Compared to patients with a low NLR (≤2.2), those with a high preoperative NLR (>2.2) had worse OS and RFS (P = 0.017, P = 0.029, respectively). For early-stage tumors, tumor size ≥20 mm and a high NLR were independent risk factors for poor OS (hazard ratio (HR): 3.255, 95% confidence interval (CI): 1.082–9.789, P = 0.036; HR: 3.690, 95% CI: 1.026–13.272, P = 0.046, respectively) and RFS (HR: 3.575, 95% CI: 1.174–10.892, P = 0.025; HR: 5.380, 95% CI: 1.587–18.234, P = 0.007, respectively). The NLR was not correlated with prognosis in patients with advanced stages.

Conclusions

An elevated preoperative NLR was an important prognosticator for early TNM stage PDAC. The NLR, which is calculated using inexpensive and readily available biomarkers, could be a novel tool for predicting long-term survival in patients, especially those with early stage PDAC.  相似文献   

15.

Background

Proteasome inhibitors used in the treatment of multiple myeloma act primarily through the disruption of intrinsic cellular protein quality maintenance, resulting in proteotoxic stress, cellular dysfunction, and, ultimately, cell death. We assessed whether evidence has shown off-target myocardial dysfunction related to the administration of bortezomib-based chemotherapy for multiple myeloma.

Patients and Methods

Patients aged 18 to 70 years who were free of significant cardiovascular disease were included. They underwent evaluations before and after each dose of bortezomib to assess for clinical, subclinical, and transient cardiotoxicity using echocardiography and serum biomarker measurement. Cardiac magnetic resonance imaging was performed at 3 separately defined intervals. The primary modality for determining subclinical myocardial dysfunction was echocardiographic assessment of the global longitudinal strain (GLS).

Results

Eleven patients (7 men) with an average age of 55 years were included. No evidence of cumulative myocardial dysfunction was found using echocardiographic markers, primarily GLS (average change in absolute GLS, ?1.17; P = .064). Additionally, no echocardiographic evidence of transient cardiotoxicity was found. The left ventricular ejection fraction (LVEF) also did not show any significant changes (ΔLVEF, ?2.17%; P = .15). Magnetic resonance imaging confirmed no changes in structure or function (ΔLVEF, ?2.6%; P = .54) and extracellular volume fraction (Δ = 2%; P = .46). The serum biomarker levels also did not change significantly over time.

Conclusion

We did not observe cardiotoxicity from bortezomib-based chemotherapy despite very intensive evaluation with multiple modalities. Neither cumulative nor transient alterations were found in our metrics, suggesting that bortezomib is safe from a cardiovascular standpoint for patients free of cardiovascular disease.  相似文献   

16.

Introduction

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis classification system (TNM) staging manual has been updated and provides more specified stage grouping for prostate cancer (PCa). We aimed to validate the updated AJCC stage groups for PCa using a radical prostatectomy (RP) cohort.

Patients and Methods

We analyzed the data of 3032 patients previously treated with RP for localized PCa. We stratified patients into stage groups according to the 8th edition of the AJCC manual and compared biochemical recurrence (BCR)-free survival using Kaplan-Meier analyses.

Results

There were 217 patients in stage group I, 33 in IIA, 1101 in IIB, 535 in IIC, 129 in IIIA, 781 in IIIB, and 236 in IIIC. There were no significant differences in BCR-free survival between stage groups IIC and IIIA (P = .875). Subsequently, the low–Gleason score (GS) IIIA subgroup (GS ≤ 3 + 4, P = .025) showed superior BCR-free survival than the IIC group, and the high-GS IIIA subgroups (GS ≥ 4 + 3, P = .004) showed a poorer BCR-free survival than the IIC group. Furthermore, there were no significant differences between groups I and IIA (P = 330) and between groups IIA and IIB (P = .942). Our new staging system provided a better ability to discriminate the prognosis of each group. However, our study has several limitations, such as retrospective design, relatively short follow-up period, and need for further validation.

Conclusion

The current AJCC prognostic groups show some contradictory results, particularly concerning prognosis of the IIC and IIIA groups. We suggest that GS be given more weight than serum prostate-specific antigen level in stage group stratification.  相似文献   

17.
18.

Background

Resistance mechanisms in the androgen receptor (AR) signaling pathway remain key drivers in the progression to castration-resistant prostate cancer (CRPC) and relapse under antihormonal therapy.

Materials and Methods

We evaluated the circulating AR gene copy number (CN) gain using droplet digital polymerase chain reaction in 21 control and 91 prostate cancer serum samples and its prognostic and therapeutic implications in prostate cancer.

Results

In CRPC, AR CN gain was associated with faster progression to CRPC (P = .026), a greater number of previous treatments (P = .045), and previous chemotherapy (P = .016). Comparing patients with and without CN gain, the median progression-free survival (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004), and the median overall survival (OS) was 7 months versus 20.9 months (P = .020). In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus 6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The presence of more AR copies correlated with shorter androgen deprivation (P = .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039) therapy.

Conclusion

Circulating AR CN gain predicts for a poor prognosis in CRPC. It is a promising biomarker predetermining rapid CRPC progression and predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is associated with multiple previous treatments and previous chemotherapy.  相似文献   

19.

Introduction

Lysosomal-associated membrane protein 1 (LAMP1) is a lysosomal and plasma membrane protein that contributes to tumor metastatic potential and differentiation.

Patients and Methods

We performed immunohistochemical staining to investigate LAMP1 protein expression levels in 122 diffuse large B-cell lymphoma (DLBCL) tumor samples and 45 reactive hyperplasia tissues. Correlations between LAMP1 expression, various clinicopathologic features, and patient prognosis were evaluated by univariate and multivariate analyses.

Results

LAMP1 expression was greater in the DLBCL tissues than in the reactive hyperplasia tissues. High LAMP1 expression was significantly associated with a high international prognostic index (score, 3-5; P = .023) and elevated lactate dehydrogenase level (P = .028). Moreover, high LAMP1 expression (P = .026), elevated serum lactate dehydrogenase level (P = .011), and high international prognostic index (P < .001) were independently associated with worse overall survival and progression-free survival.

Conclusion

These data provide the first evidence that LAMP1 expression is associated with a poor prognosis in patients with DLBCL.  相似文献   

20.

Introduction

C-reactive protein (CRP), a representative inflammatory marker, could serve as a biomarker in renal cell carcinoma because CRP is an important prognostic factor. However, its detailed mechanism remains unknown. This study showed that higher CRP levels correlated with the tumor immune microenvironment, which leads to a worse prognosis. These findings can help to clarify the underlying mechanisms between the presence of systemic inflammatory reaction and prognosis. The aim of this study is to investigate the association between tumor immune microenvironment and CRP in patients with renal cell carcinoma (RCC) to explore the underlying mechanisms between CRP level and prognosis.

Patients and Methods

Immunohistochemical measurement of CD4, CD8, CD163 (M2 macrophages), and Foxp3 (Regulatory T [Treg] cells) was performed in patients with clear-cell RCC (n = 111) treated with radical or partial nephrectomy at our institution. The association between immunohistochemical status and preoperative serum CRP level and cancer-specific survival (CSS) was analyzed.

Results

Thirty-three patients (30%) had a high CRP level (≥ 5.0 mg/L), and the CSS rate was significantly worse among these patients than among the remaining patients (P < .001). In patients with strong infiltration of CD8+, Foxp3+, or CD163+ cells, CRP levels were significantly higher (P = .041, P = .001, and P = .035, respectively), and CSS was significantly worse compared with patients with weak infiltration (P = .040, P = .026, and P < .001, respectively). In multivariate analysis, strong CD163+ cells infiltration (P = .001) as well as pathologic T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P < .001), and Fuhrman nuclear grade 4 (P = .003) were independent prognostic factors for CSS.

Conclusions

Infiltration of the immunosuppressive cells known as Tregs and M2 macrophages in the tumor microenvironment is associated with higher CRP and poor prognosis in patients with clear-cell RCC. CRP could reflect an immunosuppressive microenvironment.  相似文献   

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