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1.
Elio Mazzone Felix Preisser Sebastiano Nazzani Zhe Tian Nicola Fossati Giorgio Gandaglia Andrea Gallina Denis Soulieres Derya Tilki Francesco Montorsi Shahrokh F. Shariat Fred Saad Alberto Briganti Pierre I. Karakiewicz 《Clinical genitourinary cancer》2019,17(2):105-113.e2
Background
Radical cystectomy (RC) may occasionally be performed in individuals with metastatic urothelial carcinoma of the bladder (mUCB). However, the role of lymph node dissection (LND) for such cases is unknown. Thus, we tested the effect of RC on cancer-specific mortality (CSM) and overall mortality in mUCB patients and the effect of LND and its extent on CSM.Patients and Methods
Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013), we identified patients with mUCB who underwent RC with or without LND or non-RC management. Kaplan-Meier analyses and multivariable Cox regression models (CRMs) were used, after propensity score matching. The number of removed nodes best predicting CSM was identified using cubic splines and then was tested in multivariable CRMs.Results
Of 2314 patients, 319 (13.8%) underwent RC. After 2:1 propensity score matching, CSM-free survival was 14 versus 8 months (P < .001), and overall mortality–free survival was 12 versus 7 months (P < .001) for, respectively, RC and non-RC patients. In multivariable CRMs, lower CSM (hazard ratio = 0.48; P < .001) and lower overall mortality (hazard ratio = 0.49; P < .001) rates were recorded in RC patients. LND status did not affect CSM-free survival (13 vs. 10 months; P = .1). Cubic splines-derived cutoff of ≥ 13 number of removed nodes showed better CSM-free survival (20 vs. 11 months; P = .02) and reduced CSM in CRMs (hazard ratio = 0.67; P = .02).Conclusion
Our study validates the survival benefit of RC in mUCB and highlights the importance of more extensive LND. These findings may corroborate the hypothesis of potential cytoreductive effect of surgery in the context of metastatic disease. 相似文献2.
Alp Tuna Beksac Mesude Bicak Ishan Paranjpe David J. Paulucci John P. Sfakianos Ketan K. Badani 《Clinical genitourinary cancer》2019,17(2):e314-e322
Background
Chromophobe renal cell carcinoma (chRCC) is known as an indolent tumor; however, mortality still occurs. We sought to determine the clinicopathologic and genomic factors associated with aggressive chRCC.Patients and Methods
Two different datasets were used to identify patients with clinical stage III and IV chRCC. Eighteen patients from The Cancer Genome Atlas (TCGA) database and 1693 patients from the American College of Surgeons National Cancer Database (NCDB) were used for analysis. From the TCGA, RNA-Seq expression analysis of 18,745 genes was conducted between the recurrent (n = 5; 27.8%) and nonrecurrent patients (n = 13; 72.2%). Biological significance was identified via pathway enrichment and gene function analyses. From the NCDB, Cox proportion hazards regression models were used to identify variables associated with overall survival (OS) at a median follow-up of 41.4 months.Results
Between the 2 groups, 2182 genes were differentially expressed. The most commonly overexpressed pathways were neuroactive ligand-receptor interactions and cytokine-cytokine receptor interactions. The most activated gene functions were cellular, metabolic, and multicellular organismal processes. In the NCDB, multivariable analysis, age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03-1.05; P < .001), TNM stage IV versus III (HR, 3.86; 95% CI, 2.98-5.00; P < .001), and positive surgical margin (HR, 1.68; 95% CI, 1.45-1.96; P < .001) were associated with worse OS at a median follow-up of 41.4 months. Five-year OS was significantly lower for stage IV patients compared with stage III patients (80.0% vs. 29.9%; P < .001).Conclusions
Patients with recurrent chRCC demonstrated a differential gene expression of specific biochemical pathways. Clinical parameters associated with worse OS included age, stage, and positive surgical margin. 相似文献3.
Background
Studies of various prostate cancer patient cohorts found men receiving external-beam radiotherapy (EBRT) had higher mortality than men undergoing radical prostatectomy (RP). Conversely, a recent clinical trial showed no survival differences between treatment groups. We used the National Cancer Data Base (NCDB) to evaluate overall survival in intermediate-risk (T2b-T2c or Gleason 7 [grade group II or III] or prostate-specific antigen 10-20 ng/mL) prostate cancer patients undergoing EBRT with or without androgen deprivation therapy (ADT), RP, or no initial treatment.Patients and Methods
We analyzed 268,378 men with intermediate-risk prostate cancer from 2004 to 2012. Kaplan-Meier estimates and multivariable Cox proportional hazards models were used to compare survival between treatments.Results
After adjusting for patient and facility covariables, men receiving no initial treatment averaged greater adjusted mortality risk than men receiving EBRT (hazard ratio [HR], 1.71; 95% confidence interval [CI] 1.62-1.80; P < .001), EBRT + ADT (HR, 1.73; 95% CI 1.64-1.81; P < .001), or RP (HR, 4.18; 95% CI 3.94-4.43; P < .001). Men undergoing RP had significantly lower adjusted mortality risk than men receiving either EBRT (HR, 0.41; 95% CI 0.39-0.43; P < .001) or EBRT + ADT (HR, 0.41; 95% CI 0.39-0.43; P < .001). No difference was observed between men receiving EBRT or EBRT + ADT (HR, 1.01; 95% CI 0.97-1.05; P = .624).Conclusion
Men treated with RP experienced significantly lower overall mortality risk than EBRT with or without ADT and no treatment patients, regardless of patient, demographic, or facility characteristics. The results are limited by the lack of cancer-specific mortality in this database. 相似文献4.
Mounsif Azizi Dominic H. Tang Daniel Verduzco Charles C. Peyton Juan Chipollini Zhigang Yuan Braydon J. Schaible Jun-Min Zhou Peter A. Johnstone Anna Giuliano Jasreman Dhillon Philippe E. Spiess 《Clinical genitourinary cancer》2019,17(1):e80-e91
Purpose
To assess the prognostic value of PI3K-AKT-mTOR signaling pathway up-regulation in a contemporary cohort of penile squamous-cell carcinoma (PSCC) patients.Patients and Methods
Tissue microarrays were constructed for 57 patients with invasive PSCC treated at our institution between 2000 and 2013. Immunohistochemical staining was performed for PTEN, AKT, and S6. Human papillomavirus (HPV) in-situ hybridization for high-risk subtypes was also performed. Biomarker expression was evaluated by a semiquantitative H score. Overall survival, disease-specific survival and recurrence-free survival stratified by biomarker expression (low vs. high) were estimated by the Kaplan-Meier method. Multivariable Cox regression models were used to determine predictors of mortality and recurrence.Results
HPV in-situ hybridization was positive in 23 patients (40%). PTEN was down-regulated in 43 patients (75%), while phosphorylated-AKT (p-AKT) and phosphorylated-S6 (p-S6) were up-regulated in 27 (47%) and 12 patients (21%), respectively. In multivariable Cox regression models, patients with low expression of p-AKT had an increased risk of recurrence (hazard ratio [HR] = 3.95; 95% confidence interval [CI], 1.47-10.59; P = .02), while those with low expression of p-S6 had an increased risk of overall mortality (HR = 6.15; 95% CI, 1.55-24.36; P = .01). HPV status was an independent predictor of overall survival (HR = 6.99; 95% CI, 2.42-20.16; P < .001) and disease-specific survival (HR = 6.74; 95% CI, 2.02-22.48; P = .002).Conclusion
PI3K-AKT-mTOR signaling pathway up-regulation and HPV coinfection in PSCC are associated with favorable disease. mTOR pathway biomarkers along with HPV status may represent novel prognosticators for risk stratification of PSCC patients and may help guide treatment decisions and follow-up strategies. These findings require further investigation. 相似文献5.
Matthew M. Symer Natalie Z. Wong Jonathan S. Abelson Jeffrey W. Milsom Heather L. Yeo 《Clinical colorectal cancer》2018,17(2):e281-e288
Introduction
Hormone replacement therapy has been shown to reduce colorectal cancer incidence, but its effect on colorectal cancer mortality is controversial. The objective of this study was to determine the effect of hormone replacement therapy on survival from colorectal cancer.Patients and Methods
We performed a secondary analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter randomized trial run from 1993 to 2001, with follow-up data recently becoming mature. Participants were women aged 55 to 74 years, without recent colonoscopy. Data from the trial were analyzed to evaluate colorectal cancer incidence, disease-specific mortality, and all-cause mortality based on subjects’ use of hormone replacement therapy at the time of randomization: never, current, or former users.Results
A total of 75,587 women with 912 (1.21%) incident colorectal cancers and 239 associated deaths were analyzed, with median follow-up of 11.9 years. Overall, 88.6% were non-Hispanic white, and < 10% had not completed high school. The never-user group was slightly older than the current or former user groups (average, 63.8 vs. 61.4 vs. 63.3 years; P < .001). Almost one-half (47.1%) of the current users had undergone hysterectomy, compared with 21.6% of never-users and 34.0% of former users (P < .001). Adjusted colorectal cancer incidence in current users compared to never-users was lower (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.94; P = .005), as was death from colorectal cancer (HR, 0.63; 95% CI, 0.47-0.85; P = .002) and all-cause mortality (HR, 0.76; 95% CI, 0.72-0.80; P < .001).Conclusions
Hormone replacement therapy is associated with a reduced risk of colorectal cancer incidence and improved colorectal cancer-specific survival, as well as all-cause mortality. 相似文献6.
Madeline Grade Julie Koenig Yushen Qian Navjot Sandhu Yufei Liu Brandon Turner Rie von Eyben Susan Knox Sara Dudley 《Practical radiation oncology》2019,9(2):e203-e209
Purpose
Emergent palliative radiation therapy (PRT) of symptomatic metastases can significantly increase the quality of life of patients with cancer. In some contexts, this treatment may be underused, but in others PRT may represent an excessively aggressive intervention. The characterization of the current use of emergent PRT is warranted for optimized value and patient-centered care.Methods and Materials
This study is a cross-sectional retrospective analysis of all emergent PRT courses at a single academic tertiary institution across 1 year.Results
A total of 214 patients received a total of 238 treatment courses. The most common indications were bone (39%) and brain (14%) metastases. Compared with outpatients, inpatients had lower mean survival rates (2 months vs 6 months; P < .001), higher rates of stopping treatment early (19.1% vs 9.0%; P = .034), and greater involvement of palliative care (44.8% vs 24.1%; P < .001), but the same mean planned fractions (9.10 vs 9.40 fractions; P = .669). In a multiple predictor survival analysis, palliative care involvement (P = .025), male sex (P = .001), ending treatment early (P = .011), and having 1 of 3 serious indications (airway compromise, leptomeningeal disease, and superior/inferior vena cava involvement; P = .007) were significantly associated with worse overall survival.Conclusions
Survival is particularly poor in patients who receive emergent PRT, and patient characteristics such as functional status and indication should be considered when determining fractionation schedule and dosing. A multi-institutional study of practice patterns and outcomes is warranted. 相似文献7.
Omar Abdel-Rahman 《Clinical colorectal cancer》2019,18(1):e61-e68
Background
Baseline albumin-bilirubin (ALBI) score has been shown to be a reliable prognostic predictor among patients with hepatocellular carcinoma. The current study aims at evaluating its prognostic impact among patients with colorectal liver metastases treated with first-line systemic therapy.Materials and Methods
Through the Project Data Sphere portal, de-identified clinical trial datasets of 2 clinical trials (NCT00115765; PACCE [Panitumumab Advanced Colorectal Cancer Evaluation Study] trial) and (NCT00364013; PRIME [Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy] trial) were downloaded. Baseline ALBI score was calculated for each included patient in this study. Kaplan-Meier curve/log-rank testing was used to evaluate overall and progression-free survival according to ALBI grades. Additional Cox regression models were run in order to evaluate factors affecting overall and progression-free survival. Factors with P-value < .05 in univariate analysis were included in multivariate analysis.Results
A total of 1434 patients with colorectal liver metastases were included in this study. Kaplan-Meier survival analysis was conducted to assess the impact of ALBI grade on overall and progression-free survival in the study cohort. For both endpoints, higher ALBI grade was associated with worse overall and progression-free survival (P < .001 for both endpoints). The following factors were significant for overall survival in univariate Cox regression analysis (P < .05): age, Eastern Cooperative Oncology Group (ECOG) score, lactate dehydrogenase (LDH), number of metastatic sites, body mass index, and ALBI score. When these factors were evaluated in multivariate Cox regression analysis, the following factors were predictive of worse overall survival: higher ALBI score (P < .001), higher number of metastatic sites (P < .001), higher LDH (P < .001), higher ECOG score (P < .001), and older age (P < .001). Similarly, the following factors were significant for progression-free survival in univariate Cox regression analysis (P < .05): age, race, ECOG score, LDH, number of metastatic sites, body mass index, type of chemotherapy, and ALBI score. When these factors were evaluated in multivariate Cox regression analysis, the following factors were predictive of worse progression-free survival: higher ECOG score (P < .001), higher LDH level (P < .001), higher number of metastatic sites (P < .001), and higher ALBI score (P < .001).Conclusions
Higher baseline ALBI score is associated with worse overall and progression-free survival among patients with colorectal liver metastases treated with first-line systemic therapy. 相似文献8.
Suzanne B. Merrill Brian S. Sohl Ashiya Hamirani Erik B. Lehman Kathleen K. Lehman Matthew G. Kaag Jay D. Raman 《Clinical genitourinary cancer》2019,17(2):132-138
Introduction
The purpose of this study was to explore whether the practice of postoperative renal cell carcinoma (RCC) surveillance affords a survival benefit by investigating whether detection of RCC recurrences in an asymptomatic versus symptomatic manner influences mortality.Patients and Methods
We identified 737 patients who underwent partial or radical nephrectomy for M0 RCC between 1998 and 2016. Overall survival and disease-specific survival stratified by the type of recurrence detection (asymptomatic vs. symptomatic) was estimated using Kaplan-Meier probabilities both from the time of surgery and from the time of recurrence. Cox proportional hazard regression models were used to evaluate the impact of the type of recurrence detection on mortality.Results
A total of 78 patients (10.6%) experienced recurrence after surgery, of whom 63 (80.8%) were asymptomatic (detected using routine surveillance) and 15 (19.2%) were symptomatic. The median postoperative follow-up was 47.2 months (interquartile range, 26.3-89.4 months). Five- and 10-year overall survival, from time of surgery, among patients with asymptomatic versus symptomatic recurrences was 57% and 39% versus 24% and 8%, respectively (P = .0002). As compared with asymptomatic recurrences, patients with symptomatic recurrences had an increased risk of overall (OD) and disease-specific death (DSD) both when examined from the time of surgery (OD: hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.33-7.49; P = .0091 and DSD: HR, 3.44; 95% CI, 1.38-8.57; P = .0079) and from the time of recurrence (OD: HR, 2.93; 95% CI, 1.24-6.93; P = .0143 and DSD: HR, 3.62; 95% CI, 1.45-9.01; P = .0058).Conclusions
Capturing RCC recurrences in an asymptomatic manner during routine surveillance is associated with improved patient survival. 相似文献9.
Kang Wang Gui-Qi Zhu Yang Shi Zhu-Yue Li Xiang Zhang Hong-Yuan Li 《Clinical breast cancer》2019,19(1):e101-e115
Background
The role of histology subtype on the prognosis of T1-2 breast cancer patients receiving breast-conserving surgery (BCS) is not clear.Methods
The Surveillance, Epidemiology, and End Results (SEER) Program was used to compare overall survival, second primary cancer-free survival (CFS), and local recurrence risk (LR) for patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), both receiving BCS.Results
The study enrolled 196,688 patients with T1-2 disease receiving BCS, including 12,906 with ILC and 183,782 with IDC. Patients with IDC showed higher unadjusted annual rates of BCS than ILC. Five- and 10-year estimated survival rates were, respectively, 92.06% and 86.14% in ILC, compared to 90.50% and 85.26% in IDC (P = .12). In multivariable Cox regression, ILC patients showed advantage over IDC in overall survival (hazard ratio [HR] = 0.93, P = .001), whereas no significant differences in CFS (HR = 1.03, P = .33) and LR (HR = 1.17, P = .06) were found, which were consistent with results from matched cohort. In subgroup analyses, patients with grade III ILC had poorer CFS (HR = 1.23, P = .009) and higher LR (HR = 1.59, P = .01) than IDC.Conclusion
Histologic type is of prognostic importance in T1-2 patients receiving BCS, and surgeons should be cautious in performing BCS for individuals with grade III ILC. 相似文献10.
Marina Baretti Lorenza Rimassa Nicola Personeni Laura Giordano Maria Chiara Tronconi Tiziana Pressiani Silvia Bozzarelli Armando Santoro 《Clinical colorectal cancer》2018,17(3):e489-e498
Background
Comorbidity has a detrimental effect on cancer survival, however, it is difficult to disentangle its direct effect from its influence on treatment choice. In this study we assessed the effect of comorbidity on survival in patients who received standard treatment for resected stage II and III colorectal cancer (CRC).Patients and Methods
In total, 230 CRC patients, 68 rectal (29.6%) and 162 colon cancer (70.4%) treated with surgical resection and neoadjuvant/adjuvant chemotherapy from December 2002 to December 2009 at Humanitas Cancer Center were retrospectively reviewed. The key independent variable was the Charlson Comorbidity Index (CCI) score, measured as a continuous variable. The differences between groups for categorical data were tested using the χ2 test. Actuarial survival curves were generated using the Kaplan–Meier method.Results
Median follow-up was 113 (range, 8.2-145.0) months. Median age was 63 (range, 37-78) years. In univariate analysis CCI score was significantly associated with poorer disease-free survival (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.52-1.80; P < .001), and overall survival (OS; HR, 1.55; 95% CI, 1.41-1.71; P < .001). Factors associated with poorer outcome also included (stage III vs. stage II, P < .029) and age (age >70 vs. ≤70 years, P < .001). After adjusting for these factors, a significant negative prognostic role of CCI score was still observed (adjusted HR for OS, 1.59; 95% CI, 1.43-1.76; P < .001).Conclusion
Among CRC patients who underwent surgical resection and chemotherapy, a higher CCI score was associated with poorer outcome and might predict long-term survival. 相似文献11.
Walker Mainwaring John Bowers Ngoc Pham Todd Pezzi Mihir Shukla Mark Bonnen Michelle Ludwig 《Clinical breast cancer》2019,19(2):e343-e351
Background
Metastases to the brain occur in 10%-16% of patients with breast cancer, with incidence reportedly increasing. Historically, brain metastases (BM) have been treated with whole-brain radiation therapy (WBRT), but stereotactic radiosurgery (SRS) is an increasingly favored treatment option. In this study we used a population-level database to compare patterns of care and survival between WBRT and SRS for BM from breast cancer.Materials and Methods
The National Cancer Database was used to select patients treated with radiation for BM from primary breast cancer. Groups were classified on the basis of the modality of radiation delivered to the brain and compared across several demographic factors. A Kaplan–Meier survival curve and Cox multivariate analysis were used to compare overall survival. A matched analysis using propensity scores was used to further reduce confounders and compare survival.Results
The treatment groups were significantly different across several socioeconomic variables including income, insurance status, and treatment setting. The percentage of patients who received SRS increased dramatically in the second half of the analyzed time period (P < .001). Unadjusted median survival was significantly longer for patients who received SRS versus those who received WBRT (P < .001). This finding persisted after propensity score-matching.Conclusion
Receipt of SRS was associated with different socioeconomic variables and longer overall survival compared with WBRT, highlighting the need for less toxic treatment for patients who are now living longer. The results revealed important socioeconomic differences between patients selected for SRS versus WBRT and emphasizes disparities in access to modern radiation techniques across the United States. 相似文献12.
Omar Abdel-Rahman 《Clinical genitourinary cancer》2019,17(2):e329-e338
Background
The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.Patients and Methods
Within the PLCO (Prostate, Lung, Colorectal, and Ovary) trial, patients who were diagnosed with clinically localized prostate cancer and subsequently received treatment with prostatectomy or radiation therapy (with or without hormonal treatment) were included. Univariate and multivariate Cox regression analyses were then performed to determine factors affecting overall and prostate cancer-specific survival. Factors with P < .05 in univariate analysis were included in the multivariate analysis.Results
A total of 3953 patients were included in the current analysis. These included 2044 patients treated with prostatectomy and 1909 patients treated with radiation therapy with or without hormonal treatment. In an adjusted multivariate analysis for factors affecting overall survival, prostatectomy was associated with better overall survival compared with radiation therapy (hazard ratio, 0.548; 95% confidence interval [CI], 0.440- 681; P < .001). Likewise, in an adjusted multivariate analysis for factors affecting prostate cancer-specific survival, prostatectomy was associated with better prostate cancer-specific survival compared with radiation therapy (hazard ratio, 0.485; 95% CI, 0.286- 0.822; P = .007). Similar findings were found with propensity score matching and repeating the same analyses on the post-matching cohort.Conclusion
Prostatectomy seems to predict better overall and prostate cancer-specific survival compared with radiation therapy among patients with clinically localized prostate cancer diagnosed within the PLCO trial. 相似文献13.
Marco Maruzzo Umberto Basso Eugenio Borsatti Laura Evangelista Filippo Alongi Orazio Caffo Francesca Maines Sara Galuppo Rocco De Vivo Fable Zustovich Dario Palleschi Andrea Zivi Teodoro Sava Mariella Sorarù Roberto Iacovelli Maurizio Nicodemo Susanne Baier Lucia Fratino Vittorina Zagonel 《Clinical genitourinary cancer》2019,17(1):e187-e194
Background
Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.Patients and Methods
We conducted a multicenter retrospective analysis in the Triveneto region of Italy.Results
One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.Conclusion
This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined. 相似文献14.
Mitsukuni Suenaga Marta Schirripa Shu Cao Wu Zhang Dongyun Yang Yan Ning Chiara Cremolini Carlotta Antoniotti Beatrice Borelli Tetsuo Mashima Satoshi Okazaki Martin D. Berger Yuji Miyamoto Roel Gopez Afsaneh Barzi Sara Lonardi Toshiharu Yamaguchi Alfredo Falcone Heinz-Josef Lenz 《Clinical colorectal cancer》2018,17(2):e395-e414
Background
The C-C motif chemokine ligand 5/C-C motif chemokine receptor 5 (CCL5/CCR5) pathway has been shown to induce endothelial progenitor cell migration, resulting in increased vascular endothelial growth factor A expression. We hypothesized that genetic polymorphisms in the CCL5/CCR5 pathway predict efficacy and toxicity in patients with metastatic colorectal cancer (mCRC) treated with regorafenib.Patients and Methods
We analyzed genomic DNA extracted from 229 tumor samples from 2 different cohorts of patients who received regorafenib: an evaluation cohort of 79 Japanese patients and a validation cohort of 150 Italian patients. Single nucleotide polymorphisms of CCL5/CCR5 pathway-related genes were analyzed by PCR-based direct sequencing.Results
CCL4 rs1634517 and CCL3 rs1130371 were associated with progression-free survival in the evaluation cohort (hazard ratio [HR] 1.54, P = .043; HR 1.48, P = .064), and progression-free survival (HR 1.74, P < .001; HR 1.66, P = .002) and overall survival (HR 1.65, P = .004; HR 1.65, P = .004) in the validation cohort. The allelic frequencies of CCL5 single nucleotide polymorphisms varied between the evaluation and validation cohorts (G/G variant in rs2280789, 21.5% vs. 1.3%, P < .001; T/T variant in rs3817655, 22.8% vs. 2.7%, P < .001). In the evaluation cohort, patients with the G/G variant in rs2280789 had a higher incidence of grade 3+ hand–foot skin reaction compared to any A allele (53% vs. 27%, P = .078), and similarly to the T/T variant in rs3817655 compared to any A allele (56% vs. 26%, P = .026).Conclusion
Genetic variants in the CCL5/CCR5 pathway may serve as prognostic markers and may predict severe hand–foot skin reaction in mCRC patients receiving regorafenib therapy. 相似文献15.
Aleksandra Semeniuk-Wojtaś Arkadiusz Lubas Rafał Stec Tomasz Syryło Stanisław Niemczyk Cezary Szczylik 《Clinical genitourinary cancer》2018,16(3):e685-e693
Background
Inflammation plays a crucial role in cancer development. In this study, we evaluate the prognostic values of systemic inflammation markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) for the progression-free survival and overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.Materials and Methods
PubMed and the Cochrane Library databases were searched for published studies on the effect of NLR, PLR, and CRP in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.Results
In the meta-analysis, NLR (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.27-3.18; P = .003) and PLR (HR, 6.96; 95% CI, 5.04-9.62; P < .001) had a significant influence on progression-free survival, whereas all considered proinflammatory markers had a significant impact on overall survival: NLR (HR, 2.14; 95% CI, 1.67-2.73; P < .001), PLR (HR, 14.67; 95% CI, 11.10-19.57; P < .001), and CRP (HR, 1.96; 95% CI, 1.26-3.05; P = .003).Conclusions
Inflammation markers such as NLR, PLR, and CRP are predictors of clinical outcome and could provide additional information to individualize treatment. 相似文献16.
Nils Kroeger Haoran Li Guillermo De Velasco Frede Donskov Hao-Wen Sim Viktoria Stühler J. Connor Wells Igor Stukalin Johannes Heide Jens Bedke Neeraj Agarwal Hiral Parekh Brian I. Rini Jennifer J. Knox Allan Pantuck Toni K. Choueiri Daniel Yick Chin Heng 《Clinical genitourinary cancer》2019,17(1):65-71
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17.
Jianai Sun Jingjing Zhu De Zhou Lixia Zhu Xiudi Yang Mixue Xie Li Li Xianbo Huang Mingyu Zhu Yanlong Zheng Wanzhuo Xie Xiujin Ye 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(1):e63-e70
Purpose
To perform a retrospective analysis of the prognostic relevance of clinicopathologic parameters in a well-documented cohort of patients treated with all-trans-retinoic acid (ATRA)-based induction regimens in order to discover which indicators can predict a high risk of early death (ED) and patient survival.Patients and Methods
We analyzed data of 288 newly diagnosed adult acute promyelocytic leukemia patients in Hangzhou, China. The median follow-up time was 32 months (range, 6-78 months).Results
The 3-year disease-free and overall survival rates were 90.83% and 91.69%, respectively. In the multivariable analysis, older age (≥ 60 years) was the only independent risk factor for ED (hazard ratio [HR] = 15.057; P = .004). High white blood cell count was not a risk factor for ED (P = .055), but it was for relapse (HR = 2.7; P = .009). FLT3 mutation (HR = 3.9; 95% confidence interval, 1.4 to 10; P = .007) and older age (≥ 60 years) (HR = 5.3; 95% confidence interval, 2.4 to 11; P < .001) were prognostic factors for poorer disease-free and overall survival. Interestingly, CD15 negativity (HR = 0.23; P = .049) was a prognostic factor for relapse. The ED rate was 5.9% (17/288 patients).Conclusion
The perceived impact of the identification of these high-risk factors should be described in order to decide whether any modifications to treatment strategy should be entertained. 相似文献18.
Omar Abdel-Rahman Yuan Xu Shiying Kong Joseph Dort May Lynn Quan Safiya Karim Antoine Bouchard-Fortier HyoKeun Cho Winson Y. Cheung 《Clinical breast cancer》2019,19(2):e297-e305
Introduction
The aim of this study was to characterize treatment trends and outcomes of women who have preexisting cardiovascular disease (CVD) prior to the diagnosis of breast cancer.Patients and Methods
This represented a retrospective, population-based cohort study that analyzed pooled data from the provincial cancer registry, physician billing claims, hospital discharge abstracts, ambulatory care, and the 2011 census in a large Canadian province. Multivariable logistic regression was performed to identify the associations of CVD with breast cancer treatment and outcomes. Kaplan-Meier analyses were conducted and survival was compared between CVD and non-CVD groups. Cox regression models were constructed to determine the effect of CVD on overall and cancer-specific survival.Results
A total of 25,594 women with breast cancer were eligible and included in the current analysis. Preexisting CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.48-0.66; P < .0001) and radiotherapy (OR, 0.75; 95% CI, 0.67-0.83; P < .0001), but a higher probability of undergoing mastectomy (OR, 1.13; 95% CI, 1.03-1.25; P = .011). Unadjusted Kaplan-Meier analyses showed that individuals with preexisting CVD experienced worse median overall and cancer-specific survival when compared with those without CVD (87 vs. 150 months and 106 vs. 131 months, respectively; both P < .0001). Adjusting for measured confounders, the presence of preexisting CVD continued to predict for worse overall survival (hazard ratio, 1.55; 95% CI, 1.43-1.67; P < .0001), but not cancer-specific survival (hazard ratio, 1.11; 95% CI, 0.98-1.27; P = .099).Conclusions
Patients with breast cancer with preexisting CVD are less likely to receive recommended treatment for their cancer and more likely to exhibit worse overall survival. 相似文献19.
Yeon Joo Kim Su Ssan Kim Si Yeol Song Seung-Il Park Dong Kwan Kim Yong-Hee Kim Hyeong Ryul Kim Eun Kyung Choi 《Clinical lung cancer》2019,20(1):e91-e96
Introduction
We evaluated the clinical outcome of patients with stage III to IV thymomas (Ts) or stage II to IV thymic carcinomas (TCs) treated with complete thymectomy and local radiation therapy (LRT, targeting the tumor bed and anterior mediastinal areas only) or elective nodal irradiation (ENI, targeting the entire mediastinal and supraclavicular regions).Materials and Methods
Data from 47 patients diagnosed with Ts or TCs and treated with surgery and adjuvant RT from May 2002 to May 2015 were analyzed. The standard RT dose was 50.4 Gy in 28 fractions; patients with a positive resection margin received a further 4 to 10 Gy. Survival outcomes determined at 5 years included local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival.Results
Five-year local recurrence-free survival was similar in both groups (LRT, 94.7% vs. ENI, 96.2%; P = .849). Significant differences were seen in 5-year regional recurrence-free survival (LRT, 55.1% vs. ENI, 83.7%; P = .006); however, tumor size was seen to be a significant factor (< 7 cm, 95.2% vs. ≥ 7 cm, 48.9%; P < .001), and the LRT group contained a greater proportion of patients with ≥ 7-cm tumors (70% vs. 33%). Multivariate analysis demonstrated that tumor size was the only significant prognostic factor (P < .001). No differences in 5-year overall survival were seen (LRT, 91.7% vs. ENI, 100%; P = .106).Conclusion
ENI may not be indicated in all cases, as additional benefit in reducing recurrence or improving survival was not predominant. LRT seems to be a feasible option with favorable patient outcomes. 相似文献20.
Anas M. Saad Mohamed M. Gad Muneer J. Al-Husseini Inas A. Ruhban Mohamad Bassam Sonbol Thai H. Ho 《Clinical genitourinary cancer》2019,17(1):46-57.e5