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1.
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2.
Nizar M. Tannir Robert A. Figlin Martin E. Gore M. Dror Michaelson Robert J. Motzer Camillo Porta Brian I. Rini Caroline Hoang Xun Lin Bernard Escudier 《Clinical genitourinary cancer》2018,16(1):6-12.e4
Background
We characterized clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib who were long-term responders (LTRs), defined as patients having progression-free survival (PFS) > 18 months.Patients and Methods
A retrospective analysis of data from 5714 patients with mRCC treated with sunitinib in 8 phase II/III clinical trials and the expanded access program. Duration on-study and objective response rate (ORR) were compared between LTRs and patients with PFS ≤ 18 months (“others”). PFS and overall survival (OS) were summarized using Kaplan–Meier methodology.Results
Overall, 898 (15.7%) patients achieved a long-term response and 4816 (84.3%) patients did not achieve long-term response. The median (range) duration on-study was 28.6 (16.8-70.7) months in LTRs and 5.5 (0-68.8) months in others. ORR was 51% in LTRs versus 14% in others (P < .0001). Median PFS in LTRs was 32.11 months and median OS was not reached. LTRs had higher percentage of early tumor shrinkage ≥ 10% at the first scan (67.1% vs. 51.2%; P = .0018) and greater median maximum on-study tumor shrinkage from baseline (?56.9 vs. ?27.1; P < .0001) versus others. White race, Eastern Cooperative Oncology Group performance status 0, time from diagnosis to treatment ≥ 1 year, clear cell histology, no liver metastasis, lactate dehydrogenase ≤ 1.5 upper limit of normal (ULN), corrected calcium ≤ 10 mg/dL, hemoglobin greater than the lower limit of normal, platelets less than or equal to ULN, body mass index ≥ 25 kg/m2, and low neutrophil-to-lymphocyte ratio were associated with LTR.Conclusion
A subset of patients with mRCC treated with sunitinib achieved long-term response. LTRs had improved ORR, PFS, and OS. 相似文献3.
Mehmet Asim Bilen Giselle Marie Almeida Dutcher Yuan Liu Deepak Ravindranathan Haydn T. Kissick Bradley C. Carthon Omer Kucuk Wayne B. Harris Viraj A. Master 《Clinical genitourinary cancer》2018,16(3):e563-e575
Background
Biomarkers to guide treatment in metastatic renal-cell carcinoma (mRCC) are lacking. We aimed to investigate the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and outcome of patients with mRCC receiving nivolumab.Patients and Methods
Through retrospective chart review, we identified 38 patients with mRCC treated with standard-of-care nivolumab between 2015 and 2016 at Winship Cancer Institute of Emory University. NLR was determined from complete blood count collected before starting treatment, and imaging was performed to assess progression. The NLR cutoff value of 5.5 was determined by log-rank test, and the univariate association with overall survival (OS) or progression-free survival (PFS) was assessed by the Cox proportional hazard model and Kaplan-Meier method.Results
The 38 patients had a median age of 69 years. The PFS and OS for all patients at 12 months was 54% and 69%, respectively. The median PFS was 2.6 months in the high NLR group but not reached in the low NLR group. Low NLR was strongly associated with increased PFS with hazard ratio of 0.20 (95% confidence interval, 0.07-0.64; P = .006). The median OS was 2.7 months in the high NLR group but not reached in the low NLR group. Low NLR was significantly associated with a prolonged OS with hazard ratio of 0.06 (95% confidence interval, 0.01-0.55; P = .012).Conclusion
Pretreatment NLR < 5.5 is associated with superior PFS and OS. NLR is a biomarker that can inform prognosis for patients with mRCC and should be further validated in larger cohorts and in prospective studies. 相似文献4.
Pedro C. Barata Prateek Mendiratta Rupesh Kotecha Dharmesh Gopalakrishnan Aditya Juloori Samuel T. Chao Vadim Koshkin Moshe Ornstein Timothy D. Gilligan Laura S. Wood Brian I. Rini Lilyana Angelov Jorge A. Garcia 《Clinical genitourinary cancer》2018,16(5):413-419.e1
Background
We assessed the clinical outcomes of patients with oligoprogressive renal cell carcinoma (mRCC) treated with stereotactic radiosurgery (SRS), stratified by changing or continuing systemic treatment.Patients and Methods
Ninety-five consecutive patients with clear cell mRCC who had undergone SRS to the central nervous system (CNS) or spine during systemic treatment were divided into 3 cohorts: those who continued the same systemic therapy (STAY), those who changed systemic treatment after SRS (SWITCH), and patients with progression outside the SRS sites, who also changed systemic treatment (PD-SYS). The primary outcome was treatment duration after SRS, defined as the interval between SRS and discontinuation of the current systemic therapy for the STAY group and discontinuation of the first subsequent therapy in the SWITCH and PD-SYS groups.Results
Local control with SRS was achieved in 85% of the patients. The most common systemic treatment at SRS included anti–vascular endothelial growth factor (67%), mammalian target of rapamycin (14%), and programmed cell death protein 1 inhibitors (9%). The median treatment duration for the STAY group was 5.2 months (95% confidence interval [CI], 3.5-6.9) compared with 5.0 months (95% CI, 4.3-5.7) for the SWITCH group (P = .549) and 3.1 months (95% CI, 1.7-4.5) for the PD-SYS group (P = .07, compared with all other patients). No difference in median overall survival was found for the STAY and SWITCH groups (24.2 vs. 27.1 months; P = .381) but was significantly longer than that for the PD-SYS group (P = .025).Conclusion
The decision to continue the same systemic therapy at SRS to treat CNS or spinal lesions did not compromise the clinical outcomes of patients with oligoprogressive mRCC. 相似文献5.
Kriti Mittal Lisa Derosa Laurence Albiges Laura Wood Paul Elson Timothy Gilligan Jorge Garcia Robert Dreicer Bernard Escudier Brian Rini 《Clinical genitourinary cancer》2018,16(3):e663-e667
Introduction
Tyrosine kinase inhibitor (TKI) therapy in metastatic renal-cell carcinoma (mRCC) is noncurative and may be associated with significant toxicities. Some patients may receive treatment breaks as a result of TKI-related adverse effects or planned drug holidays.Patients and Methods
In this retrospective study, mRCC patients who underwent drug holidays during TKI therapy at 2 different institutions were analyzed. A drug holiday was defined as a period of drug cessation for ≥ 3 months for reasons other than progressive disease.Results
Of the 112 patients, the median duration of the first drug holiday for the overall cohort was 16.8 months (95% confidence interval, 12.5-26.4), and 40 patients (36%) remain on the first drug holiday. Overall, patients received a median of 2 lines of treatment. Complete response before the initial drug holiday (n = 14) was associated with a longer surveillance period (P = .0004). The observed median survival of this cohort was 71.7 months (range, 1.3 to 93+ months).Conclusion
Some selected mRCC patients with a favorable response to TKIs may be eligible for drug holidays. The cohort evaluated in this retrospective study represents a highly selected group of patients with indolent disease biology. 相似文献6.
Angeline Denouel Natacha Heutte Bernard Escudier Jean-Emmanuel Kurtz Melanie Dos Santos Nadine Longato Laurence Desrues Sarah Dauchy Marie Lange Emmanuel Sevin Chantal Rieux Benedicte Clarisse Helene Castel Sabien Noal Florence Joly 《Clinical genitourinary cancer》2018,16(5):369-375.e1
Background
Targeted therapies, in particular antiangiogenic therapies (AATs), have become the standard of treatment for metastatic renal cell carcinoma (mRCC). Although common adverse effects like fatigue have been well-established, sexual disorders induced by these treatments, although often reported, have been poorly evaluated. The aim of this study was to evaluate the impact of AATs on the sexual life of patients with mRCC and the relationships with quality of life (QoL), fatigue, and biologic parameters.Patients and Methods
This longitudinal study included patients with mRCC on first- or second-line AATs. Sexuality was evaluated by the French version of Changes in Sexual Functioning Questionnaire short-Form (CSFQ); QoL and fatigue were measured by the Functional Assessment of Cancer Therapy General (FACT-G) and the Multidimensional Fatigue Inventory (MFI-20), respectively. Biologic parameters were also assessed.Results
Among 75 patients included in the study, 39 agreed to respond to the sexual functioning questionnaire (CSFQ). At baseline, all patients had at least 1 sexual dysfunction. No relationship with QoL, fatigue, and biologic parameters was shown. After 3 months of treatment, a decrease in at least 1 sexual dimension was observed in 69% of patients. The most affected sexual dimensions were pleasure (34%) and desire/interest (38%). No significant relationship between sexual dysfunctions and biologic parameters was found. The percentage of non-participants (50%) and the absence of a control arm are the main limitations.Discussion
Patients with mRCC exhibit sexual dysfunction that could be increased by AATs independently of the impact on fatigue and QoL. Further studies aiming to define the role of biologic parameters like inflammatory markers and thyroid parameters are warranted.Conclusion
Sexual disorders induced or degraded by AAT are an independent side effect that should be taken into account in oncology supportive care departments. 相似文献7.
Annelies Verbiest Gabrielle Couchy Sylvie Job Jessica Zucman-Rossi Laure Caruana Evelyne Lerut Raymond Oyen Aurélien de Reyniès Brigitte Laguerre Nathalie Rioux-Leclercq Agnieszka Wozniak Steven Joniau Hendrik Van Poppel Kathleen Van Den Eynde Benoit Beuselinck 《Clinical genitourinary cancer》2018,16(3):e605-e612
Background
We previously described 4 molecular subtypes of metastatic clear cell renal cell carcinoma (mccRCC), named ccrcc1-4 (Beuselinck et al, 2015). These have both prognostic and predictive value for patients treated with first-line sunitinib, with distinctive objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ccrcc2 and ccrcc3 tumors have the best outcomes, followed by ccrcc1 and then ccrcc4. We hypothesized that these molecular subtypes would show similar outcomes with first-line pazopanib treatment.Patients and Methods
We classified 28 mccRCC tumors treated with pazopanib as first-line therapy, as described previously. The primary endpoints were PFS and OS from the start of pazopanib. A secondary endpoint was ORR. Because there were only 2 ccrcc3 tumors, they were pooled with the ccrcc2 tumors for outcome analysis.Results
PFS was 9 months for the ccrcc2 and ccrcc3 tumors, 5 months for ccrcc1 tumors, and 3 months for the ccrcc4 tumors (P = .011). The corresponding OS duration was 69, 19, and 5 months (P = .003). The corresponding ORR was 50%, 33%, and 0%. The corresponding mean tumor size decreased by 34%, 6%, and 2% (P = .032). The ccrcc1-4 classification was a stronger predictor of outcome than the International Metastatic Renal Cell Carcinoma Database Consortium score on univariate analysis (P = .011 vs. P = .094 for PFS and P = .003 vs. .013 for OS). Both remained independent on bivariate analysis.Conclusion
The molecular subtypes of mccRCC are associated with outcome on pazopanib as first-line therapy. The prognostic and predictive value of the ccrcc1-4 molecular classification requires validation in prospective trials. 相似文献8.
Clément Korenbaum Laure Pierard Alicia Thiéry Fleur Story Véronique Lindner Hervé Lang Jean-Emmanuel Kurtz Philippe Barthélémy 《Clinical genitourinary cancer》2018,16(3):e577-e586
Introduction
Metastatic renal cell carcinoma (RCC) with a sarcomatoid component is a rare disease associated with a poor prognosis. We report the outcomes of 47 patients with metastatic sarcomatoid RCC (SRCC) treated with different modalities including chemotherapy, tyrosine kinase inhibitors, or immunotherapy over 2 decades in a French cancer center. Furthermore, we assessed the validity of prognostic scores in this subset of RCC.Patients and Methods
Patients were retrospectively identified from the database of the pathology department of the University Hospital of Strasbourg. We enrolled all patients with RCC with a sarcomatoid component diagnosed between 1995 and 2016. Patients with nonmetastatic RCC were excluded. Recorded variables included: clinical stage, metastatic sites, pathologic stage, type of treatments, prognostic group, and survival data. The primary end point was overall survival. The institutional ethical committee approved the study protocol.Results
Of 104 patients with SRCC, 47 patients with metastatic SRCC were included. The median age was 60 years (range, 41-77 years). Median length of follow-up was 34 months (range, 1-180 months). Fifty-five percent of patients had known metastases at diagnosis. Lung represented the first metastatic site (70%) followed by glandular (28%), bone (23%), liver (21%), and brain (6%). Fifteen percent of patients received immunotherapy including cytokine-based therapy (n = 7), or checkpoint inhibitors (n = 2). Moreover, 7 patients received chemotherapy. Five patients received no systemic treatment because of their poor performance status. Of 42 treated patients, 2 patients achieved complete response and 9 partial response (24%). Median overall survival was 13.3 months. International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic groups were valid in this subset of SRCC patients. A sarcomatoid percentage cutoff of 30% had the strongest influence on overall survival.Conclusion
Despite the arrival of tyrosine kinase inhibitors 10 years ago, metastatic SRCC remains a disease of poor prognosis and difficult to treat. Chemotherapy regimen and targeted therapies showed little activity in SRCC. IMDC score is a relevant prognostic factor in SRCC patients. Additionally, the MSKCC score, the sarcomatoid percentage, the necrotic fraction, and the vascular invasion could prove useful in identifying patients with a more favorable prognosis. These findings could help toward better patient stratification in clinical trials. Prospective trials assessing new drugs including immune checkpoint inhibitors are currently ongoing to improve SRCC survival. 相似文献9.
Chang Il Choi Minyong Kang Hyun Hwan Sung Hwang Gyun Jeon Byong Chang Jeong Seong Soo Jeon Hyun Moo Lee Seong I.L. Seo 《Clinical genitourinary cancer》2018,16(6):e1189-e1199
Purpose
To evaluate the prognostic role of cytoreductive nephrectomy (CN) in patients with synchronous metastatic renal-cell carcinoma (mRCC).Patients and Methods
We analyzed the electronic medical records of 294 patients with synchronous mRCC treated at Samsung Medical Center from January 2005 to December 2015. Primary and secondary end points were overall survival (OS) and cancer-specific survival (CSS), respectively. OS and CSS were estimated by the Kaplan-Meier method and compared between patients with and without CN, particularly by performing 1:1 propensity score matching. Multivariate Cox regression analysis was used to identify independent predictors of survival outcomes.Results
Among the overall population of synchronous mRCC patients, 189 patients (64.3%) underwent CN. Compared to mRCC patients without CN, those who underwent CN have a higher proportion of single metastasis (63.0% vs. 32.4%) and clear-cell histology (87.8% vs. 72.4%). In the matched cohort, the patients who underwent CN had better OS and CSS outcomes compared to those who did not undergo CN (median OS, 23.0 months vs. 11.0 months; P < .001; median CSS, 34.0 months vs. 14.0 months; P < .001). On multivariable analysis, undergoing CN, body mass index, and Heng risk score were found as significant predictive factors of both OS and CSS. In subgroup analyses stratified by Heng risk criteria, the patients who received CN had better OS and CSS in all risk groups.Conclusion
CN significantly improved survival outcomes in synchronous mRCC patients treated with targeted therapies and independently associated with prolonged survival, regardless of Heng risk criteria. 相似文献10.
Roberto Iacovelli Ugo De Giorgi Luca Galli Paolo Zucali Franco Nolè Roberto Sabbatini Anna Paola Fraccon Umberto Basso Alessandra Mosca Francesco Atzori Daniele Santini Gaetano Facchini Giuseppe Fornarini Felice Pasini Cristina Masini Francesco Massari Sebastiano Buti Teodoro Sava Camillo Porta 《Clinical genitourinary cancer》2018,16(5):355-359.e1
Background
The International mRCC (metastatic renal cell carcinoma) Database Consortium (IMDC) is the standard classification for mRCC. We aimed to evaluate the outcomes of a large cohort of patients with an intermediate or a poor prognosis treated with sunitinib using a different cutoff point for IMDC to improve the classification.Patients and Methods
Patients with an intermediate or a poor prognosis according to the IMDC criteria and treated with sunitinib were included in the present study. A new cutoff point was used to categorize the patients. The new score was validated in an independent cohort of patients.Results
A total of 457 patients were included in the present study. Significant differences in overall survival (OS) were highlighted regarding the number of prognostic factors. Three categories were identified according to the presence of 1 (ie, favorable-intermediate group), 2 (ie, real-intermediate group), and > 2 (ie, poor group) factors. The corresponding median OS periods were 32.9, 20.0, and 8.9 months, with significant differences among the groups. The validation cohort included 389 patients. The median OS period for the favorable-intermediate group, real-intermediate group, and poor group was 34.3, 19.4, and 9.0 months, respectively, with confirmed significant differences among the groups.Conclusion
Our analysis revealed significant differences among patients with an intermediate prognosis using the IMDC prognostic factors. Further investigations to optimize the use of available and upcoming therapies are required. 相似文献11.
Introduction
The introduction of active new agents, such as small molecules and checkpoint inhibitors, for the treatment of metastatic renal-cell cancer (mRCC) is associated with a relevant increase in costs, and it is therefore important to strike a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as progression-free survival (PFS) and overall survival (OS).Methods
This analysis was conducted to assess the pharmacologic costs of second-line treatments for mRCC and was restricted to pivotal phase 3 randomized controlled trials (RCTs) used as second-line therapy.Results
Our analysis evaluated 4 phase 3 RCTs including a total of 2454 patients. The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) reached high scores (grade 5) for the CheckMate 025 trial, medium scores (grade 3) for the RECORD-1 and AXIS trials, and low scores (grade 2) for the INTORSECT trial. When we combined the costs of therapy with the measure of efficacy represented by the PFS and OS, we found that the most relevant increase of costs was associated with the use of nivolumab but that it differed according to the difference in costs in terms of life gained, with the highest costs per week of PFS gained (€11,960) but the lowest cost for month of OS gain (€1772).Conclusion
When pharmacologic costs of drugs are combined with the measure of efficacy represented by the OS, nivolumab is a cost-effective second-line treatment for patients with mRCC. 相似文献12.
Kimiharu Takamatsu Ryuichi Mizuno Minami Omura Shinya Morita Kazuhiro Matsumoto Kazunobu Shinoda Takeo Kosaka Toshikazu Takeda Toshiaki Shinojima Eiji Kikuchi Hiroshi Asanuma Masafumi Oyama Shuji Mikami Mototsugu Oya 《Clinical genitourinary cancer》2018,16(4):e927-e933
Background
Almost half of patients with metastatic renal-cell carcinoma (mRCC) are classified as intermediate risk by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. The aim of this study was to evaluate whether baseline C-reactive protein (CRP) levels predict overall survival (OS) in intermediate-risk group mRCC patients.Patients and Methods
Data from 107 intermediate-risk group mRCC patients receiving first-line targeted therapy were retrospectively reviewed. We evaluated the correlation between baseline CRP levels as well as other indices and OS.Results
Of the 107 patients with intermediate-risk disease, 46 patients (43%) were classified as having elevated CRP levels. The elevation of pretreatment serum CRP levels was the independent prognostic factor of OS in patients with intermediate risk (hazard ratio, 4.609; P = .001). The 1- and 3-year survival rates of patients with intermediate–nonelevated CRP were 90.0% and 64.7% compared to the favorable-risk group, at 92.1% and 68.5%, respectively. In contrast, the 1- and 3-year survival rates of patients with intermediate–elevated CRP were 80.5% and 37.4% compared to the poor-risk group, at 65.2% and 24.2%, respectively.Conclusion
Baseline CRP levels could divide mRCC patients in the intermediate-risk group into 2 prognostic subgroups. 相似文献13.
Daniel Keizman Maya Gottfried Maya Ish‐Shalom Natalie Maimon Avivit Peer Avivit Neumann Hans Hammers Mario A. Eisenberger Victoria Sinibaldi Roberto Pili Henry Hayat Svetlana Kovel Avishay Sella Ben Boursi Rony Weitzen Wilmosh Mermershtain Keren Rouvinov Raanan Berger Michael A. Carducci 《The oncologist》2014,19(1):51-60
Background.
Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC).Methods.
An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors.Results.
Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p < .0001), non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p < .0001), use of angiotensin system inhibitors (HR: 0.63, p = .01), sunitinib dose reduction or treatment interruption (HR: 0.72, p = .045), and Heng risk (good and intermediate risk: HR: 1.07, p = .77; poor risk: HR: 1.87, p = .046). Factors associated with OS were smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p < .0001), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 2.95, p < .0001), and sunitinib-induced hypertension (HR: 0.57, p = .002).Conclusion.
Active smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC. 相似文献14.
Raffaele Ratta Elena Verzoni Massimo Di Maio Paolo Grassi Maurizio Colecchia Giovanni Fucà Filippo de Braud Giuseppe Procopio 《Clinical genitourinary cancer》2018,16(4):e735-e742
Background
The purpose of the present retrospective analysis was to describe the trends in exposure to multiple lines of treatment and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who started therapy in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017).Patients and Methods
The proportion of patients who received subsequent lines of treatment after disease progression was compared between the 2 groups. OS was measured from the start of first-line treatment for metastatic disease to death or the last follow-up examination. Both univariate and multivariate analyses were performed.Results
A total of 500 patients were included in the study; 274 started treatment in period 1 and 226 in period 2. Of those patients who stopped first-line treatment because of disease progression, the patients in period 2 had a greater conditional probability to receive second- and third-line treatment compared with patients in period 1 (77.2% vs. 63.7%; odds ratio [OR], 1.93; 95% confidence interval [CI], 1.20-3.11; P = .0065; and 69.6% vs. 48.1%; OR, 2.48; 95% CI, 1.40-4.40; P = .002, respectively). The median OS improved from 22.8 months for patients in period 1 to 38.2 months for patients in period 2 (univariate analysis: hazard ratio, 0.65; 95% CI, 0.50-0.83; P = .001).Conclusion
Patients who started treatment during the past 5 years were exposed to a greater number of treatment lines compared with patients treated before 2011. Our data suggest that the increase of treatment options available and clinician expertise could be associated with better outcomes. 相似文献15.
Hideaki Miyake Takayuki Sugiyama Ryota Aki Yuto Matsushita Keita Tamura Daisuke Motoyama Toshiki Ito Atsushi Otsuka 《Clinical genitourinary cancer》2018,16(3):219-225
Background
The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC).Patients and Methods
The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor-axis-targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA-to-Enz, n = 49; Enz-to-AA, n = 59) and 114 received docetaxel (DTX; AA-to-DTX, n = 54; Enz-to-DTX, n = 60).Results
The prostate-specific antigen (PSA) level in the 114 patients receiving DTX was significantly greater than that in the 108 patients receiving ARATA. However, no significant differences were found in the remaining parameters between the 2 groups. The PSA response rate, PSA progression-free survival (PFS), and overall survival (OS) during second-line therapy in the DTX group (n = 114) were significantly superior to those for the ARATA group (n = 108; PSA response rate, 42.1% vs. 21.3%; median PSA PFS, 7.2 vs. 4.2 months; median OS, 17.5 vs. 14.5 months). Similar trends were confirmed by comparing these outcomes among 4 therapy groups, with significant differences (PSA response rate, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX; PSA PFS, AA-to-Enz vs. Enz-to-AA, AA-to-Enz vs. AA-to-DTX, Enz-to-AA vs. AA-to-DTX, and Enz-to-AA vs. Enz-to-DTX; and OS, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX). Furthermore, the introduction of DTX was independently associated with improved PSA PFS, but not OS, on multivariate analysis.Conclusion
Favorable oncologic outcomes can be expected with DTX treatment, rather than with alternative ARATA, for mCRPC patients after failure of an initial ARATA. 相似文献16.
Yoshimasa Miyagawa Kazuhiro Araki Ayako Bun Hiromi Ozawa Yukie Fujimoto Tomoko Higuchi Arisa Nishimukai Ayako Kira Michiko Imamura Yuichi Takatsuka Yasuo Miyoshi 《Clinical breast cancer》2018,18(5):400-409
Introduction
Although eribulin and nab-paclitaxel are chemotherapy agents widely used for locally advanced or metastatic breast cancer (MBC), their predictive factors remain unknown. Because the absolute neutrophil-to-lymphocyte ratio (NLR) is a significant prognostic factor for early-stage breast cancer, we investigated its usefulness in terms of the eribulin or nab-paclitaxel treatment efficacy for MBC.Patients and Methods
A total of 85 patients with MBC treated with eribulin (n = 59) or nab-paclitaxel (n = 26) were recruited. NLR values were collected at baseline, after 1 cycle, after 2 cycles, and at the end of treatment. The NLR cutoff value was set at 3.Results
The progression-free survival (PFS) of patients with an NLR < 3 at baseline (median, 242 days; n = 24) was significantly better than that of patients with an NLR of ≥ 3 (median, 98 days; n = 35; hazard ratio, 0.37, 95% confidence interval, 0.18-0.71; P = .0032). Similarly, the overall survival was marginally significantly better in patients with an NLR < 3 who were treated with eribulin (P = .058). However, the NLR was not significantly associated with PFS or overall survival for patients treated with nab-paclitaxel. No significant association was found between the NLR during treatment and PFS in the eribulin group. The significance of the NLR for the efficacy of eribulin was consistent, irrespective of estrogen receptor status, previous anthracycline or endocrine use, and the number of previous chemotherapy regimens.Conclusion
A low NLR at baseline was significantly associated with improved PFS in patients treated with eribulin but not in those treated with nab-paclitaxel. Therefore, the baseline NLR might be clinically useful for selecting patients who would benefit from eribulin. 相似文献17.
Zabi Wardak Alana Christie Alex Bowman Strahinja Stojadinovic Lucien Nedzi Sam Barnett Toral Patel Bruce Mickey Tony Whitworth Raquibul Hannan James Brugarolas Robert Timmerman 《Clinical genitourinary cancer》2019,17(2):e273-e280
Background
Brain metastases (BM) pose a significant problem in patients with metastatic renal-cell carcinoma (mRCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.Patients and Methods
The mRCC patients with BM treated with SRS were reviewed. Patient demographics, clinical history, and SRS treatment parameters were identified.Results
Among 268 patients with mRCC treated between 2006 and 2015, 38 patients were identified with BM. A total of 243 BM were treated with SRS with 1 to 26 BMs treated per SRS session (median, 2 BMs). The median (range) BM size was 0.6 (0.2-3.1) cm and median (range) SRS treatment dose was 18 (12-24) Gy. Treated BM local control rates at 1 and 2 years were 91.8% (95% confidence interval, 85.7-95.4) and 86.1% (95% confidence interval, 77.1-91.7), respectively. BM control declined for larger tumors. Survival after 1-year was 57.5% (95% CI 40.2-71.4) for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM. Survival was prognostic based on International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups in patients with < 5 BM. Two patients experienced grade 3 radiation necrosis requiring surgical intervention.Conclusion
SRS is effective in controlling BM in patients with mRCC. Over half of treated patients survive past a year, and no differences in survival were noted in patients with > 5 metastases. Prognostic risk categories based on systemic disease (IMDC) are predictive of survival in this BM population, with limited rates of symptomatic radiation necrosis. 相似文献18.
Takashi Ikeda Hiroki Ishihara Toshio Takagi Tsunenori Kondo Kazuhiko Yoshida Junpei Iizuka Kazunari Tanabe 《Targeted oncology》2018,13(3):379-387
Background
According to the Response Evaluation Criteria in Solid Tumors (RECIST) classification, progressive disease (PD) is defined as target lesion growth (TLG), unequivocal non-target lesion growth (NTLG), or new lesion appearance (NLA). The prognostic impact of the components of PD in tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC) remains unknown.Objective
We retrospectively evaluated the prognostic impact of these PD components on survival in patients with mRCC after first-line TKI therapy.Patients and Methods
Patients were divided into three groups (TLG, NTLG, and NLA) based on the components of PD. Progression-free survival (PFS) and overall survival (OS) after first-line TKI therapy were compared between groups using the Kaplan-Meier method and log-rank test. The predictive impact of the PD components was evaluated using multivariate analyses.Results
Among the 116 patients included, 80 (69.0%) had TLG, 18 (15.5%) NTLG, and 69 (58.6%) NLA. The mean PFS and OS were shorter for patients with TLG than those without TLG (PFS, 7.1 vs. 11.6 months, p?=?0.0071; OS, 18.2 vs. 25.5 months, p?=?0.0091). TLG was an independent predictor of PFS (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.02–2.51; p?=?0.0395) and OS (HR, 1.67; 95% CI, 1.02–2.83; p?=?0.040). NTLG and NLA were not associated with survival.Conclusions
In this retrospective single-center study, patients with TLG had poor survival after first-line TKI therapy for mRCC. Thus, individual components of PD influence patient prognosis.19.
Anders Overby Lone Duval Morten Ladekarl Britt Elmedal Laursen Frede Donskov 《Clinical genitourinary cancer》2019,17(1):e32-e37
Background
Carcinoma of unknown primary site (CUP) is a heterogenous group of metastatic cancer with no detectable primary tumor site. Diagnostic assessment occasionally presents CUP with metastatic renal-cell carcinoma (mRCC) histologic and immunohistochemical characteristics (CUP-mRCC). Efficacy and toxicity data for vascular endothelial growth factor inhibitor therapies in CUP-mRCC patients are few.Patients and Methods
We retrospectively reviewed consecutive patients with CUP-mRCC at a single institution between 2007 and 2018. Treatment outcomes were assessed from initiation of renal-cell carcinoma–specific therapy, including response rate, progression-free survival, and overall survival.Results
Ten patients with CUP-mRCC were identified. Median age was 64 years. Histologies were clear-cell (30%), papillary type II (20%), and unclassified renal-cell (50%) carcinoma. International Metastatic Renal Cell Carcinoma Database Consortium risk group were favorable, intermediate, and poor in 0, 40%, and 60%, respectively. One patient received empiric first-line chemotherapy. Targeted treatments were pazopanib (n = 7), sunitinib (n = 2), and sorafenib (n = 1). Objective response rate was 40%, progression-free survival was 2.5 months (95% confidence interval, 1.2-3.8), and overall survival was 5.7 months (95% confidence interval, 0-24.0). Stratified for International Metastatic Renal Cell Carcinoma Database Consortium risk, overall survival in intermediate versus poor risk group were 18.6 months and 2.3 months, respectively. Second-line therapy did not result in disease control. No new or unexpected toxicities were observed.Conclusion
CUP-mRCC treated with vascular endothelial growth factor–targeted therapy is valid, feasible, and safe even though these patients had several negative prognostic factors. CUP-mRCC patients should be identified among CUP patients for specific renal-cell carcinoma therapy. 相似文献20.
Malte Rieken Luis A. Kluth Harun Fajkovic Umberto Capitanio Alberto Briganti Laura-Maria Krabbe Vitaly Margulis Mohammad Abufaraj Andrea Mari Beat Foerster Jay D. Raman Mikhail Regelman Sabine Brookman-May Daniel D. Sjoberg Pierre I. Karakiewicz Shahrokh F. Shariat 《Clinical genitourinary cancer》2018,16(4):e903-e908